An Unsupervised Classifier for Whole-Genome Phylogenies, the Maxwell© Tool.

The development of phylogenetic trees based on RNA or DNA sequences generally requires a precise and limited choice of important RNAs, e.g., messenger RNAs of essential proteins or ribosomal RNAs (like 16S), but rarely complete genomes, making it possible to explain evolution and speciation. In this article, we propose revisiting a classic phylogeny of archaea from only the information on the succession of nucleotides of their entire genome. For this purpose, we use a new tool, the unsupervised classifier Maxwell, whose principle lies in the Burrows-Wheeler compression transform, and we show its efficiency in clustering whole archaeal genomes.

Review and Analysis of German Mobile Apps for Inflammatory Bowel Disease Management Using the Mobile Application Rating Scale: Systematic Search in App Stores and Content Analysis.

BACKGROUND: Patients suffering from inflammatory bowel disease (IBD) frequently need long-term medical treatment. Mobile apps promise to complement and improve IBD management, but so far there has been no scientific analysis of their quality. OBJECTIVE: This study evaluated the quality of German mobile apps targeting IBD patients and physicians treating IBD patients using the Mobile Application Rating Scale (MARS). METHODS: The German Apple App Store and Google Play Store were systematically searched to identify German IBD mobile apps for patient and physician use. MARS was used by 6 physicians (3 using Android smartphones and 3 using iPhones) to independently assess app quality. Apps were randomly assigned so that the 4 apps with the most downloads were rated by all raters and the remaining apps were rated by 1 Android and 1 iOS user. RESULTS: In total, we identified 1764 apps in the Apple App Store and Google Play Store. After removing apps that were not related to IBD (n=1386) or not available in German (n=317), 61 apps remained. After removing duplicates (n=3) and apps for congresses (n=7), journals (n=4), and clinical studies (n=6), as well as excluding apps that were available in only 1 of the 2 app stores (n=20) and apps that could only be used with an additional device (n=7), we included a total of 14 apps. The app "CED Dokumentation und Tipps" had the highest overall median MARS score at 4.11/5. On the whole, the median MARS scores of the 14 apps ranged between 2.38/5 and 4.11/5. As there was no significant difference between iPhone and Android raters, we used the Wilcoxon comparison test to calculate P values. CONCLUSIONS: The MARS ratings showed that the quality of German IBD apps varied. We also discovered a discrepancy between app store ratings and MARS ratings, highlighting the difficulty of assessing perceived app quality. Despite promising results from international studies, there is little evidence for the clinical benefits of German IBD apps. Clinical studies and patient inclusion in the app development process are needed to effectively implement mobile apps in routine care.

Accuracy and tolerability of self-sampling of capillary blood for analysis of inflammation and autoantibodies in rheumatoid arthritis patients-results from a randomized controlled trial.

BACKGROUND: Rheumatoid arthritis (RA) requires early diagnosis and tight surveillance of disease activity. Remote self-collection of blood for the analysis of inflammation markers and autoantibodies could improve the monitoring of RA and facilitate the identification of individuals at-risk for RA. OBJECTIVE: Randomized, controlled trial to evaluate the accuracy, feasibility, and acceptability of an upper arm self-sampling device (UA) and finger prick-test (FP) to measure capillary blood from RA patients for C-reactive protein (CRP) levels and the presence of IgM rheumatoid factor (RF IgM) and anti-cyclic citrullinated protein antibodies (anti-CCP IgG). METHODS: RA patients were randomly assigned in a 1:1 ratio to self-collection of capillary blood via UA or FP. Venous blood sampling (VBS) was performed as a gold standard in both groups to assess the concordance of CRP levels as well as RF IgM and CCP IgG. General acceptability and pain during sampling were measured and compared between UA, FP, and VBS. The number of attempts for successful sampling, requests for assistance, volume, and duration of sample collection were also assessed. RESULTS: Fifty seropositive RA patients were included. 49/50 (98%) patients were able to successfully collect capillary blood. The overall agreement between capillary and venous analyses for CRP (0.992), CCP IgG (0.984), and RF IgM (0.994) were good. In both groups, 4/25 (16%) needed a second attempt and 8/25 (32%) in the UA and 7/25 (28%) in the FP group requested assistance. Mean pain scores for capillary self-sampling (1.7/10 ± 1.1 (UA) and 1.9/10 ± 1.9 (FP)) were significantly lower on a numeric rating scale compared to venous blood collection (UA: 2.8/10 ± 1.7; FP: 2.1 ± 2.0) (p=0.003). UA patients were more likely to promote the use of capillary blood sampling (net promoter score: +28% vs. -20% for FP) and were more willing to perform blood collection at home (60% vs. 32% for FP). CONCLUSIONS: These data show that self-sampling is accurate and feasible within one attempt by the majority of patients without assistance, allowing tight monitoring of RA disease activity as well as identifying individuals at-risk for RA. RA patients seem to prefer upper arm-based self-sampling to traditional finger pricking. TRIAL REGISTRATION: DRKS.de Identifier: DRKS00023526 . Registered on November 6, 2020.

Objective Measurements of Physical Activity and Sedentary Behavior Using Wearable Devices in Patients With Axial Spondyloarthritis: Protocol for a Systematic Review.

BACKGROUND: Axial spondyloarthritis (axSpA) is a subgroup of inflammatory rheumatic diseases. Practicing regular exercise is critical to manage pain and stiffness, reduce disease activity, and improve physical functioning, spinal mobility, and cardiorespiratory function. Accordingly, monitoring physical activity and sedentary behavior in patients with axSpA is relevant for clinical outcomes and disease management. OBJECTIVE: This review aims to determine which wearable devices, assessment methods, and associated metrics are commonly used to quantify physical activity or sedentary behavior in patients with axSpA. METHODS: The PubMed, Physiotherapy Evidence Database (PEDro), and Cochrane electronic databases will be searched, with no limit on publication date, to identify all the studies matching the inclusion criteria. Only original English-language articles published in a peer-reviewed journal will be included. The search strategy will include a combination of keywords related to the study population, wearable devices, physical activity, and sedentary behavior. We will use the Boolean operators "AND" and "OR" to combine keywords as well as Medical Subject Headings terms. RESULTS: Search strategy was completed in June 2020 with 23 records obtained. Data extraction and synthesis are currently ongoing. Dissemination of study results in peer-reviewed journals is expected at the end of 2021. CONCLUSIONS: This review will provide a comprehensive and detailed synthesis of published studies that examine the use of wearable devices for objective assessment of physical activity and sedentary behavior in patients with axSpA. TRIAL REGISTRATION: PROSPERO CRD42020182398; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=182398. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/23359.

Comparison of Energy Expenditure Assessed Using Wrist- and Hip-Worn ActiGraph GT3X in Free-Living Conditions in Young and Older Adults.

The World Health Organization has presented their recommendations for energy expenditure to improve public health. Activity trackers do represent a modern solution for measuring physical activity, particularly in terms of steps/day and energy expended in physical activity (active energy expenditure). According to the manufacturer's instructions, these activity trackers can be placed on different body locations, mostly at the wrist and the hip, in an undifferentiated manner. The objective of this study was to compare the absolute error rate of active energy expenditure measured by a wrist-worn and hip-worn ActiGraph GT3X+ over a 24-h period in free-living conditions in young and older adults. Over the period of a 24-h period, 22 young adults and 22 older adults were asked to wear two ActiGraph GT3X+ at two different body locations recommended by the manufacturer, namely one around the wrist and one above the hip. Freedson algorithm was applied for data analysis. For both groups, the absolute error rate tended to decrease from 1,252 to 43% for older adults and from 408 to 46% for young participants with higher energy expenditure. Interestingly, for both young and older adults, the wrist-worn ActiGraph provided a significantly higher values of active energy expenditure (943 ± 264 cal/min) than the hip-worn (288 ± 181 cal/min). Taken together, these results suggest that caution is needed when using active energy expenditure as an activity tracker-based metric to quantify physical activity.

Quality of a Supporting Mobile App for Rheumatic Patients: Patient-Based Assessment Using the User Version of the Mobile Application Scale (uMARS).

Introduction: Mobile applications promise to improve current health care. However, current mobile app quality ratings are mostly physician-based. The aim of this study was (1) to assess the quality of the self-management app Rheuma Auszeit using the validated uMARS (User Version of the Mobile App Rating Scale) app quality assessment tool and (2) to evaluate the association between uMARS scores and patients' characteristics. Materials and Methods: Consecutive patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis were seen at the rheumatology clinic at university hospital Erlangen, Germany. They were asked to test Rheuma Auszeit, evaluate its quality using uMARS and complete a paper-based survey evaluating the individual preferences, attitudes and ehealth literacy. The association between uMARS scores and patients' characteristics was further explored. Results: Between December 2018 and January 2019, a total of 126 patients evaluated Rheuma Auszeit using uMARS and filled out the paper-based survey. The median uMARS score was 3.9, IQR 0.7. Functionality was the domain with the highest rating (median 4.8, IQR 0.8), followed by aesthetics (median 4.0, IQR 0.7), information (median 3.5, IQR 0.8), and engagement (median 3.2, IQR 1.0). Subjective quality was average (median 3.0, IQR 1.0). The lowest scoring individual item was customization with a median of 2.5/5. Lower functionality scores were reported among older female rheumatic patients (P < 0.004). Older male rheumatic patients reported a higher subjective quality score (P < 0.024). Perceived disease activity and disease duration did not significantly correlate with any uMARS subdomain scores. eHealth literacy significantly correlated with functionality uMARS subdomain ratings (Rho = 0.18; P < 0.042). Preferred time of app usage significantly correlated with engagement (Rho = 0.20; P < 0.024), functionality (Rho = 0.19; P < 0.029), total uMARS score (Rho = 0.21; P < 0.017) and subjective quality score (Rho = 0.21; P < 0.017). The vast majority of rheumatic patients would consider recommending Rheuma Auszeit to other patients (117/126; 92.9%). Conclusion: Rheuma Auszeit was well-accepted by German patients suffering from rheumatoid arthritis, psoriatic arthritis and ankylosing spondyloarthritis. Lacking customization could lead to low app compliance and should be improved. Lower functionality scores among older female rheumatic patients highlight the need for patient education. The study underlines the potential and feasibility of therapeutic complementary digital solutions in rheumatology.

Gaining Insights Into the Estimation of the Circadian Rhythms of Social Activity in Older Adults From Their Telephone Call Activity With Statistical Learning: Observational Study.

BACKGROUND: Understanding the social mechanisms of the circadian rhythms of activity represents a major issue in better managing the mechanisms of age-related diseases occurring over time in the elderly population. The automated analysis of call detail records (CDRs) provided by modern phone technologies can help meet such an objective. At this stage, however, whether and how the circadian rhythms of telephone call activity can be automatically and properly modeled in the elderly population remains to be established. OBJECTIVE: Our goal for this study is to address whether and how the circadian rhythms of social activity observed through telephone calls could be automatically modeled in older adults. METHODS: We analyzed a 12-month data set of outgoing telephone CDRs of 26 adults older than 65 years of age. We designed a statistical learning modeling approach adapted for exploratory analysis. First, Gaussian mixture models (GMMs) were calculated to automatically model each participant's circadian rhythm of telephone call activity. Second, k-means clustering was used for grouping participants into distinct groups depending on the characteristics of their personal GMMs. RESULTS: The results showed the existence of specific structures of telephone call activity in the daily social activity of older adults. At the individual level, GMMs allowed the identification of personal habits, such as morningness-eveningness for making calls. At the population level, k-means clustering allowed the structuring of these individual habits into specific morningness or eveningness clusters. CONCLUSIONS: These findings support the potential of phone technologies and statistical learning approaches to automatically provide personalized and precise information on the social rhythms of telephone call activity of older individuals. Futures studies could integrate such digital insights with other sources of data to complete assessments of the circadian rhythms of activity in elderly populations.

Novel statistical approach for assessing the persistence of the circadian rhythms of social activity from telephone call detail records in older adults.

How circadian rhythms of activity manifest themselves in social life of humans remains one of the most intriguing questions in chronobiology and a major issue for personalized medicine. Over the past years, substantial advances have been made in understanding the personal nature and the robustness-i.e. the persistence-of the circadian rhythms of social activity by the analysis of phone use. At this stage however, the consistency of such advances as their statistical validity remains unclear. The present paper has been specifically designed to address this issue. To this end, we propose a novel statistical procedure for the measurement of the circadian rhythms of social activity which is particularly well-suited for the existing framework of persistence analysis. Furthermore, we illustrate how this procedure works concretely by assessing the persistence of the circadian rhythms of telephone call activity from a 12-month call detail records (CDRs) dataset of adults over than 65 years. The results show the ability of our approach for assessing persistence with a statistical significance. In the field of CDRs analysis, this novel statistical approach can be used for completing the existing methods used to analyze the persistence of the circadian rhythms of a social nature. More importantly, it provides an opportunity to open up the analysis of CDRs for various domains of application in personalized medicine requiring access to statistical significance such as health care monitoring.

Exploitation of Outgoing and Incoming Telephone Calls in the Context of Circadian Rhythms of Social Activity Among Elderly People: Observational Descriptive Study.

BACKGROUND: In the elderly population, analysis of the circadian rhythms of social activity may help in supervising homebound disabled and chronically ill populations. Circadian rhythms are monitored over time to determine, for example, the stability of the organization of daily social activity rhythms and the occurrence of particular desynchronizations in the way older adults act and react socially during the day. Recently, analysis of telephone call detail records has led to the possibility of determining circadian rhythms of social activity in an objective unobtrusive way for young patients from their outgoing telephone calls. At this stage, however, the analysis of incoming call rhythms and the comparison of their organization with respect to outgoing calls remains to be performed in underinvestigated populations (in particular, older populations). OBJECTIVE: This study investigated the persistence and synchronization of circadian rhythms in telephone communication by older adults. METHODS: The study used a longitudinal 12-month data set combining call detail records and questionnaire data from 26 volunteers aged 70 years or more to determine the existence of persistent and synchronized circadian rhythms in their telephone communications. The study worked with the following four specific telecommunication parameters: (1) recipient of the telephone call (alter), (2) time at which the call began, (3) duration of the call, and (4) direction of the call. We focused on the following two issues: (1) the existence of persistent circadian rhythms of outgoing and incoming telephone calls in the older population and (2) synchronization with circadian rhythms in the way the older population places and responds to telephone calls. RESULTS: The results showed that older adults have their own specific circadian rhythms for placing telephone calls and receiving telephone calls. These rhythms are partly structured by the way in which older adults allocate their communication time over the day. In addition, despite minor differences between circadian rhythms for outgoing and incoming calls, our analysis suggests the two rhythms could be synchronized. CONCLUSIONS: These results suggest the existence of potential persistent and synchronized circadian rhythms in the outgoing and incoming telephone activities of older adults.

Circadian Rhythms in the Telephone Calls of Older Adults: Observational Descriptive Study.

BACKGROUND: Recent studies have thoughtfully and convincingly demonstrated the possibility of estimating the circadian rhythms of young adults' social activity by analyzing their telephone call-detail records (CDRs). In the field of health monitoring, this development may offer new opportunities for supervising a patient's health status by collecting objective, unobtrusive data about their daily social interactions. However, before considering this future perspective, whether and how similar results could be observed in other populations, including older ones, should be established. OBJECTIVE: This study was designed specifically to address the circadian rhythms in the telephone calls of older adults. METHODS: A longitudinal, 12-month dataset combining CDRs and questionnaire data from 26 volunteers aged 65 years or older was used to examine individual differences in the daily rhythms of telephone call activity. The study used outgoing CDRs only and worked with three specific telecommunication parameters: (1) call recipient (alter), (2) time of day, and (3) call duration. As did the studies involving young adults, we analyzed three issues: (1) the existence of circadian rhythms in the telephone call activity of older adults, (2) their persistence over time, and (3) the alter-specificity of calls by calculating relative entropy. RESULTS: We discovered that older adults had their own specific circadian rhythms of outgoing telephone call activity whose salient features and preferences varied across individuals, from morning until night. We demonstrated that rhythms were consistent, as reflected by their persistence over time. Finally, results suggested that the circadian rhythms of outgoing telephone call activity were partly structured by how older adults allocated their communication time across their social network. CONCLUSIONS: Overall, these results are the first to have demonstrated the existence, persistence, and alter-specificity of the circadian rhythms of the outgoing telephone call activity of older adults. These findings suggest an opportunity to consider modern telephone technologies as potential sensors of daily activity. From a health care perspective, these sensors could be harnessed for unobtrusive monitoring purposes.

Author Correction: Association between social asymmetry and depression in older adults: A phone Call Detail Records analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Comparison of Step Count Assessed Using Wrist- and Hip-Worn Actigraph GT3X in Free-Living Conditions in Young and Older Adults.

Background: Walking represents a major component of physical activity (PA), and its restriction could degrade autonomy and quality of life. An important objective for preventive and/or rehabilitative strategies to improve balance and gait in normal and pathological aging conditions is to focus on physical activity. Activity monitors have recently been getting increasingly popular and represent a modern solution to measure-and communicate-PA notably in terms of steps/day. These activity monitors are well-suited for various populations as they can be worn on a variety of locations on the body, including the wrist and the hip (i.e., the two most common locations), in an undifferentiated way according to the manufacturer's instruction. The aim of this study was hence to verify potential differences in step count (SC) by comparing this parameter assessed using wrist- and hip-worn activity trackers over a 24-h period in free-living conditions in young and older adults. Methods: Young adults (n = 22) and older adults (n = 22) voluntarily participated in this study. They were required to wear two commercially-available Actigraph GT3X+ activity monitors simultaneously at two locations recommended by the manufacturer, i.e., one positioned around the wrist and one above the hip, over a 24-h period in free-living conditions. The manufacturer's software was used to obtain estimates of the SC. Results: For both groups, the wrist-worn activity tracker provided significantly higher SC than the hip-worn activity tracker did. For both placements on the body, older adults exhibited significantly lower SC than young adults. Interestingly, for both young and older participants, the difference between both measurements tended to decrease for longer distances. Conclusion: The different estimations of the step count provided by the comparison between two identical Actigraph GT3x on the wrist or the hip during the 24-h observation period in free-living conditions in young and older adults strongly suggests that caution is needed when using total step per day values as an outcome to quantify walking behavior. Probably we can suggest the same caution across implementation of different activity Tracker.

Association between social asymmetry and depression in older adults: A phone Call Detail Records analysis.

Analyzing social interactions on a passive and non-invasive way through the use of phone call detail records (CDRs) is now recognized as a promising approach in health monitoring. However, deeper investigations are required to confirm its relevance in social interaction modeling. Particularly, no clear consensus exists in the use of the direction parameter characterizing the directed nature of interactions in CDRs. In the present work, we specifically investigate, in a 26-older-adults population over 12 months, whether and how this parameter could be used in CDRs analysis. We then evaluate its added-value for depression assessment regarding the Geriatric Depression Scale score assessed within our population during the study. The results show the existence of three clusters of phone call activity named (1) proactive, (2) interactive, and (3) reactive. Then, we introduce the notion of asymmetry that synthesizes these activities. We find significant correlations between asymmetry and the depressive state assessed in the older individual. Particularly, (1) reactive users are more depressed than the others, and (2) not depressed older adults tend to be proactive. Taken together, the present findings suggest the phone's potential to be used as a social sensor containing relevant health-related insights when the direction parameter is considered.

Maxwell®: An Unsupervised Learning Approach for 5P Medicine.

In the 5P medicine (Personalized, Preventive, Participative, Predictive and Pluri-expert), the general trend is to process data by displacing the barycenter of the information from hospital centered systems to the patient centered ones through his personal medical records. Today, the use of artificial intelligence for supporting this transition shows real limitations in its implementation in operational practice, both at the level of patient care, but also in the general daily life of the health professional, because of the medico-legal imperatives induced by the promises of the '5P medicine'. In this paper, we propose to fill this gap by introducing an original artificial intelligence platform, named Maxwell, which follows an unsupervised learning approach in line with the medico-legal imperatives of the '5P medicine'. We describe the functional platform characteristics and illustrate them by two examples of clustering in genomics and magnetic resonance imaging.

How to Measure Circadian Rhythms of Activity and Their Disruptions in Humans Using Passive and Unobtrusive Capture of Phone Call Activity.

Monitoring circadian rhythms of social activity is crucial for preserving the health and wellness of ill elderly people. In this paper, we assess the ability of phones to be used as a temporal and social daily activity sensor from a passive and unobstructive measure of phone call activity. To this end, we introduce a methodology specifically designed to automatically measure both persistence and disruptions in circadian rhythms of phone call activity with 26 adults older than 65 years.