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Anatomy learning has traditionally relied on drawings, plastic models, and cadaver dissections/prosections to help students understand the three-dimensional (3D) relationships within the human body. However, the landscape of anatomy education has been transformed with the introduction of digital media. In this light, the Open Anatomy Explorer (OPANEX) was developed. It includes two user interfaces (UI): one for students and one for administrators. The administrator UI offers features such as uploading and labelling of 3D models, and customizing 3D settings. Additionally, the OPANEX facilitates content sharing between institutes through its import-export functionality. To evaluate the integration of OPANEX within the existing array of learning resources, a survey was conducted as part of the osteology course at Ghent University, Belgium. The survey aimed to investigate the frequency of use of five learning resources, attitudes towards 3D environments, and the OPANEX user experience. Analysis revealed that the OPANEX was the most frequently used resource. Students' attitudes towards 3D learning environments further supported this preference. Feedback on the OPANEX user experience indicated various reasons for its popularity, including the quality of the models, regional annotations, and customized learning content. In conclusion, the outcomes underscore the educational value of the OPANEX, reflecting students' positive attitudes towards 3D environments in anatomy education.

Photosynthesis is an essential process in plants that synthesizes sugars used for growth and development, highlighting the importance of establishing robust methods to monitor photosynthetic activity. Infrared gas analysis (IRGA) can be used to track photosynthetic rates by measuring plant CO 2 assimilation and release. Although much progress has been made in the development of IRGA technologies, challenges remain when using this technique on small herbaceous plants such as Arabidopsis thaliana. The use of whole plant chambers can overcome the difficulties associated with applying bulky leaf clamps to small delicate leaves. However, respiration from the roots and from soil-based microorganisms may skew these gas exchange measurements. Here, we present a simple method to efficiently perform IRGA on A. thaliana plants using a whole plant chamber that removes the confounding effects of respiration from roots and soil-based microorganisms from the measurements. We show that this method can be used to detect subtle changes in photosynthetic rates measured at different times of day, under different growth conditions, and between wild-type and plants with deficiencies in the photosynthetic machinery. Furthermore, we show that this method can be used to detect changes in photosynthetic rates even at very young developmental stages such as 10 d-old seedlings. This method contributes to the array of techniques currently used to perform IRGA on A. thaliana and can allow for the monitoring of photosynthetic rates of whole plants from young ages., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: In healthcare, an increasing collaboration can be noticed between different caregivers, especially considering the shift to homecare. To provide optimal patient care, efficient coordination of data and workflows between these different stakeholders is required. To achieve this, data should be exposed in a machine-interpretable, reusable manner. In addition, there is a need for smart, dynamic, personalized and performant services provided on top of this data. Flexible workflows should be defined that realize their desired functionality, adhere to use case specific quality constraints and improve coordination across stakeholders. User interfaces should allow configuring all of this in an easy, user-friendly way., Methods: A distributed, generic, cascading reasoning reference architecture can solve the presented challenges. It can be instantiated with existing tools built upon Semantic Web technologies that provide data-driven semantic services and constructing cross-organizational workflows. These tools include RMLStreamer to generate Linked Data, DIVIDE to adaptively manage contextually relevant local queries, Streaming MASSIF to deploy reusable services, AMADEUS to compose semantic workflows, and RMLEditor and Matey to configure rules to generate Linked Data., Results: A use case demonstrator is built on a scenario that focuses on personalized smart monitoring and cross-organizational treatment planning. The performance and usability of the demonstrator's implementation is evaluated. The former shows that the monitoring pipeline efficiently processes a stream of 14 observations per second: RMLStreamer maps JSON observations to RDF in 13.5 ms, a C-SPARQL query to generate fever alarms is executed on a window of 5 s in 26.4 ms, and Streaming MASSIF generates a smart notification for fever alarms based on severity and urgency in 1539.5 ms. DIVIDE derives the C-SPARQL queries in 7249.5 ms, while AMADEUS constructs a colon cancer treatment plan and performs conflict detection with it in 190.8 ms and 1335.7 ms, respectively., Conclusions: Existing tools built upon Semantic Web technologies can be leveraged to optimize continuous care provisioning. The evaluation of the building blocks on a realistic homecare monitoring use case demonstrates their applicability, usability and good performance. Further extending the available user interfaces for some tools is required to increase their adoption., (© 2024. The Author(s).)

Background: Digital interventions are a promising avenue to promote physical activity in healthy adults. Current practices recommend to include end-users early on in the development process. This study focuses on the wishes and needs of users regarding an a mobile health (mHealth) application that promotes physical activity in healthy adults, and on the differences between participants who do or do not meet the World Health Organization's recommendation of an equivalent of 150 minutes of moderate intensity physical activity., Methods: We used a mixed-method design called Group Concept Mapping. In a first phase, we collected statements completing the prompt "In an app that helps me move more, I would like to see/ do/ learn the following…" during four brainstorming sessions with physically inactive individuals ( n  = 19). The resulting 90 statements were then sorted and rated by a new group of participants ( n  = 46). Sorting data was aggregated, and (dis)similarity matrices were created using multidimensional scaling. Hierarchical clustering was applied using Ward's method. Analyses were carried out for the entire group, a subgroup of active participants and a subgroup of inactive participants. Explorative analyses further investigated ratings of the clusters as a function of activity level, gender, age and education., Results: Six clusters of statements were identified, namely 'Ease-of-use and Self-monitoring', 'Technical Aspects and Advertisement', 'Personalised Information and Support', 'Motivational Aspects', 'Goal setting, goal review and rewards', and 'Social Features'. The cluster 'Ease-of-use and Self-monitoring' was rated highest in the overall group and the active subgroup, whereas the cluster 'Technical Aspects and Advertisement' was scored as most relevant in the inactive subgroup. For all groups, the cluster 'Social Features' was scored the lowest. Explorative analysis revealed minor between-group differences., Discussion: The present study identified priorities of users for an mHealth application that promotes physical activity. First, the application should be user-friendly and accessible. Second, the application should provide personalized support and information. Third, users should be able to monitor their behaviour and compare their current activity to their past performance. Fourth, users should be provided autonomy within the app, such as over which and how many notifications they would like to receive, and whether or not they want to engage with social features. These priorities can serve as guiding principles for developing mHealth applications to promote physical activity in the general population., Competing Interests: The authors declare there are no competing interests., (©2024 Braun et al.)

Introduction: Ontologies are a formal way to represent knowledge in a particular field and have the potential to transform the field of health promotion and digital interventions. However, few researchers in physical activity (PA) are familiar with ontologies, and the field can be difficult to navigate. This systematic review aims to (1) identify ontologies in the field of PA, (2) assess their content and (3) assess their quality., Methods: Databases were searched for ontologies on PA. Ontologies were included if they described PA or sedentary behavior, and were available in English language. We coded whether ontologies covered the user profile, activity, or context domain. For the assessment of quality, we used 12 criteria informed by the Open Biological and Biomedical Ontology (OBO) Foundry principles of good ontology practice., Results: Twenty-eight ontologies met the inclusion criteria. All ontologies covered PA, and 19 included information on the user profile. Context was covered by 17 ontologies (physical context, n = 12; temporal context, n = 14; social context: n = 5). Ontologies met an average of 4.3 out of 12 quality criteria. No ontology met all quality criteria., Discussion: This review did not identify a single comprehensive ontology of PA that allowed reuse. Nonetheless, several ontologies may serve as a good starting point for the promotion of PA. We provide several recommendations about the identification, evaluation, and adaptation of ontologies for their further development and use., (© 2023. The Author(s).)

Background: The use of serious games in health care is on the rise, as these games motivate treatment adherence, reduce treatment costs, and educate patients and families. However, current serious games fail to offer personalized interventions, ignoring the need to abandon the one-size-fits-all approach. Moreover, these games, with a primary objective other than pure entertainment, are costly and complex to develop and require the constant involvement of a multidisciplinary team. No standardized approach exists on how serious games can be personalized, as existing literature focuses on specific use cases and scenarios. The serious game development domain fails to consider any transfer of domain knowledge, which means this labor-intensive process must be repeated for each serious game., Objective: We proposed a software engineering framework that aims to streamline the multidisciplinary design process of personalized serious games in health care and facilitates the reuse of domain knowledge and personalization algorithms. By focusing on the transfer of knowledge to new serious games by reusing components and personalization algorithms, the comparison and evaluation of different personalization strategies can be simplified and expedited. In doing so, the first steps are taken in advancing the state of the art of knowledge regarding personalized serious games in health care., Methods: The proposed framework aimed to answer 3 questions that need to be asked when designing personalized serious games: Why is the game personalized? What parameters can be used for personalization? and How is the personalization achieved? The 3 involved stakeholders, namely, the domain expert, the (game) developer, and the software engineer, were each assigned a question and then assigned responsibilities regarding the design of the personalized serious game. The (game) developer was responsible for all the game-related components; the domain expert was in charge of the modeling of the domain knowledge using simple or complex concepts (eg, ontologies); and the software engineer managed the personalization algorithms or models integrated into the system. The framework acted as an intermediate step between game conceptualization and implementation; it was illustrated by developing and evaluating a proof of concept., Results: The proof of concept, a serious game for shoulder rehabilitation, was evaluated using simulations of heart rate and game scores to assess how personalization was achieved and whether the framework responded as expected. The simulations indicated the value of both real-time and offline personalization. The proof of concept illustrated how the interaction between different components worked and how the framework was used to simplify the design process., Conclusions: The proposed framework for personalized serious games in health care identifies the responsibilities of the involved stakeholders in the design process, using 3 key questions for personalization. The framework focuses on the transferability of knowledge and reusability of personalization algorithms to simplify the design process of personalized serious games., (©Stéphanie Carlier, Vince Naessens, Femke De Backere, Filip De Turck. Originally published in JMIR Serious Games (https://games.jmir.org), 06.03.2023.)

Recently proposed methods in intrusion detection are iterating on machine learning methods as a potential solution. These novel methods are validated on one or more datasets from a sparse collection of academic intrusion detection datasets. Their recognition as improvements to the state-of-the-art is largely dependent on whether they can demonstrate a reliable increase in classification metrics compared to similar works validated on the same datasets. Whether these increases are meaningful outside of the training/testing datasets is rarely asked and never investigated. This work aims to demonstrate that strong general performance does not typically follow from strong classification on the current intrusion detection datasets. Binary classification models from a range of algorithmic families are trained on the attack classes of CSE-CIC-IDS2018, a state-of-the-art intrusion detection dataset. After establishing baselines for each class at various points of data access, the same trained models are tasked with classifying samples from the corresponding attack classes in CIC-IDS2017, CIC-DoS2017 and CIC-DDoS2019. Contrary to what the baseline results would suggest, the models have rarely learned a generally applicable representation of their attack class. Stability and predictability of generalized model performance are central issues for all methods on all attack classes. Focusing only on the three best-in-class models in terms of interdataset generalization, reveals that for network-centric attack classes (brute force, denial of service and distributed denial of service), general representations can be learned with flat losses in classification performance (precision and recall) below 5%. Other attack classes vary in generalized performance from stark losses in recall (-35%) with intact precision (98+%) for botnets to total degradation of precision and moderate recall loss for Web attack and infiltration models. The core conclusion of this article is a warning to researchers in the field. Expecting results of proposed methods on the test sets of state-of-the-art intrusion detection datasets to translate to generalized performance is likely a serious overestimation. Four proposals to reduce this overestimation are set out as future work directions.

Background: Insomnia, eating disorders, heart problems and even strokes are just some of the illnesses that reveal the negative impact of stress overload on health and well-being. Early detection of stress is therefore of utmost importance. Whereas the gold-standard for detecting stress is by means of questionnaires, more recent work uses wearable sensors to find continuous and qualitative physical markers of stress. As some physiological stress responses, e.g. increased heart rate or sweating and chills, might also occur when doing sports, a more profound approach is needed for stress detection than purely considering physiological data., Methods: In this paper, we analyse the added value of context information during stress detection from wearable data. We do so by comparing the performance of models trained purely on physiological data and models trained on physiological and context data. We consider the user's activity and hours of sleep as context information, where we compare the influence of user-given context versus machine learning derived context., Results: Context-aware models reach higher accuracy and lower standard deviations in comparison to the baseline (physiological) models. We also observe higher accuracy and improved weighted F1 score when incorporating machine learning predicted, instead of user-given, activities as context information., Conclusions: In this paper we show that considering context information when performing stress detection from wearables leads to better performance. We also show that it is possible to move away from human labeling and rely only on the wearables for both physiology and context., (© 2022. The Author(s).)

Background: Anxiety disorders are highly prevalent in mental health problems. The lives of people suffering from an anxiety disorder can be severely impaired. Virtual Reality Exposure Therapy (VRET) is an effective treatment, which immerses patients in a controlled Virtual Environment (VE). This creates the opportunity to confront feared stimuli and learn how to deal with them, which may result in the reduction of anxiety. The configuration of these VEs requires extensive effort to maximise the potential of Virtual Reality (VR) and the effectiveness of the therapy. Manual configuration becomes infeasible when the number of possible virtual stimuli combinations is infinite. Due to the growing complexity, acquiring the skills to truly master a VR system is difficult and it increases the threshold for psychotherapists to use such useful systems. We therefore developed a prototype of a supportive algorithm to facilitate the use of VRET in a clinical setting. This automatised system assists psychotherapists to use the wide range of functionalities without burdening them with technical challenges. Thus, psychotherapists can focus their attention on the patient., Methods: In this paper both the prototype of the algorithm and a first proof of concept are described. The algorithm suggests environment configurations for VRET, tailored to the individual therapeutic needs of each patient. The system aims to maximise learning during exposure therapy for different combinations of stimuli by using the Rescorla-Wagner model as a predictor for learning. In a first proof of concept, the VE configurations suggested by the algorithm for three anonymised clinical vignettes were compared with prior manual configurations by two psychotherapists., Results: The prototype of the algorithm and a first proof of concept are described. The first proof of concept demonstrated the relevance and potential of the proposed system, as it managed to propose similar configurations for the clinical vignettes compared to those made by therapists. Nonetheless, because of the exploratory nature of the study, no claims can yet be made about its efficacy., Conclusions: With the increasing ubiquity of immersive technologies, this technology for assisted configuration of VEs could make VRET a valuable tool for psychotherapists., Competing Interests: Declaration of Competing Interest Authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The diagnosis of headache disorders relies on the correct classification of individual headache attacks. Currently, this is mainly done by clinicians in a clinical setting, which is dependent on subjective self-reported input from patients. Existing classification apps also rely on self-reported information and lack validation. Therefore, the exploratory mBrain study investigates moving to continuous, semi-autonomous and objective follow-up and classification based on both self-reported and objective physiological and contextual data., Methods: The data collection set-up of the observational, longitudinal mBrain study involved physiological data from the Empatica E4 wearable, data-driven machine learning (ML) algorithms detecting activity, stress and sleep events from the wearables' data modalities, and a custom-made application to interact with these events and keep a diary of contextual and headache-specific data. A knowledge-based classification system for individual headache attacks was designed, focusing on migraine, cluster headache (CH) and tension-type headache (TTH) attacks, by using the classification criteria of ICHD-3. To show how headache and physiological data can be linked, a basic knowledge-based system for headache trigger detection is presented., Results: In two waves, 14 migraine and 4 CH patients participated (mean duration 22.3 days). 133 headache attacks were registered (98 by migraine, 35 by CH patients). Strictly applying ICHD-3 criteria leads to 8/98 migraine without aura and 0/35 CH classifications. Adapted versions yield 28/98 migraine without aura and 17/35 CH classifications, with 12/18 participants having mostly diagnosis classifications when episodic TTH classifications (57/98 and 32/35) are ignored., Conclusions: Strictly applying the ICHD-3 criteria on individual attacks does not yield good classification results. Adapted versions yield better results, with the mostly classified phenotype (migraine without aura vs. CH) matching the diagnosis for 12/18 patients. The absolute number of migraine without aura and CH classifications is, however, rather low. Example cases can be identified where activity and stress events explain patient-reported headache triggers. Continuous improvement of the data collection protocol, ML algorithms, and headache classification criteria (including the investigation of integrating physiological data), will further improve future headache follow-up, classification and trigger detection. Trial registration This trial was retrospectively registered with number NCT04949204 on 24 June 2021 at www., Clinicaltrials: gov ., (© 2022. The Author(s).)

Epigenomics is the study of molecular signatures associated with discrete regions within genomes, many of which are important for a wide range of nuclear processes. The ability to profile the epigenomic landscape associated with genes, repetitive regions, transposons, transcription, differential expression, cis-regulatory elements, and 3D chromatin interactions has vastly improved our understanding of plant genomes. However, many epigenomic and single-cell genomic assays are challenging to perform in plants, leading to a wide range of data quality issues; thus, the data require rigorous evaluation prior to downstream analyses and interpretation. In this commentary, we provide considerations for the evaluation of plant epigenomics and single-cell genomics data quality with the aim of improving the quality and utility of studies using those data across diverse plant species., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

In today's data landscape, data streams are well represented. This is mainly due to the rise of data-intensive domains such as the Internet of Things (IoT), Smart Industries, Pervasive Health, and Social Media. To extract meaningful insights from these streams, they should be processed in real time, while solving an integration problem as these streams need to be combined with more static data and their domain knowledge. Ontologies are ideal for modeling this domain knowledge and facilitate the integration of heterogeneous data within data-intensive domains such as the IoT. Expressive reasoning techniques, such as OWL2 DL reasoning, are needed to completely interpret the domain knowledge and for the extraction of meaningful decisions. Expressive reasoning techniques have mainly focused on static data environments, as it tends to become slow with growing datasets. There is thus a mismatch between expressive reasoning and the real-time requirements of data-intensive domains. In this paper, we take a first step towards bridging the gap between expressivity and efficiency while reasoning over high-velocity IoT data streams for the task of event enrichment. We present a structural caching technique that eliminates reoccurring reasoning steps by exploiting the characteristics of most IoT streams, i.e., streams typically produce events that are similar in structure and size. Our caching technique speeds up reasoning time up to thousands of times for fully fledged OWL2 DL reasoners and even tenths and hundreds of times for less expressive OWL2 RL and OWL2 EL reasoners., (© The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature 2022.)

Photoperiod plays a key role in controlling the phase transition from vegetative to reproductive growth in flowering plants. Leaves are the major organs perceiving day-length signals, but how specific leaf cell types respond to photoperiod remains unknown. We integrated photoperiod-responsive chromatin accessibility and transcriptome data in leaf epidermis and vascular companion cells of Arabidopsis thaliana by combining isolation of nuclei tagged in specific cell/tissue types with assay for transposase-accessible chromatin using sequencing and RNA-sequencing. Despite a large overlap, vasculature and epidermis cells responded differently. Long-day predominantly induced accessible chromatin regions (ACRs); in the vasculature, more ACRs were induced and these were located at more distal gene regions, compared with the epidermis. Vascular ACRs induced by long days were highly enriched in binding sites for flowering-related transcription factors. Among the highly ranked genes (based on chromatin and expression signatures in the vasculature), we identified TREHALOSE-PHOSPHATASE/SYNTHASE 9 (TPS9) as a flowering activator, as shown by the late flowering phenotypes of T-DNA insertion mutants and transgenic lines with phloem-specific knockdown of TPS9. Our cell-type-specific analysis sheds light on how the long-day photoperiod stimulus impacts chromatin accessibility in a tissue-specific manner to regulate plant development., (© American Society of Plant Biologists 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In the time series classification domain, shapelets are subsequences that are discriminative of a certain class. It has been shown that classifiers are able to achieve state-of-the-art results by taking the distances from the input time series to different discriminative shapelets as the input. Additionally, these shapelets can be visualized and thus possess an interpretable characteristic, making them appealing in critical domains, where longitudinal data are ubiquitous. In this study, a new paradigm for shapelet discovery is proposed, which is based on evolutionary computation. The advantages of the proposed approach are that: (i) it is gradient-free, which could allow escaping from local optima more easily and supports non-differentiable objectives; (ii) no brute-force search is required, making the algorithm scalable; (iii) the total amount of shapelets and the length of each of these shapelets are evolved jointly with the shapelets themselves, alleviating the need to specify this beforehand; (iv) entire sets are evaluated at once as opposed to single shapelets, which results in smaller final sets with fewer similar shapelets that result in similar predictive performances; and (v) the discovered shapelets do not need to be a subsequence of the input time series. We present the results of the experiments, which validate the enumerated advantages.

Information extracted from electrohysterography recordings could potentially prove to be an interesting additional source of information to estimate the risk on preterm birth. Recently, a large number of studies have reported near-perfect results to distinguish between recordings of patients that will deliver term or preterm using a public resource, called the Term/Preterm Electrohysterogram database. However, we argue that these results are overly optimistic due to a methodological flaw being made. In this work, we focus on one specific type of methodological flaw: applying over-sampling before partitioning the data into mutually exclusive training and testing sets. We show how this causes the results to be biased using two artificial datasets and reproduce results of studies in which this flaw was identified. Moreover, we evaluate the actual impact of over-sampling on predictive performance, when applied prior to data partitioning, using the same methodologies of related studies, to provide a realistic view of these methodologies' generalization capabilities. We make our research reproducible by providing all the code under an open license., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Leveraging graphs for machine learning tasks can result in more expressive power as extra information is added to the data by explicitly encoding relations between entities. Knowledge graphs are multi-relational, directed graph representations of domain knowledge. Recently, deep learning-based techniques have been gaining a lot of popularity. They can directly process these type of graphs or learn a low-dimensional numerical representation. While it has been shown empirically that these techniques achieve excellent predictive performances, they lack interpretability. This is of vital importance in applications situated in critical domains, such as health care., Methods: We present a technique that mines interpretable walks from knowledge graphs that are very informative for a certain classification problem. The walks themselves are of a specific format to allow for the creation of data structures that result in very efficient mining. We combine this mining algorithm with three different approaches in order to classify nodes within a graph. Each of these approaches excels on different dimensions such as explainability, predictive performance and computational runtime., Results: We compare our techniques to well-known state-of-the-art black-box alternatives on four benchmark knowledge graph data sets. Results show that our three presented approaches in combination with the proposed mining algorithm are at least competitive to the black-box alternatives, even often outperforming them, while being interpretable., Conclusions: The mining of walks is an interesting alternative for node classification in knowledge graphs. Opposed to the current state-of-the-art that uses deep learning techniques, it results in inherently interpretable or transparent models without a sacrifice in terms of predictive performance.

This paper contributes to the pursuit of leveraging unstructured medical notes to structured clinical decision making. In particular, we present a pipeline for clinical information extraction from medical notes related to preterm birth, and discuss the main challenges as well as its potential for clinical practice. A large collection of medical notes, created by staff during hospitalizations of patients who were at risk of delivering preterm, was gathered and analyzed. Based on an annotated collection of notes, we trained and evaluated information extraction components to discover clinical entities such as symptoms, events, anatomical sites and procedures, as well as attributes linked to these clinical entities. In a retrospective study, we show that these are highly informative for clinical decision support models that are trained to predict whether delivery is likely to occur within specific time windows, in combination with structured information from electronic health records., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In order to successfully reproduce, plants must sense changes in their environment and flower at the correct time. Many plants utilize day length and vernalization, a mechanism for verifying that winter has occurred, to determine when to flower. Our study used available temperature and day length data from different climates to provide a general understanding how this information processing of environmental signals could have evolved in plants. For climates where temperature fluctuation correlations decayed exponentially, a simple stochastic model characterizing vernalization was able to reconstruct the switch-like behavior of the core flowering regulatory genes. For these and other climates, artificial neural networks were used to predict flowering gene expression patterns. For temperate plants, long-term cold temperature and short-term day length measurements were sufficient to produce robust flowering time decisions from the neural networks. Additionally, evolutionary simulations on neural networks confirmed that the combined signal of temperature and day length achieved the highest fitness relative to neural networks with access to only one of those inputs. We suggest that winter temperature memory is a well-adapted strategy for plants' detection of seasonal changes, and absolute day length is useful for the subsequent triggering of flowering., Competing Interests: The authors have declared that no competing interests exist.

A large fraction of plant genomes is composed of transposable elements (TE), which provide a potential source of novel genes through "domestication"-the process whereby the proteins encoded by TE diverge in sequence, lose their ability to catalyse transposition and instead acquire novel functions for their hosts. In Arabidopsis, ANTAGONIST OF LIKE HETEROCHROMATIN PROTEIN 1 (ALP1) arose by domestication of the nuclease component of Harbinger class TE and acquired a new function as a component of POLYCOMB REPRESSIVE COMPLEX 2 (PRC2), a histone H3K27me3 methyltransferase involved in regulation of host genes and in some cases TE. It was not clear how ALP1 associated with PRC2, nor what the functional consequence was. Here, we identify ALP2 genetically as a suppressor of Polycomb-group (PcG) mutant phenotypes and show that it arose from the second, DNA binding component of Harbinger transposases. Molecular analysis of PcG compromised backgrounds reveals that ALP genes oppose silencing and H3K27me3 deposition at key PcG target genes. Proteomic analysis reveals that ALP1 and ALP2 are components of a variant PRC2 complex that contains the four core components but lacks plant-specific accessory components such as the H3K27me3 reader LIKE HETEROCHROMATION PROTEIN 1 (LHP1). We show that the N-terminus of ALP2 interacts directly with ALP1, whereas the C-terminus of ALP2 interacts with MULTICOPY SUPPRESSOR OF IRA1 (MSI1), a core component of PRC2. Proteomic analysis reveals that in alp2 mutant backgrounds ALP1 protein no longer associates with PRC2, consistent with a role for ALP2 in recruitment of ALP1. We suggest that the propensity of Harbinger TE to insert in gene-rich regions of the genome, together with the modular two component nature of their transposases, has predisposed them for domestication and incorporation into chromatin modifying complexes., Competing Interests: The authors have declared that no competing interests exist.

Citizen engagement is one of the key factors for smart city initiatives to remain sustainable over time. This in turn entails providing citizens and other relevant stakeholders with the latest data and tools that enable them to derive insights that add value to their day-to-day life. The massive volume of data being constantly produced in these smart city environments makes satisfying this requirement particularly challenging. This paper introduces Explora, a generic framework for serving interactive low-latency requests, typical of visual exploratory applications on spatiotemporal data, which leverages the stream processing for deriving-on ingestion time -synopsis data structures that concisely capture the spatial and temporal trends and dynamics of the sensed variables and serve as compacted data sets to provide fast (approximate) answers to visual queries on smart city data. The experimental evaluation conducted on proof-of-concept implementations of Explora, based on traditional database and distributed data processing setups, accounts for a decrease of up to 2 orders of magnitude in query latency compared to queries running on the base raw data at the expense of less than 10% query accuracy and 30% data footprint. The implementation of the framework on real smart city data along with the obtained experimental results prove the feasibility of the proposed approach.

Autism Spectrum Disorder (ASD) is characterized by social interaction difficulties and communication difficulties. Moreover, children with ASD often suffer from other co-morbidities, such as anxiety and depression. Finding appropriate treatment can be difficult as symptoms of ASD and co-morbidities often overlap. Due to these challenges, parents of children with ASD often suffer from higher levels of stress. This research aims to investigate the feasibility of empowering children with ASD and their parents through the use of a serious game to reduce stress and anxiety and a supporting parent application. The New Horizon game and the SpaceControl application were developed together with therapists and according to guidelines for e-health patient empowerment. The game incorporates two mini-games with relaxation techniques. The performance of the game was analyzed and usability studies with three families were conducted. Parents and children were asked to fill in the Spence's Children Anxiety Scale (SCAS) and Spence Children Anxiety Scale-Parents (SCAS-P) anxiety scale. The game shows potential for stress and anxiety reduction in children with ASD.

Purpose: To predict the session rating of perceived exertion (sRPE) in soccer and determine its main predictive indicators., Methods: A total of 70 external-load indicators (ELIs), internal-load indicators, individual characteristics, and supplementary variables were used to build a predictive model., Results: The analysis using gradient-boosting machines showed a mean absolute error of 0.67 (0.09) arbitrary units (AU) and a root-mean-square error of 0.93 (0.16) AU. ELIs were found to be the strongest predictors of the sRPE, accounting for 61.5% of the total normalized importance (NI), with total distance as the strongest predictor. The included internal-load indicators and individual characteristics accounted only for 1.0% and 4.5%, respectively, of the total NI. Predictive accuracy improved when including supplementary variables such as group-based sRPE predictions (10.5% of NI), individual deviation variables (5.8% of NI), and individual player markers (17.0% of NI)., Conclusions: The results showed that the sRPE can be predicted quite accurately using only a relatively limited number of training observations. ELIs are the strongest predictors of the sRPE. However, it is useful to include a broad range of variables other than ELIs, because the accumulated importance of these variables accounts for a reasonable component of the total NI. Applications resulting from predictive modeling of the sRPE can help coaching staff plan, monitor, and evaluate both the external and internal training load.

Background: Mobile apps generate vast amounts of user data. In the mobile health (mHealth) domain, researchers are increasingly discovering the opportunities of log data to assess the usage of their mobile apps. To date, however, the analysis of these data are often limited to descriptive statistics. Using data mining techniques, log data can offer significantly deeper insights., Objective: The purpose of this study was to assess how Markov Chain and sequence clustering analysis can be used to find meaningful usage patterns of mHealth apps., Methods: Using the data of a 25-day field trial (n=22) of the Start2Cycle app, an app developed to encourage recreational cycling in adults, a transition matrix between the different pages of the app was composed. From this matrix, a Markov Chain was constructed, enabling intuitive user behavior analysis., Results: Through visual inspection of the transitions, 3 types of app use could be distinguished (route tracking, gamification, and bug reporting). Markov Chain-based sequence clustering was subsequently used to demonstrate how clusters of session types can otherwise be obtained., Conclusions: Using Markov Chains to assess in-app navigation presents a sound method to evaluate use of mHealth interventions. The insights can be used to evaluate app use and improve user experience., (©Jeroen Stragier, Gilles Vandewiele, Paulien Coppens, Femke Ongenae, Wendy Van den Broeck, Filip De Turck, Lieven De Marez. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 07.06.2019.)

Introduction: Blood cultures are often performed in the intensive care unit (ICU) to detect bloodstream infections and identify pathogen type, further guiding treatment. Early detection is essential, as a bloodstream infection can give cause to sepsis, a severe immune response associated with an increased risk of organ failure and death., Problem Statement: The early clinical detection of a bloodstream infection is challenging but rapid targeted treatment, within the first place antimicrobials, substantially increases survival chances. As blood cultures require time to incubate, early clinical detection using physiological signals combined with indicative lab values is pivotal., Objective: In this work, a novel method is constructed and explored for the potential prediction of the outcome of a blood culture test. The approach is based on a temporal computational model which uses nine clinical parameters measured over time., Methodology: We use a bidirectional long short-term memory neural network, a type of recurrent neural network well suited for tasks where the time lag between a predictive event and outcome is unknown. Evaluation is performed using a novel high-quality database consisting of 2177 ICU admissions at the Ghent University Hospital located in Belgium., Results: The network achieves, on average, an area under the receiver operating characteristic curve of 0.99 and an area under the precision-recall curve of 0.82. In addition, our results show that predicting several hours upfront is possible with only a small decrease in predictive power. In this setting, it outperforms traditional non-temporal, machine learning models., Conclusion: Our proposed computational model accurately predicts the outcome of blood culture tests using nine clinical parameters. Moreover, it can be used in the ICU as an early warning system to detect patients at risk of blood stream infection., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The Internet-of-Things (IoT) and Smart Cities continue to expand at enormous rates. Centralized Cloud architectures cannot sustain the requirements imposed by IoT services. Enormous traffic demands and low latency constraints are among the strictest requirements, making cloud solutions impractical. As an answer, Fog Computing has been introduced to tackle this trend. However, only theoretical foundations have been established and the acceptance of its concepts is still in its early stages. Intelligent allocation decisions would provide proper resource provisioning in Fog environments. In this article, a Fog architecture based on Kubernetes, an open source container orchestration platform, is proposed to solve this challenge. Additionally, a network-aware scheduling approach for container-based applications in Smart City deployments has been implemented as an extension to the default scheduling mechanism available in Kubernetes. Last but not least, an optimization formulation for the IoT service problem has been validated as a container-based application in Kubernetes showing the full applicability of theoretical approaches in practical service deployments. Evaluations have been performed to compare the proposed approaches with the Kubernetes standard scheduling feature. Results show that the proposed approaches achieve reductions of 70% in terms of network latency when compared to the default scheduling mechanism., Competing Interests: The authors declare no conflict of interest.

FLOWERING LOCUS T (FT) plays a major role in regulating the floral transition in response to an inductive long day photoperiod in Arabidopsis thaliana. Expression of FT in leaves is dependent on the distal transcriptional enhancer Block C, located 5-kilobases (kb) upstream of the transcriptional start site (TSS). We expressed an inverted repeat of Block C to induce local DNA methylation and heterochromatin formation, which lead to FT downregulation in an inductive photoperiod. Using targeted DNA methylation as a tool to uncover further regulatory regions at the FT locus, we identified Block E, located 1 kb downstream of the gene, as a novel enhancer of FT. As Block C, Block E is conserved across Brassicaceae and located in accessible chromatin. Block C and E act as additive transcriptional enhancers that, in combination with the proximal FT promoter, control expression of FT in response to photoperiod in the leaf phloem.

Background: Headache disorders are an important health burden, having a large health-economic impact worldwide. Current treatment & follow-up processes are often archaic, creating opportunities for computer-aided and decision support systems to increase their efficiency. Existing systems are mostly completely data-driven, and the underlying models are a black-box, deteriorating interpretability and transparency, which are key factors in order to be deployed in a clinical setting., Methods: In this paper, a decision support system is proposed, composed of three components: (i) a cross-platform mobile application to capture the required data from patients to formulate a diagnosis, (ii) an automated diagnosis support module that generates an interpretable decision tree, based on data semantically annotated with expert knowledge, in order to support physicians in formulating the correct diagnosis and (iii) a web application such that the physician can efficiently interpret captured data and learned insights by means of visualizations., Results: We show that decision tree induction techniques achieve competitive accuracy rates, compared to other black- and white-box techniques, on a publicly available dataset, referred to as migbase. Migbase contains aggregated information of headache attacks from 849 patients. Each sample is labeled with one of three possible primary headache disorders. We demonstrate that we are able to reduce the classification error, statistically significant (ρ≤0.05), with more than 10% by balancing the dataset using prior expert knowledge. Furthermore, we achieve high accuracy rates by using features extracted using the Weisfeiler-Lehman kernel, which is completely unsupervised. This makes it an ideal approach to solve a potential cold start problem., Conclusion: Decision trees are the perfect candidate for the automated diagnosis support module. They achieve predictive performances competitive to other techniques on the migbase dataset and are, foremost, completely interpretable. Moreover, the incorporation of prior knowledge increases both predictive performance as well as transparency of the resulting predictive model on the studied dataset.

In the Internet of Things (IoT), multiple sensors and devices are generating heterogeneous streams of data. To perform meaningful analysis over multiple of these streams, stream processing needs to support expressive reasoning capabilities to infer implicit facts and temporal reasoning to capture temporal dependencies. However, current approaches cannot perform the required reasoning expressivity while detecting time dependencies over high frequency data streams. There is still a mismatch between the complexity of processing and the rate data is produced in volatile domains. Therefore, we introduce Streaming MASSIF, a Cascading Reasoning approach performing expressive reasoning and complex event processing over high velocity streams. Cascading Reasoning is a vision that solves the problem of expressive reasoning over high frequency streams by introducing a hierarchical approach consisting of multiple layers. Each layer minimizes the processed data and increases the complexity of the data processing. Cascading Reasoning is a vision that has not been fully realized. Streaming MASSIF is a layered approach allowing IoT service to subscribe to high-level and temporal dependent concepts in volatile data streams. We show that Streaming MASSIF is able to handle high velocity streams up to hundreds of events per second, in combination with expressive reasoning and complex event processing. Streaming MASSIF realizes the Cascading Reasoning vision and is able to combine high expressive reasoning with high throughput of processing. Furthermore, we formalize semantically how the different layers in our Cascading Reasoning Approach collaborate.

In hospitals and smart nursing homes, ambient-intelligent care rooms are equipped with many sensors. They can monitor environmental and body parameters, and detect wearable devices of patients and nurses. Hence, they continuously produce data streams. This offers the opportunity to collect, integrate and interpret this data in a context-aware manner, with a focus on reactivity and autonomy. However, doing this in real time on huge data streams is a challenging task. In this context, cascading reasoning is an emerging research approach that exploits the trade-off between reasoning complexity and data velocity by constructing a processing hierarchy of reasoners. Therefore, a cascading reasoning framework is proposed in this paper. A generic architecture is presented allowing to create a pipeline of reasoning components hosted locally, in the edge of the network, and in the cloud. The architecture is implemented on a pervasive health use case, where medically diagnosed patients are constantly monitored, and alarming situations can be detected and reacted upon in a context-aware manner. A performance evaluation shows that the total system latency is mostly lower than 5 s, allowing for responsive intervention by a nurse in alarming situations. Using the evaluation results, the benefits of cascading reasoning for healthcare are analyzed.

The arbuscular mycorrhizal (AM) symbiosis, a widespread mutualistic association between land plants and fungi, depends on reciprocal exchange of phosphorus driven by proton-coupled phosphate uptake into host plants and carbon supplied to AM fungi by host-dependent sugar and lipid biosynthesis. The molecular mechanisms and cis -regulatory modules underlying the control of phosphate uptake and de novo fatty acid synthesis in AM symbiosis are poorly understood. Here, we show that the AP2 family transcription factor CTTC MOTIF-BINDING TRANSCRIPTION FACTOR1 (CBX1), a WRINKLED1 (WRI1) homolog, directly binds the evolutionary conserved CTTC motif that is enriched in mycorrhiza-regulated genes and activates Lotus japonicus phosphate transporter 4 ( LjPT4 ) in vivo and in vitro. Moreover, the mycorrhiza-inducible gene encoding H + -ATPase ( LjHA1 ), implicated in energizing nutrient uptake at the symbiotic interface across the periarbuscular membrane, is coregulated with LjPT4 by CBX1. Accordingly, CBX1 -defective mutants show reduced mycorrhizal colonization. Furthermore, genome-wide-binding profiles, DNA-binding studies, and heterologous expression reveal additional binding of CBX1 to AW box, the consensus DNA-binding motif for WRI1, that is enriched in promoters of glycolysis and fatty acid biosynthesis genes. We show that CBX1 activates expression of lipid metabolic genes including glycerol-3-phosphate acyltransferase RAM2 implicated in acylglycerol biosynthesis. Our finding defines the role of CBX1 as a regulator of host genes involved in phosphate uptake and lipid synthesis through binding to the CTTC/AW molecular module, and supports a model underlying bidirectional exchange of phosphorus and carbon, a fundamental trait in the mutualistic AM symbiosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Polycomb repressive complexes (PRCs) control organismic development in higher eukaryotes through epigenetic gene repression 1-4 . PRC proteins do not contain DNA-binding domains, thus prompting questions regarding how PRCs find their target loci 5 . Here we present genome-wide evidence of PRC2 recruitment by telomere-repeat-binding factors (TRBs) through telobox-related motifs in Arabidopsis. A triple trb1-2, trb2-1, and trb3-2 (trb1/2/3) mutant with a developmental phenotype and a transcriptome strikingly similar to those of strong PRC2 mutants showed redistribution of trimethyl histone H3 Lys27 (H3K27me3) marks and lower H3K27me3 levels, which were correlated with derepression of TRB1-target genes. TRB1-3 physically interacted with the PRC2 proteins CLF and SWN. A SEP3 reporter gene with a telobox mutation showed ectopic expression, which was correlated with H3K27me3 depletion, whereas tethering TRB1 to the mutated cis element partially restored repression. We propose that telobox-related motifs recruit PRC2 through the interaction between TRBs and CLF/SWN, a mechanism essential for H3K27me3 deposition at a subset of target genes.

In 2013, the Flemish Government launched the Vitalink platform. This initiative focuses on the sharing of health and welfare data to support primary healthcare. In this paper, the objectives and mission of the Vitalink initiative are discussed. Security and privacy measures are reviewed, and the technical implementation of the Vitalink platform is presented. Through a case study, the possibility of interaction with cloud solutions for healthcare is also investigated upon; this was initially not the focus of Vitalink. The Vitalink initiative provides support for secure data sharing in primary healthcare, which in the long term will improve the efficiency of care and will decrease costs. Based on the results of the case study, Vitalink allowed cloud solutions or applications not providing end-to-end security to use their system. The most important lesson learned during this research was the need for firm regulations and stipulations for cloud solutions to interact with the Vitalink platform. However, these are currently still vague.

Fog computing extends the cloud computing paradigm by placing resources close to the edges of the network to deal with the upcoming growth of connected devices. Smart city applications, such as health monitoring and predictive maintenance, will introduce a new set of stringent requirements, such as low latency, since resources can be requested on-demand simultaneously by multiple devices at different locations. It is then necessary to adapt existing network technologies to future needs and design new architectural concepts to help meet these strict requirements. This article proposes a fog computing framework enabling autonomous management and orchestration functionalities in 5G-enabled smart cities. Our approach follows the guidelines of the European Telecommunications Standards Institute (ETSI) NFV MANO architecture extending it with additional software components. The contribution of our work is its fully-integrated fog node management system alongside the foreseen application layer Peer-to-Peer (P2P) fog protocol based on the Open Shortest Path First (OSPF) routing protocol for the exchange of application service provisioning information between fog nodes. Evaluations of an anomaly detection use case based on an air monitoring application are presented. Our results show that the proposed framework achieves a substantial reduction in network bandwidth usage and in latency when compared to centralized cloud solutions., Competing Interests: The authors declare no conflict of interest.

Background: While most cells in multicellular organisms carry the same genetic information, in each cell type only a subset of genes is being transcribed. Such differentiation in gene expression depends, for a large part, on the activation and repression of regulatory sequences, including transcriptional enhancers. Transcriptional enhancers can be located tens of kilobases from their target genes, but display characteristic chromatin and DNA features, allowing their identification by genome-wide profiling. Here we show that integration of chromatin characteristics can be applied to predict distal enhancer candidates in Zea mays, thereby providing a basis for a better understanding of gene regulation in this important crop plant., Result: To predict transcriptional enhancers in the crop plant maize (Zea mays L. ssp. mays), we integrated available genome-wide DNA methylation data with newly generated maps for chromatin accessibility and histone 3 lysine 9 acetylation (H3K9ac) enrichment in young seedling and husk tissue. Approximately 1500 intergenic regions, displaying low DNA methylation, high chromatin accessibility and H3K9ac enrichment, were classified as enhancer candidates. Based on their chromatin profiles, candidate sequences can be classified into four subcategories. Tissue-specificity of enhancer candidates is defined based on the tissues in which they are identified and putative target genes are assigned based on tissue-specific expression patterns of flanking genes., Conclusions: Our method identifies three previously identified distal enhancers in maize, validating the new set of enhancer candidates and enlarging the toolbox for the functional characterization of gene regulation in the highly repetitive maize genome.

Background: Polycomb group complexes PRC1 and PRC2 repress gene expression at the chromatin level in eukaryotes. The classic recruitment model of Polycomb group complexes in which PRC2-mediated H3K27 trimethylation recruits PRC1 for H2A monoubiquitination was recently challenged by data showing that PRC1 activity can also recruit PRC2. However, the prevalence of these two mechanisms is unknown, especially in plants as H2AK121ub marks were examined at only a handful of Polycomb group targets., Results: By using genome-wide analyses, we show that H2AK121ub marks are surprisingly widespread in Arabidopsis thaliana, often co-localizing with H3K27me3 but also occupying a set of transcriptionally active genes devoid of H3K27me3. Furthermore, by profiling H2AK121ub and H3K27me3 marks in atbmi1a/b/c, clf/swn, and lhp1 mutants we found that PRC2 activity is not required for H2AK121ub marking at most genes. In contrast, loss of AtBMI1 function impacts the incorporation of H3K27me3 marks at most Polycomb group targets., Conclusions: Our findings show the relationship between H2AK121ub and H3K27me3 marks across the A. thaliana genome and unveil that ubiquitination by PRC1 is largely independent of PRC2 activity in plants, while the inverse is true for H3K27 trimethylation.

The medical staff in a hospital could benefit from a specialized task management system, considering their high workload covering different patients. This article presents an intelligent task management platform that automatically prioritizes and (re-)assigns tasks to the appropriate caregivers based on the current health care context captured in a continuous care ontology. Moreover, this platform provides the caregivers with a smartphone allowing them to easily view and process their assigned tasks.

Objectives: With the uprise of the Internet of Things, wearables and smartphones are moving to the foreground. Ambient Assisted Living solutions are, for example, created to facilitate ageing in place. One example of such systems are fall detection systems. Currently, there exists a wide variety of fall detection systems using different methodologies and technologies. However, these systems often do not take into account the fall handling process, which starts after a fall is identified or this process only consists of sending a notification. The FallRisk system delivers an accurate analysis of incidents occurring in the home of the older adults using several sensors and smart devices. Moreover, the input from these devices can be used to create a social-aware event handling process, which leads to assisting the older adult as soon as possible and in the best possible way., Methods: The FallRisk system consists of several components, located in different places. When an incident is identified by the FallRisk system, the event handling process will be followed to assess the fall incident and select the most appropriate caregiver, based on the input of the smartphones of the caregivers. In this process, availability and location are automatically taken into account., Results: The event handling process was evaluated during a decision tree workshop to verify if the current day practices reflect the requirements of all the stakeholders. Other knowledge, which is uncovered during this workshop can be taken into account to further improve the process., Conclusions: The FallRisk offers a way to detect fall incidents in an accurate way and uses context information to assign the incident to the most appropriate caregiver. This way, the consequences of the fall are minimized and help is at location as fast as possible. It could be concluded that the current guidelines on fall handling reflect the needs of the stakeholders. However, current technology evolutions, such as the uptake of wearables and smartphones, enables the improvement of these guidelines, such as the automatic ordering of the caregivers based on their location and availability.