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Nilakash Das,1 Marko Topalovic,1 Jean-Marie Aerts,2 Wim Janssens1 1Laboratory of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing, Katholieke Universiteit Leuven, Leuven, Belgium; 2Division of Animal and Human Health Engineering, Department of Biosystems, Katholieke Universiteit Leuven, Leuven, Belgium Background: Severe hyperinflation causes detrimental effects such as dyspnea and reduced exercise capacity and is an independent predictor of mortality in COPD patients. Static lung volumes are required to diagnose severe hyperinflation, which are not always accessible in primary care. Several studies have shown that the area under the forced expiratory flow-volume loop (AreaFE) is highly sensitive to bronchodilator response and is correlated with residual volume/total lung capacity (RV/TLC), a common index of air trapping. In this study, we investigate the role of AreaFE% (AreaFE expressed as a percentage of reference value) and conventional spirometry parameters in indicating severe hyperinflation. Materials and methods: We used a cohort of 215 individuals with COPD. The presence of severe hyperinflation was defined as elevated air trapping (RV/TLC >60%) or reduced inspiratory fraction (inspiratory capacity [IC]/TLC 60% and IC/TLC

Background: The presence of decoupling, i.e. the absence of coupling between fundamental frequency variation and intensity contour during phonetic crying, and its extent, reflects the degree of maturation of the central nervous system.Objectives: The aim of this work was to evaluate whether Empirical Mode Decomposition (EMD) is a suitable technique for analyzing infant cries. We hereby wanted to assess the existence and extent of decoupling in term neonates and whether an association between decoupling (derived from EMD) and clinical pain expression could be unveiled.Methods: To assess decoupling in healthy term neonates during procedural pain, 24 newborns were videotaped and crying was recorded during venous blood sampling. Besides acoustic analysis, pain expression was quantified based on the Modified Behavioral Pain Scale (MBPS). Fundamental frequency and the intensity contour of the cry signals were extracted by applying the EMD to the data, and the correlation between the two was studied.Results: Based on data collected in healthy term neonates, correlation coefficients varied between 0.39 and 0.83. The degree of decoupling displayed extended variability between the neonates and also in different cry bouts in a crying sequence within an individual neonate.Conclusion: When considering the individual ratio between the mean correlation of cry bouts during a crying sequence and their standard deviation, there seems to be a positive trend with increasing MBPS value. This might indicate that higher stressed subjects have less consistency in the investigated acoustic cry features, concluding that EMD has potential in the assessment of infant cry analysis. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate clinical utility of 2D-markerless motion analysis (2DMMA) from a single camera during a reaching-sideways-task in individuals with dyskinetic cerebral palsy (DCP) by determining (1) concurrent validity by correlating 2DMMA against marker-based 3D-motion analysis (3DMA) and (2) construct validity by assessing differences in 2DMMA features between DCP and typically developing (TD) peers. 2DMMA key points were tracked from frontal videos of a single camera by DeepLabCut and accuracy was assessed against human labelling. Shoulder, elbow and wrist angles were calculated from 2DMMA and 3DMA (as gold standard) and correlated to assess concurrent validity. Additionally, execution time and variability features such as mean point-wise standard deviation of the angular trajectories (i.e. shoulder elevation, elbow and wrist flexion/extension) and wrist trajectory deviation by mean overshoot and convex hull were calculated from key points. 2DMMA features were compared between the DCP group and TD peers to assess construct validity. Fifty-one individuals (30 DCP;21 TD; age:5-24 years) participated. An accuracy of approximately 1.5 cm was reached for key point tracking. While significant correlations were found for wrist (ρ = 0.810;p < 0.001) and elbow angles (ρ = 0.483;p < 0.001), 2DMMA shoulder angles were not correlated (ρ = 0.247;p = 0.102) to 3DMA. Wrist and elbow angles, execution time and variability features all differed between groups (Effect sizes 0.35-0.81;p < 0.05). Videos of a reaching-sideways-task processed by 2DMMA to assess upper extremity movements in DCP showed promising validity. The method is especially valuable to assess movement variability., 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 Elsevier Ltd. All rights reserved.)

Background: Movement disorders in children and adolescents with dyskinetic cerebral palsy (CP) are commonly assessed from video recordings, however scoring is time-consuming and expert knowledge is required for an appropriate assessment., Objective: To explore a machine learning approach for automated classification of amplitude and duration of distal leg dystonia and choreoathetosis within short video sequences., Methods: Available videos of a heel-toe tapping task were preprocessed to optimize key point extraction using markerless motion analysis. Postprocessed key point data were passed to a time series classification ensemble algorithm to classify dystonia and choreoathetosis duration and amplitude classes (scores 0, 1, 2, 3, and 4), respectively. As ground truth clinical scoring of dystonia and choreoathetosis by the Dyskinesia Impairment Scale was used. Multiclass performance metrics as well as metrics for summarized scores: absence (score 0) and presence (score 1-4) were determined., Results: Thirty-three participants were included: 29 with dyskinetic CP and 4 typically developing, age 14 years:6 months ± 5 years:15 months. The multiclass accuracy results for dystonia were 77% for duration and 68% for amplitude; for choreoathetosis 30% for duration and 38% for amplitude. The metrics for score 0 versus score 1 to 4 revealed an accuracy of 81% for dystonia duration, 77% for dystonia amplitude, 53% for choreoathetosis duration and amplitude., Conclusions: This methodology study yielded encouraging results in distinguishing between presence and absence of dystonia, but not for choreoathetosis. A larger dataset is required for models to accurately represent distinct classes/scores. This study presents a novel methodology of automated assessment of movement disorders solely from video data., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective. The fact that ramp incremental exercise yields quasi-linear responses for pulmonary oxygen uptake (V˙O2) and heart rate (HR) seems contradictory to the well-known non-linear behavior of underlying physiological processes. Prior research highlights this issue and demonstrates how a balancing of system gain and response time parameters causes linearV˙O2responses during ramp tests. This study builds upon this knowledge and extracts the time-varying dynamics directly from HR andV˙O2data of single ramp incremental running tests. Approach. A large-scale open access dataset of 735 ramp incremental running tests is analyzed. The dynamics are obtained by means of 1st order autoregressive and exogenous models with time-variant parameters. This allows for the estimates of time constant ( τ ) and steady state gain (SSG) to vary with work rate. Main results. As the work rate increases, τ -values increase on average from 38 to 132 s for HR, and from 27 to 35 s forV˙O2. Both increases are statistically significant ( p < 0.01). Further, SSG-values decrease on average from 14 to 9 bpm (km·h -1 ) -1 for HR, and from 218 to 144 ml·min -1 forV˙O2( p < 0.01 for decrease parameters of HR andV˙O2). The results of this modeling approach are line with literature reporting on cardiorespiratory dynamics obtained using standard procedures. Significance. We show that time-variant modeling is able to determine the time-varying dynamics HR andV˙O2responses to ramp incremental running directly from individual tests. The proposed method allows for gaining insights into the cardiorespiratory response characteristics when no repeated measurements are available., (© 2024 Institute of Physics and Engineering in Medicine.)

Introduction: Impaired upper limb movements are a key feature in dyskinetic cerebral palsy (CP). However, information on how specific movement patterns relate to manual ability, performance and underlying movement disorders is lacking. Insight in these associations may contribute to targeted upper limb management in dyskinetic CP. This study aimed to explore associations between deviant upper limb movement patterns and (1) manual ability, (2) severity of dystonia/choreoathetosis, and (3) movement time/trajectory deviation during reaching and grasping., Participants/methods: Participants underwent three-dimensional upper limb analysis during reaching forwards (RF), reaching sideways (RS) and reach-and-grasp vertical (RGV) as well as clinical assessment. Canonical correlation and regression analysis with statistical parametric mapping were used to explore associations between clinical/performance parameters and movement patterns (mean and variability)., Results: Thirty individuals with dyskinetic CP participated (mean age 16±5 y; 20 girls). Lower manual ability was related to higher variability in wrist flexion/extension during RF and RS early in the reaching cycle (p < 0.05). Higher dystonia severity was associated with higher mean wrist flexion (40-82 % of the reaching cycle; p = 0.004) and higher variability in wrist flexion/extension (31-75 %; p < 0.001) and deviation (2-14 %; p = 0.007/60-73 %; p = 0.006) during RF. Choreoathetosis severity was associated with higher elbow pro/supination variability (12-19 %; p = 0.009) during RGV. Trajectory deviation was associated with wrist and elbow movement variability (p < 0.05)., Conclusion: Current novel analysis of upper limb movement patterns and respective timings allows to detect joint angles and periods in the movement cycle wherein associations with clinical parameters occur. These associations are not present at each joint level, nor during the full movement cycle. This knowledge should be considered for individualized treatment strategies., 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., (© 2024 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

Background: Despite being the gold-standard method for objectively assessing sleep, polysomnography (PSG) faces several limitations as it is expensive, time-consuming, and labor-intensive; requires various equipment and technical expertise; and is impractical for long-term or in-home use. Consumer wrist-worn wearables are able to monitor sleep parameters and thus could be used as an alternative for PSG. Consequently, wearables gained immense popularity over the past few years, but their accuracy has been a major concern., Objective: A systematic review of the literature was conducted to appraise the performance of 3 recent-generation wearable devices (Fitbit Charge 4, Garmin Vivosmart 4, and WHOOP) in determining sleep parameters and sleep stages., Methods: Per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, a comprehensive search was conducted using the PubMed, Web of Science, Google Scholar, Scopus, and Embase databases. Eligible publications were those that (1) involved the validity of sleep data of any marketed model of the candidate wearables and (2) used PSG or an ambulatory electroencephalogram monitor as a reference sleep monitoring device. Exclusion criteria were as follows: (1) incorporated a sleep diary or survey method as a reference, (2) review paper, (3) children as participants, and (4) duplicate publication of the same data and findings., Results: The search yielded 504 candidate articles. After eliminating duplicates and applying the eligibility criteria, 8 articles were included. WHOOP showed the least disagreement relative to PSG and Sleep Profiler for total sleep time (-1.4 min), light sleep (-9.6 min), and deep sleep (-9.3 min) but showed the largest disagreement for rapid eye movement (REM) sleep (21.0 min). Fitbit Charge 4 and Garmin Vivosmart 4 both showed moderate accuracy in assessing sleep stages and total sleep time compared to PSG. Fitbit Charge 4 showed the least disagreement for REM sleep (4.0 min) relative to PSG. Additionally, Fitbit Charge 4 showed higher sensitivities to deep sleep (75%) and REM sleep (86.5%) compared to Garmin Vivosmart 4 and WHOOP., Conclusions: The findings of this systematic literature review indicate that the devices with higher relative agreement and sensitivities to multistate sleep (ie, Fitbit Charge 4 and WHOOP) seem appropriate for deriving suitable estimates of sleep parameters. However, analyses regarding the multistate categorization of sleep indicate that all devices can benefit from further improvement in the assessment of specific sleep stages. Although providers are continuously developing new versions and variants of wearables, the scientific research on these wearables remains considerably limited. This scarcity in literature not only reduces our ability to draw definitive conclusions but also highlights the need for more targeted research in this domain. Additionally, future research endeavors should strive for standardized protocols including larger sample sizes to enhance the comparability and power of the results across studies., (© An-Marie Schyvens, Nina Catharina Van Oost, Jean-Marie Aerts, Federica Masci, Brent Peters, An Neven, Hélène Dirix, Geert Wets, Veerle Ross, Johan Verbraecken. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org).)

Background: Digital technologies are increasingly being used to deliver health care services and promote public health. Mobile wireless technologies or mobile health (mHealth) technologies are particularly relevant owing to their ease of use, broad reach, and wide acceptance. Unlike developed countries, Sub-Saharan Africa experiences more challenges and obstacles when it comes to deploying, using, and expanding mHealth systems. In addition to barriers, there are enabling factors that could be exploited for the design, implementation, and scaling up of mHealth systems. Sub-Saharan Africa may require tailored solutions that address the specific challenges facing the region., Objective: The overall aim of this study was to identify the barriers and enablers for using mHealth systems in Sub-Saharan Africa from the perspectives of patients, physicians, and health care executives., Methods: Multi-level and multi-actor in-depth semistructured interviews were employed to qualitatively explore the barriers and enablers of the use of mHealth systems. Data were collected from patients, physicians, and health care executives. The interviews were audio recorded, transcribed verbatim, translated, and coded. Thematic analysis methodology was adopted, and NVivo software was used for the data analysis., Results: Through this rigorous study, a total of 137 determinants were identified. Of these determinants, 68 were identified as barriers and 69 were identified as enablers. Perceived barriers in patients included lack of awareness about mHealth systems and language barriers. Perceived enablers in patients included need for automated tools for health monitoring and an increasing literacy level of the society. According to physicians, barriers included lack of available digital health systems in the local context and concern about patients' mHealth capabilities, while enablers included the perceived usefulness in reducing workload and improving health care service quality, as well as the availability of mobile devices and the internet. As perceived by health care executives, barriers included competing priorities alongside digitalization in the health sector and lack of interoperability and complete digitalization of implemented digital health systems, while enablers included the perceived usefulness of digitalization for the survival of the highly overloaded health care system and the abundance of educated manpower specializing in technology., Conclusions: mHealth systems in Sub-Saharan Africa are hindered and facilitated by various factors. Common barriers and enablers were identified by patients, physicians, and health care executives. To promote uptake, all relevant stakeholders must actively mitigate the barriers. This study identified a promising outlook for mHealth in Sub-Saharan Africa, despite the present barriers. Opportunities exist for successful integration into health care systems, and a user-centered design is crucial for maximum uptake., (©Genet Tadese Aboye, Gizeaddis Lamesgin Simegn, Jean-Marie Aerts. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 27.03.2024.)

Background: Dyskinetic cerebral palsy (DCP) is clinically characterized by involuntary movements and abnormal postures, which can aggravate with activity. While upper limb movement variability is often detected in the clinical picture, it remains unknown how movement patterns of individuals with DCP differ from typically developing (TD) peers., Research Question: Do individuals with DCP show i) higher time-dependent standard deviations of upper limb joint angles and ii) altered upper limb kinematics in time and/or amplitude during functional upper limb tasks in comparison with TD individuals?, Methods: Three-dimensional upper limb movement patterns were cross-sectionally compared in 50 individuals with and without DCP during three functional tasks: reach forward (RF), reach and grasp vertical (RGV) and reach sideways (RS). Mean and point-wise standard deviations of angular waveform of the upper limb joint angles were compared between groups to evaluate differences in time and/or amplitude using traditional and non-linear registration statistical parametric mapping., Results: Thirty-five extremities from 30 individuals (mean age 17y4m, range 5-25 y; MACS level I(n = 2); II(n = 15); III(n = 16); IV(n = 2)) with DCP and twenty TD individuals (mean age 16y8m, range 8-25 y) were evaluated. The DCP compared to TD group showed higher point-wise standard deviations at the level of all joints, which was time-dependent and varied between tasks. Mean wrist and elbow flexion was higher for the DCP group during RF (0-83 % wrist; 57-100 % elbow), RGV (0-82 % wrist; 12-100 % elbow) and RS (0-43 % wrist; 70-100 % elbow)., Significance: This is the first study exploring the movement patterns of individuals with DCP during reaching using quantitative measures. Analyzing these individual movement patterns by statistical parametric mapping (SPM) allows us to focus on both specific joint or on specific timing during the movement cycle. The individual information that this method yields can guide individual therapy aiming to improve reaching function in different parts of the movement cycle or evaluate intervention effects on upper extremity treatment., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In Gaucher disease (GD), a relatively common sphingolipidosis, the mutant lysosomal enzyme acid β-glucocerebrosidase (GCase), encoded by the GBA1 gene, fails to properly hydrolyze the sphingolipid glucosylceramide (GlcCer) in lysosomes, particularly of tissue macrophages. As a result, GlcCer accumulates, which, to a certain extent, is converted to its deacylated form, glucosylsphingosine (GlcSph), by lysosomal acid ceramidase. The inability of mutant GCase to degrade GlcSph further promotes its accumulation. The amount of mutant GCase in lysosomes depends on the amount of mutant ER enzyme that shuttles to them. In the case of many mutant GCase forms, the enzyme is largely misfolded in the ER. Only a fraction correctly folds and is subsequently trafficked to the lysosomes, while the rest of the misfolded mutant GCase protein undergoes ER-associated degradation (ERAD). The retention of misfolded mutant GCase in the ER induces ER stress, which evokes a stress response known as the unfolded protein response (UPR). GD is remarkably heterogeneous in clinical manifestation, including the variant without CNS involvement (type 1), and acute and subacute neuronopathic variants (types 2 and 3). The present review discusses animal models developed to study the molecular and cellular mechanisms underlying GD.

Background: mHealth can help with healthcare service delivery for various health issues, but there's a significant gap in the availability and use of mHealth systems between sub-Saharan Africa and Europe, despite the ongoing digitalization of the global healthcare system., Objective: This work aims to compare and investigate the use and availability of mHealth systems in sub-Saharan Africa and Europe, and identify gaps in current mHealth development and implementation in both regions., Methods: The study adhered to the PRISMA 2020 guidelines for article search and selection to ensure an unbiased comparison between sub-Saharan Africa and Europe. Four databases (Scopus, Web of Science, IEEE Xplore, and PubMed) were used, and articles were evaluated based on predetermined criteria. Details on the mHealth system type, goal, patient type, health concern, and development stage were collected and recorded in a Microsoft Excel worksheet., Results: The search query produced 1020 articles for sub-Saharan Africa and 2477 articles for Europe. After screening for eligibility, 86 articles for sub-Saharan Africa and 297 articles for Europe were included. To minimize bias, two reviewers conducted the article screening and data retrieval. Sub-Saharan Africa used SMS and call-based mHealth methods for consultation and diagnosis, mainly for young patients such as children and mothers, and for issues such as HIV, pregnancy, childbirth, and child care. Europe relied more on apps, sensors, and wearables for monitoring, with the elderly as the most common patient group, and the most common health issues being cardiovascular disease and heart failure., Conclusion: Wearable technology and external sensors are heavily used in Europe, whereas they are seldom used in sub-Saharan Africa. More efforts should be made to use the mHealth system to improve health outcomes in both regions, incorporating more cutting-edge technologies like wearables internal and external sensors. Undertaking context-based studies, identifying determinants of mHealth systems use, and considering these determinants during mHealth system design could enhance mHealth availability and utilization., (© The Author(s) 2023.)

Introduction: The advent of digital systems and global mobile phone availability presents an opportunity for better healthcare access and equity. However, the disparity in the usage and availability of mHealth systems between Europe and Sub-Saharan Africa (SSA) has not been explored in relation to current health, healthcare status, and demographics., Objective: This study aimed to compare mHealth system availability and use in SSA and Europe in the above-mentioned context., Methods: The study analyzed health, healthcare status, and demographics in both regions. It assessed mortality, disease burden, and universal health coverage. A systematic narrative review was conducted to thoroughly assess available data on mHealth availability and use, guiding future research in the field., Results: SSA is on the verge of stages 2 and 3 in the demographic transition with a youthful population and high birth rate. Communicable, maternal, neonatal, and nutritional diseases contribute to high mortality and disease burden, including child mortality. Europe is on the verge of stages 4 and 5 in the demographic transition with low birth and death rates. Europe's population is old, and non-communicable diseases (NCDs) pose major health challenges. The mHealth literature adequately covers cardiovascular disease/heart failure, and cancer. However, it lacks approaches for respiratory/enteric infections, malaria, and NCDs., Conclusions: mHealth systems in SSA are underutilized than in Europe, despite alignment with the region's demographics and major health issues. Most initiatives in SSA lack implementation depth, with only pilot tests or small-scale implementations. Europe's reported cases highlight actual implementation and acceptability, indicating a strong implementation depth of mHealth systems., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Allergic rhinitis includes a certain degree of autonomic imbalance. However, no information is available on how daily changes in allergy burden affect autonomic imbalance. We aimed to estimate associations between daily allergy burden (allergy symptoms and mood) and daily heart rate characteristics (resting heart rate and sample entropy, both biomarkers of autonomic balance) of adults with allergic rhinitis, based on real-world measurements with a wearable telemonitoring system., Methods: Adults with a tree pollen allergy used a smartphone application to self-report daily allergy symptoms (score 0-44) and mood (score 0-4), and a Mio Alpha 2 wristwatch to collect heart rate characteristics during two pollen seasons of hazel, alder and birch in Belgium. Associations between daily allergy burden and heart rate characteristics were estimated using linear mixed effects distributed lag models with a random intercept for individuals and adjusted for potential confounders., Results: Analyses included 2497 participant-days of 72 participants. A one-point increase in allergy symptom score was associated with an increase in next-day resting heart rate of 0.08 (95% CI: 0.02-0.15) beats per minute. A one-point increase in mood score was associated with an increase in same-day sample entropy of 0.80 (95% CI: 0.34-1.26) × 10 -2 . No associations were found between allergy symptoms and heart rate sample entropy, nor between mood and resting heart rate., Conclusion: Daily repeated measurements with a wearable telemonitoring system revealed that the daily allergy burden of adults with allergic rhinitis has systemic effects beyond merely the respiratory system., (© 2023 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Objective: Continuous physiological measurements during a laboratory-based exercise test can provide physiological biomarkers, such as heart rate (HR) and oxygen uptake (V̇O 2 ) kinetics, that carry clinically relevant information. In contrast, it is not clear how continuous data generated by wearable devices during daily-life routines could provide meaningful biomarkers. We aimed to determine whether valid HR and V̇O 2 kinetics can be obtained from measurements with wearable devices during outdoor walks in patients with chronic obstructive pulmonary disease (COPD)., Methods: HR (Polar Belt) and V̇O 2 (METAMAX3B) were measured during 93 physical activity transitions performed by eight patients with COPD during three different outdoor walks (n tr  = 77) and a 6-minute walk test (n tr  = 16). HR and V̇O 2 kinetics were calculated every time a participant started a walk, finished a walk or walked upstairs. HR and V̇O 2 kinetics were considered valid if the response magnitude and model fit were adequate, and model parameters were reliable., Results: Continuous measurements with wearable devices provided valid HR kinetics when COPD patients started or finished (range 63%-100%) the different outdoor walks and valid V̇O 2 kinetics when they finished (range 63%-100%) an outdoor walk. The amount of valid kinetics and kinetic model performance was comparable between outdoor walks and a laboratory-based exercise test ( p  > .05)., Conclusion: We envision that the presented approach could improve telemonitoring applications of patients with COPD by providing regular, unsupervised assessments of HR kinetics during daily-life routines. This could allow to early identify a decline in the patients' dynamic physiological functioning, physical fitness and/or health status., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background -Movement patterns in dyskinetic cerebral palsy (DCP) are characterized by abnormal postures and involuntary movements. Current evaluation tools in DCP are subjective and time-consuming. Sensors could yield objective information on pathological patterns in DCP, but their reliability has not yet been evaluated. The objectives of this study were to evaluate (i) reliability and (ii) discriminative ability of sensor parameters. Methods -Inertial measurement units were placed on the arm, forearm, and hand of individuals with and without DCP while performing reach-forward, reach-and-grasp-vertical, and reach-sideways tasks. Intra-class correlation coefficients (ICC) were calculated for reliability, and Mann-Whitney U-tests for between-group differences. Results -Twenty-two extremities of individuals with DCP (mean age 16.7 y) and twenty individuals without DCP (mean age 17.2 y) were evaluated. ICC values for all sensor parameters except jerk and sample entropy ranged from 0.50 to 0.98 during reach forwards/sideways and from 0.40 to 0.95 during reach-and-grasp vertical. Jerk and maximal acceleration/angular velocity were significantly higher for the DCP group in comparison with peers. Conclusions -This study was the first to assess the reliability of sensor parameters in individuals with DCP, reporting high between- and within-session reliability for the majority of the sensor parameters. These findings suggest that pathological movements of individuals with DCP can be reliably captured using a selection of sensor parameters.

Thermal discomfort due to accumulated sweat increasing head skin wettedness may contribute to low wearing rates of bicycle helmets. Using curated data on human head sweating and helmet thermal properties, a modelling framework for the thermal comfort assessment of bicycle helmet use is proposed. Local sweat rates (LSR) at the head were predicted as the ratio to the gross sweat rate (GSR) of the whole body or by sudomotor sensitivity (SUD), the change in LSR per change in body core temperature (Δt re ). Combining those local models with Δt re and GSR output from thermoregulation models, we simulated head sweating depending on the characteristics of the thermal environment, clothing, activity, and exposure duration. Local thermal comfort thresholds for head skin wettedness were derived in relation to thermal properties of bicycle helmets. The modelling framework was supplemented by regression equations predicting the wind-related reductions in thermal insulation and evaporative resistance of the headgear and boundary air layer, respectively. Comparing the predictions of local models coupled with different thermoregulation models to LSR measured at the frontal, lateral and medial head under bicycle helmet use revealed a large spread in LSR predictions predominantly determined by the local models and the considered head region. SUD tended to overestimate frontal LSR but performed better for lateral and medial head regions, whereas predictions by LSR/GSR ratios were lower and agreed better with measured frontal LSR. However, even for the best models root mean squared prediction errors exceeded experimental SD by 18-30%. From the high correlation (R > 0.9) of skin wettedness comfort thresholds with local sweating sensitivity reported for different body regions, we derived a threshold value of 0.37 for head skin wettedness. We illustrate the application of the modelling framework using a commuter-cycling scenario, and discuss its potential as well as the needs for further research., Competing Interests: Declarations of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Studies aiming to objectively quantify movement disorders during upper limb tasks using wearable sensors have recently increased, but there is a wide variety in described measurement and analyzing methods, hampering standardization of methods in research and clinics. Therefore, the primary objective of this review was to provide an overview of sensor set-up and type, included tasks, sensor features and methods used to quantify movement disorders during upper limb tasks in multiple pathological populations. The secondary objective was to identify the most sensitive sensor features for the detection and quantification of movement disorders on the one hand and to describe the clinical application of the proposed methods on the other hand. Methods: A literature search using Scopus, Web of Science, and PubMed was performed. Articles needed to meet following criteria: 1) participants were adults/children with a neurological disease, 2) (at least) one sensor was placed on the upper limb for evaluation of movement disorders during upper limb tasks, 3) comparisons between: groups with/without movement disorders, sensor features before/after intervention, or sensor features with a clinical scale for assessment of the movement disorder. 4) Outcome measures included sensor features from acceleration/angular velocity signals. Results: A total of 101 articles were included, of which 56 researched Parkinson's Disease. Wrist(s), hand(s) and index finger(s) were the most popular sensor locations. Most frequent tasks were: finger tapping, wrist pro/supination, keeping the arms extended in front of the body and finger-to-nose. Most frequently calculated sensor features were mean, standard deviation, root-mean-square, ranges, skewness, kurtosis/entropy of acceleration and/or angular velocity, in combination with dominant frequencies/power of acceleration signals. Examples of clinical applications were automatization of a clinical scale or discrimination between a patient/control group or different patient groups. Conclusion: Current overview can support clinicians and researchers in selecting the most sensitive pathology-dependent sensor features and methodologies for detection and quantification of upper limb movement disorders and objective evaluations of treatment effects. Insights from Parkinson's Disease studies can accelerate the development of wearable sensors protocols in the remaining pathologies, provided that there is sufficient attention for the standardisation of protocols, tasks, feasibility and data analysis methods., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vanmechelen, Haberfehlner, De Vleeschhauwer, Van Wonterghem, Feys, Desloovere, Aerts and Monbaliu.)

Adherent cell cultures are often dissociated from their culture vessel (and each other) through enzymatic harvesting, where the detachment response is monitored by an operator. However, this approach is lacking standardisation and reproducibility, and prolonged exposure or too high concentrations can affect the cell's viability and differentiation potential. Quantitative monitoring systems are required to characterise the cell detachment response and objectively determine the optimal time-point to inhibit the enzymatic reaction. State-of-the-art methodologies rely on bulky imaging systems and/or features (e.g. circularity) that lack robustness. In this study, lens-free imaging (LFI) technology was used to develop a novel cell detachment feature. Seven different donors were cultured and subsequently harvested with a (diluted) enzymatic harvesting solution after 3, 5 and 7 days of culture. Cell detachment was captured with the LFI set-up over a period of 20 min (every 20 s) and by optimising the reconstruction of the LFI intensity images, a new feature could be identified. Bright regions in the intensity image were identified as detaching cells and using image analysis, a method was developed to automatically extract this feature, defined as the percentage of detached cell regions. Next, the method was quantitatively and qualitatively validated on a diverse set of images. Average absolute error values of 1.49%, 1.34% and 1.97% were obtained for medium to high density and overconfluent cultures, respectively. The detachment response was quantified for all conditions and the optimal time for enzyme inhibition was reached when approximately 92.5% of the cells were detached. On average, inhibition times of 9.6-11.1 and 16.2-17.2 min were obtained for medium to high density and overconfluent cultures, respectively. In general, overconfluent cultures detached much slower, while their detachment rate was also decreased by the diluted harvesting solution. Moreover, several donors exhibited similar trends in cell detachment behaviour, with two clear outliers. Using the novel feature, measurements can be performed with an increased robustness, while the compact LFI design could pave the way for in situ monitoring in a variety of culture vessels, including bioreactors., (© 2022. The Author(s).)

Green space could influence adult cognition and childhood neurodevelopment , and is hypothesized to be partly driven by epigenetic modifications. However, it remains unknown whether some of these associations are already evident during foetal development. Similar biological signals shape the developmental processes in the foetal brain and placenta.Therefore, we hypothesize that green space can modify epigenetic processes of cognition-related pathways in placental tissue, such as DNA-methylation of the serotonin receptor HTR2A. HTR2A- methylation was determined within 327 placentas from the ENVIR ON AGE (ENVIRonmental influence ON early AGEing) birth cohort using bisulphite-PCR-pyrosequencing. Total green space exposure was calculated using high-resolution land cover data derived from the Green Map of Flanders in seven buffers (50 m-3 km) and stratified into low (<3 m) and high (≥3 m) vegetation. Residential nature was calculated using the Land use Map of Flanders. We performed multivariate regression models adjusted for several a priori chosen covariables. For an IQR increment in total green space within a 1,000 m, 2,000 m and 3,000 m buffer the methylation of HTR2A increased with 1.47% (95%CI:0.17;2.78), 1.52% (95%CI:0.21;2.83) and 1.42% (95%CI:0.15;2.69), respectively. Additionally,, we found 3.00% (95%CI:1.09;4.91) and 1.98% (95%CI:0.28;3.68) higher HTR2A- methylation when comparing residences with and without the presence of nature in a 50 m and 100 m buffer, respectively. The methylation status of HTR2A in placental tissue is positively associated with maternal green space exposure. Future research is needed to understand better how these epigenetic changes are related to functional modifications in the placenta and the consequent implications for foetal development.

Aim: This study aimed to explore eye movements and stress during eye-tracking gaming performance in children with dyskinetic cerebral palsy (CP) compared with typically developing children, and associations between eye-tracking performance, eye movements, stress, and participants' characteristics., Method: This cohort study included 12 children with dyskinetic CP aged 5 to 12 years (mean age 8 years 7 months, standard deviation [SD] 2 years 3 months) and 23 typically developing children aged 5 to 13 years (mean age 9 years 0 months, SD 2 years 7 months). Participants played 10 eye-tracking games. Tobii X3-120 and Tobii Pro Lab were used to record and analyse eye movements. Stress was assessed through heart rate variability (HRV), recorded during rest, and eye-tracking performance using the Bittium Faros360° ECG Holter device. Eye-tracking performance was measured using gaming completion time. Fixation and saccade variables were used to quantify eye movements, and time- and frequency-domain variables to quantify HRV. Non-parametric statistics were used., Results: Gaming completion time was significantly different (p < 0.001) between groups, and it was negatively correlated with experience (r s  = -0.63, p = 0.029). No significant differences were found between groups in fixation and saccade variables. HRV significantly changed from rest to eye-tracking performance only in typically developing children and not in children with dyskinetic CP., Interpretation: Children with dyskinetic CP took longer to perform the 10 games, especially the inexperienced users, indicating the importance of the early provision of eye-tracking training opportunities. It seems that eye-tracking tasks are not a source of increased stress and effort in children with dyskinetic CP., What This Paper Adds: Participants with dyskinetic cerebral palsy (CP) took twice as long to perform 10 eye-tracking games than typically developing peers. Participants with dyskinetic CP with previous eye-tracking experience performed the games faster. Fixation and saccade variables were not significantly different between children with and without dyskinetic CP. Heart rate variability showed no differences between rest and performance in participants with dyskinetic CP. Gross Motor Function Classification System, Manual Ability Classification System, and Viking Speech Scale levels were not correlated to the eye movements or stress variables., (© 2022 Mac Keith Press.)

Dyskinetic cerebral palsy (DCP) is characterised by involuntary movements, and the movement patterns of children with DCP have not been extensively studied during upper limb tasks. The aim of this study is to evaluate psychometric properties of upper limb kinematics in participants with DCP and typically developing (TD) participants. In current repeatability and validity study, forty individuals with typical development (n = 20) and DCP (n = 20) performed a reach forward/sideways and a reach and grasp task during motion analysis on two occasions. Joint angles at point of task achievement (PTA) and spatio-temporal parameters were evaluated within-and between-sessions using intra-class correlation coefficients (ICC) and standard error of measurement (SEM). Independent t-tests/Mann-Whitney-U tests were used to compare parameters between groups. Within-session ICC values ranged from 0.45 to 1.0 for all parameters for both groups. Within-session SEM values ranged from 1.1° to 11.7° for TD participants and from 1.9° to 13.0° for participants with DCP. Eight within-session repetitions resulted in the smallest change in ICC and SEM values for both groups. Within-session variability was higher for participants with DCP in comparison with the TD group for the majority of the joint angles and spatio-temporal parameters. Intrinsic variability over time was small for all angles and spatio-temporal parameters, whereas extrinsic variability was higher for elbow and scapula angles. Between-group differences revealed lower shoulder adduction and higher elbow flexion, pronation and wrist flexion, as well as higher trajectory deviation and a lower maximal velocity for participants with DCP. This is the first study to assess the psychometric properties of upper limb kinematics in children and adolescents with DCP, showing that children with DCP show higher variability during task execution, requiring a minimum of eight repetitions. However, their variable movement pattern can be reliably captured within-and between-sessions, confirming the potential of three-dimensional motion analysis for assessment of rehabilitation interventions in DCP., Competing Interests: The authors have declared that no competing interests exist.

Background Recognition of precapillary pulmonary hypertension (PH) has significant implications for patient management. However, the low a priori chance to find this rare condition in community hospitals may create a barrier against performing a right heart catheterization (RHC). This could result in misclassification of PH and delayed diagnosis/treatment of precapillary PH. Therefore, we investigated patient characteristics and echocardiographic parameters associated with the decision whether to perform an RHC in patients with incident PH in 12 Dutch community hospitals. Methods and Results In total, 275 patients were included from the OPTICS (Optimizing PH Diagnostic Network in Community Hospitals) registry, a prospective cohort study with patients with incident PH; 157 patients were diagnosed with RHC (34 chronic thromboembolic PH, 38 pulmonary arterial hypertension, 81 postcapillary PH, 4 miscellaneous PH), while 118 patients were labeled as probable postcapillary PH without hemodynamic confirmation. Multivariable analysis showed that older age (>60 years), left ventricular diastolic dysfunction grade 2-3, left atrial dilatation were independently associated with the decision to not perform an RHC, while presence of prior venous thromboembolic events or pulmonary arterial hypertension-associated conditions, right atrial dilatation, and tricuspid regurgitation velocity ≥3.7 m/s favor an RHC performance. Conclusions Older age and echocardiographic parameters of left heart disease were independently associated with the decision to not perform an RHC, while presence of prior venous thromboembolic events or pulmonary arterial hypertension-associated conditions, right atrial dilation, and severe PH on echocardiography favored an RHC performance. As such, especially elderly patients may be at an increased risk of diagnostic delays and missed diagnoses of treatable precapillary PH, which could lead to a worse prognosis.

Spheroids are widely applied as building blocks for biofabrication of living tissues, where they exhibit spontaneous fusion toward an integrated structure upon contact. Tissue fusion is a fundamental biological process, but due to a lack of automated monitoring systems, the in-depth characterization of this process is still limited. Therefore, a quantitative high-throughput platform was developed to semi-automatically select doublet candidates and automatically monitor their fusion kinetics. Spheroids with varying degrees of chondrogenic maturation (days 1, 7, 14, and 21) were produced from two different cell pools, and their fusion kinetics were analyzed via the following steps: (1) by applying a novel spheroid seeding approach, the background noise was decreased due to the removal of cell debris while a sufficient number of doublets were still generated. (2) The doublet candidates were semi-automatically selected, thereby reducing the time and effort spent on manual selection. This was achieved by automatic detection of the microwells and building a random forest classifier, obtaining average accuracies, sensitivities, and precisions ranging from 95.0% to 97.4%, from 51.5% to 92.0%, and from 66.7% to 83.9%, respectively. (3) A software tool was developed to automatically extract morphological features such as the doublet area, roundness, contact length, and intersphere angle. For all data sets, the segmentation procedure obtained average sensitivities and precisions ranging from 96.8% to 98.1% and from 97.7% to 98.8%, respectively. Moreover, the average relative errors for the doublet area and contact length ranged from 1.23% to 2.26% and from 2.30% to 4.66%, respectively, while the average absolute errors for the doublet roundness and intersphere angle ranged from 0.0083 to 0.0135 and from 10.70 to 13.44°, respectively. (4) The data of both cell pools were analyzed, and an exponential model was used to extract kinetic parameters from the time-series data of the doublet roundness. For both cell pools, the technology was able to characterize the fusion rate and quality in an automated manner and allowed us to demonstrate that an increased chondrogenic maturity was linked with a decreased fusion rate. The platform is also applicable to other spheroid types, enabling an increased understanding of tissue fusion. Finally, our approach to study spheroid fusion over time will aid in the design of controlled fabrication of "assembloids" and bottom-up biofabrication of living tissues using spheroids., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Deckers, Hall, Papantoniou, Aerts and Bloemen.)

Purpose: To explore the relation between exercise load, physical activity intensity, and movement disorders during powered wheelchair (PW) mobility in people with severe dyskinetic cerebral palsy (DCP)., Methods: Ten participants with DCP, 6-21 years old, users of a head/foot steering system were included. Dystonia and choreoathetosis were assessed using the Dyskinesia Impairment Mobility Scale (DIMS), heart rate (HR) was used to assess the exercise load of the tasks on the participants, and the accelerometry-based activity index (AI) to measure the physical activity intensity and energy expenditure during mobility task performance., Results: Neck- and distal arm dystonia showed significant correlations with HR (0.64 <  r s  < 0.77; 0.009 <  p  < 0.048), whereas neck- and proximal arm choreoathetosis with AI (0.64 <  r s  < 0.76, 0.011 <  p  < 0.044). Total-body AI was strongly correlated to the AI of the arms (0.66 <  r s  < 0.90,  < 0.001 <  p  < 0.038), but not to the AI of the head., Conclusions: During PW mobility tasks, dystonia is associated to exercise load and choreoathetosis to physical activity intensity and energy expenditure. Findings highlight the difficulties in measuring exercise load and activity intensity in PW users with DCP due to the involuntary hypertonic and/or hyperkinetic hallmark of the movement disorders. Nevertheless, a relaxed surrounding with minimal distractions during PW training may increase learning efficiency. Future studies with a bigger sample size are highly recommended to fully establish the relationship between the variables and to allow generalizability of results.Implications for rehabilitationDystonia is positively related to heart rate during powered mobility, which may be explained by the hypertonic hallmark of dystonia causing an increase in exercise load.Choreoathetosis is positively related to the physical activity index during powered mobility where the hyperkinetic hallmark of choreoathetosis may lead to an increase in physical activity intensity and energy expenditure.Arm overflow movements are the component which contribute the most to total-body activity index, thus, minimizing these movements may lower the overall energy expenditure during powered mobility.Mobility training in a relaxed surrounding with minimal distractions and minimized arm overflow movements may lead to a less-demanding powered wheelchair mobility experience and increased learning efficiency.

Background: The analysis of in vitro cultures of human adult muscle stem cells obtained from biopsies delineates the potential of skeletal muscles and may help to understand altered muscle morphology in patients. In these analyses, the fusion index is a commonly used quantitative metric to assess the myogenic potency of the muscle stem cells. Since the fusion index only partly describes myogenic potency, we developed the Myotube Analyzer tool, which combines the definition of the fusion index with extra features of myonuclei and myotubes obtained from satellite cell cultures., Results: The software contains image adjustment and mask editing functions for preprocessing and semi-automatic segmentation, while other functions can be used to determine the features of nuclei and myotubes. The fusion index and a set of five novel parameters were tested for reliability and validity in a comparison between satellite cell cultures from children with cerebral palsy and typically developing children. These novel parameters quantified extra nucleus and myotube properties and can be used to describe nucleus clustering and myotube shape. Two analyzers who were trained in cell culture defined all parameters using the Myotube Analyzer app. Out of the six parameters, five had good reliability reflected by good intra-class correlation coefficients (> 0.75). Children with cerebral palsy were significantly different from the typically developing children (p < 0.05) for five parameters, and for three of the six parameters, these differences exceeded the minimal detectable differences., Conclusions: The Myotube Analyzer can be used for the analysis of fixed differentiated myoblast cultures with nuclear and MyHC staining. The app can calculate the fusion index, an already existing parameter, but also provides multiple new parameters to comprehensively describe myogenic potential in its output. The raw data used to determine these parameters are also available in the output. The parameters calculated by the tool can be used to detect differences between cultures from children with cerebral palsy and typically developing children. Since the program is open source, users can customize it to fit their own analysis requirements., (© 2022. The Author(s).)

Background: Neoadjuvant chemotherapy (NACT) and radical gastrectomy are the gold standard treatments for resectable advanced gastric cancer (GC). However, the prognostic value of the pathological tumor regression grade (TRG) of NACT remains controversial. This retrospective study aimed to investigate the correlation between the TRG after NACT and clinicopathological features as well as its prognostic value in advanced GC., Methods: In total, 551 patients with GC who received NACT combined with surgical resection at the Zhejiang Cancer Hospital from April 2004 to December 2019 were included. The demographic characteristics, treatment response, tumor characteristics, treatment regimens, and survival data were reviewed from the medical records of all patients. The Chi-square test was used to analyze the correlation between TRG and clinicopathological factors. Kaplan-Meier univariate analysis and Cox regression multivariate analysis were used to determine the independent risk factors affecting the prognosis of GC patients., Results: Among the 551 patients with advanced GC who accepted NACT treatment, 14 were determined to be in TRG 0, 98 in TRG 1, 257 in TRG 2, and 182 in TRG 3. Also, TRG was significantly correlated with the cT stage (P=0.015), ypT stage (P<0.001), ypN stage (P<0.001), ypTNM stage (P<0.001), vascular tumor thrombus (P<0.001), Borrmann classification (P=0.042), and lymph node ratio (LNR) (P<0.001). Furthermore, patients who had a good pathological response to NACT had a better prognosis, with a 3-year overall survival (OS) of 70.9% versus 48.8% in patients who had a poor pathological response. We also found that TRG (P=0.042, HR =1.65) was an independent prognostic factor affecting the OS of GC patients., Conclusions: TRG plays a significant role in the prognostic value in neoadjuvant chemotherapy for gastric adenocarcinoma. Patients with higher cT stage, higher levels of pre-CA199 and pre-CA125 may have worse pathological response., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-537/coif). All authors report funding support from the Diagnosis and Therapy Center of Upper Gastrointestinal Tumor (No. JBZX-202006), the Natural Science Foundation of Zhejiang Province (No. LY18H290006), the Key research and development project of Zhejiang Science and Technology Department (No. 2019C03049), the National Natural Science Foundation of China (Nos. 81973634 and 82074245), and the Program of Zhejiang Provincial TCM Sci-tech Plan (Nos. 2019ZZ010 and 2021ZA020). The authors have no other conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

Purpose: The aim of this study was to identify the relationships between continuously measured internal and external load variables during volleyball competition., Methods: A total of 8 male elite volleyball athletes (Belgian Liga A and Liga B) were monitored during official competition matches. In total, 63 individual measurements are included in this study. The authors used heart-rate (HR) data as internal load and accelerometer-based activity as external load. Data were recorded at a sampling frequency of 1 Hz using wearable technology during official competition. Workload during continuous game play and individual jumps performed while serving and spiking (selected by means of video analysis) were studied using correlation analysis and dynamic time-series modeling., Results: Significant linear correlations were observed between peak acceleration and maximal HR of individual serves (ρ = .62; P = 1.6e-5) and spikes (ρ = .49; P = 1.2e-3) that were performed during the warm-up. These same actions performed during the match did not show significant correlations. The correlation between the mean HR and mean activity throughout the entire match was also found to be significant (ρ = .67; P = 2.0e-9). With respect to the time-series models, the mean value for the goodness of fit (RT2) between HR and activity was equal to .83 and .67 for the individual actions and the entire matches, respectively., Conclusions: The results show that there are strong relationships between internal and external load during volleyball competition. Second-order transfer function models are capable of explaining the main dynamics of HR (internal load) in response to accelerometer-based activity (external load). Time-series analysis of continuously measured workload is proposed for use in practice.

This study introduces machine learning predictive models to predict the future values of the monitored vital signs of COVID-19 ICU patients. The main vital sign predictors include heart rate, respiration rate, and oxygen saturation. We investigated the performances of the developed predictive models by considering different approaches. The first predictive model was developed by considering the following vital signs: heart rate, blood pressure (systolic, diastolic and mean arterial, pulse pressure), respiration rate, and oxygen saturation. Similar to the first approach, the second model was developed using the same vital signs, but it was trained and tested based on a leave-one-subject-out approach. The third predictive model was developed by considering three vital signs: heart rate (HR), respiration rate (RR), and oxygen saturation (SpO2). The fourth model was a leave-one-subject-out model for the three vital signs. Finally, the fifth predictive model was developed based on the same three vital signs, but with a five-minute observation rate, in contrast with the aforementioned four models, where the observation rate was hourly to bi-hourly. For the five models, the predicted measurements were those of the three upcoming observations (on average, three hours ahead). Based on the obtained results, we observed that by limiting the number of vital sign predictors (i.e., three vital signs), the prediction performance was still acceptable, with the average mean absolute percentage error (MAPE) being 12%,5%, and 21.4% for heart rate, oxygen saturation, and respiration rate, respectively. Moreover, increasing the observation rate could enhance the prediction performance to be, on average, 8%,4.8%, and 17.8% for heart rate, oxygen saturation, and respiration rate, respectively. It is envisioned that such models could be integrated with monitoring systems that could, using a limited number of vital signs, predict the health conditions of COVID-19 ICU patients in real-time.

Background: The prevalence of pollen allergy has increased due to urbanization, climate change and air pollution. The effects of green space and air pollution on respiratory health of pollen allergy patients are complex and best studied in spatio-temporal detail., Methods: We tracked 144 adults sensitized to Betulaceae pollen during the tree pollen season (January-May) of 2017 and 2018 and assessed their spatio-temporal exposure to green space, allergenic trees, air pollutants and birch pollen. Participants reported daily symptom severity scores. We extracted 404 case days with high symptom severity scores and matched these to 404 control days. The data were analyzed using conditional logistic regression with a 1:1 case-crossover design., Results: Case days were associated with exposure to birch pollen concentration (100 grains/m 3 ) [adjusted odds ratio 1.045 and 95% confidence interval (1.014-1.078)], O 3 concentration (10 μg/m 3 ) [1.504 (1.281-1.766)] and PM 10 concentration (10 μg/m 3 ) [1.255 (1.007-1.565)] on the day of the severe allergy event and with the cumulative exposure of one and two days before. Exposure to grass cover (10% area fraction) [0.655 (0.446-0.960)], forest cover (10% area fraction) [0.543 (0.303-0.973)] and density of Alnus (10%) [0.622 (0.411-0.942)] were protective for severe allergy, but only on the day of the severe allergy event. Increased densities of Betula trees (10%) were a risk factor [unadjusted OR: 2.014 (1.162-3.490)]., Conclusion: Exposure to green space may mitigate tree pollen allergy symptom severity but only when the density of allergenic trees is low. Air pollutants contribute to more severe allergy symptoms. Spatio-temporal tracking allows for a more realistic exposure assessment., 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 © 2021 Elsevier B.V. All rights reserved.)

Purpose: Not all patients with chronic obstructive pulmonary disease (COPD) experience similar benefits after pulmonary rehabilitation (PR). This pre-post PR study used a large sample of patients with COPD to determine whether PR-induced changes of oxygen uptake (V˙O2) kinetics and exercise responses of V˙O2, carbon dioxide output (V˙CO2), minute ventilation (V˙E), V˙E/V˙CO2, breathing frequency, and tidal volume differed between responders and nonresponders to PR., Methods: Responders to PR were defined as patients with a minimal clinically important increase in endurance time of 105 s. Isotime (=180 s) values of V˙O2, V˙CO2, V˙E, V˙E/V˙CO2, breathing frequency, and tidal volume; gains of V˙O2, V˙CO2, and V˙E; and V˙O2 mean response time of 183 patients with COPD (forced expiratory volume in 1 s: 56% ± 19% predicted) were compared between pre- and post-PR constant work rate tests., Results: After PR, only the group of responders significantly decreased V˙O2 mean response time (P < 0.05), V˙CO2 gain, V˙E gain, and isotime values of V˙CO2, V˙E, and V˙E/V˙CO2 (all, P < 0.001), while also improving their breathing pattern (e.g., decreased breathing frequency isotime value; P < 0.0001). These changes were not observed in the group of nonresponders. Changes in physiological exercise responses were correlated with changes in physical performance (e.g., correlation between changes in V˙O2 mean response time and endurance time: P = 0.0002, r = -0.32)., Conclusions: PR-induced changes in physiological exercise responses differed between responders and nonresponders. Physiological changes are relevant to explain the variable improvements of physical performance after PR in patients with COPD., (Copyright © 2020 by the American College of Sports Medicine.)

An increasing need toward a more efficient expansion of adherent progenitor cell types arises with the advancements of cell therapy. The use of a dynamic expansion instead of a static planar expansion could be one way to tackle the challenges of expanding adherent cells at a large scale. Microcarriers are often reported as a biomaterial for culturing cells in suspension. However, the type of microcarrier has an effect on the cell expansion. In order to find an efficient expansion process for a specific adherent progenitor cell type, it is important to investigate the effect of the type of microcarrier on the cell expansion. Human periosteum-derived progenitor cells are extensively used in skeletal tissue engineering for the regeneration of bone defects. Therefore, we evaluated the use of different microcarriers on human periosteum-derived progenitor cells. In order to assess the potency, identity and viability of these cells after being cultured in the spinner flasks, this study performed several in vitro and in vivo analyses. The novelty of this work lies in the combination of screening different microcarriers for human periosteum-derived progenitor cells with in vivo assessments of the cells' potency using the microcarrier that was selected as the most promising one. The results showed that expanding human periosteum-derived progenitor cells in spinner flasks using xeno-free medium and Star-Plus microcarriers, does not affect the potency, identity or viability of the cells. The potency of the cells was assured with an in vivo evaluation, where bone formation was achieved. In summary, this expansion method has the potential to be used for large scale cell expansion with clinical relevance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Van Beylen, Papantoniou and Aerts.)

Purpose: To assess the utility of globotriaosylsphingosine (lyso-Gb 3 ) for clinical monitoring of treatment response in patients with Fabry disease receiving migalastat., Methods: A post hoc analysis evaluated data from 97 treatment-naive and enzyme replacement therapy (ERT)-experienced patients with migalastat-amenable GLA variants from FACETS (NCT00925301) and ATTRACT (NCT01218659) and subsequent open-label extension studies. The relationship between plasma lyso-Gb 3 and measures of Fabry disease progression (left ventricular mass index [LVMi], estimated glomerular filtration rate [eGFR], and pain) and the relationship between lyso-Gb 3 and incidence of Fabry-associated clinical events (FACEs) were assessed in both groups. The relationship between changes in lyso-Gb 3 and kidney interstitial capillary (KIC) globotriaosylceramide (Gb 3 ) inclusions was assessed in treatment-naive patients., Results: No significant correlations were identified between changes in lyso-Gb 3 and changes in LVMi, eGFR, or pain. Neither baseline lyso-Gb 3 levels nor the rate of change in lyso-Gb 3 levels during treatment predicted FACE occurrences in all patients or those receiving migalastat for ≥24 months. Changes in lyso-Gb 3 correlated with changes in KIC Gb 3 inclusions in treatment-naive patients., Conclusions: Although used as a pharmacodynamic biomarker in research and clinical studies, plasma lyso-Gb 3 may not be a suitable biomarker for monitoring treatment response in migalastat-treated patients.

Deficiency of glucocerebrosidase (GBA), a lysosomal β-glucosidase, causes Gaucher disease. The enzyme hydrolyzes β-glucosidic substrates and transglucosylates cholesterol to cholesterol-β-glucoside. Here we show that recombinant human GBA also cleaves β-xylosides and transxylosylates cholesterol. The xylosyl-cholesterol formed acts as an acceptor for the subsequent formation of di-xylosyl-cholesterol. Common mutant forms of GBA from patients with Gaucher disease with reduced β-glucosidase activity were similarly impaired in β-xylosidase, transglucosidase, and transxylosidase activities, except for a slightly reduced xylosidase/glucosidase activity ratio of N370S GBA and a slightly reduced transglucosylation/glucosidase activity ratio of D409H GBA. XylChol was found to be reduced in spleen from patients with Gaucher disease. The origin of newly identified XylChol in mouse and human tissues was investigated. Cultured human cells exposed to exogenous β-xylosides generated XylChol in a manner dependent on active lysosomal GBA but not the cytosol-facing β-glucosidase GBA2. We later sought an endogenous β-xyloside acting as donor in transxylosylation reactions, identifying xylosylated ceramide (XylCer) in cells and tissues that serve as donor in the formation of XylChol. UDP-glucosylceramide synthase (GCS) was unable to synthesize XylChol but could catalyze the formation of XylCer. Thus, food-derived β-D-xyloside and XylCer are potential donors for the GBA-mediated formation of XylChol in cells. The enzyme GCS produces XylCer at a low rate. Our findings point to further catalytic versatility of GBA and prompt a systematic exploration of the distribution and role of xylosylated lipids., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: While American Thoracic Society (ATS)/European Respiratory Society (ERS) quality control criteria for spirometry include several quantitative limits, it also requires manual visual inspection. The current approach is time consuming and leads to high intertechnician variability. We propose a deep-learning approach called convolutional neural network (CNN), to standardise spirometric manoeuvre acceptability and usability., Methods and Methods: In 36 873 curves from the National Health and Nutritional Examination Survey USA 2011-2012, technicians labelled 54% of curves as meeting ATS/ERS 2005 acceptability criteria with satisfactory start and end of test, but identified 93% of curves with a usable forced expiratory volume in 1 s. We processed raw data into images of maximal expiratory flow-volume curve (MEFVC), calculated ATS/ERS quantifiable criteria and developed CNNs to determine manoeuvre acceptability and usability on 90% of the curves. The models were tested on the remaining 10% of curves. We calculated Shapley values to interpret the models., Results: In the test set (n=3738), CNN showed an accuracy of 87% for acceptability and 92% for usability, with the latter demonstrating a high sensitivity (92%) and specificity (96%). They were significantly superior (p<0.0001) to ATS/ERS quantifiable rule-based models. Shapley interpretation revealed MEFVC<1 s (MEFVC pattern within first second of exhalation) and plateau in volume-time were most important in determining acceptability, while MEFVC<1 s entirely determined usability., Conclusion: The CNNs identified relevant attributes in spirometric curves to standardise ATS/ERS manoeuvre acceptability and usability recommendations, and further provides individual manoeuvre feedback. Our algorithm combines the visual experience of skilled technicians and ATS/ERS quantitative rules in automating the critical phase of spirometry quality control., Competing Interests: Conflict of interest: N. Das has a patent spirometry evaluation method (application number 1914446.8 UK patent office) pending. Conflict of interest: K. Verstraete has nothing to disclose. Conflict of interest: S. Stanojevic has nothing to disclose. Conflict of interest: M. Topalovic is a co-founder of a spin-off company ArtiQ. Conflict of interest: J-M. Aerts has not nothing to disclose. Conflict of interest: W. Janssens reports grants from AstraZeneca and Chiesi, fees for lectures and advisory boards from AstraZeneca and Chiesi, outside the submitted work; has a patent on pulmonary function loops pending; and is co-founder of ArtiQ, a spin-off company of KU Leuven., (Copyright ©ERS 2020.)

In this prospective, interventional, international study, we investigate continuous monitoring of hospitalised patients' vital signs using wearable technology as a basis for real-time early warning scores (EWS) estimation and vital signs time-series prediction. The collected continuous monitored vital signs are heart rate, blood pressure, respiration rate, and oxygen saturation of a heterogeneous patient population hospitalised in cardiology, postsurgical, and dialysis wards. Two aspects are elaborated in this study. The first is the high-rate (every minute) estimation of the statistical values (e.g., minimum and mean) of the vital signs components of the EWS for one-minute segments in contrast with the conventional routine of 2 to 3 times per day. The second aspect explores the use of a hybrid machine learning algorithm of kNN-LS-SVM for predicting future values of monitored vital signs. It is demonstrated that a real-time implementation of EWS in clinical practice is possible. Furthermore, we showed a promising prediction performance of vital signs compared to the most recent state of the art of a boosted approach of LSTM. The reported mean absolute percentage errors of predicting one-hour averaged heart rate are 4.1, 4.5, and 5% for the upcoming one, two, and three hours respectively for cardiology patients. The obtained results in this study show the potential of using wearable technology to continuously monitor the vital signs of hospitalised patients as the real-time estimation of EWS in addition to a reliable prediction of the future values of these vital signs is presented. Ultimately, both approaches of high-rate EWS computation and vital signs time-series prediction is promising to provide efficient cost-utility, ease of mobility and portability, streaming analytics, and early warning for vital signs deterioration.

Objectives: To investigate the operational competences screen navigation and dwell function underlying eye gaze performance, and the relation of dystonia and choreoathetosis with eye gaze performance in children with dyskinetic cerebral palsy (DCP)., Methods: During a 5-week intervention, ten participants with DCP played eye gaze video games daily for 30 minutes. Six games were used to assess task performance, fixation count, and eye movement accuracy during four measurements. Dystonia and choreoathetosis were evaluated using the Dyskinesia Impairment Scale., Results: Eye gaze performance improved over time ( p = .013). Moderate to strong within-subject correlations were found between eye movement accuracy and task performance, and between eye movement accuracy and fixation count. No significant correlations were found with the movement disorders., Conclusions: Eye gaze technology shows great potential to be a successful computer interface for children with severe DCP, thereby potentially improving their communication skills, participation levels, and quality of life.

Introduction: Power wheelchairs (PW) with head/foot steering systems are used as an alternative to joysticks in children with severe dyskinetic cerebral palsy (DCP). Mobility training programs are unstandardized to date, and insight on dystonia, choreoathetosis, and mobility performance may lead to greater independent mobility., Objective: To map the presence and severity of dystonia and choreoathetosis during PW mobility in DCP and their relation with mobility performance., Methods: Ten participants with DCP performed four PW mobility tasks using a head/foot steering system. Dystonia and choreoathetosis in the neck and arm regions were evaluated using the Dyskinesia Impairment Mobility Scale (DIMS). PW mobility performance was assessed using time-on-task and the number of errors during performance. The Wilcoxon-signed rank test and the Spearman's correlation coefficients were used to explore differences and correlations., Results: Median levels of dystonia (83.6%) were significantly higher (p < 0.01) than median levels of choreoathetosis (34.4%). Positive significant correlations were found between the Arm Proximal DIMS and the PW mobility experience (r s= -0.92, p < 0.001), and between the Arm Distal DIMS and the number of errors (r s  = 0.66, p = 0.039) during mobility performance., Conclusions: Dystonia is more present and severe during PW mobility than choreoathetosis. The hypertonic hallmark of dystonia may mask the hyperkinetic hallmark of choreoathetosis, resulting in lower median levels. Results may suggest that with an increase in driving experience, children with DCP adopt deliberate strategies to minimize the negative impact of arm overflow movements on mobility performance, however, future research with bigger sample size and additional outcome measures is strongly encouraged., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Background: Living in green environments has been associated with various health benefits, but the evidence for positive effects on respiratory health in children is ambiguous., Objective: To investigate if residential exposure to different types of green space is associated with childhood asthma prevalence in Belgium., Methods: Asthma prevalence was estimated from sales data of reimbursed medication for obstructive airway disease (OAD) prescribed to children between 2010 and 2014, aggregated at census tract level (n = 1872) by sex and age group (6-12 and 13-18 years). Generalized log-linear mixed effects models with repeated measures were used to estimate effects of relative covers of forest, grassland and garden in the census tract of the residence on OAD medication sales. Models were adjusted for air pollution (PM 10 ), housing quality and administrative region., Results: Consistent associations between OAD medication sales and relative covers of grassland and garden were observed (unadjusted parameter estimates per IQR increase of relative cover, range across four strata: grassland, β = 0.15-0.17; garden, β = 0.13-0.17). The associations remained significant after adjusting for housing quality and chronic air pollution (adjusted parameter estimates per IQR increase of relative cover, range across four strata: grassland, β = 0.10-0.14; garden, β = 0.07-0.09). There was no association between OAD medication sales and forest cover., Conclusions: Based on aggregated data, we found that living in close proximity to areas with high grass cover (grasslands, but also residential gardens) may negatively impact child respiratory health. Potential allergic and non-allergic mechanisms that underlie this association include elevated exposure to grass pollen and fungi and reduced exposure to environmental biodiversity. Reducing the dominance of grass in public and private green space might be beneficial to reduce the childhood asthma burden and may simultaneously improve the ecological value of urban green space., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background Although most newly presenting patients with pulmonary hypertension (PH) have elevated pulmonary artery wedge pressure, identification of so-called postcapillary PH can be challenging. A noninvasive tool predicting elevated pulmonary artery wedge pressure in patients with incident PH may help avoid unnecessary invasive diagnostic procedures. Methods and Results A combination of clinical data, ECG, and echocardiographic parameters was used to refine a previously developed left heart failure risk score in a retrospective cohort of pre- and postcapillary PH patients. This updated score (renamed the OPTICS risk score) was externally validated in a prospective cohort of patients from 12 Dutch nonreferral centers the OPTICS network. Using the updated OPTICS risk score, the presence of postcapillary PH could be predicted on the basis of body mass index ≥30, diabetes mellitus, atrial fibrillation, dyslipidemia, history of valvular surgery, sum of SV1 (deflection in V1 in millimeters) and RV6 (deflection in V6 in millimeters) on ECG, and left atrial dilation. The external validation cohort included 81 postcapillary PH patients and 66 precapillary PH patients. Using a predefined cutoff of >104, the OPTICS score had 100% specificity for postcapillary PH (sensitivity, 22%). In addition, we investigated whether a high probability of heart failure with preserved ejection fraction, assessed by the H 2 FPEF score (obesity, atrial fibrillation, age >60 yrs, ≥2 antihypertensives, E/e' >9, and pulmonary artery systolic pressure by echo >35 mmHg), similarly predicted the presence of elevated pulmonary artery wedge pressure. High probability of heart failure with preserved ejection fraction (H 2 FPEF score ≥6) was less specific for postcapillary PH. Conclusions In a community setting, the OPTICS risk score can predict elevated pulmonary artery wedge pressure in PH patients without clear signs of left-sided heart disease. The OPTICS risk score may be used to tailor the decision to perform invasive diagnostic testing.

Implementing a personalised feeding strategy for each individual batch of a bioprocess could significantly reduce the unnecessary costs of overfeeding the cells. This paper uses lactate measurements during the cell culture process as an indication of cell growth to adapt the feeding strategy accordingly. For this purpose, a model predictive control is used to follow this a priori determined reference trajectory of cumulative lactate. Human progenitor cells from three different donors, which were cultivated in 12-well plates for five days using six different feeding strategies, are used as references. Each experimental set-up is performed in triplicate and for each run an individualised model-based predictive control (MPC) controller is developed. All process models exhibit an accuracy of 99.80% ± 0.02%, and all simulations to reproduce each experimental run, using the data as a reference trajectory, reached their target with a 98.64% ± 0.10% accuracy on average. This work represents a promising framework to control the cell growth through adapting the feeding strategy based on lactate measurements.