Transforming growth factor-ß challenge alters the N-, O-, and glycosphingolipid glycomes in PaTu-S pancreatic adenocarcinoma cells.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognosis and high mortality. Transforming growth factor-ß (TGF-ß) plays a key role in PDAC tumor progression, which is often associated with aberrant glycosylation. However, how PDAC cells respond to TGF-ß and the role of glycosylation therein is not well known. Here, we investigated the TGF-ß-mediated response and glycosylation changes in the PaTu-8955S (PaTu-S) cell line deficient in SMA-related and MAD-related protein 4 (SMAD4), a signal transducer of the TGF-ß signaling. PaTu-S cells responded to TGF-ß by upregulating SMAD2 phosphorylation and target gene expression. We found that TGF-ß induced expression of the mesenchymal marker N-cadherin but did not significantly affect epithelial marker E-cadherin expression. We also examined differences in N-glycans, O-glycans, and glycosphingolipid-linked glycans in PaTu-S cells upon TGF-ß stimulation. TGF-ß treatment primarily induced N-glycome aberrations involving elevated levels of branching, core fucosylation, and sialylation in PaTu-S cells, in agreement with TGF-ß-induced changes in the expression of glycosylation-associated genes. In addition, we observed differences in O glycosylation and glycosphingolipid glycosylation profiles after TGF-ß treatment, including lower levels of sialylated Tn antigen and neoexpression of globosides. Furthermore, the expression of transcription factor sex-determining region Y-related high-mobility group box 4 was upregulated upon TGF-ß stimulation, and its depletion blocked TGF-ß-induced N-glycomic changes. Thus, TGF-ß-induced N-glycosylation changes can occur in a sex-determining region Y-related high-mobility group box 4-dependent and SMAD4-independent manner in the pancreatic PaTu-S cancer cell line. Our results open up avenues to study the relevance of glycosylation in TGF-ß signaling in SMAD4-inactivated PDAC.

Factors affecting augmented reality head-mounted device performance in real OR.

PURPOSE: Over the last years, interest and efforts to implement augmented reality (AR) in orthopedic surgery through head-mounted devices (HMD) have increased. However, the majority of experiments were preclinical and within a controlled laboratory environment. The operating room (OR) is a more challenging environment with various confounding factors potentially affecting the performance of an AR-HMD. The aim of this study was to assess the performance of an AR-HMD in a real-life OR setting. METHODS: An established AR application using the HoloLens 2 HMD was tested in an OR and in a laboratory by two users. The accuracy of the hologram overlay, the time to complete the trial, the number of rejected registration attempts, the delay in live overlay of the hologram, and the number of completely failed runs were recorded. Further, different OR setting parameters (light condition, setting up partitions, movement of personnel, and anchor placement) were modified and compared. RESULTS: Time for full registration was higher with 48 s (IQR 24 s) in the OR versus 33 s (IQR 10 s) in the laboratory setting (p < 0.001). The other investigated parameters didn't differ significantly if an optimal OR setting was used. Within the OR, the strongest influence on performance of the AR-HMD was different light conditions with direct light illumination on the situs being the least favorable. CONCLUSION: AR-HMDs are affected by different OR setups. Standardization measures for better AR-HMD performance include avoiding direct light illumination on the situs, setting up partitions, and minimizing the movement of personnel.

Flexible transition timing in discrete-time multistate life tables using Markov chains with rewards.

Discrete-time multistate life tables are attractive because they are easier to understand and apply in comparison with their continuous-time counterparts. While such models are based on a discrete time grid, it is often useful to calculate derived magnitudes (e.g. state occupation times), under assumptions which posit that transitions take place at other times, such as mid-period. Unfortunately, currently available models allow very few choices about transition timing. We propose the use of Markov chains with rewards as a general way of incorporating information on the timing of transitions into the model. We illustrate the usefulness of rewards-based multistate life tables by estimating working life expectancies using different retirement transition timings. We also demonstrate that for the single-state case, the rewards approach matches traditional life-table methods exactly. Finally, we provide code to replicate all results from the paper plus R and Stata packages for general use of the method proposed.

CAVE and HMD: distance perception comparative study.

This paper proposes to analyse user experience using two different immersive device categories: a cave automatic virtual environment (CAVE) and a head-mounted display (HMD). While most past studies focused on one of these devices to characterize user experience, we propose to fill the gap in comparative studies by conducting investigations using both devices, considering the same application, method and analysis. Through this study, we want to highlight the differences in user experience induced when using either one of these technologies in terms of visualization and interaction. We performed two experiments, each focusing on a specific aspect of the devices employed. The first one is related to distance perception when walking and the possible influence of the HMD's weight, which does not occur with CAVE systems as they do not require wearing any heavy equipment. Past studies found that weight may impact distance perception. Several walking distances were considered. Results revealed that the HMD's weight does not induce significant differences over short distances (above three meters). In the second experiment, we focused on distance perception over short distances. We considered that the HMD's screen being closer to the user's eyes than in CAVE systems might induce substantial distance perception differences, especially for short-distance interaction. We designed a task in which users had to move an object from one place to another at several distances using the CAVE and an HMD. Results revealed significant underestimation compared to reality as in past work, but no significant differences between the immersive devices. These results provide a better understanding of the differences between the two emblematic virtual reality displays.

Toward the validation of VR-HMDs for medical education: a systematic literature review.

The latest technological advancements in the domain of virtual reality (VR) have created new opportunities to use VR as a training platform for medical students and practitioners more broadly. Despite the growing interest in the use of VR as a training tool, a commonly identified gap in VR-training for medical education is the confidence in the long-term validity of the applications. A systematic literature review was undertaken to explore the extent of VR (in particular head-mounted displays) applications for medical training with an additional focus on validation measures. The papers included in this review discussed empirical case studies of specific applications; however, these were mostly concerned with human-computer interaction and were polarized between demonstrating that a conceptual technology solution was feasible for simulation or looked at specific areas of VR usability with little discussion on validation measures for long-term training effectiveness and outcomes. The review uncovered a wide range of ad hoc applications and studies in terms of technology vendors, environments, tasks, envisaged users and effectiveness of learning outcomes. This presents decision-making challenges for those seeking to adopt, implement and embed such systems in teaching practice. The authors of this paper then take a wider socio-technical systems perspective to understand how the holistic training system can be engineered and validated effectively as fit for purpose, through distillation of a generic set of requirements from the literature review to aid design specification and implementation, and to drive more informed and traceable validation of these types of systems. In this review, we have identified 92 requirement statements in 11 key areas against which a VR-HMD training system could be validated; these were grouped into design considerations, learning mechanisms and implementation considerations.

Quantifying self-rated age.

Chronological age, in conjunction with population life tables, is widely used for estimating future life expectancy. The aims of this study are to estimate a subjective ageing indicator, namely self-rated age, and to evaluate its concurrent validity in comparison with other age indicators: subjective survival probabilities, subjective age, and biological age. We use data from the Wave 6 of the Survey of Health, Ageing and Retirement in Europe, Wave 12 of the Health and Retirement Study in the United States, and life tables from the Human Mortality Database. For the statistical analysis we use multinomial regression models. Our results indicate that health status and frequency of physical activities imply similar patterns of self- rated age, subjective survival probabilities, subjective age, and biological age. However, the impact of cognitive function differs by geographical region. Self-rated age can be interpreted as a subjective adjustment that better reflects the ageing process.

Trends of Augmented Reality for Agri-Food Applications.

Recent years have witnessed an increasing interest in deploying state-of-the-art augmented reality (AR) head-mounted displays (HMDs) for agri-food applications. The benefits of AR HMDs to agri-food industry stakeholders (e.g., food suppliers, retail/food service) have received growing attention and recognition. AR HMDs enable users to make healthier dietary choices, experience novel changes in their perception of taste, enhance the cooking and food shopping experience, improve productivity at work and enhance the implementation of precision farming. Therefore, although development costs are still high, the case for integration of AR in food chains appears to be compelling. This review will present the most recent developments of AR HMDs for agri-food relevant applications. The summarized applications can be clustered into different themes: (1) dietary and food nutrition assessment; (2) food sensory science; (3) changing the eating environment; (4) retail food chain applications; (5) enhancing the cooking experience; (6) food-related training and learning; and (7) food production and precision farming. Limitations of current practices will be highlighted, along with some proposed applications.

Assessing Electroencephalography as a Stress Indicator: A VR High-Altitude Scenario Monitored through EEG and ECG.

Over the last decade, virtual reality (VR) has become an increasingly accessible commodity. Head-mounted display (HMD) immersive technologies allow researchers to simulate experimental scenarios that would be unfeasible or risky in real life. An example is extreme heights exposure simulations, which can be utilized in research on stress system mobilization. Until recently, electroencephalography (EEG)-related research was focused on mental stress prompted by social or mathematical challenges, with only a few studies employing HMD VR techniques to induce stress. In this study, we combine a state-of-the-art EEG wearable device and an electrocardiography (ECG) sensor with a VR headset to provoke stress in a high-altitude scenarios while monitoring EEG and ECG biomarkers in real time. A robust pipeline for signal clearing is implemented to preprocess the noise-infiltrated (due to movement) EEG data. Statistical and correlation analysis is employed to explore the relationship between these biomarkers with stress. The participant pool is divided into two groups based on their heart rate increase, where statistically important EEG biomarker differences emerged between them. Finally, the occipital-region band power changes and occipital asymmetry alterations were found to be associated with height-related stress and brain activation in beta and gamma bands, which correlates with the results of the self-reported Perceived Stress Scale questionnaire.

Pedestrian Crossing Decisions in Virtual Environments: Behavioral Validity in CAVEs and Head-Mounted Displays.

OBJECTIVE: To contribute to the validation of virtual reality (VR) as a tool for analyzing pedestrian behavior, we compared two types of high-fidelity pedestrian simulators to a test track. BACKGROUND: While VR has become a popular tool in pedestrian research, it is uncertain to what extent simulator studies evoke the same behavior as nonvirtual environments. METHOD: An identical experimental procedure was replicated in a CAVE automatic virtual environment (CAVE), a head-mounted display (HMD), and on a test track. In each group, 30 participants were instructed to step forward whenever they felt the gap between two approaching vehicles was adequate for crossing. RESULTS: Our analyses revealed distinct effects for the three environments. Overall acceptance was highest on the test track. In both simulators, crossings were initiated later, but a relationship between gap size and crossing initiation was apparent only in the CAVE. In contrast to the test track, vehicle speed significantly affected acceptance rates and safety margins in both simulators. CONCLUSION: For a common decision task, the results obtained in virtual environments deviate from those in a nonvirtual test bed. The consistency of differences indicates that restrictions apply when predicting real-world behavior based on VR studies. In particular, the higher susceptibility to speed effects warrants further investigation, since it implies that differences in perceptual processing alter experimental outcomes. APPLICATION: Our observations should inform the conclusions drawn from future research in pedestrian simulators, for example by accounting for a higher sensitivity to speed variations and a greater uncertainty associated with crossing decisions.

Immersive virtual reality health games: a narrative review of game design.

BACKGROUND: High quality head-mounted display based virtual reality (HMD-VR) has become widely available, spurring greater development of HMD-VR health games. As a behavior change approach, these applications use HMD-VR and game-based formats to support long-term engagement with therapeutic interventions. While the bulk of research to date has primarily focused on the therapeutic efficacy of particular HMD-VR health games, how developers and researchers incorporate best-practices in game design to achieve engaging experiences remains underexplored. This paper presents the findings of a narrative review exploring the trends and future directions of game design for HMD-VR health games. METHODS: We searched the literature on the intersection between HMD-VR, games, and health in databases including MEDLINE, Embase, CINAHL, PsycINFO, and Compendex. We identified articles describing HMD-VR games designed specifically as health applications from 2015 onwards in English. HMD-VR health games were charted and tabulated according to technology, health context, outcomes, and user engagement in game design. FINDINGS: We identified 29 HMD-VR health games from 2015 to 2020, with the majority addressing health contexts related to physical exercise, motor rehabilitation, and pain. These games typically involved obstacle-based challenges and extrinsic reward systems to engage clients in interventions related to physical functioning and pain. Less common were games emphasizing narrative experiences and non-physical exercise interventions. However, discourse regarding game design was diverse and often lacked sufficient detail. Game experience was evaluated using primarily ad-hoc questionnaires. User engagement in the development of HMD-VR health games primarily manifested as user studies. CONCLUSION: HMD-VR health games are promising tools for engaging clients in highly immersive experiences designed to address diverse health contexts. However, more in-depth and structured attention to how HMD-VR health games are designed as game experiences is needed. Future development of HMD-VR health games may also benefit from greater involvement of end-users in participatory approaches.

User discomfort while using a virtual reality headset as a personal viewing system for text-intensive office tasks.

Ergonomics issues while using virtual reality (VR) headsets for text-intensive applications have not been studied. Measures of neck and shoulder discomfort and simulator sickness symptoms were quantified while participants were performing a document creation task for 60 min using a VR headset and a desktop monitor. During the task with the headset, participants rotated the head 2.7 times more frequently and used the neck extensor muscles 25.9% more, in average. They also rated the neck and shoulder discomfort 60% and 17.5% higher after the task. The simulator sickness symptoms were also rated significantly higher (p < .05) for the headset condition, with more pronounced differences in the symptoms related to visual discomfort. Results indicate that the physical discomforts due to the frequent head rotations and the headset weight, and visual discomforts due to difficulty in reading texts were the main issues of the VR headset for common office tasks. Practitioner summary: Ergonomics issues associated with the use of a VR headset for conducting office productivity work tasks have been evaluated in an experiment. Study results indicate that the development in the neck physical discomfort and visual discomfort may be the main barriers to the use of current VR headsets for office works. Abbreviations: VR: virtual reality; VDT: video display terminal; EMG: electromyography; MVC: maximum voluntary contraction; SSQ: simulator sickness questionnaire; ECG: electrocardiogram; NEMG: normalised electromyography.

Postural responses to sinusoidal modulations of viewpoint position in a virtual environment.

Visual self-motion information is known to contribute to postural control, but it is unclear precisely which aspects of visual motion information drive changes in posture. We report here results for standing humans which suggest that there is a speed of movement threshold that must be exceeded by a visual stimulus if a posture response is to be generated. We use signal-to-noise ratio (SNR) methods to measure the strength of steady-state visually evoked posture responses (SSVEPRs) to sinusoidal modulations of visual viewpoint position in a virtual environment (VE). Using threshold estimates found from data which show how posture responses depend on visual stimulus amplitude, we show that the sensitivity of the visuo-postural response system increases with the temporal frequency at which the position of one's viewpoint is modulated. We show further that there is a speed of movement threshold, on average 1.85 cm/s, which must be exceeded by a left-right modulation of viewpoint position if a posture response is to be generated. A comparison of visual stimulus visibility to posture response thresholds suggests that one tends to not make postural responses to visual stimuli that are unseen. Finally, we found small correlations between motion sickness in these experiments and both the time spent in the VE and the frequency of viewpoint movement.

Foveation Pipeline for 360° Video-Based Telemedicine.

Pan-tilt-zoom (PTZ) and omnidirectional cameras serve as a video-mediated communication interface for telemedicine. Most cases use either PTZ or omnidirectional cameras exclusively; even when used together, images from the two are shown separately on 2D displays. Conventional foveated imaging techniques may offer a solution for exploiting the benefits of both cameras, i.e., the high resolution of the PTZ camera and the wide field-of-view of the omnidirectional camera, but displaying the unified image on a 2D display would reduce the benefit of "omni-" directionality. In this paper, we introduce a foveated imaging pipeline designed to support virtual reality head-mounted displays (HMDs). The pipeline consists of two parallel processes: one for estimating parameters for the integration of the two images and another for rendering images in real time. A control mechanism for placing the foveal region (i.e., high-resolution area) in the scene and zooming is also proposed. Our evaluations showed that the proposed pipeline achieved, on average, 17 frames per second when rendering the foveated view on an HMD, and showed angular resolution improvement on the foveal region compared with the omnidirectional camera view. However, the improvement was less significant when the zoom level was 8× and more. We discuss possible improvement points and future research directions.

Head-Mounted Display-Based Microscopic Imaging System with Customizable Field Size and Viewpoint.

In recent years, the use of microinjections has increased in life science and biotechnology fields; specific examples include artificial insemination and gene manipulation. Microinjections are mainly performed based on visual information; thus, the operator needs high-level skill because of the narrowness of the visual field. Additionally, microinjections are performed as the operator views a microscopic image on a display; the position of the display requires the operator to maintain an awkward posture throughout the procedure. In this study, we developed a microscopic image display apparatus for microinjections based on a view-expansive microscope. The prototype of the view-expansive microscope has problems related to the variations in brightness and focal blur that accompany changes in the optical path length and amount of reflected light. Therefore, we propose the use of a variable-focus device to expand the visual field and thus circumvent the above-mentioned problems. We evaluated the observable area of the system using this variable-focus device. We confirmed that the observable area is 261.4 and 13.9 times larger than that of a normal microscope and conventional view-expansive microscopic system, respectively. Finally, observations of mouse embryos were carried out by using the developed system. We confirmed that the microscopic images can be displayed on a head-mounted display in real time with the desired point and field sizes.

A General Age-Specific Mortality Model With an Example Indexed by Child Mortality or Both Child and Adult Mortality.

The majority of countries in Africa and nearly one-third of all countries require mortality models to infer the complete age schedules of mortality that are required to conduct population estimates, projections/forecasts, and other tasks in demography and epidemiology. Models that relate child mortality to mortality at other ages are important because almost all countries have measures of child mortality. A general, parameterizable component model (SVD-Comp) of mortality is defined using the singular value decomposition and calibrated to the relationship between child or child/adult mortality and mortality at other ages in the observed mortality schedules of the Human Mortality Database. Cross-validation is used to validate the model, and the predictive performance of the model is compared with that of the log-quadratic (Log-Quad) model, which is designed to do the same thing. Prediction and cross-validation tests indicate that the child mortality-calibrated SVD-Comp is able to accurately represent the observed mortality schedules in the Human Mortality Database, is robust to the selection of mortality schedules used for calibration, and performs better than the Log-Quad model. The child mortality-calibrated SVD-Comp can be used where and when child mortality is available but mortality at other ages is unknown.

Real-Time Eyeblink Detector and Eye State Classifier for Virtual Reality (VR) Headsets (Head-Mounted Displays, HMDs).

The aim of the study is to develop a real-time eyeblink detection algorithm that can detect eyeblinks during the closing phase for a virtual reality headset (VR headset) and accordingly classify the eye's current state (open or closed). The proposed method utilises analysis of a motion vector for detecting eyelid closure, and a Haar cascade classifier (HCC) for localising the eye in the captured frame. When the downward motion vector (DMV) is detected, a cross-correlation between the current region of interest (eye in the current frame) and a template image for an open eye is used for verifying eyelid closure. A finite state machine is used for decision making regarding eyeblink occurrence and tracking the eye state in a real-time video stream. The main contributions of this study are, first, the ability of the proposed algorithm to detect eyeblinks during the closing or the pause phases before the occurrence of the reopening phase of the eyeblink. Second, realising the proposed approach by implementing a valid real-time eyeblink detection sensor for a VR headset based on a real case scenario. The sensor is used in the ongoing study that we are conducting. The performance of the proposed method was 83.9% for accuracy, 91.8% for precision and 90.40% for the recall. The processing time for each frame took approximately 11 milliseconds. Additionally, we present a new dataset for non-frontal eye monitoring configuration for eyeblink tracking inside a VR headset. The data annotations are also included, such that the dataset can be used for method validation and performance evaluation in future studies.

Quantification of thiols and disulfides.

BACKGROUND: Disulfide bond formation is a key posttranslational modification, with implications for structure, function and stability of numerous proteins. While disulfide bond formation is a necessary and essential process for many proteins, it is deleterious and disruptive for others. Cells go to great lengths to regulate thiol-disulfide bond homeostasis, typically with several, apparently redundant, systems working in parallel. Dissecting the extent of oxidation and reduction of disulfides is an ongoing challenge due, in part, to the facility of thiol/disulfide exchange reactions. SCOPE OF REVIEW: In the present account, we briefly survey the toolbox available to the experimentalist for the chemical determination of thiols and disulfides. We have chosen to focus on the key chemical aspects of current methodology, together with identifying potential difficulties inherent in their experimental implementation. MAJOR CONCLUSIONS: While many reagents have been described for the measurement and manipulation of the redox status of thiols and disulfides, a number of these methods remain underutilized. The ability to effectively quantify changes in redox conditions in living cells presents a continuing challenge. GENERAL SIGNIFICANCE: Many unresolved questions in the metabolic interconversion of thiols and disulfides remain. For example, while pool sizes of redox pairs and their intracellular distribution are being uncovered, very little is known about the flux in thiol-disulfide exchange pathways. New tools are needed to address this important aspect of cellular metabolism. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.

Development of a surgical navigation system based on augmented reality using an optical see-through head-mounted display.

The surgical navigation system has experienced tremendous development over the past decades for minimizing the risks and improving the precision of the surgery. Nowadays, Augmented Reality (AR)-based surgical navigation is a promising technology for clinical applications. In the AR system, virtual and actual reality are mixed, offering real-time, high-quality visualization of an extensive variety of information to the users (Moussa et al., 2012) [1]. For example, virtual anatomical structures such as soft tissues, blood vessels and nerves can be integrated with the real-world scenario in real time. In this study, an AR-based surgical navigation system (AR-SNS) is developed using an optical see-through HMD (head-mounted display), aiming at improving the safety and reliability of the surgery. With the use of this system, including the calibration of instruments, registration, and the calibration of HMD, the 3D virtual critical anatomical structures in the head-mounted display are aligned with the actual structures of patient in real-world scenario during the intra-operative motion tracking process. The accuracy verification experiment demonstrated that the mean distance and angular errors were respectively 0.809±0.05mm and 1.038°±0.05°, which was sufficient to meet the clinical requirements.

Experimental identification of the behaviour of and lateral forces from freely-walking pedestrians on laterally oscillating structures in a virtual reality environment.

Modelling pedestrian loading on lively structures such as bridges remains a challenge. This is because pedestrians have the capacity to interact with vibrating structures which can lead to amplification of the structural response. Current design guidelines are often inaccurate and limiting as they do not sufficiently acknowledge this effect. This originates in scarcity of data on pedestrian behaviour on vibrating ground and uncertainty as to the accuracy of results from previous experimental campaigns aiming to quantify pedestrian behaviour in this case. To this end, this paper presents a novel experimental setup developed to evaluate pedestrian actions on laterally oscillating ground in the laboratory environment while avoiding the implications of artificiality and allowing for unconstrained gait. A biologically-inspired approach was adopted in its development, relying on appreciation of operational complexities of biological systems, in particular their adaptability and control requirements. In determination of pedestrian forces to the structure consideration was given to signal processing issues which have been neglected in past studies. The results from tests conducted on the setup are related to results from previous experimental investigations and outputs of the inverted pendulum pedestrian model for walking on laterally oscillating ground, which is capable of generating self-excited forces.

Estimating postural control with the balance rehabilitation unit: measurement consistency, accuracy, validity, and comparison with dynamic posturography.

OBJECTIVE: To examine the psychometric properties (test-retest reliability, concurrent validity, construct validity) of the Balance Rehabilitation Unit (BRU) during testing of sensory integration processes in healthy adults and individuals with vestibular disorders. DESIGN: Experimental cross-sectional design. SETTING: Clinic. PARTICIPANTS: Participants (N=90) included 30 subjects with vestibular disorders (age range, 18-85y), 30 young healthy adults (age range, 18-50y), and 30 older healthy adults (age range, 60-85y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants were tested twice with the BRU and once with the SMART EquiTest Sensory Organization Test (SOT). The center of pressure (COP) in the anteroposterior direction (COPap) and the COP in the mediolateral direction (COPml) were recorded. The COPap and COPml time series were used to estimate the area and velocity of the COP. RESULTS: The intraclass correlation coefficient of the COP area and velocity measures for the BRU for all subjects was at least .76 in all sensory organization conditions (P<.001). Significant correlations were found between the BRU and the SOT, ranging from .64 to .81 for COP area and from .44 to .76 for COP velocity. The older control group had significantly greater COP area and velocity compared with younger controls for the BRU and the SOT. The COP (area, velocity) was significantly higher for the younger individuals in the vestibular group than the younger controls. CONCLUSIONS: The reliability and validity of COP measurements obtained during testing of the sensory integration processes were demonstrated using the BRU. Future work should examine the responsiveness of these measures when individuals with balance disorders participate in rehabilitation.