The convergence of traditional and digital biomarkers through AI-assisted biosensing: A new era in translational diagnostics?

Advances in consumer electronics, alongside the fields of microfluidics and nanotechnology have brought to the fore low-cost wearable/portable smart devices. Although numerous smart devices that track digital biomarkers have been successfully translated from bench-to-bedside, only a few follow the same fate when it comes to track traditional biomarkers. Current practices still involve laboratory-based tests, followed by blood collection, conducted in a clinical setting as they require trained personnel and specialized equipment. In fact, real-time, passive/active and robust sensing of physiological and behavioural data from patients that can feed artificial intelligence (AI)-based models can significantly improve decision-making, diagnosis and treatment at the point-of-procedure, by circumventing conventional methods of sampling, and in person investigation by expert pathologists, who are scarce in developing countries. This review brings together conventional and digital biomarker sensing through portable and autonomous miniaturized devices. We first summarise the technological advances in each field vs the current clinical practices and we conclude by merging the two worlds of traditional and digital biomarkers through AI/ML technologies to improve patient diagnosis and treatment. The fundamental role, limitations and prospects of AI in realizing this potential and enhancing the existing technologies to facilitate the development and clinical translation of "point-of-care" (POC) diagnostics is finally showcased.

A Conceptual Framework (2D-ME) for Explaining Self-first and Self-third Person Views of Prototyping Dynamics in Serious Games Design: Experimental Case Study.

BACKGROUND: Design dynamics that evolve during a designer's prototyping process encapsulate important insights about the way the designer is using his or her knowledge, creativity, and reflective thinking. Nevertheless, the capturing of such dynamics is not always an easy task, as they are built through alternations between the self-first and self-third person views. OBJECTIVE: This study aimed at introducing a conceptual framework, namely 2D-ME, to provide an explainable domain that could express the dynamics across the design timeline during a prototyping process of serious games. METHODS: Within the 2D-ME framework, the Technological-Pedagogical-Content Knowledge (TPACK), its adaptation to the serious games (TPACK-Game), and the activity theory frameworks were combined to produce dynamic constructs that incorporate self-first and self-third person extension of the TPACK-Game to Games TPACK, rules, division of labor, and object. The dynamic interplay between such constructs was used as an adaptation engine within an optimization prototype process, so each sequential version of the latter could converge to the designer's initial idea of the serious game. Moreover, higher-order thinking is scaffolded with the internal Activity Interview Script proposed in this paper. RESULTS: An experimental case study of the application of the 2D-ME conceptual framework in the design of a light reflection game was showcased, revealing all the designer's dynamics, both from internal (via a diary) and external (via the prototype version) views. The findings of this case study exemplified the convergence of the prototyping process to an optimized output, by minimizing the mean square error between the conceptual (initial and updated) idea of the prototype, following explainable and tangible constructs within the 2D-ME framework. CONCLUSIONS: The generic structure of the proposed 2D-ME framework allows its transferability to various levels of expertise in serious games mastering, and it is used both for the designer's process exploration and training of the novice ones.

A scoping review of neurodegenerative manifestations in explainable digital phenotyping.

Neurologists nowadays no longer view neurodegenerative diseases, like Parkinson's and Alzheimer's disease, as single entities, but rather as a spectrum of multifaceted symptoms with heterogeneous progression courses and treatment responses. The definition of the naturalistic behavioral repertoire of early neurodegenerative manifestations is still elusive, impeding early diagnosis and intervention. Central to this view is the role of artificial intelligence (AI) in reinforcing the depth of phenotypic information, thereby supporting the paradigm shift to precision medicine and personalized healthcare. This suggestion advocates the definition of disease subtypes in a new biomarker-supported nosology framework, yet without empirical consensus on standardization, reliability and interpretability. Although the well-defined neurodegenerative processes, linked to a triad of motor and non-motor preclinical symptoms, are detected by clinical intuition, we undertake an unbiased data-driven approach to identify different patterns of neuropathology distribution based on the naturalistic behavior data inherent to populations in-the-wild. We appraise the role of remote technologies in the definition of digital phenotyping specific to brain-, body- and social-level neurodegenerative subtle symptoms, emphasizing inter- and intra-patient variability powered by deep learning. As such, the present review endeavors to exploit digital technologies and AI to create disease-specific phenotypic explanations, facilitating the understanding of neurodegenerative diseases as "bio-psycho-social" conditions. Not only does this translational effort within explainable digital phenotyping foster the understanding of disease-induced traits, but it also enhances diagnostic and, eventually, treatment personalization.

Digital Biomarkers for Well-being Through Exergame Interactions: Exploratory Study.

BACKGROUND: Ecologically valid evaluations of patient states or well-being by means of new technologies is a key issue in contemporary research in health and well-being of the aging population. The in-game metrics generated from the interaction of users with serious games (SG) can potentially be used to predict or characterize a user's state of health and well-being. There is currently an increasing body of research that investigates the use of measures of interaction with games as digital biomarkers for health and well-being. OBJECTIVE: The aim of this paper is to predict well-being digital biomarkers from data collected during interactions with SG, using the values of standard clinical assessment tests as ground truth. METHODS: The data set was gathered during the interaction with patients with Parkinson disease with the webFitForAll exergame platform, an SG engine designed to promote physical activity among older adults, patients, and vulnerable populations. The collected data, referred to as in-game metrics, represent the body movements captured by a 3D sensor camera and translated into game analytics. Standard clinical tests gathered before and after the long-term interaction with exergames (preintervention test vs postintervention test) were used to provide user baselines. RESULTS: Our results showed that in-game metrics can effectively categorize participants into groups of different cognitive and physical states. Different in-game metrics have higher descriptive values for specific tests and can be used to predict the value range for these tests. CONCLUSIONS: Our results provide encouraging evidence for the value of in-game metrics as digital biomarkers and can boost the analysis of improving in-game metrics to obtain more detailed results.

Diagnostic accuracy of keystroke dynamics as digital biomarkers for fine motor decline in neuropsychiatric disorders: a systematic review and meta-analysis.

The unmet timely diagnosis requirements, that take place years after substantial neural loss and neuroperturbations in neuropsychiatric disorders, affirm the dire need for biomarkers with proven efficacy. In Parkinson's disease (PD), Mild Cognitive impairment (MCI), Alzheimers disease (AD) and psychiatric disorders, it is difficult to detect early symptoms given their mild nature. We hypothesize that employing fine motor patterns, derived from natural interactions with keyboards, also knwon as keystroke dynamics, could translate classic finger dexterity tests from clinics to populations in-the-wild for timely diagnosis, yet, further evidence is required to prove this efficiency. We have searched PubMED, Medline, IEEEXplore, EBSCO and Web of Science for eligible diagnostic accuracy studies employing keystroke dynamics as an index test for the detection of neuropsychiatric disorders as the main target condition. We evaluated the diagnostic performance of keystroke dynamics across 41 studies published between 2014 and March 2022, comprising 3791 PD patients, 254 MCI patients, and 374 psychiatric disease patients. Of these, 25 studies were included in univariate random-effect meta-analysis models for diagnostic performance assessment. Pooled sensitivity and specificity are 0.86 (95% Confidence Interval (CI) 0.82-0.90, I2 = 79.49%) and 0.83 (CI 0.79-0.87, I2 = 83.45%) for PD, 0.83 (95% CI 0.65-1.00, I2 = 79.10%) and 0.87 (95% CI 0.80-0.93, I2 = 0%) for psychomotor impairment, and 0.85 (95% CI 0.74-0.96, I2 = 50.39%) and 0.82 (95% CI 0.70-0.94, I2 = 87.73%) for MCI and early AD, respectively. Our subgroup analyses conveyed the diagnosis efficiency of keystroke dynamics for naturalistic self-reported data, and the promising performance of multimodal analysis of naturalistic behavioral data and deep learning methods in detecting disease-induced phenotypes. The meta-regression models showed the increase in diagnostic accuracy and fine motor impairment severity index with age and disease duration for PD and MCI. The risk of bias, based on the QUADAS-2 tool, is deemed low to moderate and overall, we rated the quality of evidence to be moderate. We conveyed the feasibility of keystroke dynamics as digital biomarkers for fine motor decline in naturalistic environments. Future work to evaluate their performance for longitudinal disease monitoring and therapeutic implications is yet to be performed. We eventually propose a partnership strategy based on a "co-creation" approach that stems from mechanistic explanations of patients' characteristics derived from data obtained in-clinics and under ecologically valid settings. The protocol of this systematic review and meta-analysis is registered in PROSPERO; identifier CRD42021278707. The presented work is supported by the KU-KAIST joint research center.

Machine Learning-Based Analysis of Digital Movement Assessment and ExerGame Scores for Parkinson's Disease Severity Estimation.

Neurodegenerative Parkinson's Disease (PD) is one of the common incurable diseases among the elderly. Clinical assessments are characterized as standardized means for PD diagnosis. However, relying on medical evaluation of a patient's status can be subjective to physicians' experience, making the assessment process susceptible to human errors. The use of ICT-based tools for capturing the status of patients with PD can provide more objective and quantitative metrics. In this vein, the Personalized Serious Game Suite (PGS) and intelligent Motor Assessment Tests (iMAT), produced within the i-PROGNOSIS European project (www.i-prognosis.eu), are explored in the current study. More specifically, data from 27 patients with PD at Stage 1 (9) and Stage 3 (18) produced from their interaction with PGS/iMAT are analyzed. Five feature vector (FV) scenarios are set, including features from PGS or iMAT scores or their combination, after also taking into consideration the age of patients with PD. These FVs are fed into three machine learning classifiers, i.e., K-Nearest Neighbor (KNN), Support Vector Machines (SVM), and Random Forest (RF), to infer the stage of each patient with PD. A Leave-One-Out Cross-Validation (LOOCV) method is adopted for testing the classification performance. The experimental results show that a high (>90%) classification accuracy is achieved from both data sources (PGS/iMAT), justifying the effectiveness of PGS/iMAT to efficiently reflect the motor skill status of patients with PD and further potentiating PGS/iMAT enhancement with a machine learning a part to infer for the stage of patients with PD. Clearly, this integrated approach provides new opportunities for remote monitoring of the stage of patients with PD, contributing to a more efficient organization and set up of personalized interventions.

Parkinson's Disease Detection Based on Running Speech Data From Phone Calls.

OBJECTIVE: Parkinson's Disease (PD) is a progressive neurodegenerative disorder, manifesting with subtle early signs, which, often hinder timely and early diagnosis and treatment. The development of accessible, technology-based methods for longitudinal PD symptoms tracking in daily living, offers the potential for transforming disease assessment and accelerating diagnosis. METHODS: A privacy-aware method for classifying patients and healthy controls (HC), on the grounds of speech impairment present in PD, is proposed. Voice features from running speech signals were extracted from passively-captured recordings over voice calls. Language-aware training of multiple- and single-instance learning classifiers was employed to fuse and predict on voice features and demographic data from a multilingual cohort of 498 subjects (392/106 self-reported HC/PD patients). RESULTS: By means of leave-one-subject-out cross-validation, the best-performing models yielded 0.69/0.68/0.63/0.83 area under the Receiver Operating Characteristic curve (AUC) for the binary classification of PD patient vs. HC in sub-cohorts of English/Greek/German/Portuguese-speaking subjects, respectively. Out-of sample testing of the best performing models was conducted in an additional dataset, generated by 63 clinically-assessed subjects (24/39 HC/early PD patients). Testing has resulted in 0.84/0.93/0.83 AUC for the English/Greek/German-speaking sub-cohorts, respectively. CONCLUSIONS: The proposed approach outperforms other methods proposed for language-aware PD detection considering the ecological validity of the voice data. SIGNIFICANCE: This paper introduces for the first time a high-frequency, privacy-aware and unobtrusive PD screening tool based on analysis of voice samples captured during routine phone calls.

DeepLMS: a deep learning predictive model for supporting online learning in the Covid-19 era.

Coronavirus (Covid-19) pandemic has imposed a complete shut-down of face-to-face teaching to universities and schools, forcing a crash course for online learning plans and technology for students and faculty. In the midst of this unprecedented crisis, video conferencing platforms (e.g., Zoom, WebEx, MS Teams) and learning management systems (LMSs), like Moodle, Blackboard and Google Classroom, are being adopted and heavily used as online learning environments (OLEs). However, as such media solely provide the platform for e-interaction, effective methods that can be used to predict the learner's behavior in the OLEs, which should be available as supportive tools to educators and metacognitive triggers to learners. Here we show, for the first time, that Deep Learning techniques can be used to handle LMS users' interaction data and form a novel predictive model, namely DeepLMS, that can forecast the quality of interaction (QoI) with LMS. Using Long Short-Term Memory (LSTM) networks, DeepLMS results in average testing Root Mean Square Error (RMSE) [Formula: see text], and average correlation coefficient between ground truth and predicted QoI values [Formula: see text] [Formula: see text], when tested on QoI data from one database pre- and two ones during-Covid-19 pandemic. DeepLMS personalized QoI forecasting scaffolds user's online learning engagement and provides educators with an evaluation path, additionally to the content-related assessment, enriching the overall view on the learners' motivation and participation in the learning process.

Early Parkinson's Disease Detection via Touchscreen Typing Analysis using Convolutional Neural Networks.

Parkinson's Disease (PD) is the second most common neurodegenerative disorder worldwide, causing both motor and non-motor symptoms. In the early stages, symptoms are mild and patients may ignore their existence. As a result, they do not undergo any related clinical examination; hence delaying their PD diagnosis. In an effort to remedy such delay, analysis of data passively captured from user's interaction with consumer technologies has been recently explored towards remote screening of early PD motor signs. In the current study, a smartphone-based method analyzing subjects' finger interaction with the smartphone screen is developed for the quantification of fine-motor skills decline in early PD using Convolutional Neural Networks. Experimental results from the analysis of keystroke typing in-the-clinic data from 18 early PD patients and 15 healthy controls have shown a classification performance of 0.89 Area Under the Curve (AUC) with 0.79/0.79 sensitivity/specificity, respectively. Evaluation of the generalization ability of the proposed approach was made by its application on typing data arising from a separate self-reported cohort of 27 PD patients' and 84 healthy controls' daily usage with their personal smartphones (data in-the-wild), achieving 0.79 AUC with 0.74/0.78 sensitivity/specificity, respectively. The results show the potentiality of the proposed approach to process keystroke dynamics arising from users' natural typing activity to detect PD, which contributes to the development of digital tools for remote pathological symptom screening.

Exergames for Parkinson's Disease Patients: How Participatory Design Led to Technology Adaptation.

Parkinson's disease (PD) is a neurodegenerative disorder that affects more than 10 million people worldwide. Assistive technology and exergames come to play a beneficial role in positive mood and socialization improvement, overall quality of life and improved confidence with everyday functional activities. More and more Exergames inserts in the market but how many of that are fitting the patient's needs? How many of that took into consideration theirs's opinion. This study describes the Minimum Viable Product (MVP) model "Develop-measure-learn" circle in a co-creation way with the PD patients to develop and improve Exergames for them, and the tools that are needed to accomplish. The most important outcome of this procedure was the proposed development of more realistic games, giving the researchers the step of starting the investigation of 3D solutions.