Dermal features derived from optoacoustic tomograms via machine learning correlate microangiopathy phenotypes with diabetes stage.

Skin microangiopathy has been associated with diabetes. Here we show that skin-microangiopathy phenotypes in humans can be correlated with diabetes stage via morphophysiological cutaneous features extracted from raster-scan optoacoustic mesoscopy (RSOM) images of skin on the leg. We obtained 199 RSOM images from 115 participants (40 healthy and 75 with diabetes), and used machine learning to segment skin layers and microvasculature to identify clinically explainable features pertaining to different depths and scales of detail that provided the highest predictive power. Features in the dermal layer at the scale of detail of 0.1-1 mm (such as the number of junction-to-junction branches) were highly sensitive to diabetes stage. A 'microangiopathy score' compiling the 32 most-relevant features predicted the presence of diabetes with an area under the receiver operating characteristic curve of 0.84. The analysis of morphophysiological cutaneous features via RSOM may allow for the discovery of diabetes biomarkers in the skin and for the monitoring of diabetes status.

Users' Perspective on the AI-Based Smartphone PROTEIN App for Personalized Nutrition and Healthy Living: A Modified Technology Acceptance Model (mTAM) Approach.

The ubiquitous nature of smartphone ownership, its broad application and usage, along with its interactive delivery of timely feedback are appealing for health-related behavior change interventions via mobile apps. However, users' perspectives about such apps are vital in better bridging the gap between their design intention and effective practical usage. In this vein, a modified technology acceptance model (mTAM) is proposed here, to explain the relationship between users' perspectives when using an AI-based smartphone app for personalized nutrition and healthy living, namely, PROTEIN, and the mTAM constructs toward behavior change in their nutrition and physical activity habits. In particular, online survey data from 85 users of the PROTEIN app within a period of 2 months were subjected to confirmatory factor analysis (CFA) and regression analysis (RA) to reveal the relationship of the mTAM constructs, i.e., perceived usefulness (PU), perceived ease of use (PEoU), perceived novelty (PN), perceived personalization (PP), usage attitude (UA), and usage intention (UI) with the users' behavior change (BC), as expressed via the acceptance/rejection of six related hypotheses (H1-H6), respectively. The resulted CFA-related parameters, i.e., factor loading (FL) with the related p-value, average variance extracted (AVE), and composite reliability (CR), along with the RA results, have shown that all hypotheses H1-H6 can be accepted (p < 0.001). In particular, it was found that, in all cases, FL > 0.5, CR > 0.7, AVE > 0.5, indicating that the items/constructs within the mTAM framework have good convergent validity. Moreover, the adjusted coefficient of determination (R 2) was found within the range of 0.224-0.732, justifying the positive effect of PU, PEoU, PN, and PP on the UA, that in turn positively affects the UI, leading to the BC. Additionally, using a hierarchical RA, a significant change in the prediction of BC from UA when the UI is used as a mediating variable was identified. The explored mTAM framework provides the means for explaining the role of each construct in the functionality of the PROTEIN app as a supportive tool for the users to improve their healthy living by adopting behavior change in their dietary and physical activity habits. The findings herein offer insights and references for formulating new strategies and policies to improve the collaboration among app designers, developers, behavior scientists, nutritionists, physical activity/exercise physiology experts, and marketing experts for app design/development toward behavior change.

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.

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.

DeepFoG: An IMU-Based Detection of Freezing of Gait Episodes in Parkinson's Disease Patients via Deep Learning.

Freezing of Gait (FoG) is a movement disorder that mostly appears in the late stages of Parkinson's Disease (PD). It causes incapability of walking, despite the PD patient's intention, resulting in loss of coordination that increases the risk of falls and injuries and severely affects the PD patient's quality of life. Stress, emotional stimulus, and multitasking have been encountered to be associated with the appearance of FoG episodes, while the patient's functionality and self-confidence are constantly deteriorating. This study suggests a non-invasive method for detecting FoG episodes, by analyzing inertial measurement unit (IMU) data. Specifically, accelerometer and gyroscope data from 11 PD subjects, as captured from a single wrist-worn IMU sensor during continuous walking, are processed via Deep Learning for window-based detection of the FoG events. The proposed approach, namely DeepFoG, was evaluated in a Leave-One-Subject-Out (LOSO) cross-validation (CV) and 10-fold CV fashion schemes against its ability to correctly estimate the existence or not of a FoG episode at each data window. Experimental results have shown that DeepFoG performs satisfactorily, as it achieves 83%/88% and 86%/90% sensitivity/specificity, for LOSO CV and 10-fold CV schemes, respectively. The promising performance of the proposed DeepFoG reveals the potentiality of single-arm IMU-based real-time FoG detection that could guide effective interventions via stimuli, such as rhythmic auditory stimulation (RAS) and hand vibration. In this way, DeepFoG may scaffold the elimination of risk of falls in PD patients, sustaining their quality of life in everyday living activities.

Unobtrusive detection of Parkinson's disease from multi-modal and in-the-wild sensor data using deep learning techniques.

Parkinson's Disease (PD) is the second most common neurodegenerative disorder, affecting more than 1% of the population above 60 years old with both motor and non-motor symptoms of escalating severity as it progresses. Since it cannot be cured, treatment options focus on the improvement of PD symptoms. In fact, evidence suggests that early PD intervention has the potential to slow down symptom progression and improve the general quality of life in the long term. However, the initial motor symptoms are usually very subtle and, as a result, patients seek medical assistance only when their condition has substantially deteriorated; thus, missing the opportunity for an improved clinical outcome. This situation highlights the need for accessible tools that can screen for early motor PD symptoms and alert individuals to act accordingly. Here we show that PD and its motor symptoms can unobtrusively be detected from the combination of accelerometer and touchscreen typing data that are passively captured during natural user-smartphone interaction. To this end, we introduce a deep learning framework that analyses such data to simultaneously predict tremor, fine-motor impairment and PD. In a validation dataset from 22 clinically-assessed subjects (8 Healthy Controls (HC)/14 PD patients with a total data contribution of 18.305 accelerometer and 2.922 typing sessions), the proposed approach achieved 0.86/0.93 sensitivity/specificity for the binary classification task of HC versus PD. Additional validation on data from 157 subjects (131 HC/26 PD with a total contribution of 76.528 accelerometer and 18.069 typing sessions) with self-reported health status (HC or PD), resulted in area under curve of 0.87, with sensitivity/specificity of 0.92/0.69 and 0.60/0.92 at the operating points of highest sensitivity or specificity, respectively. Our findings suggest that the proposed method can be used as a stepping stone towards the development of an accessible PD screening tool that will passively monitor the subject-smartphone interaction for signs of PD and which could be used to reduce the critical gap between disease onset and start of treatment.

Smartwatch-based Activity Analysis During Sleep for Early Parkinson's Disease Detection.

Parkinson's Disease (PD) is the second most common neurodegenerative disorder with the non-motor symptoms preceding the motor impairment that is needed for clinical diagnosis. In the current study, an angle-based analysis that processes activity data during sleep from a smartwatch for quantification of sleep quality, when applied on controls and PD patients, is proposed. Initially, changes in their arm angle due to activity are captured from the smartwatch triaxial accelerometry data and used for the estimation of the corresponding binary state (awake/sleep). Then, sleep metrics (i.e., sleep efficiency index, total sleep time, sleep fragmentation index, sleep onset latency, and wake after sleep onset) are computed and used for the discrimination between controls and PD patients. A process of validation of the proposed approach when compared with the PSG-based ground truth in an in-the-clinic setting, resulted in comparable state estimation. Moreover, data from 15 early PD patients and 11 healthy controls were used as a test set, including 1,376 valid sleep recordings in-the-wild setting. The univariate analysis of the extracted sleep metrics achieved up to 0.77 AUC in early PD patients vs. healthy controls classification and exhibited a statistically significant correlation (up to 0.46) with the clinical PD Sleep Scale 2 counterpart Items. The findings of the proposed method show the potentiality to capture non-motor behavior from users' nocturnal activity to detect PD in the early stage.

Screening of Parkinsonian subtle fine-motor impairment from touchscreen typing via deep learning.

Fine-motor impairment (FMI) is progressively expressed in early Parkinson's Disease (PD) patients and is now known to be evident in the immediate prodromal stage of the condition. The clinical techniques for detecting FMI may not be robust enough and here, we show that the subtle FMI of early PD patients can be effectively estimated from the analysis of natural smartphone touchscreen typing via deep learning networks, trained in stages of initialization and fine-tuning. In a validation dataset of 36,000 typing sessions from 39 subjects (17 healthy/22 PD patients with medically validated UPDRS Part III single-item scores), the proposed approach achieved values of area under the receiver operating characteristic curve (AUC) of 0.89 (95% confidence interval: 0.80-0.96) with sensitivity/specificity: 0.90/0.83. The derived estimations result in statistically significant ([Formula: see text]) correlation of 0.66/0.73/0.58 with the clinical standard UPDRS Part III items 22/23/31, respectively. Further validation analysis on 9 de novo PD patients vs. 17 healthy controls classification resulted in AUC of 0.97 (0.93-1.00) with 0.93/0.90. For 253 remote study participants, with self-reported health status providing 252.000 typing sessions via a touchscreen typing data acquisition mobile app (iPrognosis), the proposed approach predicted 0.79 AUC (0.66-0.91) with 0.76/0.71. Remote and unobtrusive screening of subtle FMI via natural smartphone usage, may assist in consolidating early and accurate diagnosis of PD.

Detection of Mild Cognitive Impairment Through Natural Language and Touchscreen Typing Processing.

Mild cognitive impairment (MCI), an identified prodromal stage of Alzheimer's Disease (AD), often evades detection in the early stages of the condition, when existing diagnostic methods are employed in the clinical setting. From an alternative perspective, smartphone interaction behavioral data, unobtrusively acquired in a non-clinical setting, can assist the screening and monitoring of MCI and its symptoms' progression. In this vein, the diagnostic ability of digital biomarkers, drawn from Fine Motor Impairment (FMI)- and Spontaneous Written Speech (SWS)-related data analysis, are examined here. In particular, keystroke dynamics derived from touchscreen typing activities, using Convolutional Neural Networks, along with linguistic features of SWS through Natural Language Processing (NLP), were used to distinguish amongst MCI patients and healthy controls (HC). Analytically, three indices of FMI (rigidity, bradykinesia and alternate finger tapping) and nine NLP features, related with lexical richness, grammatical, syntactical complexity, and word deficits, formed the feature space. The proposed approach was tested on two demographically matched groups of 11 MCI patients and 12 HC, having undergone the same neuropsychological tests, producing 4,930 typing sessions and 78 short texts, within 6 months, for analysis. A cascaded-classifier scheme was realized under three different feature combinations and validated via a Leave-One-Subject-Out cross-validation scheme. The acquired results have shown: (a) keystroke features with a k-NN classifier achieved an Area Under Curve (AUC) of 0.78 [95% confidence interval (CI):0.68-0.88; specificity/sensitivity (SP/SE): 0.64/0.92], (b) NLP features with a Logistic regression classifier achieved an AUC of 0.76 (95% CI: 0.65-0.85; SP/SE: 0.80/0.71), and (c) an ensemble model with the fusion of keystroke and NLP features resulted in AUC of 0.75 (95% CI:0.63-0.86; SP/SE 0.90/0.60). The current findings indicate the potentiality of new digital biomarkers to capture early stages of cognitive decline, providing a highly specific remote screening tool in-the-wild.

Assistive HCI-Serious Games Co-design Insights: The Case Study of i-PROGNOSIS Personalized Game Suite for Parkinson's Disease.

Human-Computer Interaction (HCI) and games set a new domain in understanding people's motivations in gaming, behavioral implications of game play, game adaptation to player preferences and needs for increased engaging experiences in the context of HCI serious games (HCI-SGs). When the latter relate with people's health status, they can become a part of their daily life as assistive health status monitoring/enhancement systems. Co-designing HCI-SGs can be seen as a combination of art and science that involves a meticulous collaborative process. The design elements in assistive HCI-SGs for Parkinson's Disease (PD) patients, in particular, are explored in the present work. Within this context, the Game-Based Learning (GBL) design framework is adopted here and its main game-design parameters are explored for the Exergames, Dietarygames, Emotional games, Handwriting games, and Voice games design, drawn from the PD-related i-PROGNOSIS Personalized Game Suite (PGS) (www.i-prognosis.eu) holistic approach. Two main data sources were involved in the study. In particular, the first one includes qualitative data from semi-structured interviews, involving 10 PD patients and four clinicians in the co-creation process of the game design, whereas the second one relates with data from an online questionnaire addressed by 104 participants spanning the whole related spectrum, i.e., PD patients, physicians, software/game developers. Linear regression analysis was employed to identify an adapted GBL framework with the most significant game-design parameters, which efficiently predict the transferability of the PGS beneficial effect to real-life, addressing functional PD symptoms. The findings of this work can assist HCI-SG designers for designing PD-related HCI-SGs, as the most significant game-design factors were identified, in terms of adding value to the role of HCI-SGs in increasing PD patients' quality of life, optimizing the interaction with personalized HCI-SGs and, hence, fostering a collaborative human-computer symbiosis.

Touchscreen typing pattern analysis for remote detection of the depressive tendency.

Depressive disorder (DD) is a mental illness affecting more than 300 million people worldwide, whereas social stigma and subtle, variant symptoms impede diagnosis. Psychomotor retardation is a common component of DD with a negative impact on motor function, usually reflected on patients' routine activities, including, nowadays, their interaction with mobile devices. Therefore, such interactions constitute an enticing source of information towards unsupervised screening for DD symptoms in daily life. In this vein, this paper proposes a machine learning-based method for discriminating between subjects with depressive tendency and healthy controls, as denoted by self-reported Patient Health Questionnaire-9 (PHQ-9) compound scores, based on typing patterns captured in-the-wild. The latter consisted of keystroke timing sequences and typing metadata, passively collected during natural typing on touchscreen smartphones by 11/14 subjects with/without depressive tendency. Statistical features were extracted and tested in univariate and multivariate classification pipelines to reach a decision on subjects' status. The best-performing pipeline achieved an AUC = 0.89 (0.72-1.00; 95% Confidence Interval) and 0.82/0.86 sensitivity/specificity, with the outputted probabilities significantly correlating (>0.60) with the respective PHQ-9 scores. This work adds to the findings of previous research associating typing patterns with psycho-motor impairment and contributes to the development of an unobtrusive, high-frequency monitoring of depressive tendency in everyday living.

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.

Touchscreen typing-pattern analysis for detecting fine motor skills decline in early-stage Parkinson's disease.

Parkinson's disease (PD) is a degenerative movement disorder causing progressive disability that severely affects patients' quality of life. While early treatment can produce significant benefits for patients, the mildness of many early signs combined with the lack of accessible high-frequency monitoring tools may delay clinical diagnosis. To meet this need, user interaction data from consumer technologies have recently been exploited towards unsupervised screening for PD symptoms in daily life. Similarly, this work proposes a method for detecting fine motor skills decline in early PD patients via analysis of patterns emerging from finger interaction with touchscreen smartphones during natural typing. Our approach relies on low-/higher-order statistical features of keystrokes timing and pressure variables, computed from short typing sessions. Features are fed into a two-stage multi-model classification pipeline that reaches a decision on the subject's status (PD patient/control) by gradually fusing prediction probabilities obtained for individual typing sessions and keystroke variables. This method achieved an AUC = 0.92 and 0.82/0.81 sensitivity/specificity (matched groups of 18 early PD patients/15 controls) with discriminant features plausibly correlating with clinical scores of relevant PD motor symptoms. These findings suggest an improvement over similar approaches, thereby constituting a further step towards unobtrusive early PD detection from routine activities.

Fuzzy logic-based risk of fall estimation using smartwatch data as a means to form an assistive feedback mechanism in everyday living activities.

This Letter aims to create a fuzzy logic-based assistive prevention tool for falls, based on accessible sensory technology, such as smartwatch, resulting in monitoring of the risk factors of falls caused by orthostatic hypotension (OH); a drop in systolic blood pressure (DSBP) >20 mmHg due to postural changes. Epidemiological studies have shown that OH is a high risk factor for falls and has a strong impact in quality of life (QoL) of the elderly's, especially for some cases such as Parkinsonians. Based on smartwatch data, it is explored here how statistical features of heart rate variability (HRV) can lead to DSBP prediction and estimation of the risk of fall. In this vein, a pilot study was conducted in collaboration with five Greek Parkinson's Foundation patients and ten healthy volunteers. Taking into consideration, the estimated DSBP and additional statistics of the user's medical/behavioural history, a fuzzy logic inference system was developed, to estimate the instantaneous risk of fall. The latter is fed back to the user with a mechanism chosen by him/her (i.e. vibration and/or sound), to prevent a possible fall, and also sent to the attentive carers and/or healthcare professionals for a home-based monitoring beyond the clinic. The proposed approach paves the way for effective exploitation of the contribution of smartwatch data, such as HRV, in the sustain of QoL in everyday living activities.