A Smart Digital Health Platform to Enable Monitoring of Quality of Life and Frailty in Older Patients with Cancer: A Mixed-Methods, Feasibility Study Protocol.

OBJECTIVES: LifeChamps is an EU Horizon 2020 project that aims to create a digital platform to enable monitoring of health-related quality of life and frailty in patients with cancer over the age of 65. Our primary objective is to assess feasibility, usability, acceptability, fidelity, adherence, and safety parameters when implementing LifeChamps in routine cancer care. Secondary objectives involve evaluating preliminary signals of efficacy and cost-effectiveness indicators. DATA SOURCES: This will be a mixed-methods exploratory project, involving four study sites in Greece, Spain, Sweden, and the United Kingdom. The quantitative component of LifeChamps (single-group, pre-post feasibility study) will integrate digital technologies, home-based motion sensors, self-administered questionnaires, and the electronic health record to (1) enable multimodal, real-world data collection, (2) provide patients with a coaching mobile app interface, and (3) equip healthcare professionals with an interactive, patient-monitoring dashboard. The qualitative component will determine end-user usability and acceptability via end-of-study surveys and interviews. CONCLUSION: The first patient was enrolled in the study in January 2023. Recruitment will be ongoing until the project finishes before the end of 2023. IMPLICATIONS FOR NURSING PRACTICE: LifeChamps provides a comprehensive digital health platform to enable continuous monitoring of frailty indicators and health-related quality of life determinants in geriatric cancer care. Real-world data collection will generate "big data" sets to enable development of predictive algorithms to enable patient risk classification, identification of patients in need for a comprehensive geriatric assessment, and subsequently personalized care.

Neurorehabilitation Through Synergistic Man-Machine Interfaces Promoting Dormant Neuroplasticity in Spinal Cord Injury: Protocol for a Nonrandomized Controlled Trial.

BACKGROUND: Spinal cord injury (SCI) constitutes a major sociomedical problem, impacting approximately 0.32-0.64 million people each year worldwide; particularly, it impacts young individuals, causing long-term, often irreversible disability. While effective rehabilitation of patients with SCI remains a significant challenge, novel neural engineering technologies have emerged to target and promote dormant neuroplasticity in the central nervous system. OBJECTIVE: This study aims to develop, pilot test, and optimize a platform based on multiple immersive man-machine interfaces offering rich feedback, including (1) visual motor imagery training under high-density electroencephalographic recording, (2) mountable robotic arms controlled with a wireless brain-computer interface (BCI), (3) a body-machine interface (BMI) consisting of wearable robotics jacket and gloves in combination with a serious game (SG) application, and (4) an augmented reality module. The platform will be used to validate a self-paced neurorehabilitation intervention and to study cortical activity in chronic complete and incomplete SCI at the cervical spine. METHODS: A 3-phase pilot study (clinical trial) was designed to evaluate the NeuroSuitUp platform, including patients with chronic cervical SCI with complete and incomplete injury aged over 14 years and age-/sex-matched healthy participants. Outcome measures include BCI control and performance in the BMI-SG module, as well as improvement of functional independence, while also monitoring neuropsychological parameters such as kinesthetic imagery, motivation, self-esteem, depression and anxiety, mental effort, discomfort, and perception of robotics. Participant enrollment into the main clinical trial is estimated to begin in January 2023 and end by December 2023. RESULTS: A preliminary analysis of collected data during pilot testing of BMI-SG by healthy participants showed that the platform was easy to use, caused no discomfort, and the robotics were perceived positively by the participants. Analysis of results from the main clinical trial will begin as recruitment progresses and findings from the complete analysis of results are expected in early 2024. CONCLUSIONS: Chronic SCI is characterized by irreversible disability impacting functional independence. NeuroSuitUp could provide a valuable complementary platform for training in immersive rehabilitation methods to promote dormant neural plasticity. TRIAL REGISTRATION: ClinicalTrials.gov NCT05465486; https://clinicaltrials.gov/ct2/show/NCT05465486. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/41152.

Studying Physiological Synchrony in Couple Therapy through Partial Directed Coherence: Associations with the Therapeutic Alliance and Meaning Construction.

In line with the growing recognition of the role of embodiment, affect and implicit processes in psychotherapy, several recent studies examine the role of physiological synchrony in the process and outcome of psychotherapy. This study aims to introduce Partial Directed Coherence (PDC) as a novel approach to calculating psychophysiological synchrony and examine its potential to contribute to our understanding of the therapy process. The study adopts a single-case, mixed-method design and examines physiological synchrony in one-couple therapy in relation to the therapeutic alliance and a narrative analysis of meaning construction in the sessions. Interpersonal Physiological Synchrony (IPS) was calculated, via a windowed approach, through PDC of a Heart Rate Variability-derived physiological index, which was measured in the third and penultimate sessions. Our mixed-method analysis shows that PDC quantified significant moments of IPS within and across the sessions, modeling the characteristics of interpersonal interaction as well as the effects of therapy on the interactional dynamics. The findings of this study point to the complex interplay between explicit and implicit levels of interaction and the potential contribution of including physiological synchrony in the study of interactional processes in psychotherapy.

Children and Parents' Awareness Regarding Potential Hazards Derived from the Use of Chemical Products in Greece.

Over the last decades, human activities prompted the high production and widespread use of household chemical products, leading to daily exposure of humans to several chemicals. The objective of this study was to investigate the frequency of chemicals' use by children and parents in Greece and estimate the level of risk awareness and understanding among them. A total of 575 parents and children were asked to answer an anonymous, closed-ended, validated, and self-administered questionnaire. One-third of the children and almost half of the parents participating in the study believed that commonly used chemical products do not pose any risk to human health or to the environment, despite the product labelling. The majority of both children (61.8%) and parents (70.6%) were informed about product safety via the product labelling. Around 20% in both groups could not differentiate between systemic toxicity and acute lethal effects depicted by pictograms on the label and milder hazards, such as skin irritation. Moreover, the information on hazard and precautionary statements appearing on the label was very poorly perceived. Therefore, as both children and parents seem not to clearly identify the hazards and risks arising from the use of everyday chemical products, targeted awareness policies should be implemented to support the safe use of household products.

Physical Training In-Game Metrics for Cognitive Assessment: Evidence from Extended Trials with the Fitforall Exergaming Platform.

Conventional clinical cognitive assessment has its limitations, as evidenced by the environmental shortcomings of various neuropsychological tests conducted away from an older person's everyday environment. Recent research activities have focused on transferring screening tests to computerized forms, as well as on developing short screening tests for screening large populations for cognitive impairment. The purpose of this study was to present an exergaming platform, which was widely trialed (116 participants) to collect in-game metrics (built-in game performance measures). The potential correlation between in-game metrics and cognition was investigated in-depth by scrutinizing different in-game metrics. The predictive value of high-resolution monitoring games was assessed by correlating it with classical neuropsychological tests; the area under the curve (AUC) in the receiver operating characteristic (ROC) analysis was calculated to determine the sensitivity and specificity of the method for detecting mild cognitive impairment (MCI). Classification accuracy was calculated to be 73.53% when distinguishing between MCI and normal subjects, and 70.69% when subjects with mild dementia were also involved. The results revealed evidence that careful design of serious games, with respect to in-game metrics, could potentially contribute to the early and unobtrusive detection of cognitive decline.

Computerized physical and cognitive training improves the functional architecture of the brain in adults with Down syndrome: A network science EEG study.

Understanding the neuroplastic capacity of people with Down syndrome (PwDS) can potentially reveal the causal relationship between aberrant brain organization and phenotypic characteristics. We used resting-state EEG recordings to identify how a neuroplasticity-triggering training protocol relates to changes in the functional connectivity of the brain's intrinsic cortical networks. Brain activity of 12 PwDS before and after a 10-week protocol of combined physical and cognitive training was statistically compared to quantify changes in directed functional connectivity in conjunction with psychosomatometric assessments. PwDS showed increased connectivity within the left hemisphere and from left-to-right hemisphere, as well as increased physical and cognitive performance. Our findings reveal a strong adaptive neuroplastic reorganization as a result of the training that leads to a less-random network with a more pronounced hierarchical organization. Our results go beyond previous findings by indicating a transition to a healthier, more efficient, and flexible network architecture, with improved integration and segregation abilities in the brain of PwDS. Resting-state electrophysiological brain activity is used here for the first time to display meaningful relationships to underlying Down syndrome processes and outcomes of importance in a translational inquiry. This trial is registered with ClinicalTrials.gov Identifier NCT04390321.

Transcriptomic and Immunophenotypic Characterization of Tumor Immune Microenvironment in Squamous Cell Carcinoma of the Oral Tongue.

The tumor immune microenvironment of oral tongue squamous cell carcinoma may be accountable for differences in clinical behavior, particularly between different age groups. We performed RNA expression profiling and evaluated tumor infiltrating lymphocytes (TILs) and their T-cell subsets in order to assess the functional status of oral tongue squamous cell carcinoma tumor microenvironment and detect potentially clinically useful associations. Archival surgical pathology material from sixteen oral tongue squamous cell carcinoma patients was microscopically evaluated for TIL densities. RNA was extracted from macrodissected whole tumor sections and normal controls and RNA expression profiling was performed by the NanoString PanCancer IO 360 Gene Expression Panel. Immunostains for CD4, CD8 and FOXP3 were evaluated manually and by digital image analysis. Oral tongue squamous cell carcinomas had increased TIL densities, numerically dominated by CD4 + T cells, followed by CD8 + and FOXP3 + T cells. RNA expression profiling of tumors versus normal controls showed tumor signature upregulation in inhibitory immune signaling (CTLA4, TIGIT and PD-L2), followed by inhibitory tumor mechanisms (IDO1, TGF-ß, B7-H3 and PD-L1). Patients older than 44 years showed a tumor microenvironment with increased Tregs and CTLA4 expression. Immunohistochemically assessed CD8% correlated well with molecular signatures related to CD8 + cytotoxic T-cell functions. FOXP3% correlated significantly with CTLA4 upregulation. CTLA4 molecular signature could be predicted by FOXP3% assessed by immunohistochemistry (R2 = 0.619, p = 0.026). Oral tongue squamous cell carcinoma hosts a complex inhibitory immune microenvironment, partially reflected in immunohistochemically quantified CD8 + and FOXP3 + T-cell subsets. Immunohistochemistry can be a useful screening tool for detecting tumors with upregulated expression of the targetable molecule CTLA4.

Reduced pain and analgesic use after acoustic binaural beats therapy in chronic pain - A double-blind randomized control cross-over trial.

BACKGROUND: Binaural Beats (BB) consist of two artificial acoustic stimuli with different frequency, presented simultaneously but independently to each ear. The human brain perceives and synchronizes to this frequency difference (entrainment). Aim of this study was to test the hypothesis that brain entrainment to a lower function rhythm, with BB application, can decrease pain perception and analgesic medication use, in chronic pain patients. METHODS: In a double blind, randomized, cross-over trial, BB at 5Hz (theta rhythm) were applied for 30 minutes, under simultaneous electroencephalogram recordings, followed by liberal, on demand use by chronic pain patients for a week, compared to sham stimulation (SS). Pain as the main outcome (numeric scale, NRS), stress (STAI) and medication usage (defined daily doses, DDD) were assessed at baseline, 30 minutes and week's end. RESULTS: Perceived pain (NRS) was significantly reduced in BB intervention (5.6±2.3 to 3.4±2.6, p<0.001), compared to SS (5.2±2.1 to 4.8±2.3, p=0.78), during the first 30-minute phase, as well as at the week's end (to 3.9±2.5 compared to 5.5±2.6 respectively, p<0.001). The mean EEG theta power at 5Hz was significantly increased only during BB application. Stress was significantly reduced at 30 minutes in both interventions but remained reduced only in the BB group at the week's end. Analgesic medication consumption (DDD, g) during the week was significantly less in the BB intervention (3.9±3.7 vs. 4.6±4.1, p<0.05), while reporting equal to SS mean levels of pain. CONCLUSIONS: Acoustic BB reduced pain intensity, stress and analgesic use, compared to SS, in chronic pain patients. SIGNIFICANCE: This study provides evidence that theta rhythm binaural beats can alleviate pain intensity, both after a brief 30 minute and a longer one week on-demand intervention. The subsequent significant reduction in analgesic medication consumption in chronic pain patients' daily living could offer a valuable tool, augmenting the effect of existing pain therapies.

Statistical learning of multisensory regularities is enhanced in musicians: An MEG study.

The present study used magnetoencephalography (MEG) to identify the neural correlates of audiovisual statistical learning, while disentangling the differential contributions of uni- and multi-modal statistical mismatch responses in humans. The applied paradigm was based on a combination of a statistical learning paradigm and a multisensory oddball one, combining an audiovisual, an auditory and a visual stimulation stream, along with the corresponding deviances. Plasticity effects due to musical expertise were investigated by comparing the behavioral and MEG responses of musicians to non-musicians. The behavioral results indicated that the learning was successful for both musicians and non-musicians. The unimodal MEG responses are consistent with previous studies, revealing the contribution of Heschl's gyrus for the identification of auditory statistical mismatches and the contribution of medial temporal and visual association areas for the visual modality. The cortical network underlying audiovisual statistical learning was found to be partly common and partly distinct from the corresponding unimodal networks, comprising right temporal and left inferior frontal sources. Musicians showed enhanced activation in superior temporal and superior frontal gyrus. Connectivity and information processing flow amongst the sources comprising the cortical network of audiovisual statistical learning, as estimated by transfer entropy, was reorganized in musicians, indicating enhanced top-down processing. This neuroplastic effect showed a cross-modal stability between the auditory and audiovisual modalities.

Towards Rehabilitation Robotics: Off-the-Shelf BCI Control of Anthropomorphic Robotic Arms.

Advances in neural interfaces have demonstrated remarkable results in the direction of replacing and restoring lost sensorimotor function in human patients. Noninvasive brain-computer interfaces (BCIs) are popular due to considerable advantages including simplicity, safety, and low cost, while recent advances aim at improving past technological and neurophysiological limitations. Taking into account the neurophysiological alterations of disabled individuals, investigating brain connectivity features for implementation of BCI control holds special importance. Off-the-shelf BCI systems are based on fast, reproducible detection of mental activity and can be implemented in neurorobotic applications. Moreover, social Human-Robot Interaction (HRI) is increasingly important in rehabilitation robotics development. In this paper, we present our progress and goals towards developing off-the-shelf BCI-controlled anthropomorphic robotic arms for assistive technologies and rehabilitation applications. We account for robotics development, BCI implementation, and qualitative assessment of HRI characteristics of the system. Furthermore, we present two illustrative experimental applications of the BCI-controlled arms, a study of motor imagery modalities on healthy individuals' BCI performance, and a pilot investigation on spinal cord injured patients' BCI control and brain connectivity. We discuss strengths and limitations of our design and propose further steps on development and neurophysiological study, including implementation of connectivity features as BCI modality.

Neuroplastic effects of combined computerized physical and cognitive training in elderly individuals at risk for dementia: an eLORETA controlled study on resting states.

The present study investigates whether a combined cognitive and physical training may induce changes in the cortical activity as measured via electroencephalogram (EEG) and whether this change may index a deceleration of pathological processes of brain aging. Seventy seniors meeting the clinical criteria of mild cognitive impairment (MCI) were equally divided into 5 groups: 3 experimental groups engaged in eight-week cognitive and/or physical training and 2 control groups: active and passive. A 5-minute long resting state EEG was measured before and after the intervention. Cortical EEG sources were modelled by exact low resolution brain electromagnetic tomography (eLORETA). Cognitive function was assessed before and after intervention using a battery of neuropsychological tests including the minimental state examination (MMSE). A significant training effect was identified only after the combined training scheme: a decrease in the post- compared to pre-training activity of precuneus/posterior cingulate cortex in delta, theta, and beta bands. This effect was correlated to improvements in cognitive capacity as evaluated by MMSE scores. Our results indicate that combined physical and cognitive training shows indices of a positive neuroplastic effect in MCI patients and that EEG may serve as a potential index of gains versus cognitive declines and neurodegeneration. This trial is registered with ClinicalTrials.gov Identifier NCT02313935.