Data Mining and Fusion Framework for In-Home Monitoring Applications.

Sensor Data Fusion (SDT) algorithms and models have been widely used in diverse applications. One of the main challenges of SDT includes how to deal with heterogeneous and complex datasets with different formats. The present work utilised both homogenous and heterogeneous datasets to propose a novel SDT framework. It compares data mining-based fusion software packages such as RapidMiner Studio, Anaconda, Weka, and Orange, and proposes a data fusion framework suitable for in-home applications. A total of 574 privacy-friendly (binary) images and 1722 datasets gleaned from thermal and Radar sensing solutions, respectively, were fused using the software packages on instances of homogeneous and heterogeneous data aggregation. Experimental results indicated that the proposed fusion framework achieved an average Classification Accuracy of 84.7% and 95.7% on homogeneous and heterogeneous datasets, respectively, with the help of data mining and machine learning models such as Naïve Bayes, Decision Tree, Neural Network, Random Forest, Stochastic Gradient Descent, Support Vector Machine, and CN2 Induction. Further evaluation of the Sensor Data Fusion framework based on cross-validation of features indicated average values of 94.4% for Classification Accuracy, 95.7% for Precision, and 96.4% for Recall. The novelty of the proposed framework includes cost and timesaving advantages for data labelling and preparation, and feature extraction.

ST6GAL1-mediated aberrant sialylation promotes prostate cancer progression.

Aberrant glycosylation is a universal feature of cancer cells, and cancer-associated glycans have been detected in virtually every cancer type. A common change in tumour cell glycosylation is an increase in α2,6 sialylation of N-glycans, a modification driven by the sialyltransferase ST6GAL1. ST6GAL1 is overexpressed in numerous cancer types, and sialylated glycans are fundamental for tumour growth, metastasis, immune evasion, and drug resistance, but the role of ST6GAL1 in prostate cancer is poorly understood. Here, we analyse matched cancer and normal tissue samples from 200 patients and verify that ST6GAL1 is upregulated in prostate cancer tissue. Using MALDI imaging mass spectrometry (MALDI-IMS), we identify larger branched α2,6 sialylated N-glycans that show specificity to prostate tumour tissue. We also monitored ST6GAL1 in plasma samples from >400 patients and reveal ST6GAL1 levels are significantly increased in the blood of men with prostate cancer. Using both in vitro and in vivo studies, we demonstrate that ST6GAL1 promotes prostate tumour growth and invasion. Our findings show ST6GAL1 introduces α2,6 sialylated N-glycans on prostate cancer cells and raise the possibility that prostate cancer cells can secrete active ST6GAL1 enzyme capable of remodelling glycans on the surface of other cells. Furthermore, we find α2,6 sialylated N-glycans expressed by prostate cancer cells can be targeted using the sialyltransferase inhibitor P-3FAX -Neu5Ac. Our study identifies an important role for ST6GAL1 and α2,6 sialylated N-glycans in prostate cancer progression and highlights the opportunity to inhibit abnormal sialylation for the development of new prostate cancer therapeutics. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth.

Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion. One of the key drivers of aberrant glycosylation is the dysregulated expression of glycosylation enzymes within the cancer cell. Here, we demonstrate using multiple independent clinical cohorts that the glycosyltransferase enzyme GALNT7 is upregulated in prostate cancer tissue. We show GALNT7 can identify men with prostate cancer, using urine and blood samples, with improved diagnostic accuracy than serum PSA alone. We also show that GALNT7 levels remain high in progression to castrate-resistant disease, and using in vitro and in vivo models, reveal that GALNT7 promotes prostate tumour growth. Mechanistically, GALNT7 can modify O-glycosylation in prostate cancer cells and correlates with cell cycle and immune signalling pathways. Our study provides a new biomarker to aid the diagnosis of clinically significant disease and cements GALNT7-mediated O-glycosylation as an important driver of prostate cancer progression.

Gene expression analysis reveals a 5-gene signature for progression-free survival in prostate cancer.

Prostate cancer (PCa) is the second most common male cancer worldwide, but effective biomarkers for the presence or progression risk of disease are currently elusive. In a series of nine matched histologically confirmed PCa and benign samples, we carried out an integrated transcriptome-wide gene expression analysis, including differential gene expression analysis and weighted gene co-expression network analysis (WGCNA), which identified a set of potential gene markers highly associated with tumour status (malignant vs. benign). We then used these genes to establish a minimal progression-free survival (PFS)-associated gene signature (GS) (PCBP1, PABPN1, PTPRF, DANCR, and MYC) using least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox regression analyses from The Cancer Genome Atlas prostate adenocarcinoma (TCGA-PRAD) dataset. Our signature was able to predict PFS over 1, 3, and 5 years in TCGA-PRAD dataset, with area under the curve (AUC) of 0.64-0.78, and our signature remained as a prognostic factor independent of age, Gleason score, and pathological T and N stages. A nomogram combining the signature and Gleason score demonstrated improved predictive capability for PFS (AUC: 0.71-0.85) and was superior to the Cambridge Prognostic Group (CPG) model alone and some conventionally used clinicopathological factors in predicting PFS. In conclusion, we have identified and validated a novel five-gene signature and established a nomogram that effectively predicted PFS in patients with PCa. Findings may improve current prognosis tools for PFS and contribute to clinical decision-making in PCa treatment.

Speed of Rapid Serial Visual Presentation of Pictures, Numbers and Words Affects Event-Related Potential-Based Detection Accuracy.

Rapid serial visual presentation (RSVP) based brain-computer interfaces (BCIs) can detect target images among a continuous stream of rapidly presented images, by classifying a viewer's event related potentials (ERPs) associated with the target and non-targets images. Whilst the majority of RSVP-BCI studies to date have concentrated on the identification of a single type of image, namely pictures, here we study the capability of RSVP-BCI to detect three different target image types: pictures, numbers and words. The impact of presentation duration (speed) i.e., 100-200ms (5-10Hz), 200-300ms (3.3-5Hz) or 300-400ms (2.5-3.3Hz), is also investigated. 2-way repeated measure ANOVA on accuracies of detecting targets from non-target stimuli (ratio 1:9) measured via area under the receiver operator characteristics curve (AUC) for N=15 subjects revealed a significant effect of factor Stimulus-Type (pictures, numbers, words) (F (2,28) = 7.243, p = 0.003 ) and for Stimulus-Duration (F (2,28) = 5.591, p = 0.011). Furthermore, there is an interaction between stimulus type and duration: F (4,56) = 4.419, p = 0.004 ). The results indicate that when designing RSVP-BCI paradigms, the content of the images and the rate at which images are presented impact on the accuracy of detection and hence these parameters are key experimental variables in protocol design and applications, which apply RSVP for multimodal image datasets.

Patient and carer survey of remote vital sign telemonitoring for self-management of long-term conditions.

BACKGROUND: Home-based self-monitoring has failed to show intended savings to healthcare budgets yet it continues to emerge and gain popularity. OBJECTIVE: We set out to verify stakeholders' perspectives of remote vital sign telemonitoring. DESIGN: An observational design was adopted by devising a survey for distribution to service users and their informal carers. SAMPLE: Service users in South Eastern Health and Social Care Trust were included. A total of 274 questionnaires were issued. Data from 97 patients (35% response rate) and 49 carers were analysed. Of these, 81 patients and 48 of their carers experienced a monitoring service known as TF3 and 16 patients and 1 carer experienced a service known as U-Tell. The cohorts comprised people living with a number of long-term conditions: diabetes, hypertension after stroke, chronic heart failure, chronic obstructive pulmonary disorder, bronchiectasis and those requiring anticoagulation using warfarin. RESULTS: Analysis showed that respondents were supportive of the technology with 90.7% of patients agreeing or strongly agreeing with the statement: the remote monitoring system assisted me in managing my health on a day-to-day basis. The patients liked the technology largely because it provided empowerment and control for self-management and allowed them to continue with their lives without major disruption. These views were independent of the technology used and not associated with the patient's long-term conditions, gender or age. There were no reported adverse incidents. CONCLUSION: As self-monitoring becomes more relevant to healthcare delivery, the technology will be accepted by many in the population with long-term conditions.

Androgen-regulated transcription of ESRP2 drives alternative splicing patterns in prostate cancer.

Prostate is the most frequent cancer in men. Prostate cancer progression is driven by androgen steroid hormones, and delayed by androgen deprivation therapy (ADT). Androgens control transcription by stimulating androgen receptor (AR) activity, yet also control pre-mRNA splicing through less clear mechanisms. Here we find androgens regulate splicing through AR-mediated transcriptional control of the epithelial-specific splicing regulator ESRP2. Both ESRP2 and its close paralog ESRP1 are highly expressed in primary prostate cancer. Androgen stimulation induces splicing switches in many endogenous ESRP2-controlled mRNA isoforms, including splicing switches correlating with disease progression. ESRP2 expression in clinical prostate cancer is repressed by ADT, which may thus inadvertently dampen epithelial splice programmes. Supporting this, treatment with the AR antagonist bicalutamide (Casodex) induced mesenchymal splicing patterns of genes including FLNB and CTNND1. Our data reveals a new mechanism of splicing control in prostate cancer with important implications for disease progression.

Wearable technology-based metrics for predicting operator performance during cardiac catheterisation.

INTRODUCTION: Unobtrusive metrics that can auto-assess performance during clinical procedures are of value. Three approaches to deriving wearable technology-based metrics are explored: (1) eye tracking, (2) psychophysiological measurements [e.g. electrodermal activity (EDA)] and (3) arm and hand movement via accelerometry. We also measure attentional capacity by tasking the operator with an additional task to track an unrelated object during the procedure. METHODS: Two aspects of performance are measured: (1) using eye gaze and psychophysiology metrics and (2) measuring attentional capacity via an additional unrelated task (to monitor a visual stimulus/playing cards). The aim was to identify metrics that can be used to automatically discriminate between levels of performance or at least between novices and experts. The study was conducted using two groups: (1) novice operators and (2) expert operators. Both groups made two attempts at a coronary angiography procedure using a full-physics virtual reality simulator. Participants wore eye tracking glasses and an E4 wearable wristband. Areas of interest were defined to track visual attention on display screens, including: (1) X-ray, (2) vital signs, (3) instruments and (4) the stimulus screen (for measuring attentional capacity). RESULTS: Experts provided greater dwell time (63% vs 42%, p = 0.03) and fixations (50% vs 34%, p = 0.04) on display screens. They also provided greater dwell time (11% vs 5%, p = 0.006) and fixations (9% vs 4%, p = 0.007) when selecting instruments. The experts' performance for tracking the unrelated object during the visual stimulus task negatively correlated with total errors (r = - 0.95, p = 0.0009). Experts also had a higher standard deviation of EDA (2.52 µS vs 0.89 µS, p = 0.04). CONCLUSIONS: Eye tracking metrics may help discriminate between a novice and expert operator, by showing that experts maintain greater visual attention on the display screens. In addition, the visual stimulus study shows that an unrelated task can measure attentional capacity. Trial registration This work is registered through clinicaltrials.gov, a service of the U.S. National Health Institute, and is identified by the trial reference: NCT02928796.

Automatic Annotation for Human Activity Recognition in Free Living Using a Smartphone.

Data annotation is a time-consuming process posing major limitations to the development of Human Activity Recognition (HAR) systems. The availability of a large amount of labeled data is required for supervised Machine Learning (ML) approaches, especially in the case of online and personalized approaches requiring user specific datasets to be labeled. The availability of such datasets has the potential to help address common problems of smartphone-based HAR, such as inter-person variability. In this work, we present (i) an automatic labeling method facilitating the collection of labeled datasets in free-living conditions using the smartphone, and (ii) we investigate the robustness of common supervised classification approaches under instances of noisy data. We evaluated the results with a dataset consisting of 38 days of manually labeled data collected in free living. The comparison between the manually and the automatically labeled ground truth demonstrated that it was possible to obtain labels automatically with an 80⁻85% average precision rate. Results obtained also show how a supervised approach trained using automatically generated labels achieved an 84% f-score (using Neural Networks and Random Forests); however, results also demonstrated how the presence of label noise could lower the f-score up to 64⁻74% depending on the classification approach (Nearest Centroid and Multi-Class Support Vector Machine).

A review of rapid serial visual presentation-based brain-computer interfaces.

Rapid serial visual presentation (RSVP) combined with the detection of event-related brain responses facilitates the selection of relevant information contained in a stream of images presented rapidly to a human. Event related potentials (ERPs) measured non-invasively with electroencephalography (EEG) can be associated with infrequent targets amongst a stream of images. Human-machine symbiosis may be augmented by enabling human interaction with a computer, without overt movement, and/or enable optimization of image/information sorting processes involving humans. Features of the human visual system impact on the success of the RSVP paradigm, but pre-attentive processing supports the identification of target information post presentation of the information by assessing the co-occurrence or time-locked EEG potentials. This paper presents a comprehensive review and evaluation of the limited, but significant, literature on research in RSVP-based brain-computer interfaces (BCIs). Applications that use RSVP-based BCIs are categorized based on display mode and protocol design, whilst a range of factors influencing ERP evocation and detection are analyzed. Guidelines for using the RSVP-based BCI paradigms are recommended, with a view to further standardizing methods and enhancing the inter-relatability of experimental design to support future research and the use of RSVP-based BCIs in practice.

The cancer-associated cell migration protein TSPAN1 is under control of androgens and its upregulation increases prostate cancer cell migration.

Cell migration drives cell invasion and metastatic progression in prostate cancer and is a major cause of mortality and morbidity. However the mechanisms driving cell migration in prostate cancer patients are not fully understood. We previously identified the cancer-associated cell migration protein Tetraspanin 1 (TSPAN1) as a clinically relevant androgen regulated target in prostate cancer. Here we find that TSPAN1 is acutely induced by androgens, and is significantly upregulated in prostate cancer relative to both normal prostate tissue and benign prostate hyperplasia (BPH). We also show for the first time, that TSPAN1 expression in prostate cancer cells controls the expression of key proteins involved in cell migration. Stable upregulation of TSPAN1 in both DU145 and PC3 cells significantly increased cell migration and induced the expression of the mesenchymal markers SLUG and ARF6. Our data suggest TSPAN1 is an androgen-driven contributor to cell survival and motility in prostate cancer.

Glycosylation is an Androgen-Regulated Process Essential for Prostate Cancer Cell Viability.

Steroid androgen hormones play a key role in the progression and treatment of prostate cancer, with androgen deprivation therapy being the first-line treatment used to control cancer growth. Here we apply a novel search strategy to identify androgen-regulated cellular pathways that may be clinically important in prostate cancer. Using RNASeq data, we searched for genes that showed reciprocal changes in expression in response to acute androgen stimulation in culture, and androgen deprivation in patients with prostate cancer. Amongst 700 genes displaying reciprocal expression patterns we observed a significant enrichment in the cellular process glycosylation. Of 31 reciprocally-regulated glycosylation enzymes, a set of 8 (GALNT7, ST6GalNAc1, GCNT1, UAP1, PGM3, CSGALNACT1, ST6GAL1 and EDEM3) were significantly up-regulated in clinical prostate carcinoma. Androgen exposure stimulated synthesis of glycan structures downstream of this core set of regulated enzymes including sialyl-Tn (sTn), sialyl Lewis(X) (SLe(X)), O-GlcNAc and chondroitin sulphate, suggesting androgen regulation of the core set of enzymes controls key steps in glycan synthesis. Expression of each of these enzymes also contributed to prostate cancer cell viability. This study identifies glycosylation as a global target for androgen control, and suggests loss of specific glycosylation enzymes might contribute to tumour regression following androgen depletion therapy.

A Personalized Self-Management Rehabilitation System for Stroke Survivors: A Quantitative Gait Analysis Using a Smart Insole.

BACKGROUND: In the United Kingdom, stroke is the single largest cause of adult disability and results in a cost to the economy of £8.9 billion per annum. Service needs are currently not being met; therefore, initiatives that focus on patient-centered care that promote long-term self-management for chronic conditions should be at the forefront of service redesign. The use of innovative technologies and the ability to apply these effectively to promote behavior change are paramount in meeting the current challenges. OBJECTIVE: Our objective was to gain a deeper insight into the impact of innovative technologies in support of home-based, self-managed rehabilitation for stroke survivors. An intervention of daily walks can assist with improving lower limb motor function, and this can be measured by using technology. This paper focuses on assessing the usage of self-management technologies on poststroke survivors while undergoing rehabilitation at home. METHODS: A realist evaluation of a personalized self-management rehabilitation system was undertaken in the homes of stroke survivors (N=5) over a period of approximately two months. Context, mechanisms, and outcomes were developed and explored using theories relating to motor recovery. Participants were encouraged to self-manage their daily walking activity; this was achieved through goal setting and motivational feedback. Gait data were collected and analyzed to produce metrics such as speed, heel strikes, and symmetry. This was achieved using a "smart insole" to facilitate measurement of walking activities in a free-living, nonrestrictive environment. RESULTS: Initial findings indicated that 4 out of 5 participants performed better during the second half of the evaluation. Performance increase was evident through improved heel strikes on participants' affected limb. Additionally, increase in performance in relation to speed was also evident for all 5 participants. A common strategy emerged across all but one participant as symmetry performance was sacrificed in favor of improved heel strikes. This paper evaluates compliance and intensity of use. CONCLUSION: Our findings suggested that 4 out of the 5 participants improved their ability to heel strike on their affected limb. All participants showed improvements in their speed of gait measured in steps per minute with an average increase of 9.8% during the rehabilitation program. Performance in relation to symmetry showed an 8.5% average decline across participants, although 1 participant improved by 4%. Context, mechanism, and outcomes indicated that dual motor learning and compensatory strategies were deployed by the participants.

The PI3K regulatory subunit gene PIK3R1 is under direct control of androgens and repressed in prostate cancer cells.

Androgen receptor (AR) signalling and the PI3K pathway mediate survival signals in prostate cancer, and have been shown to regulate each other by reciprocal negative feedback, such that inhibition of one activates the other. Understanding the reciprocal regulation of these pathways is important for disease management as tumour cells can adapt and survive when either single pathway is inhibited pharmacologically. We recently carried out genome-wide exon-specific profiling of prostate cancer cells to identify novel androgen-regulated transcriptional events. Here we interrogated this dataset for novel androgen-regulated genes associated with the PI3K pathway. We find that the PI3K regulatory subunits PIK3R1 (p85α) and PIK3R3 (p55γ) are direct targets of the AR which are rapidly repressed by androgens in LNCaP cells. Further characterisation revealed that the PIK3CA p110α catalytic subunit is also indirectly regulated by androgens at the protein level. We show that PIK3R1 mRNA is significantly under-expressed in prostate cancer (PCa) tissue, and provide data to suggest a context-dependent regulatory mechanism whereby repression of the p85α protein by the AR results in destabilisation of the PI3K p110α catalytic subunit and downstream PI3K pathway inhibition that functionally affects the properties of prostate cancer cells.

The androgen receptor controls expression of the cancer-associated sTn antigen and cell adhesion through induction of ST6GalNAc1 in prostate cancer.

Patterns of glycosylation are important in cancer, but the molecular mechanisms that drive changes are often poorly understood. The androgen receptor drives prostate cancer (PCa) development and progression to lethal metastatic castration-resistant disease. Here we used RNA-Seq coupled with bioinformatic analyses of androgen-receptor (AR) binding sites and clinical PCa expression array data to identify ST6GalNAc1 as a direct and rapidly activated target gene of the AR in PCa cells. ST6GalNAc1 encodes a sialytransferase that catalyses formation of the cancer-associated sialyl-Tn antigen (sTn), which we find is also induced by androgen exposure. Androgens induce expression of a novel splice variant of the ST6GalNAc1 protein in PCa cells. This splice variant encodes a shorter protein isoform that is still fully functional as a sialyltransferase and able to induce expression of the sTn-antigen. Surprisingly, given its high expression in tumours, stable expression of ST6GalNAc1 in PCa cells reduced formation of stable tumours in mice, reduced cell adhesion and induced a switch towards a more mesenchymal-like cell phenotype in vitro. ST6GalNAc1 has a dynamic expression pattern in clinical datasets, beingsignificantly up-regulated in primary prostate carcinoma but relatively down-regulated in established metastatic tissue. ST6GalNAc1 is frequently upregulated concurrently with another important glycosylation enzyme GCNT1 previously associated with prostate cancer progression and implicated in Sialyl Lewis X antigen synthesis. Together our data establishes an androgen-dependent mechanism for sTn antigen expression in PCa, and are consistent with a general role for the androgen receptor in driving important coordinate changes to the glycoproteome during PCa progression.

Qualitative evaluation of the SMART2 self-management system for people in chronic pain.

PURPOSE: Technology could support the self-management of long-term health conditions such as chronic pain. This article describes an evaluation of SMART2, a personalised self-management system incorporating activity planning and review, feedback on behaviour- and acceptance-based therapeutic exercises. METHOD: The SMART2 system was evaluated over a four-week trial in the homes of people in chronic pain. At conclusion, participants were interviewed to understand the experience of using and living with the SMART2 system as a therapeutic tool. RESULTS: Qualitative analysis of the interviews found that participants liked the system and reported making associated changes to their behaviour. Goal setting and feedback were the most useful elements of the system. A third key and unexpected element was that by simulating some of the functions of a therapist, SMART2 also simulated some of the process of interacting with a therapist. CONCLUSIONS: People in chronic pain may experience positive outcomes when using a self-management system designed for behaviour change. Furthermore, some of the supportive aspects of the therapeutic context can be elicited by self-management technologies. Implications of Rehabilitation Self-management technology has the potential to assist rehabilitation by supporting goal setting and providing feedback. By simulating some of the functions of a therapist, technology can simulate some of the process of therapy during rehabilitation. People in chronic pain liked using the technology in their own home and thought it could augment services delivered by clinical practitioners. Complex programmes of therapeutic exercises delivered by technology had limited success in engaging people in chronic pain.

Participatory research to design a novel telehealth system to support the night-time needs of people with dementia: NOCTURNAL.

Strategies to support people living with dementia are broad in scope, proposing both pharmacological and non-pharmacological interventions as part of the care pathway. Assistive technologies form part of this offering as both stand-alone devices to support particular tasks and the more complex offering of the "smart home" to underpin ambient assisted living. This paper presents a technology-based system, which expands on the smart home architecture, orientated to support people with daily living. The system, NOCTURNAL, was developed by working directly with people who had dementia, and their carers using qualitative research methods. The research focused primarily on the nighttime needs of people living with dementia in real home settings. Eight people with dementia had the final prototype system installed for a three month evaluation at home. Disturbed sleep patterns, night-time wandering were a focus of this research not only in terms of detection by commercially available technology but also exploring if automated music, light and visual personalized photographs would be soothing to participants during the hours of darkness. The NOCTURNAL platform and associated services was informed by strong user engagement of people with dementia and the service providers who care for them. NOCTURNAL emerged as a holistic service offering a personalised therapeutic aspect with interactive capabilities.

Science versus design; comparable, contrastive or conducive?

Science and design are two completely separated areas of expertise with their own specialists. Science analyses the existing world to create new knowledge, design uses existing knowledge to create a new world. This tunnel-vision mentality and narrow-minded approach is dangerous for problem solving, where a broad view on potential solutions is required to realise a high-quality answer on the defined problem. We state that design benefits from scientific methods, resulting in a more effective design process and in better products, while science benefits from a design approach, resulting in more efficient and effective results. Our philosophy is illustrated using examples from the field of biomedical engineering. Both methods can benefit tremendously from each other. By applying scientific methods, superior choices will be made in the design process. With design, more accurate, effective and efficient science will be performed.

Primary high-grade serous carcinoma arising in the urethra or urethral diverticulum: a report of 2 cases of an extremely rare phenomenon.

Serous carcinomas most commonly arise within the uterine corpus or ovary/fallopian tube, but there are 2 prior case reports of primary vaginal serous carcinoma. We report 2 examples of high-grade serous carcinoma arising within the urethra or a urethral diverticulum (1 case each). Both neoplasms exhibited the classic morphologic features of high-grade serous carcinoma, and a combination of clinical, radiologic, and pathologic examination excluded other possible sites of primary neoplasm.