Patients' experiences and perspectives regarding the use of digital technology to support exercise-based cardiac rehabilitation: a qualitative interview study.

Introduction: Despite the well-known benefits of exercise-based cardiac rehabilitation for the secondary prevention of cardiovascular disease, participation in cardiac rehabilitation programmes and adherence to secondary prevention recommendations remain limited. Digital technologies have the potential to address low participation and adherence but attempts at implementing digital health interventions in real-life clinical practice frequently encounter various barriers. Studies about patients' experiences and perspectives regarding the use of digital technology can assist developers, researchers and clinicians in addressing or pre-empting patient-related barriers. This study was therefore conducted to investigate the experiences and perspectives of cardiac rehabilitation patients in Austria with regard to using digital technology for physical activity and exercise. Methods: Twenty-five current and former cardiac rehabilitation patients (18 men and 7 women, age range 39 to 83) with various cardiac conditions were recruited from a clinical site in Salzburg, Austria. Semi-structured qualitative interviews were audio-recorded and transcribed verbatim. The analysis followed a descriptive phenomenological approach, applying the framework analysis method. Results: The sample was diverse, including interviewees who readily used digital devices to support their physical activity, exercise and health monitoring, and interviewees who did not. Simplicity, convenience and accessibility were highlighted as important facilitators for the use of digital technology, while annoyance with digital devices, concerns about becoming dependent on them, or simply a preference to not use digital technology were commonly stated reasons for non-use. Interviewees' views on data protection, data sharing and artificial intelligence revealed wide variations in individuals' prior knowledge and experience about these topics, and a need for greater accessibility and transparency of data protection regulation and data sharing arrangements. Discussion: These findings support the importance that is attributed to user-centred design methodologies in the conceptualisation and design of digital health interventions, and the imperative to develop solutions that are simple, accessible and that can be personalised according to the preferences and capabilities of the individual patient. Regarding data protection, data sharing and artificial intelligence, the findings indicate opportunity for information and education, as well as the need to offer patients transparency and accountability in order to build trust in digital technology and digital health interventions.

Circulating serum miR-362-3p and miR-6721-5p as potential biomarkers for classification patients with adult-type diffuse glioma.

According to the fifth edition of the WHO Classification of Tumours of the Central Nervous System (CNS) published in 2021, grade 4 gliomas classification includes IDH-mutant astrocytomas and wild-type IDH glioblastomas. Unfortunately, despite precision oncology development, the prognosis for patients with grade 4 glioma remains poor, indicating an urgent need for better diagnostic and therapeutic strategies. Circulating miRNAs besides being important regulators of cancer development could serve as promising diagnostic biomarkers for patients with grade 4 glioma. Here, we propose a two-miRNA miR-362-3p and miR-6721-5p screening signature for serum for non-invasive classification of identified glioma cases into the highest-grade 4 and lower-grade gliomas. A total of 102 samples were included in this study, comprising 78 grade 4 glioma cases and 24 grade 2-3 glioma subjects. Using the NanoString platform, seven miRNAs were identified as differentially expressed (DE), which was subsequently confirmed via RT-qPCR analysis. Next, numerous combinations of DE miRNAs were employed to develop classification models. The dual panel of miR-362-3p and miR-6721-5p displayed the highest diagnostic value to differentiate grade 4 patients and lower grade cases with an AUC of 0.867. Additionally, this signature also had a high AUC = 0.854 in the verification cohorts by RT-qPCR and an AUC = 0.842 using external data from the GEO public database. The functional annotation analyses of predicted DE miRNA target genes showed their primary involvement in the STAT3 and HIF-1 signalling pathways and the signalling pathway of pluripotency of stem cells and glioblastoma-related pathways. For additional exploration of miRNA expression patterns correlated with glioma, we performed the Weighted Gene-Co Expression Network Analysis (WGCNA). We showed that the modules most associated with glioma grade contained as many as six DE miRNAs. In conclusion, this study presents the first evidence of serum miRNA expression profiling in adult-type diffuse glioma using a classification based on the WHO 2021 guidelines. We expect that the discovered dual miR-362-3p and miR-6721-5p signatures have the potential to be utilised for grading gliomas in clinical applications.

Identification of serum miR-1246 and miR-150-5p as novel diagnostic biomarkers for high-grade serous ovarian cancer.

Epithelial ovarian cancer (EOC) is one of the leading cancers in women, with high-grade serous ovarian cancer (HGSOC) being the most common and lethal subtype of this disease. A vast majority of HGSOC are diagnosed at the late stage of the disease when the treatment and total recovery chances are low. Thus, there is an urgent need for novel, more sensitive and specific methods for early and routine HGSOC clinical diagnosis. In this study, we performed miRNA expression profiling using the NanoString miRNA assay in 34 serum samples from patients with HGSOC and 36 healthy women. We identified 13 miRNAs that were differentially expressed (DE). For additional exploration of expression patterns correlated with HGSOC, we performed weighted gene co-expression network analysis (WGCNA). As a result, we showed that the module most correlated with tumour size, nodule and metastasis contained 8 DE miRNAs. The panel including miR-1246 and miR-150-5p was identified as a signature that could discriminate HGSOC patients with AUCs of 0.98 and 1 for the training and test sets, respectively. Furthermore, the above two-miRNA panel had an AUC = 0.946 in the verification cohorts of RT-qPCR data and an AUC = 0.895 using external data from the GEO public database. Thus, the model we developed has the potential to markedly improve the diagnosis of ovarian cancer.

Development of an extensive workflow for comprehensive clinical pharmacogenomic profiling: lessons from a pilot study on 100 whole exome sequencing data.

This pilot study is aimed at implementing an approach for comprehensive clinical pharmacogenomics (PGx) profiling. Fifty patients with cardiovascular diseases and 50 healthy individuals underwent whole-exome sequencing. Data on 1800 PGx genes were extracted and analyzed through deep filtration separately. Theoretical drug induced phenoconversion was assessed for the patients, using sequence2script. In total, 4539 rare variants (including 115 damaging non-synonymous) were identified. Four publicly available PGx bioinformatics algorithms to assign PGx haplotypes were applied to nine selected very important pharmacogenes (VIP) and revealed a 45-70% concordance rate. To ensure availability of the results at point-of-care, actionable variants were stored in a web-hosted database and PGx-cards were developed for quick access and handed to the study subjects. While a comprehensive clinical PGx profile could be successfully extracted from WES data, available tools to interpret these data demonstrated inconsistencies that complicate clinical application.

ßhCG and PAPP-A in first trimester: predictive factors for preeclampsia?

OBJECTIVE: The aim of our study was to investigate a possible correlation between the expression of the placenta-secreted hormones, ß-subunit of human chorionic gonadotrophin (ßhCG) and pregnancy-associated plasma protein A (PAPP-A), during the first trimester screening and the development of preeclampsia. METHODS: A total of 155 patients between 11 + 0 and 13 + 6 weeks of gestation were enrolled in this study. PAPP-A and ßhCG levels were measured using the KRYPTOR® system. RESULTS: The serum levels of ßhCG were significantly higher in pregnancies which subsequently developed preeclampsia. The PAPP-A concentration did not differ significantly in pregnancies complicated by preeclampsia than in uncomplicated pregnancies. CONCLUSION: These results might contribute to developing new tests in the prediction of preeclampsia.