Decreased Gene Expression of Antiangiogenic Factors in Endometrial Cancer: qPCR Analysis and Machine Learning Modelling.

Endometrial cancer (EC) is an increasing health concern, with its growth driven by an angiogenic switch that occurs early in cancer development. Our study used publicly available datasets to examine the expression of angiogenesis-related genes and proteins in EC tissues, and compared them with adjacent control tissues. We identified nine genes with significant differential expression and selected six additional antiangiogenic genes from prior research for validation on EC tissue in a cohort of 36 EC patients. Using machine learning, we built a prognostic model for EC, combining our data with The Cancer Genome Atlas (TCGA). Our results revealed a significant up-regulation of IL8 and LEP and down-regulation of eleven other genes in EC tissues. These genes showed differential expression in the early stages and lower grades of EC, and in patients without deep myometrial or lymphovascular invasion. Gene co-expressions were stronger in EC tissues, particularly those with lymphovascular invasion. We also found more extensive angiogenesis-related gene involvement in postmenopausal women. In conclusion, our findings suggest that angiogenesis in EC is predominantly driven by decreased antiangiogenic factor expression, particularly in EC with less favourable prognostic features. Our machine learning model effectively stratified EC based on gene expression, distinguishing between low and high-grade cases.

Lipoprotein(a) As a Risk Factor in a Cohort of Hospitalised Cardiovascular Patients: A Retrospective Clinical Routine Data Analysis.

INTRODUCTION: Lipoprotein(a) (Lp(a)) is a well-recognised risk factor for ischemic heart disease (IHD) and calcific aortic valve stenosis (AVS). METHODS: A retrospective observational study of Lp(a) levels (mg/dL) in patients hospitalised for cardiovascular diseases (CVD) in our clinical routine was performed. The Lp(a)-associated risk of hospitalisation for IHD, AVS, and concomitant IHD/AVS versus other non-ischemic CVDs (oCVD group) was assessed by means of logistic regression. RESULTS: In total of 11,767 adult patients, the association with Lp(a) was strongest in the IHD/AVS group (eß = 1.010, p < 0.001), followed by the IHD (eß = 1.008, p < 0.001) and AVS group (eß = 1.004, p < 0.001). With increasing Lp(a) levels, the risk of IHD hospitalisation was higher compared with oCVD in women across all ages and in men aged ≤75 years. The risk of AVS hospitalisation was higher only in women aged ≤75 years (eß = 1.010 in age < 60 years, eß = 1.005 in age 60-75 years, p < 0.05). CONCLUSIONS: The Lp(a)-associated risk was highest for concomitant IHD/AVS hospitalisations. The differential impact of sex and age was most pronounced in the AVS group with an increased risk only in women aged ≤75 years.

Models including preoperative plasma levels of angiogenic factors, leptin and IL-8 as potential biomarkers of endometrial cancer.

Background: The diversity of endometrial cancer (EC) dictates the need for precise early diagnosis and pre-operative stratification to select treatment options appropriately. Non-invasive biomarkers invaluably assist clinicians in managing patients in daily clinical practice. Currently, there are no validated diagnostic or prognostic biomarkers for EC that could accurately predict the presence and extent of the disease. Methods: Our study analyzed 202 patients, of whom 91 were diagnosed with EC and 111 were control patients with the benign gynecological disease. Using Luminex xMAP™ multiplexing technology, we measured the pre-operative plasma concentrations of six previously selected angiogenic factors - leptin, IL-8, sTie-2, follistatin, neuropilin-1, and G-CSF. Besides basic statistical methods, we used a machine-learning algorithm to create a robust diagnostic model based on the plasma concentration of tested angiogenic factors. Results: The plasma levels of leptin were significantly higher in EC patients than in control patients. Leptin was higher in type 1 EC patients versus control patients, and IL-8 was higher in type 2 EC versus control patients, particularly in poorly differentiated endometrioid EC grade 3. IL-8 plasma levels were significantly higher in EC patients with lymphovascular or myometrial invasion. Among univariate models, the model based on leptin reached the best results on both training and test datasets. A combination of age, IL-8, leptin and G-CSF was determined as the most important feature for the multivariate model, with ROC AUC 0.94 on training and 0.81 on the test dataset. The model utilizing a combination of all six AFs, BMI and age reached a ROC AUC of 0.89 on both the training and test dataset, strongly indicating the capability for predicting the risk of EC even on unseen data. Conclusion: According to our results, measuring plasma concentrations of angiogenic factors could, provided they are confirmed in a multicentre validation study, represent an important supplementary diagnostic tool for early detection and prognostic characterization of EC, which could guide the decision-making regarding the extent of treatment.

Lipoprotein(a) in Cardiovascular Diseases: Insight From a Bibliometric Study.

Lipoprotein(a) [Lp(a)] is a complex polymorphic lipoprotein comprised of a low-density lipoprotein particle with one molecule of apolipoprotein B100 and an additional apolipoprotein(a) connected through a disulfide bond. The serum concentration is mostly genetically determined and only modestly influenced by diet and other lifestyle modifications. In recent years it has garnered increasing attention due to its causal role in pre-mature atherosclerotic cardiovascular disease and calcific aortic valve stenosis, while novel effective therapeutic options are emerging [apolipoprotein(a) antisense oligonucleotides and ribonucleic acid interference therapy]. Bibliometric descriptive analysis and mapping of the research literature were made using Scopus built-in services. We focused on the distribution of documents, literature production dynamics, most prolific source titles, institutions, and countries. Additionally, we identified historical and influential papers using Reference Publication Year Spectrography (RPYS) and the CRExplorer software. An analysis of author keywords showed that Lp(a) was most intensively studied regarding inflammation, atherosclerosis, cardiovascular risk assessment, treatment options, and hormonal changes in post-menopausal women. The results provide a comprehensive view of the current Lp(a)-related literature with a specific interest in its role in calcific aortic valve stenosis and potential emerging pharmacological interventions. It will help the reader understand broader aspects of Lp(a) research and its translation into clinical practice.

Role of Agile in Digital Public Health Transformation.

The digitalisation of healthcare, fueled by advances in technology and the COVID-19 pandemic can not only empower equitable access to global expert-level healthcare but also make healthcare more patient-centric. Every digital health solution has one common fundamental component: they all run on computing platforms and are powered by complex software. Traditional software development life cycles have often failed in designing complex software; consequently, the agile approach was introduced. To assess the role of agile in digital public health transformation, we used the synthetic knowledge synthesis, a triangulation of bibliometric mapping, and thematic analysis to analyse the available literature harvested from PubMed. The analysis showed that the use of the agile approach is underutilised in developing digital health software. Moreover, the study revealed that health organisations did not yet embrace the agile culture and should adapt using innovative agile solutions to deliver clinical value to patients and public health systems. Following the software industry, where agile software development is becoming the mainstream approach also for sensitive and regulated software, it is becoming even more essential that the digital health software development process should be modernised. Furthermore, a shift to agile collaboration, agile decision-making, trial tolerance, active engagement, purposeful technology adoption, knowledge sharing, and an open agile innovation ecosystem must be achieved.

The quality of digital health software: Should we be concerned?

The digitalization of healthcare fuelled by advances in technology and the increased prevalence of mobile smart devices and health-related internet of things can offer equitable access to expert-level healthcare globally. Growing demand for telemedicine, mobile health apps, and advanced data analytics have further established their role in a modern information society during the Covid-19 crisis. Digital health is, in essence, powered by software (DHSW), which has to operate in the specific digital health environment characteristics and is therefore highly and intrinsically complex and prone to software defects and faults. Given the lack of standardization regarding DHSW quality, we explored the available reviewed research on this crucial topic in this brief paper, using a synthetic thematic analysis approach. We assert that neither the volume, distribution nor scope of the DHSW quality research content is satisfactory, and significant research gaps exist. Based on the presented evidence, we can only conclude that we should be concerned and that the time to act is now to ensure that the unavoidable increase of usage and prevalence of DHSW will not - in the end - reduce the quality of care due to subpar software and software-based digital health systems.

Machine learning on small size samples: A synthetic knowledge synthesis.

Machine Learning is an increasingly important technology dealing with the growing complexity of the digitalised world. Despite the fact, that we live in a 'Big data' world where, almost 'everything' is digitally stored, there are many real-world situations, where researchers are still faced with small data samples. The present bibliometric knowledge synthesis study aims to answer the research question 'What is the small data problem in machine learning and how it is solved?' The analysis a positive trend in the number of research publications and substantial growth of the research community, indicating that the research field is reaching maturity. Most productive countries are China, United States and United Kingdom. Despite notable international cooperation, the regional concentration of research literature production in economically more developed countries was observed. Thematic analysis identified four research themes. The themes are concerned with to dimension reduction in complex big data analysis, data augmentation techniques in deep learning, data mining and statistical learning on small datasets.