Adoptive cell therapy with macrophage-drug conjugates facilitates cytotoxic drug transfer and immune activation in glioblastoma models.

The treatment of solid tumors faces substantial hurdles because of inadequate drug delivery and the immunosuppressive tumor microenvironment. To address these challenges, we developed a therapeutic platform using macrophages loaded with ferritin-drug conjugates, referred to as macrophage-drug conjugates (MDC), and applied it to glioblastoma, an immunologically cold solid tumor. MDC loaded with ferritin-conjugated monomethyl auristatin E enabled efficient, cell contact-dependent transfer of the payload by a mechanism involving transfer of iron-binding proteins, from either mouse or human macrophages preferentially into glioma cells.

A Neural Network for Atrial Fibrillation Detection via PPG.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with severe complications such as ischemic stroke and heart failure. Early detection is essential for timely intervention; however, traditional diagnostic methods often lack scalability and accessibility. This project explores the use of photoplethysmography (PPG) signals recorded via smartphone applications to develop a predictive neural network model for AF detection.

FOX BOXes as Fundamental Enablers for EHR-Standardised Data Sharing - Building the Austrian Health Data Donation Space.

Efficient secondary use of real-world data (RWD) is a cornerstone for advancing data-driven medical research and personalised healthcare. However, significant challenges persist, including data fragmentation in silos, the lack of record linkage, and legal constraints that often hinder data utilisation. Especially Electronic Health Records (EHRs) represent a valuable data source, yet their potential remains largely untapped due to these barriers.

Support of Home-Based Structured Walking Training and Prediction of the 6-Minute Walk Test Distance in Patients With Peripheral Arterial Disease Based on Telehealth Data: Prospective Cohort Study.

Background: Telehealth has been effective in managing cardiovascular diseases like stroke and heart failure and has shown promising results in managing patients with peripheral arterial disease. However, more work is needed to fully understand the effect of telehealth-based predictive modeling on the physical fitness of patients with peripheral arterial disease.

Objective: For this work, data from the Keep Pace study were analyzed in depth to gain insights on temporal developments of patients' conditions and to develop models to predict the patients' total walking distance at the study end.

The Digital Health Competencies in Medical Education Framework: An International Consensus Statement Based on a Delphi Study.

Importance: Rapid digitalization of health care and a dearth of digital health education for medical students and junior physicians worldwide means there is an imperative for more training in this dynamic and evolving field.

Objective: To develop an evidence-informed, consensus-guided, adaptable digital health competencies framework for the design and development of digital health curricula in medical institutions globally.

Evidence Review: A core group was assembled to oversee the development of the Digital Health Competencies in Medical Education (DECODE) framework.

Conditionally Activated ROS Generation by MMP2/9-Specific C-Based Fluorescence Probes.

A C-coumarin conjugate, covalently connected via a matrix metalloproteinase (MMP2/9)-cleavable peptide linker (Pro-Leu-Gly-Val-Arg-Gly), is developed as a probe for both imaging and photodynamic treatment of MMP2/9-expressing malignant cells. In the synthesized probe, the coumarin fluorescence is completely suppressed intramolecularly by the C moiety, while an intensive fluorescence increase is observed in the presence of MMP2/9 dependent on cleavage of the peptide linker. The specificity of the probe to detect MMP2 is confirmed by control experiments resulting in no emission 1) with a control probe bearing a shuffled peptide (Val-Arg-Leu-Gly-Pro-Gly) or 2) in the presence of an MMP2 inhibitor (1,10-phenantheoline).

MAP4 kinase-regulated reduced CLSTN1 expression in medulloblastoma is associated with increased invasiveness.

De-regulated protein expression contributes to tumor growth and progression in medulloblastoma (MB), the most common malignant brain tumor in children. MB is associated with impaired differentiation of specific neural progenitors, suggesting that the deregulation of proteins involved in neural physiology could contribute to the transformed phenotype in MB. Calsynthenin 1 (CLSTN1) is a neuronal protein involved in cell-cell interaction, vesicle trafficking, and synaptic signaling.

Aurora kinase B is required for growth and expansion of medulloblastoma cells in the tissue context.

The impact of the tissue context on tumor growth and drug response in medulloblastoma (MB) is poorly understood. To gain insights into the growth and dissemination behavior of the MB tumor cells under treatment, we combined three-dimensional cell culture screening with ex vivo organotypic cerebellum slice co-culture (OCSC), which allowed the assessment of tumor cell behavior in the tissue context. To identify druggable kinase pathways involved in invasion, we screened a panel of 274 kinase inhibitors and identified aurora kinase B (AURKB) as a potential anti-invasion drug target in MB.

A Novel Deep Ensemble Method for Selective Classification of Electrocardiograms.

Objective: Telehealth paradigms are essential for remotely managing patients with chronic conditions. To assist clinicians in handling the large volumes of data collected through these systems, clinical decision support systems (CDSSs) have been developed. However, the effectiveness of CDSSs depends on the quality of remotely recorded physiological data and the reliability of the algorithms used for processing this data.

Targeting the cancer cells and cancer-associated fibroblasts with next-generation FGFR inhibitors in prostate cancer co-culture models.

Background: Inhibition of androgen receptor (AR) signaling is the main treatment strategy in advanced prostate cancer (PCa). A subset of castration resistant prostate cancer (CRPC) bypasses the AR blockade by increased fibroblast growth factor receptor (FGFR) signaling. The first- and second-generation, non-covalent FGFR inhibitors (FGFRis) have largely failed in the clinical trials against PCa.

Use Cases Requiring Privacy-Preserving Record Linkage in Paediatric Oncology.

Large datasets in paediatric oncology are inherently rare. Therefore, it is paramount to fully exploit all available data, which are distributed over several resources, including biomaterials, images, clinical trials, and registries. With privacy-preserving record linkage (PPRL), personalised or pseudonymised datasets can be merged, without disclosing the patients' identities.

Analysis of the impact of a university distance learning course on digitalization in medicine on students and healthcare professionals.

Purpose: The public medical universities in Austria (educating 11,000 students) developed a joint public distance learning series in which clinicians discussed current digital lighthouse projects in their specialty. This study aims to examine the changes in attitude and knowledge of the participants before and after the lecture series to gain insights for future curriculum developments.

Method: The lecture series was announced via various channels at the universities, in health newsletters and in social media.

Health data space nodes for privacy-preserving linkage of medical data to support collaborative secondary analyses.

Introduction: The potential for secondary use of health data to improve healthcare is currently not fully exploited. Health data is largely kept in isolated data silos and key infrastructure to aggregate these silos into standardized bodies of knowledge is underdeveloped. We describe the development, implementation, and evaluation of a federated infrastructure to facilitate versatile secondary use of health data based on Health Data Space nodes.

Introduction and Comparison of Novel Decentral Learning Schemes with Multiple Data Pools for Privacy-Preserving ECG Classification.

Artificial intelligence and machine learning have led to prominent and spectacular innovations in various scenarios. Application in medicine, however, can be challenging due to privacy concerns and strict legal regulations. Methods that centralize knowledge instead of data could address this issue.

Classification of Clinical Notes from a Heart Failure Telehealth Network.

Heart failure is a common chronic disease which is associated with high re-hospitalization and mortality rates. Within the telemedicine-assisted transitional care disease management program HerzMobil, monitoring data such as daily measured vital parameters and various other heart failure related data are collected in a structured way. Additionally, involved healthcare professionals communicate with one another via the system using free-text clinical notes.

Towards a Verification Approach of a Smart Registry for Chronic Heart Failure Patients.

Background: The daily increasing amount of health data from different sources like electronic medical records and telehealth systems go hand in hand with the ongoing development of novel digital and data-driven analytics. Unifying this in a privacy-preserving data aggregation infrastructure can enable services for clinical decision support in personalized patient therapy.

Objectives: The goal of this work was to consider such an infrastructure, implemented in a smart registry for heart failure, as a comparative method for the analysis of health data.

Leveraging molecular structure and bioactivity with chemical language models for de novo drug design.

Generative chemical language models (CLMs) can be used for de novo molecular structure generation by learning from a textual representation of molecules. Here, we show that hybrid CLMs can additionally leverage the bioactivity information available for the training compounds. To computationally design ligands of phosphoinositide 3-kinase gamma (PI3Kγ), a collection of virtual molecules was created with a generative CLM.

The molecular basis of the dichotomous functionality of MAP4K4 in proliferation and cell motility control in cancer.

The finely tuned integration of intra- and extracellular cues by components of the mitogen-activated protein kinase (MAPK) signaling pathways controls the mutually exclusive phenotypic manifestations of uncontrolled growth and tumor cell dissemination. The Ser/Thr kinase MAP4K4 is an upstream integrator of extracellular cues involved in both proliferation and cell motility control. Initially identified as an activator of the c-Jun N-terminal kinase (JNK), the discovery of diverse functions and additional effectors of MAP4K4 beyond JNK signaling has considerably broadened our understanding of this complex kinase.

Discovery of a small molecule ligand of FRS2 that inhibits invasion and tumor growth.

Purpose: Aberrant activation of the fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases drives oncogenic signaling through its proximal adaptor protein FRS2. Precise disruption of this disease-causing signal transmission in metastatic cancers could stall tumor growth and progression. The purpose of this study was to identify a small molecule ligand of FRS2 to interrupt oncogenic signal transmission from activated FGFRs.

Digital health understanding and preparedness of medical students: a cross-sectional study.

Digitalisation is changing all areas of our daily life. This changing environment requires new competences from physicians in all specialities. This study systematically surveyed the knowledge, attitude, and interests of medical students.

Cooperation of Striatin 3 and MAP4K4 promotes growth and tissue invasion.

MAP4K4 is associated with increased motility and reduced proliferation in tumor cells, but the regulation of this dichotomous functionality remained elusive. We find that MAP4K4 interacts with striatin 3 and 4 (STRN3/4) and that STRN3 and MAP4K4 exert opposing functions in Hippo signaling and clonal growth. However, depletion of either STRN3 or MAP4K4 in medulloblastoma cells reduces invasion, and loss of both proteins abrogates tumor cell growth in the cerebellar tissue.