Decentralized Identities for Self-sovereign End-users (DISSENS)

This paper describes a comprehensive architecture and reference implementation for privacy-preserving identity management that bucks the trend towards centralization present in contemporary proposals. DISSENS integrates a technology stack which combines privacy-friendly online payments with self-sovereign personal data management using a decentralized directory service. This enables users to be in complete control of their digital identity and personal information while at the same time being able to selectively share information necessary to easily use commercial services. Our pilot demonstrates the viability of a sustainable, user-centric, standards-compliant and accessible use case for public service employees and students in the domain of retail e-commerce. We leverage innovative technologies including self-sovereign identity, privacy credentials, and privacy-friendly digital payments in combination with established standards to provide easy-to-adapt templates for the integration of various scenarios and use cases

Secure Multiparty Computation in Clinical Research and Digital Health

The free flow of information is the lifeblood of the digital economy. In research, the exchange of data is a prime requisite for the generation of new knowledge. In practice, however, there are many barriers to data sharing. Collaborators are reluctant to reveal their proprietary knowledge, consumers are wary of large scale data collection and profiling, regulation restricts what personal information can and cannot be shared across institutional borders. In clinical research and digital health, there are particulary strict data protection rules in force. Here, we are motivated to seek new methods for knowledge generation, without the problematic exchange of actual patient data. In fact, there is a technology, secure multiparty computation, which allows a number of collaborators to jointly compute about any function, without revealing their private inputs. The method relies entirely on calculations over an encrypted network, without the need for a trusted third party, a central data repository, or even trust between the collaborators. In a pilot experiment, we demonstrate joint survival analysis based on two separate data bases at LMU Munich and Charité Berlin. Using secure multiparty computation, we are able to identify confounding factors for the survival of patients with glioblastoma. We obtain the same sensitivity as one would achieve by completely pooling the two data bases, and yet we do not actually need to exchange any patient data to perform the calculation. Going forward, we hope to assemble a collection of libraries for secure multiparty computation in clinical research and digital health. By providing turn-key solutions to the most often used calculations, we hope to reduce barriers to entry for interested researchers and developers. We also hope to create a scientific network of interested institutions and individuals

The Role of Stereotactic Radiosurgery in the Management of Foramen Magnum Meningiomas—A Multicenter Analysis and Review of the Literature

Background: Foramen magnum meningiomas (FMMs) represent a considerable neurosurgical challenge given their location and potential morbidity. Stereotactic radiosurgery (SRS) is an established non-invasive treatment modality for various benign and malignant brain tumors. However, reports on single-session or multisession SRS for the management and treatment of FMMs are exceedingly rare. We report the largest FMM SRS series to date and describe our multicenter treatment experience utilizing robotic radiosurgery. Methods: Patients who underwent SRS between 2005 and 2020 as a treatment for a FMM at six different centers were eligible for analysis. Results: Sixty-two patients met the inclusion criteria. The median follow-up was 28.9 months. The median prescription dose and isodose line were 14 Gy and 70%, respectively. Single-session SRS accounted for 81% of treatments. The remaining patients received three to five fractions, with doses ranging from 19.5 to 25 Gy. Ten (16%) patients were treated for a tumor recurrence after surgery, and thirteen (21%) underwent adjuvant treatment. The remaining 39 FMMs (63%) received SRS as their primary treatment. For patients with an upfront surgical resection, histopathological examination revealed 22 World Health Organization grade I tumors and one grade II FMM. The median tumor volume was 2.6 cubic centimeters. No local failures were observed throughout the available follow-up, including patients with a follow-up ≥ five years (16 patients), leading to an overall local control of 100%. Tumor volume significantly decreased after treatment, with a median volume reduction of 21% at the last available follow-up (p < 0.01). The one-, three-, and five-year progression-free survival were 100%, 96.6%, and 93.0%, respectively. Most patients showed stable (47%) or improved (21%) neurological deficits at the last follow-up. No high-grade adverse events were observed. Conclusions: SRS is an effective and safe treatment modality for FMMs. Despite the paucity of available data and previous reports, SRS should be considered for selected patients, especially those with subtotal tumor resections, recurrences, and patients not suitable for surgery

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P &lt;.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

Meningeal Solitary Fibrous Tumor: A Single-Center Retrospective Cohort Study

Background. Meningeal solitary fibrous tumors (SFTs) are rare, malignant, mesenchymal tumors of the central nervous system. While surgical gross total resection is widely accepted as a positive prognostic factor for local control (LC), the role of postoperative radiotherapy (PORT) remains controversial. We sought to report our institutional experience with a particular focus on outcomes after PORT. Materials and Methods. In this single-center, retrospective cohort study, 20 patients with the primary diagnosis of histopathologically confirmed meningeal SFT were analyzed. Data on patient characteristics, imaging, treatment modalities, histopathology, and oncological outcomes were collected. LC and overall survival (OS) were assessed using the Kaplan–Meier estimator. Results. The median follow-up time was 95.8 months. After surgery only, 9 out of 11 patients (81.8%) developed a local recurrence while, after surgery and PORT, 3 out of 9 patients (33.33%) showed local failure. The 5- and 10-year LC rates were 50.5% and 40.4% in the surgery-only group and 80% at both time points in the surgery with the PORT group. In the surgery-only group, 4 out of 11 patients (36.4%) died, and 4 out of 9 patients (44.4%) died in the surgery and PORT group. OS rates after 5 and 10 years were 88.9% and 66.7% in the surgery-only group and 88.9% and 76.2% in the surgery with PORT group. Conclusions. Our findings suggest that PORT may improve LC in patients with meningeal SFT. The low incidence of meningeal SFT impedes prospective studies and requires further international collaborative efforts to exploit retrospective datasets and molecular analysis to improve patient outcomes

Image-Guided Robotic Radiosurgery for the Management of Intramedullary Spinal Cord Metastases-A Multicenter Experience

Simple Summary Due to recent medical advancements, patients suffering from metastatic cancer have a prolonged life expectancy compared to several decades ago. Thus, the number of patients who experience metastasis to the spinal cord is increasing. Intramedullary metastases bear a dismal prognosis and cause considerable morbidity. Limited data are available on the treatment of such lesions. As surgery may be the mainstay of treatment for resectable and localized metastatic spread, previous case reports and series suggest radiosurgery to be a treatment alternative. This first multicenter study analyzes the efficacy of robotic radiosurgery (RRS) for the management of intramedullary metastases. Outcomes provide evidence that RRS is a safe, time-saving and effective treatment modality, especially for patients with unresectable lesions. Most patients die from systemic disease progression, while the majority of treated lesions remain controlled until death. Most symptoms improve or stay stable after treatment. These findings may guide further palliative care of affected patients. Background: Intramedullary metastases are rare and bear a dismal prognosis. Limited data are available on the treatment of such lesions. As surgery may be the mainstay of treatment for patients with resectable and localized metastatic spread, previous case reports and case series suggest radiosurgery to be another viable treatment modality. This multicenter study analyzes the efficacy and safety of robotic radiosurgery (RRS) for intramedullary metastases. Methods: Patients who received RRS for the treatment of at least one intramedullary metastasis were included. Results: Thirty-three patients with 46 intramedullary metastases were treated with a median dose of 16 Gy prescribed to a median isodose of 70%. The local control was 79% after a median follow-up of 8.5 months. The median overall survival (OS) was 11.7 months, with a 12- and 24-month OS of 47 and 31%. The 12-month progression-free survival was 42% and at 24 months 25%. In addition, 57% of patients showed either an improved or stable neurological function after treatment delivery. Systemic disease progression was the main cause of death. No significant treatment-related toxicities were observed. Conclusions: RRS appears to be a safe, time-saving and effective treatment modality for intramedullary metastases, especially for patients with unresectable lesions and high burden of disease

Dedicated Interventional Instruments for Magnetic Particle Imaging

Vascular interventions are a very promising application of Magnetic Particle Imaging. The possibility to visualize the devices is a prerequisite for diagnosis and treatment of vascular diseases. In this contribution, we present a balloon catheter from a polymer mixed with nanoparticles. A dynamic imaging is performed to show that the inflation and deflation of the balloon can be imaged with MPI