Supervised learning with word embeddings derived from PubMed captures latent knowledge about protein kinases and cancer.

Inhibiting protein kinases (PKs) that cause cancers has been an important topic in cancer therapy for years. So far, almost 8% of \u3e530 PKs have been targeted by FDA-approved medications, and around 150 protein kinase inhibitors (PKIs) have been tested in clinical trials. We present an approach based on natural language processing and machine learning to investigate the relations between PKs and cancers, predicting PKs whose inhibition would be efficacious to treat a certain cancer. Our approach represents PKs and cancers as semantically meaningful 100-dimensional vectors based on word and concept neighborhoods in PubMed abstracts. We use information about phase I-IV trials in ClinicalTrials.gov to construct a training set for random forest classification. Our results with historical data show that associations between PKs and specific cancers can be predicted years in advance with good accuracy. Our tool can be used to predict the relevance of inhibiting PKs for specific cancers and to support the design of well-focused clinical trials to discover novel PKIs for cancer therapy

GivEn -- Shape Optimization for Gas Turbines in Volatile Energy Networks

This paper describes the project GivEn that develops a novel multicriteria optimization process for gas turbine blades and vanes using modern "adjoint" shape optimization algorithms. Given the many start and shut-down processes of gas power plants in volatile energy grids, besides optimizing gas turbine geometries for efficiency, the durability understood as minimization of the probability of failure is a design objective of increasing importance. We also describe the underlying coupling structure of the multiphysical simulations and use modern, gradient based multicriteria optimization procedures to enhance the exploration of Pareto-optimal solutions

Communication, social capital and workplace health management as determinants of the innovative climate in German banks

The present study aims to measure the determinants of the innovative climate in German banks with a focus on workplace health management (WHM). We analyze the determinants of innovative climate with multiple regressions using a dataset based on standardized telephone interviews conducted with health promotion experts from 198 randomly selected German banks. The regression analysis provided a good explanation of the variance in the dependent variable (RA(2)A = 55%). Communication climate (beta = 0.55; p < 0.001), social capital (beta = 0.21; p < 0.01), the establishment of a WHM program (beta = 0.13; p < 0.05) as well as company size (beta = 0.15; p < 0.01) were found to have a significant impact on an organization's innovative climate. In order to foster an innovation-friendly climate, organizations should establish shared values. An active step in this direction involves strengthening the organizations' social capital and communication climate through trustworthy management decisions such as the implementation of a WHM program

The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics

Schons M, Pilgram L, Reese J-P, et al. The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics. European Journal of Epidemiology . 2022.The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584. © 2022. The Author(s)

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Identifizierung von bona fide Interaktionspartnern der Transkriptionsfaktoren c-Myc und Miz-1

Das Proto-Onkogen c-myc ist durch seine Funktion als Transkriptionsfaktor entscheidend an vielen Prozessen beteiligt, welche die zelluläre Homöostase aufrechterhalten. Wegen seiner Rolle als Aktivator und Repressor vieler Gene, führt die Deregulation der Expression von c-Myc auch zur Deregulation physiologischer Prozesse wie Zellzykluskontrolle, Zellwachstum oder Apoptose und begünstigt die Tumorentstehung. Wie die meisten Proteine kann auch c-Myc seine Funktion nur durch Interaktion mir anderen Polypeptiden in Multiproteinkomplexen ausüben. Ein wichtiger Interaktionspartner von c-Myc ist Miz-1. Durch Bindung an DNA kann Miz-1 Gene aktivieren. c-Myc reprimiert die Aktivierung durch Miz-1, indem es an Miz-1 bindet. Der genaue Mechanismus dieser Repression ist jedoch unbekannt. In der vorliegenden Arbeit wurden zwei experimentelle Ansätze zur Identifizierung von möglichen Interaktionspartnern von c-Myc und Miz-1 etabliert. Eine Tandem-Affinitäts-Aufreinigung (TAP), um Protein-Protein Wechselwirkungen des Miz-1 Proteins zu identifizieren und eine chromatographische Fraktionierung, um Komplexe mit c-Myc bzw. Miz-1 als Untereinheiten zu identifizieren. In beiden Ansätzen erfolgte die Identifzierung durch Massenspektroskopie. Mit der Tandem-Affinitäts-Aufreinigung gelang zum einen die Identifizierung des Hitzschockproteins Hsp70 als potentieller Interaktionspartner. Zum anderen konnten drei verschiedene Varianten von Miz-1 mit der TAP Methode gefunden werden. Die Fraktionierung lieferte eine Liste mit 171 verschiedenen potentiellen Bindungspartnern von c-Myc bzw. Miz-1. Es konnten Proteine aus der Transkription, RNA Prozessierung, DNA-Reparatur, der Proteinmodifikation und-degradation, der Zellstruktur, des Metabolismus und der Proteinsynthese identifiziert werden. Die Ergebnisse der Arbeit liefern eine Grundlage für die weitere Untersuchung der Funktion von c-Myc und Miz-1. Dies gilt aber nicht nur für den schon bekannten Kontext der Transkription. c-Myc und Miz-1 sind vermutlich an einer Reihe weiterer Prozesse beteiligt, die für die Tumorigenese eine entscheidende Rolle spielen könnten

Quality Management Systems in the Ambulant Sector: An Analytical Comparison of Different Quality Management Systems

Background: Since 1 January 2004, all physicians, psychotherapists, and medical care centers that are under contract to statutory healthcare in Germany are obliged, according to &#167; 135a Section 2 of the Fifth Social Security Statute Book, to introduce an intra-institutional quality management system. Methods: A total of 24 medical practices were chosen through random sampling. In total, there were 12 family physicians and specialist practices each and eight practices each per quality management system. The analysis was carried out with the help of three specially developed questionnaires (physician, employee, and patient). A total of 26 quality categories with different questions were available in the three survey groups (physicians, employees, and patients). The Kruskal&#8315;Wallis test checked the extent to which the different scores between the quality management systems were significant and effective for specialists or family physicians. Results: &#8222;Quality and Development in Practices (QEP)&#8222; had the highest average score. Due to a specific family practitioner specialism, &#8220;Quality management in Saxony medical practices (QisA)&#8222; followed with good average scores. The individual quality categories in the quality management systems, such as the &#8220;range of services&#8222; or &#8220;allocation of appointments&#8222;, received the highest average scores among the specialists. In contrast, categories such as &#8220;telephone enquiries&#8222; and &#8220;external cooperation and communication&#8222; received the highest average scores among the family physicians. Conclusion: Differences in the evaluation of quality management systems and medical groups (specialists/family physicians) were found in the study. The reasons for these differences could be found in the quality categories

Studiendesign zur Entwicklung eines Fragebogens zur Identifikation der Motivationsstufe bei Jugendlichen mit Adipositas

Pankatz M, Stachow R, Reese J-P. Studiendesign zur Entwicklung eines Fragebogens zur Identifikation der Motivationsstufe bei Jugendlichen mit Adipositas. Das Gesundheitswesen. 2015;77(08/09):A 271

Studiendesign zur Entwicklung eines Fragebogens zur Identifikation der Motivationsstufe bei Jugendlichen und Erwachsenen mit Adipositas

Pankatz M, Stachow R, Reese J-P. Studiendesign zur Entwicklung eines Fragebogens zur Identifikation der Motivationsstufe bei Jugendlichen und Erwachsenen mit Adipositas. Presented at the DGSMP-/DGMS-/LGL-Kongress 2015, Regensburg