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Die Netzwerke sozialer Medien spielen heutzutage eine wichtige Rolle bei der Mobilisierung zu Demonstrationen. Insbesondere Telegram bietet viele technologische Vorteile für die Koordinierung von Protesten. Die „Querdenken“-Bewegung nutzt Telegram als primäres Kommunikationsinstrument. Bislang existieren wenige Analysen zur Struktur ihrer Kommunikation und konkreten Mobilisierung über Telegram. In einer quantitativen Inhaltsanalyse von 9.088.629 Nachrichten aus 943 Kanälen und Gruppen der „Querdenken“-Bewegung auf Telegram gehen wir dieser Forschungslücke nach. Mithilfe einer Netzwerkanalyse von geteilten Inhalten beschreiben wir die Struktur der Kommunikation, identifizieren zentrale Knoten wie den Kanal „@haintz“ und betrachten die funktionale Rolle, die sie im Netzwerk einnehmen. Anhand von Ortsnennungen in Nachrichten erkennen wir, dass „Querdenken“ vor allem in Ballungszentren wie Berlin und Stuttgart mobilisiert hat. Jedoch gibt es auch einen Mobilisierungstrend hin zu Mittel- und Kleinstädten. Zuletzt prüfen wir durch die Analyse zweier Zeitreihen, ob ein Zusammenhang zwischen den Protestaufrufen auf Telegram und der Presseberichterstattung über das Offline-Protestgeschehen besteht. Die mittlere Korrelation zwischen den Zeitreihen interpretieren wir als Beleg der mobilisierenden Kraft von Protestaufrufen auf Telegram.

Abstract Background In patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA), concomitant depression might have a negative impact on the course of disease and treatment outcomes. The aims of this analysis are to determine the prevalence of depressive symptoms in axSpA and PsA patients in a real-world cohort study and to identify sociodemographic and clinical associated factors for moderate or severe depressive symptoms in both diseases. Methods Patients from the RABBIT-SpA cohort with an axSpA or PsA diagnosis and a valid WHO-5 Well-Being Index score at baseline were included. A descriptive analysis of baseline and outcome parameters by category of depressive symptoms was performed and factors associated with the presence of depressive symptoms (moderate or severe) were examined in a logistic regression. Results Two thousand four hundred seventy patients (1,245 axSpA; 1,225 PsA) were included in the analysis. In both diagnoses, the proportion of patients with moderate depressive symptoms was 8% and 21% with severe symptoms. Patients with moderate or severe depressive symptoms were less likely to engage in sports than those with no or mild depressive symptoms, had more comorbidities and higher scores for disease activity, functional limitations, fatigue, and pain and took more analgesics. In axSpA, patients with a higher disease activity, a greater functional impairment and more severe fatigue were more likely to experience depressive symptoms, while patients with more years in education and engaging in sports for at least 1 h/week were less likely to experience depressive symptoms. PsA patients with a greater functional impairment and more severe fatigue were more likely to experience depressive symptoms while those engaging in sports for at least 1 h/week were less likely to experience depressive symptoms. Conclusion We confirmed a high prevalence of depressive symptoms in both PsA and axSpA. Factors negatively associated with the presence of depressive symptoms were fatigue, not engaging in sports, and greater functional limitations. Depressive symptoms may affect the perception of disease activity / severity by patients. Thus, depressive symptoms are an important condition in axSpA and PsA that should be considered when evaluating disease activity and treatment outcomes.

The emergence of generative language models (GLMs), such as OpenAI’s ChatGPT, is changing the way we communicate with computers and has a major impact on the educational landscape. While GLMs have great potential to support education, their use is not unproblematic, as they suffer from hallucinations and misinformation. In this paper, we investigate how a very limited amount of domain-specific data, from lecture slides and transcripts, can be used to build knowledge-based and generative educational chatbots. We found that knowledge-based chatbots allow full control over the system’s response but lack the verbosity and flexibility of GLMs. The answers provided by GLMs are more trustworthy and offer greater flexibility, but their correctness cannot be guaranteed. Adapting GLMs to domain-specific data trades flexibility for correctness.

Abstract Background Clinical data collection requires correct and complete data sets in order to perform correct statistical analysis and draw valid conclusions. While in randomized clinical trials much effort concentrates on data monitoring, this is rarely the case in observational studies- due to high numbers of cases and often-restricted resources. We have developed a valid and cost-effective monitoring tool, which can substantially contribute to an increased data quality in observational research. Methods An automated digital monitoring system for cohort studies developed by the German Rheumatism Research Centre (DRFZ) was tested within the disease register RABBIT-SpA, a longitudinal observational study including patients with axial spondyloarthritis and psoriatic arthritis. Physicians and patients complete electronic case report forms (eCRF) twice a year for up to 10 years. Automatic plausibility checks were implemented to verify all data after entry into the eCRF. To identify conflicts that cannot be found by this approach, all possible conflicts were compiled into a catalog. This “conflict catalog” was used to create queries, which are displayed as part of the eCRF. The proportion of queried eCRFs and responses were analyzed by descriptive methods. For the analysis of responses, the type of conflict was assigned to either a single conflict only (affecting individual items) or a conflict that required the entire eCRF to be queried. Results Data from 1883 patients was analyzed. A total of n = 3145 eCRFs submitted between baseline (T0) and T3 (12 months) had conflicts (40–64%). Fifty-six to 100% of the queries regarding eCRFs that were completely missing were answered. A mean of 1.4 to 2.4 single conflicts occurred per eCRF, of which 59–69% were answered. The most common missing values were CRP, ESR, Schober’s test, data on systemic glucocorticoid therapy, and presence of enthesitis. Conclusion Providing high data quality in large observational cohort studies is a major challenge, which requires careful monitoring. An automated monitoring process was successfully implemented and well accepted by the study centers. Two thirds of the queries were answered with new data. While conventional manual monitoring is resource-intensive and may itself create new sources of errors, automated processes are a convenient way to augment data quality.

During an outbreak of Q fever in Germany, we identified an infected sheep flock from which animals were routinely used as a source for life cell therapy (LCT), the injection of fetal cells or cell extracts from sheep into humans. Q fever developed in 7 LCT recipients from Canada, Germany, and the United States.

BackgroundA novel non-invasive asthma prediction tool from the Leicester Cohort, UK, forecasts asthma at age 8 years based on 10 predictors assessed in early childhood, including current respiratory symptoms, eczema, and parental history of asthma.ObjectiveWe aimed to externally validate the proposed asthma prediction method in a German birth cohort.MethodsThe MAS-90 study (Multicentre Allergy Study) recorded details on allergic diseases prospectively in about yearly follow-up assessments up to age 20 years in a cohort of 1,314 children born 1990. We replicated the scoring method from the Leicester cohort and assessed prediction, performance and discrimination. The primary outcome was defined as the combination of parent-reported wheeze and asthma drugs (both in last 12 months) at age 8. Sensitivity analyses assessed model performance for outcomes related to asthma up to age 20 years.ResultsFor 140 children parents reported current wheeze or cough at age 3 years. Score distribution and frequencies of later asthma resembled the Leicester cohort: 9% vs. 16% (MAS-90 vs. Leicester) of children at low risk at 3 years had asthma at 8 years, at medium risk 45% vs. 48%. Performance of the asthma prediction tool in the MAS-90 cohort was similar (Brier score 0.22 vs. 0.23) and discrimination slightly better than in the original cohort (area under the curve, AUC 0.83 vs. 0.78). Prediction and discrimination were robust against changes of inclusion criteria, scoring and outcome definitions. The secondary outcome 'physicians' diagnosed asthma at 20 years' showed the highest discrimination (AUC 0.89).ConclusionThe novel asthma prediction tool from the Leicester cohort, UK, performed well in another population, a German birth cohort, supporting its use and further development as a simple aid to predict asthma risk in clinical settings.

ObjectiveTo examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6-10 years.DesignPooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. EXPOSURE DEFINITION: Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. OUTCOME DEFINITION: Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6-10 years of age.Data synthesisThree-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models.ResultsWe found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with "no pets" (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I(2) = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with "no pets" (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I(2) = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to "no pets" resulted in an odds ratio of 1.04 (0.59 to 1.84) (I(2) = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens.ConclusionsPet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6-10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.

IntroductionGiven a high amount of workplace stressors, burnout syndrome, as a depression-related syndrome, is highly relevant for medical service soldiers. This study aims to examine their effects with regard to moral injuries and personal values following foreign deployment.Materials and methodsThis longitudinal study included 91 soldiers of the German Armed Forces Medical Service. Participants completed the Maslach Burnout Inventory (MBI) and the Portrait-Value-Questionnaire (PVQ) before and after a foreign deployment as well as the Moral Injury Scale (SMBE) after deployment. Analysis has been conducted using t-tests to assess potential changes in MBI and PVQ scales between pre-test - t1 (2-4 weeks before deployment) and post-test – t2 (up to 6 months after deployment). In addition, correlations were examined between moral injuries (MI) after deployment and MBI scores at t1 and t2 as well as between personal values (PVQ t1) and MBI scores at t1 and t2.ResultsThe MBI subscales showed mild to moderate burnout symptoms at both pre- and post-tests, with a slight deterioration during the study period, albeit not significant. There were no significant mean differences in PVQ between measurement points. Nevertheless, PVQ self-direction and tradition at t1 correlated negatively with MBI INV at t2 (PVQ SD r = -.21, p = .043) and MBI PA at t2 (PVQ TR r = -.23, p = .027). Furthermore, the subscale PVQ power at t1 correlated positively with MBI PA at t2 (PVQ PO r = .28, p = .006), meanwhile PVQ universalism at t1 correlated positively with MBI INV at t1 (PVQ UN r = .25, p = .018). Furthermore, positive correlations were found between moral injuries at t2 (SMBE total score, SMBE_Sub1, SMBE_Sub2) and MBI subscales Emotional Exhaustion (EE; r = -.54, p = .001), Depersonalization (DP; r = .38, p = .001), and Involvement (INV; r = .30, p = .004) before and after the deployment period. No correlation was found between MI and MBI subscale Personal Accomplishment (PA).ConclusionThe results indicate that medical service soldiers exhibit mild to moderate burnout symptoms even before deployment. Significant associations between moral injuries and burnout were found in 3 out of 4 MBI subscales (EE, DP, INV). There was a significant association with a stronger moral injury and higher burnout levels, persisting both before and after the study period. Furthermore, our results suggest that personal value orientations might be meaningful predictors of burnout. Hence, causal questions regarding general work stress among medical service soldiers should be further explored in more detailed studies. Further research could lay the foundation for future approaches in psychotherapy as well as primary and secondary prevention in this field.

Abstract Prime editing is a highly versatile genome editing technology that enables the introduction of base substitutions, insertions, and deletions. However, compared to traditional Cas9 nucleases prime editors (PEs) are less active. In this study we use OrthoRep, a yeast-based platform for directed protein evolution, to enhance the editing efficiency of PEs. After several rounds of evolution with increased selection pressure, we identify multiple mutations that have a positive effect on PE activity in yeast cells and in biochemical assays. Combining the two most effective mutations – the A259D amino acid substitution in nCas9 and the K445T substitution in M-MLV RT – results in the variant PE_Y18. Delivery of PE_Y18, encoded on DNA, mRNA or as a ribonucleoprotein complex into mammalian cell lines increases editing rates up to 3.5-fold compared to PEmax. In addition, PE_Y18 supports higher prime editing rates when delivered in vivo into the liver or brain. Our study demonstrates proof-of-concept for the application of OrthoRep to optimize genome editing tools in eukaryotic cells.

In closed-bore MRI units, assistance systems play a crucial role in overcoming patient access limitations during percutaneous interventions. In this work, we present eGantryMate, a piezo-motor-driven assistance system specifically designed for MR-guided needle interventions in high-field MRI systems. eGantryMate consists of an instrument positioning unit and a control unit equipped with piezo motors, radiofrequency filters, and shielding. Paired with a real-time tracking sequence for automatic marker detection and projection of the instrument trajectory onto the MR image, eGantryMate enables precise and efficient needle interventions. Targeting experiments were performed by inserting a biopsy needle into a series of fiducial targets in a phantom, and usability experiments were conducted in vivo without needle insertion. The results show artifact-free MR imaging, minimal temperature rise on the instrument positioning unit, and precise targeting capabilities. These findings demonstrate eGantryMate’s ability to perform real-time needle alignments and insertions within the magnet bore, highlighting its potential to enhance the acceptability and efficacy of MR-guided interventions.

Several studies on the perception of impact sounds question the correlation of standardized approaches with perceived annoyance, while more recent studies have come to inconsistent conclusions. All these studies neglected the aspect of whole-body vibrations, which are known to be relevant for the perception of low-frequency sound and can be perceived especially in lightweight constructions. Basically, the contribution of vibrations to impact sound annoyance is still unknown and could be the reason for the contradictory results. To investigate this aspect, we measured vibrations on different types of floors under laboratory conditions and in situ. For this purpose, a vibration-sensing device was developed to record vibrations more cost-effectively and independently of commercial recording instruments. The vibrations of predefined impact sequences were recorded together with the sound field using a higher-order ambisonics microphone. In addition, a vibration exposure device was developed to expose the test objects to the exact vibrations that occur in the built environment. The vibration exposure device is integrated into the ambisonics reproduction system, which consists of a large number of loudspeakers in a spherical configuration. The article presents the development and performance achieved using the vibration-sensing unit and the vibration exposure device. The study is relevant for conducting future impact sound listening tests under laboratory conditions, which can be extended to include the reproduction of vibrations.

We present the case of a 46-year-old mother of a young child who was diagnosed with metastatic leiomyosarcoma. At diagnosis, the tumor had already infiltrated the vena cava, infiltration of the pancreas was suspected, and pulmonary metastases had been histologically confirmed. The goal of treatment was to prolong survival and gain quality time for the family. When the patient had not responded to 4 cycles of doxorubicin, trabectedin was initiated. After an initial partial remission with a reduction in the size of the primary leiomyosarcoma as well as some pulmonary metastases, the disease remained stable for a total of 10 months. Upon progression, the patient did not further respond to subsequent treatment lines. The presented case shows that second-line trabectedin may represent a promising option for patients with chemotherapy-resistant leiomyosarcoma to prolong survival while preserving quality of life.

Abstract SMNDC1 is a Tudor domain protein that recognizes di-methylated arginines and controls gene expression as an essential splicing factor. Here, we study the specific contributions of the SMNDC1 Tudor domain to protein-protein interactions, subcellular localization, and molecular function. To perturb the protein function in cells, we develop small molecule inhibitors targeting the dimethylarginine binding pocket of the SMNDC1 Tudor domain. We find that SMNDC1 localizes to phase-separated membraneless organelles that partially overlap with nuclear speckles. This condensation behavior is driven by the unstructured C-terminal region of SMNDC1, depends on RNA interaction and can be recapitulated in vitro. Inhibitors of the protein’s Tudor domain drastically alter protein-protein interactions and subcellular localization, causing splicing changes for SMNDC1-dependent genes. These compounds will enable further pharmacological studies on the role of SMNDC1 in the regulation of nuclear condensates, gene regulation and cell identity.

The microRNA-200 family has wide-ranging regulatory functions in cancer development and progression. Above all, it is strongly associated with the epithelial-to-mesenchymal transition (EMT), a process during which cells change their epithelial to a mesenchymal phenotype and acquire invasive characteristics. More recently, miR-200 family members have also been reported to impact the immune evasion of cancer cells by regulating the expression of immunoinhibitory immune checkpoints (ICs) like PD-L1. Therefore, we aimed to comprehensively characterize this miR-200 family as a regulatory interface between EMT and immune evasion mechanisms in biliary tract cancer. Initial correlation analyses and transient overexpression experiments using miRNA mimics suggested miR-200c-3p as a putative regulator of ICs including PD-L1, LGALS9, and IDO1. However, these effects could not be confirmed in stable miR-200c-3p overexpression cell lines, nor in cells transiently transfected with miR-200c-3p mimic from an independent manufacturer. By shifting our efforts towards dissecting the mechanisms leading to these disparate effects, we observed that the initially used miR-200c-3p mimic triggered a double-stranded (ds)RNA-dependent antiviral response. Besides upregulating the ICs, this had substantial cellular consequences including an induction of interferon type I and type III expression, increased levels of intracellular dsRNA sensors, and a significantly altered cellular growth and apoptotic activity.Our study highlights the capability of miRNA mimics to non-specifically induce a dsRNA-mediated antiviral interferon response. Consequently, phenotypic alterations crucially distort physiological miRNA functions and might result in a major misinterpretation of previous and future miRNA studies, especially in the context of IC regulation.