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Schuster, T.

Publications and source records attributed to Schuster, T..

3 recordsLinked to original sources

Causal Language Detection using Text-Document Features: Methodology and Insights from 10 Years of Gut Microbiome Research

Detecting causal language in scientific literature is critical for understanding how research fields frame evidence and inform interventions and policies, yet existing approaches commonly rely on manual annotation. The objective of this study was to evaluate four classifiers for detecting causal language and to apply the best-performing model to assess trends in microbiome research. Microbiome research, with its rapidly expanding observational literature, provides a relevant case study. We extracted Term Frequency-Inverse Document Frequency (TF-IDF) features from the last three sentences of available publication abstracts and trained four classifiers (L1- and L2-regularized logistic regression, Random Forest, and eXtreme Gradient Boosting) to detect causal language. A total of 475 sentences, as determined pragmatically based on annotation feasibility and observed stabilization of model performance, were manually labeled as causal or non-causal following established guidelines for systematic evaluation of causal language in observational health research. Of these, 75% of sentences were used for training and 25% for testing. L1-regularized logistic regression achieved the highest performance (accuracy 76%, F1 72%, prevalence detection accuracy 95%, sensitivity 72%, and specificity 80%) and was applied to 20,022 human gut microbiome abstracts published between 2015 and 2025 grouped into 20 thematic topics using structural topic modeling. Predicted causal language prevalence declined from 52% to 44% between 2015 and 2018, then rose to 51% by 2025, with notable variation across topics (range: 43.1-53.3%). Temporal trends differed across subfields, with increases in Metabolic disorders, Fecal microbiota transplantation, and decreases in Biomarkers and prediction, Antibiotic resistance, and In vitro fermentation. Analysis of influential words confirmed that causal meaning is primarily driven by verbs and modifiers lexically signaling change or intervention. The proposed approach for identifying causal claims in scientific abstracts enables systematic and automated, scalable assessment of how evidence is framed. Its application to the microbiome field highlighted heterogeneity in the reporting of causal relationships and informing the interpretation of microbiome findings for clinical and public health decision-making.

scientific communication and education↗

Common Genetic Variants of The Cardiac Sodium Channel Alter Patient Response to Class 1b Antiarrhythmics

Several common variants have been identified in SCN5A, which encodes the cardiac sodium channel -subunit Nav1.5 and is targeted by class I antiarrhythmics. Lidocaine and its analog mexiletine both have a primary amine that blocks Na+ current. While lidocaine is highly effective in terminating ventricular tachycardia after acute myocardial infarction, mexiletine has been shown to prevent arrhythmia induction in only [~]20% of patients. The factors underlying this inconsistent drug response are unclear. Here, we use cardiomyocytes that are derived from induced pluripotent stem cells to observe that a common polymorphism in the SCN5A gene, S1103Y, exhibits an altered pharmacological response to mexiletine, with enhanced use-dependent and tonic block of peak sodium current. In addition, an unexpected increase in late sodium current causes action potential prolongation. This paradoxical proarrhythmic phenotype shifts the paradigm of conventional antiarrhythmic therapy with mexiletine, suggesting that background variants may alter pharmacological responses leading to unanticipated consequences. Our results suggest that the unique genetic background of patients should inform therapeutic approaches to treat and prevent arrhythmias associated with common cardiac pathologies.

physiology↗

A Cdc42-Borg4-Septin 7 axis regulates HSCs polarity and function

Aging of hematopoietic stem cells (HSCs) is caused by an elevated activity of the small RhoGTPase Cdc42 and an apolar distribution of proteins. Mechanisms by which Cdc42 activity controls polarity of HSCs are not known. Binder of RhoGTPases proteins (borgs) are known effector proteins of Cdc42 that are able to regulate the cytoskeletal septin network. Here we show that Cdc42 interacts with borg4, which in turn interacts with septin 7 to regulate the polar distribution of Cdc42, borg4 and septin 7 within HSCs. Genetic deletion of either borg4 or septin 7 in HSCs resulted in a reduced frequency of HSCs polar for Cdc42 or borg4 or septin 7 and a reduced engraftment potential and decreased lymphoid-primed multipotent progenitors (LMPPs) frequency in the bone marrow. In aggregation our data identify a Cdc42-borg4-septin 7 axis to be essential for maintenance of polarity within HSCs and for HSC function and provide rationale for further investigating the role of borgs and septins for the regulation of compartmentalization within stem cells. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/435817v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@168dd5org.highwire.dtl.DTLVardef@b9b4a3org.highwire.dtl.DTLVardef@26e05org.highwire.dtl.DTLVardef@1851fcf_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗