Streptobacillus moniliformis and IgM and IgG Immune Response in Patient with Endocarditis1.

We describe a case of endocarditis caused by Streptobacillus moniliformis bacteria, a known cause of rat-bite fever, in a 32-year-old woman with pet rats in Germany. The patient had a strong serologic response, with high IgM and IgG titers. Serologic analysis is a promising tool to identify S. moniliformis bacterial infection.

[Macrocytic anemia and polychondritis: VEXAS syndrome]. / Makrozytäre Anämie und Polychondritis: VEXAS-Syndrom.

An adult-onset autoinflammatory syndrome caused by somatic mutations in the UBA1 gene on the X chromosome was first reported in 2020. This VEXAS syndrome (acronym for vacuoles, E1 enzyme, X­linked, autoinflammatory, somatic) is characterized by an overlap of rheumatic inflammatory diseases with separate hematologic abnormalities. A substantial number of affected patients suffer from treatment refractory relapsing polychondritis and nearly always show signs of macrocytic anemia. This case report illustrates the diagnostic key points to recognizing patients with VEXAS syndrome.

[Eosinophilic granulomatosis with polyangiitis: a review article]. / Eosinophile Granulomatose mit Polyangiitis ­ ein Übersichtsartikel.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of ANCA-associated vasculitis (AAV) within the group of small vessel vasculitides. It is defined by vasculitis of small and medium-sized vessels with granulomatous inflammation and blood and tissue eosinophilia. Almost all patients have allergic symptoms with bronchial asthma and rhinosinusitis symptoms. Further clinical manifestations vary depending on the localisation, severity, and type of disease manifestation. Eosinophilic infiltration and inflammation may result in rhinosinusitis, pneumonitis, gastrointestinal involvement, and cardiomyopathy. The latter, in particular, is associated with a worse prognosis. As a necrotising pauci-immune small-vessel vasculitis, EGPA, similar to the other AAVs, can cause pulmonary infiltrates with alveolar haemorrhage, glomerulonephritis, cutaneous vasculitis with purpura as well as central and peripheral neurologic injuries. The presence of perinuclear ANCA (pANCA) with specificity against myeloperoxidase (MPO) is observed in approximately one-third of patients but is not specific to EGPA. MPO-ANCA-positive patients are more likely to have peripheral neurologic involvement and glomerulonephritis, whereas ANCA-negative patients are more likely to have cardiac and pulmonary involvement. What is frequently challenging in the clinical routine is to differentiate EGPA from the hypereosinophilic syndrome (HES). The therapeutic approach to EGPA depends on whether the severity of the disease is potentially organ or life-threatening. For severe forms of EGPA, acute therapy mainly includes glucocorticoids in combination with cyclophosphamide. Rituximab has come to be mentioned as an alternative treatment option in the guidelines. Various immunosuppressive therapies are available for remission maintenance. In EGPA without severe organ involvement, IL-5 blockade with mepolizumab is an approved treatment.

Side-Directed Release of Differential Extracellular Vesicle-associated microRNA Profiles from Bronchial Epithelial Cells of Healthy and Asthmatic Subjects.

Extracellular vesicles (EVs) are released by virtually all cells and may serve as intercellular communication structures by transmitting molecules such as proteins, lipids, and nucleic acids between cells. MicroRNAs (miRNAs) are an abundant class of vesicular RNA playing a pivotal role in regulating intracellular processes. In this work, we aimed to characterize vesicular miRNA profiles released in a side-directed manner by bronchial epithelial cells from healthy and asthmatic subjects using an air-liquid interface cell culture model. EVs were isolated from a culture medium collected from either the basolateral or apical cell side of the epithelial cell cultures and characterized by nano-flow cytometry (NanoFCM) and bead-based flow cytometry. EV-associated RNA profiles were assessed by small RNA sequencing and subsequent bioinformatic analyses. Furthermore, miRNA-associated functions and targets were predicted and miRNA network analyses were performed. EVs were released at higher numbers to the apical cell side of the epithelial cells and were considerably smaller in the apical compared to the basolateral compartment. EVs from both compartments showed a differential tetraspanins surface marker expression. Furthermore, 236 miRNAs were differentially expressed depending on the EV secretion side, regardless of the disease phenotype. On the apical cell side, 32 miRNAs were significantly altered in asthmatic versus healthy conditions, while on the basolateral cell side, 23 differentially expressed miRNAs could be detected. Downstream KEGG pathway analysis predicted mTOR and MAPK signaling pathways as potential downstream targets of apically secreted miRNAs. In contrast, miRNAs specifically detected at the basolateral side were associated with processes of T and B cell receptor signaling. The study proves a compartmentalized packaging of EVs by bronchial epithelial cells supposedly associated with site-specific functions of cargo miRNAs, which are considerably affected by disease conditions such as asthma.

Developing a Conversational Agent's Capability to Identify Structural Wrongness in Arguments Based on Toulmin's Model of Arguments.

This article discusses the usefulness of Toulmin's model of arguments as structuring an assessment of different types of wrongness in an argument. We discuss the usability of the model within a conversational agent that aims to support users to develop a good argument. Within the article, we present a study and the development of classifiers that identify the existence of structural components in a good argument, namely a claim, a warrant (underlying understanding), and evidence. Based on a dataset (three sub-datasets with 100, 1,026, 211 responses in each) in which users argue about the intelligence or non-intelligence of entities, we have developed classifiers for these components: The existence and direction (positive/negative) of claims can be detected a weighted average F1 score over all classes (positive/negative/unknown) of 0.91. The existence of a warrant (with warrant/without warrant) can be detected with a weighted F1 score over all classes of 0.88. The existence of evidence (with evidence/without evidence) can be detected with a weighted average F1 score of 0.80. We argue that these scores are high enough to be of use within a conditional dialogue structure based on Bloom's taxonomy of learning; and show by argument an example conditional dialogue structure that allows us to conduct coherent learning conversations. While in our described experiments, we show how Toulmin's model of arguments can be used to identify structural problems with argumentation, we also discuss how Toulmin's model of arguments could be used in conjunction with content-wise assessment of the correctness especially of the evidence component to identify more complex types of wrongness in arguments, where argument components are not well aligned. Owing to having progress in argument mining and conversational agents, the next challenges could be the developing agents that support learning argumentation. These agents could identify more complex type of wrongness in arguments that result from wrong connections between argumentation components.

Role of airway epithelial cells in the development of different asthma phenotypes.

The term (bronchial) asthma describes a disorder syndrome that comprises several disease phenotypes, all characterized by chronic inflammation in the bronchial epithelium, with a variety of subsequent functional consequences. Thus, the epithelium in the conducting airways is the main localization of the complex pathological changes in the disease. In this regard, bronchial epithelial cells are not passively affected by inflammatory mechanisms induced by immunological processes but rather actively involved in all steps of disease development from initiation and perpetuation to chronification. In recent years it turned out that bronchial epithelial cells show a high level of structural and functional diversity and plasticity with epigenetic mechanisms playing a crucial role in the regulation of these processes. Thus, it is quite reasonable that differential functional activities of the bronchial epithelium are involved in the development of different asthma phenotypes and/or stages of disease. The current knowledge on this topic will be discussed in this review article.