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Auscultation methods enable non-invasive diagnosis of diseases, e.g. of the heart, based on heartbeat sounds. Regular, early examinations using machine learning techniques could help to detect diseases at an early stage to prevent serious health conditions and then provide optimal therapy through continuous monitoring. There is already a lot of work on human data using AI algorithms to detect patterns in signals or images. However, there is hardly no work on detecting heart murmurs with digital such as Myxomatous Mitral Valve Disease. In this paper, we present a canine auscultation project that aims to provide a tool to establish a baseline of classification parameters from audio signals that could be used to monitor canine health status by analyzing deviations from this baseline. In the future, data analysis could also lead to prediction and early detection of other diseases.

ZusammenfassungIn einem Schweinemastbetrieb in Süddeutschland konnten über einen Zeitraum von 4 Wochen Hinterhandlähmungen bei 2 Altersgruppen (50 kg sowie 60 kg) beobachtet werden. Die Morbidität bei den beiden Altersgruppen war mit 3,3 % niedrig, der Großteil der betroffenen Tiere musste jedoch aufgrund einer fortschreitenden Paralyse der Hintergliedmaßen euthanasiert werden. Im Rahmen der pathomorphologischen Untersuchung von 2 Mastschweinen konnte eine hochgradige und diffuse lymphohistiozytäre Meningoenzephalomyelitis und Vaskulitis festgestellt werden. Immunhistochemisch wurde in allen Arealen des zentralen Nervensystems und in mehreren Zelltypen (Neuronen, Gliazellen, Endothelzellen, mononukleäre Zellen) Porzines Teschovirus-Antigen nachgewiesen. Die Untersuchung von Rückenmarksproben mittels PCR ergab den Nachweis von Porzinen Teschoviren. Der anschließend durchgeführten phylogenetischen Analyse zufolge wiesen die PCR positiven Proben die höchste Identität (88 % Vollgenomsequenz) zum Porzinen Teschovirus A11 Stamm „Dresden“ auf. Andere differentialdiagnostisch in Frage kommende Pathogene konnten mittels PCR, bakteriologischer Untersuchung und Sequenzierung nicht nachgewiesen werden. In dem Mastbestand traten nach ca. 4 Wochen keine weiteren Fälle von Lähmungserscheinungen mehr auf.

ZusammenfassungIn einem Jungsauenerzeugerbetrieb in Niederösterreich traten über mehrere Jahre hinweg gehäuft Atemwegserkrankungen bei Jungsauen aus Eigenremontierung nach Einstallung in die Altsauenherde auf. Im Herbst 2019 wurden zudem Fruchtbarkeitsstörungen in Form von Spätaborten und Umrauschen beobachtet. Bei der Untersuchung von Nasentupfern mittels PCR auf Influenza-A-Virus (IAV) konnte bei 3 Jungsauen mit respiratorischer Symptomatik und Fieber der IAV-Subtyp H1avN1 nachgewiesen werden. Die Untersuchung der Serumproben dieser Tiere an 2 Zeitpunkten im Abstand von 3 Wochen ergab jedoch keinen Nachweis von Antikörpern im Hämagglutinationshemmtest (HAH), der standardmäßig im Labor verwendet wurde. Auch bei der Untersuchung von Sauen weiterer Altersgruppen waren keine eindeutigen Antikörpertiter gegenüber H1avN1 detektierbar. Nach Erweiterung des diagnostischen Panels des HAH um 7 H1avN1-Testantigene konnte eine Serokonversion um bis zu 3 Titerstufen bei den PCR-positiven Sauen gegenüber 2 verschiedenen H1avN1-Isolaten gemessen werden. Darüber hinaus ließen sich auch bei der Mehrzahl der restlichen untersuchten Altersgruppen hohe Antikörpertiter gegen diese beiden H1avN1-Teststämme nachweisen. Nach Anwendung des europaweit zugelassenen trivalenten Influenzaimpfstoffs konnte das klinische Erscheinungsbild in der Herde deutlich verbessert werden. Der Fallbericht verdeutlicht, dass für eine zielgerichtete Influenzadiagnostik der direkte und der indirekte Erregernachweis kombiniert verwendet werden sollten. Zudem wurde gezeigt, dass die kontinuierliche Anpassung von Testantigenen an die im Feld zirkulierenden Isolate überaus entscheidend für die Aussagekraft des HAH wäre.

Synchrotron processes, the radiative processes associated with the interaction of energetic charged particles with magnetic field, are of interest in many areas in astronomy, from the interstellar medium to extreme environments near compact objects. Consequently, observations of synchrotron sources carry information on the physical properties of the sources themselves and those of their close vicinity. In recent years, novel observations of such sources with multi-wavelength collaborations reveal complex features and peculiarities, especially near black holes. Exploring the nature of these sources in more detail necessitates numerical tools complementary to analytical one-zone modelling efforts. In this paper, we introduce an open-source Python package tailored to this purpose, FLAREMODEL. The core of the code consists of low-level utility functions to describe physical processes relevant to synchrotron sources, which are written in C for performance and parallelised with OpenMP for scalability. The Python interface provides access to these functions and built-in source models are provided as a guidance. At the same time, the modular design of the code and the generic nature of these functions enable users to build a variety of source models applicable to many astrophysical synchrotron sources. We describe our methodology and the structure of our code along with selected examples demonstrating capabilities and options for future modelling efforts.

We present a large ${\sim 30" \times 30"}$ spectroscopic survey of the Galactic Center using the SINFONI IFU at the VLT. Combining observations of the last two decades we compile spectra of over $2800$ stars. Using the Bracket-$\gamma$ absorption lines we identify $195$ young stars, extending the list of known young stars by $79$. In order to explore the angular momentum distribution of the young stars, we introduce an isotropic cluster prior. This prior reproduces an isotropic cluster in a mathematically exact way, which we test through numerical simulations. We calculate the posterior angular momentum space as function of projected separation from Sgr~A*. We find that the observed young star distribution is substantially different from an isotropic cluster. We identify the previously reported feature of the clockwise disk and find that its angular momentum changes as function of separation from the black hole, and thus confirm a warp of the clockwise disk ($p \sim 99.2\%$). At large separations, we discover three prominent overdensities of angular momentum. One overdensity has been reported previously, the counter-clockwise disk. The other two are new. Determining the likely members of these structures, we find that as many as $75\%$ of stars can be associated with one of these features. Stars belonging to the warped clockwise-disk show a top heavy K-band luminosity function, while stars belonging to the larger separation features do not. Our observations are in good agreement with the predictions of simulations of in-situ star formation, and argue for common formation of these structures., Comment: Accepted for Publication in APJL

A combination of biochemical preparation methods with microscopic, spectroscopic, and mass spectrometric analysis techniques as contemplating state of the art application, was used for direct visualization, localization, and chemical identification of europium in plants. This works illustrates the chemical journey of europium (Eu(III)) through winter rye (Secale cereale L.), providing insight into the possibilities of speciation for Rare Earth Elements (REE) and trivalent f-elements. Kinetic experiments of contaminated plants show a maximum europium concentration in Secale cereale L. after four days. Transport of the element through the vascular bundle was confirmed with Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray analysis (EDS). For chemical speciation, plants were grown in a liquid nutrition medium, whereby Eu(III) species distribution could be measured by mass spectrometry and luminescence measurements. Both techniques confirm the occurrence of Eu malate species in the nutrition medium, and further analysis of the plant was performed. Luminescence results indicate a change in Eu(III) species distribution from root tip to plant leaves. Microscopic analysis show at least three different Eu(III) species with potential binding to organic and inorganic phosphate groups and a Eu(III) protein complex. With plant root extraction, further europium species could be identified by using Electrospray Ionization Mass Spectrometry (ESI MS). Complexation with malate, citrate, a combined malate-citrate ligand, and aspartate was confirmed mostly in a 1:1 stoichiometry (Eu:ligand). The combination of the used analytical techniques opens new possibilities in direct species analysis, especially regarding to the understanding of rare earth elements (REE) uptake in plants. This work provides a contribution in better understanding of plant mechanisms of the f-elements and their species uptake.

Pregravid obesity is one of the major risk factors for pregnancy complications such as gestational diabetes mellitus (GDM) and an increased risk of cardiovascular events in children of affected mothers. However, the biological mechanisms that underpin these adverse outcomes are not well understood. High-density lipoproteins (HDLs) are antiatherogenic by promoting the efflux of cholesterol from macrophages and by suppression of inflammation. Functional impairment of HDLs in obese and GDM-complicated pregnancies may have long-term effects on maternal and offspring health. In the present study, we assessed metrics of HDL function in sera of pregnant women with overweight/obesity of the DALI lifestyle trial (prepregnancy BMI ≥ 29 kg/m2) and women with normal weight (prepregnancy BMI < 25 kg/m2), as well as HDL functionalities in cord blood at delivery. We observed that pregravid obesity was associated with impaired serum antioxidative capacity and lecithin–cholesterol acyltransferase activity in both mothers and offspring, whereas maternal HDL cholesterol efflux capacity was increased. Interestingly, functionalities of maternal and fetal HDL correlated robustly. GDM did not significantly further alter the parameters of HDL function and metabolism in women with obesity, so obesity itself appears to have a major impact on HDL functionality in mothers and their offspring.

In a gilt producing farm in Lower Austria, respiratory diseases occurred over the previous years in self-reared gilts after being introduced into the sow herd. In addition, fertility disorders in terms of late abortions and re-breeders were observed in the fall of 2019. Nasal swabs of 3 gilts with respiratory signs and fever were tested positive for influenza A virus (IAV) subtype H1avN1 by PCR. However, examination of serum samples from these animals at 2 different time points did not detect antibodies using the standard hemagglutination inhibition (HI) test of the laboratory. Examination of additional age groups likewise failed to detect H1avN1 antibody titers. In consequence to the extension of the diagnostic panel of the HI test by 7 additional H1avN1 test antigens, a clear seroconversion of the PCR positive sows against 2 different H1avN1 isolates could be measured. In addition, high antibody titers against these 2 H1avN1 strains were also detectable in the majority of the remaining age groups tested. Following the administration of the trivalent influenza vaccine, which has been approved throughout Europe, a significant improvement of the clinical presentation in the herd was achieved. The present case report illustrates that direct and indirect pathogen detection should be used in combination for targeted influenza diagnostics. In addition, it was shown that the continuous adaptation of test antigens to the isolates circulating in the field would be extremely crucial for the significance of the HI test.In einem Jungsauenerzeugerbetrieb in Niederösterreich traten über mehrere Jahre hinweg gehäuft Atemwegserkrankungen bei Jungsauen aus Eigenremontierung nach Einstallung in die Altsauenherde auf. Im Herbst 2019 wurden zudem Fruchtbarkeitsstörungen in Form von Spätaborten und Umrauschen beobachtet. Bei der Untersuchung von Nasentupfern mittels PCR auf Influenza-A-Virus (IAV) konnte bei 3 Jungsauen mit respiratorischer Symptomatik und Fieber der IAV-Subtyp H1avN1 nachgewiesen werden. Die Untersuchung der Serumproben dieser Tiere an 2 Zeitpunkten im Abstand von 3 Wochen ergab jedoch keinen Nachweis von Antikörpern im Hämagglutinationshemmtest (HAH), der standardmäßig im Labor verwendet wurde. Auch bei der Untersuchung von Sauen weiterer Altersgruppen waren keine eindeutigen Antikörpertiter gegenüber H1avN1 detektierbar. Nach Erweiterung des diagnostischen Panels des HAH um 7 H1avN1-Testantigene konnte eine Serokonversion um bis zu 3 Titerstufen bei den PCR-positiven Sauen gegenüber 2 verschiedenen H1avN1-Isolaten gemessen werden. Darüber hinaus ließen sich auch bei der Mehrzahl der restlichen untersuchten Altersgruppen hohe Antikörpertiter gegen diese beiden H1avN1-Teststämme nachweisen. Nach Anwendung des europaweit zugelassenen trivalenten Influenzaimpfstoffs konnte das klinische Erscheinungsbild in der Herde deutlich verbessert werden. Der Fallbericht verdeutlicht, dass für eine zielgerichtete Influenzadiagnostik der direkte und der indirekte Erregernachweis kombiniert verwendet werden sollten. Zudem wurde gezeigt, dass die kontinuierliche Anpassung von Testantigenen an die im Feld zirkulierenden Isolate überaus entscheidend für die Aussagekraft des HAH wäre.

Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.1J as an all-around well-performing iPSC line. We then shared KOLF2.1J with groups around the world who tested its performance in head-to-head comparisons with their own preferred iPSC lines across a diverse range of differentiation protocols and functional assays. On the strength of these findings, we have made KOLF2.1J and its gene-edited derivative clones readily accessible to promote the standardization required for large-scale collaborative science in the stem cell field.

Fully automated proteomic pipelines have the potential to achieve deep coverage of cellular proteomes with high throughput and scalability. However, it is important to evaluate performance, including both reproducibility and ability to provide meaningful levels of biological insight. Here, we present an approach combining high field asymmetric waveform ion mobility spectrometer (FAIMS) interface and data independent acquisition (DIA) proteomics approach developed as part of the induced pluripotent stem cell (iPSC) Neurodegenerative Disease Initiative (iNDI), a large-scale effort to understand how inherited diseases may manifest in neuronal cells. Our FAIMS-DIA approach identified more than 8000 proteins per mass spectrometry (MS) acquisition as well as superior total identification, reproducibility, and accuracy compared to other existing DIA methods. Next, we applied this approach to perform a longitudinal proteomic profiling of the differentiation of iPSC-derived neurons from the KOLF2.1J parental line used in iNDI. This analysis demonstrated a steady increase in expression of mature cortical neuron markers over the course of neuron differentiation. We validated the performance of our proteomics pipeline by comparing it to single cell RNA-Seq datasets obtained in parallel, confirming expression of key markers and cell type annotations. An interactive webapp of this temporal data is available for aligned-UMAP visualization and data browsing (https://share.streamlit.io/anant-droid/singlecellumap). In summary, we report an extensively optimized and validated proteomic pipeline that will be suitable for large-scale studies such as iNDI.

Reproductive disorders induced by porcine reproductive and respiratory syndrome virus (PRRSV) cause high economic losses in the pig industry worldwide. In this study, we aimed to phenotypically characterize a virulent PRRSV-1 subtype 1 isolate (AUT15-33) in a reproductive model. Furthermore, the protective effect of a heterologous modified live virus vaccine (ReproCyc® PRRS EU) was evaluated. In addition, PRRSV AUT15-33 was genotypically compared to other well-characterized isolates. Sixteen gilts were equally divided into four groups: a vaccinated and infected group (V–I), a vaccinated and non-infected group (V–NI), a non-vaccinated and infected group (NV–I), and a non-vaccinated and non-infected (NV–NI) group. After PRRSV infection on gestation day 84, all gilts were clinically examined on a daily basis, and blood samples were taken at five timepoints. Necropsy was performed 3 weeks after infection. The fetal preservation status was assessed, and PRRSV RNA concentrations were measured in the blood and tissue samples from all gilts and fetuses. After infection, all four gilts in the NV–I group were viremic throughout 17 days post-infection (dpi), whereas two gilts in the V–I group were viremic at only one timepoint at 6 dpi. The viral load was significantly higher in gilt serum, tracheobronchial lymph nodes, uterine lymph nodes, maternal endometrium, and fetal placenta of NV–I gilts compared to the V–I ones (p < 0.05). Moreover, the preservation status of the fetuses derived from NV–I gilts was significantly impaired (55.9% of viable fetuses) compared to the other groups (p < 0.001). Upon comparison with other known isolates, the phylogenetic analyses revealed the closest relation to a well-characterized PRRSV-1 subtype 1 field isolate from Belgium. In conclusion, the high virulence of AUT15-33 was phenotypically confirmed in an experimental reproductive model. The vaccination of the gilts showed promising results in reducing viremia, fetal damage, and transplacental transmission of the PRRSV-1 strain characterized in this study.

Background The prognosis of patients with brain metastases (BM) is poor despite advances in our understanding of the underlying pathophysiology. The high incidence of thrombotic complications defines tumor progression and the high mortality rate. We, therefore, postulated that von Willebrand factor (VWF) promotes BM via its ability to induce platelet aggregation and thrombosis. Methods We measured the abundance of VWF in the blood and intravascular platelet aggregates of patients with BM, and determined the specific contribution of endothelial and platelet-derived VWF using in vitro models and microfluidics. The relevance for the brain metastatic cascade in vivo was demonstrated in ret transgenic mice, which spontaneously develop BM, and by the intracardiac injection of melanoma cells. Results Higher levels of plasma VWF in patients with BM were associated with enhanced intraluminal VWF fiber formation and platelet aggregation in the metastatic tissue and peritumoral regions. Platelet activation triggered the formation of VWF multimers, promoting platelet aggregation and activation, in turn enhancing tumor invasiveness. The absence of VWF in platelets, or the blocking of platelet activation, abolished platelet aggregation, and reduced tumor cell transmigration. Anticoagulation and platelet inhibition consistently reduced the number of BM in preclinical animal models. Conclusions Our data indicate that platelet-derived VWF is involved in cerebral clot formation and in metastatic growth of melanoma in the brain. Targeting platelet activation with low-molecular-weight heparins represents a promising therapeutic approach to prevent melanoma BM.

Atherosclerosis is a disease of increased oxidative stress characterized by protein and lipid modifications in the vessel wall. One important oxidative pathway involves reactive intermediates generated by myeloperoxidase (MPO), an enzyme present mainly in neutrophils and monocytes. Tandem MS analysis identified MPO as a component of lesion derived high-density lipoprotein (HDL), showing that the two interact in the arterial wall. MPO modifies apolipoprotein A1 (apoA-I), paraoxonase 1 and certain HDL-associated phospholipids in human atheroma. HDL isolated from atherosclerotic plaques depicts extensive MPO mediated posttranslational modifications, including oxidation of tryptophan, tyrosine and methionine residues, and carbamylation of lysine residues. In addition, HDL associated plasmalogens are targeted by MPO, generating 2-chlorohexadecanal, a pro-inflammatory and endothelial barrier disrupting lipid that suppresses endothelial nitric oxide formation. Lesion derived HDL is predominantly lipid-depleted and cross-linked and exhibits a nearly 90% reduction in lecithin-cholesterol acyltransferase activity and cholesterol efflux capacity. Here we provide a current update of the pathophysiological consequences of MPO-induced changes in the structure and function of HDL and discuss possible therapeutic implications and options. Preclinical studies with a fully functional apoA-I variant with pronounced resistance to oxidative inactivation by MPO-generated oxidants are currently ongoing. Understanding the relationships between pathophysiological processes that affect the molecular composition and function of HDL and associated diseases is central to the future use of HDL in diagnostics, therapy, and ultimately disease management.