Sex and Age Characteristics in Acute or Chronic Myocarditis A Descriptive, Multicenter Cohort Study.

BACKGROUND: Understanding the clinical features of myocarditis in various age groups is required to identify age-specific disease patterns. OBJECTIVES: The objective of this study was to examine differences in sex distribution and clinical outcomes in patients with myocarditis of various ages. METHODS: Patients with acute or chronic myocarditis in 3 centers in Berlin, Germany from 2005 to 2021 and in the United States (National Inpatient Sample) from 2010 to 2019 were included. Age groups examined included "prepubescent" (below 11 years for females and below 13 years for males), adolescents (11 [female] or 13 [male] to 18 years), young adults (18-35 years), "middle-aged adults" (35-54 years), and older adults (age >54 years). In patients admitted to the hospital, hospital mortality, length of stay, and medical complication rates were examined. RESULTS: Overall, 6,023 cases in Berlin and 9,079 cases in the U.S. cohort were included. In both cohorts, there were differences in sex distribution among the 5 age categories, and differences in the distribution were most notable in adolescents (69.3% males vs 30.7% females) and in young adults (73.8% males vs 26.3% females). Prepubescent and older adults had the highest rates of in-hospital mortality, hospital length of stay, and medical complications. In the Berlin cohort, prepubescent patients had higher levels of leukocytes (P < 0.001), antistreptolysin antibody (P < 0.001), and NT-proBNP (P < 0.001) when compared to young adults. CONCLUSIONS: In this study, we found that sex differences in myocarditis and clinical features of myocarditis were age-dependent.

Risky listening behaviour to music via headphones and its determinants - 7.5 years OHRKAN cohort study.

OBJECTIVE: To examine risky leisure noise exposure from listening to music via headphones and to identify potential determinants with special focus on portable listening devices (PLDs) among adolescents over a period of 7.5-years. DESIGN: Data were collected by questionnaires at four equidistant time points (O1-O4). Music exposure via headphones was calculated based on self-reported volume setting and listening duration. Exceeding 85 dB(A) equivalent for a 40-hour working week was defined as risky noise exposure. Determinants of risky headphone and PLD exposure were investigated using generalised estimating equations and accounting for missing data by multiple imputation. STUDY SAMPLE: Closed cohort of 2148 students attending 9th grade of any secondary school type in Regensburg (Germany), during 2009 to 2011. RESULTS: Risky noise exposure from headphone usage was almost twice as high in wave O1 and O2 (at age 15 or 18) compared with 20-23-year-olds in O3 and O4. Risky exposure to headphones and PLDs were associated with younger age, low and medium education, single-parent household and smoking, whereas good self-rated hearing showed a protective effect. Additionally, not being born in Germany was associated with risky PLD exposure. CONCLUSION: Before harmful behaviours become entrenched, starting preventive efforts at a young age is essential.

Ten-year results of leisure noise exposure among adolescents and young adults-findings from the OHRKAN cohort study.

OBJECTIVE: To observe total leisure noise (TLN) exposure and to investigate determinants of risky TLN exposure among adolescents and young adults over a ten-year observation period. DESIGN: OHRKAN is a longitudinal study with five equidistantly distributed questionnaires (waves) over ten years. Risky TLN exposure was defined as exceeding ≥85dB(A) averaged over 40h per week. To identify determinants of risky TLN exposure longitudinally, generalised estimating equations were applied. STUDY SAMPLE: A subgroup (n = 661; mean age 25.6 years in the fifth wave; 58.4% female) of the closed cohort study OHRKAN was analysed. Included participants took part in the fifth wave prior to the study break due to COVID-19. RESULTS: Analysis of participants' data from all five waves showed that risky TLN exposure was highest during the second wave (72.0%), when participants were aged 17-19 years, and thereafter steadily declined. Among young adults, attendance at discotheques and private parties, especially, caused very high exposure. Determinants of risky TLN exposure were wave time point, male gender, a higher level of education, and smoking. CONCLUSIONS: As TLN exposure is highest among older adolescents, prevention programs should target younger teenagers and be tailored to the identified risk groups. The risk from private parties should be addressed.

The Prediction of Fall Circumstances Among Patients in Clinical Care - A Retrospective Observational Study.

Standardized fall risk scores have not proven to reliably predict falls in clinical settings. Machine Learning offers the potential to increase the accuracy of such predictions, possibly vastly improving care for patients at high fall risks. We developed a boosting algorithm to predict both recurrent falls and the severity of fall injuries. The model was trained on a dataset including extensive information on fall events of patients who had been admitted to Charité - Universitätsmedizin Berlin between August 2016 and July 2020. The data were recorded according to the German expert standard for fall documentation. Predictive power scores were calculated to define optimal feature sets. With an accuracy of 74% for recurrent falls and 86% for injury severity, boosting demonstrated the best overall predictive performance of all models assessed. Given that our data contain initially rated risk scores, our results demonstrate that well trained ML algorithms possibly provide tools to substantially reduce fall risks in clinical care settings.

Exposure to leisure noise and intermittent tinnitus among young adults in Bavaria: longitudinal data from a prospective cohort study.

OBJECTIVES: To investigate the association between total leisure noise exposure and intermittent tinnitus among young adults. DESIGN: Data were obtained from the Ohrkan study, an ongoing prospective cohort study conducted in South Germany since 2009. Information about exposure to impulse and leisure noise, tinnitus occurrences, sociodemographic variables, and self-rated hearing ability were analysed at four time points over a period of seven and a half years. STUDY SAMPLE: Participants of the Ohrkan cohort study, who provided data about the occurrence of tinnitus for all surveys (n = 1028). RESULTS: Intermittent tinnitus was reported in the majority of the sample (60%). The risk for intermittent tinnitus increased with higher sound pressure levels from exposure to leisure noise (full model (Odds Ratio, 95%CI): 80-<85dB(A): 1.41 [1.13-1.78], 85-<90dB(A): 1.73 [1.38-2.16], >90dB(A): 2.04 [1.59-2.61]). Visiting nightclubs was a major contributor to this relationship. Of the considered covariables, self-rated hearing as "poor", and growing up in a single-parent household were significantly associated with intermittent tinnitus. CONCLUSION: Intermittent tinnitus is very frequent among young adults and is associated with high levels of leisure noise exposure. To prevent intermittent tinnitus, reduced sound pressure levels and the use of hearing protection are necessary.

Extreme weather events in europe and their health consequences - A systematic review.

BACKGROUND: Due to climate change, the frequency, intensity and severity of extreme weather events, such as heat waves, cold waves, storms, heavy precipitation causing wildfires, floods, and droughts are increasing, which could adversely affect human health. The purpose of this systematic review is therefore to assess the current literature about the association between these extreme weather events and their impact on the health of the European population. METHODS: Observational studies published from January 1, 2007 to May 17, 2020 on health effects of extreme weather events in Europe were searched systematically in Medline, Embase and Cochrane Central Register of Controlled Trials. The exposures of interest included extreme temperature, heat waves, cold waves, droughts, floods, storms and wildfires. The health impacts included total mortality, cardiovascular mortality and morbidity, respiratory mortality and morbidity, and mental health. We conducted the systematic review following PRISMA (Preferred Reporting Items for Systematic Review and Meta-analysis). The quality of the included studies was assessed using the NICE quality appraisal checklist (National Institute for Health and Care Excellence). RESULTS: The search yielded 1472 articles, of which 35 met the inclusion criteria and were included in our review. Studies regarding five extreme weather events (extreme heat events, extreme cold events, wildfires, floods, droughts) were found. A positive association between extreme heat/cold events and overall, cardiovascular and respiratory mortality was reported from most studies. Wildfires are likely to increase the overall and cardiovascular mortality. Floods might be associated with the deterioration of mental health instead of mortality. Depending on their length, droughts could have an influence on both respiratory and cardiovascular mortality. Contradictory evidence was found in heat-associated morbidity and wildfire-associated respiratory mortality. The associations are inconclusive due to the heterogeneous study designs, study quality, exposure and outcome assessment. CONCLUSIONS: Evidence from most of the included studies showed that extreme heat and cold events, droughts, wildfires and floods in Europe have negative impacts on human health including mental health, although some of the associations are not conclusive. Additional high-quality studies are needed to confirm our results and further studies regarding the effects of other extreme weather events in Europe are to be expected.

Targeting In-Stent-Stenosis with RGD- and CXCL1-Coated Mini-Stents in Mice.

Atherosclerotic lesions that critically narrow the artery can necessitate an angioplasty and stent implantation. Long-term therapeutic effects, however, are limited by excessive arterial remodeling. We here employed a miniaturized nitinol-stent coated with star-shaped polyethylenglycole (star-PEG), and evaluated its bio-functionalization with RGD and CXCL1 for improving in-stent stenosis after implantation into carotid arteries of mice. Nitinol foils or stents (bare metal) were coated with star-PEG, and bio-functionalized with RGD, or RGD/CXCL1. Cell adhesion to star-PEG-coated nitinol foils was unaltered or reduced, whereas bio-functionalization with RGD but foremost RGD/CXCL1 increased adhesion of early angiogenic outgrowth cells (EOCs) and endothelial cells but not smooth muscle cells when compared with bare metal foils. Stimulation of cells with RGD/CXCL1 furthermore increased the proliferation of EOCs. In vivo, bio-functionalization with RGD/CXCL1 significantly reduced neointima formation and thrombus formation, and increased re-endothelialization in apoE-/- carotid arteries compared with bare-metal nitinol stents, star-PEG-coated stents, and stents bio-functionalized with RGD only. Bio-functionalization of star-PEG-coated nitinol-stents with RGD/CXCL1 reduced in-stent neointima formation. By supporting the adhesion and proliferation of endothelial progenitor cells, RGD/CXCL1 coating of stents may help to accelerate endothelial repair after stent implantation, and thus may harbor the potential to limit the complication of in-stent restenosis in clinical approaches.

Standardized benchmarking in the quest for orthologs.

Achieving high accuracy in orthology inference is essential for many comparative, evolutionary and functional genomic analyses, yet the true evolutionary history of genes is generally unknown and orthologs are used for very different applications across phyla, requiring different precision-recall trade-offs. As a result, it is difficult to assess the performance of orthology inference methods. Here, we present a community effort to establish standards and an automated web-based service to facilitate orthology benchmarking. Using this service, we characterize 15 well-established inference methods and resources on a battery of 20 different benchmarks. Standardized benchmarking provides a way for users to identify the most effective methods for the problem at hand, sets a minimum requirement for new tools and resources, and guides the development of more accurate orthology inference methods.

HMMER web server: 2015 update.

The HMMER website, available at http://www.ebi.ac.uk/Tools/hmmer/, provides access to the protein homology search algorithms found in the HMMER software suite. Since the first release of the website in 2011, the search repertoire has been expanded to include the iterative search algorithm, jackhmmer. The continued growth of the target sequence databases means that traditional tabular representations of significant sequence hits can be overwhelming to the user. Consequently, additional ways of presenting homology search results have been developed, allowing them to be summarised according to taxonomic distribution or domain architecture. The taxonomy and domain architecture representations can be used in combination to filter the results according to the needs of a user. Searches can also be restricted prior to submission using a new taxonomic filter, which not only ensures that the results are specific to the requested taxonomic group, but also improves search performance. The repertoire of profile hidden Markov model libraries, which are used for annotation of query sequences with protein families and domains, has been expanded to include the libraries from CATH-Gene3D, PIRSF, Superfamily and TIGRFAMs. Finally, we discuss the relocation of the HMMER webserver to the European Bioinformatics Institute and the potential impact that this will have.

BioJS: an open source standard for biological visualisation - its status in 2014.

BioJS is a community-based standard and repository of functional components to represent biological information on the web. The development of BioJS has been prompted by the growing need for bioinformatics visualisation tools to be easily shared, reused and discovered. Its modular architecture makes it easy for users to find a specific functionality without needing to know how it has been built, while components can be extended or created for implementing new functionality. The BioJS community of developers currently provides a range of functionality that is open access and freely available. A registry has been set up that categorises and provides installation instructions and testing facilities at http://www.ebi.ac.uk/tools/biojs/. The source code for all components is available for ready use at https://github.com/biojs/biojs.

TreeFam v9: a new website, more species and orthology-on-the-fly.

TreeFam (http://www.treefam.org) is a database of phylogenetic trees inferred from animal genomes. For every TreeFam family we provide homology predictions together with the evolutionary history of the genes. Here we describe an update of the TreeFam database. The TreeFam project was resurrected in 2012 and has seen two releases since. The latest release (TreeFam 9) was made available in March 2013. It has orthology predictions and gene trees for 109 species in 15,736 families covering ∼2.2 million sequences. With release 9 we made modifications to our production pipeline and redesigned our website with improved gene tree visualizations and Wikipedia integration. Furthermore, we now provide an HMM-based sequence search that places a user-provided protein sequence into a TreeFam gene tree and provides quick orthology prediction. The tool uses Mafft and RAxML for the fast insertion into a reference alignment and tree, respectively. Besides the aforementioned technical improvements, we present a new approach to visualize gene trees and alternative displays that focuses on showing homology information from a species tree point of view. From release 9 onwards, TreeFam is now hosted at the EBI.

A murine model of stent implantation in the carotid artery for the study of restenosis.

Despite the considerable progress made in the stent development in the last decades, cardiovascular diseases remain the main cause of death in western countries. Beside the benefits offered by the development of different drug-eluting stents, the coronary revascularization bears also the life-threatening risks of in-stent thrombosis and restenosis. Research on new therapeutic strategies is impaired by the lack of appropriate methods to study stent implantation and restenosis processes. Here, we describe a rapid and accessible procedure of stent implantation in mouse carotid artery, which offers the possibility to study in a convenient way the molecular mechanisms of vessel remodeling and the effects of different drug coatings.

Hieranoid: hierarchical orthology inference.

An accurate inference of orthologs is essential in many research fields such as comparative genomics, molecular evolution, and genome annotation. Existing methods for genome-scale orthology inference are mostly based on all-versus-all similarity searches that scale quadratically with the number of species. This limits their application to the increasing number of available large-scale datasets. Here, we present Hieranoid, a new orthology inference method using a hierarchical approach. Hieranoid performs pairwise orthology analysis using InParanoid at each node in a guide tree as it progresses from its leaves to the root. This concept reduces the total runtime complexity from a quadratic to a linear function of the number of species. The tree hierarchy provides a natural structure in multi-species ortholog groups, and the aggregation of multiple sequences allows for multiple alignment similarity searching techniques, which can yield more accurate ortholog groups. Using the recently published orthobench benchmark, Hieranoid showed the overall best performance. Our progressive approach presents a new way to infer orthologs that combines efficient graph-based methodology with aspects of compute-intensive tree-based methods. The linear scaling with the number of species is a major advantage for large-scale applications and makes Hieranoid well suited to cope with vast amounts of sequenced genomes in the future. Hieranoid is an open source and can be downloaded at Hieranoid.sbc.su.se.

Deep metazoan phylogeny: when different genes tell different stories.

Molecular phylogenetic analyses have produced a plethora of controversial hypotheses regarding the patterns of diversification of non-bilaterian animals. To unravel the causes for the patterns of extreme inconsistencies at the base of the metazoan tree of life, we constructed a novel supermatrix containing 122 genes, enriched with non-bilaterian taxa. Comparative analyses of this supermatrix and its two non-overlapping multi-gene partitions (including ribosomal and non-ribosomal genes) revealed conflicting phylogenetic signals. We show that the levels of saturation and long branch attraction artifacts in the two partitions correlate with gene sampling. The ribosomal gene partition exhibits significantly lower saturation levels than the non-ribosomal one. Additional systematic errors derive from significant variations in amino acid substitution patterns among the metazoan lineages that violate the stationarity assumption of evolutionary models frequently used to reconstruct phylogenies. By modifying gene sampling and the taxonomic composition of the outgroup, we were able to construct three different yet well-supported phylogenies. These results show that the accuracy of phylogenetic inference may be substantially improved by selecting genes that evolve slowly across the Metazoa and applying more realistic substitution models. Additional sequence-independent genomic markers are also necessary to assess the validity of the phylogenetic hypotheses.

Introduction of a high-throughput double-stent animal model for the evaluation of biodegradable vascular stents.

Current stent system efficacy for the treatment of coronary artery disease is hampered by in-stent restenosis (ISR) rates of up to 20% in certain high-risk settings and by the risk of stent thrombosis, which is characterized by a high mortality rate. In theory, biodegradable vascular devices exhibit crucial advantages. Most absorbable implant materials are based on poly-L-lactic acid (PLLA) owing to its mechanical properties; however, PLLA might induce an inflammatory reaction in the vessel wall. Evaluation of biodegradable implant efficacy includes a long-term examination of tissue response; therefore, a simple in vivo tool for thorough biocompatibility and biodegradation evaluation would facilitate future stent system development. Rats have been used for the study of in vivo degradation processes, and stent implantation into the abdominal aorta of rats is a proven model for stent evaluation. Here, we report the transformation of the porcine double-stent animal model into the high-throughput rat abdominal aorta model. As genetic manipulation of rats was introduced recently, this novel method presents a powerful tool for future in vivo biodegradable candidate stent biocompatibility and biodegradation characterization in a reliable simple model of coronary ISR.

The BioStent: novel concept for a viable stent structure.

OBJECTIVES: Percutaneous stenting of occluded peripheral vessels is a well-established technique in clinical practice. Unfortunately, the patency rates of small-caliber vessels after stenting remain unsatisfactory. The aim of the BioStent concept is to overcome in-stent restenosis by excluding the diseased vessel segment entirely from the blood stream, in addition to providing an intact endothelial cell layer. DESIGN: The concept combines the principles of vascular tissue engineering with a self-expanding stent: casting of the stent within a cellularized fibrin gel structure, followed by bioreactor conditioning, allows complete integration of the stent within engineered tissue. MATERIALS AND METHODS: Small-caliber BioStents (Ø=6 mm; n=4) were produced by casting a nitinol stent within a thin fibrin/vascular smooth muscle cell (vSMC) mixture, followed by luminal endothelial cell seeding, and conditioning of the BioStent within a bioreactor system. The potential remodeling of the fibrin component into tissue was analyzed using routine histological methods. Scanning electron microscopy was used to assess the luminal endothelial cell coverage following the conditioning phase and crimping of the stent. RESULTS: The BioStent was shown to be noncytotoxic, with no significant effect on cell proliferation. Gross and microscopic analysis revealed complete integration of the nitinol component within a viable tissue structure. Hematoxylin and eosin staining revealed a homogenous distribution of vSMCs throughout the thickness of the BioStent, while a smooth, confluent luminal endothelial cell lining was evident and not significantly affected by the crimping/release process. CONCLUSIONS: The BioStent concept is a platform technology offering a novel opportunity to generate a viable, self-expanding stent structure with a functional endothelial cell lining. This platform technology can be transferred to different applications depending on the luminal cell lining required.

Neutrophil-derived cathelicidin protects from neointimal hyperplasia.

Percutaneous transluminal angioplasty with stent implantation is used to dilate arteries narrowed by atherosclerotic plaques and to revascularize coronary arteries occluded by atherothrombosis in myocardial infarction. Commonly applied drug-eluting stents release antiproliferative or anti-inflammatory agents to reduce the incidence of in-stent stenosis. However, these stents may still lead to in-stent stenosis; they also show increased rates of late stent thrombosis, an obstacle to optimal revascularization possibly related to endothelial recovery. Here, we examined the contribution of neutrophils and neutrophilic granule proteins to arterial healing after injury. We found that neutrophil-borne cathelicidin (mouse CRAMP, human LL-37) promoted reendothelization and thereby limited neointima formation after stent implantation. We then translated these findings to an animal model using a neutrophil-instructing, biofunctionalized, miniaturized Nitinol stent coated with LL-37. This stent reduced in-stent stenosis in a mouse model of atherosclerosis, suggesting that LL-37 may promote vascular healing after interventional therapy.

Letter to the editor: SeqXML and OrthoXML: standards for sequence and orthology information.

There is a great need for standards in the orthology field. Users must contend with different ortholog data representations from each provider, and the providers themselves must independently gather and parse the input sequence data. These burdensome and redundant procedures make data comparison and integration difficult. We have designed two XML-based formats, SeqXML and OrthoXML, to solve these problems. SeqXML is a lightweight format for sequence records-the input for orthology prediction. It stores the same sequence and metadata as typical FASTA format records, but overcomes common problems such as unstructured metadata in the header and erroneous sequence content. XML provides validation to prevent data integrity problems that are frequent in FASTA files. The range of applications for SeqXML is broad and not limited to ortholog prediction. We provide read/write functions for BioJava, BioPerl, and Biopython. OrthoXML was designed to represent ortholog assignments from any source in a consistent and structured way, yet cater to specific needs such as scoring schemes or meta-information. A unified format is particularly valuable for ortholog consumers that want to integrate data from numerous resources, e.g. for gene annotation projects. Reference proteomes for 61 organisms are already available in SeqXML, and 10 orthology databases have signed on to OrthoXML. Adoption by the entire field would substantially facilitate exchange and quality control of sequence and orthology information.

CoMet--a web server for comparative functional profiling of metagenomes.

Analyzing the functional potential of newly sequenced genomes and metagenomes has become a common task in biomedical and biological research. With the advent of high-throughput sequencing technologies comparative metagenomics opens the way to elucidate the genetically determined similarities and differences of complex microbial communities. We developed the web server 'CoMet' (http://comet.gobics.de), which provides an easy-to-use comparative metagenomics platform that is well-suitable for the analysis of large collections of metagenomic short read data. CoMet combines the ORF finding and subsequent assignment of protein sequences to Pfam domain families with a comparative statistical analysis. Besides comprehensive tabular data files, the CoMet server also provides visually interpretable output in terms of hierarchical clustering and multi-dimensional scaling plots and thus allows a quick overview of a given set of metagenomic samples.

OrthoDisease: tracking disease gene orthologs across 100 species.

Orthology is one of the most important tools available to modern biology, as it allows making inferences from easily studied model systems to much less tractable systems of interest, such as ourselves. This becomes important not least in the study of genetic diseases. We here review work on the orthology of disease-associated genes and also present an updated version of the InParanoid-based disease orthology database and web site OrthoDisease, with 14-fold increased species coverage since the previous version. Using this resource, we survey the taxonomic distribution of orthologs of human genes involved in different disease categories. The hypothesis that paralogs can mask the effect of deleterious mutations predicts that known heritable disease genes should have fewer close paralogs. We found large-scale support for this hypothesis as significantly fewer duplications were observed for disease genes in the OrthoDisease ortholog groups.