Daptomycin Resistant Staphylococcus aureus Clinical Strain With Novel Non-synonymous Mutations in the mprF and vraS Genes:A New Insight Into Daptomycin Resistance

Objectives: Daptomycin (DAP) resistance in Staphylococcus aureus is uncommon but there are increasing reports of the emergence of resistance during DAP therapy. Most clinical DAP-resistant S. aureus isolates investigated carried mutations in the mprF gene. The aim of this study was to identify mutations between a clinical pair of methicillin-susceptible S. aureus (MSSA) isolates (DAP-susceptible and DAP-resistant). Additionally, the activity of genes previously associated with DAP resistance was assessed. Materials and Methods: Two MSSA isolates from patient with left-sided endocarditis were analyzed by whole genome sequencing (WGS) and reverse transcription-quantitative real-time PCR (RT-qPCR). The first isolate, DAP-susceptible, was obtained before initiation of treatment and the second isolate, DAP-resistant, was recovered after 4 weeks of DAP therapy. Results: Comparison of complete genomes of DAP-susceptible and its DAP-resistant variant identified two non-synonymous and one synonymous mutations. The non-synonymous mutations consisted of a S829L substitution in mprF and a T331I substitution in vraS. The RT-qPCR experiments revealed an increased expression of vraS, dltA, mprF, and sceD genes in DAP-resistant variant. Strikingly, the expression of dltA and mprF genes was significantly downregulated by DAP. Conclusion: The mprF and vraS genes were previously associated with DAP resistance, however, none of the mutations described in this study had been previously identified and linked to DAP resistance. Moreover, we provide a new insight into the DAP action on S. aureus, in which the expression of key genes in DAP resistance is decreased by the antibiotic

Cross-Lingual Knowledge Transfer for Clinical Phenotyping

Clinical phenotyping enables the automatic extraction of clinical conditions from patient records, which can be beneficial to doctors and clinics worldwide. However, current state-of-the-art models are mostly applicable to clinical notes written in English. We therefore investigate cross-lingual knowledge transfer strategies to execute this task for clinics that do not use the English language and have a small amount of in-domain data available. We evaluate these strategies for a Greek and a Spanish clinic leveraging clinical notes from different clinical domains such as cardiology, oncology and the ICU. Our results reveal two strategies that outperform the state-of-the-art: Translation-based methods in combination with domain-specific encoders and cross-lingual encoders plus adapters. We find that these strategies perform especially well for classifying rare phenotypes and we advise on which method to prefer in which situation. Our results show that using multilingual data overall improves clinical phenotyping models and can compensate for data sparseness.Comment: LREC 2022 submmision: January 202

Native Point Defect Measurement and Manipulation in ZnO Nanostructures

This review presents recent research advances in measuring native point defects in ZnO nanostructures, establishing how these defects affect nanoscale electronic properties, and developing new techniques to manipulate these defects to control nano- and micro- wire electronic properties. From spatially-resolved cathodoluminescence spectroscopy, we now know that electrically-active native point defects are present inside, as well as at the surfaces of, ZnO and other semiconductor nanostructures. These defects within nanowires and at their metal interfaces can dominate electrical contact properties, yet they are sensitive to manipulation by chemical interactions, energy beams, as well as applied electrical fields. Non-uniform defect distributions are common among semiconductors, and their effects are magnified in semiconductor nanostructures so that their electronic effects are significant. The ability to measure native point defects directly on a nanoscale and manipulate their spatial distributions by multiple techniques presents exciting possibilities for future ZnO nanoscale electronics

Cavity Polariton Condensate in a Disordered Environment

We report on the influence of disorder on an exciton-polariton condensate in a ZnO based bulk planar microcavity and compare experimental results with a theoretical model for a non-equilibrium condensate. Experimentally, we detect intensity fluctuations within the far-field emission pattern even at high condensate densities which indicates a significant impact of disorder. We show that these effects rely on the driven dissipative nature of the condensate and argue that they can be accounted for by spatial phase inhomogeneities induced by disorder, which occur even for increasing condensate densities realized in the regime of high excitation power. Thus, non-equilibrium effects strongly suppress the stabilization of the condensate against disorder, contrarily to what is expected for equilibrium condensates in the high density limit. Numerical simulations based on our theoretical model reproduce the experimental data.Comment: main article and supplementary, 13 pages, 8 figures (main article

Characterization of a CTX-M-15 Producing Klebsiella Pneumoniae Outbreak Strain Assigned to a Novel Sequence Type (1427)

Extended-spectrum ß-lactamase producing Klebsiella pneumoniae have emerged as one of the major nosocomial pathogens. Between July and September 2012, a CTX-M-15 producing K. pneumoniae caused an outbreak in a university hospital in the Netherlands. The outbreak isolates were characterized and assigned to a novel sequence type (ST1427). An epidemiological link between affected patients was supported by patient contact tracing and whole-genome phylogenetic analysis. Genetic diversity was detected among multiple isolates obtained from different body sites of the index patient, which may relate to antibiotic treatment and/or host adaptation. Environmental contamination caused by the outbreak clone was found in the patient rooms even on medical equipment. The novel clone was not closely related to any known endemic/epidemic clone, but carried a set of a plasmid-borne resistance genes (blaCTX-M-15, blaTEM-1, blaOXA-1, aac(6')-Ib-cr, qnrB1, tetA(A), aac(3)-II). Analysis of its virulence factors revealed a previously uncharacterized capsular biosynthesis region and two uncharacterized fimbriae gene clusters, and suggested that the new clone was not hypervirulent. To our knowledge, this is the first outbreak report of K. pneumoniae ST1427, and our study could be of help to understand the features of this newly emerging clone

Microfluidic-Chip-Based Multiple-Locus Variable-Number Tandem-Repeat Fingerprinting with New Primer Sets for Methicillin-Resistant Staphylococcus aureus

The detection of outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) infections and a rapid and accurate identification of sources and routes of transmission should be conducted in hospital settings as early and swiftly as possible. In this study, we investigated the application potential of a new approach based on multiple-locus variable-number tandem-repeat fingerprinting (MLVF) and microfluidics technology for a rapid discrimination of MRSA lineages in outbreak settings. A total of 206 nonrepetitive MRSA isolates recovered from infected patients at the University Medical Center Groningen between 2000 and 2010 were tested. The results obtained by MLVF using microcapillary electrophoresis with newly designed primers were compared to those obtained by spa typing and multiple-locus variable-number tandem-repeat analysis (MLVA). The discriminatory power was 0.980 (107 patterns), 0.969 (85 allelic profiles), and 0.959 (66 types) for MLVF, MLVA, and spa typing, respectively. All methods tested showed a good concordance of results calculated by the adjusted Rand's coefficient method. Comparisons of data obtained by the three approaches allowed us to propose an 88% cutoff value for the similarity between any two MLVF patterns, which can be used in S. aureus epidemiological studies, including analyses of outbreaks and strain transmission events. Of the three tested methods, MLVF is the cheapest, fastest, and easiest to perform. MLVF applied to microfluidic polymer chips is a rapid, cheap, reproducible, and highly discriminating tool to determine the clonality of MRSA isolates and to trace the spread of MRSA strains over periods of many years. Although spa typing should be used due to its portability of data, MLVF has a high added value because it is more discriminatory

Automated DNA Sequence-Based Early Warning System for the Detection of Methicillin-Resistant Staphylococcus aureus Outbreaks

BACKGROUND: The detection of methicillin-resistant Staphylococcus aureus (MRSA) usually requires the implementation of often rigorous infection-control measures. Prompt identification of an MRSA epidemic is crucial for the control of an outbreak. In this study we evaluated various early warning algorithms for the detection of an MRSA cluster. METHODS AND FINDINGS: Between 1998 and 2003, 557 non-replicate MRSA strains were collected from staff and patients admitted to a German tertiary-care university hospital. The repeat region of the S. aureus protein A (spa) gene in each of these strains was sequenced. Using epidemiological and typing information for the period 1998–2002 as reference data, clusters in 2003 were determined by temporal-scan test statistics. Various early warning algorithms (frequency, clonal, and infection control professionals [ICP] alerts) were tested in a prospective analysis for the year 2003. In addition, a newly implemented automated clonal alert system of the Ridom StaphType software was evaluated. A total of 549 of 557 MRSA were typeable using spa sequencing. When analyzed using scan test statistics, 42 out of 175 MRSA in 2003 formed 13 significant clusters (p < 0.05). These clusters were used as the “gold standard” to evaluate the various algorithms. Clonal alerts (spa typing and epidemiological data) were 100% sensitive and 95.2% specific. Frequency (epidemiological data only) and ICP alerts were 100% and 62.1% sensitive and 47.2% and 97.3% specific, respectively. The difference in specificity between clonal and ICP alerts was not significant. Both methods exhibited a positive predictive value above 80%. CONCLUSIONS: Rapid MRSA outbreak detection, based on epidemiological and spa typing data, is a suitable alternative for classical approaches and can assist in the identification of potential sources of infection

Reconstruction of the lipid metabolism for the microalga Monoraphidium neglectum from its genome sequence reveals characteristics suitable for biofuel production

Bogen C, Al-Dilaimi A, Albersmeier A, et al. Reconstruction of the lipid metabolism for the microalga Monoraphidium neglectum from its genome sequence reveals characteristics suitable for biofuel production. BMC Genomics. 2013;14(1): 926.BACKGROUND: Microalgae are gaining importance as sustainable production hosts in the fields of biotechnology and bioenergy. A robust biomass accumulating strainof the genus Monoraphidium (SAG 48.87) was investigated in this work as apotential feedstock for biofuel production. The genome was sequenced, annotated, and key enzymes for triacylglycerol formation were elucidated. RESULTS: Monoraphidium neglectum was identified as an oleaginous species with favourable growth characteristics as well as a high potential for crude oil production, based on neutral lipid contents of approximately 21% (dry weight) under nitrogen starvation, composed of predominantly C18:1 and C16:0 fatty acids. Further characterization revealed growth in a relatively wide pH range and salt concentrations of up to 1.0% NaCl, in which the cells exhibited larger structures. This first full genome sequencing of a member of the Selenastraceae revealed a diploid, approximately 68 Mbp genome with a G + C content of 64.7%. The circular chloroplast genome was assembled to a 135,362 bp single contig, containing 67 protein-coding genes. The assembly of the mitochondrial genome resulted in two contigs with an approximate total size of 94 kb, the largest known mitochondrial genome within algae. 16,761 protein-coding genes were assigned to the nuclear genome. Comparison of gene sets with respect to functional categories revealed a higher gene number assigned to the category "carbohydrate metabolic process" and in "fatty acid biosynthetic process" in M. neglectum when compared to Chlamydomonas reinhardtii and Nannochloropsis gaditana, indicating a higher metabolic diversity for applications in carbohydrate conversions of biotechnological relevance. CONCLUSIONS: The genome of M. neglectum, as well as the metabolic reconstruction of crucial lipid pathways, provides new insights into the diversity of the lipid metabolism in microalgae. The results of this work provide a platform to encourage the development of this strain for biotechnological applications and production concepts

Geographic Distribution of Staphylococcus aureus Causing Invasive Infections in Europe: A Molecular-Epidemiological Analysis

Hajo Grundmann and colleagues describe the development of a new interactive mapping tool for analyzing the spatial distribution of invasive Staphylococcus aureus clones

MEDBERT.de: A Comprehensive German BERT Model for the Medical Domain

This paper presents medBERTde, a pre-trained German BERT model specifically designed for the German medical domain. The model has been trained on a large corpus of 4.7 Million German medical documents and has been shown to achieve new state-of-the-art performance on eight different medical benchmarks covering a wide range of disciplines and medical document types. In addition to evaluating the overall performance of the model, this paper also conducts a more in-depth analysis of its capabilities. We investigate the impact of data deduplication on the model's performance, as well as the potential benefits of using more efficient tokenization methods. Our results indicate that domain-specific models such as medBERTde are particularly useful for longer texts, and that deduplication of training data does not necessarily lead to improved performance. Furthermore, we found that efficient tokenization plays only a minor role in improving model performance, and attribute most of the improved performance to the large amount of training data. To encourage further research, the pre-trained model weights and new benchmarks based on radiological data are made publicly available for use by the scientific community.Comment: Keno K. Bressem and Jens-Michalis Papaioannou and Paul Grundmann contributed equall