Investigating environmental transmission to resolve a Bacillus cereus group outbreak in a neonatal intensive care unit using core genome multilocus sequence typing.

BACKGROUND: We analyzed an outbreak of Bacillus cereus group (Bcg) at a single-center neonatal intensive care unit level IV by conducting comprehensive sampling of both patients and the environment. METHODS: Between 06/2020 and 10/2021, all Bcg isolates identified by both regular colonization screening and additional sampling of the environment were subjected to whole-genome sequencing, followed by in vitro extraction of MLST ST, resistance genes and virulence factors. Using publicly available genome sequences, we defined an ad hoc core genome multilocus sequence typing (cgMLST) scheme comprising 2759 target genes for Bcg typing, which we applied to the detected isolates. We have compared the results with a stable cgMLST that was published in the meantime and completed the investigation with a SNP analysis. RESULTS: We analyzed 28 Bcg isolates from patient and environmental samples using MLST and cgMLST. This revealed multiple sequence types, with ST127 being the most common (n = 13). Both cgMLST schemes grouped ten of the 13 ST127 isolates into a cluster, including two invasive isolates from two different patients and several environmental samples. SNP analysis postulated a screen from a ventilation machine as a possible reservoir. CONCLUSION: In sensitive settings such as neonatal intensive care units, considering the environment in outbreak analyses is crucial, especially when investigating potential transmission routes through shared devices. When dealing with widespread bacteria such as Bcg, high-resolution typing techniques are necessary. In this study, we successfully resolved an outbreak of Bcg infections using a custom cgMLST scheme combined with a SNP analysis.

[Influence of Fetomaternal Risk Factors on Mortality and Morbidity in Extremely Preterm Infants]. / Einfluss von fetomaternalen Risikofaktoren auf die Mortalität und Morbidität von Extremfrühgeborenen.

INTRODUCTION: The management of pregnant women at risk of preterm delivery poses a challenge to the interdisciplinary team. At the edge of viability, it is crucial to take into consideration maternal and fetal risk factors when determining individual counseling and therapeutic approaches. METHODS: At a level 4 perinatal center, all preterm infants (PI) born in the years 2017 to 2020 who had a gestational age between 230/7 and 246/7 weeks and were cared for with a curative therapeutic approach were enrolled in a retrospective observational study. Divided into two groups (230/7-236/7 and 240/7-246/7 weeks of gestation), the PI were compared in terms of mortality and morbidity based on maternal and fetal risk factors. Thirteen risk factors and their prognostic relevance for survival were analyzed. RESULTS: 41 mothers with 48 PI were included. 9 neonates received primary palliative treatment and were excluded from the analyses. The survival rates between the two groups (n=21, n=27) showed no significant difference (66.7% versus 74.1%, p=0.750). A significantly higher mortality was observed in PI with an increased number of risk factors (p=0.004), the most severe of which were hypertensive disorders of pregnancy and preterm premature rupture of membranes. Data regarding morbidity showed no significant difference. CONCLUSION: Data regarding mortality correlate with national findings. Observed morbidity in the study population was recorded. The prediction of probability of survival is more precise when risk factors are taken into consideration.

Inpatient burden of respiratory syncytial virus in children ≤2 years of age in Germany: A retrospective analysis of nationwide hospitalization data, 2019-2022.

BACKGROUND: Respiratory syncytial virus (RSV) causes respiratory tract disease in seasonal waves, primarily in infants and young children. This study aims to quantify the number of RSV-related hospitalizations in children ≤2 years of age and to determine corresponding resource use and costs in Germany. METHODS: We retrospectively analyzed population-wide hospital data from the Institute for the Hospital Remuneration System (InEK) from 2019 to 2022. RSV cases were identified using the RSV-specific 10th revision of the International Classification of Diseases (ICD-10) codes J12.1, J20.5, and J21.0. The RSV-associated proportion of all hospitalizations caused by severe acute respiratory infections (SARIs), clinical manifestations, length of stay (LOS), intensive care unit (ICU) admissions, ventilation rates, and hospitalization costs were retrieved. RESULTS: We identified 98,220 hospitalizations (26,052, 15,407, 31,362, and 25,399 in 2019, 2020, 2021, and 2022, respectively) with a principal RSV diagnosis in children aged ≤2 years in Germany. The majority of RSV hospitalizations (73,178) occurred in infants (<1 year), with annual incidence rates ranging from 14.9 to 28.6 per 1000 population. Fifty-eight percent of all SARI hospitalizations in this age group were attributable to RSV. In children aged ≤2 years, mean LOS was 4.5 days, 6.1% of cases were admitted to ICU, and 5.3% of cases were ventilated. Mean hospitalization costs per case ranged from €3001 to €3961 over the study period. CONCLUSIONS: RSV causes substantial disease burden and is a leading cause of SARI-related hospital admissions of children ≤2 years of age in Germany. Our results confirm the need to explore and evaluate strategies to prevent RSV in infants and young children.

The Plant Phenomics and Genomics Research Data Repository: An On-Premise Approach for FAIR-Compliant Data Acquisition.

The FAIR data principle as a commitment to support long-term research data management is widely accepted in the scientific community. However, although many established infrastructures provide comprehensive and long-term stable services and platforms, a large quantity of research data is still hidden. Currently, high-throughput plant genomics and phenomics technologies are producing research data in abundance, the storage of which is not covered by established core databases. This concerns the data volume, for example, time series of images or high-resolution hyperspectral data; the quality of data formatting and annotation, e.g., with regard to structure and annotation specifications of core databases; uncovered data domains; or organizational constraints prohibiting primary data storage outside institutional boundaries. To share these potentially dark data in a FAIR way and master these challenges the ELIXIR Germany/de.NBI service Plant Genomic and Phenomics Research Data Repository (PGP) implements an on-premise approach, which allows research data to be kept in place and wrapped in FAIR-aware software infrastructure. In this chapter, the e!DAL infrastructure software and the PGP repository are presented as best practice on how to easily setup FAIR-compliant and intuitive research data services.

Antitachycardia pacing at the His bundle is safer than conventional right ventricular antitachycardia pacing in a canine myocardial ischemic injury model.

INTRODUCTION: Antitachycardia pacing (ATP) is used to terminate ventricular tachycardia (VT) by delivering rapid, low energy pacing to the right ventricle (RV). Unfortunately, ATP is not effective against all VT episodes and can result in adverse outcomes, such as VT acceleration and degeneration into ventricular fibrillation (VF). Improving ATP is therefore desirable. Our objective was to compare the efficacy and safety of ATP delivered at the His bundle to traditional ATP. METHODS: Six dogs were anesthetized and pacing leads were implanted in the RV and His bundle. The left anterior descending artery was occluded for 2 h to create an ischemic injury. In a study 4-7 days later, a 128-electrode sock was placed snugly around the ventricles and VT was induced using rapid pacing. ATP was delivered from either the His bundle or RV lead, then attempted at the other location if unsuccessful. Success rates and instances of VT acceleration and degeneration into VF were calculated. RESULTS: We induced 83 runs of VT and attempted ATP 128 times. RV ATP was successful in 36% of attempts; His ATP was successful in 38% of attempts. RV ATP resulted in significantly more adverse outcomes. RV and His ATP induced VT acceleration in 9% and 3% of trains, respectively, and induced degeneration into VF in 5% and 1% of trains, respectively. CONCLUSION: His bundle ATP is safer, but not significantly more effective, than RV ATP.

CLAD: A realistic Continual Learning benchmark for Autonomous Driving.

In this paper we describe the design and the ideas motivating a new Continual Learning benchmark for Autonomous Driving (CLAD), that focuses on the problems of object classification and object detection. The benchmark utilises SODA10M, a recently released large-scale dataset that concerns autonomous driving related problems. First, we review and discuss existing continual learning benchmarks, how they are related, and show that most are extreme cases of continual learning. To this end, we survey the benchmarks used in continual learning papers at three highly ranked computer vision conferences. Next, we introduce CLAD-C, an online classification benchmark realised through a chronological data stream that poses both class and domain incremental challenges; and CLAD-D, a domain incremental continual object detection benchmark. We examine the inherent difficulties and challenges posed by the benchmark, through a survey of the techniques and methods used by the top-3 participants in a CLAD-challenge workshop at ICCV 2021. We conclude with possible pathways to improve the current continual learning state of the art, and which directions we deem promising for future research.

Management of Enteral Feeding and Application of Probiotics in Very Low Birth Weight Infants - A National Survey in German NICUs.

BACKGROUND: The advantage of breast milk feeding, and supplementation of probiotics is well known and proven. However, the lack of reliable amounts of colostrum and/or transient breast milk during the first few postnatal days might inhibit timely enteral nutrition. METHODS: The aim of this nationwide survey in German Level-1 neonatal intensive care units (NICUs) was to collect data regarding the management of feeding in the first days of life in very low birth weight infants (VLBWIs, birth weight<1500 g). In addition, we analyzed differences in the use of probiotics. An online survey was sent to all 163 Level-1 NICUs in Germany. RESULTS: 110/163 (67.5%) hospitals participated in our study. One-fifth of all participants used exclusively breast milk. The reported incidence of necrotizing enterocolitis (NEC) was lower in NICUs that exclusively used breast milk in VLBWIs (p=0.08). Two-thirds start enteral feeding independent of gestational age during the first 12 hours postnatally with either breast milk or formula. 80% of all participants checked gastric residuals routinely. The use of probiotics differs widely concerning duration and interruption during antibiotic therapy. CONCLUSION: The exclusive use of breast milk is associated with a lower incidence of NEC. The result of our survey emphasizes the paramount importance of nutrition with mother`s milk. In case of insufficient availability of mother`s milk, the use of human donor milk still appears to be superior to formula feeding. The implementation of human donor milk banks should therefore be promoted.

Effects of Biventricular Pacing Locations on Anti-Tachycardia Pacing Success in a Patient-Specific Model.

Patients with drug-refractory ventricular tachycardia (VT) often undergo implantation of a cardiac defibrillator (ICD). While life-saving, shock from an ICD can be traumatic. To combat the need for defibrillation, ICDs come equipped with low-energy pacing protocols. These anti-tachycardia pacing (ATP) methods are conventionally delivered from a lead inserted at the apex of the right ventricle (RV) with limited success. Recent studies have shown the promise of biventricular leads placed in the left ventricle (LV) for ATP delivery. This study tested the hypothesis that stimulating ATP from multiple biventricular locations will improve termination rates in a patient-specific computational model. VT was first induced in the model, followed by ATP delivery from 1-4 biventricular stimulus sites. We found that combining stimulation sites does not alter termination success so long as a critical stimulus site is included. Combining the RV stimulus site with any combination of LV sites did not affect ATP success except for one case. Including the RV site may allow biventricular ATP to be a robust approach across different scar distributions without affecting the efficacy of other stimulation sites. Combining sites may increase the likelihood of including a critical stimulus site when such information cannot be ascertained.

Transfer Learning for Improved Classification of Drivers in Atrial Fibrillation.

"Drivers" are theorized mechanisms for persistent atrial fibrillation. Machine learning algorithms have been used to identify drivers, but the small size of current driver datasets limits their performance. We hypothesized that pretraining with unsupervised learning on a large dataset of unlabeled electrograms would improve classifier accuracy on a smaller driver dataset. In this study, we used a SimCLR-based framework to pretrain a residual neural network on a dataset of 113K unlabeled 64-electrode measurements and found weighted testing accuracy to improve over a non-pretrained network (78.6±3.9% vs 71.9±3.3%). This lays ground for development of superior driver detection algorithms and supports use of transfer learning for other datasets of endocardial electrograms.

Large-scale genotyping and phenotyping of a worldwide winter wheat genebank for its use in pre-breeding.

Plant genetic resources (PGR) stored at genebanks are humanity's crop diversity savings for the future. Information on PGR contrasted with modern cultivars is key to select PGR parents for pre-breeding. Genotyping-by-sequencing was performed for 7,745 winter wheat PGR samples from the German Federal ex situ genebank at IPK Gatersleben and for 325 modern cultivars. Whole-genome shotgun sequencing was carried out for 446 diverse PGR samples and 322 modern cultivars and lines. In 19 field trials, 7,683 PGR and 232 elite cultivars were characterized for resistance to yellow rust - one of the major threats to wheat worldwide. Yield breeding values of 707 PGR were estimated using hybrid crosses with 36 cultivars - an approach that reduces the lack of agronomic adaptation of PGR and provides better estimates of their contribution to yield breeding. Cross-validations support the interoperability between genomic and phenotypic data. The here presented data are a stepping stone to unlock the functional variation of PGR for European pre-breeding and are the basis for future breeding and research activities.

Genomics-informed prebreeding unlocks the diversity in genebanks for wheat improvement.

The great efforts spent in the maintenance of past diversity in genebanks are rationalized by the potential role of plant genetic resources (PGR) in future crop improvement-a concept whose practical implementation has fallen short of expectations. Here, we implement a genomics-informed prebreeding strategy for wheat improvement that does not discriminate against nonadapted germplasm. We collect and analyze dense genetic profiles for a large winter wheat collection and evaluate grain yield and resistance to yellow rust (YR) in bespoke core sets. Breeders already profit from wild introgressions but PGR still offer useful, yet unused, diversity. Potential donors of resistance sources not yet deployed in breeding were detected, while the prebreeding contribution of PGR to yield was estimated through 'Elite × PGR' F1 crosses. Genomic prediction within and across genebanks identified the best parents to be used in crosses with elite cultivars whose advanced progenies can outyield current wheat varieties in multiple field trials.

Case report: Personalized computational model guided ablation for left atrial flutter.

Atypical atrial flutter is seen post-ablation in patients, and it can be challenging to map. These flutters are typically set up around areas of scar in the left atrium. MRI can reliably identify left atrial scar. We propose a personalized computational model using patient specific scar information, to generate a monodomain model. In the model conductivities are adjusted for different tissue regions and flutter was induced with a premature pacing protocol. The model was tested prospectively in patients undergoing atypical flutter ablation. The simulation-predicted flutters were visualized and presented to clinicians. Validation of the computational model was motivated by recording from electroanatomical mapping. These personalized models successfully predicted clinically observed atypical flutter circuits and at times even better than invasive maps leading to flutter termination at isthmus sites predicted by the model.

On the way to plant data commons - a genotyping use case.

Over the last years it has been observed that the progress in data collection in life science has created increasing demand and opportunities for advanced bioinformatics. This includes data management as well as the individual data analysis and often covers the entire data life cycle. A variety of tools have been developed to store, share, or reuse the data produced in the different domains such as genotyping. Especially imputation, as a subfield of genotyping, requires good Research Data Management (RDM) strategies to enable use and re-use of genotypic data. To aim for sustainable software, it is necessary to develop tools and surrounding ecosystems, which are reusable and maintainable. Reusability in the context of streamlined tools can e.g. be achieved by standardizing the input and output of the different tools and adapting to open and broadly used file formats. By using such established file formats, the tools can also be connected with others, improving the overall interoperability of the software. Finally, it is important to build strong communities that maintain the tools by developing and contributing new features and maintenance updates. In this article, concepts for this will be presented for an imputation service.

Management of prolonged meconium evacuation in preterm infants: A survey-based analysis in German Neonatal Intensive Care Units.

AIM: Due to the functional immaturity of bowel motility, a delayed passage frequently requires evacuation of meconium in preterm infants. Often rectal enemas and oral laxatives are used to manage these bowel evacuation disorders. METHODS: An online survey was sent to all 163 high-level Neonatal Intensive Care Units (NICUs) in Germany. The participants were queried on rectal enemas, laxative therapy and outcome incidences. RESULTS: A total of 110/163 (67.5%) hospitals participated in the study. 103/110 (93.6%) participating sites applied rectal enemas in cases of delayed meconium evacuation and 63/110 (57.3%) additionally used oral laxatives. In total, 15 different solutions and 7 different application systems were used for rectal instillation. Preterm infants receiving enemas within the first 48 hours after birth were found to have a significantly lower incidence of FIP (p = 0.006). Altogether 8 different oral laxatives were utilised. CONCLUSION: Therapeutic approaches to the management of prolongated meconium evacuation differ widely among German NICUs. Our survey highlights the diversity of applied substances, means of application and differences in duration and frequency of interventions. Macrogol was commonly used in neonates as an oral laxative despite the lack of approval from the manufacturer.

Recommendations for the formatting of Variant Call Format (VCF) files to make plant genotyping data FAIR.

In this opinion article, we discuss the formatting of files from (plant) genotyping studies, in particular the formatting of (meta-) data in Variant Call Format (VCF) files. The flexibility of the VCF format specification facilitates its use as a generic interchange format across domains but can lead to inconsistency between files in the presentation of metadata. To enable fully autonomous machine actionable data flow, generic elements need to be further specified. We strongly support the merits of the FAIR principles and see the need to facilitate them also through technical implementation specifications. VCF files are an established standard for the exchange and publication of genotyping data. Other data formats are also used to capture variant call data (for example, the HapMap format and the gVCF format), but none currently have the reach of VCF. In VCF, only the sites of variation are described, whereas in gVCF, all positions are listed, and confidence values are also provided. For the sake of simplicity, we will only discuss VCF and our recommendations for its use. However, the part of the VCF standard relating to metadata (as opposed to the actual variant calls) defines a syntactic format but no vocabulary, unique identifier or recommended content. In practice, often only sparse (if any) descriptive metadata is included. When descriptive metadata is provided, proprietary metadata fields are frequently added that have not been agreed upon within the community which may limit long-term and comprehensive interoperability. To address this, we propose recommendations for supplying and encoding metadata, focusing on use cases from the plant sciences. We expect there to be overlap, but also divergence, with the needs of other domains.

From data to knowledge - big data needs stewardship, a plant phenomics perspective.

The research data life cycle from project planning to data publishing is an integral part of current research. Until the last decade, researchers were responsible for all associated phases in addition to the actual research and were assisted only at certain points by IT or bioinformaticians. Starting with advances in sequencing, the automation of analytical methods in all life science fields, including in plant phenotyping, has led to ever-increasing amounts of ever more complex data. The tasks associated with these challenges now often exceed the expertise of and infrastructure available to scientists, leading to an increased risk of data loss over time. The IPK Gatersleben has one of the world's largest germplasm collections and two decades of experience in crop plant research data management. In this article we show how challenges in modern, data-driven research can be addressed by data stewards. Based on concrete use cases, data management processes and best practices from plant phenotyping, we describe which expertise and skills are required and how data stewards as an integral actor can enhance the quality of a necessary digital transformation in progressive research.

A Continual Learning Survey: Defying Forgetting in Classification Tasks.

Artificial neural networks thrive in solving the classification problem for a particular rigid task, acquiring knowledge through generalized learning behaviour from a distinct training phase. The resulting network resembles a static entity of knowledge, with endeavours to extend this knowledge without targeting the original task resulting in a catastrophic forgetting. Continual learning shifts this paradigm towards networks that can continually accumulate knowledge over different tasks without the need to retrain from scratch. We focus on task incremental classification, where tasks arrive sequentially and are delineated by clear boundaries. Our main contributions concern: (1) a taxonomy and extensive overview of the state-of-the-art; (2) a novel framework to continually determine the stability-plasticity trade-off of the continual learner; (3) a comprehensive experimental comparison of 11 state-of-the-art continual learning methods; and (4) baselines. We empirically scrutinize method strengths and weaknesses on three benchmarks, considering Tiny Imagenet and large-scale unbalanced iNaturalist and a sequence of recognition datasets. We study the influence of model capacity, weight decay and dropout regularization, and the order in which the tasks are presented, and qualitatively compare methods in terms of required memory, computation time, and storage.

During Early VF in Rabbit Hearts, His Bundle Pacing is Less Effective Than Working Myocardial Pacing in Modulating Left Ventricular Activation Rates.

PURPOSE: The potential of pacing and capturing the His-Purkinje system (HPS) to synchronize VF wavefronts is not known even though the HPS is thought to be electrically linked during VF. In this study the effect of selective His Bundle (HB) pacing was compared with nearby working myocardial (WM) pacing on the left ventricular (LV) endocardial activation rates. METHODS: Rabbit hearts (n = 9) were explanted and Langendorff perfused. Electrodes directly on the HB were identified and paced subsequently using an electrode array. The WM was paced through a silver wire inserted in the right ventricular septal wall. After VF was induced, the HB was paced at rates faster than the intrinsic HB activation rate (n = 18 episodes) and also at rates faster than the LV activation rate (n = 16). A basket array inserted in the LV was used to record electrograms before and during each pacing episode. Activation rates at five LV electrodes each from the earliest and latest activating sinus rhythm regions were analyzed before and during pacing. RESULTS: Both HB and WM pacing reduced LV activation rates during pacing, but WM pacing was more effective (p < 0.005). WM pacing events were more effective (p < 0.05) in reducing LV activation rates than HB pacing in episodes which were faster than LV activation rates. CONCLUSION: This study provides evidence that during early VF in rabbit hearts, the HPS cannot be driven to effectively modulate the LV activation rates.

DivBrowse-interactive visualization and exploratory data analysis of variant call matrices.

BACKGROUND: The sequencing of whole genomes is becoming increasingly affordable. In this context, large-scale sequencing projects are generating ever larger datasets of species-specific genomic diversity. As a consequence, more and more genomic data need to be made easily accessible and analyzable to the scientific community. FINDINGS: We present DivBrowse, a web application for interactive visualization and exploratory analysis of genomic diversity data stored in Variant Call Format (VCF) files of any size. By seamlessly combining BLAST as an entry point together with interactive data analysis features such as principal component analysis in one graphical user interface, DivBrowse provides a novel and unique set of exploratory data analysis capabilities for genomic biodiversity datasets. The capability to integrate DivBrowse into existing web applications supports interoperability between different web applications. Built-in interactive computation of principal component analysis allows users to perform ad hoc analysis of the population structure based on specific genetic elements such as genes and exons. Data interoperability is supported by the ability to export genomic diversity data in VCF and General Feature Format 3 files. CONCLUSION: DivBrowse offers a novel approach for interactive visualization and analysis of genomic diversity data and optionally also gene annotation data by including features like interactive calculation of variant frequencies and principal component analysis. The use of established standard file formats for data input supports interoperability and seamless deployment of application instances based on the data output of established bioinformatics pipelines.

PhenoApp: A mobile tool for plant phenotyping to record field and greenhouse observations.

With the ongoing cost decrease of genotyping and sequencing technologies, accurate and fast phenotyping remains the bottleneck in the utilizing of plant genetic resources for breeding and breeding research. Although cost-efficient high-throughput phenotyping platforms are emerging for specific traits and/or species, manual phenotyping is still widely used and is a time- and money-consuming step. Approaches that improve data recording, processing or handling are pivotal steps towards the efficient use of genetic resources and are demanded by the research community. Therefore, we developed PhenoApp, an open-source Android app for tablets and smartphones to facilitate the digital recording of phenotypical data in the field and in greenhouses. It is a versatile tool that offers the possibility to fully customize the descriptors/scales for any possible scenario, also in accordance with international information standards such as MIAPPE (Minimum Information About a Plant Phenotyping Experiment) and FAIR (Findable, Accessible, Interoperable, and Reusable) data principles. Furthermore, PhenoApp enables the use of pre-integrated ready-to-use BBCH (Biologische Bundesanstalt für Land- und Forstwirtschaft, Bundessortenamt und CHemische Industrie) scales for apple, cereals, grapevine, maize, potato, rapeseed and rice. Additional BBCH scales can easily be added. The simple and adaptable structure of input and output files enables an easy data handling by either spreadsheet software or even the integration in the workflow of laboratory information management systems (LIMS). PhenoApp is therefore a decisive contribution to increase efficiency of digital data acquisition in genebank management but also contributes to breeding and breeding research by accelerating the labour intensive and time-consuming acquisition of phenotyping data.