Assessment of HL7 FHIR Interoperability Between EHR Systems and the Survivorship Passport v2.0 Platform to Generate Treatment Summaries for Childhood Cancer Survivors in Six Clinics: Preliminary Testing Results.

The Survivorship Passport (SurPass) for childhood cancer survivors provides a personalized treatment summary together with a care plan for long-term screening of possible late effects. HL7 FHIR connectivity of Electronic Health Record (EHR) systems with the SurPass has been proposed to reduce the burden of collecting and organizing the relevant information. We present the results of testing and validation efforts conducted across six clinics in Austria, Belgium, Germany, Italy, Lithuania, and Spain. We also discuss ways in which this experience can be used to reduce efforts for the SurPass integration in other clinics across Europe.

Childhood Cancer Survivorship Passport Challenges in the European Health Data Space.

Innovation in cancer therapy has increased childhood cancer survival rates. However, survivors are still at risk of developing late effects. In the digital transformation of the health sector, the Survivorship Passport (SurPass) can support long-term follow-up care plans. Gaps in seamless connectivity among hospital departments, primary care, combined with the time of health professionals required to collect and fill-in health data in SurPass, are barriers to its adoption in daily clinical practice. The PanCareSurPass (PCSP) project was motivated to address these gaps by a new version of SurPass (v2.0) that supports semi-automatic assembly from organizational Electronic Health Record (EHR) systems of the treatment summary data using HL7 FHIR, to create SurPass, and to link it to regional or national digital health infrastructures in six European countries. In this paper we present the methodology used to develop the SurPass technical implementation strategy with special focus on the European Health Data Space (EHDS). The recently provisionally approved EHDS regulation instruments a digital health data ecosystem with opportunities for cost-effective SurPass implementation across Europe. Moving forward, a European HL7 FHIR SurPass Implementation Guide along with synthetic data sets, and validation tools can enrich the European Electronic Health Record Exchange Format (EEHRxF) with use cases on health & wellness of childhood cancer survivors.

Towards an Electronic Health Prevention Record Based on HL7 FHIR and the OMOP Common Data Model.

BACKGROUND: Approximately 40% of all recorded deaths in Austria are due to behavioral risks. These risks could be avoided with appropriate measures. OBJECTIVES: Extension of the concept of EHR and EMR to an electronic prevention record, focusing on primary and secondary prevention. METHODS: The concept of a structured prevention pathway, based on the principles of P4 Medicine, was developed for a multidisciplinary prevention network. An IT infrastructure based on HL7 FHIR and the OHDSI OMOP common data model was designed. RESULTS: An IT solution supporting a structured and modular prevention pathway was conceptualized. It contained a personalized management of prevention, risk assessment, diagnostic and preventive measures supported by a modular, interoperable IT infrastructure including a health app, prevention record web-service, decision support modules and a smart prevention registry, separating primary and secondary use of data. CONCLUSION: A concept was created on how an electronic health prevention record based on HL7 FHIR and the OMOP common data model can be implemented.

Neural Network-Based Prediction of Perceived Sleep Quality Through Wearable Device Data.

BACKGROUND: This study focuses on the development of a neural network model to predict perceived sleep quality using data from wearable devices. We collected various physiological metrics from 18 participants over four weeks, including heart rate, physical activity, and both device-measured and self-reported sleep quality. OBJECTIVES: The primary objective was to correlate wearable device data with subjective sleep quality perceptions. METHODS: Our approach used data processing, feature engineering, and optimizing a Multi-Layer Perceptron classifier. RESULTS: Despite comprehensive data analysis and model experimentation, the predictive accuracy for perceived sleep quality was moderate (59%), highlighting the complexities in accurately quantifying subjective sleep experiences through wearable data. Applying a tolerance of 1 grade (on a scale from 1-5), increased accuracy to 92%. DISCUSSION: More in-depth analysis is required to fully comprehend how wearables and artificial intelligence might assist in understanding sleep behavior.

Scaling up and implementing the digital Survivorship Passport tool in routine clinical care - The European multidisciplinary PanCareSurPass project.

BACKGROUND: Childhood cancer survivors (CCS), of whom there are about 500,000 living in Europe, are at an increased risk of developing health problems [1-6] and require lifelong Survivorship Care. There are information and knowledge gaps among CCS and healthcare providers (HCPs) about requirements for Survivorship Care [7-9] that can be addressed by the Survivorship Passport (SurPass), a digital tool providing CCS and HCPs with a comprehensive summary of past treatment and tailored recommendations for Survivorship Care. The potential of the SurPass to improve person-centred Survivorship Care has been demonstrated previously [10,11]. METHODS: The EU-funded PanCareSurPass project will develop an updated version (v2.0) of the SurPass allowing for semi-automated data entry and implement it in six European countries (Austria, Belgium, Germany, Italy, Lithuania and Spain), representative of three infrastructure healthcare scenarios typically found in Europe. The implementation study will investigate the impact on person-centred care, as well as costs and processes of scaling up the SurPass. Interoperability between electronic health record systems and SurPass v2.0 will be addressed using the Health Level Seven (HL7) International interoperability standards. RESULTS: PanCareSurPass will deliver an interoperable digital SurPass with comprehensive evidence on person-centred outcomes, technical feasibility and health economics impacts. An Implementation Toolkit will be developed and freely shared to promote and support the future implementation of SurPass across Europe. CONCLUSIONS: PanCareSurPass is a novel European collaboration that will improve person-centred Survivorship Care for CCS across Europe through a robust assessment of the implementation of SurPass v2.0 in different healthcare settings.

Complete genome sequence of the myxobacterium Sorangium cellulosum.

The genus Sorangium synthesizes approximately half of the secondary metabolites isolated from myxobacteria, including the anti-cancer metabolite epothilone. We report the complete genome sequence of the model Sorangium strain S. cellulosum So ce56, which produces several natural products and has morphological and physiological properties typical of the genus. The circular genome, comprising 13,033,779 base pairs, is the largest bacterial genome sequenced to date. No global synteny with the genome of Myxococcus xanthus is apparent, revealing an unanticipated level of divergence between these myxobacteria. A large percentage of the genome is devoted to regulation, particularly post-translational phosphorylation, which probably supports the strain's complex, social lifestyle. This regulatory network includes the highest number of eukaryotic protein kinase-like kinases discovered in any organism. Seventeen secondary metabolite loci are encoded in the genome, as well as many enzymes with potential utility in industry.

Spiroketal polyketide formation in Sorangium: identification and analysis of the biosynthetic gene cluster for the highly cytotoxic spirangienes.

Natural products constitute important lead structures in drug discovery. In bacteria, they are often synthesized by large, modular multienzyme complexes. Detailed analysis of the biosynthetic machinery should enable its directed engineering and production of desirable analogs. The myxobacterium Sorangium cellulosum So ce90 produces the cytotoxic spiroketal polyketide spirangien, for which we describe the identification and functional analysis of the biosynthetic pathway. The gene cluster spans 88 kb and encodes 7 type I polyketide synthases and additional enzymes such as a stand-alone thioesterase and 2 methyltransferases. Inactivation of two cytochrome P(450) monooxygenase genes resulted in the production of acyclic spirangien derivatives, providing direct evidence for the involvement of these enzymes in spiroketal formation. The presence of large DNA repeats is consistent with multiple rounds of gene duplication during the evolution of the biosynthetic gene locus.

A modular DNA signal translator for the controlled release of a protein by an aptamer.

Owing to the intimate linkage of sequence and structure in nucleic acids, DNA is an extremely attractive molecule for the development of molecular devices, in particular when a combination of information processing and chemomechanical tasks is desired. Many of the previously demonstrated devices are driven by hybridization between DNA 'effector' strands and specific recognition sequences on the device. For applications it is of great interest to link several of such molecular devices together within artificial reaction cascades. Often it will not be possible to choose DNA sequences freely, e.g. when functional nucleic acids such as aptamers are used. In such cases translation of an arbitrary 'input' sequence into a desired effector sequence may be required. Here we demonstrate a molecular 'translator' for information encoded in DNA and show how it can be used to control the release of a protein by an aptamer using an arbitrarily chosen DNA input strand. The function of the translator is based on branch migration and the action of the endonuclease FokI. The modular design of the translator facilitates the adaptation of the device to various input or output sequences.

Identification of StiR, the first regulator of secondary metabolite formation in the myxobacterium Cystobacter fuscus Cb f17.1.

Myxobacteria are well established as proficient producers of natural products with numerous biological activities. Although some knowledge has been gained regarding the biosynthesis of secondary metabolites in this class of bacteria, almost nothing is known about the underlying regulatory mechanisms. In order to identify regulatory elements, we submitted the argyrin and stigmatellin producer Cystobacter fuscus to a random transposon mutagenesis strategy and screened 1,000 mutants for the occurrence of strains showing remarkably increased or decreased production of these compounds. In addition to the identification of the stigmatellin biosynthetic gene cluster, a novel positive regulator (stiR) of stigmatellin production was identified after transposon recovery. In order to exclude secondary mutagenesis effects, a double cross-over mutagenesis strategy was applied to the strain resulting in the repeated generation of the transposon genotype. This strain was shown to be equally effected in natural product biosynthesis.

Periodic DNA nanotemplates synthesized by rolling circle amplification.

Rolling circle amplification (RCA) is an elegant biochemical method by which long single-stranded DNA molecules with a repeating sequence motif can be readily synthesized. In RCA, small circular single-stranded oligonucleotides serve as templates for the polymerization of the complementary strand. A DNA polymerase with an efficient strand displacement activity can copy the circular template without stopping. This results in a long DNA strand with periodic sequence. We here demonstrate that this method, using DNA recognition and biotin-streptavidin binding, provides a simple procedure for DNA-directed nanoscale organization of matter. As an example, a 74 nucleotide (nt) long circular DNA molecule is amplified into a sequence-periodic single strand with a length up to several micrometers. Hybridization of this long periodic DNA template to the biotinylated complement of the sequence motif results in a long DNA duplex with a periodic arrangement of biotin binding sites. On this duplex, streptavidin-coated particles can be organized into one-dimensional arrays. The resulting DNA constructs are characterized by gel electrophoresis and atomic force microscopy.

Myxobacteria: proficient producers of novel natural products with various biological activities--past and future biotechnological aspects with the focus on the genus Sorangium.

Myxobacteria are gram-negative bacteria which are most noted for their ability to form fruiting bodies upon starvation. Within the last two decades, they increasingly gained attention as producers of natural products with biological activity. Here, recent and future biotechnological research on certain key myxobacteria and on their ability to produce natural products is reviewed with the focus on the production of myxovirescin, soraphen and epothilone. Aspects of product improvement and yield as well as statistics regarding secondary metabolite formation are discussed. Future research will deal with the exploitation of the biosynthetic potential of the myxobacteria, for example via the isolation of new myxobacterial species with different physiological properties. Additionally, the genetic potential of myxobacteria to form natural products can be exploited by the identification and activation of biosynthetic gene clusters. These can be found frequently within their genomes, which is shown by the analysis of the unfinished genomes of Myxococcus xanthus and Sorangium cellulosum. The current status of the S. cellulosum functional genome project with model strain So ce56 is discussed.

Characterisation, genome size and genetic manipulation of the myxobacterium Sorangium cellulosum So ce56.

In this study, Sorangium cellulosum So ce56 was phenotypically and genotypically analysed in order to evaluate whether this strain can be used in a comprehensive genome project as a representative of the secondary metabolite-producing myxobacteria. In contrast to many other strains of S. cellulosum, strain So ce56 was found to have various advantageous features, including fast and homogeneous growth in submerged cultures and the ability to complete its morphological differentiation cycle on agar, even when the inoculant originates from a liquid culture. Two groups of secondary metabolites isolated from the culture broth were identified, the polyketides etnangien and chivosazole. The presence of polyketide synthase-encoding genes in the genome of strain So ce56 was demonstrated via PCR. The phenotypic classification was confirmed by comparison of 16S rDNA sequences which showed that S. cellulosum So ce56 clusters within a separate lineage together with S. cellulosum ATCC 25531 and the epothilone producer S. cellulosum So ce90. The genome of S. cellulosum So ce56 belongs to the largest bacterial genomes described so far. It is estimated to be 12.2 Mb in size, by pulsed-field gel electrophoresis. In order to demonstrate that S. cellulosum So ce56 is a convenient strain for molecular biological studies, a genetic manipulation system was developed. Using triparental mating, polyketide synthase-encoding genes were inactivated, leading to chivosazole-negative mutants.