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At least 19 recordsLinked to original sources

VisPan: real-time visualisation of multiplex amplicon-based sequencing panels for rapid syndromic surveillance and pathogen detection.

MOTIVATION: Infectious diseases persist as a major global public health challenge. Diverse factors, including climate change, globalization, deforestation, human-animal interactions, lifestyle choices, and various biological factors, can contribute to their emergence and reemergence. Rapid detection and characterization of (re)emerging pathogens are therefore critical for effective outbreak management and for enhancing our understanding of epidemics by monitoring the transmission, spread, evolution, and genomics of pathogens. In this context, next-generation sequencing technologies (NGS), particularly long-read platforms such as Oxford Nanopore Technologies (ONT), have opened new avenues for real-time pathogen monitoring. However, the bioinformatics bottleneck remains a challenge, emphasizing the need for efficient, accessible, and user-friendly analysis tools. RESULTS: Here, we present a tool adapted from the RAMPART software that enables real-time data visualisation of multiplex PCR syndromic panels combined with Oxford Nanopore sequencing. This real-time analysis enables rapid pathogen detection, from raw data acquisition to taxonomic assignment, within minutes. The interface offers dynamic visual tracking of the sequencing run and amplicon coverage, facilitating immediate insights during diagnostic workflows. Validation experiments confirmed the system's reliability, accurately identifying all pathogens present in complex clinical or environmental samples. This tool provides an integrated, user-friendly solution for genomic pathogen surveillance in field or clinical settings.

Software

Development of methodology to support molecular endotype discovery from synovial fluid of individuals with knee osteoarthritis: The STEpUP OA consortium.

OBJECTIVES: To develop a protocol for largescale analysis of synovial fluid proteins, for the identification of biological networks associated with subtypes of osteoarthritis. METHODS: Synovial Fluid To detect molecular Endotypes by Unbiased Proteomics in Osteoarthritis (STEpUP OA) is an international consortium utilising clinical data (capturing pain, radiographic severity and demographic features) and knee synovial fluid from 17 participating cohorts. 1746 samples from 1650 individuals comprising OA, joint injury, healthy and inflammatory arthritis controls, divided into discovery (n = 1045) and replication (n = 701) datasets, were analysed by SomaScan Discovery Plex V4.1 (>7000 SOMAmers/proteins). An optimised approach to standardisation was developed. Technical confounders and batch-effects were identified and adjusted for. Poorly performing SOMAmers and samples were excluded. Variance in the data was determined by principal component (PC) analysis. RESULTS: A synovial fluid standardised protocol was optimised that had good reliability (<20% co-efficient of variation for >80% of SOMAmers in pooled samples) and overall good correlation with immunoassay. 1720 samples and >6290 SOMAmers met inclusion criteria. 48% of data variance (PC1) was strongly correlated with individual SOMAmer signal intensities, particularly with low abundance proteins (median correlation coefficient 0.70), and was enriched for nuclear and non-secreted proteins. We concluded that this component was predominantly intracellular proteins, and could be adjusted for using an 'intracellular protein score' (IPS). PC2 (7% variance) was attributable to processing batch and was batch-corrected by ComBat. Lesser effects were attributed to other technical confounders. Data visualisation revealed clustering of injury and OA cases in overlapping but distinguishable areas of high-dimensional proteomic space. CONCLUSIONS: We have developed a robust method for analysing synovial fluid protein, creating a molecular and clinical dataset of unprecedented scale to explore potential patient subtypes and the molecular pathogenesis of OA. Such methodology underpins the development of new approaches to tackle this disease which remains a huge societal challenge.

Humans

RNAcare: integrating clinical data with transcriptomic evidence using rheumatoid arthritis as a case study.

BACKGROUND: Gene expression analysis is a crucial tool for uncovering the biological mechanisms that underlie differences between patient subgroups, offering insights that can inform clinical decisions. However, despite its potential, gene expression analysis remains challenging for clinicians due to the specialised skills required to access, integrate, and analyse large datasets. Existing tools primarily focus on RNA-Seq data analysis, providing user-friendly interfaces but often falling short in several critical areas: they typically do not integrate clinical data, lack support for patient-specific analyses, and offer limited flexibility in exploring relationships between gene expression and clinical outcomes in disease cohorts. Users, including clinicians with a general knowledge of transcriptomics, however, who may have limited programming experience, are increasingly seeking tools that go beyond traditional analysis. To overcome these issues, computational tools must incorporate advanced techniques, such as machine learning, to better understand how gene expression correlates with patient symptoms of interest. RESULTS: Our RNAcare platform, addresses these limitations by offering an interactive and reproducible solution specifically designed for analysing transcriptomic data from patient samples in a clinical context. This enables researchers to directly integrate gene expression data with clinical features, perform exploratory data analysis, and identify patterns among patients with similar diseases. By enabling users to integrate transcriptomic and clinical data, and customise the target label, the platform facilitates the analysis of the relationships between gene expression and clinical symptoms like pain and fatigue. This allows users to generate hypotheses and illustrative visualisations/reports to support their research. As proof of concept, we use RNAcare to link inflammation-related genes to pain and fatigue in rheumatoid arthritis (RA) and detect signatures in the drug response group, confirming previous findings. CONCLUSION: We present a novel computational platform allowing the interpretation of clinical and transcriptomics data in real-time. The platform can be used for data generated by the user, such as the patient data presented here or using published datasets. The platform is available at https://rna-care.mvls.gla.ac.uk/ , and its source code is https://github.com/sii-scRNA-Seq/RNAcare/ .

Humans

A graph-based approach for the visualisation and analysis of bacterial pangenomes.

BACKGROUND: The advent of low cost, high throughput DNA sequencing has led to the availability of thousands of complete genome sequences for a wide variety of bacterial species. Examining and interpreting genetic variation on this scale represents a significant challenge to existing methods of data analysis and visualisation. RESULTS: Starting with the output of standard pangenome analysis tools, we describe the generation and analysis of interactive, 3D network graphs to explore the structure of bacterial populations, the distribution of genes across a population, and the syntenic order in which those genes occur, in the new open-source network analysis platform, Graphia. Both the analysis and the visualisation are scalable to datasets of thousands of genome sequences. CONCLUSIONS: We anticipate that the approaches presented here will be of great utility to the microbial research community, allowing faster, more intuitive, and flexible interaction with pangenome datasets, thereby enhancing interpretation of these complex data.

Bacteria

Global inequities in hepatitis B and C genomic surveillance revealed through an interactive data integration dashboard.

OBJECTIVES: To assess global disparities in hepatitis B virus (HBV) and hepatitis C virus (HCV) genomic surveillance and to develop an integrated platform that links genomic data with epidemiological burden. STUDY DESIGN: Retrospective observational analysis. METHODS: We reviewed existing viral genomic repositories to identify structural and analytical limitations. Subsequently, we integrated 10&#xa0;996 HBV and 3533 HCV whole-genome sequences (WGS) from public databases with Global Burden of Disease (GBD) estimates to quantify inequities in genomic surveillance across countries and genotypes. Using these data, we developed the open-access Hepatitis Dashboard, incorporating >14&#xa0;000 sequences from 141 countries with GBD metrics to evaluate representativeness and sequencing coverage relative to disease burden. RESULTS: Marked inequities in hepatitis genomic surveillance were identified. Despite increasing HBV- and HCV-associated mortality, virus sequence availability remains geographically and genotypically skewed-dominated by China and the United States, with substantial underrepresentation of HBV genotype E and HCV genotypes 5 and 8. Many high-endemic countries in Africa and the Western Pacific remain severely undersampled. We detected circulating antiviral drug-resistance mutations and developed a burden-adjusted sequencing coverage metric, revealing that several high-burden countries, including China, Nigeria and India, are among the least represented in global genomic datasets. Projections to 2030 indicate that neither HBV nor HCV are currently on track to meet WHO elimination targets. CONCLUSIONS: The Hepatitis Dashboard provides an integrated, continuously updated resource that links genomic and epidemiological data to quantify and visualise global surveillance gaps. This analysis highlights a critical disconnect between sequencing efforts and public health needs, which may limit the effectiveness of surveillance-informed strategies to support progress toward WHO 2030 elimination goals. By enabling burden-adjusted prioritisation and longitudinal tracking of genomic coverage, the platform supports evidence-based sampling strategies, equitable resource allocation, and monitoring of global progress toward hepatitis elimination.

Humans

A new technique for fractal analysis applied to human, intracerebrally recorded, ictal electroencephalographic signals.

Application of a new method of fractal analysis to human, intracerebrally recorded, ictal electroencephalographic (EEG) signals is reported. 'Frameshift-Richardson' (FR) analysis involves estimation of fractal dimension (1 < FD < 2) of consecutive, overlapping 10-s epochs of digitised EEG data; it is suggested that this technique offers significant operational advantages over use of algorithms for FD estimation requiring preliminary reconstruction of EEG data in phase space. FR analysis was found to reduce substantially the volume of EEG data, without loss of diagnostically important information concerning onset, propagation and evolution of ictal EEG discharges. Arrhythmic EEG events were correlated with relatively increased FD; rhythmic EEG events with relatively decreased FD. It is proposed that development of this method may lead to: (i) enhanced definition and localisation of initial ictal changes in the EEG presumed due to multi-unit activity; and (ii) synoptic visualisation of long periods of EEG data.

Algorithms

Visualization of multimodal image information in medicine.

Radiological and clinical practice can be enhanced by improved access to multimodal image informations. Analysis, visualization, method characteristic image processing and image synthesis is needed not only for the interpretation of the images but also for performing effective consultations with clinical colleagues and computer supported therapy planning and control strategies. The distributed system RADVIS (radiological visualization) is presented which enables the fast display, three dimensional visualization and the modality oriented analysis of multimodal image informations. Based on a unique image format, modality specific evaluation procedures and two- or three dimensional processing tools of image analysis produce the input data for therapy planning programs. The easy use of this multimedia visualisation tool enables radiologists and clinicians to deal with their image data. The description of methods and procedures of the prototype, as well as typical examples of radiologic practice will demonstrate the efficiency of the presented system.

Humans

Gastrointestinal endoscopy: an accurate and safe primary diagnostic and therapeutic modality.

OBJECTIVE: To review the place of gastrointestinal endoscopy in the management of upper and lower gastrointestinal disorders. DATA SOURCES: We reviewed articles on endoscopy reported over two decades. A Medline search complementing our experience and knowledge of the literature was used to identify the articles. STUDY SELECTION: Papers were selected which focused on indications, comparison with radiology, including clinical outcome measures, and complications. One hundred papers, including those from radiology journals, were reviewed. DATA EXTRACTION: Results of studies are referenced as appropriate. DATA SYNTHESIS AND CONCLUSIONS: Endoscopy allows direct visualisation of the mucosa of the upper gastrointestinal tract, colon and terminal ileum. Subtleties of colour change, vascular pattern abnormalities and scarring are easily detected at endoscopy and are often of diagnostic importance. Endoscopy also provides access for tissue biopsy and allows a wide variety of therapeutic interventions. Traditionally barium studies have been the first step in the evaluation of many gastrointestinal symptoms and still retain cost advantages over endoscopy. However, endoscopy is frequently more sensitive and specific than barium studies. Costs associated with incorrect diagnoses may undermine the apparent cost benefits of barium studies. Advances in endoscopic design have allowed wider therapeutic options and increased safety. Gastrointestinal endoscopy should now be the first line of investigation where diagnostic precision is required or where therapeutic intervention is likely.

Barium Sulfate

On the visualisation of nonstationarities in point processes.

A method is described for graphically presenting interval data, such as neural interspike intervals or electrocardiographic R-R intervals, in a form that facilitates the identification of nonstationaries. The method is essentially a plot of isoprobability contours of the cumulative interval histogram, as functions of time. A sequential algorithm is used for updating the contour-line positions. This display is used in an interactive system for visually identifying nonstationarities, and for subsequently comparing selected segments of the data quantitatively using the Kolmogorov-Smirnov test.

Computers

Computed tomography of the abdomen with fat density oral contrast medium.

A 12.5% corn oil-emulsion (COE) was tested as an oral contrast agent for abdominal computed tomography (CT) examinations in 100 patients. The results were compared with those obtained from another group of patients who received a conventional, high-density, oral contrast agent (2-3% iodinated solution). There was no statistically significant difference in the subjects' tolerance to the two agents (P greater than 0.05). There was, however, a significant improvement in image quality with COE (P less than 0.05). Gastrointestinal tract discrimination, and mucosal and mural visualisation was of higher quality with fat density oral contrast medium than with the high-density contrast agent. These data suggest that COE should be considered for routine use as an alternative to conventional high density oral contrast agents in upper abdominal CT.

Contrast Media

Autoradiography of adrenoceptors in rat and human brain: alpha-adrenoceptor and idazoxan binding sites.

This chapter reviews the current classification of adrenoceptors, and notes the difficulties of combining the molecular biological and pharmacological classifications of adrenoceptors. Possibilities for mapping the distribution of the proposed subtypes of adrenoceptors using currently available ligands are discussed, and the autoradiographic visualisation of the broad subtypes of alpha 1-, alpha 2-, beta 1-, and beta 2-adrenoceptors in the rat, monkey and human brain described and illustrated. The non-selectivity of ligands currently being used to label alpha-adrenoceptors is shown; we compare the distribution of [3H]idazoxan binding sites with the distribution of alpha 2-adrenoceptors visualised using other ligands. Resolution limitations of current autoradiographic approaches are considered and we shown how in situ hybridisation can complement data from receptor labelling studies used to localise receptors to pre- or postsynaptic sites.

Animals

Population genetics and forensic efficiency data of 4 AMPFLP's.

Family studies were carried out in a population sample from north west Germany using 4 amplifiable VNTR polymorphic systems D1S80 (MCT118), ApoB, D17S30 (YNZ22) and COL2A1. Separation was carried out in polyacrylamide gels and visualised using silver staining. In family studies (n = 30) no evidence of new mutations was found. The population study of unrelated individuals (mothers and putative fathers) showed that all 4 systems were highly polymorphic and similar to other population studies. The combined exclusion chance was calculated to be approximately 99% and the combined discrimination index 1.5.10(-4). The Hardy-Weinberg equilibrium was checked by forming groups of alleles and no significant deviations could be found in all systems.

Alleles

Properties of chicken cardiac dystrophin.

We investigated the presence of dystrophin by immunoblot and immunofluorescence analyses, negative staining, rotatory shadowing and immunogold electron microscopy in chicken cardiac muscle. Saponin was found to be better than Triton X-100 for providing a new 'dystrophin-enriched' solution for use in biochemical studies of the molecule. By Western blot analysis, only a 400-kDa band was revealed with polyclonal antibodies directed against a central region (residues 1178-1723) of the dystrophin molecule and no cross-reactions with other proteins or degraded products were observed. Specific cleavage of the dystrophin molecule showed that the central rod-shaped domain corresponded to a resistant 'core'. This structure might rigidify the protein. By immunofluorescence, dystrophin was localized at the periphery of cardiac ventricular cells. The molecule was examined by electron microscopy and found to have variable lengths (140-160 nm for the monomeric from and about 260 +/- 10 nm or more for oligomeric forms). These oligomeric structures are considered to be associated molecules which are only partially overlapped lengthwise. The precise distribution of dystrophin within the cardiac muscle was determined by visualisation of gold particles in immuno-electron microscopy. Gold particles were found on the sarcolemma with no evidence of any association with cytoplasmic structures. The present data provide further details on the cardiac dystrophin molecule and suggest that its capacity of self-association may elasticize the dystrophin dimer.

Animals

[The detailed imaging of vessels in MR angiography via projections from irregularly restricted data sets].

A new method for postprocessing of three dimensional magnetic resonance angiography data sets is described. Two operations are performed with the data set prior to maximum intensity projection. First, an irregular part of interest is marked interactively within the data set. By restricting the projection algorithm to this region, a disturbing overlay by vessels of other regions is avoided. Secondly, a three dimensional interpolation of the original data set is performed. While the spatial resolution of vessel representation is unchanged, the quality of the maximum intensity projection is improved significantly. The diagnostic value of this method is demonstrated by visualisation of a carotid aneurysm and of the deep and superficial cerebral veins.

Algorithms

Development of glycine receptor alpha subunit in cultivated rat spinal neurons: an immunocytochemical study.

Ontogenesis of the inhibitory glycine receptor was studied up to 12 days in vitro in spinal neurons placed previously in culture at embryonic day 14. The alpha subunit of the receptor was detected using standard and confocal immunofluorescence and a specific monoclonal antibody. The immunostaining was compared to that of synaptophysin, a synaptic vesicle antigen, which was taken as an index of synaptic maturity. Glycine receptors could be detected intracellularly, and not at the cellular surface in some cells as early as 2-3 days in vitro (DIV) prior to any synaptic contact. At 4-5 DIV, the number of cells which expressed the immunoreactivity and the fluorescence intensity increased. At this stage, spherical fluorescent blobs started to migrate in the neurites. From 6 DIV, the glycine receptor alpha subunit was detected at the neuronal surface and was organized in clusters whose number increased progressively with time. From 7 DIV, the intrasomatic immunoreactivity decreased, and at day 12, the pattern of labelling was similar to that observed in the adult spinal cord. A diffuse presence of the receptor at the surface of neurons could never be visualised, and when detected, the glycine receptors were always clustered. Thus, the increasing expression of clusters of glycine receptors at the neuronal surface was paralleled by that of synaptophysin in neuritic varicosities. These data suggest that transport of glycine receptors to the plasmamembrane and the formation of aggregates occurs simultaneously to synaptogenesis.

Animals

[Substraction in gastrointestinal angiography (author's transl)].

On the basis of a comparative study of 100 angiograms, the authors stress the value of photographic substraction in gastrointestinal angiography. From a technical viewpoint, after a brief review of the theoretical background, the authors emphasise the need to use reproductions of different tonality, and the problems of blurring due to movement, which may be overcome by the use of an effective premedication (diazepam) and by limiting the substraction to a very limited arca. From the standpoint of results, photographic substraction gives improved radiological data in the arterial phase in 60% of cases. This improvement concerns the prevertebral vessels. During the venous phase, in all cases there is an improvement in mesenterico-portal return and the visualisation of oesophageal varices. In all, photographic substraction, a simple technique, appears to be of value in gastrointestinal angiography essentially in the arteriographic study of the pancreas and of spleno-portal and mesenterico-portal venous return.

Angiography

A computer program for topographic analysis of biomolecular systems.

This program essentially generates a picture of a space filling molecular model. By precise simulation of the intersections between atoms, leaving out the 'hidden line', a good perspective is produced. Additional three dimensional information is provided by simulating reflection spots on the surface. This program has been used to visualise three dimensional surface features of biologically important molecules (e.g., valinomycin). With slight modification the program can be used to visualise enzyme active sites and receptor surfaces. It can also be used to create animated motion pictures of molecular dynamics.

Chemical Phenomena

Electron microscope observations on the entry of avian infectious bronchitis virus into susceptible cells.

Infectious bronchitis virus was observed to enter cells of chicken chorioallantoic membrane by viropexis. There was no support for the suggestion that entry took place by fusion of viral and plasma membranes. The results of electron microscopy showed that virus attachment occurred both at 4 degrees and at 37 degrees C. Viropexis was not observed until the preparations were warmed. Similar results were obtained using chicken kidney cells. Quantitative data obtained from a plaque counting system employing chicken kidney cells indicated that attachment was the same at both temperatures and that some virus particles were taken up at 4 degrees C. Virus uptake was triggered by attachment of the virus to the cell membrane and the subsequent process of virus entry visualised by E. M. appeared to proceed without the involvement of lysosomal enzymes. No intracellular virus was located by electron microscopy in warmed preparations when virus was treated with specific antiserum, either before or after adsorption to the cells.

Adsorption