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Introduction. Each disease consists of predictors, symptoms, syndromes, which form the signs of the disease. However, the syndrome is not identical with the disease, it is not a nosological unit. It can be a manifestation of various diseases. Syndrome is a collection of different symptoms. Often syndromes are present in the nosological form. And it is unlikely that in the doctrine of nosology to “open” new syndromes, including several known diseases. Aim. To discuss the problem of transformation of nosological forms into syndromes in medical practice. Materials and methods. The content analysis, the method of system and comparative analysis, the bibliosemantic method of studying the actual scientific opinions of scientists about the doctrine of the diagnose, the problems of transformation of nosological forms into syndromes, some new tendencies of formulation, completeness of the diagnoses were used. Results. The structure of the diagnosis was developed by Ukrainian pathologists in the second half of the last century. The expanded diagnosis – both clinical and pathologoanatomic – is based on a certain principle. At the centre of it are causal relationships. The full diagnosis is: the underlying disease, the complication of the underlying disease, and concomitant diseases. Several logical tendencies can be singled out in the wording in modern clinical practice. The first trend is the combination of several diseases into the syndrome, the second – the transfer of the symptom into the syndrome, the third trend – the obvious complication of treatment is called syndrome, the fourth – the desire to combine several diseases in one, replacing, for example, the well-known complication of a disease (lack of organs’ function), giving this complication a “new”, generalized “disease”, the fifth – comorbidity – the real situation when two or more syndromes or nosological forms are detected in the same patient. Full “diagnose should be nosological, etiologic, pathogenic and “historical”, that is to reflect the disease in the form of a consistent causally caused change in its various stages. It is a document that presents the history of the disease in a concretised, most concise statement. Conclusions. The concept and doctrine of the diagnoses for foreign clinicians are obviously not known. We do not know the theoretical justification of new foreign trends in constructing of the diagnose. And moreover, we emphasize, it is unlikely that the syndrome-molecular approach can contribute to nosological statistics, the search for primary prevention, and the resolution of the problems of preventive medicine.

A present case showing giant cell aortitis (GGA) with coarctation of the aorta can be considered unique, even after reviewing the literature. The case of a 3.5-month-old girl who suffered an acute viral infection with an increase in body temperature (up to 39.5°C), difficulty breathing, and diarrhea is described. The girl was diagnosed with nasopharyngitis, enterocolitis, meningoencephalitis; she died 20 hours after being hospitalized from multiple organ failure. Clinical and laboratory data were collected, and a pathological examination was performed. Histological examination of the aorta and its main branches, such as the brachiocephalic trunk, left common carotid artery, left subclavian artery, as well as internal organs, was performed using hematoxylin-eosin, Hart's resorcin-fuchsin, Weigert's picrofuchsin, and Masson's trichrome. Pathological examination revealed giant cell aortitis and arteritis with coarctation of the aorta. GCA, in our case, had pathomorphological signs. First, many plaques that protruded into the lumen of the aorta and main branches, such as the brachiocephalic trunk, left common carotid artery and left subclavian artery, had a conical end that resembled the appearance of a rash. Second, granulomatous inflammation was localized in the intima of the aorta and all layers of the above-mentioned arteries. Our case of GCA in a 3.5-month-old girl is the youngest patient among those described. We first describe GCA in relation to other severe aortic diseases. Coarctation, in combination with an aneurysm of the ascending aorta and aortitis, is a pathology that has not yet been described., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Sequence Ontology (SO) is a structured, controlled vocabulary that provides terms and definitions for genomic annotation. The Gene Regulation Ensemble Effort for the Knowledge Commons (GREEKC) initiative has gathered input from many groups of researchers, including the SO, the Gene Ontology (GO), and gene regulation experts, with the goal of curating information about how gene expression is regulated at the molecular level. Here we discuss recent updates to the SO reflecting current knowledge. We have developed more accurate human-readable terms (also known as classes), including new definitions, and relationships related to the expression of genes. New findings continue to give us insight into the biology of gene regulation, including the order of events, and participants in those events. These updates to the SO support logical reasoning with the current understanding of gene expression regulation at the molecular level., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The Functional Annotation of ANimal Genomes (FAANG) project is a worldwide coordinated action creating high-quality functional annotation of farmed and companion animal genomes. The generation of a rich genome-to-phenome resource and supporting informatic infrastructure advances the scope of comparative genomics and furthers the understanding of functional elements. The project also provides terrestrial and aquatic animal agriculture community powerful resources for supporting improvements to farmed animal production, disease resistance, and genetic diversity. The FAANG Data Portal (https://data.faang.org) ensures Findable, Accessible, Interoperable and Reusable (FAIR) open access to the wealth of sample, sequencing, and analysis data produced by an ever-growing number of FAANG consortia. It is developed and maintained by the FAANG Data Coordination Centre (DCC) at the European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI). FAANG projects produce a standardised set of multi-omic assays with resulting data placed into a range of specialised open data archives. To ensure this data is easily findable and accessible by the community, the portal automatically identifies and collates all submitted FAANG data into a single easily searchable resource. The Data Portal supports direct download from the multiple underlying archives to enable seamless access to all FAANG data from within the portal itself. The portal provides a range of predefined filters, powerful predictive search, and a catalogue of sampling and analysis protocols and automatically identifies publications associated with any dataset. To ensure all FAANG data submissions are high-quality, the portal includes powerful contextual metadata validation and data submissions brokering to the underlying EMBL-EBI archives. The portal will incorporate extensive new technical infrastructure to effectively deliver and standardise FAANG's shift to single-cellomics, cell atlases, pangenomes, and novel phenotypic prediction models. The Data Portal plays a key role for FAANG by supporting high-quality functional annotation of animal genomes, through open FAIR sharing of data, complete with standardised rich metadata. Future Data Portal features developed by the DCC will support new technological developments for continued improvement for FAANG projects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Harrison, Sokolov, Nayak, Fan, Zerbino, Cochrane and Flicek.)

Background: Many types of data from genomic analyses can be represented as genomic tracks, i.e. features linked to the genomic coordinates of a reference genome. Examples of such data are epigenetic DNA methylation data, ChIP-seq peaks, germline or somatic DNA variants, as well as RNA-seq expression levels. Researchers often face difficulties in locating, accessing and combining relevant tracks from external sources, as well as locating the raw data, reducing the value of the generated information. Description of work: We propose to advance the application of FAIR data principles (Findable, Accessible, Interoperable, and Reusable) to produce searchable metadata for genomic tracks. Findability and Accessibility of metadata can then be ensured by a track search service that integrates globally identifiable metadata from various track hubs in the Track Hub Registry and other relevant repositories. Interoperability and Reusability need to be ensured by the specification and implementation of a basic set of recommendations for metadata. We have tested this concept by developing such a specification in a JSON Schema, called FAIRtracks, and have integrated it into a novel track search service, called TrackFind. We demonstrate practical usage by importing datasets through TrackFind into existing examples of relevant analytical tools for genomic tracks: EPICO and the GSuite HyperBrowser. Conclusion: We here provide a first iteration of a draft standard for genomic track metadata, as well as the accompanying software ecosystem. It can easily be adapted or extended to future needs of the research community regarding data, methods and tools, balancing the requirements of both data submitters and analytical end-users., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Gundersen S et al.)

The GENCODE project annotates human and mouse genes and transcripts supported by experimental data with high accuracy, providing a foundational resource that supports genome biology and clinical genomics. GENCODE annotation processes make use of primary data and bioinformatic tools and analysis generated both within the consortium and externally to support the creation of transcript structures and the determination of their function. Here, we present improvements to our annotation infrastructure, bioinformatics tools, and analysis, and the advances they support in the annotation of the human and mouse genomes including: the completion of first pass manual annotation for the mouse reference genome; targeted improvements to the annotation of genes associated with SARS-CoV-2 infection; collaborative projects to achieve convergence across reference annotation databases for the annotation of human and mouse protein-coding genes; and the first GENCODE manually supervised automated annotation of lncRNAs. Our annotation is accessible via Ensembl, the UCSC Genome Browser and https://www.gencodegenes.org., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Motivation: Genome-wide association studies (GWAS) are a powerful method to detect even weak associations between variants and phenotypes; however, many of the identified associated variants are in non-coding regions, and presumably influence gene expression regulation. Identifying potential drug targets, i.e. causal protein-coding genes, therefore, requires crossing the genetics results with functional data., Results: We present a novel data integration pipeline that analyses GWAS results in the light of experimental epigenetic and cis-regulatory datasets, such as ChIP-Seq, Promoter-Capture Hi-C or eQTL, and presents them in a single report, which can be used for inferring likely causal genes. This pipeline was then fed into an interactive data resource., Availability and Implementation: The analysis code is available at www.github.com/Ensembl/postgap and the interactive data browser at postgwas.opentargets.io., (© The Author(s) 2020. Published by Oxford University Press.)

The accurate identification and description of the genes in the human and mouse genomes is a fundamental requirement for high quality analysis of data informing both genome biology and clinical genomics. Over the last 15 years, the GENCODE consortium has been producing reference quality gene annotations to provide this foundational resource. The GENCODE consortium includes both experimental and computational biology groups who work together to improve and extend the GENCODE gene annotation. Specifically, we generate primary data, create bioinformatics tools and provide analysis to support the work of expert manual gene annotators and automated gene annotation pipelines. In addition, manual and computational annotation workflows use any and all publicly available data and analysis, along with the research literature to identify and characterise gene loci to the highest standard. GENCODE gene annotations are accessible via the Ensembl and UCSC Genome Browsers, the Ensembl FTP site, Ensembl Biomart, Ensembl Perl and REST APIs as well as https://www.gencodegenes.org.

Bicuspid aortic valve (BAV) is the most common congenital heart defect. Although many BAV patients remain asymptomatic, at least 20% develop thoracic aortic aneurysm (TAA). Historically, BAV-related TAA was considered as a hemodynamic consequence of the valve defect. Multiple lines of evidence currently suggest that genetic determinants contribute to the pathogenesis of both BAV and TAA in affected individuals. Despite high heritability, only very few genes have been linked to BAV or BAV/TAA, such as NOTCH1, SMAD6 , and MAT2A . Moreover, they only explain a minority of patients. Other candidate genes have been suggested based on the presence of BAV in knockout mouse models (e.g., GATA5, NOS3 ) or in syndromic (e.g., TGFBR1/2, TGFB2/3 ) or non-syndromic (e.g., ACTA2 ) TAA forms. We hypothesized that rare genetic variants in these genes may be enriched in patients presenting with both BAV and TAA. We performed targeted resequencing of 22 candidate genes using Haloplex target enrichment in a strictly defined BAV/TAA cohort ( n = 441; BAV in addition to an aortic root or ascendens diameter ≥ 4.0 cm in adults, or a Z-score ≥ 3 in children) and in a collection of healthy controls with normal echocardiographic evaluation ( n = 183). After additional burden analysis against the Exome Aggregation Consortium database, the strongest candidate susceptibility gene was SMAD6 ( p = 0.002), with 2.5% ( n = 11) of BAV/TAA patients harboring causal variants, including two nonsense, one in-frame deletion and two frameshift mutations. All six missense mutations were located in the functionally important MH1 and MH2 domains. In conclusion, we report a significant contribution of SMAD6 mutations to the etiology of the BAV/TAA phenotype.

The Ensembl software resources are a stable infrastructure to store, access and manipulate genome assemblies and their functional annotations. The Ensembl 'Core' database and Application Programming Interface (API) was our first major piece of software infrastructure and remains at the centre of all of our genome resources. Since its initial design more than fifteen years ago, the number of publicly available genomic, transcriptomic and proteomic datasets has grown enormously, accelerated by continuous advances in DNA-sequencing technology. Initially intended to provide annotation for the reference human genome, we have extended our framework to support the genomes of all species as well as richer assembly models. Cross-referenced links to other informatics resources facilitate searching our database with a variety of popular identifiers such as UniProt and RefSeq. Our comprehensive and robust framework storing a large diversity of genome annotations in one location serves as a platform for other groups to generate and maintain their own tailored annotation. We welcome reuse and contributions: our databases and APIs are publicly available, all of our source code is released with a permissive Apache v2.0 licence at http://github.com/Ensembl and we have an active developer mailing list ( http://www.ensembl.org/info/about/contact/index.html )., Database Url: http://www.ensembl.org., (© The Author(s) 2017. Published by Oxford University Press.)

Marfan syndrome is an autosomal dominant connective tissue disorder, predominantly affecting the ocular, skeletal and cardiovascular systems. Here, we present the results of the first genetic testing in 40 Ukrainian Marfan (-like) patients and 10 relatives. We applied a targeted next generation sequencing panel comprising FBN1 and 13 thoracic aortic aneurysm genes. We identified 27 causal mutations in FBN1, obtaining a mutation yield of 67·5%. A significant difference in age at aortic surgery between mutation positive and negative patients was observed. Thus, we conclude that genetic testing is important to identify patients at higher risk for developing life-threatening cardiovascular complications.

Capture Hi-C (CHi-C) is a method for profiling chromosomal interactions involving targeted regions of interest, such as gene promoters, globally and at high resolution. Signal detection in CHi-C data involves a number of statistical challenges that are not observed when using other Hi-C-like techniques. We present a background model and algorithms for normalisation and multiple testing that are specifically adapted to CHi-C experiments. We implement these procedures in CHiCAGO ( http://regulatorygenomicsgroup.org/chicago ), an open-source package for robust interaction detection in CHi-C. We validate CHiCAGO by showing that promoter-interacting regions detected with this method are enriched for regulatory features and disease-associated SNPs.

Thromboangiitis obliterans (Buerger's disease) is systemic vasculitis with predominant development of thrombotic occlusions of small-to-medium diameter arteries of distal portions of both upper and lower limbs. A distinctive feature of Buerger's disease from other vasculitides is the involvement of the venous bed into the pathological process in the form of migrating thrombophlebitis. The disease is encountered more often in young adult males, predominantly tobacco smokers. The clinical pattern is presented by symptoms of increasing insufficiency of blood supply of tissues of extremities. The diagnosis is made by means of ruling out other vascular diseases (atherosclerosis, diabetes mellitus, systemic diseases of connective tissue, hypercoagulation conditions) based on clinical and laboratory findings, as well as modern methods of visualization, including multislice spiral computed tomographic angiography. Of special importance is a pathomorphological examination aimed at detecting the signs specific for Buerger's disease: arteries showing intimal hyperplasia (from stenosis to complete obliteration according to the capillary angiomatosis type, vascular "recalibration", obliteration of lumens by thrombi, lack of calcification of the tunica media; venous alterations are presented by panphlebitis with intimal hyperplasia, and occlusion with thrombi. Treatment is aimed at eliminating the aetiological stimulus (i. e, smoking), improving blood circulation by means of regular, dosed physical exercises, and administration of anti-ischaemic agents (analogues of prostaglandins, calcium channel antagonists, antiaggregants and anticoagulants). Failure of conservative treatment failed should be followed by making a decision to perform revascularization (endovascular interventions, bypass reconstructive operations, arterialization of the venous blood flow of the foot, resection of the posterior tibial veins, transplantation of the greater omentum onto the crus).

The authors examined the state of patients suffering from Marfan syndrome (MS) who endured operation for ascending aorta aneurysm with replacement of the ascending aorta and aortic valve (Bentall operation), studying alterations of the skeleton, face, heart and eyes, as well as pathomorphological restructurings in the aortic wall. The study was carried out 7.0 ± 4.2 years after the operation. We examined a total of 39 patients with MS - 27 (69.2%) men and 12 (30.8%) women aged from 22 to 70 years old (average age - 42.1 ± 13.4 years). All patients were operated on for dissecting aneurysm of the ascending aorta accompanied by a considerable degree of aortic valve insufficiency or aortic ostium stenosis. The mean diameter of the aorta at the level of the sinuses of Valsalva amounted to 7.0 ± 1.3 cm (minimal - 5.0 cm, maximal - 12.0 cm), the Z-score prior to operation was 12.7 ± 6.5. The time form making the diagnosis of MS to surgical intervention for aortic aneurysm amounted to 9.6 ± 5.9 years. The condition after operative treatment in all patients was satisfactory, with the haemodynamic indices stable: systolic AP - 133.5 ± 19.1 mm Hg, diastolic AP 85.1 ± 12.9 mm Hg, heart rate 74.8 ± 7.2 bpm. The average systemic score for the symptoms and tests of MS patients amounted to 8.2 ± 3.3 points. Pathohistological alterations of the aorta in patients with Marfan syndrome consisted in pronounced restructuring of the wall with deep irreversible alternative changes. The pathological process extended in the middle aortic layer all alone the length, but not only in the portions of rupture and dissection. The main pathomorphological signs in MS were as follows: focal accumulations of mucoid substances, dystrophic alterations of smooth-muscle cells, ribbon-like anuclear zones, formation of cystlike cavities, alterations of elastic fibres - fragmentation, hyperelastosis, multiplication, thinning and straightening, zones of elastolysis.