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Background: The purpose of this paper is to describe long-term outcomes for patients discharged over a 12-year period from a medium secure service for people with intellectual disabilities (ID). Methods: A cohort study using case-notes analysis and a structured interview of current key informants. Results: Eleven per cent of the sample was reconvicted. Fifty-eight per cent of the sample showed offending-like behaviour that did not lead to police contact. Twenty-eight per cent of the sample was currently detained in hospital under the Mental Health Act. The presence of a personality disorder, a history of theft or burglary, and young age increased the risk of reconviction. Contact with the police was less likely in those with schizophrenia. Re-admission to hospital was associated with the presence of offending-like behaviours, rather than any specific diagnosis. Conclusion: In terms of reconviction, these results are good compared with those from general forensic services; however, behavioural problems continue for many years and are managed without recourse to the criminal justice system. There is a borderline group whose needs are poorly defined and serviced.

To investigate the influence of attitudes of carers of people with intellectual disability (ID) towards giving medication. Ninety-three carers of service users who are currently attending outpatients clinic (Harrow Learning Disability service) were interviewed, using the RAMS (Rating of Attitude to Medication Scale) interview schedule. A significant association was found between relationship of the carer to the service user and overall positive or negative attitude towards medication, with a disproportionate number of parents expressing a negative attitude in comparison with professional carers (46% vs. 11%). This study suggests more work needs to be done with family carers than with professional carers to improve compliance with medication. Stigma is still associated with ID and psychiatric disorders. The family carers responses may be projecting their feelings related to the impact of having a child not only with ID, but also with additional psychiatric problems. The implication of the study for psychiatrists is the identification of a number of areas that could be usefully explored before writing a prescription.

As sequencing genomes has become increasingly popular, the need for annotation of the resulting assemblies is growing. Structural and functional annotation is still challenging as it includes finding the correct gene sequences, annotating other elements such as RNA and being able to submit those data to databases to share it with the community. Compared to de novo assembly where contiguous chromosomes are a sign of high quality, it is difficult to visualize and assess the quality of annotation. We developed the Companion web server to allow non-experts to annotate their genome using a reference-based method, enabling them to assess the output before submitting to public databases. In this update paper, we describe how we have included novel methods for gene finding and made the Companion server more efficient for annotation of genomes of up to 1 Gb in size. The reference set was increased to include genomes of interest for human and animal health from the fungi and arthropod kingdoms. We show that Companion outperforms existing comparable tools where closely related references are available., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

FungiDB (https://fungidb.org) serves as a valuable online resource that seamlessly integrates genomic and related large-scale data for a wide range of fungal and oomycete species. As an integral part of the VEuPathDB Bioinformatics Resource Center (https://veupathdb.org), FungiDB continually integrates both published and unpublished data addressing various aspects of fungal biology. Established in early 2011, the database has evolved to support 674 datasets. The datasets include over 300 genomes spanning various taxa (e.g. Ascomycota, Basidiomycota, Blastocladiomycota, Chytridiomycota, Mucoromycota, as well as Albuginales, Peronosporales, Pythiales, and Saprolegniales). In addition to genomic assemblies and annotation, over 300 extra datasets encompassing diverse information, such as expression and variation data, are also available. The resource also provides an intuitive web-based interface, facilitating comprehensive approaches to data mining and visualization. Users can test their hypotheses and navigate through omics-scale datasets using a built-in search strategy system. Moreover, FungiDB offers capabilities for private data analysis via the integrated VEuPathDB Galaxy platform. FungiDB also permits genome improvements by capturing expert knowledge through the User Comments system and the Apollo genome annotation editor for structural and functional gene curation. FungiDB facilitates data exploration and analysis and contributes to advancing research efforts by capturing expert knowledge for fungal and oomycete species., Competing Interests: Conflicts of interest: The author(s) declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) is a Bioinformatics Resource Center funded by the National Institutes of Health with additional funding from the Wellcome Trust. VEuPathDB supports >600 organisms that comprise invertebrate vectors, eukaryotic pathogens (protists and fungi) and relevant free-living or non-pathogenic species or hosts. Since 2004, VEuPathDB has analyzed omics data from the public domain using contemporary bioinformatic workflows, including orthology predictions via OrthoMCL, and integrated the analysis results with analysis tools, visualizations, and advanced search capabilities. The unique data mining platform coupled with >3000 pre-analyzed data sets facilitates the exploration of pertinent omics data in support of hypothesis driven research. Comparisons are easily made across data sets, data types and organisms. A Galaxy workspace offers the opportunity for the analysis of private large-scale datasets and for porting to VEuPathDB for comparisons with integrated data. The MapVEu tool provides a platform for exploration of spatially resolved data such as vector surveillance and insecticide resistance monitoring. To address the growing body of omics data and advances in laboratory techniques, VEuPathDB has added several new data types, searches and features, improved the Galaxy workspace environment, redesigned the MapVEu interface and updated the infrastructure to accommodate these changes., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Middle-aged adults have the highest obesity rates, leading to significant health complications in later years. Obesity triggers the release of altered molecules, including extracellular vesicles (EVs) from excess adipose tissue (AT), contributing to various health complications. In this study, we assessed the effects of age and a high-fat diet on AT-derived EV miRNA profiles to understand their potential roles in aging and obesity., Method: C57BL/6 male mice were subjected to a normal chow diet (NCD) or a high-fat diet (HFD) for either 10-12 weeks (young mice, n = 10) or 50-61 weeks (middle-aged mice, n = 12). After evaluating metabolic characteristics, peri-gonadal white AT was isolated and cultured to obtain EVs. AT-derived EV miRNAs were profiled using a NanoString miRNA panel ( n = 599)., Results: Middle-aged mice exhibited obesity regardless of diet. Young mice fed an HFD showed similar metabolic traits to middle-aged mice. In the NCD group, 131 differentially expressed miRNAs (DE-miRNAs) emerged in middle-aged mice compared to young mice, including miR-21, miR-148a, and miR-29a, associated with cancer, neuro/psychological disorders, and reproductive diseases. In the HFD group, 55 DE-miRNAs were revealed in middle-aged mice compared to young mice. These miRNAs were associated with significantly suppressed IGF1R activity., Conclusion: This study demonstrates the potential significant impact of miRNAs of AT EVs on aging- and obesity-related diseases.

Background: Eukaryotes such as fungi and protists frequently accompany bacteria and archaea in microbial communities. Unfortunately, their presence is difficult to study with "shotgun" metagenomic sequencing since prokaryotic signals dominate in most environments. Recent methods for eukaryotic detection use eukaryote-specific marker genes, but they do not incorporate strategies to handle the presence of eukaryotes that are not represented in the reference marker gene set, and they are not compatible with web-based tools for downstream analysis., Results: Here, we present CORRAL (for Clustering Of Related Reference ALignments), a tool for the identification of eukaryotes in shotgun metagenomic data based on alignments to eukaryote-specific marker genes and Markov clustering. Using a combination of simulated datasets, mock community standards, and large publicly available human microbiome studies, we demonstrate that our method is not only sensitive and accurate but is also capable of inferring the presence of eukaryotes not included in the marker gene reference, such as novel strains. Finally, we deploy CORRAL on our MicrobiomeDB.org resource, producing an atlas of eukaryotes present in various environments of the human body and linking their presence to study covariates., Conclusions: CORRAL allows eukaryotic detection to be automated and carried out at scale. Implementation of CORRAL in MicrobiomeDB.org creates a running atlas of microbial eukaryotes in metagenomic studies. Since our approach is independent of the reference used, it may be applicable to other contexts where shotgun metagenomic reads are matched against redundant but non-exhaustive databases, such as the identification of bacterial virulence genes or taxonomic classification of viral reads. Video Abstract., (© 2023. The Author(s).)

Summary: Annotation of nonmodel organisms is an open problem, especially the detection of untranslated regions (UTRs). Correct annotation of UTRs is crucial in transcriptomic analysis to accurately capture the expression of each gene yet is mostly overlooked in annotation pipelines. Here we present peaks2utr, an easy-to-use Python command line tool that uses the UTR enrichment of single-cell technologies, such as 10× Chromium, to accurately annotate 3' UTRs for a given canonical annotation., Availability and Implementation: peaks2utr is implemented in Python 3 (≥3.8). It is available via PyPI at https://pypi.org/project/peaks2utr and GitHub at https://github.com/haessar/peaks2utr. It is licensed under GNU GPLv3., (© The Author(s) 2023. Published by Oxford University Press.)

Parasitic diseases caused by kinetoplastid parasites are a burden to public health throughout tropical and subtropical regions of the world. TriTrypDB (https://tritrypdb.org) is a free online resource for data mining of genomic and functional data from these kinetoplastid parasites and is part of the VEuPathDB Bioinformatics Resource Center (https://veupathdb.org). As of release 59, TriTrypDB hosts 83 kinetoplastid genomes, nine of which, including Trypanosoma brucei brucei TREU927, Trypanosoma cruzi CL Brener and Leishmania major Friedlin, undergo manual curation by integrating information from scientific publications, high-throughput assays and user submitted comments. TriTrypDB also integrates transcriptomic, proteomic, epigenomic, population-level and isolate data, functional information from genome-wide RNAi knock-down and fluorescent tagging, and results from automated bioinformatics analysis pipelines. TriTrypDB offers a user-friendly web interface embedded with a genome browser, search strategy system and bioinformatics tools to support custom in silico experiments that leverage integrated data. A Galaxy workspace enables users to analyze their private data (e.g., RNA-sequencing, variant calling, etc.) and explore their results privately in the context of publicly available information in the database. The recent addition of an annotation platform based on Apollo enables users to provide both functional and structural changes that will appear as 'community annotations' immediately and, pending curatorial review, will be integrated into the official genome annotation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shanmugasundram et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Breast milk has abundant extracellular vesicles (EVs) containing various biological molecules (cargo), including miRNAs. EVs are not degraded in the gastrointestinal system and circulation; thus, breast milk EVs (bEVs) are expected to interact with other organs in breastfed infants and modify the gene expression of recipient cells using miRNAs. Maternal pre-pregnancy BMI is a critical factor influencing the composition of breast milk. Thus, in mothers with obesity, miRNAs in bEVs can be altered, which might be associated with adverse health outcomes in infants. In this study, we examined 798 miRNAs to determine which miRNAs are altered in the bEVs of mothers with obesity and their potential impact on breastfed infants., Methods: We recruited healthy nursing mothers who were either of normal weight (BMI < 25) or with obesity (BMI ≥ 30) based on their pre-pregnancy BMI, and delivered a singleton baby in the prior 6 months. EVs were isolated from breast milk with ultracentrifugation. bEV characteristics were examined by flow cytometry and fluorescence imaging of EV markers. A total of 798 miRNAs were screened using a NanoString human miRNA panel to find differentially expressed miRNAs in bEVs of mothers with obesity compared to mothers of normal weight., Results: We included 65 nursing mothers: 47 of normal weight and 18 with obesity based on pre-pregnancy BMI. After bEV isolation, we confirmed the expression of various EV markers. Out of 37 EV markers, CD326 (EpCaM) was the most highly expressed in bEVs. The most abundant miRNAs in bEVs include miR-30b-5p, miR-4454, miR-494-3p , and let-7 miRNAs . Target genes of the top 10 miRNAs were associated with cancer, prolactin pathway, EGFR, ErbB, and FoxO signaling pathway. In bEVs of mothers with obesity, 19 miRNAs were differentially expressed (adjusted p < 0.05 cut-off), which include miR-575, miR-630, miR-642a-3p , and miR-652-5p . These miRNAs and their target genes were associated with neurological diseases and psychological disorders., Conclusion: In this study, we characterized bEVs and demonstrated altered miRNAs in bEVs of mothers with obesity and identified the pathways of their potential target genes. Our findings will provide insight for future studies investigating the role of bEVs in breastfed infants., 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 © 2022 Cho, Vorn, Chimenti, Crouch, Shaoshuai, Narayanaswamy, Harken, Schmidt, Gill and Lee.)

Over the last few decades, the nature of life sciences research has changed enormously, generating a need for a workforce with a variety of computational skills such as those required to store, manage, and analyse the large biological datasets produced by next-generation sequencing. Those with such expertise are increasingly in demand for employment in both research and industry. Despite this, bioinformatics education has failed to keep pace with advances in research. At secondary school level, computing is often taught in isolation from other sciences, and its importance in biological research is not fully realised, leaving pupils unprepared for the computational component of Higher Education and, subsequently, research in the life sciences. The 4273pi Bioinformatics at School project (https://4273pi.org) aims to address this issue by designing and delivering curriculum-linked, hands-on bioinformatics workshops for secondary school biology pupils, with an emphasis on equitable access. So far, we have reached over 180 schools across Scotland through visits or teacher events, and our open education resources are used internationally. Here, we describe our project, our aims and motivations, and the practical lessons we have learned from implementing a successful bioinformatics education project over the last 5 years., Competing Interests: The authors have declared that no competing interests exist.

The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) represents the 2019 merger of VectorBase with the EuPathDB projects. As a Bioinformatics Resource Center funded by the National Institutes of Health, with additional support from the Welllcome Trust, VEuPathDB supports >500 organisms comprising invertebrate vectors, eukaryotic pathogens (protists and fungi) and relevant free-living or non-pathogenic species or hosts. Designed to empower researchers with access to Omics data and bioinformatic analyses, VEuPathDB projects integrate >1700 pre-analysed datasets (and associated metadata) with advanced search capabilities, visualizations, and analysis tools in a graphic interface. Diverse data types are analysed with standardized workflows including an in-house OrthoMCL algorithm for predicting orthology. Comparisons are easily made across datasets, data types and organisms in this unique data mining platform. A new site-wide search facilitates access for both experienced and novice users. Upgraded infrastructure and workflows support numerous updates to the web interface, tools, searches and strategies, and Galaxy workspace where users can privately analyse their own data. Forthcoming upgrades include cloud-ready application architecture, expanded support for the Galaxy workspace, tools for interrogating host-pathogen interactions, and improved interactions with affiliated databases (ClinEpiDB, MicrobiomeDB) and other scientific resources, and increased interoperability with the Bacterial & Viral BRC., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Subspecies of the protozoan parasite Trypanosoma brucei are the causative agents of Human African Trypanosomiasis (HAT), a debilitating neglected tropical disease prevalent across sub-Saharan Africa. HAT case numbers have steadily decreased since the start of the century, and sustainable elimination of one form of the disease is in sight. However, key to this is the development of novel drugs to combat the disease. Acoziborole is a recently developed benzoxaborole, currently in advanced clinical trials, for treatment of stage 1 and stage 2 HAT. Importantly, acoziborole is orally bioavailable, and curative with one dose. Recent studies have made significant progress in determining the molecular mode of action of acoziborole. However, less is known about the potential mechanisms leading to acoziborole resistance in trypanosomes. In this study, an in vitro-derived acoziborole-resistant cell line was generated and characterised. The AcoR line exhibited significant cross-resistance with the methyltransferase inhibitor sinefungin as well as hypersensitisation to known trypanocides. Interestingly, transcriptomics analysis of AcoR cells indicated the parasites had obtained a procyclic- or stumpy-like transcriptome profile, with upregulation of procyclin surface proteins as well as differential regulation of key metabolic genes known to be expressed in a life cycle-specific manner, even in the absence of major morphological changes. However, no changes were observed in transcripts encoding CPSF3, the recently identified protein target of acoziborole. The results suggest that generation of resistance to this novel compound in vitro can be accompanied by transcriptomic switches resembling a procyclic- or stumpy-type phenotype., Competing Interests: The authors have declared that no competing interests exist.

Animal African Trypanosomiasis (AAT) is a debilitating livestock disease prevalent across sub-Saharan Africa, a main cause of which is the protozoan parasite Trypanosoma congolense. In comparison to the well-studied T. brucei, there is a major paucity of knowledge regarding the biology of T. congolense. Here, we use a combination of omics technologies and novel genetic tools to characterise core metabolism in T. congolense mammalian-infective bloodstream-form parasites, and test whether metabolic differences compared to T. brucei impact upon sensitivity to metabolic inhibition. Like the bloodstream stage of T. brucei, glycolysis plays a major part in T. congolense energy metabolism. However, the rate of glucose uptake is significantly lower in bloodstream stage T. congolense, with cells remaining viable when cultured in concentrations as low as 2 mM. Instead of pyruvate, the primary glycolytic endpoints are succinate, malate and acetate. Transcriptomics analysis showed higher levels of transcripts associated with the mitochondrial pyruvate dehydrogenase complex, acetate generation, and the glycosomal succinate shunt in T. congolense, compared to T. brucei. Stable-isotope labelling of glucose enabled the comparison of carbon usage between T. brucei and T. congolense, highlighting differences in nucleotide and saturated fatty acid metabolism. To validate the metabolic similarities and differences, both species were treated with metabolic inhibitors, confirming that electron transport chain activity is not essential in T. congolense. However, the parasite exhibits increased sensitivity to inhibition of mitochondrial pyruvate import, compared to T. brucei. Strikingly, T. congolense exhibited significant resistance to inhibitors of fatty acid synthesis, including a 780-fold higher EC50 for the lipase and fatty acid synthase inhibitor Orlistat, compared to T. brucei. These data highlight that bloodstream form T. congolense diverges from T. brucei in key areas of metabolism, with several features that are intermediate between bloodstream- and insect-stage T. brucei. These results have implications for drug development, mechanisms of drug resistance and host-pathogen interactions., Competing Interests: The authors have declared that no competing interests exist.