Genome-wide Association Studies in Ancestrally Diverse Populations: Opportunities, Methods, Pitfalls, and Recommendations.

Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well.

Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation.

Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIA-PET), we mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered intragenic, extragenic, and intergenic interactions. These interactions further aggregated into higher-order clusters, wherein proximal and distal genes were engaged through promoter-promoter interactions. Most genes with promoter-promoter interactions were active and transcribed cooperatively, and some interacting promoters could influence each other implying combinatorial complexity of transcriptional controls. Comparative analyses of different cell lines showed that cell-specific chromatin interactions could provide structural frameworks for cell-specific transcription, and suggested significant enrichment of enhancer-promoter interactions for cell-specific functions. Furthermore, genetically-identified disease-associated noncoding elements were found to be spatially engaged with corresponding genes through long-range interactions. Overall, our study provides insights into transcription regulation by three-dimensional chromatin interactions for both housekeeping and cell-specific genes in human cells.

The mutational constraint spectrum quantified from variation in 141,456 humans.

Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes that are crucial for the function of an organism will be depleted of such variants in natural populations, whereas non-essential genes will tolerate their accumulation. However, predicted loss-of-function variants are enriched for annotation errors, and tend to be found at extremely low frequencies, so their analysis requires careful variant annotation and very large sample sizes1. Here we describe the aggregation of 125,748 exomes and 15,708 genomes from human sequencing studies into the Genome Aggregation Database (gnomAD). We identify 443,769 high-confidence predicted loss-of-function variants in this cohort after filtering for artefacts caused by sequencing and annotation errors. Using an improved model of human mutation rates, we classify human protein-coding genes along a spectrum that represents tolerance to inactivation, validate this classification using data from model organisms and engineered human cells, and show that it can be used to improve the power of gene discovery for both common and rare diseases.

Hypomorphic and dominant-negative impact of truncated SOX9 dysregulates Hedgehog-Wnt signaling, causing campomelia.

Haploinsufficiency for SOX9, the master chondrogenesis transcription factor, can underlie campomelic dysplasia (CD), an autosomal dominant skeletal malformation syndrome, because heterozygous Sox9 null mice recapitulate the bent limb (campomelia) and some other phenotypes associated with CD. However, in vitro cell assays suggest haploinsufficiency may not apply for certain mutations, notably those that truncate the protein, but in these cases in vivo evidence is lacking and underlying mechanisms are unknown. Here, using conditional mouse mutants, we compared the impact of a heterozygous Sox9 null mutation (Sox9+/-) with the Sox9+/Y440X CD mutation that truncates the C-terminal transactivation domain but spares the DNA-binding domain. While some Sox9+/Y440X mice survived, all Sox9+/- mice died perinatally. However, the skeletal defects were more severe and IHH signaling in developing limb cartilage was significantly enhanced in Sox9+/Y440X compared with Sox9+/-. Activating Sox9Y440X specifically in the chondrocyte-osteoblast lineage caused milder campomelia, and revealed cell- and noncell autonomous mechanisms acting on chondrocyte differentiation and osteogenesis in the perichondrium. Transcriptome analyses of developing Sox9+/Y440X limbs revealed dysregulated expression of genes for the extracellular matrix, as well as changes consistent with aberrant WNT and HH signaling. SOX9Y440X failed to interact with ß-catenin and was unable to suppress transactivation of Ihh in cell-based assays. We propose enhanced HH signaling in the adjacent perichondrium induces asymmetrically localized excessive perichondrial osteogenesis resulting in campomelia. Our study implicates combined haploinsufficiency/hypomorphic and dominant-negative actions of SOX9Y440X, cell-autonomous and noncell autonomous mechanisms, and dysregulated WNT and HH signaling, as the cause of human campomelia.

Whole-genome sequencing of African Americans implicates differential genetic architecture in inflammatory bowel disease.

Whether or not populations diverge with respect to the genetic contribution to risk of specific complex diseases is relevant to understanding the evolution of susceptibility and origins of health disparities. Here, we describe a large-scale whole-genome sequencing study of inflammatory bowel disease encompassing 1,774 affected individuals and 1,644 healthy control Americans with African ancestry (African Americans). Although no new loci for inflammatory bowel disease are discovered at genome-wide significance levels, we identify numerous instances of differential effect sizes in combination with divergent allele frequencies. For example, the major effect at PTGER4 fine maps to a single credible interval of 22 SNPs corresponding to one of four independent associations at the locus in European ancestry individuals but with an elevated odds ratio for Crohn disease in African Americans. A rare variant aggregate analysis implicates Ca2+-binding neuro-immunomodulator CALB2 in ulcerative colitis. Highly significant overall overlap of common variant risk for inflammatory bowel disease susceptibility between individuals with African and European ancestries was observed, with 41 of 241 previously known lead variants replicated and overall correlations in effect sizes of 0.68 for combined inflammatory bowel disease. Nevertheless, subtle differences influence the performance of polygenic risk scores, and we show that ancestry-appropriate weights significantly improve polygenic prediction in the highest percentiles of risk. The median amount of variance explained per locus remains the same in African and European cohorts, providing evidence for compensation of effect sizes as allele frequencies diverge, as expected under a highly polygenic model of disease.

The IBD Clinic of Tomorrow: Holistic, Patient-Centric, and Value-based Care.

There is increasing recognition of the associated bi-directional impact of inflammatory bowel disease (IBD) on patient well-being and the potential benefit of multidisciplinary teams to address these unique needs. At certain IBD centers, there has been an evolution towards patient-centric, holistic care to enhance well-being and improve health-related outcomes. Multiple models, incorporating various disciplines, care modalities, digital tools and care delivery, and resource support have arisen in IBD. Although most IBD centers of excellence are now incorporating such multidisciplinary care models, many practices still practice IBD-limited specialty care, limiting evaluations and interventions to the IBD itself and its direct consequences (eg, extraintestinal manifestations). In this piece, we seek to review the evolution of IBD care towards a patient-centric, holistic model (termed 360 IBD Care) including the role and impact of digital health tools, monitoring, and delivery in IBD, and a shift towards value-based care models with discussion of payor priorities in IBD. We also suggest potential opportunities for IBD practitioners to incorporate elements of holistic care on a local scale. Together, we hope such care models will enhance not only IBD-specific health outcomes, but also improve the general well-being of our patients with IBD today and tomorrow.

AGA Clinical Practice Update on Telemedicine in Gastroenterology: Commentary.

DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to review the available evidence and provide expert advice regarding best practices for use of telemedicine in gastroenterology and hepatology. METHODS: This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. This expert commentary incorporates important, as well as recently published, studies in this field, and it reflects the experiences of the authors who are active gastroenterologists and hepatologists with extensive experience using telemedicine in clinical practice.

Long-Term Effectiveness and Durability of COVID-19 Vaccination Among Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: COVID-19 vaccination prevents severe disease in most patients with inflammatory bowel disease (IBD), but immunosuppressive medications can blunt serologic response. We followed adults with IBD for >1 year post-COVID-19 vaccination to describe factors associated with SARS-CoV-2 infection after vaccination, evaluate for a protective SARS-CoV-2 antibody level, characterize SARS-CoV-2 antibody persistence, and identify factors associated with humoral immune response durability. METHODS: Using a prospective cohort of COVID-19 immunized adults with IBD, we analyzed factors associated with SARS-CoV-2 infection after vaccination. We evaluated for an association between SARS-CoV-2 antibody level 12 weeks postvaccination and subsequent SARS-CoV-2 infection and assessed for a threshold of protection using receiver-operating characteristic curve analysis. We then conducted a separate analysis evaluating factors associated with persistence of SARS-CoV-2 antibodies 52 weeks postimmunization. RESULTS: Almost half (43%) of 1869 participants developed COVID-19 after vaccination, but most infections were mild, and <1% required hospitalization. Older age and corticosteroid use were associated with a decreased risk of SARS-CoV-2 infection postvaccination (50-59 years of age vs 18-29 years of age: adjusted hazard ratio, 0.57; 95% confidence interval, 0.44-0.74; steroid users vs nonusers: adjusted hazard ratio, 0.58; 95% confidence interval, 0.39-0.87). Most (98%) participants had detectable antibody levels at 52 weeks postvaccination. Antibody levels at 12 weeks and number of vaccine doses were positively associated with higher antibody levels at 52 weeks, while anti-tumor necrosis factor α therapy was negatively associated. CONCLUSIONS: COVID-19 vaccination generates an effective and durable protective response for the vast majority of adults with IBD, including vulnerable populations such as corticosteroid users and older individuals. Patients with IBD benefit from COVID-19 booster vaccination.

Monitoring Patients With Inflammatory Bowel Disease at High Risk of Anal Cancer.

Anal cancer is a rare but deadly disease that disproportionately affects patients with inflammatory bowel disease (IBD). Rates of adenocarcinoma and human papillomavirus-related squamous cell carcinoma have been consistently demonstrated to be higher in patients with ulcerative colitis and Crohn's disease. Despite this increased risk, uniform screening, diagnosis, and treatment algorithms are lacking. This review describes the most recent literature surrounding anal cancer in the IBD population as well as the unique challenges inherent in diagnosing and treating this population. We conclude by proposing a new screening motif based off literature review and multidisciplinary clinical experience that aims to increase early detection of anal cancers in the IBD population.

Changes in Therapy Are Not Associated With Increased Remission in Patients With Crohn's Disease of the Pouch.

INTRODUCTION: There is a paucity of data on the real-world effectiveness of therapies in patients with Crohn's disease of the pouch. METHODS: This was a prospective multicenter study evaluating the primary outcome of remission at 12 months of therapy for Crohn's disease of the pouch. RESULTS: One hundred thirty-four patients were enrolled. Among the 77 patients with symptoms at baseline, 35 (46.7%) achieved remission at 12 months. Of them, 12 (34.3%) changed therapy. There was no significant association between therapy patterns and remission status. DISCUSSION: Approximately 50% with symptoms at enrollment achieved clinical remission at 12 months, most of whom did so without a change in therapy.

Humoral immune response and safety of SARS-CoV-2 vaccination in very early onset inflammatory bowel disease.

Children with very early onset inflammatory bowel disease (VEO-IBD) may respond differently to coronavirus disease 2019 (COVID-19) immunization compared to healthy children or other patients with IBD. We recruited children with VEO-IBD <6 years of age and younger following receipt of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Demographics, IBD characteristics, medication use, adverse events (AEs) and IBD exacerbations were collected. Blood draws (optional) were obtained for measurement of antireceptor binding domain (RBD) IgG antibodies following vaccination. Of 41 participants, none required emergency department visit or hospitalization due to AE, and only one experienced IBD exacerbation. Detectable antibody was present in 19/19 participants who provided blood sample; 6/7 participants (86%) had durable humoral response 12 months postvaccination. Children with VEO-IBD experience robust humoral immune response to COVID-19 immunization. Severe AEs were rare. These findings provide reassurance that children with VEO-IBD respond well and safely to SARS-CoV-2 vaccination.

Delay-related activity in marmoset prefrontal cortex.

Persistent delay-period activity in prefrontal cortex (PFC) has long been regarded as a neural signature of working memory (WM). Electrophysiological investigations in macaque PFC have provided much insight into WM mechanisms; however, a barrier to understanding is the fact that a portion of PFC lies buried within the principal sulcus in this species and is inaccessible for laminar electrophysiology or optical imaging. The relatively lissencephalic cortex of the New World common marmoset (Callithrix jacchus) circumvents such limitations. It remains unknown, however, whether marmoset PFC neurons exhibit persistent activity. Here, we addressed this gap by conducting wireless electrophysiological recordings in PFC of marmosets performing a delayed-match-to-location task on a home cage-based touchscreen system. As in macaques, marmoset PFC neurons exhibited sample-, delay-, and response-related activity that was directionally tuned and linked to correct task performance. Models constructed from population activity consistently and accurately predicted stimulus location throughout the delay period, supporting a framework of delay activity in which mnemonic representations are relatively stable in time. Taken together, our findings support the existence of common neural mechanisms underlying WM performance in PFC of macaques and marmosets and thus validate the marmoset as a suitable model animal for investigating the microcircuitry underlying WM.

Correlation Between Serum and Fecal Biomarkers and Patient-Reported Outcomes in Patients with Crohn's Disease and Ulcerative Colitis.

BACKGROUND: Patient-reported outcomes (PROs), such as the short CD activity index (sCDAI) and partial Mayo Score (PMS), are used to define clinical remission in IBD, but may not represent the true degree of inflammation and endoscopy is invasive. Non-invasive testing options include c-reactive protein (CRP) and fecal calprotectin (FCP). AIM: The aim of this study was to assess the degree of correlation of non-invasive biomarkers with PROs and the impact other clinical variables can have on their levels. METHODS: We reviewed data collected from the prospective cohort, Study of a Prospective Adult Research Cohort with IBD (SPARC-IBD), comprised of over 3000 patients from 17 tertiary referral centers. Demographic and clinical variables were analyzed by disease type, disease severity was based on PROs, and baseline CRP and FCP were measured. For comparative analysis, we performed Fisher's exact test and Welch's t test, where p < 0.05 was significant. RESULTS: 1547 patients were included; 63% had CD, 56% were female, with an average disease duration of 13.6 years. CRP and FCP were associated with symptom severity in inflammatory CD. CRP was useful to differentiate symptoms across different disease locations in CD, whereas FCP was associated with symptom severity in Crohn's colitis only. For UC, FCP was able to distinguish symptom severity better in distal UC, whereas in extensive or pancolitis, it was useful only to distinguish severe symptoms from other categories of symptom severity. CONCLUSION: PROs correlate with CRP and FCP; however, disease location and phenotype impact their ability to distinguish symptom severity.

Upadacitinib as Rescue Therapy for the Treatment of Acute Severe Colitis in an Acute Care Setting.

BACKGROUND: Inflammatory bowel disease is a chronic, relapsing, and remitting inflammatory disorder that despite advances in medical therapy often requires hospitalization for treatment of acute flares with intravenous corticosteroids. Many patients will not respond to corticosteroids and require infliximab or cyclosporine as rescue therapy. If medical therapy fails, definitive surgical management is required. Recently, Janus Kinase inhibitors, including upadacitinib, have been proposed as an alternative rescue therapy. AIMS: We hypothesized that upadacitinib may be effective in treating acute severe colitis. METHODS: A retrospective review of 12 inflammatory bowel disease patients admitted for acute severe colitis who received upadacitinib induction therapy was performed. The rates of surgery, repeat or prolonged steroid use, and re-admission within 90 days of index hospitalization were measured. The need for re-induction with upadacitinib, change in medical therapy, rates of clinical remission, change in 6-point partial Mayo score, and laboratory markers of inflammation were measured as secondary outcomes. RESULTS: Five patients met the primary composite endpoint including four patients requiring surgery and one additional patient being unable to withdraw steroids within 90 days of hospital discharge. One patient required re-induction with upadacitinib within 90 days and no patients required change in medical therapy within 90 days. Most patients who did not undergo surgery were in clinical remission within 90 days and showed clinical improvement with decreased 6-point partial Mayo scores. CONCLUSION: Upadacitinib may be effective salvage therapy for acute severe colitis, but larger controlled trials are required to validate these results.

The Burden of Work Productivity and Activity Impairment in Patients with Psoriasis, Psoriatic Arthritis, Ulcerative Colitis, and Crohn's Disease.

BACKGROUND: Comparisons among autoimmune diseases enable understanding of the burden and factors associated with work productivity loss and impairment. AIMS: The objective was to compare work productivity and activity and associated factors among patients with inflammatory bowel diseases and other autoimmune conditions. METHODS: This cross-sectional study included employed, adult patients (age 20-64 years) in the CorEvitas Inflammatory Bowel Disease, Psoriasis, and Psoriatic Arthritis/Spondyloarthritis Registries between 5/2017 and 6/2020. Any patient-reported impairment on four domains of the Work Productivity and Activity Index (WPAI) was collected across registries. Prevalence for each autoimmune disease was reported and stratified by disease activity using direct age-sex-standardization. Factors associated with the presence of any WPAI were identified in logistic regression models. RESULTS: A total of 7,169 patients with psoriasis (n = 4,768, 67%), psoriatic arthritis (n = 1,208, 17%), Crohn's disease (CD, n = 621, 9%), and ulcerative colitis (UC, n = 572, 8%) met inclusion criteria. Among patients not in remission across all disease cohorts, the age-sex-standardized prevalence of any presenteeism, work productivity loss, and activity impairment ranged from 54 to 97%. Patients with CD in remission had higher standardized prevalence of presenteeism (53% [48-57%]) and work productivity loss (54% [49-59%]), compared to those from other cohorts (presenteeism [range: 33-39%] and work productivity loss [range: 37-41%]). For all WPAI domains, the strongest adjusted associations were for moderate to severe disease activity and psychosocial symptoms. CONCLUSIONS: Patients with moderate to severe disease activity reported the highest WPAI burden. However, patients in remission or mild disease activity also report some WPAI burden, emphasizing a multidisciplinary treatment approach to improve work productivity loss and impairment.

Inflammatory Bowel Disease-Associated Arthritis Is Associated with Concomitant Autoimmune and Inflammatory Disorders.

BACKGROUND: Extraintestinal Manifestations (EIMs) are a common and potentially debilitating complication of Inflammatory Bowel Diseases (IBD), sometimes requiring additional treatment beyond those used to control intestinal disease. IBD-associated arthritis (IAA), a form of spondyloarthritis, is associated with several factors including disease location, sex, and IBD type. However, much remains unknown about other clinical factors predicting development of EIMs. Our goal was to identify additional factors associated with IAA. METHODS: Participants in the LOCATION-IBD cohort were included in this analysis. We performed univariate and multivariate analysis of demographics, clinical data, and patient-reported outcomes data. RESULTS: The LOCATION-IBD cohort included 182 participants with (n = 53) and without (n = 110) joint EIMs and with joint pain of unclear etiology (n = 19). In a multivariate analysis comparing those with and without joint EIMs, female sex (OR = 2.5, p = 0.014), the presence of concomitant autoimmune and inflammatory disorders (OR = 2.5, p = 0.038), and Crohn's disease (OR = 2.9, p = 0.026) were associated with the presence of joint EIMs. CONCLUSION: This analysis reveals patients with IAA are more likely to have concomitant autoimmune disorders. Further studies are needed to confirm this association, understand the mechanisms underlying the common pathogenesis of these concurrent disorders, and evaluate their impact on the treatment of IAA.

Risk for Chronic Kidney Disease Progression After Acute Kidney Injury: Findings From the Chronic Renal Insufficiency Cohort Study.

BACKGROUND: Prior studies associating acute kidney injury (AKI) with more rapid subsequent loss of kidney function had methodological limitations, including inadequate control for differences between patients who had AKI and those who did not. OBJECTIVE: To determine whether AKI is independently associated with subsequent kidney function trajectory among patients with chronic kidney disease (CKD). DESIGN: Multicenter prospective cohort study. SETTING: United States. PARTICIPANTS: Patients with CKD (n = 3150). MEASUREMENTS: Hospitalized AKI was defined by a 50% or greater increase in inpatient serum creatinine (SCr) level from nadir to peak. Kidney function trajectory was assessed using estimated glomerular filtration rate (eGFR) based on SCr level (eGFRcr) or cystatin C level (eGFRcys) measured at annual study visits. RESULTS: During a median follow-up of 3.9 years, 433 participants had at least 1 AKI episode. Most episodes (92%) had stage 1 or 2 severity. There were decreases in eGFRcr (-2.30 [95% CI, -3.70 to -0.86] mL/min/1.73 m2) and eGFRcys (-3.61 [CI, -6.39 to -0.82] mL/min/1.73 m2) after AKI. However, in fully adjusted models, the decreases were attenuated to -0.38 (CI, -1.35 to 0.59) mL/min/1.73 m2 for eGFRcr and -0.15 (CI, -2.16 to 1.86) mL/min/1.73 m2 for eGFRcys, and the CI bounds included the possibility of no effect. Estimates of changes in eGFR slope after AKI determined by either SCr level (0.04 [CI, -0.30 to 0.38] mL/min/1.73 m2 per year) or cystatin C level (-0.56 [CI, -1.28 to 0.17] mL/min/1.73 m2 per year) also had CI bounds that included the possibility of no effect. LIMITATIONS: Few cases of severe AKI, no adjudication of AKI cause, and lack of information about nephrotoxic exposures after hospital discharge. CONCLUSION: After pre-AKI eGFR, proteinuria, and other covariables were accounted for, the association between mild to moderate AKI and worsening subsequent kidney function in patients with CKD was small. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.

Ontologies related to livestock for the Global Burden of Animal Diseases programme: a review.

The Global Burden of Animal Diseases (GBADs) programme aims to assess the impact of animal health on agricultural animals, livestock production systems and associated communities worldwide. As part of the objectives of GBADs'Animal Health Ontology theme, the programme reviewed conceptual frameworks, ontologies and classification systems in biomedical science. The focus was on data requirements in animal health and the connections between animal health and human and environmental health. In May 2023, the team conducted searches of recognised repositories of biomedical ontologies, including BioPortal, Open Biological and Biomedical Ontology Foundry, and Ontology Lookup Service, to identify animal and livestock ontologies and those containing relevant concepts. Sixteen ontologies were found, covering topics such as surveillance, anatomy and genetics. Notable examples include the Animal Trait Ontology for Livestock, the Animal Health Surveillance Ontology, the National Center for Biotechnology Information Taxonomy and the Uberon Multi-Species Anatomy Ontology. However, some ontologies lacked class definitions for a significant portion of their classes. The review highlights the need for domain evidence to support proposed models, critical appraisal of external ontologies before reuse, and external expert reviews along with statistical tests of agreements. The findings from this review informed the structural framework, concepts and rationales of the animal health ontology for GBADs. This animal health ontology aims to increase the interoperability and transparency of GBADs data, thereby enabling estimates of the impacts of animal diseases on agriculture, livestock production systems and associated communities globally.

Le programme " Impact mondial des maladies animales " (GBADs) vise à évaluer l'impact de la santé animale sur les animaux d'élevage, les systèmes de production animale et les communautés liées à ce secteur d'activités dans le monde. Afin de définir une ontologie de la santé animale répondant aux objectifs du GBADs, le programme a procédé à un examen des cadres conceptuels, des ontologies et des systèmes de classification actuellement appliqués en sciences biomédicales. Il s'agissait de définir les besoins en données dans le domaine de la santé animale ainsi que les connexions entre la santé animale, la santé publique et la santé environnementale. En mai 2023, l'équipe a procédé à des recherches dans des référentiels reconnus d'ontologies biomédicales, notamment BioPortal, Open Biological and Biomedical Ontology Foundry et Ontology Lookup Service, afin de recenser les ontologies relatives aux animaux et au bétail ainsi que celles contenant des concepts pertinents. Seize ontologies ont été relevées, couvrant des thèmes tels que la surveillance, l'anatomie et la génétique. Parmi les exemples notables on peut citer : Animal Trait Ontology for Livestock (ontologie dédiée aux caractères phénotypiques des animaux d'élevage), Animal Health Surveillance Ontology (ontologie dédiée à la surveillance de la santé animale), National Center for Biotechnology Information Taxonomy (la base de données Taxonomie du Centre américain pour les informations biotechnologiques), et Uberon Multi-Species Anatomy Ontology (ontologie anatomique représentant diverses espèces animales). Il a cependant été constaté que certaines ontologies ne disposent pas de définitions de classes pour une grande partie des classes qui les composent. L'examen a souligné l'importance d'étayer les modèles proposés par des données issues des spécialités en question, de procéder à une évaluation critique des ontologies externes avant de les réutiliser et de faire effectuer des examens complémentaires par des experts externes ainsi que des tests statistiques de concordance. Les résultats de cette étude ont apporté des éléments permettant de définir le cadre structurel, les concepts et les principes de l'ontologie relative à la santé animale destinée au GBADs. Cette ontologie de la santé animale vise à accroître l'interopérabilité et la transparence des données du GBADs, ce qui permet d'effectuer des estimations de l'impact des maladies animales sur l'agriculture, les systèmes de production animale et les communautés associées à ce secteur d'activités à l'échelle mondiale.

El programa sobre el impacto global de las enfermedades animales (GBADs) tiene como objetivo evaluar el impacto de la sanidad animal en los animales de granja, los sistemas de producción ganadera y las comunidades conexas en todo el mundo. Como parte de los objetivos en torno al tema de la ontología de la sanidad animal del GBADs, el programa revisó marcos conceptuales, ontologías y sistemas de clasificación en el ámbito de la ciencia biomédica. Se hizo hincapié en los requisitos de datos sobre la sanidad animal y en las conexiones entre la sanidad animal y la salud humana y ambiental. En mayo de 2023, el equipo realizó búsquedas en repositorios reconocidos de ontologías biomédicas, como BioPortal, Open Biological and Biomedical Ontology Foundry y Ontology Lookup Service, para identificar no solo ontologías animales y ganaderas, sino también aquellas que incluyeran conceptos relevantes. En este sentido, se encontraron dieciséis ontologías, que abarcan temas como vigilancia, anatomía y genética. Entre los ejemplos más destacados figuran Animal Trait Ontology for Livestock (Ontología de Características Animales para el Ganado), Animal Health Surveillance Ontology (Ontología de Vigilancia de la Sanidad Animal), National Center for Biotechnology Information Taxonomy (la base de datos Taxonomía del Centro Nacional para la Información Biotecnológica) y Uberon Multi-Species Anatomy Ontology (Ontología Anatómica de Especies Múltiples). Sin embargo, algunas ontologías carecían de definiciones para una parte significativa de sus clases. La revisión pone de relieve la necesidad de contar con datos probatorios del ámbito en cuestión que respalden los modelos propuestos, una evaluación crítica de las ontologías externas antes de su reutilización y revisiones de expertos externos junto con pruebas estadísticas de los acuerdos. Los resultados de esta revisión han servido de base para el marco estructural, los conceptos y los fundamentos de la ontología de la sanidad animal para el GBADs. Esta ontología pretende aumentar la interoperabilidad y la transparencia de los datos del GBADs, permitiendo así estimar el impacto de las enfermedades animales en la agricultura, los sistemas de producción ganadera y las comunidades conexas en todo el mundo.

Global Burden of Animal Diseases informatics strategy, data quality and model interoperability.

The estimation of the global burden of animal diseases requires the integration of multidisciplinary models: economic, statistical, mathematical and conceptual. The output of one model often serves as input for another; therefore, consistency of the model components is critical. The Global Burden of Animal Diseases (GBADs) Informatics team aims to strengthen the scientific foundations of modelling by creating tools that address challenges related to reproducibility, as well as model, data and metadata interoperability. Aligning with these aims, several tools are under development: a) GBADs'Trusted Animal Information Portal (TAIL) is a data acquisition platform that enhances the discoverability of data and literature and improves the user experience of acquiring data. TAIL leverages advanced semantic enrichment techniques (natural language processing and ontologies) and graph databases to provide users with a comprehensive repository of livestock data and literature resources. b) The interoperability of GBADs'models is being improved through the development of an R-based modelling package and standardisation of parameter formats. This initiative aims to foster reproducibility, facilitate data sharing and enable seamless collaboration among stakeholders. c) The GBADs Knowledge Engine is being built to foster an inclusive and dynamic user community by offering data in multiple formats and providing user-friendly mechanisms to garner feedback from the community. These initiatives are critical in addressing complex challenges in animal health and underscore the importance of combining scientific rigour with user-friendly interfaces to empower global efforts in safeguarding animal populations and public health.

L'estimation de l'impact mondial des maladies animales nécessite l'utilisation intégrée de modèles issus de diverses disciplines : économiques, statistiques, mathématiques et conceptuels. Les données de sortie d'un modèle constituent souvent celles d'entrée d'un autre modèle ; la cohérence des composantes des différents modèles est donc primordiale. L'équipe informatique du programme " Impact mondial des maladies animales " (GBADs) s'efforce de consolider les bases scientifiques de l'utilisation des modèles en mettant au point des outils permettant de résoudre les problèmes de reproductibilité et d'améliorer l'interopérabilité entre les différents modèles, données et métadonnées. En phase avec ces objectifs, plusieurs outils sont en cours de développement : a) le Portail du GBADs " Trusted Animal Information Portal " (TAIL) est une plateforme d'acquisition de données qui facilite l'accès aux données et à la littérature, tout en améliorant l'expérience utilisateur lors de l'acquisition des données. Le portail TAIL s'appuie sur des techniques avancées d'enrichissement sémantique (traitement du langage naturel et ontologies) et sur des bases de données graphiques pour apporter aux utilisateurs un référentiel complet des données et des ressources documentaires relatives aux animaux d'élevage ; b) l'interopérabilité des modèles du GBADs est en voie d'amélioration grâce à la mise au point d'un progiciel de modélisation fondé sur R et à la normalisation des formats de paramètres. Cette initiative vise à favoriser la reproductibilité, à faciliter le partage de données et à permettre une collaboration transparente entre les parties prenantes ; c) le moteur de connaissances du GBADs, en cours de construction, vise à encourager une communauté d'utilisateurs inclusive et dynamique en proposant des données dans une multiplicité de formats ainsi que des mécanismes conviviaux pour recueillir les commentaires de la communauté. Ces initiatives se révéleront indispensables pour relever les défis complexes de la santé animale et soulignent l'importance d'associer une grande rigueur scientifique à la convivialité des interfaces, afin de donner encore plus d'élan aux efforts déployés dans le monde pour protéger les populations animales et la santé publique.

La estimación del impacto global de las enfermedades animales requiere la integración de modelos multidisciplinarios: económicos, estadísticos, matemáticos y conceptuales. El resultado de un modelo a menudo sirve de entrada para otro; por lo tanto, la coherencia entre los distintos componentes es fundamental. El equipo de informática del programa sobre el Impacto Global de las Enfermedades Animales (GBADs) tiene como objetivo fortalecer los fundamentos científicos de la modelización mediante la creación de herramientas que aborden los retos relacionados con la reproducibilidad, así como con la interoperabilidad de los modelos, datos y metadatos. En consonancia con estos objetivos, se están desarrollando varias herramientas: a) El Portal del GBADs "Trusted Animal Information Portal" (TAIL) es una plataforma de adquisición de datos que mejora tanto la descubribilidad de datos y bibliografía como la experiencia del usuario a la hora de obtener datos. El portal TAIL utiliza técnicas avanzadas de enriquecimiento semántico (procesamiento del lenguaje natural y ontologías), así como bases de datos de grafos, para ofrecer a los usuarios un repositorio completo de datos sobre ganadería y recursos bibliográficos. b) Se está mejorando la interoperabilidad de los modelos del GBADs mediante el desarrollo de un paquete de modelización en R y la normalización de los formatos de los parámetros. Esta iniciativa pretende fomentar la reproducibilidad, facilitar el intercambio de datos y permitir una colaboración fluida entre las partes interesadas. c) El Motor de Conocimiento del GBADs se está construyendo con el objetivo de fomentar una comunidad de usuarios inclusiva y dinámica, ofreciendo datos en diferentes formatos y proporcionando mecanismos fáciles de usar para recopilar comentarios de la comunidad. Estas iniciativas son fundamentales para hacer frente a los complejos retos en el ámbito de la sanidad animal y subrayan la importancia de combinar el rigor científico con interfaces fáciles de usar para potenciar los esfuerzos mundiales encaminados a proteger a las poblaciones animales y la salud pública.

Assessment of Combined Resection-Anastomosis and Urethropexy in Dogs with Urethral Prolapse.

The literature regarding surgical repair of urethral prolapse in dogs is limited and associated with a high recurrence rate. We hypothesized that combined resection and anastomosis (R&A) with urethropexy would be associated with less recurrence of urethral prolapse compared with R&A alone. Medical records of dogs managed surgically for urethral prolapse were reviewed (2013-2023) from three tertiary care hospitals. Inclusion criteria included complete medical records, including surgery reports, short-term postoperative complications, and longer-term follow-up. Forty-six male dogs successfully met the inclusion criteria (16 castrated; 30 intact). Brachycephalic breeds were overrepresented (37/46, 80%). Surgical repair by R&A alone (n = 27), urethropexy alone (n = 6), or a combined R&A and urethropexy (n = 13) was performed. Recurrence rates for these techniques were 13/27 (48%), 2/6 (33%), and 1/13 (8%), respectively. The recurrence rate of urethral prolapse treated by a combined R&A and urethropexy was significantly lower (P < .05) than R&A alone, despite more dogs being overweight and less surgeon experience (each P < .05). Interestingly, dogs neutered before initial diagnosis may be more likely to have postoperative recurrence. Considering general anesthesia risks, an initial combination procedure for urethral prolapse may help prevent recurrence.