Plasma proteome-wide analysis of cerebral small vessel disease identifies novel biomarkers and disease pathways.

Cerebral small vessel disease (SVD), as defined by neuroimaging characteristics such as white matter hyperintensities (WMHs), cerebral microhemorrhages (CMHs), and lacunar infarcts, is highly prevalent and has been associated with dementia risk and other clinical sequelae. Although conditions such as hypertension are known to contribute to SVD, little is known about the diverse set of subclinical biological processes and molecular mediators that may also influence the development and progression of SVD. To better understand the mechanisms underlying SVD and to identify novel SVD biomarkers, we used a large-scale proteomic platform to relate 4,877 plasma proteins to MRI-defined SVD characteristics within 1,508 participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort. Our proteome-wide analysis of older adults (mean age: 76) identified 13 WMH-associated plasma proteins involved in synaptic function, endothelial integrity, and angiogenesis, two of which remained associated with late-life WMH volume when measured nearly 20 years earlier, during midlife. We replicated the relationship between 9 candidate proteins and WMH volume in one or more external cohorts; we found that 11 of the 13 proteins were associated with risk for future dementia; and we leveraged publicly available proteomic data from brain tissue to demonstrate that a subset of WMH-associated proteins was differentially expressed in the context of cerebral atherosclerosis, pathologically-defined Alzheimer's disease, and cognitive decline. Bidirectional two-sample Mendelian randomization analyses examined the causal relationships between candidate proteins and WMH volume, while pathway and network analyses identified discrete biological processes (lipid/cholesterol metabolism, NF-kB signaling, hemostasis) associated with distinct forms of SVD. Finally, we synthesized these findings to identify two plasma proteins, oligodendrocyte myelin glycoprotein (OMG) and neuronal pentraxin receptor (NPTXR), as top candidate biomarkers for elevated WMH volume and its clinical manifestations.

Proteomic Profile of the ICAM1 p.K56M HFpEF Risk Variant.

A common missense variant in ICAM1 among African American individuals (rs5491; pK56M) has been associated with risk of heart failure with preserved ejection fraction (HFpEF), but the pathways that lead to HFpEF among those with this variant are not clear. In this analysis of 92 circulating proteins and their associated networks, we identified 7 circulating inflammatory proteins associated with rs5491 among >600 African American individuals. Using weighted coexpression network analysis, 3 protein networks were identified, one of which was associated with rs5491. This protein network was most highly represented by members of the tumor necrosis receptor superfamily. The rs5491 variant demonstrated an inflammatory proteomic profile in a separate cohort of African American individuals. This analysis identifies inflammatory pathways that may drive HFpEF among African American individuals with the ICAM1 pK56M (rs5491) variant.

Whole-genome sequencing in 333,100 individuals reveals rare non-coding single variant and aggregate associations with height.

The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N = 200,003), TOPMed (N = 87,652) and All of Us (N = 45,445). We performed rare ( < 0.1% minor-allele-frequency) single-variant and aggregate testing of non-coding variants in regulatory regions based on proximal-regulatory, intergenic-regulatory and deep-intronic annotation. We observed 29 independent variants associated with height at P < 6 × 10 - 10 after conditioning on previously reported variants, with effect sizes ranging from -7cm to +4.7 cm. We also identified and replicated non-coding aggregate-based associations proximal to HMGA1 containing variants associated with a 5 cm taller height and of highly-conserved variants in MIR497HG on chromosome 17. We have developed an approach for identifying non-coding rare variants in regulatory regions with large effects from whole-genome sequencing data associated with complex traits.

Transdiagnostic modeling of clinician-rated symptoms in affective and nonaffective psychotic disorders.

Prevailing factor models of psychosis are centered on schizophrenia-related disorders defined by the Diagnostic and Statistical Manual of Mental Disorders and International Classification of Diseases, restricting generalizability to other clinical presentations featuring psychosis, even though affective psychoses are more common. This study aims to bridge this gap by conducting exploratory and confirmatory factor analyses, utilizing clinical ratings collected from patients with either affective or nonaffective psychoses (n = 1,042). Drawing from established clinical instruments, such as the Positive and Negative Syndrome Scale, Young Mania Rating Scale, and Montgomery-Åsberg Depression Rating Scale, a broad spectrum of core psychotic symptoms was considered for the model development. Among the candidate models considered, including correlated factors and multifactor models, a model with seven correlated factors encompassing positive symptoms, negative symptoms, depression, mania, disorganization, hostility, and anxiety was most interpretable with acceptable fit. The seven factors exhibited expected associations with external validators, were replicable through cross-validation, and were generalizable across affective and nonaffective psychoses. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Comparison of a new type of Dark Matter with the Milky Way and M31 grand rotation curves.

In the electron Born self-energy (eBse) model, free electrons are of finite-size and possess both a rest mass, me, as well as, a Born mass, meB = 74,000 me. The Born mass, which originates from the energy contained within the electric field that surrounds a finite-sized electron, serves as a Dark Matter (DM) particle in this theory (designated eBDM, electron Born Dark Matter). The equation of state for meB is w = -1, which implies that two Born masses experience a repulsive gravitational interaction. This repulsive gravitational interaction stabilizes the formation of a DM halo of meB particles, of typical halo size ~ 100 kpc, around a central mass M (e.g. a galaxy), where this gravitational stability arises from the competing attractive M - meB and repulsive meB - meB interactions. A solution of the linearized Poisson-Boltzmann equation, for this system, allows one to derive an expression for the rotational velocity VeBDM(R), as a function of radius R from the galactic center. A composite model composed of rotational velocity contributions from the galactic bulge, galactic disk, as well as, VeBDM(R) is found to provide a good description of the Grand Rotation Curves for the Milky Way and M31 galaxies.

Rare variant contribution to the heritability of coronary artery disease.

Whole genome sequences (WGS) enable discovery of rare variants which may contribute to missing heritability of coronary artery disease (CAD). To measure their contribution, we apply the GREML-LDMS-I approach to WGS of 4949 cases and 17,494 controls of European ancestry from the NHLBI TOPMed program. We estimate CAD heritability at 34.3% assuming a prevalence of 8.2%. Ultra-rare (minor allele frequency ≤ 0.1%) variants with low linkage disequilibrium (LD) score contribute ~50% of the heritability. We also investigate CAD heritability enrichment using a diverse set of functional annotations: i) constraint; ii) predicted protein-altering impact; iii) cis-regulatory elements from a cell-specific chromatin atlas of the human coronary; and iv) annotation principal components representing a wide range of functional processes. We observe marked enrichment of CAD heritability for most functional annotations. These results reveal the predominant role of ultra-rare variants in low LD on the heritability of CAD. Moreover, they highlight several functional processes including cell type-specific regulatory mechanisms as key drivers of CAD genetic risk.

Preoperative Immersive Virtual Reality (iVR) Applied to Percutaneous Nephrolithotomy: A Prospective Randomized Clinical Study of Surgical Planning and Clinical Outcomes.

PURPOSE: Percutaneous nephrolithotomy (PCNL) is the procedure of choice for the management of complex or large renal stones. A major challenge for the surgeon, however, is the need to assimilate the nearly 2000 static images from a CT scan into a functional mental image to enable surgical planning. Accordingly, we investigated the potential of immersive virtual reality (iVR) to enhance surgical planning and its impact on the outcomes among patients undergoing PCNL. MATERIALS AND METHODS: Between 2019-2023, 175 patients undergoing PCNL were pre-operatively randomized into a CT-only group (N=89) or a CT+iVR group (N=86). CT scans were rendered into iVR models that allowed the surgeon not only to visualize and manipulate each patient's relevant anatomy, but also simulate the percutaneous approach to the proposed calyx. Post-operative CT scans were defined as absolute stone-free, <2mm remnants or 2.1-4mm remnants. RESULTS: Pre-operative visualization of the iVR model resulted in a changed calyx of entry in 30% of cases. The CT+iVR group had a significant improvement in absolute stone-free rate (33.70% vs. 20.22%, p=0.043) and overall <4mm remnant rate (62.79% vs. 48.20%, p=0.044). Clavien-Dindo II+IIIa complications were less in the iVR group (3.48% vs. 12.30%, p=0.03). The results were independent of the surgeon's years of PCNL experience. CONCLUSIONS: Pre-operative iVR model visualization benefited surgeons and patients alike. From a surgical standpoint, viewing the iVR model resulted in a safer, more effective percutaneous stone removal procedure.

Clinical implications of reconsideration of enthesitis/enthesopathy/enthesial erosion, as tendon attachment-localized avulsions and stress fracture equivalents.

Recognizing the mechanical origin of enthesitis/enthesopathy and the avulsion-nature of what had previously been considered erosions, it seems inappropriate to attribute it to stresses related to a person's normal activities. Conversely, sudden or unconditioned repetitive stresses appears the more likely culprit. Studies of enthesial reaction have lacked standardization as to findings present among individuals who appear to be healthy. Clinical evaluation by palpation and manipulation may be as effective as application of radiologic techniques. Recognition of the mechanical nature of the disease, including individuals with inflammatory arthritis suggests prescription of mechanical solutions that reduce stresses across the involved enthesis.

Comparative efficacy and safety of anti-cryptosporidial agents: an in vitro study on nitazoxanide, halofuginone lactate, KDU731, and paromomycin against Cryptosporidium parvum.

This study evaluated the in vitro effectiveness of anti-cryptosporidial agents nitazoxanide, halofuginone, the pyrazolopyridine analog KDU731, and paromomycin (PMC) in combating the significant zoonotic pathogen Cryptosporidium parvum. The study utilized HCT-8 host cells to culture C. parvum and fluorescent microscopy/quantitative PCR (qPCR) for detecting parasitic growth. The efficacy of the compounds was assessed by calculating their inhibitory concentrations (IC) against the total growth of C. parvum at 48 h post-infection. The study further investigated the impact of these compounds on early parasitophorous vacuole (PV) formation, merozoite egress, host cell viability, and cell growth cycle. KDU731 displayed the most promising profile, with low nanomolar (102 nM ± 2.28) activity and negligible host cell toxicity. This study offers new insights into the relative efficacy and safety of various anti-cryptosporidial compounds, highlighting their stage-specific effects on C. parvum and the consequential impacts on host cells. Identifying safe and effective anti-cryptosporidial agents contributes significantly to the One Health approach, which emphasizes the importance of integrated strategies in controlling zoonotic diseases.

p38α kinase governs muscle strength through PGC1α in mice.

AIMS: Skeletal muscle, with its remarkable plasticity and dynamic adaptation, serves as a cornerstone of locomotion and metabolic homeostasis in the human body. Muscle tissue, with its extraordinary capacity for force generation and energy expenditure, plays a fundamental role in the movement, metabolism, and overall health. In this context, we sought to determine the role of p38α in mitochondrial metabolism since mitochondrial dynamics play a crucial role in the development of muscle-related diseases that result in muscle weakness. METHODS: We conducted our study using male mice (MCK-cre, p38αMCK-KO and PGC1α MCK-KO) and mouse primary myoblasts. We analyzed mitochondrial metabolic, physiological parameters as well as proteomics, western blot, RNA-seq analysis from muscle samples. RESULTS: Our findings highlight the critical involvement of muscle p38α in the regulation of mitochondrial function, a key determinant of muscle strength. The absence of p38α triggers changes in mitochondrial dynamics through the activation of PGC1α, a central regulator of mitochondrial biogenesis. These results have substantial implications for understanding the complex interplay between p38α kinase, PGC1α activation, and mitochondrial content, thereby enhancing our knowledge in the control of muscle biology. CONCLUSIONS: This knowledge holds relevance for conditions associated with muscle weakness, where disruptions in these molecular pathways are frequently implicated in diminishing physical strength. Our research underscores the potential importance of targeting the p38α and PGC1α pathways within muscle, offering promising avenues for the advancement of innovative treatments. Such interventions hold the potential to improve the quality of life for individuals affected by muscle-related diseases.

Association of Socioeconomic Status and Reasons for Companion Animal Relinquishment.

It is important to understand the reasons for companion animal relinquishment to help reduce the financial and ethical problems arising from too many dogs and cats in shelters. This study investigates the socioeconomic factors and reasons behind companion animal relinquishment in Australia, utilizing data from five animal shelters, over a five-year period (Financial Year 2018/19 to 2022/23). Descriptive statistics reveal that the median Index of Relative Socio-Economic Advantage and Disadvantage (IRSAD) decile of companion animal guardians who relinquished their companion animal was decile 4 out of 10, indicating that they live in areas of lower-than-average socioeconomic status. Cats accounted for 59.4% and dogs for 40.6% of all relinquishments, with more relinquishments from lower socioeconomic deciles (1-5) (cats: 62.6%, dogs: 65.8%). The median age of relinquished cats was 5 months and dogs 16 months, with human factor-related issues (e.g., Housing, Financial Constraints, Human Healthcare) cited in 86% of cases. Descriptive analysis for the five financial years shows a declining trend in numbers of relinquishments, with housing issues (31.2%) identified as the primary reason, followed by ownership decisions (16.2%), financial constraints (11.2%), and human health issues (10.4%). Comparing the reasons for relinquishment between lower (decile 1-5) and higher (decile 6-10) socioeconomic status demonstrated that financial difficulties were a more common reason in lower vs. higher socioeconomic groups, while human health and family-related issues are more common in higher vs. lower socioeconomic groups. These findings highlight the critical role of socioeconomic factors in understanding why people relinquish their companion animals, which can inform targeted interventions to support companion animal welfare across different socioeconomic backgrounds.

Association analysis of mitochondrial DNA heteroplasmic variants: Methods and application.

We rigorously assessed a comprehensive association testing framework for heteroplasmy, employing both simulated and real-world data. This framework employed a variant allele fraction (VAF) threshold and harnessed multiple gene-based tests for robust identification and association testing of heteroplasmy. Our simulation studies demonstrated that gene-based tests maintained an appropriate type I error rate at α = 0.001. Notably, when 5 % or more heteroplasmic variants within a target region were linked to an outcome, burden-extension tests (including the adaptive burden test, variable threshold burden test, and z-score weighting burden test) outperformed the sequence kernel association test (SKAT) and the original burden test. Applying this framework, we conducted association analyses on whole-blood derived heteroplasmy in 17,507 individuals of African and European ancestries (31 % of African Ancestry, mean age of 62, with 58 % women) with whole genome sequencing data. We performed both cohort- and ancestry-specific association analyses, followed by meta-analysis on both pooled samples and within each ancestry group. Our results suggest that mtDNA-encoded genes/regions are likely to exhibit varying rates in somatic aging, with the notably strong associations observed between heteroplasmy in the RNR1 and RNR2 genes (p < 0.001) and advance aging by the Original Burden test. In contrast, SKAT identified significant associations (p < 0.001) between diabetes and the aggregated effects of heteroplasmy in several protein-coding genes. Further research is warranted to validate these findings. In summary, our proposed statistical framework represents a valuable tool for facilitating association testing of heteroplasmy with disease traits in large human populations.

Mesenchymal Tumors of the Head and Neck.

The majority of neoplasms of the head and neck are of epithelial origin primarily including mucosal squamous cell neoplasms (papillomas; squamous cell carcinoma) as well as salivary gland neoplasms. However, the full spectrum of mesenchymal neoplasms (benign and malignant) typically arising in soft tissue sites may also develop in superficial layers of the upper aerodigestive tract. The diversity of mesenchymal neoplasms arising in the head and neck is beyond the scope of this article, and our focus will be on some of the more common and/or diagnostic problematic mesenchymal tumors occurring in the sinonasal tract, oral cavity/odontogenic, pharynx, larynx, and neck.

A Comparison of Skeletal Muscle Diffusion Tensor Imaging Tractography Seeding Methods.

The internal arrangement of a muscle's fibers with respect to its mechanical line of action (muscle architecture) is a major determinant of muscle function. Muscle architecture can be quantified using diffusion tensor magnetic resonance imaging-based tractography, which propagates streamlines from a set of seed points by integrating vectors that represent the direction of greatest water diffusion (and by inference, the local fiber orientation). Previous work has demonstrated that tractography outcomes are sensitive to the method for defining seed points, but this sensitivity has not been fully examined. To do so, we developed a realistic simulated muscle architecture and implemented four novel methods for tract seeding: seeding along the muscle-aponeurosis boundary with an updated procedure for rounding seed points prior to lookup in the muscle boundary mask and diffusion tensor matrix (APO-3); voxel-based seeding throughout the muscle volume at a user-specified spatial frequency (VXL-1); voxel-based seeding throughout the muscle volume at a variable spatial frequency (VXL-2), and seeding near external and internal muscle boundaries (VXL-3). We then implemented these methods in an example human dataset. The updated aponeurosis seeding procedures allow more accurate and robust tract propagation from seed points. The voxel-based seeding methods had quantification outcomes that closely matched the updated aponeurosis seeding method. Further, the voxel-based methods can accelerate the overall workflow and may be beneficial in high throughput analysis of multi-muscle datasets. Continued evaluation of these methods in a wider range of muscle architectures is warranted.

The Genetic Determinants and Genomic Consequences of Non-Leukemogenic Somatic Point Mutations.

Clonal hematopoiesis (CH) is defined by the expansion of a lineage of genetically identical cells in blood. Genetic lesions that confer a fitness advantage, such as point mutations or mosaic chromosomal alterations (mCAs) in genes associated with hematologic malignancy, are frequent mediators of CH. However, recent analyses of both single cell-derived colonies of hematopoietic cells and population sequencing cohorts have revealed CH frequently occurs in the absence of known driver genetic lesions. To characterize CH without known driver genetic lesions, we used 51,399 deeply sequenced whole genomes from the NHLBI TOPMed sequencing initiative to perform simultaneous germline and somatic mutation analyses among individuals without leukemogenic point mutations (LPM), which we term CH-LPMneg. We quantified CH by estimating the total mutation burden. Because estimating somatic mutation burden without a paired-tissue sample is challenging, we developed a novel statistical method, the Genomic and Epigenomic informed Mutation (GEM) rate, that uses external genomic and epigenomic data sources to distinguish artifactual signals from true somatic mutations. We performed a genome-wide association study of GEM to discover the germline determinants of CH-LPMneg. After fine-mapping and variant-to-gene analyses, we identified seven genes associated with CH-LPMneg (TCL1A, TERT, SMC4, NRIP1, PRDM16, MSRA, SCARB1), and one locus associated with a sex-associated mutation pathway (SRGAP2C). We performed a secondary analysis excluding individuals with mCAs, finding that the genetic architecture was largely unaffected by their inclusion. Functional analyses of SMC4 and NRIP1 implicated altered HSC self-renewal and proliferation as the primary mediator of mutation burden in blood. We then performed comprehensive multi-tissue transcriptomic analyses, finding that the expression levels of 404 genes are associated with GEM. Finally, we performed phenotypic association meta-analyses across four cohorts, finding that GEM is associated with increased white blood cell count and increased risk for incident peripheral artery disease, but is not significantly associated with incident stroke or coronary disease events. Overall, we develop GEM for quantifying mutation burden from WGS without a paired-tissue sample and use GEM to discover the genetic, genomic, and phenotypic correlates of CH-LPMneg.

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.