The Gene Ontology knowledgebase in 2023.

The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms. Here, we provide an updated overview of the GO knowledgebase, as well as the efforts of the broad, international consortium of scientists that develops, maintains, and updates the GO knowledgebase. The GO knowledgebase consists of three components: (1) the GO-a computational knowledge structure describing the functional characteristics of genes; (2) GO annotations-evidence-supported statements asserting that a specific gene product has a particular functional characteristic; and (3) GO Causal Activity Models (GO-CAMs)-mechanistic models of molecular "pathways" (GO biological processes) created by linking multiple GO annotations using defined relations. Each of these components is continually expanded, revised, and updated in response to newly published discoveries and receives extensive QA checks, reviews, and user feedback. For each of these components, we provide a description of the current contents, recent developments to keep the knowledgebase up to date with new discoveries, and guidance on how users can best make use of the data that we provide. We conclude with future directions for the project.

Usefulness of Combining NT-proBNP Level and Right Atrial Diameter for Simple and Early Noninvasive Detection of Pulmonary Hypertension Among Adult Patients with Atrial Septal Defect.

BACKGROUND: Atrial septal defect developed pulmonary hypertension (ASD-PH) at first diagnosis due to late presentation are common in Indonesia. Transthoracic echocardiogram (TTE) is a common tool to detect ASD-PH, before proceeding to invasive procedure. The NT-proBNP measurement to screen ASD-PH is not yet considered the standard approach, especially in limited resource conditions. The objective of this study is to assess the value of NT-proBNP, along with simple TTE parameter, to screen PH among adults with ASD. METHODS: This was a cross-sectional study. The subjects were adult ASD-PH patients from the COHARD-PH  registry (n=357). Right heart catheterization (RHC) was performed to diagnose PH. Blood sample was withdrawn during RHC for NT-proBNP measurement. The TTE was performed as standard procedure and its regular parameters were assessed, along with NT-proBNP, to detect PH. RESULTS: Two parameters significantly predicted PH, namely NT-proBNP and right atrial (RA) diameter. The cut-off of NT-proBNP to detect PH was ≥140 pg/mL. The cut-off of RA diameter to detect PH was ≥46.0 mm. The combined values of NT-proBNP level ≥140 pg/mL and RA diameter ≥46.0 mm yielded 46.6% sensitivity, 91.8% specificity, 54.3% accuracy, 96.5% positive predictive value and 26.2% negative predictive value to detect PH, which were better than single value. CONCLUSION: NT-proBNP level ≥140 pg/mL represented PH in adult ASD patients. The NT-proBNP level ≥140 pg/mL and RA diameter ≥46.0 mm had a pre-test probability measures to triage patients needing more invasive procedure and also to determine when and if to start the PH-specific treatment.

The screening of congenital heart disease by cardiac auscultation and 12-lead electrocardiogram among Indonesian elementary school students.

BACKGROUND: Screening for congenital heart disease (CHD) in school students is well-established in high-income countries; however, data from low-to-middle-income countries including Indonesia are limited. AIM: This study aimed to evaluate CHD screening methods by cardiac auscultation and 12-lead electrocardiogram to obtain the prevalence of CHD, confirmed by transthoracic echocardiography, among Indonesian school students. METHODS: We conducted a screening programme in elementary school students in the Province of Special Region of Yogyakarta, Indonesia. The CHD screening was integrated into the annual health screening. The trained general practitioners and nurses participated in the screening. The primary screening was by cardiac auscultation and 12-lead electrocardiogram. The secondary screening was by transthoracic echocardiography performed on school students with abnormal findings in the primary screening. RESULTS: A total of 6116 school students were screened within a 2-year period. As many as 329 (5.38%) school students were detected with abnormalities. Of those, 278 students (84.49%) had an abnormal electrocardiogram, 45 students (13.68%) had heart murmurs, and 6 students (1.82%) had both abnormalities. The primary screening programme was successfully implemented. The secondary screening was accomplished for 260 school students, and 18 students (6.9%) had heart abnormalities with 7 (2.7%) who were confirmed with septal defects and 11 (4.2%) had valve abnormalities. The overall prevalence was 0.29% (18 out of 6116). CONCLUSIONS: The primary screening by cardiac auscultation and 12-lead electrocardiogram was feasible and yielded 5.38% of elementary school students who were suspected with CHD. The secondary screening resulted in 6.9% confirmed cardiac abnormalities. The cardiac abnormality prevalence was 0.29%.