Background In recent years, several hundred autism spectrum disorder (ASD) implicated genes have been discovered impacting a wide range of molecular pathways. However, the molecular underpinning of ASD, particularly from the point of view of ‘brain to behaviour’ pathogenic mechanisms, remains largely unknown. Methods We undertook a study to investigate patterns of spatiotemporal and cell type expression of ASD-implicated genes by integrating large-scale brain single-cell transcriptomes (> million cells) and de novo loss-of-function (LOF) ASD variants (impacting 852 genes from 40,122 cases). Results We identified multiple single-cell clusters from three distinct developmental human brain regions (anterior cingulate cortex, middle temporal gyrus and primary visual cortex) that evidenced high evolutionary constraint through enrichment for brain critical exons and high pLI genes. These clusters also showed significant enrichment with ASD loss-of-function variant genes (p < 5.23 × 10–11) that are transcriptionally highly active in prenatal brain regions (visual cortex and dorsolateral prefrontal cortex). Mapping ASD de novo LOF variant genes into large-scale human and mouse brain single-cell transcriptome analysis demonstrate enrichment of such genes into neuronal subtypes and are also enriched for subtype of non-neuronal glial cell types (astrocyte, p < 6.40 × 10–11, oligodendrocyte, p < 1.31 × 10–09). Conclusion Among the ASD genes enriched with pathogenic de novo LOF variants (i.e. KANK1, PLXNB1), a subgroup has restricted transcriptional regulation in non-neuronal cell types that are evolutionarily conserved. This association strongly suggests the involvement of subtype of non-neuronal glial cells in the pathogenesis of ASD and the need to explore other biological pathways for this disorder.

Understanding host cell heterogeneity is critical for unravelling disease mechanism. Utilizing large scale single-cell transcriptomics, we analysed multiple tissue specimens from patients with life-threatening COVID-19 pneumonia, compared with healthy controls. We identified a subtype of monocyte-derived alveolar macrophages (MoAM) where genes associated with severe COVID-19 comorbidities are significantly upregulated in broncho-alveolar lavage fluid (BALF) of critical cases. FCGR3B consistently demarcated MoAM subset in different samples from severe COVID-19 cohorts and in CCL3L1 -upregulated cells from nasopharyngeal swabs. In silico findings were validated by upregulation of FCGR3B in nasopharyngeal swabs of severe ICU COVID-19 cases, particularly in older patients and those with comorbidities. Additional lines of evidence from transcriptomic data and in vivo of severe COVID-19 cases suggest that FCGR3B may identify a specific subtype of MoAM in patients with severe COVID-19 that may present a novel biomarker for screening and prognosis as well as a potential therapeutic target.

Background: Unnecessary antibiotic prescription to patients with upper respiratory tract infections (URTIs) has led to the increase in antibiotics resistant bacteria rates. In this study, we evaluated the diagnostic accuracy of QuickVue® Dipstick Strep A test (QV-SAT) in children presenting with acute pharyngotonsillitis and its effect on antibiotic prescribing. Methods: A single-gated diagnostic accuracy study of children with fever, runny nose, and tonsillitis presenting to a paediatric clinic between March 2016 and September 2018. Paired throat swabs for QV-SAT and culture were collected. None of the children received antibiotics prior to sample collection. Furthermore, positive predictive value (PPV), negative predictive value (NPV) and likelihood ratios of the test were calculated. Results: 204 children were included in this study. 111 (54.4%) were boys and 146 (71.6%) were under the age of five years. QV-SAT was positive in 44 (21.6%) and throat culture was positive for Group A β- haemolytic Streptococcus (GAS) in 42 (20.6%) of the children. The results of QV-SAT were highly consistent with culture results: only 2 (0.9%) children with negative results had a positive throat culture. The sensitivity of the QV-SAT in the identification of GAS infection was 100% (95% CI 91.6%, 100%) and the NPV was 100% (95% CI 70%, 95%). Only 42 children (21%) were given antibiotics, while 162 (79%) were not. Conclusion: The QV-SAT is a quick and reliable test that can help dramatically reduce antibiotic prescriptions to children presenting with fever and acute pharyngotonsillitis.

BackgroundUnnecessary antibiotic prescription to patients with upper respiratory tract infections (URTIs) has led to the increase in antibiotics resistant bacteria rates. In this study, we evaluated the diagnostic accuracy of QuickVue® Dipstick Strep A test (QV-SAT) in children presenting with acute pharyngotonsillitis and its effect on antibiotic prescribing.MethodsA single-gated diagnostic accuracy study of children with fever, runny nose, and tonsillitis presenting to a paediatric clinic between March 2016 and September 2018. Paired throat swabs for QV-SAT and culture were collected. None of the children received antibiotics prior to sample collection. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the test were calculated.ResultsTwo hundred four children were included in this study. 111 (54.4%) were boys and 146 (71.6%) were under the age of 5 years. QV-SAT was positive in 44 (21.6%) and throat culture was positive for Group A β- haemolytic Streptococcus (GAS) in 42 (20.6%) of the children. The results of QV-SAT were highly consistent with culture results: only 2 (0.9%) children with negative results had a positive throat culture. The sensitivity of the QV-SAT in the identification of GAS infection was 100% (95% CI 91.6%, 100%) and the NPV was 100% (95% CI 99.9%, 100%). Only 42 children ( 20.6%) were given antibiotics, while 162 (79.4%) were not.ConclusionThe QV-SAT is a quick and reliable test that can help dramatically reduce antibiotic prescriptions to children presenting with fever and acute pharyngotonsillitis.

Background In recent years, several hundred autism spectrum disorder (ASD) implicated genes have been discovered impacting a wide range of molecular pathways. However, the molecular underpinning of ASD, particularly from the point of view of ‘brain to behaviour’ pathogenic mechanisms, remains largely unknown. Methods We undertook a study to investigate patterns of spatiotemporal and cell type expression of ASD-implicated genes by integrating large-scale brain single cell transcriptomes (> million cells) and de novo loss of function (LOF) ASD mutations (impacting 852 genes from 40122 cases). Results We identified multiple single cell clusters from three distinct developmental human brain regions (anterior cingulate cortex, middle temporal gyrus and primary visual cortex) that evidenced high evolutionary constraint through enrichment for brain critical exons and high PLi genes. These clusters also showed significant enrichment with ASD loss of function mutation genes (p < 5.23 x 10− 11) that are transcriptionally highly active in prenatal brain regions (visual cortex and dorsolateral prefrontal cortex). Mapping ASD de novo LOF mutated genes into large scale human and mouse brain single cell transcriptome analysis demonstrate enrichment of such genes into neuronal subtypes and are also enriched for subtype of non-neuronal glial cell types (astrocyte, p < 6.40 x 10− 11; oligodendrocyte, p < 1.31 x 10− 09). Conclusion Among the ASD genes enriched with pathogenic de novo LOF mutations (i.e., KANK1, PLXNB1), a subgroup has restricted transcriptional regulation in non-neuronal cell types that are evolutionarily conserved. This association strongly suggests the involvement of subtype of non-neuronal glial cells in the pathogenesis of ASD, and the need to explore other biological pathways for this disorder.