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Distinct airway epithelial immune responses after infection with SARS-CoV-2 compared to H1N1
Children are less likely than adults to suffer severe symptoms when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while influenza A H1N1 severity is comparable across ages except for the very young or elderly. Airway epithelial cells play a vital role in the early defence against viruses via their barrier and immune functions. We investigated viral replication and immune responses in SARS-CoV-2-infected bronchial epithelial cells from healthy paediatric (n = 6; 2.5–5.6 years old) and adult (n = 4; 47–63 years old) subjects and compared cellular responses following infection with SARS-CoV-2 or Influenza A H1N1. While infection with either virus triggered robust transcriptional interferon responses, including induction of type I (IFNB1) and type III (IFNL1) interferons, markedly lower levels of interferons and inflammatory proteins (IL-6, IL-8) were released following SARS-CoV-2 compared to H1N1 infection. Only H1N1 infection caused disruption of the epithelial layer. Interestingly, H1N1 infection resulted in sustained upregulation of SARS-CoV-2 entry factors FURIN and NRP1. We did not find any differences in the epithelial response to SARS-CoV-2 infection between paediatric and adult cells. Overall, SARS-CoV-2 had diminished potential to replicate, affect morphology and evoke immune responses in bronchial epithelial cells compared to H1N1.
The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics
A genomic database of all Earth’s eukaryotic species could contribute to many scientific discoveries; however, only a tiny fraction of species have genomic information available. In 2018, scientists across the world united under the Earth BioGenome Project (EBP), aiming to produce a database of high-quality reference genomes containing all ~1.5 million recognized eukaryotic species. As the European node of the EBP, the European Reference Genome Atlas (ERGA) sought to implement a new decentralised, equitable and inclusive model for producing reference genomes. For this, ERGA launched a Pilot Project establishing the first distributed reference genome production infrastructure and testing it on 98 eukaryotic species from 33 European countries. Here we outline the infrastructure and explore its effectiveness for scaling high-quality reference genome production, whilst considering equity and inclusion. The outcomes and lessons learned provide a solid foundation for ERGA while offering key learnings to other transnational, national genomic resource projects and the EBP.
Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia
X-linked hypophosphataemia (XLH) is a rare metabolic bone disorder caused by pathogenic variants in the PHEX gene, which is predominantly expressed in osteoblasts, osteocytes and odontoblasts. XLH is characterized by increased synthesis of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23), which results in renal phosphate wasting with consecutive hypophosphataemia, rickets, osteomalacia, disproportionate short stature, oral manifestations, pseudofractures, craniosynostosis, enthesopathies and osteoarthritis. Patients with XLH should be provided with multidisciplinary care organized by a metabolic bone expert. Historically, these patients were treated with frequent doses of oral phosphate supplements and active vitamin D, which was of limited efficiency and associated with adverse effects. However, the management of XLH has evolved in the past few years owing to the availability of burosumab, a fully humanized monoclonal antibody that neutralizes circulating FGF23. Here, we provide updated clinical practice recommendations for the diagnosis and management of XLH to improve outcomes and quality of life in these patients.
Benchmarking nanopore sequencing and rapid genomics feasibility: validation at a quaternary hospital in New Zealand
Approximately 200 critically ill infants and children in New Zealand are in high-dependency care, many suspected of having genetic conditions, requiring scalable genomic testing. We adopted an acute care genomics protocol from an accredited laboratory and established a clinical pipeline using Oxford Nanopore Technologies PromethION 2 solo system and Fabric GEM™ software. Benchmarking of the pipeline was performed using Global Alliance for Genomics and Health benchmarking tools and Genome in a Bottle samples (HG002-HG007). Evaluation of single nucleotide variants resulted in a precision and recall of 0.997 and 0.992, respectively. Small indel identification approached a precision of 0.922 and recall of 0.838. Large genomic variations from Coriell Copy Number Variation Reference Panel 1 were reliably detected with ~2 M long reads. Finally, we present results obtained from fourteen trio samples, ten of which were processed in parallel with a clinically accredited short-read rapid genomic testing pipeline (Newborn Genomics Programme; NCT06081075; 2023-10-12).
Impact of patient care teams on blood pressure control in patients with hypertension: a systematic review and meta-analysis
Hypertension is a significant risk factor for cardiovascular diseases, with its global prevalence doubling over the past three decades. Despite advancements in antihypertensive therapies, approximately 50% of patients with hypertension fail to achieve their target blood pressure (BP) levels, underscoring the need for innovative care strategies. Patient care teams comprising multidisciplinary healthcare providers have shown promise in improving BP management. This systematic review and meta-analysis were aimed at evaluating the effectiveness of patient care teams involving physicians in hypertension management. To this end, PubMed, Cochrane CENTRAL, and IchuShi-Web were comprehensively searched and 61 randomized controlled trials including 64,857 participants were identified. Compared with usual care, interventions by patient care teams significantly reduced office systolic BP (mean difference: −6.31 mmHg; 95% confidence interval: −7.71 to −4.90) and decreased the risk of uncontrolled BP by 27% (risk ratio: 0.73; 95% confidence interval: 0.68–0.79). Subgroup analyses demonstrated consistent BP reductions across various team leadership roles, such as physicians, nurses, and pharmacists, and across different intervention durations. These findings highlight the effectiveness of team-based BP management in achieving improved BP control, regardless of team composition or the follow-up period. Multidisciplinary care offers a viable approach to addressing the unmet needs of patients with hypertension, potentially improving cardiovascular outcomes. This evidence supports integrating patient care teams into hypertension management, particularly in settings requiring physician oversight. Future research should focus on refining team structures and tailoring interventions to diverse healthcare environments to enhance their impact.
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