Publications by authors named "Metcalf J"

Hospitalized COVID-19 patients exhibit diverse immune responses during acute infection, which are associated with a wide range of clinical outcomes. However, understanding these immune heterogeneities and their links to various clinical complications, especially long COVID, remains a challenge. In this study, we performed unsupervised subtyping of longitudinal multi-omics immunophenotyping in over 1,000 hospitalized patients, identifying two critical subtypes linked to mortality or mechanical ventilation with prolonged hospital stay and three severe subtypes associated with timely acute recovery.

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  • Chronic viral infections can reactivate during acute illnesses, and this study looked at how SARS-CoV-2 infection affects latent viruses like Epstein-Barr Virus (EBV) and cytomegalovirus (CMV) in over 1,154 hospitalized COVID-19 patients.* -
  • The analysis showed significant reactivation of multiple virus families during the acute stage of COVID-19, which correlated with disease severity, demographics, and clinical outcomes, including higher mortality rates.* -
  • Additionally, persistent viral reactivation after recovery was linked to ongoing symptoms of Post-Acute Sequelae of COVID-19 (PASC), emphasizing the importance of understanding these interactions for better treatment and management strategies.*
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  • The text discusses a specific fungus that survives in the acidic environment of the human stomach, potentially causing conditions like ulcers and gastritis.
  • In research on mice, it was found that this fungus can induce localized gastritis without affecting the intestine, highlighting the stomach's vulnerability to fungal infections.
  • The study identified immune responses and gene expressions linked to fungal infection in a specific stomach region, suggesting the importance of further research on how this infection interacts with the host's immune system and microbiota.
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The urgent need for effective treatments for acute and chronic lung diseases underscores the significance of developing innovative preclinical human research tools. The 2023 ATS Workshop on Precision Cut Lung Slices (PCLS) brought together 35 experts to discuss and address the role of human tissue-derived PCLS as a unique tool for target and drug discovery and validation in pulmonary medicine. With increasing interest and usage, along with advancements in methods and technology, there is a growing need for consensus on PCLS methodology and readouts.

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Glioblastoma (GBM) is the most aggressive cancer originating in the brain, but unfortunately combination treatments with resection, radiation, and chemotherapy are relatively ineffective. Therefore, novel methods of adjuvant therapy are critically needed. Cyclotides are plant-derived circular peptides that chemosensitize drug-resistant breast cancer to doxorubicin.

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Previous research demonstrated the distribution of distinct microbial communities in the equine hindgut surrounding the pelvic flexure. The current study evaluated gene expression in epithelial tissues surrounding the pelvic flexure to characterize patterns that might correlate with microbial distribution. Gene expression was determined by analyzing RNA sequence data from the pelvic flexure, the left and right ventral colon, and the left and right dorsal colon.

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Direct RNA nanopore sequencing reveals changes in gene expression, polyadenylation, splicing, m6A methylation, and pseudouridylation in response to influenza virus exposure in primary human bronchial epithelial cells. This study focuses on the epitranscriptomic profile of genes in the host immune response. In addition to polyadenylated noncoding RNA, we purified and sequenced nonpolyadenylated noncoding RNA and observed changes in expression, N6-methyl-adenosine (m6A), and pseudouridylation (Ψ) in these novel RNA.

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Biocrusts dominate the soil surface in deserts and are composed of diverse microbial communities that provide important ecosystem services. Cyanobacteria in biocrusts produce many secondary metabolites, including the neurotoxins BMAA, AEG, DAB, anatoxin-a() (guanitoxin), and the microcystin hepatotoxins, all known or suspected to cause disease or illness in humans and other animals. We examined cyanobacterial growth and prevalence of these toxins in biocrusts at millimeter-scales, under a desert-relevant illumination gradient.

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  • Nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic have changed how respiratory syncytial virus (RSV) subtypes, specifically RSV-A and RSV-B, behave globally.
  • The study used a model based on historical data from the UK and Finland to show that RSV-A is likely to dominate over RSV-B shortly after NPIs were implemented.
  • The findings, supported by a global genetic dataset, suggest RSV-A's increased prevalence post-pandemic may influence the effectiveness of new vaccines and treatments for RSV in infants and high-risk groups.
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Background: Age > 65 years is a key risk factor for poor outcomes after human influenza infection. Specifically, in addition to respiratory disease, non-neurotropic influenza A virus (IAV) causes neuro-cognitive complications, e.g.

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Sepsis is a common, heterogeneous, and frequently lethal condition of organ dysfunction and immune dysregulation due to infection. The causes of its heterogeneity, including the contribution of the pathogen, remain unknown. Using cecal slurry, a widely used murine model of intraperitoneal polymicrobial sepsis, as well as 16S ribosomal RNA sequencing and measurement of immune markers, we performed a series of translational analyses to determine whether microbial variation in cecal slurry composition (representing intra-abdominal pathogens) mediated variation in septic response.

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Background: Complex descriptions of new strains of cyanobacteria appear very frequently. The main importance of these descriptions concerns potential new substances that they could synthesise, as well as their different properties as a result of their different ecological niches. The main gene used for these descriptions is 16 S with ITS or whole genome sequencing.

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BACKGROUNDPatients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes for some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity.METHODSWe performed deep immunophenotyping and conducted longitudinal multiomics modeling, integrating 10 assays for 1,152 Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study participants and identifying several immune cascades that were significant drivers of differential clinical outcomes.

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Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) primarily targets the respiratory system. Physiologically relevant human lung models are indispensable to investigate virus-induced host response and disease pathogenesis. In this study, we generated human induced pluripotent stem cell (iPSC)-derived alveolar organoids (AOs) using an established protocol that recapitulates the sequential steps of in vivo lung development.

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Obesity and metabolic dysfunction have been shown to be associated with overproduction of reactive oxygen species (ROS) in the gastrointestinal (GI) tract, which contributes to dysbiosis or imbalances in the gut microbiota. Recently, the reversal of dysbiosis has been observed as a result of dietary supplementation with antioxidative compounds including polyphenols. Likewise, dietary polyphenols have been associated with scavenging of GI ROS, leading to the hypothesis that radical scavenging in the GI tract is a potential mechanism for the reversal of dysbiosis.

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  • In 2020, researchers discovered cancer-specific microbial signals in The Cancer Genome Atlas (TCGA), leading to multiple papers confirming their findings.
  • They addressed concerns about batch correction and contamination affecting results, showing that their methods yielded consistent results despite these issues.
  • The development of a new method, Exhaustive, significantly improved sensitivity in data cleaning, reinforcing the validity of cancer type-specific microbial signatures in TCGA.
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  • Scientists studied how tiny living things called microbes break down dead bodies in different places.
  • They found that these microbes work together in a special way to recycle the materials from the bodies, even though the climate and location can change.
  • This research could help figure out how long someone has been dead by looking at the types of microbes present.
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Introduction: Bronchiolitis is the most common viral lower respiratory tract infection in children under 2 years of age. Respiratory support with high-flow nasal cannula (HFNC) is increasingly used in this patient population with limited understanding of the patients most likely to benefit and considerable practice variability of use. This study aims to understand the factors associated with failure of HFNC support among patients with bronchiolitis and to describe the current practice variations of HFNC use in patients with bronchiolitis in Canadian hospitals including fluid management and parameters to initiate, escalate and discontinue HFNC support.

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Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities.

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Oral microbiota associate with diseases of the mouth and serve as a source of lung microbiota. However, the role of oral microbiota in lung disease is unknown. To determine associations between oral microbiota and disease severity and death in idiopathic pulmonary fibrosis (IPF).

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The Great Salt Lake in Utah is the largest saline lake in the Western hemisphere and one of the largest terminal lakes in the world. Situated at the eastern edge of the Great Basin, it is a remnant of the freshwater Lake Bonneville whose water level precipitously lowered about 12,000 years ago due to a natural break in Red Rock pass to the north. It contains a diverse assemblage of cyanobacteria which vary spatially dependent on salinity.

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  • BMAA, a neurotoxic compound from cyanobacteria, is linked to chronic diseases like ALS and Alzheimer's, necessitating specific detection methods.
  • Current analytical techniques struggle to distinguish between BMAA enantiomers, and the enantiomeric configuration of BMAA in cyanobacteria remains largely unexamined.
  • A new chiral UPLC-MS/MS method identified both L- and D-BMAA in cyanobacterial materials, but only L-BMAA in mussels, highlighting the need to explore the implications of D-BMAA in neurological diseases.
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Hospitalized COVID-19 patients exhibit diverse clinical outcomes, with some individuals diverging over time even though their initial disease severity appears similar. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity. In this study, we carried out deep immunophenotyping and conducted longitudinal multi-omics modeling integrating ten distinct assays on a total of 1,152 IMPACC participants and identified several immune cascades that were significant drivers of differential clinical outcomes.

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