Publications by authors named "HUME A"

Article Synopsis
  • - RNA viruses like influenza and coronaviruses pose significant health threats, often lacking effective vaccines or treatments, while others like filo- and henipaviruses have high mortality rates despite limited outbreaks.
  • - The antiviral drug 4'-Fluorouridine (4'-FlU) inhibits RNA virus replication by targeting the RNA-dependent RNA polymerase, but its effectiveness varies across different viruses, necessitating strategies to improve its potency.
  • - Researchers found that inhibiting dihydroorotate dehydrogenase (DHODH) enhances the antiviral effects of 4'-FlU against several RNA viruses, including in models of infection, potentially by depleting uridine, which boosts 4'-FlU's incorporation into viral
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Here, we describe the transcription- and replication-competent virus-like particle (trVLP) system for Marburg virus (MARV), which recapitulates transcription and replication of the viral genome in addition to viral particle assembly, egress, and entry. This protocol includes instructions for transfections for producer and acceptor cells and the use of trVLPs for infection.

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Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia, mostly in infants. To identify molecular targets of intervention during RSV infection in infants, we investigated how age regulates RSV interaction with the bronchial epithelium barrier. Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium.

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Resistance mechanisms in brain tumors, such as medulloblastoma and glioblastoma, frequently involve the entrapment of chemotherapeutic agents within endosomes and the extracellular expulsion of drugs. These barriers to effective treatment are exacerbated in nanotechnology-based drug delivery systems, where therapeutic nanoparticles often remain confined within endosomes, thus diminishing their therapeutic efficacy. Addressing this challenge necessitates the development of novel strategies to enhance the efficiency of cancer therapies.

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Background: Non-tuberculous mycobacteria (NTM) are rare causes of bone and joint infection (BJI) and there is limited evidence on which to base management decisions. This study describes 1 year of experience from a multi-disciplinary BJI team which collects data on all cases reviewed at a tertiary referral centre in Queensland, Australia.

Methods: The database was interrogated for all cases in which NTM were recovered from operative samples.

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Previous research has demonstrated a critical link between maternal mental health and infant development. However, there is limited understanding of the role of autonomic regulation in postpartum maternal mental health and infant outcomes. In the current study, we tested 76 mother-infant dyads from diverse socioeconomic backgrounds when infants were 3-months of age.

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Article Synopsis
  • Next-generation sequencing (NGS) struggles to fully capture the critical 5' and 3' ends of RNA virus genomes, which are essential for understanding their replication and transcription.
  • The newly developed ViBE-Seq method offers high-resolution sequencing of these genome ends using minimal RNA, improving the reliability of data collection for RNA viruses like Ebola and Marburg.
  • ViBE-Seq also helps identify the activity of different reverse transcriptases, providing a comprehensive approach to sequencing emerging viral genomes.
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Recent advances in high-throughput sequencing technologies have led to the discovery of a plethora of previously unknown viruses in animal samples. Some of these newly detected viruses are closely related to human pathogens. A prime example are the henipaviruses.

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Filoviruses are some of the most lethal viruses in the modern world, and increasing numbers of filovirus species and genera have been discovered in recent years. Despite the potential severity of filovirus outbreaks in the human population, comparably few sensitive pan-filovirus RT-PCR assays have been described that might facilitate early detection and prevention. Here, we present a new pan-filovirus RT-PCR assay targeting the L polymerase gene for detection of all known mammalian filoviruses.

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Article Synopsis
  • The study investigates the evolution and function of SPIRE actin nucleators, crucial for organelle transport in mammalian cells.
  • SPIRE proteins are found in holozoans, including choanoflagellates, and they interact with various proteins to facilitate actin filament formation and organelle movement.
  • The findings suggest that SPIRE originated in unicellular ancestors of animals, potentially playing a key role in the development of more complex multicellular organisms.
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Objectives: Modifications to opioid regimens for persistent pain are typically made after an initial period of short-acting opioid (SAO) use. Regimen changes may include an escalation of the SAO dosage or an initiation of a long-acting opioid (LAO) as a switch or add-on therapy. This study evaluates the comparative effectiveness between these alternative regimens in nursing home residents.

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tervening pro (inteins) are translated as subdomains within host proteins and removed through an intein-driven splicing reaction where the flanking sequences (exteins) are joined with a peptide bond. Previously, we developed a self-removing translation reporter for labeling Ebola virus (EBOV). In this reporter, an intein (RadA) containing the fluorescent protein ZsGreen (ZsG) is inserted within the EBOV protein VP30.

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PARP14 is a 203 kDa multi-domain protein that is primarily known as an ADP-ribosyltransferase, and is involved in a variety of cellular functions including DNA damage, microglial activation, inflammation, and cancer progression. In addition, PARP14 is upregulated by interferon (IFN), indicating a role in the antiviral response. Furthermore, PARP14 has evolved under positive selection, again indicating that it is involved in host-pathogen conflict.

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Article Synopsis
  • * A harmonized curation approach was developed to create comparable patient groups across different datasets from England, Wales, and Scotland, addressing inconsistencies in data coding.
  • * Tools and resources, including codelists and metadata, have been provided to assist researchers in recreating these patient cohorts in various EHR systems, facilitating future respiratory research.
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is a family of negative-sense RNA viruses with genomes of about 13.1-20.9 kb that infect fish, mammals and reptiles.

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Article Synopsis
  • Minor intron-containing genes (MIGs) represent less than 2% of human protein-coding genes but are crucial for the minor spliceosome process for gene excision.
  • Despite their small numbers, proteins encoded by MIGs (MIG-Ps) are considerably present in the interaction networks of various RNA and DNA viruses, including SARS-CoV and HIV-1.
  • The study suggests that MIG-Ps provide a stable, evolutionarily conserved foundation that viruses may exploit to infect and replicate within human cells.
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Background: Little to no data exist to guide treatment decision in patients with venous thromboembolism (VTE) and chronic liver disease.

Objectives: To assess the effectiveness and safety of direct oral anticoagulants (DOACs)-individually and as a class-vs warfarin and between 2 DOACs in patients with acute VTE and chronic liver disease.

Methods: We conducted a retrospective, US claims-based, propensity score-matched cohort study in adults with acute VTE and chronic liver disease who had newly initiated oral anticoagulants between 2011 and 2017.

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Single-cell RNA sequencing (scRNA-seq) technologies are instrumental to improving our understanding of virus-host interactions in cell culture infection studies and complex biological systems because they allow separating the transcriptional signatures of infected versus non-infected bystander cells. A drawback of using biosafety level (BSL) 4 pathogens is that protocols are typically developed without consideration of virus inactivation during the procedure. To ensure complete inactivation of virus-containing samples for downstream analyses, an adaptation of the workflow is needed.

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MRI, Imaging Sequences, Ultrasound, Mammography, CT, Angiography, Conventional Radiography Published under a CC BY 4.0 license. See also the commentary by Whitman and Vining in this issue.

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Objectives: To examine guideline-concordant care (GCC) for ovarian cancer, identify its predictors, and evaluate the associations between GCC and survival, health care expenditures, and utilization.

Study Design: A retrospective cohort study using Surveillance, Epidemiology, and End Results-Medicare data.

Methods: Women aged 66 to 90 years who received a diagnosis of stage II or higher epithelial ovarian cancer during 2011-2015 were included (N = 3237).

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Respiratory syncytial virus (RSV) can cause severe disease especially in infants; however, mechanisms of age-associated disease severity remain elusive. Here, employing human bronchial epithelium models generated from tracheal aspirate-derived basal stem cells of neonates and adults, we investigated whether age regulates RSV-epithelium interaction to determine disease severity. We show that following RSV infection, only neonatal epithelium model exhibited cytopathy and mucus hyperplasia, and neonatal epithelium had more robust viral spread and inflammatory responses than adult epithelium.

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Background: The COVID-19 pandemic dramatically altered the psychosocial environment of pregnant women and new mothers. In addition, prenatal infection is a known risk factor for altered fetal development. Here we examine joint effects of maternal psychosocial stress and COVID-19 infection during pregnancy on infant attention at 6 months postpartum.

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Article Synopsis
  • In April 2023, the International Committee on Taxonomy of Viruses (ICTV) approved changes to the phylum's classification during their annual vote.
  • The update included the addition of one new family, 14 new genera, and 140 new species.
  • Additionally, the taxonomy featured the renaming of two genera and 538 species, along with the removal of one species and the abolition of four others.
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Article Synopsis
  • - The 3' untranslated regions (UTRs) of Ebola virus mRNAs are rich in AU sequences, making them targets for RNA binding proteins (ARE-BPs) that regulate RNA stability and translation.
  • - Researchers identified potential AU-rich elements (AREs) in EBOV mRNA 3' UTRs and found that these elements can enhance mRNA stability and activity when tested in mammalian and zebrafish models.
  • - Coexpressing the Ebola nucleoprotein's (NP) 3' UTR with TTP, an ARE-BP known to destabilize mRNAs, led to reduced gene activity and protein expression, highlighting the role of AU content in regulating Ebola mRNA behavior.
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The International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group continues to prospectively refine the established nomenclature for taxa included in family Filoviridae in an effort to decrease confusion of genus, species, and virus names and to adhere to amended stipulations of the International Code of Virus Classification and Nomenclature (ICVCN). Recently, the genus names Ebolavirus and Marburgvirus were changed to Orthoebolavirus and Orthomarburgvirus, respectively. Additionally, all established species names in family Filoviridae now adhere to the ICTV-mandated binomial format.

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