Publications by authors named "G.A. Higgins"

Article Synopsis
  • Duplex sequencing (DS) is a precise method that uses molecular barcodes to trace PCR copies back to their original DNA, allowing for effective error correction in sequencing results.
  • TwinStrand Biosciences has created a DS-based assay to examine genetic mutations in rats for toxicity testing, using a time-course study with ENU exposure.
  • Results showed significant increases in mutation frequency in rats' stomach and bone marrow as early as 24 hours post-exposure, establishing a specific mutational signature across different tissues, indicating the assay's effectiveness and reproducibility in assessing mutagenesis.
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Article Synopsis
  • Duplex sequencing (DuplexSeq) is an advanced method that links DNA strands to correct sequencing errors, allowing for accurate detection of mutations in tissues.
  • A study with male rats exposed to a chemical (ENU) showed significant increases in mutation frequency within 24 hours for certain tissues and confirmed a specific mutation pattern by day 7.
  • Results from different labs showed strong agreement, marking DuplexSeq as a reliable advancement over traditional gene mutation assays for testing genetic toxicity.
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Group 2B β-coronaviruses (sarbecoviruses) have caused regional and global epidemics in modern history. Here, we evaluate the mechanisms of cross-sarbecovirus protective immunity, currently less clear yet important for pan-sarbecovirus vaccine development, using a panel of alphavirus-vectored vaccines covering bat to human strains. While vaccination does not prevent virus replication, it protects against lethal heterologous disease outcomes in both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and clade 2 bat sarbecovirus challenge models.

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Article Synopsis
  • Oligonucleotides (ONs) have therapeutic potential, but their effectiveness is limited by their inability to escape endosomes and reach cellular targets.
  • The study introduces two new endosomolytic compounds that enhance the delivery of splice-switching oligonucleotides (SSOs) by causing endosomal membrane rupture and promoting SSO release into the cytosol.
  • The research uses advanced microscopy and functional assays to demonstrate that these compounds can improve the functional activity of ONs and suggest their promising role as fast-acting transfection reagents in antisense therapies.
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Sickle cell disease (SCD) is associated with hemolysis, vascular inflammation, and organ damage. Affected patients experience chronic painful vaso-occlusive events requiring hospitalization. Hypoxia-induced polymerization of sickle hemoglobin S (HbS) contributes to sickling of red blood cells (RBCs) and disease pathophysiology.

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Background: Meniscal extrusion refers to meniscal displacement out of the joint space and over the tibial margin, altering knee mechanics and increasing the risk of osteoarthritis. The meniscotibial ligaments have been shown to have an important role in meniscal stability. However, it remains unclear whether an isolated lesion of the medial meniscotibial ligaments will result in meniscal extrusion and whether repairing the detached ligament will reduce extrusion.

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Background: We have shown that administration of mesenchymal stem cell-derived exosomes (single dose given within 1 hour) in models of traumatic brain injury (TBI) and hemorrhagic shock is neuroprotective. The precise mechanisms responsible for the neuroprotection are not fully understood. This study was designed to investigate the transcriptomic changes in the brain that are associated with this treatment strategy.

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Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk.

Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used.

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Background: Administration of human mesenchymal stem cell (MSC)-derived exosomes can enhance neurorestoration in models of traumatic brain injury (TBI) and hemorrhagic shock (HS). The impact of early treatment with MSC-derived exosomes on brain injury in a large animal model remains unknown. We sought to evaluate the impact of early single-dose exosome treatment on brain swelling and lesion size, blood-based cerebral biomarkers, and blood-brain barrier (BBB) integrity.

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Chromosome conformation capture methods have revealed the dynamics of genome architecture which is spatially organized into topologically associated domains, with gene regulation mediated by enhancer-promoter pairs in chromatin space. New evidence shows that endogenous hormones and several xenobiotics act within circumscribed topological domains of the spatial genome, impacting subsets of the chromatin contacts of enhancer-gene promoter pairs in and Results from the National Institutes of Health-funded PsychENCODE project and the study of chromatin remodeling complexes have converged to provide a clearer understanding of the organization of the neurogenic epigenome in humans. Neuropsychiatric diseases, including schizophrenia, bipolar spectrum disorder, autism spectrum disorder, attention deficit hyperactivity disorder, and other neuropsychiatric disorders are significantly associated with mutations in neurogenic transcriptional networks.

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Background: Negative attitudes toward hospice care might prevent patients with cancer from discussing and choosing hospice as they approach end of life. When making a decision, people often naturally focus on either expected benefits or the avoidance of harm. Behavioral research has demonstrated that framing information in an incongruent manner with patients' underlying motivational focus reduces their negative attitudes toward a disliked option.

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Background: Early treatment with valproic acid (VPA) has demonstrated benefit in preclinical models of traumatic brain injury, including smaller brain lesion size, decreased edema, reduced neurologic disability, and faster recovery. Mechanisms underlying these favorable outcomes are not fully understood. We hypothesized that VPA treatment would upregulate genes involved in cell survival and proliferation and downregulate those associated with cell death and the inflammatory response.

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Purpose To analyze the diagnostic accuracy of native T1 and T2 mapping compared with visual and quantitative assessment of edema on T2-weighted cardiac magnetic resonance (MR) images to differentiate between acute and chronic myocardial infarction. Materials and Methods This study had institutional ethics committee approval. Written informed consent was obtained from 67 consecutive patients (57 years ± 12; 78% men) with a first acute myocardial infarction, who were prospectively enrolled between April 2011 and June 2015.

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Many significant changes occur during human childhood, including cognitive, social-cognitive, and socioemotional changes. This article reviews some key phenomena associated with some of these changes and attempts to capture them within a single conceptual umbrella-changes in children's shared realities with others Shared reality is the experience that you have an inner state about something (e.g.

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After tuning their message to suit their audience's attitude, communicators' own memories for the original information (e.g., a target person's behaviors) often reflect the biased view expressed in their message--producing an audience-congruent memory bias.

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Owing to the generally higher values observed in the initial establishment of immunoglobulins (Ig) G, A, and M assays with the Behring Nephelometer, we elected to verify five commercial protein calibrators. This initial verification was performed by standardizing the Behring Nephelometer with the World Health Organization (WHO) International Reference Preparation for Human Serum Immunoglobulins G, A, and M. The instrument was also standardized for immunoglobulins and transferrin with use of the Reference Preparation for Serum Proteins (RPSP II).

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