Publications by authors named "John Howe"

The plasmon-mediated growth of noble metal nanoplates through the reduction of metal precursors onto resonantly excited seeds lined with planar defects stands out as one of the triumphs of photochemistry and nanometal synthesis. Such growth modes are, however, not without their drawbacks and, with a lack of suitable alternatives, limitations remain on the use of light as a synthetic control. Herein, a two-reagent seed-mediated gold nanoplate synthesis is demonstrated as a photochemical pathway where the illumination of the growth solution, as opposed to the emerging nanoplates, is the key requirement for growth.

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Introduction: Myeloid neoplasms (MNs) frequently harbor pathogenic mutations not detected by karyotyping and fluorescence in situ hybridization; hence, next-generation sequencing (NGS) is necessary for diagnosis, risk stratification, and therapy. If, however, NGS is not clinically indicated but still performed, the results may promote futile avenues of investigation, heighten patient distress, and increase cost.

Methods: We created criteria to approve NGS testing for MN (MN-NGS) with the goal of maximizing actionable results.

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This case discusses a male in his 40s with no prior medical history who presented to the emergency room with headaches and blurred vision and was found to have ring-enhancing lesions on brain MRI. Chest imaging revealed bilateral pulmonary nodules with a dominant right upper lobe nodule. On lung tissue sampling, he was found to have concurrent sarcoidosis and non-small cell lung cancer.

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Respiratory Syncytial Virus (RSV) causes severe respiratory infections and concomitant disease resulting in significant morbidity and mortality in infants, elderly, and immunocompromised adults. Vaccines, monoclonal antibodies, and small-molecule antivirals are now either available or in development to prevent and treat RSV infections. Although rodent and non-rodent preclinical animal models have been used to evaluate these emerging agents, there is still a need to improve our understanding of the pharmacokinetic (PK)-pharmacodynamic (PD) relationships within and between animal models to enable better design of human challenge studies and clinical trials.

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Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC), which first emerged in 2012, persist and continue to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging.

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As SARS-CoV-2 continues to circulate, antiviral treatments are needed to complement vaccines. The virus's main protease, 3CLPro, is an attractive drug target in part because it recognizes a unique cleavage site, which features a glutamine residue at the P1 position and is not utilized by human proteases. Herein, we report the invention of MK-7845, a novel reversible covalent 3CLPro inhibitor.

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Described here is the evaluation of a luciferase (luc) and respiratory syncytial virus (RSV) messenger RNA / lipid nanoparticle (mRNA/LNP) vaccine using a Needle-free Injection System, Tropis®, from PharmaJet® (Golden, Colorado USA). Needle-free jet delivery offers an alternative to needle/syringe. To perform this assessment, compatibility studies with Tropis were first performed with a luc mRNA/LNP and compared to needle/syringe.

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Molnupiravir, an oral prodrug of N-hydroxycytidine (NHC), previously demonstrated broad antiviral activity against multiple RNA viruses and has shown a high barrier to the development of resistance. Here, we present the antiviral activity of NHC against recent SARS-CoV-2 variants and the results of resistance selection studies to better understand the potential for viral resistance to NHC. NHC activity against SARS-CoV-2 variants omicron (BA.

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Background: Polypeptide blood group antigens are typically identified through investigation of the antibodies they induce. Human genome sequence databases are a new tool to identify AA substitutions that potentially create blood group antigens.

Study Design And Methods: The Erythrogene genomic sequence database was searched for missense mutations not known to be blood group antigens in the extracellular domains of selected RBC proteins in European populations.

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Article Synopsis
  • - Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are RNA viruses that cause serious respiratory issues mainly in infants, the elderly, and those with weakened immune systems.
  • - Researchers have discovered an allosteric inhibitory site on the viral polymerase of both RSV and HMPV; a small molecule inhibitor called MRK-1 can effectively target this site and block viral replication.
  • - Structural studies reveal that MRK-1 prevents crucial conformational changes in the polymerase, inhibiting RNA synthesis initiation and elongation, which helps in developing better treatments for both viruses.
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Background: The immunogenicities of polypeptide blood group antigens vary, despite most being created by single amino acid (AA) substitutions. To study the basis of these differences, we employed an immunoinformatics approach to determine whether AA substitution sites of blood group antigens have structural features typical of B-cell epitopes and whether the extent of B-cell epitope properties is positively related to immunogenicity.

Study Design And Methods: Fifteen structural property prediction programs were used to determine the likelihood of β-turns, surface accessibility, flexibility, hydrophilicity, particular AA composition and AA pairs, and other B-cell epitope properties at AA substitution sites of polypeptide blood group antigens.

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Background: The sensitivity to endocrine therapy assay (SET2,3) predicts treatment outcomes in Stage II-III breast cancer. SET2,3 measures transcription related to estrogen and progesterone receptors (SETER/PR index) and the molecular subtype (RNA4: ESR1, PGR, ERBB2, AURKA) from formalin-fixed paraffin-embedded (FFPE) tissue sections.

Methods: We designed a nested study across 3 pathology laboratories, each testing 60 breast cancers twice in controlled batches.

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Background: Social context guides care; stories sustain meaning; neither is routinely prioritized in residency training. Healing Through History (HTH) is a social medicine consultation curriculum integrating social determinants of health narrative into clinical care for medically and socially complex patients. The curriculum is part of an internal medicine (IM) residency outpatient clinical rotation at a Veterans Health Administration hospital.

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A hallmark of lymphoid malignancies is the presence of a monoclonal lymphocyte population. Monoclonality of B- and T-cell populations can be established through immunoglobulin (IG) or T-cell receptor (TCR) gene rearrangement analysis, respectively. The biological rationale of IG and TCR gene rearrangement analysis is that due to the extensive combinatorial repertoire made possible by V(D)J recombination in lymphocytes, it is unlikely that any substantive lymphocyte population would share the same IG or TCR gene rearrangement pattern unless there is an underlying neoplastic or reactive origin.

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Understanding anthropogenic radionuclide biogeochemistry and mobility in natural systems is key to improving the management of radioactively contaminated environments and radioactive wastes. Here, we describe the contemporary depth distribution and phase partitioning of Cs, Pu, and Am in two sediment cores taken from the Irish Sea (Site 1: the Irish Sea Mudpatch; Site 2: the Esk Estuary). Both sites are located ~10 km from the Sellafield nuclear site.

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Polar and subpolar ecosystems are highly vulnerable to global climate change with consequences for biodiversity and community composition. Bacteria are directly impacted by future environmental change and it is therefore essential to have a better understanding of microbial communities in fluctuating ecosystems. Exploration of Polar environments, specifically sediments, represents an exciting opportunity to uncover bacterial and chemical diversity and link this to ecosystem and evolutionary parameters.

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