Publications by authors named "Josh Smith"

Objective: We evaluate the safety of outpatient parotidectomy. We evaluate factors that lead to planned admission and compare costs. We evaluate trends toward outpatient, and the outcomes of switching admission status, total versus superficial approach, and ambulatory versus hospital site.

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Objectives: We sought to study the incidence of patient-initiated communication after parotidectomy, identify patient and surgical factors associated with patient-initiated communication, and evaluate trends and possible areas for improvement.

Methods: A retrospective cohort study of patients who underwent parotidectomy without combined procedures from 2018 to 2022 in a single tertiary-care institution was performed. We reviewed all patient communications documented within the electronic medical record within 30 days of discharge.

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Adeno-associated viruses (AAVs) are commonly used as vectors for the delivery of gene therapy targets. Characterization of AAV capsid proteins (VPs) and their post-translational modifications (PTMs) have become a critical attribute monitored to evaluate product quality. Liquid chromatography-mass spectrometry (LC-MS) analysis of intact AAV VPs provides both quick and reliable serotype identification as well as proteoform information on each VP.

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Adeno-associated viruses (AAVs) are viral vectors used as delivery systems for gene therapies. Intact protein characterization of AAV viral capsid proteins (VPs) and their post-translational modifications is critical to ensuring product quality. In this study, microchip-based ZipChip capillary electrophoresis-mass spectrometry (CE-MS) was applied for the rapid characterization of AAV intact VPs, specifically full and empty viral capsids of serotypes AAV6, AAV8 and AAV9, which was accomplished using 5 min of analysis time.

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Article Synopsis
  • Identifying impactful rare genetic variants is difficult, but using personal multi-omics can help overcome this challenge, as shown in a study involving several hundred individuals over 10 years.
  • By analyzing whole-genome sequencing and other omics data, researchers found that combining expression and protein data significantly increased the detection of rare stop and frameshift variants.
  • A new Bayesian hierarchical model called "Watershed" was used to prioritize rare variants linked to significant traits, revealing variants that influence complex conditions like height, schizophrenia, and Alzheimer's disease.
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Residual host cell proteins (HCPs) represent a critical quality attribute of biotherapeutic drug products. Workflows enabling reliable HCP detection in monoclonal antibodies and recombinant proteins have been developed, which facilitated process optimization to improve product stability and safety, and allowed setting of acceptance limits for HCP content. However, the detection of HCPs in gene therapy products such as adeno-associated viral (AAV) vectors has been limited.

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Integrative approaches that simultaneously model multi-omics data have gained increasing popularity because they provide holistic system biology views of multiple or all components in a biological system of interest. Canonical correlation analysis (CCA) is a correlation-based integrative method designed to extract latent features shared between multiple assays by finding the linear combinations of features-referred to as canonical variables (CVs)-within each assay that achieve maximal across-assay correlation. Although widely acknowledged as a powerful approach for multi-omics data, CCA has not been systematically applied to multi-omics data in large cohort studies, which has only recently become available.

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Exome sequencing of genes associated with heritable thoracic aortic disease (HTAD) failed to identify a pathogenic variant in a large family with Marfan syndrome (MFS). A genome-wide linkage analysis for thoracic aortic disease identified a peak at 15q21.1, and genome sequencing identified a novel deep intronic FBN1 variant that segregated with thoracic aortic disease in the family (LOD score 2.

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Objective: To determine the facilitators of and barriers to adherence to use of intranasal pharmacotherapy (daily intranasal corticosteroids and/or antihistamine, and nasal saline irrigation [NSI]), for allergic rhinitis (AR).

Methods: Patients were recruited from an academic tertiary care rhinology and allergy clinic. Semi-structured interviews were conducted after the initial visit and/or 4-6 weeks following treatment.

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Background: Chronic obstructive pulmonary disease (COPD) varies significantly in symptomatic and physiologic presentation. Identifying disease subtypes from molecular data, collected from easily accessible blood samples, can help stratify patients and guide disease management and treatment.

Methods: Blood gene expression measured by RNA-sequencing in the COPDGene Study was analyzed using a network perturbation analysis method.

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Mucoepidermoid Carcinomas (MEC) represent the most common malignancies of salivary glands. Approximately 50% of all MEC cases are known to harbor gene fusions, but the additional molecular drivers remain largely uncharacterized. Here, we sought to resolve controversy around the role of human papillomavirus (HPV) as a potential driver of mucoepidermoid carcinoma.

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Self-injurious behavior (SIB) can lead to serious injury and occurs in approximately 1%-4% of the adult population, with higher incidences in adolescent and institutionalized populations, as well as in children with developmental disorders such as Autism. SIB also spontaneously occurs in a low percentage of captive monkeys. Rhesus macaque (Macaca mulatta) monkeys are evolutionarily and physiologically similar to humans, share 93% genetic sequence similarity to humans, and have long been used as testing subjects for vaccine and clinical trials.

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Despite the growing number of genome-wide association studies (GWASs), it remains unclear to what extent gene-by-gene and gene-by-environment interactions influence complex traits in humans. The magnitude of genetic interactions in complex traits has been difficult to quantify because GWASs are generally underpowered to detect individual interactions of small effect. Here, we develop a method to test for genetic interactions that aggregates information across all trait-associated loci.

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Glycosylation is a prominent co- and post-translational modification which contributes to a variety of important biological functions. Protein glycosylation characteristics, particularly N-glycosylation, are influenced by changes in one's pathological state, such as through the presence of disease, and as such, there is great interest in N-glycans as potential disease biomarkers. Human serum is an attractive source for N-glycan based biomarker studies as circulatory proteins are representative of one's physiology, with many serum proteins containing N-glycosylation.

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Protein bound uremic toxins (PBUTs), a series of chemicals that remain a challenge for removal strategies used on patients suffering with chronic kidney disease, could be strong candidates for MD study in order to better understand the interactions and time scales associated with binding mode transitions. Currently, traditional dialysis methods cannot satisfactorily remove PBUTs from the bloodstream. This is at least partly due to these toxin's high level of affinity for protein binding sites, particularly the prominent human serum albumin (HSA) and two of its drug binding sites (Sudlow site I and II).

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The volumetric oxygen mass transfer coefficient ([Formula: see text]) is an essential parameter in aerobic high-cell density fermentation where the availability of oxygen to growing microorganisms is a limiting factor. Bioprocess teams looking to scale-up/down between the Eppendorf BioBLU 0.3f single-use vessel and the BioFlo® 320 reusable vessel bioreactors may find it challenging using a matched [Formula: see text].

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Endothelial dysfunction in small arteries is a ubiquitous, early feature of cardiovascular disease, including hypertension. Dysfunction reflects reduced bioavailability of endothelium-derived nitric oxide (NO) and depressed endothelium-dependent hyperpolarization that enhances vasoreactivity. We measured smooth muscle membrane potential and tension, smooth muscle calcium, and used real-time quantitative polymerase chain reaction in small arteries and isolated tubes of endothelium to investigate how dysfunction enhances vasoreactivity.

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Protein bound uremic toxins (PBUTs) have been correlated to poor clinical outcomes for patients with chronic kidney disease (CKD) and are not susceptible to the traditional dialysis techniques. Several PBUTs are known to bind strongly with the primary drug carrying sites of human serum albumin (HSA): Sudlow site I and Sudlow site II. A detailed energetic and structural description of PBUT interactions with these binding sites would provide useful insight into the design of materials that specifically displace and capture PBUTs.

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The therapeutic potential of protein drugs has been hindered by difficulties with long-term stability and rapid clearance from the body. Recombinant fusion proteins provide a scalable platform for engineered biologics, whereby a polypeptide domain is appended to alter the physical characteristics of a therapeutic protein and enhance its pharmaceutical viability. Two simple design principles for recombinant fusion proteins, based on the physical properties of the polypeptide domain, have been separately applied to address issues with the stability and delivery of biologics.

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Peritonsillar abscess (PTA) is a difficult diagnosis to make clinically, with clinical examination of even otolaryngologists showing poor sensitivity and specificity. Machine learning is a form of artificial intelligence that "learns" from data to make predictions. We developed a machine learning classifier to predict the diagnosis of PTA based on patient symptoms.

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Materials that resist nonspecific protein adsorption are needed for many applications. However, few are able to achieve ultralow fouling in complex biological milieu. Zwitterionic polymers emerge as a class of highly effective ultralow fouling materials due to their superhydrophilicity, outperforming other hydrophilic materials such as poly(ethylene glycol).

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Objective: Peritonsillar abscess (PTA) is a common infectious complication of pharyngeal infection managed by otolaryngologists and emergency room physicians. Streptococcus and Fusobacterium (e.g.

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Objectives/hypothesis: An uncommon phenomenon in relation to the peritonsillar abscess (PTA) is the intratonsillar abscess (ITA) or formation of an abscess within tonsillar parenchyma. This study sought to characterize our experience with diagnosis and management of ITAs in the context of the PTA patient population.

Study Design: Case-control series.

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Objective: To determine the incidence of intratonsillar abscess (ITA) patients within the population of patients diagnosed with peritonsillar abscess (PTA) and to further characterize the differences in symptomatology and successful treatment strategies between the two groups.

Methods: This study is a retrospective chart review of patients diagnosed with PTA or ITA at our institution from 2000 to 2017. Descriptive and inferential statistics are reported, including univariate and multivariate analyses.

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Serum remains an attractive source for the discovery of disease related biomarkers due to its intimate interaction with the majority of tissues within the body. The dynamic range of proteins present within serum has long complicated the ability to detect low level tissue leakage proteins that offer more promise as potential biomarkers due to their higher degree of specificity. Depletion strategies, using affinity based sorbents, to remove the most abundant serum proteins are routinely used for matrix simplification during discovery strategies focused on the serum proteome or glycoproteome.

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