Publications by authors named "Mary E Clark"

Germline genomic sequencing is increasingly integrated into pediatric cancer care, with pathogenic cancer-predisposing variants identified among 5-18% of affected children and variants of uncertain significance (VUS) in up to 70%. Given the potential medical implications for children and their families, parents' psychosocial responses to learning results are important to understand. Parents of children with cancer who learned their children's germline pathogenic or VUS results following paired tumor and germline genomic sequencing described their cognitive and affective responses to results in an open-ended write-in question after disclosure (M = 10 months post-disclosure; range = 1-28).

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Rhabdoviral vectors can induce lysis of cancer cells. While studied almost exclusively at 37 °C, viruses are subject to a range of temperatures , including temperatures ≤31 °C. Despite potential implications, the effect of temperatures <37 °C on the performance of rhabdoviral vectors is unknown.

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Purpose: Genetic counselors (GCs) increasingly play key roles in advancing genomic medicine through innovative research. Here, we examine one large cohort of GCs' evolving contributions to the literature, with the goal of facilitating worldwide professional development for GCs through scholarly activities.

Methods: Publications were cataloged by members of the Section of Genetic Counseling (Section), established at the Children's Hospital of Philadelphia and the University of Pennsylvania in 2014, including publication year, journal, impact factor, and author position.

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Purpose: To characterize parents' quality of life (QoL) after germline genomic sequencing for their children with cancer.

Methods: Participants were n = 104 parents of children with cancer enrolled in a prospective study of clinical tumor and germline genomic sequencing. Parents completed surveys at study consent (T0), before disclosure of their child's germline results (T1), and again ≥5 weeks after results disclosure (T2).

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Article Synopsis
  • Prompt diagnosis of cancer predisposition syndromes (CPS) in children is crucial for effective management and genetic counseling, but many institutions lack the necessary resources for accurate diagnoses.
  • The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) tool was evaluated for its accuracy in predicting CPS in pediatric oncology patients, involving 1,071 participants across multiple centers.
  • Results showed that MIPOGG successfully identified 99.5% of patients with confirmed CPS, outperforming standard clinical practices in early detection.
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Background: Constitutive and inducible defenses protect the respiratory tract from bacterial infection. The objective of this study was to characterize the response to an aerosolized lysate of killed bacteria, as a basis for studying the regulation and in vivo effects of these inducible innate immune responses.

Results: Bacterial lysate consisting of heat-killed and sonicated Staphylococcus aureus and Escherichia coli was aerosolized to 6 calves and systemic and pulmonary innate immune and inflammatory responses were measured in the first 24 h relative to baseline.

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: Historically, the majority of childhood cancers, including acute lymphoblastic leukemia (ALL), were not thought to have a hereditary basis. However, recent germline genomic studies have revealed that at least 5 - 10% of children with cancer (and approximately 3 - 4% of children with ALL) develop the disease due to an underlying genetic predisposition.: This review discusses several recently identified ALL predisposing conditions and provides updates on other more well-established syndromes.

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Mannheimia haemolytica is an important cause of bovine respiratory disease (BRD). BRD is usually a multifactorial disease with host factors and viral infections influencing pathogenesis. Previous studies that have attempted to experimentally induce pneumonia using aerosolized M.

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Objectives: The aim of this study was to design and carry out a preliminary evaluation of a urine point-of-care test for kidney injury molecule 1 (KIM-1) in healthy and diseased cats.

Methods: Part of the feline gene was amplified, ligated into a plasmid with a signal peptide and monomeric human IgGFc, and transfected into a mammalian cell line. Supernatant was purified and tested for the fusion protein by gel electrophoresis and Western blot.

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Severe equine asthma is a chronic inflammatory condition of the lower airways similar to adult-onset asthma in humans. Exacerbations are characterized by bronchial and bronchiolar neutrophilic inflammation, mucus hypersecretion and airway constriction. In this study we analyzed the gene expression response of the bronchial epithelium within groups of asthmatic and non-asthmatic animals following exposure to a dusty hay challenge.

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Respiratory disease is an important cause of morbidity and mortality in cetaceans, which are also threatened by environmental degradation caused by crude oil spills. Following oil spills, cetaceans at the water surface may inhale droplets of oil containing toxic polycyclic aromatic hydrocarbons (PAHs), which could potentially alter respiratory immunity via activation of the aryl hydrocarbon receptor (AHR) and its subsequent interaction with nuclear factor kappa B (NF-κB). β-defensins are antimicrobial peptides secreted by airway epithelial cells and their expression is known to be dependent on NF-κB.

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Daytime sleepiness is recognized in childhood brain tumor survivors. Our objective was to determine prevalence, risk factors for PSG/MLST proven hypersomnia/narcolepsy, and response to stimulants in childhood brain tumor survivors. Standard PSG/MSLT criteria were used to diagnose hypersomnia/narcolepsy.

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Background: Severe equine asthma is a naturally occurring lung inflammatory disease of mature animals characterized by neutrophilic inflammation, bronchoconstriction, mucus hypersecretion and airway remodeling. Exacerbations are triggered by inhalation of dust and microbial components. Affected animals eventually are unable of aerobic performance.

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Article Synopsis
  • Bordetella bronchiseptica is often associated with nonfatal tracheobronchitis, but its role in fatal pneumonia in dogs and cats is less understood, prompting this study.
  • The research analyzed 36 canine and 31 feline cases of fatal bronchopneumonia, identifying B. bronchiseptica through various methods including immunohistochemistry and PCR testing.
  • Results indicated that the presence of cilia-associated bacteria in histologic samples, which is often overlooked by pathologists, is a critical diagnostic feature for confirming B. bronchiseptica pneumonia and highlights its implications for disease transmission and prevention in both animals and immunocompromised humans.
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β-defensins are an important element of the mucosal innate immune response against bacterial pathogens. Tracheal antimicrobial peptide (TAP) has microbicidal activity against the bacteria that cause bovine respiratory disease, and its expression in tracheal epithelial cells is upregulated by bacterial products including lipopolysaccharide (LPS, a TLR4 agonist), Pam3CSK4 (an agonist of Toll-like receptor 2/1), and interleukin (IL)-17A. The objectives of this study were to identify the signalling pathway by which LPS, Pam3CSK4 and IL-17A induce TAP gene expression, and to determine the effect of glucocorticoid as a model of stress on this epithelial innate immune response.

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Here, we present a rare case of intestinal type adenocarcinoma arising in mature cystic teratoma (MCT) and review all previously reported similar cases with emphasis on the immunohistochemical characteristics of prior cases. Nine prior cases of intestinal type adenocarcinoma arising in MCT have been previously reported. Two of the prior cases as well as this case have been associated with CA19-9 elevation.

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Background: Many species of frogs secrete cutaneous antimicrobial peptides that are capable of killing Batrachochytrium dendrobatidis. Some of these species are nonetheless susceptible to chytridiomycosis, suggesting that host factors causing dysregulation of this innate immune response may be important in pathogenesis. Since stresses, such as from environmental perturbations, are a potential cause of such dysregulation, this study investigated the effect of glucocorticoid on cutaneous gene expression of these antimicrobial peptides.

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Bovine respiratory disease is a complex of bacterial and viral infections of economic and welfare importance to the beef industry. Although tracheal antimicrobial peptide (TAP) has microbicidal activity against bacterial pathogens causing bovine respiratory disease, risk factors for bovine respiratory disease including BVDV and stress (glucocorticoids) have been shown to inhibit the induced expression of this gene. Lipopolysaccharide is known to stimulate TAP gene expression, but the maximum effect is only observed after 16 h of stimulation.

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Secretoglobin family 1A member 1 (SCGB 1A1) is a small protein mainly secreted by mucosal epithelial cells of the lungs and uterus. SCGB 1A1, also known as club (Clara) cell secretory protein, represents a major constituent of airway surface fluid. The protein has anti-inflammatory properties, and its concentration is reduced in equine recurrent airway obstruction (RAO) and human asthma.

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Strategies to control bovine respiratory disease depend on accurate classification of disease risk. An objective method to refine the risk classification of beef calves could be economically beneficial, improve welfare by preventing unexpected disease occurrences, refine and reduce the use of antibiotics in beef production, and facilitate alternative methods of disease control. The objective of this study was to identify proteins in bronchoalveolar lavage fluid (BALF) of stressed healthy calves that predict later disease outcome, serve as biomarkers of susceptibility to pneumonia, and play a role in pathogenesis.

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Background: Secretoglobin 1A1 (SCGB 1A1), also called Clara cell secretory protein, is the most abundantly secreted protein of the airway. The SCGB1A1 gene has been characterized in mammals as a single copy in the genome. However, analysis of the equine genome suggested that horses might have multiple SCGB1A1 gene copies.

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Objective: To determine the prevalence of Mycoplasma bovis infection in the lungs of cattle at various times after arrival at a feedlot, to measure the relationship between clinical disease status and the concentration and genotype of M bovis within the lungs, and to investigate changes in the genotype of M bovis over time.

Sample: Bronchoalveolar lavage fluid (BALF) from 328 healthy or pneumonic beef cattle and 20 M bovis isolates obtained from postmortem samples.

Procedures: The concentration of M bovis in BALF was determined via real-time PCR assays, and M bovis isolates from BALF were genotyped via amplified fragment length polymorphism (AFLP) analysis.

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