Publications by authors named "Clara M Pelfrey"

To understand how translational science efforts lead to outcomes, it is common to examine publications as a key step in the translational process. The National Institutes of Health's Clinical and Translational Science Awards (CTSA) program aims to accelerate that process by providing support to investigators. Although it is challenging to measure the impact of such support on translational outcomes, CTSA-supported research that arises in research publications can advance translation through use of these publications in public policy and guideline documents from government health agencies, intergovernmental organizations, and other outlets.

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Under-representation of women in leadership at Academic Medical Centers (AMCs) is a known challenge such that, in 2021, women made up only 28% of department chairs. AMCs are addressing the dearth of women leaders through targeted programming to create leadership pipelines of qualified women. The FLEX Leadership Development Program at the Case Western Reserve University (CWRU) School of Medicine prepares women faculty for increased leadership opportunities.

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Evaluation researchers at Clinical and Translational Science Award (CTSA) hubs are conducting retrospective case studies to evaluate the translational research process. The objective of this study was to deepen knowledge of the translational process and identify contributors to successful translation. We investigated the successful translation of the HemeChip, a low-cost point-of-care diagnostic device for sickle cell disease, using a protocol for retrospective translational science case studies of health interventions developed by evaluators at the National Health Institutes (NIH) and CTSA hubs.

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Background: Evaluating outcomes of the clinical and translational research (CTR) training of a Clinical and Translational Science Award (CTSA) hub (eg, the KL2 program) requires the selection of reliable, accessible, and standardized measures. As measures of scholarly success usually focus on publication output and extramural funding, CTSA hubs have started to use bibliometrics to evaluate the impact of their supported scholarly activities. However, the evaluation of KL2 programs across CTSAs is limited, and the use of bibliometrics and follow-on funding is minimal.

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Introduction: The Great CTSA Team Science Contest (GTSC) was developed to discover how Clinical and Translational Science Award (CTSA) hubs promote and support team science [1]. The purpose of this study was a secondary qualitative analysis of the GTSC submissions to better understand the diversity of team science initiatives across the CTSA consortium.

Methods: Secondary qualitative analysis of the GTSC data addressed the following research questions, which defined the top-level coding: (1) What CTSA component sponsored it? (2) Who was the team doing the work? (3) Who were the intended beneficiaries? (4) What was the intended outcome? (5) What strategies did they use? (6) What translational science (TS) stage was addressed? (7) How do they align with the NCATS team science strategic goals? (8) How do the CTSA's team science efforts align with the National Academies Research Council (NRC) recommendations for enhancing the effectiveness of team science?

Results: The GTSC received 170 submissions from 45 unique CTSA hubs.

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Introduction: Evaluating clinical and translational research (CTR) mentored training programs is challenging because no two programs are alike. Careful selection of appropriate metrics is required to make valid comparisons between individuals and between programs. The KL2 program provides mentored-training for early-stage CTR investigators.

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The critical processes driving successful research translation remain understudied. We describe a mixed-method case study protocol for analyzing translational research that has led to the successful development and implementation of innovative health interventions. An overarching goal of these case studies is to describe systematically the chain of events between basic, fundamental scientific discoveries and the adoption of evidence-based health applications, including description of varied, long-term impacts.

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Purpose: This study describes the design, operation and evaluation of a community-based research (CBR) consult service within the setting of a Clinical and Translational Science Award (CTSA) institution. To our knowledge, there are no published evaluations of a CBR consult service at a CTSA hub.

Methods: A community-based research Consult Service was created to support faculty, health care providers/research coordinators, trainees, community-based organizations and community members.

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Background: Cross-institutional cross-disciplinary collaboration has become a trend as researchers move toward building more productive and innovative teams for scientific research. Research collaboration is significantly changing the organizational structure and strategies used in the clinical and translational science domain. However, due to the obstacles of diverse administrative structures, differences in area of expertise, and communication barriers, establishing and managing a cross-institutional research project is still a challenging task.

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Background: Approximately 20% of patients with idiopathic dilated cardiomyopathy (iDCM) have autoantibodies (AAbs) specific to cardiac troponin-I (cTnI). However, there has been no work evaluating active cellular autoimmunity. We aimed to identify a cTnI-stimulated cellular autoimmune response and to correlate our findings with cTnI AAb production.

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Dilated cardiomyopathy is a devastating disease associated with poor outcomes. Although the etiology of this disease remains largely unknown, so-called "idiopathic" dilated cardiomyopathy (iDCM) is associated with evidence of an autoimmune process that may be contributing to the pathophysiology of this disease. Indeed, iDCM shares many characteristics with other autoimmune diseases, including an association with systemic and organ-specific inflammation, an association with viral infections, a genetic predisposition, and a correlation with specific human leukocyte antigen subtypes.

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Background: Interferon (IFN) gamma (IFNG) allelic variants are associated with susceptibility to multiple sclerosis (MS) in men but not in women.

Objectives: To conduct a high-density linkage disequilibrium association study of IFNG and the surrounding region for sex-associated MS susceptibility bias and to evaluate whether IFNG allelic variants associated with MS susceptibility are associated with expression.

Design: Genotype case-control study, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay expression analyses for IFN gamma.

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Multiple sclerosis affects more women than men. The reasons for this are unknown. Previously, we have shown significant differences in women versus men in inflammatory cytokine responses to the major protein component of myelin, proteolipid protein (PLP), which is thought to be a target in MS patients.

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Mitoxantrone (MX) has demonstrated efficacy in multiple sclerosis (MS), but its immunologic mechanisms of action are poorly understood. Furthermore, no study has examined the immunological effects of MX in primary progressive MS (PPMS). This study investigated the immunological effects of MX therapy in PPMS patients.

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Sex hormones play a central role as modulators of immune responses and autoimmune diseases. We hypothesized that suppression of MS disease during pregnancy may be mediated by sex steroid hormones via regulation of costimulatory molecules such as CD40L or CD80/CD86 (B7-1/B7-2). We tested two sex hormones that are implicated in immune suppression during pregnancy: estriol and progesterone.

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Multiple sclerosis (MS) is thought to be an autoimmune disease in which an unknown trigger initiates an immune response against brain proteins. This autoaggressive response causes the breakdown of the myelin sheaths that protect nerve axons, leading to impaired nerve conduction and subsequent neurodegeneration that are characteristic of MS. Many studies have attempted to determine the exact target within the brain.

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The relationship between autoreactivity to myelin antigens and disease progression in multiple sclerosis (MS) is not fully understood. We addressed this relationship by cross-sectionally comparing an objective measure of MS disability with immune cytokine responses to myelin proteins. The ELISPOT assay was used to determine the ex vivo interferon gamma (IFNgamma) and interleukin-10 (IL-10) production by peripheral blood mononuclear cells (PBMCs) in response to peptides spanning the entire proteolipid protein (PLP) and myelin basic protein (MBP) molecules in 20 patients with relapsing-remitting (RR) MS and 27 age- and sex-matched healthy controls.

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Many autoimmune diseases preferentially affect women; however, the underlying mechanisms for the sex differences are poorly understood. We examined sex-dependent differences in the immunologic response to myelin proteins in 22 multiple sclerosis (MS) patients and 22 healthy controls. Using ELISA spot assay (ELISPOT) methodology, interferon (IFN) gamma and IL-5 secretions were examined at the single cell level in response to overlapping proteolipid protein (PLP) peptides.

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Autoimmune sensorineural hearing loss (ASNHL) typically produces bilateral rapidly progressive loss of hearing over a few days or weeks, but may also produce sudden loss over a few hours. The diagnosis is made by excluding ototoxicity, systemic disease, and other factors that mimic ASNHL and by showing a therapeutic response to corticosteroid treatment. Antibody production and T-cell proliferative responses to inner ear antigens have been implicated in the etiopathogenesis of ASNHL.

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