bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Expression of NRG1‐ERBB4‐PSEN1‐NUP98 (NEPN) Signaling Axis as Potential Blood‐Based Biomarkers for Viral Myocarditis
Authors: Hanson Paul J , Lin Veena , McManus Bruce M 
Published: June 2021

BackgroundMyocarditis, inflammation of the myocardium, is a leading cause of unexpected heart failure in young adults, commonly attributable to viral infections. Myocarditis manifests in a wide range of clinical presentations, from asymptomatic to acute heart failure. The current gold standard for diagnosis relies upon invasive endomyocardial biopsy, requiring histopathological demonstration of inflammation with/without associated myocyte damage. Under these guidelines, diagnostic sensitivity in independent published studies is <30%. We have previously demonstrated that detection of biomarkers within the NEPN pathway (implicated in immune response and heart failure) significantly improved diagnostic sensitivity to ~80%, however, this approach still relies upon biopsy. Thus, in the present study, our aim is to develop a non‐invasive, blood‐based diagnostic assay for viral myocarditis by examining the NEPN signaling axis and their cleavage fragments during the evolution of myocarditis.DesignHeLa cells and human induced pluripotent stem cell (iPSC)‐derived cardiomyocytes (CM) were CVB3‐ or sham‐infected. Western blot analysis and confocal microscopy were performed to determine the expression and subcellular localization of NEPN signaling axis proteins in tissue culture. In addition, tissue and blood from murine models of viral myocarditis (A/J and C57BL/6 mice) were collected at 4 dpi (viremic phase) and 5 to 8 dpi (acute phase), and were analyzed by Western blot analysis, IHC and IF to detect protein expression.ResultsNEPN proteins all show changes in expression and subcellular localization throughout the infection time course. NUP98 is upregulated and cleaved during infection. NRG1 is upregulated in both lysates and supernatants. ERBB4 co‐localizes at the cell membrane with the protease PSEN1. ERBB4 and NRG1 cleavage fragments are secreted and detected in both tissue culture supernatant and mouse plasma. In the plasma of the less susceptible C57BL/6 mice, ERBB4 and NRG1 cleavage fragments increase throughout the viremic and acute phases. However, in the highly susceptible A/J mice, ERBB4 and NRG1 cleavage fragments were not detected in the plasma until 6 dpi (acute phase), when they are highly upregulated as compared to C57BL/6 mice (p=0.001).ConclusionDifferential expression, subcellular localization and cleavage fragments of NEPN signaling axis proteins were detected during the pathogenesis of viral myocarditis. These composite changes may be useful in the development of a blood‐based diagnostic.Support or Funding InformationDr. Hanson's research is supported by the Myocarditis Foundation and Michael Smith Foundation for Health ResearchThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Understanding Leukocyte Recruitment in Murine Ozone‐Induced Lung Inflammation
Authors: Brocos Jessica Andrea , Aulakh Gurpreet Kaur , Snead Elisabeth , Singh Jaswant 
Published: June 2021

Ozone, a highly reactive air pollutant, has been linked to a variety of acute and chronic respiratory diseases in humans. Health Canada guidelines suggest acute (1 h) ozone exposures should not exceed 120 ppb. Studies exposing mice to much higher levels of ozone (2 ppm) suggest significant recruitment of lung neutrophils and macrophages at 24 h. However, to our knowledge, no studies have been conducted at ambient ozone concentrations. Daytime “ground” ozone levels can easily reach 50 ppb. We report that ambient ozone, at 50 ppb, induces alveolar cell death, leukocyte recruitment and has the ability to cause lung damage and thus is of relevance to public health. We hypothesized that CX3CR1 macrophages are protective in murine ozone‐induced lung inflammation and mediate lung neutrophil recruitment. We exposed wild‐type and CX3CR1‐null mice to 50 ppb ozone or filtered air for 2 hours, and collected peripheral blood, lung vascular perfusate and bronchoalveolar lavage at 0 h, 6 h and 22 h after exposure. Our preliminary data suggest alveolar macrophage, epithelial and endothelial cell toxicity, alveolar and systemic nuclear chromatin and actin deposits, with vascular neutrophil recruitment being observed as early as 0 h, 6 h and 22 h after ozone exposure. Moreover, absence of CX3CR1 leads to an exaggerated inflammatory response marked by enhanced neutrophil recruitment. We aim to further characterize the cellular metabolic and cytokine responses in our model, which will allow us to better understand how and why leukocytes are recruited in ozone‐induced lung inflammation, and will guide development of protective health strategies and environmental standards.Support or Funding InformationFedoruk Centre and Innovation SaskatchewanThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Antibody blockade of CD47‐SIRPα axis is protective in the murine model of Experimental Autoimmune Encephalomyelitis
Authors: Velazquez Francisco E , Autio Anu , Newton Gail , Luscinskas Francis William 
Published: June 2021

CD47 and its interaction with Signal Regulatory Protein alpha (SIRPα) play an important role in immune cell homeostasis. Our lab has previously demonstrated that CD47 on both endothelium and T cells plays an important role in T cell adhesion and diapedesis in vivo and in vitro, and that CD47−/− CD4+ T cells have impaired antigen‐mediated proliferation in the mouse model of Experimental Autoimmune Encephalomyelitis (EAE). Given the reports that CD47−/− mice and mice expressing a nonsignaling mutant SIRPα transgene are protected from developing EAE, suggests CD47 is a therapeutic target. However, a previous study found anti‐CD47 monoclonal antibody (mAb) MIAP301 treatment at the same time as myelin oligodendrocyte glycoprotein (MOG) immunization of mice delayed onset of disease and that treatment at peak of disease in animals resulted in a more severe disease. This “Janus like” effect has not been studied further. Using in vitro flow adhesion assays, here we show that mAb MIAP301 blocks both in cis (with LFA‐1 integrin) and in trans (with SIRPα) interactions of CD47 and that a different mAb MIAP410, blocks the SIRPα interaction and not LFA‐1‐ICAM‐1 interaction. We hypothesized that targeting only the “in trans” SIRPα interaction with MIAP410 in EAE would be protective. Thus we treated MOG immunized mice with MIAP410 or an isotype control IgG1 and investigated the leukocyte infiltration into the spinal cord using mass cytometry. Strikingly, treatment with MIAP410 prevented a more severe form of EAE when given at disease peak and was protective when given simultaneously with MOG. Mechanistically, MIAP410 had a profound inhibitory effect (68% inhibition) on the infiltration of IL‐23+ IFN‐γ producing γδ T cells into the spinal cord of the CNS with no significant differences observed on other immune cell infiltration such as Th17 cells. Additionally, we observed that there was decreased neutrophil and conventional dendritic cell infiltration in the spinal cord of MIAP410 as compared to IgG treated mice. Based on these findings, we conclude that CD47‐SIRPα interactions are necessary for the infiltration of pathogenic γδ T cells that express IL‐23R and promote leukocyte infiltration and neuronal damage in EAE.Support or Funding InformationT32 HL007627R01 HL125780RThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Novel Junctional Adhesion Molecule‐Like (JAML) Regulates Neutrophil Transepithelial Migration During Intestinal Inflammation
Authors: Azcutia Veronica , Kelm Matthias , Hilgarth Roland , Nusrat Asma , Parkos Charles A. 
Published: June 2021

Neutrophil (PMN) migration in the intestine is an essential component of host defense and wound repair. However, dysregulated PMN recruitment is a hallmark of inflammatory bowel disease (IBD). Disease flares in IBD are associated with robust PMN migrating across the intestinal mucosa resulting in crypt abscess formation and mucosal ulceration. Despite strong association of PMN infiltration into the gut with patient symptoms in IBD, the molecular basis of PMN transepithelial migration (TEpM) represents a significantly understudied area. It is now appreciated that PMN migration into intestinal mucosa requires multiple adhesive interactions between migrating PMN and intestinal epithelial cells (IECs), that represents a multi‐step process facilitated by complex interactions between PMN and IEC expressed proteins including members of the Junctional Adhesion Molecules (JAMs) family. We have reported that the novel JAM‐like protein termed JAML expressed on PMN, associates with the coxsackie and adenovirus receptor (CAR) expressed on epithelial cells. Binding of soluble JAML ectodomains to CAR has been shown to disrupt JAML‐CAR interactions and reduce PMN TEpM in‐vitro. To define the molecular mechanism of JAML regulation of PMN TEpM during intestinal inflammation in‐vivo, we generated JAML knockout mice (JAML−/−). PMN TEpM was evaluated using a small intestinal loop model, and PMN migration in response to the chemoattractant LTB4 (1nM) quantified by flow cytometry. While WT and JAML−/− mice had similar numbers of circulating leukocytes, we observed reduced PMN TEpM in‐vivo in JAML−/− mice compared to WT animals. This decrease in PMN traffic into the lumen was associated with increased retention of PMN within the intestinal epithelium in JAML−/− mice. In addition, epithelial accumulation of PMN in JAML−/− mice paralleled an increase in intestinal permeability to a 4KDa FITC‐dextran as detected by fluorescence intensity in serum. Finally, we studied the role of JAML on susceptibility to DSS induced colitis. Loss of JAML markedly increased disease activity index, inflammation and mucosal ulceration compared to WT mice. Overall, these observations suggest that JAML is an important adhesion molecule that regulates PMN TEpM in the intestinal mucosa. JAML thus represents a new therapeutic target to dampen excessive PMN migration during intestinal inflammation as seen in IBD.Support or Funding InformationCCFA CDA454814 and NIH 3R01 DK072564‐23S1This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
“This Is How You Do It, Right?!” Practical Suggestions for Designing and Implementing Education Research Projects within the Anatomy Classroom
Authors: Bentley Danielle Christine , Rosner Tamara , Hum Gregory , McCloy Cora 
Published: June 2021

Anatomy educators have become leaders in the Scholarship of Teaching and Learning (SoTL) within the biomedical sciences. Our classrooms and laboratories are learning hubs filled with innovative, evidence‐based pedagogies that we commonly systematically evaluate for learning effectiveness. As we continue to push the boundaries of innovative teaching, we must be careful to ensure we are developing, implementing, and disseminating education research projects with strong and resilient designs. Within the broad field of SoTL and education research there are common design flaws that can be avoided with careful preparation and forethought. Specifically, this presentation will focus on six themes of education research each with common concerns: 1) selecting an appropriate methodology and data collection strategy that best aligns with the specific research question(s), 2) establishing appropriate and informative comparison groups, 3) using randomization to control for between‐student factors (and to avoid self‐selection bias), 4) including appropriate considerations of power differential when using one's own students as research participants, 5) obtaining informed consent in a manner that respects student autonomy, and 6) selecting robust statistical analyses that fit the research design. Each theme will be thoroughly expanded upon in the context of the anatomy classroom/laboratory with concrete, practical suggestions for effective and meaningful SoTL projects. Positive examples will be extracted from recently published works to showcase exemplary research designs in the field. Ultimately, the goal of this presentation is to initiate and fuel constructive conversations on education research design elements; a conversation that will benefit junior and senior anatomy educators alike. By encouraging and facilitating strong, resilient, and thoughtful education research projects, anatomy educators can continue to be at the forefront of innovative SoTL practices that enhance learning for our students and positively impact biomedical education at large.Support or Funding Informationn/aThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Creating Educator Scholar Leaders—Curriculum Development of a New PhD Program in Anatomy Education
Authors: Terrell Mark , Kulesza Randy 
Published: June 2021

INTRODUCTIONAnatomy education is perhaps experiencing the best and the worst of times. It may be the best of times because so much hard work has been done by many anatomists over the past three decades to develop more effective and evidence‐based educational practices and technological tools to maximize student learning. The worst of times may be near as forces transform medical curricula and create a paucity of new anatomists as faculty retire and new schools are created/expanded.AIMUsing the arguments from both contexts, we sought to create a unique PhD program in Anatomy Education.METHODSApplying Kern's six step approach to curriculum development in medical education, we successfully merged the strengths and existing resources of two educational programs at LECOM to create a new PhD program in Anatomy Education.RESULTSThree critical components of this curricular endeavor include the educational preparation in transforming teaching and learning practices in anatomy; tight coherence and integration among anatomical and pedagogical knowledge, skills, and behaviors through clinical and educational supervision; and developing strategies for meeting challenges facing program approval at the institutional and accreditation levels. Several PhD students have marticulated and positively favor the new program.CONCLUSIONThis program has a strong commitment to producing a unique breed of new anatomists as education specialists who have the knowledge, skills and behaviors needed to lead health professions education development and research, thereby enhancing academic programs, improving health care outcomes, and strengthening the anatomical profession.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Comparison of Students' Performance in Multiple‐Choice vs. Short Answer Question Formats in Anatomy Spotter Exams
Authors: Bataineh Ziad Mohydeen 
Published: June 2021

IntroductionAnatomy spotter exam in the Anatomy Department at Sultan Qaboos University comprised identification of macroscopic and microscopic structures and questions related to their blood supply, innervation, normal and abnormal X‐rays, MRI and CT scan images, and embryological origins and abnormalities. We used the multiple choice format (MCF) and the short answer format (SAF) to assess the medical students. The students' performance in different courses across the test type were not assessedAimIn this study, medical students' performance in two formats of anatomy spotter exams were compared; the multiple choice format (MCF) and the short answer format (SAF).ResultsResults of spotter exams from three courses were used in this study, the cardiovascular system (CVS) and the respiratory system (RS), third year students, and the head and neck (H&N) fourth year students. For each system, a comparison of students' performance in SAF vs. MCF was made. The main factors in this comparison were the question type and the subject material of the course assessed.Our results indicate that in all courses assessed students' performance in MCF was either similar or slightly better than in the SAF. Students performed best in the CVS course and worst in the RS course regardless of the spotter type used. In addition, the MCF required less time to carryout.Discussion and ConclusionOn the other hand, student's performance in the SAF may have partially depended more on his ability to recall factual knowledge such as anatomical terminologies, structures' names and their correct spelling. We conclude that the spotter exams with the MCF are at least as effective as the SAF and may equally depend on Student's problem solving skills, and his ability to synthesize, communicate knowledge and make rational decisions.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Assessing Self‐assessment in Anatomy
Authors: Kingston Amanda K. , Garofalo Evan M. , Cardoza Kristinmae , Fisher Rebecca E. 
Published: June 2021

IntroductionFormative self‐assessments are frequently utilized in anatomy courses to gauge learning. Self‐assessment tools have been demonstrated to improve student learning and performance on exams. However, few studies have assessed how specific elements, such as the inclusion of visual components, Bloom's taxonomy level, and the degree of topic integration, influence the efficacy of self‐assessments in an anatomy course.AimThis study retrospectively examined the relationships between self‐assessment construction characteristics, exam construction characteristics, and student exam performance. Specifically, 1) What elements of exam question construction correlated with performance? and 2) What elements of self‐assessment questions correlated with performance on corresponding exam questions?MethodsSelf‐assessment and exam questions administered during the Clinical Anatomy Block at the University of Arizona College of Medicine ‐ Phoenix from 2014–2018 for the Thorax and Abdomen and Pelvis and Lower Extremity units were examined. Self‐assessment questions were distributed to students via email, while exams took place in the anatomy laboratory, with a majority of questions incorporating structures on the donors, images, or anatomical models. For all questions, the constituent learning objectives, use of visual components, Bloom's taxonomy level, and degree of topic integration were noted. Exam performance data were collected for each class as the percentage correct for each question. These variables were entered into linear multiple regression models to assess their relationship to student performance for individual learning objectives. Because no individually identifiable data were utilized in this study, IRB approval was waived by the University of Arizona Office of Research, Discovery & Innovation (Protocol #: 1810045386).ResultsRegression analysis indicates that having visual components in exam questions is negatively associated with performance (t = −5.53, p <0.00). Conversely, a higher average Bloom's level for targeted learning objectives in self‐assessments (t = 2.02, p = 0.04), and a greater number of image‐based questions (t = 2.33, p = 0.02) are positively correlated with performance on corresponding exam questions.ConclusionsThese findings provide evidence that elements of self‐assessment construction, such as a visual component and a higher cognitive level, influence student exam performance when the exam format also incorporates these elements.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Does Familiarization with Virtual Reality Improve Anatomy Learning in a Virtual Reality Environment?
Authors: Gill Jaskaran , Aggarwal Akanksha , Birk Sapriya , Hass Katrina , Mitchell Josh , Fenesi Barbara , Wainman Bruce 
Published: June 2021

Despite a scarcity in substantive evidence, virtual reality (VR) is heralded as the future of anatomy education. Recent research in our lab suggests that VR headsets are substantially inferior to traditional plastic models as educational tools. This effect appears to be mediated by the VR headsets' inability to create convincing stereopsis. Our study aims to investigate if familiarization with the VR environment improves performance. When presented with a new learning environment (e.g., a room in VR), one may encounter a “novelty effect” where the new environment demands focus and distracts from learning. An introduction to the VR environment prior to learning could minimize this effect. Therefore, we hypothesize that familiarization will improve test scores. Undergraduate university students with no prior formal anatomy education (n=50) will be randomized to a familiarization or non‐familiarization group. The former group is allowed to orient themselves with a VR car engine model, ad libitum. Then, both groups will undergo a learning phase with a VR pelvis model for 10 minutes. Participants will be tested using a 15‐item evaluation, consisting of an equal amount of nominal, spatial, and functional questions, immediately and 48 hours after learning. Preliminary data (n=8) suggest that there are currently no statistically significant differences in short‐ or long‐term evaluation scores (p=0.109, p=0.254, respectively) between the familiarization and non‐familizarization groups. If this trend persists through completion of the study, it would suggest that a familiarization phase does not improve test scores. Data collection and analysis are anticipated to be completed in January 2019. Gaining an understanding of which factors influence VR learning allows it to become a more effective, evidence‐based tool for anatomy education.Support or Funding InformationSelf‐funded.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.