bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNAJB1‐PKRACA ‐ A Novel PKa Fusion Protein That Drives Fibrolamellar Hepatocellular Carcinoma
Authors: Simon Sandy 
Published: November 2023

Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare liver tumor that usually occurs in adolescents and young adults. Characterized by hepatocytes with deeply eosinophilic, granular cytoplasm interspersed with fibrous bands, FLHCC is without signs of cirrhosis as in Hepatocellular Carcinoma. To characterize its molecular pathogenesis, we performed RNA‐seq and whole genome sequencing of FLHCC paired with normal liver from the same patient.The majority of the DNA was unremarkable with few recurrent mutations or structural variants such as amplifications or inversions. The exception was a heterogeneous deletion of ~400 kB in one copy of chromosome 19. This produced a chimeric transcript and a fusion between the heat shock protein DNAJB1 and the catalytic subunit of protein kinase A (PRKACA) which retained full enzymatic activity. This chimera has been found in every patient (n>200). Differential expression analysis of RNA‐seq revealed many changes in the gene expression in FLHCC. These were generally consistent between patients with FLHCC and different from HCC samples from the TCGA or published reports of other cancers. Some of the observed changes can directly be linked to increased activity of PRKACA. Other changes involve pathways known to participate in the initiation and progression of other cancers, which, along with an increase of PRKACA activity, represent targets for therapeutic intervention. Several of these targets are now being explored in cellular models, genetic, and PDX mouse models, as well as clinical trials.Support or Funding InformationThe Rockefeller University Center for Clinical and Translational Science Grant 2UL1RR024143, The Sohn Foundation, The Rockefeller University, The Fibrolamellar Cancer Foundation
Transformation of the Introductory Biology Experience for Biology Majors: Progress of the Northwest Bioscience Consortium RCN‐UBE
Authors: Kruchten Anne , Baumgartner Erin , Beadles‐Bohling Amy , Whitman Jeffrey , Duncan Jason , Kayes Lori , Kiser Stacey , Shriner Walter , Stavrianeas Stasinos 
Published: November 2023

The Northwest Biosciences Consortium is a group of two‐year and four‐year college faculty at both public and private institutions in the State of Oregon. Funded by an NSF RCN‐UBE grant, this group is working towards creating modern, student‐centered, integrated, and investigative introductory biology experiences for all students aligned with the Vision and Change: A Call to Action mandate. In our third year of the grant we now report on the activities of this group including two recent faculty workshops to encourage broad faculty involvement in our project goals. At the 2015 Winter Institute, faculty were introduced to active learning techniques that would help foster an inclusive environment for our students. At the 2016 Winter Institute, faculty participated in the development of instructional modules and assessment techniques in core areas identified by faculty as essential areas in the study of introductory biology. In addition to the results of the Winter Institutes, we will report on obstacles we have encountered especially in the area of smoothing the transition for transfer students taking an introductory sequence at a two year college followed by advanced coursework in biology at a four year college and plans for professional development activities for faculty across our institutions to encourage the adoption of student‐centered pedagogies aligned with Vision and Change and collaboration with other networks such as NW PULSE, PKAL, and NABT who are engaged in similar work. As a long‐term goal, we are particularly interested in helping faculty develop scaleable classroom modules and assessment practices that will encourage consistency in introductory biology outcomes across our diverse two‐year and four‐year institutions.Support or Funding InformationSupported by the National Science Foundation RCN‐UBE grant (DBI‐1248121).
The Design And Impact of a New Biomedical Seminar Deconstruction Course on Undergraduate Learning‐A Pilot Study
Authors: Osborne Sally , Schroeter Sara 
Published: November 2023

We designed and piloted a research seminar deconstruction course to expose second year undergraduate students to high impact research, bridge the gap in their understanding of the scientific process and provide the opportunity to formulate their own research proposals. Deconstruction sessions included small and large discussion groups using flipped model of classroom teaching facilitated by problem sets with strong emphasis on web‐based resource library developed specifically for each seminar. Students were assessed based on written mini‐journals, seminar summaries, problem sets, and the oral presentation of their research proposal. Didactic sessions on guidelines for scientific presentation and writing research proposal were built‐in the course. Semi‐structured interviews and pre and post course surveys administered to ten students registered in the inaugural course show key learning gains in written and oral presentation of scientific material, interpretation of scientific results, understanding of the scientific process, confidence in developing realistic scientific research questions. The key challenges reported by students included coping with the high workload and planning their research proposal. The majority of the students reported learning skills that were transferable to other classes highlighting time management and critical thinking skills which they felt would enable them succeed in upper level research streams; some even described it as their favorite course.Support or Funding InformationUBC Centre for Teaching, Learning & Technology
Navigating from Vision to Change: Tools to help biology departments align curriculum with the core concepts of biology
Authors: Brownell Sara , Wright Christian E , Couch Brian , Crowe Alison , Freeman Scott , Wenderoth Mary Pat 
Published: November 2023

Vision and Change in Undergraduate Biology Education outlined five core concepts intended to guide undergraduate biology education: 1) evolution; 2) structure and function; 3) information flow, exchange, and storage; 4) pathways and transformations of energy and matter; and 5) systems.We have taken these general recommendations and created the BioCore Guide—a set of general principles and specific statements that expand upon the core concepts, creating a framework that biology departments can use to align with the goals of Vision and Change. We used a grassroots approach to generate the BioCore Guide, beginning with faculty ideas as the basis for an iterative process that incorporated feedback from more than 240 biologists and biology educators at a diverse range of academic institutions throughout the United States. The final validation step in this process demonstrated strong national consensus, with more than 90% of respondents agreeing with the importance and scientific accuracy of the statements.We are using the BioCore Guide to create a general biology programmatic assessment called Gen‐BioMaps that biology departments could use to monitor the progression of student understanding of the core concepts as they move through the major. Gen‐BioMaps uses a format of multiple T/F questions that span the sub‐disciplines of biology to test student understanding of the core concepts outlined in the BioCore Guide. We have implemented an iterative process in developing the stems and statements, including (1) revising based on student feedback from over 150 think aloud interviews, (2) piloting to over 1900 students nationally, and (3) incorporating expert feedback. We are currently revising the assessment and will be performing a final set of interviews, expert validation, and administration of the final version of GenBio‐MAPS in the spring of 2016.Biology departments can use the BioCore Guide and Gen‐BioMaps as resources to guide curricular design, including helping faculty to articulate learning objectives aligned with Vision and Change, develop a more cohesive undergraduate biology curriculum, identify current gaps in the curriculum, and monitor student understanding of the core concepts of biology. It is our hope that both the BioCore Guide and the Gen‐BioMaps programmatic assessment will serve as agents of change for biology departments as we move toward transforming undergraduate biology education.Support or Funding InformationNSF DUE 1323010
Modeling Aortic Insufficiency in the Scranton Cardiovascular Model
Authors: Graham Michelle Theresa 
Published: November 2023

The effects of aortic insufficiency (AI) on cardiovascular hemodynamics are well known. Mean arterial pressure (MAP) decreases, driving compensatory mechanisms to reestablish MAP within a normal range. However, there are few pedagogical models designed to address instruction in the cardiovascular ramifications of valvular dysfunction. The Scranton Cardiovascular Model (SCM), a computer‐driven, fluid pumping, mechanical model of the cardiovascular system, was developed to improve cardiovascular physiology education1. We have extended the capabilities of the SCM to enable modeling of the hemodynamics of valvular dysfunction. A new component was fabricated to allow the normal SCM aortic valve to be quickly and reversibly replaced by a dysfunctional aortic valve. Insufficient valves of quantifiable regurgitant orifice area were designed and implemented to demonstrate systemic effects of progressive dysfunction, comparable to clinical data. The capability to model acute uncompensated AI and acute compensated AI was demonstrated through analysis of cardiac parameters such as mean arterial pressure, cardiac output, pulse pressure, and left ventricular end diastolic pressure. To simulate acute compensated AI, total peripheral resistance (TPR), contractility, and central venous tone were manipulated in the SCM until normal MAP was reestablished. Corresponding forward cardiac output (CO) reflected cardiovascular system efficacy. In uncompensated severe AI, MAP and CO, respectively, decreased to 66% and 73% of basal values. Multiple compensatory settings successfully reestablished normal MAP. The magnitude of the individual contributions of TPR and contractility to the restoration of MAP differentially impacted CO. Increased TPR restored MAP while decreasing CO. Increased contractility restored MAP while improving CO. We continue to fine‐tune SCM AI to more closely match clinical data. This “proof of concept” opens up a new pedagogical application for the SCM.Support or Funding InformationSupported by the University of Scranton
Examining the immunomodulatory effects of IL‐12 in a mouse model of Alzheimer's Disease
Authors: Klaidman Lori , Ellefson Dolph D , Gallaher Tim , Stark Elena , Schettler Stephen P 
Published: November 2023

Interleukin‐12 (IL‐12) is known to be a differentiation factor for naïve T‐cells into Th1 cells. We have previously used IL‐12 as a systemic therapeutic agent to clear Amyloid Beta (Aβ) peptides in a transgenic APPswe/PS1dE9 mouse model for Alzheimer's Disease. It was found that a modest decrease in Aβ plaque formation in this model using IL‐12 was associated with increased microglial activation using the marker, Ionized calcium‐binding adaptor molecule 1 (Iba1), also known as Allograft inflammatory factor 1 (AIF‐1). Iba1 is known to be expressed on activated microglial cells during an inflammatory response in the brain. In this study, we examined whether additional consecutive doses of IL‐12 would further magnify microglial activation in the brain. At 18 months old, wild type or AD mice were injected subcutaneously with IL‐12 once a week (20 ng) and sacrificed at day 21 or 42 (3 weeks vs 6 weeks). Mice were divided into the following groups: 1) WT mice, 2) WT mice with IL‐12 (3 weeks), 3) WT mice with IL‐12 (6 weeks) 4) AD mice, 5) AD mice with IL‐12 (3 weeks), and 6) AD mice with IL‐12 (6 weeks). Mouse brains were perfused and brain slices were quantitated by immunohistochemical (IHC) methods using imaging software for Aβ 1–40 or Aβ 1–42 peptides in AD brains, and for Iba1 in all groups. We further quantitated IL‐12rβ2 (IL‐12 receptor) using similar IHC techniques, in order to examine whether systemic IL‐12 administration also resulted in upregulated IL‐12 receptors in the brain. The results indicate a complex neuromodulatory effect.Support or Funding InformationUCLA Department of Pathology and Laboratory Medicine
Neuritin, a New Potential Target for Optic Nerve Injury Therapy
Authors: Xu Jiajun , Cao Wenluo , Liu Weiye , Ma Haoqian , Qi Aiqing , Huang Tingting , Li Lin , Liu Fang 
Published: November 2023

Optic nerve, which also belongs to the central nervous system, is difficult to repair once get injured. Neuritin, a novel member of the neurotrophic factor family, serves as a common downstream effector of neurotrophic factors and neural activity. Our experiment investigated the spatiotemporal expression of neuritin in adult rat retina and optic nerve in normal and after optic nerve crush. Following crush, neuritin protein and mRNA transiently increased in retina and optic nerve. In vivo, after neuritin lentivirus infection of rat retina, the number of retinal ganglion cells and optic nerve axons were increased significantly after injury, this profective effects was further confirmed by the functional tests like pupillary light reflex and visual evoked potential, suggesting that neuritin play a critical role in optic nerve regeneration. Further more, our results showed exogenous rhneuritin promotes RGC5 cell line survival and neuritin overexpression promotes neurite outgrowth which may through the upregulation of phosphorylation of Akt and Erk, and reduces cell apoptosis which may through the inhibition of caspase 3 activation after RGC5 damage in vitro. Our experiments suggested that neuritin is a potential new target for optic nerve injury therapy and provide alternative way for repairing injury of central nervous system.Support or Funding InformationNational Natural Science Foundation of China (Grant No. 31271282)
Accuracy of localisation and cause of preclinically suspected diagnoses. Explorative analysis of retrospective data of 700 patients
Authors: Hirtler Lena , Huber Florian 
Published: November 2023

IntroductionThe preclinical acute patient management by non‐physicians (i.e. paramedics, EMTs, etc.) is known to have large‐scale differences in accuracy and specificity, depending on numerous variables, such as rural vs. metropolitan regions or international differences in education of paramedics. The primary aim of our study was to find out differences in accuracy of anatomic localization and etiologic cause of preclinically suspected diagnoses between traumatic and atraumatic patients.Patients & MethodsSeven‐hundred patients were randomly chosen as cases from the archived protocols of 2014 of a large city emergency medical service. The patients were assorted into two same‐sized groups, “atraumatic” and “traumatic”, which was performed depending on the designated clinical department. To find out suspected diagnosis, symptoms and respective anatomic region, and to match these with the eventual diagnosis, patient data was retrieved from EMS protocols and hospital reports. Statistical analysis of the two groups was performed and compared. We also evaluated side‐parameters such as presence or absence of intensified trauma training of transport leading paramedic and others.ResultsPreliminary results showed differences in the accuracy of anatomic localization and cause of preclinically suspected diagnoses in traumatic and atraumatic patients. Especially anatomic localization is more precise in traumatic patients than in the other collective. There was no significant increase in anatomic accuracy in traumatic patients who were treated by paramedics with certified special trauma course skills, compared to patients who were evaluated by staff without intensified EMS education.DiscussionThe effect of intensified trauma training is known to have had an impact on quality of practical skills in preclinical and hospital settings. It is discuss, whether and how training in anatomy and internal medicine could improve the accuracy and quality of patient evaluation by non‐physician EMS workers.Support or Funding InformationThe authors have nothing to declare.
How do Alternative and Traditional Dissemination Metrics Compare in Medical Education Scholarship?
Authors: Ramnanan Christopher J , Ambacher Kristin , Amath Aysah , O'Brien Cameron , Wood Timothy J , Leddy John J 
Published: November 2023

PurposeMedical educators need to demonstrate the dissemination of scholarship for academic promotion. Dissemination impact has traditionally been measured using citation‐based metrics. In recent years, other platforms (such as social media tools like Twitter and Facebook) have provided new avenues for authors to promote their work to both scholarly and non‐scholarly audiences. While alternative metrics (altmetrics) can capture non‐traditional dissemination data such as attention generated on social media, the academic value of altmetrics in medical education is unclear. The aim of this study was to determine which altmetrics are indices of access counts and citations in a highly cited, general interest medical education journal.MethodsA database study was performed (August 2015) for all Medical Education papers in 2012 (n=236) and 2013 (n=246). Citation, altmetric and access (HTML views + PDF downloads) data were obtained from Scopus, the Altmetric Bookmarklet Tool, and the journal Medical Education, respectively. Correlation coefficients (r values) between variables were determined and statistical significance was calculated.ResultsFacebook, Google+, Reddit, and LinkedIn were each only used in the dissemination of a small fraction of papers and were not characterized further. Twitter and Mendeley were the only Altmetric‐tracked platforms utilized in the dissemination of greater than 50% of articles. For access counts versus Mendeley downloads, Twitter mentions, and Altmetric Scores, the correlation coefficients were r = 0.79, 0.56, and 0.52 for 2012 papers and 0.65, 0.32, and 0.35 for 2013 papers, respectively. For citation counts versus access counts, Mendeley downloads, Twitter mentions and Altmetric Scores, the correlation coefficients were r = 0.77, 0.81, 0.57, and 0.58 for 2012 papers and 0.62, 0.61, 0.18, and. 0.22 for 2013 papers, respectively. All correlations were statistically significant (P<0.01).ConclusionsMendeley downloads appear to be the strongest altmetric index of both readership and citations for articles in the high‐impact, general interest journal Medical Education. We conclude that access‐based indices (i.e. views and downloads) may be the best Altmetric tool to use in conjunction with citations for the purposes of measuring the impact of medical education scholarship.
X‐perience – an Interactive Viewing Platform Displaying Radiographic Profiles of Cadavers for Educational Purposes
Authors: Riogh Eithne Nic an , Perry Gary F , Jones James FX , Tattersall Adam , Heduan Martin , Stern Richard H , MacMahon Peter , Giannotti Nicola , Davis Michaela 
Published: November 2023

Traditionally anatomy teaching has involved both learning from cadaveric dissection and formal lectures. The aim of our project was to introduce another dimension to students’ experiences of learning anatomy through the medium of radiology.This project presents donor specific radiographic profiles of University College Dublin's cadavers for educational purposes. An interactive viewing platform Xperience was developed to vividly display these non‐generic images. Comprehensive donor profiles were created by adding medical histories and consultant radiologists’ reports. These self‐guided image‐based clinical cases enhance anatomical learning and offer early introduction of clinical radiography. X‐perience complements the dissection process by reinforcing the concept of the donor as the student's first patient.Full skeletal radiographs were obtained from 13 donors (10 Female, 3 Male) aged 58–101 years. Radiographic images were produced digitally, labelled and stored using unique identifiers. These images were systemically labelled for normal and pathological findings and integrated with known medical history. Articulate Storyline 2 was used to build X‐perience, a HTML5 interactive interface. To assess the value of X‐perience Stage 3 Locomotor Biology students were surveyed. This cohort (n=50) had prior traditional anatomical teaching and could compare anatomical learning with and without X‐perience.The workflow of profiling cadavers and constructing X‐perience proved successful. X‐perience is currently used by students during Dissecting Room practical classes and can be revisited via Blackboard, an online learning management system. Results of student acceptability survey, Kirkpatrick Level‐1, are extremely positive. 84% of students agree that X‐perience is relevant, easy to use and provides an integrated view of the human body. 88% appreciated the clinical relevance that X‐perience offers. 92% of students acknowledged that they now had a greater understanding of the importance of radiology.The introduction of similar viewing platforms in other medical schools is recommended. Imaging modalities such as CT and/or histology could further refine X‐perience.In addition to its educational value, X‐perience strengthens the body donation program, highlighting the individuality and dignity of each donor and generating enthusiasm amongst students.
FPR1 and Activation of Intestinal Fibroblasts
Authors: Reaves Titus A. , Anderson‐Thomas Meghan , Nillas Andrea , Lecher Mackenzie 
Published: November 2023

Fibroblasts are mesenchymal cells that produced the connective tissue consisting of collagens, laminins, and proteoglycans. Myofibroblasts are activated fibroblasts that express α‐smooth muscle actin and contract during wound healing. If activation continues, myofibroblasts become over‐activated and intestinal fibrosis (excessive and dysregulated collagen production that affects the function of the intestine) may result. Despite this information, the molecular events of fibrosis are not completely understood. We have shown that fibroblasts express the Nα‐formyl‐L‐methionyl‐L‐phenyalanine receptor (FPR1), which is a G‐protein coupled receptor that regulates the leukocyte response to bacterial formylated peptides. We initially exposed intestinal fibroblasts to a variety of inflammatory mediators that include lipopolysaccharide (LPS), IL‐6, and IL‐8. Interestingly, LPS treatment resulted substantial upregulation of FPR1, while IL‐8 treatment resulted in a substantial down‐regulation of FPR1. Using Flow Cytometry, similar results were obtained. We examined whether constitutive activation of the FPR1 (and inhibitors) resulted in the over‐activation of myofibroblasts and ultimate release of excessive and dysregulated collagen. Studies revealed that reducing FPR1 exacerbates the inflammatory response of fibroblasts. Taken together, the FPR1 appears to modulate the activation of fibroblasts. Down‐regulation of the FPR1 may lead to a better understanding the fibrotic response and better treatments of dysregulated inflammatory conditions involving fibroblasts.Support or Funding InformationNational Science Foundation RII