bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross‐talk Among Kupffer Cells and Hepatic Stellate Cells is Critical for Kupffer Cell Activation during Liver Injury
Authors: Roth Katherine , Copple Bryan , Albee Ryan 
Published: November 2023

The mechanisms that regulate Kupffer cell activation in the liver after injury are not fully understood. Our recent studies demonstrated that activation of hypoxia‐inducible factor‐1a (HIF‐1α) in hepatic stellate cells (HSCs) is critical for Kupffer cell activation after liver injury. This indicates that cross‐talk among HSCs and Kupffer cells during liver injury is critically important for Kupffer cell activation. In our current studies, we tested the hypothesis that necrotic hepatocytes activate HIF‐1a in HSCs which stimulates release of a mediator that activates Kupffer cells. Our results demonstrate that treatment of primary, mouse HSCs with necrotic hepatocytes activates HIF‐1a. Necrotic hepatocytes failed to activate HIF‐1a in HSCs isolated from MyD88 knockout mice or in HSCs pretreated with the NF‐kB inhibitor MG132. This indicated a key role for toll‐like receptor and/or interleukin receptor signaling in activation of HIF‐1a in HSCs by necrotic hepatocytes. Treatment of Kupffer cells with necrotic hepatocytes did not increase expression of inflammatory cytokines, however, treatment of Kupffer cells with conditioned medium from HSCs treated with necrotic hepatocytes upregulated Cxcl2 and other inflammatory cytokines in Kupffer cells. Pretreatment of HSCs with the phospholipase A2 inhibitor, methyl arachidonyl fluorophosphonate, prevented HSC‐mediated Kupffer cell activation, suggesting that HSCs release an arachidonic acid metabolite after exposure to necrotic hepatocytes that activates Kupffer cells. In conclusion, these in vitro studies support our in vivo findings, and expand upon these studies by demonstrating that necrotic cells activate HIF‐1α in HSCs in a Myd88‐ and NF‐kB‐dependent manner, leading to the release of an arachidonic acid metabolite that activates Kupffer cells. Further characterization of this pathway could lead to the development of therapies aimed at reducing Kupffer cell‐mediated liver injury or increasing Kupffer cell‐mediated liver repair.Support or Funding InformationThis study was supported by NIH grant 2 R01 DK073566 to Bryan Copple. Katherine Roth was supported by NIH Training Grant T32 ES007255.
A Balancing Act: Role of HNF4α and β ‐catenin in Hepatobiliary Development and Cholangiocarcinoma Pathogenesis
Authors: Walesky Chad , Goessling Wolfram 
Published: November 2023

Cholangiocarcinoma (CC) is among the deadliest cancers worldwide, with a five‐year survival rate of ~15% in intrahepatic cholangiocarcinoma (ICC) and ~30% in extrahepatic cholangiocarcinoma (ECC). It is a rare cancer, affecting ~8,500 patients in the U.S. each year. The incidence of CC has increased, and there are few effective strategies for prevention, diagnosis, or treatment, indicating a significant unmet medical need. Often, altered developmental signaling can shed light on pathways that may also be altered during cancer pathogenesis. Therefore, our strategy is to understand mechanisms that are important in hepatobiliary development and examine these pathways in the context of CC pathogenesis in hopes of discovering novel therapeutic targets.We have recently shown that loss of hepatocyte nuclear factor 4 alpha (HNF4α) contributes to the pathogenesis of CC. Further, Wnt/β‐catenin has recently been shown to be upregulated in patients with CC. Therefore, we hypothesized that an HNF4α/β‐catenin interaction may be important in the context of CC pathogenesis.Hepatocytes and cholangiocytes are thought to originate from a bipotent progenitor cell population called hepatoblasts (Prox1‐positive). In the current study we have demonstrated the importance of proper HNF4α/β‐catenin signaling in the development of both hepatocytes and cholangiocytes within the zebrafish liver. HNF4α knockdown results in a loss of the hepatoblast marker Prox1. Interestingly, zebrafish maintain development of cholangiocytes following a loss of the Prox1‐positive hepatoblast population. Further, genetic or chemical increase in β‐catenin (APC‐/‐ ; Wnt agonist) results in a loss of HNF4α, Prox1, and a maintenance of cholangiocyte differentiation. Therefore, we hypothesize that over‐activation of β‐catenin results in a loss of HNF4α, causing hepatoblasts to preferentially differentiate into cholangiocytes.These studies demonstrate that HNF4α/β‐catenin signaling are directly linked to regulate hepatobiliary development. Further investigation into the mechanisms by which these pathways interact can provide valuable knowledge in understanding hepatobiliary development and how alterations in these pathways may contribute to cholangiocarcinoma pathogenesis.Support or Funding InformationSupported by a research fellowship from the Cholangiocarcinoma Foundation
Cells lining the lateral ventricle show dynamic protein expression following tail loss in the leopard gecko
Authors: McDonald Rebecca Paula , Gilbert Emily Anne Beatrice , Macdonald Alaina , Vickaryous Matthew Kenneth 
Published: November 2023

Neural stem progenitor cells (NSPCs) have been identified in the adult mammalian central nervous system, specifically in the dentate gyrus of the hippocampus and in the subventricular zone of the lateral ventricle. Despite this, mammals are incapable of central nervous system regeneration following injury. In contrast, many lizard species can regenerate their spinal cord (following tail loss) and some can even repair the optic nerve and parts of the brain. However, the source of cells contributing to brain regeneration remains unclear. Here we characterize cells lining the lateral ventricle of the brain in the leopard gecko, Eublepharis macularius. We show that these ventricular lining, or periventricular cells are a potential progenitor population capable of responding to central nervous system injury. Using a bromodeoxyuridine (BrdU) pulse‐chase experiment we determined that, prior to injury, periventricular cells are slow‐cycling. Moreover, periventricular cells show widespread expression of several common NSPC markers, including the transcription factor Sox2 and the intermediate filament glial fibrillary acidic protein (GFAP). In addition, a subset of periventricular cells express the neural progenitor cell marker Sox9. Following injury to the spinal cord (as a result of tail loss) populations of periventricular cells lining the lateral ventricle continue to express NSPC markers but also begin to proliferate, as evidenced by expression of both proliferating cell nuclear antigen (PCNA) and phosphohistone H3. Intriguingly, some of these cells newly express HuC/D, a marker of neuronal differentiation. Dynamic protein expression by periventricular cells indicates that this population is activated in response to injury, and points towards their potential to participate in neural regeneration.Support or Funding InformationNatural Sciences and Engineering Research Council (NSERC) Discovery Grant 400358
Use of iPad and ExamSoft&[trade] in administering morphological sciences practical examination in an integrated curriculum
Authors: Vasan Cheryl , Goldman Evan , Gentile Matthew , Perlis Susan , Ferrarie Joseph , Ferretti Colin , Greenfield Pete , Vasan Nagaswami 
Published: November 2023

At Cooper Medical School of Rowan University, morphological sciences are taught in an integrated organ system based curriculum. In the first year students in the last 8 weeks completed the skin, muscle and skeleton module. In the second year, the remainder of the organ systems is studied. Each practical exam includes cadaver, histology, pathology, radiology and embryology questions. As the class size has increased and with a limited number of faculty, manual grading of the practical exam had become onerous. Furthermore, manual grading challenged the validity and reliability of the assessment instrument. Therefore migration to an automated testing system was made. This move has proven to increase the validity, made the grading process more efficient and students are able to receive their practical exam scores faster with greater qualitative feedback than previous years. Recognizing the deficiency, the authors of the abstract met and operationalized the innovative system and purchased the required number of iPads through the Office of Medical Education. Student and faculty development using a mock exam was conducted. On the day of the practical exam, unique exam specific password was distributed to each student prior to the start of the practical. In addition, instructions were given on how to navigate, submit answers, and close out of the exam. IT personnel were on‐hand to solve technical problems. This poster will describe the step‐by‐step process of the approach, as well as present student and faculty perceptions.Support or Funding InformationThis study was supported by the Office of Medical Education.
Teaching Ultrasound Of The Musculoskeletal System During Anatomy Using the 7D Interactive Software Program
Authors: Blandford Ian , Benninger Brion 
Published: November 2023

INTRODUCTIONUltrasound (US) is increasingly being applied to thoracic and abdominal cavities with incredible momentum. However, there is a demand for musculoskeletal (MSK) US imaging as well. Although life‐threatening diagnosis can be made via US of the cavities, there are enormous numbers of everyday MSK complaints presented to the healthcare system. The objective of this study was to investigate if the MSK US educational software could develop MSK ultrasound users.METHODSLiterature search was conducted to find MSK US educational software use while teaching anatomy. The 7D Imaging interactive educational software (mskNAV) was provided to 20 students to navigate through the proximal upper limb (shoulder to elbow) section of the software during a one‐week period while dissecting the shoulder to elbow region. The students were evaluated on US machine use, probe skill, structure identification and clinical application on a standardized patient and didactic knowledge via a written exam. Fukuda Denshi UF‐760AG ultrasound machine with SonicEye finger probes was used.SUMMARYLiterature search revealed no known studies with interactive MSK US software. Students scored an average of 86% when evaluated on all aspects of the US examination of shoulder structures (machine & probe use, structure identification, and clinical relevance). Given the number of patients that present with MSK complaints, MSK US is underused and under taught. Medical students and residents are keen to learn MSK US techniques, however, there is insufficient qualified users to instruct them. There is a great need for interactive US education software that allows comprehensive self‐teaching. This study used the mskNAV iPad app to assess whether students can acquire ultrasound skills and knowledge during an anatomy course.CONCLUSIONThis study revealed the interactive mskNAV module was successful in integrating US skills with relevant structures and clinical applications while learning anatomy.
Self‐ and Peer Assessment of Professional Speaking Skills Using a Classroom Response System: Three “Clicker” Systems and Ten Years of Data Collection
Authors: Sprunger Leslie K 
Published: November 2023

A gross anatomy lab offers many opportunities for professional skills development. We have used an exercise in a gross anatomy laboratory for first year veterinary medical students which is focused on delivery of short educational presentations using new vocabulary to a small audience. At the end of a lab session, students present a brief overview of the day's work to 2–3 incoming students from another section. Each presenter is required to submit a self assessment using a rubric and a classroom response device. Similarly, their classmates are required to submit a peer assessment at the end of the presentation using the same rubric. The rubric incorporates five questions with quantitative scale responses, two optional questions with a menu of qualitative feedback (developed by students) and two questions to match presenters to their audience in subsequent data processing. Presenters receive an email within 24–48 hrs with their own self assessment data aligned with the peer feedback (names removed). Each student presents five to eight times over the course of the semester.Three different commercial classroom response systems have been used for this activity. All have served the purpose of the exercise but the most recent one (Top Hat, a bring your own device system) has met with the the most favorable response from the students and the smallest number of problems with data entry. A macro‐enabled template spreadsheet was developed in Microsoft Excel to facilitate processing of data prior to emailing feedback to presenters. Data has been collected to assess whether the exercise facilitates development of students’ professional speaking skills as reported by themselves as well as by their peers. In addition, students have been surveyed to measure their perception of the value of the exercise itself and also the value of the self‐ and peer assessments that are part of the exercise. Peer vs. self assessment scores from the qualitative responses are compared in the aggregate, as well as for individual students. Likewise, scores are tracked over the semester to identify, for example, trends in developing vocabulary skills or changes in the ability to organize a 5–10 minute informative presentation. There is often a tendency for students to give each other somewhat inflated scores, leaving little room to indicate improvement over time. Coaching students on the value of realistic feedback and the lack of value of hyperbole helps in this regard.Feedback about the value and effect of the presentations has also been collected during most years. Overall, students have indicated that the process is very valuable in helping keep them on task during the lab sessions (in anticipation of having to summarize it for their peers later), in increasing their confidence in the use of medical vocabulary, and that they appreciate having the opportunity to provide similar feedback for their peers.
Effectiveness of BlueLink Cadaveric Multimedia Resources in a Pre‐professional Course
Authors: Dudgeon Sarah Nixon , Alsup B. Kathleen , Fox Glenn M 
Published: November 2023

Self‐directed study is a skill necessary in successful learning. One method of self‐directed study is usage of multimedia resources. We have chosen to assess the effectiveness and usage of BlueLink multimedia resources, including course‐specific labeled cadaveric visuals, in illustrating learning objectives for two semesters of a pre‐professional 400‐level anatomy course (n=400). Resources typically supplied to these students, including textbooks, Netter atlases, and lecture slides were held constant in the study. On a five‐point Likert scale, students self‐reported usage of BlueLink resources and increased comprehension of course material. Data showed a strong, positive correlation between usage of BlueLink resources and increased comprehension of course material.Support or Funding InformationFunded by the University of Michigan Medical School Division of Anatomical Sciences, Department of Surgery.
Implementing the Sony Action Cam® and Camtasia® Software to Supplement Dissection‐Based Anatomy in DPT Programs
Authors: Immonen Jessica , Siefring Chris , Chung‐Hoon Kaiwi , McWhorter J. Wesley 
Published: November 2023

The average length of doctor of physical therapy (DPT) programs is three years; however, some programs are shorter in duration and may experience unique demands. A dissection‐based course can improve student understanding and retention of information, but this approach may be time consuming (1–4). One possible consideration may be the implementation of the Sony Action Cam® and Camtasia® video editing software to capture real‐time anatomical dissection to meet accelerated curriculum demands. Thus, the objective of this report is to explore whether instruction utilizing this technology is effective in the delivery of anatomical curriculum and relieving time constraints in the lab.The Sony® camera and editing software was used to create video tutorials of dissections for DPT students’ cadaver lab. During labs, the Sony® camera was also employed to live‐stream dissections to a HD t.v., allowing students to see real‐time manipulations of structure. Videos created using this technology were high resolution and provided students with more than narration by including tracers, mnemonics and notes. First‐year DPT students (N=54) were surveyed with SurveyMonkey® regarding the efficacy of the technology in the delivery of anatomy curriculum and correlating didactic curriculum to clinical work.In the first year DPT class, 93% found the technology “beneficial” in correlating didactic material to their future clinical work. 71% of students surveyed declared that live streaming of the dissections provided better understanding of material when students learned in large groups (N=16). In conclusion, this report is significant to improving the delivery of DPT applied anatomy curriculum. For this purpose, the Sony® camera has greater capabilities than the GoPro® and editing the videos with Camtasia® was deemed more helpful than videos with unedited narration. Live streaming of dissections improved understanding of material at the time of presentation and video tutorials provided a concise review method after class hours.Support or Funding InformationInternal Funding from Rocky Mountain University of Health Professions
Hypoxia‐Regulated Autophagic Pathways Mediate Epithelial Defense during Mucosal Inflammation
Authors: Kitzenberg David , Saeedi Bejan , Kelly Caleb , Schwisow Kayla , Campbell Eric , Lanis Jordi , Curtis Valerie , Glover Louise 
Published: November 2023

Intestinal epithelia provide the primary cellular interface between microbiota and host in the mammalian mucosal ecosystem. As such, epithelia actively participate as innate immune sensors of luminal bacteria that breach this barrier. Defects in epithelial autophagy have been identified in inflammatory bowel disease (IBD). Autophagy, a primordial degradation pathway, is implicated in diverse but interconnected immune responses such as mitochondrial signaling and elimination of invasive bacteria. Improved epithelial mitochondrial function proves protective in IBD, and a functional link between mitochondrial autophagy and bacterial autophagy has recently been established. However, crosstalk between these seemingly disparate processes is poorly characterized, and the regulatory pathways involved in epithelial cell‐intrinsic autophagy remain unknown. Recent work has defined a central role for the hypoxia‐inducible factor HIF in promoting epithelial bioenergetics and antimicrobial defense. Using a ChIP‐on‐chip approach, we identified autophagy as a novel pathway coordinately regulated by HIF, and highlighted a cohort of IBD‐implicated genes involved in the selective autophagy of mitochondria (mitophagy) and bacteria (xenophagy). Enteropathogen invasion was found to be an inherent driver of epithelial hypoxia and HIF‐depleted epithelia displayed dysregulated mitochondrial energetics and abrogated mitophagic and xenophagic responses. Conditional epithelial HIF‐deficient mice demonstrated increased bacterial dissemination and disease activity following acute invasive bacterial challenge. Moreover, augmentation of HIF‐regulated mitochondrial bioenergetics proved protective in mouse models of colitis. These findings place epithelial HIF as a central orchestrator of mitophagic and xenophagic responses during mucosal inflammation.Support or Funding InformationThis work was supported by a Crohn's and Colitis Foundation of America Career Development Award (LEG) and National Institute of Health NIDDK R01 grant DK103712 (LEG).
Differential Regulation of Macrophage Glucose Metabolism by M‐CSF and GM‐CSF: Implications for 18F‐FDG PET Imaging of Inflammation
Authors: Tavakoli Sina , Short John D , Downs Kevin , Nga Nguyen Huynh , Asmis Reto 
Published: November 2023

BackgroundThe high glycolytic capacity of macrophages allows for the utilization of 18F‐FDG in the detection of inflammation associated with various diseases. Microenvironmental signals (such as growth factors, cytokines and pathogen‐derived products) have profound effects on determining the activation state of macrophages, which in turn is delicately regulated through reprogramming of cell metabolism. Specifically, glycolysis has been suggested to enhance the pro‐inflammatory macrophage phenotype induced by pathogen‐derived stimuli. Here, we examined whether this phenomenon extends to endogenous microenvironmental activators by investigating the metabolic effects of two critical myeloid growth factors with opposing effects on the macrophage inflammatory state, i.e., macrophage colony‐stimulating factor (M‐CSF) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF).MethodsMurine peritoneal macrophages (Mϕ) were incubated ex vivo for two days in the absence (Mϕ0) or presence of M‐CSF (MϕM‐CSF) or GM‐CSF (MϕGM‐CSF). Glucose uptake was measured using 3H‐2‐deoxyglucose. Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), markers of oxidative and glycolytic metabolism, as well as mitochondrial content of the cells and lactate production were quantified. Expression of activation markers, glucose transporters and metabolic enzymes was measured by high‐throughput quantitative reverse‐transcription PCR.ResultsM‐CSF and GM‐CSF stimulated comparable levels of 3H‐2‐deoxyglucose uptake and induced similar expression levels of glucose transporter‐1 and ‐6 in Mϕ. Similarly, mitochondrial biogenesis and oxidative metabolism were induced to the same levels in MϕM‐CSF and MϕGM‐CSF. Unexpectedly, activation of glycolysis was more pronounced in MϕM‐CSF compared to MϕGM‐CSF, as evidenced by higher basal ECAR and ECAR‐to‐OCR ratio, as well as lactate production. A number of critical glycolytic enzymes were also differentially upregulated in MϕM‐CSF compared to MϕGM‐CSF.ConclusionDespite their pro‐inflammatory activation state, MϕGM‐CSF showed the same level of glucose uptake and oxidative metabolism as MϕM‐CSF, which are associated with inflammation resolution. Furthermore, MϕM‐CSF, not the pro‐inflammatory MϕGM‐CSF, demonstrate the higher glycolytic activity. These findings strongly suggest that the reported association between a pro‐inflammatory macrophage phenotype and increased glucose uptake and glycolysis is limited to certain microenvironmental signals, and does not represent a universal phenomenon, calling for a more prudent approach in the interpretation of 18F‐FDG imaging of inflammation.Support or Funding InformationThis work was supported by grants from Radiological Society of North America Grant to S.T. (RR1131) and the National Institute of Health (HL115858) to R.A.