bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of Wnt5a in urothelial carcinoma as potential prognostic marker
Authors: Saling Mark , Duckett Jordan , Jenkinson Scott , Malgor Ramiro
Published: June 2021

Bladder cancer is the fourth most common cancer in males and the most common malignancy of the urinary tract. According to American Cancer Society 74,690 new cases and 15,580 deaths from bladder cancer are expected for 2014 in the US. Our group recently reported a positive correlation between the expression of Wnt5a, a member of the Wnt proteins family, and histopathological grade and stage of urothelial carcinoma (UC). The objective of the study was to analyze the correlation between the expression of Wnt5a, E‐cadherin, and β‐catenin and histopathological grade of the UC in human tissue samples. The expression of the receptor tyrosine kinase‐like orphan receptor 2 (Ror2) in the tumor as a mechanism of Wnt5a in the metastatic process was also explored

Tissue samples were obtained via transurethral resection for diagnostic purposes, formalin fixed and paraffin embedded. Wnt5a, E‐cadherin, β‐catenin, and Ror‐2 expression was characterized in UC samples using immunohistochemistry (IHC). The histopathological grade of each sample was determined using H&E stained sections and applying International Society of Urological Pathology (ISUP) criteria.

The IHC results show that low grade tumors show strong staining for E‐cadherin and β‐catenin and weak staining for Wnt5a while, high grade tumors show opposite result. Interestingly, high grade tumors that show invasion into the muscularis propria show strong immunostaining for both Wnt5a and Ror2 while in noninvasive tumors a weak staining for Ror2 was detected.

These results are in agreement with previous reports from our laboratory and support the potential application of Wnt5a as a prognostic marker for UC. Based on our results, Wnt5a‐Ror2 signaling may play a role in the invasiveness of UC.
Using Protein Microarray Technology to Screen Anti‐PD‐1 Monoclonal Antibodies for Specificity and Applications in Anatomic Pathology
Authors: Chen Caiwei , Wei Haitao , Yuan Kehu , Wu Guiyin , Chen Jian , Chu Boyang , Wang Guangli , Shu Youmin , He Weiwu , Ma Donghui
Published: June 2021

Programmed death‐1 (PD‐1) expresses in many tumors in response to inflammation. It is up‐regulated in activated T lymphocytes and inhibits T‐cell function upon binding to its ligands PD‐L1 and PDL2 and serves as a key checkpoint of the immune system. KEYTRUDA (pembrolizumab) is the first anti‐PD‐1 therapy approved in the United States and received FDA's Breakthrough Therapy designation for advanced melanoma. Thus, to evaluate PD1 protein levels in formalin‐fixed paraffin‐embedded tissue samples, a high quality monoclonal antibody validated for immunohistochemistry (IHC) is needed.

To develop the best monoclonal antibody for PD‐1 IHC analysis, 41 monoclonal antibodies were generated. 8 of them work for IHC application on FFPE tissue sections. To identify clones that are mono‐specific on target, only two clones passed our high density protein microarray chip tests. Other immunoassays and species cross‐reactivity tests were also explored.

In summary, two newly generated monoclonal antibodies demonstrated ultra‐specificity against PD‐1 protein and superior performance for IHC analyses. These two clones could be utilized as companion diagnostic reagents to stratify cancer patients before KEYTRUDA prescription.

This research is partly supported by Chinese 863 research grant number 2014AA020909.
Effect of Rapamycin on the Gene Expression Signature of Focal Lesions in a Model of Progenitor‐Derived HCC
Authors: Adebayo Adeola , Francois‐Vaughan Heather , Brilliant Kate , Gruppuso Philip , Sanders Jennifer
Published: June 2021

Given that current treatment options for hepatocellular carcinoma (HCC) are of limited efficacy, we have focused on chemoprevention and the mechanistic Target Of Rapamycin (mTOR), a nutrient‐sensing serine/threonine protein kinase that regulates cell growth and metabolism. Using the Solt‐Farber model of progenitor‐derived HCC, we have shown that mTOR is activated in the early stages of preneoplastic foci development. Rapamycin, an mTOR inhibitor, blocks this activation. The aim of this study is to characterize the genetic signature and molecular pathogenesis of rapamycin‐inhibited foci as compared to placebo progressive preneoplastic foci. Persistent foci, which were reduced by up to 80% in the rapamycin group, were isolated by laser capture microdissection and the transcriptome of the captured tissue analyzed by microarray. Gene Set Enrichment Analysis (GSEA) showed that rapamycin significantly (FDR<0.05) suppressed genes associated with ribosomal biogenesis, cell cycle progression, glutathione metabolism and ubiquitin‐mediated proteolysis. Ingenuity Pathway Analysis (IPA) was performed using input that consist of genes showing a 2.4 fold change and FDR<0.05. Results revealed several canonical pathways, including FXR/RXR function and activation, and upstream regulators, PPARA and HNF1A. These results indicate that inhibition of mTOR signaling early in the process of hepatic carcinogenesis has a persistent, anti‐growth effect associated with marked changes in gene expression.
Origin and Diversity of Fibroblastic Cells From Intrahepatic Cholangiocarcinoma
Authors: Sirica Alphonse , Usui Akihiro , Campbell Deanna , Dumur Catherine
Published: June 2021

To elucidate cancer‐associated fibroblast (CAF) origins and diversity within intrahepatic cholangiocarcinoma (ICC), we analyzed the phenotypic, cytogenetic, gene expression profiles, growth properties, and select functions of two novel CAF cell strains (BDEsp‐TDFSM and BDEsp‐TDFDE) along with those of a cholangiocarcinoma (CC) cell strain (BDEsp‐TDECC). Each cell strain was derived from desmoplastic CC formed in rat liver following bile duct inoculation of spontaneously‐transformed rat cholangiocytes. Unlike the CAF strains, BDEsp‐TDECC exhibited anchorage‐independent growth, contained more numerous chromosomal aberrations, and was tumorigenic in rat liver. Both CAF strains exhibited similar, but distinct gene expression profiles compatible with their having a mesenchymal cell origin. TDFSM cells could be distinguished from TDFDE cells by being strongly immunoreactive for α‐smooth muscle actin (SM), positive for the portal fibroblast (PF) marker cofilin 1, negative for the hepatic stellate cell marker desmin (DE), and by producing significantly greater amounts of collagen type I. Co‐culturing BDE‐TDFSM with BDE‐TDECC in a novel 3‐D culture model dramatically potentiated the production of collagen type I and greatly enhanced the numbers of both cytokeratin 19+/Ki‐67+ spheroid/ductal CC structures and TDFSM cells within the matrix when compared with TDECC/TDFDE co‐culture or TDECC, TDFSM, or TDEDE monocultures. The vast majority of CAFs accumulated within the stroma of analyzed rat and human ICC were further found to be SM+/DE‐ , with DE+ fibroblastic cells comprising only a small minority population. Our results suggest that SM+/cofilin1+/DE‐ CAFs promoting desmoplasia and ICC growth may largely be derived from PF.
Identification of MicroRNA‐mRNA Dysregulations in Paroxysmal Atrial Fibrillation
Authors: Chiang David , Zhang Min , Voigt Niels , Alsina Katherina , Jakob Heinz , Martin James , Dobrev Dobromir , Wehrens Xander , Li Na
Published: June 2021

Background

The molecular mechanisms underlying the early development of atrial fibrillation remain poorly understood. Emerging evidence suggests that abnormal epigenetic modulation via microRNAs (miRNAs) may be involved in the pathogenesis of paroxysmal atrial fibrillation (pAF).

Objective

To identify key molecular changes associated with pAF, we conducted state‐of‐the‐art transcriptomic studies to identify the abnormal miRNA‐mRNA interactions potentially driving AF development.

Methods and Results

High quality total RNA including miRNA was isolated from atrial biopsies of age‐matched and sex‐matched pAF patients and control patients in sinus rhythm (SR; n=4 per group) and used for RNA‐sequencing and miRNA microarrays. 113 genes and 49 miRNAs were differentially expressed (DE) in pAF versus SR patients. Gene ontology analysis revealed an enrichment of DE genes in the “gonadotropin releasing hormone receptor pathway” and “p53 pathway”. Also, bioinformatic analyses identified 23 pairs of putative miRNA‐mRNA interactions that were altered in pAF (including 15 miRNAs and 17 mRNAs). Using quantitative real‐time (qRT)‐PCR and 3′UTR luciferase assays, the interaction between upregulation of miR‐199a‐5p and downregulation of FKBP5 was confirmed in pAF samples (P<0.05 vs. SR).

Conclusion

This is the first transcriptomic and miRNA microarray study using samples from pAF patients. Combined with bioinformatics and molecular validation, we provide novel insights into the pathways and miRNA‐mRNA dysregulations that may drive AF development. This opens up new avenues of research into AF pathogenesis as well as therapeutic development.
Circulating CXCL‐9, ‐10 and ‐11 Levels Improve the Discrimination of Risk Prediction Models for Left Ventricular Dysfunction
Authors: Altara Raffaele , Gu Yumei , Struijker‐Boudier Harry , Staessen Jan , Blankesteijn W Matthijs
Published: June 2021

Introduction

Detection of left ventricular dysfunction (LVD), a condition preceding heart failure, can be challenging. Because inflammation contributes to heart failure development, we measured serum levels of three related chemokines, CXCL‐9, ‐10 and ‐11, and NT‐proBNP in serum from subjects with LVD and controls and determined their improvement of risk prediction.

Methods

Subjects with subclinical (n=17) or advanced (N=14) LVD and age‐ and sex‐matched controls (n=31) were recruited from the large‐scale family‐based study on the genetic epidemiology of cardiovascular phenotypes (FLEMENGHO). Cytokine levels were determined by ELISA. Integration Discrimination Improvement (IDI) and Net Reclassification Improvement (NRI) were determined using SAS software.

Results

Increased serum levels of CXCL‐9, ‐10 and ‐11 were observed in the LVD groups (1.5, 1.3 and 1.8‐fold in the subclinical LVD and 2.2, 2.5 and 4‐fold in the advanced LVD group, respectively; p<0.01). NT‐proBNP was 1.5 and 1.8‐fold higher in the subclinical and advanced LVD groups; p<0.01). Adding the biomarker levels in a dichotomized way to a model already including established risk factors resulted in an improved NRI of 14.2% (P<0.01) and IDI of 155% (P<0.001)

Conclusion

Addition of CXCL‐9, ‐10 and ‐11 levels to established risk factors significantly improves the risk prediction models for LVD. This study underscores the importance of using a panel of biomarkers to better characterize subjects with LVD.
PKGIα Leucine Zipper Domain Mediates a Novel Interaction with MLK3, a Potential Anti‐Remodeling Substrate in the Heart
Authors: Calamaras Timothy , Baumgartner Robert , Wang Guang‐Rong , Lane Angela , Aronovitz Mark , Davis Roger , Mendelsohn Michael , Kass David , Karas Richard , Blanton Robert
Published: June 2021

Background

Heart failure is a significant contributor to cardiovascular mortality. cGMP inhibits cardiac remodeling in part via cGMP‐dependent protein kinase G I α (PKGIα). Knock in mice with a mutant PKGIα Leucine Zipper (LZ) have both decreased cardiac function and JNK activity after transaortic constriction (TAC). JNK is regulated by MAPKs including mixed lineage kinase 3 (MLK3) which contains an LZ interacting motif. We hypothesized PKGIα interacts with MLK3 via the PKGIα LZ domain to regulate JNK.

Results

The MLK3‐PKGIα interaction was observed in mouse heart by co‐immunoprecipitation of MLK3 and PKGIα (n=3). In Cos1 cells MLK3 co‐precipitated with PKGIα but was prevented by mutation of the PKGIα LZ domain (n=3). In cardiomyocytes JNK stimulation by 8‐Br‐cGMP was prevented in MLK3‐depleted cells (siRNA, n=3). The role of MLK3 in the heart was tested by subjecting MLK3 knockout mice (MLK3‐/‐) to TAC (7 days). Compared to WT littermates MLK3‐/‐ hearts had increased hypertrophy and LV end diastolic pressure indicating advanced cardiac dysfunction (n=8‐10)

Conclusion

These data reveal a novel interaction between PKGIα‐MLK3 that requires the LZ domain. In cardiomyocytes MLK3 is necessary for cGMP dependent JNK activation. Loss of MLK3 in vivo promotes adverse cardiac remodeling.

This work was supported by the NIH.
Diet, Microbiota, and Microbial Metabolites in Rural Africans and African Americans
Authors: O'Keefe Stephen
Published: June 2021

Epidemiological studies have provided strong evidence that sporadic colon cancer risk is driven by diet, with red meat and fat increasing, and fibre suppressing risk 1,2 and yet human dietary intervention studies with low fat, high fibre diets have yielded disappointing results 3. To investigate this controversy, we performed strictly controlled in‐house studies where the diets of high risk African Americans (high meat and fat, low fibre) and low risk rural Africans (low meat and fat, high fibre) were switched for two weeks, and at the same time interrogated the hypothesis that diet mediates cancer risk through its effects on microbiota metabolism. Diet switch induced significant reciprocal changes in mucosal biomarkers of inflammation and cancer risk, with reductions in African Americans and increases in Africans. That these changes were mediated by the microbiota was evidenced by similar reciprocal changes in its composition and function, exemplified by a loosening of the robust interaction structure geared to complex plant carbohydrate degradation and butyrate production in Africans, and a strengthening of intermicrobial connectivity in African Americans. Furthermore, phenotypic shifts in the metabolome revealed potential mechanisms responsible for the mucosa changes, with increased saccharolytic fermentation and anti‐neoplastic butyrate production and reduced microbial generation of pro‐carcinogenic secondary bile acids in Americans, and the reverse in Africans. In conclusion, our study reveals mechanisms responsible for the epidemiological association between western diets and high colon cancer risk, and indicates that halving fat intake and increasing fibre intake to approximately 50g/d (i.e. far greater changes than those achieved by past intervention studies) can be expected to have an immediate effect on cancer risk. Our findings also warn against the progressive westernization of the traditional African diet, where a reduction in butyrogenesis may permit the progression of chronic inflammation to neoplasia.
Entamoeba histolytica‐Induced Caspase‐4/11 Activation Elicits a Pro‐Inflammatory Response in Macrophages
Authors: Quach Jeanie , Mortimer Leanne , Moreau France , Chadee Kris
Published: June 2021

Entamoeba histolytica (Eh) is a protozoan parasite that colonizes in/on the mucus layer and in 10% of individuals, Eh invades the colonic mucosa to cause amebic colitis. A hallmark of amebiasis is acute intestinal inflammation dominated by the secretion of pro‐inflammatory cytokines, interleukin (IL)‐1β and tumour necrosis factor (TNF)‐α. Eh in contact with macrophages activates caspase‐1 by the inflammasome complex resulting in the maturation of IL‐1β and ‐18. The role of inflammatory caspase‐4, ‐5, and ‐12 in humans are less understood. Caspase‐11, the murine homolog of caspase‐4, mediates non‐canonical inflammasome activation in response to particular pathogens, suggesting that caspase‐4 may have similar roles. As caspase‐4/11 might be an immune sensor in Eh infection the aim of this study was to identify a signature role for caspase‐4/11 in Eh‐induced macrophage responses. To determine if caspase‐4/11 was involved in inflammasome signalling, the gene was silenced with siRNA. Knockdown of caspase‐4/11 did not affect caspase‐1 activation or IL‐1β secretion in response to Eh. However, multiplex cytokine arrays showed marked up regulation of TNF‐α, MIP‐1β, and KC suggesting that caspase‐4/11 may have regulatory roles in the secretion of distinct cytokines/chemokines. Although there was no evidence for crosstalk between caspase‐4/11 and caspase‐1, these inflammatory caspases seem to play a critical role in regulating other cytokines/chemokines that shape the overall macrophage response towards Eh infection. Elucidating the role these inflammatory caspases play in Eh disease pathogenesis may shed light on new therapeutics to treat amebiasis.

Grant Support: NSERC
Parenchymal Platelet‐Derived Growth Factor Receptor Alpha Expression Is Dispensable For Hepatic Fibrosis During Chronic Liver Injury
Authors: Kikuchi Alexander , Monga Satdarshan
Published: June 2021

Platelet‐derived growth factor receptor a (PDGFRa) is a tyrosine kinase receptor with roles in cell survival, proliferation, and differentiation, and is involved in liver development, regeneration, hepatic fibrosis and cirrhosis. While myofibroblasts derived from hepatic stellate cells and portal fibroblasts are the primary mediators of fibrosis, hepatocytes contribute to disease progression through cell death, release of cytokines and growth factors to influence myofibroblast activation, and by undergoing proliferation for regeneration. However the potential expression and function of PDGFRa in hepatocytes in the setting of chronic liver injury is unclear. In this study we investigate the role of hepatocyte PDGFRα in two murine models of chronic liver injury representing toxic (carbon tetrachloride, CCl4) and cholestatic injury (bile duct ligation, BDL). We show that PDGFRa is up‐regulated in a subset of hepatocytes in murine livers following BDL as well as following chronic CCl4 administration. Next, we generated liver‐specific PDGFRα knockout (KO) mice by interbreeding PDGFRa‐floxed and FoxA3‐cre mice. We show that following 4 weeks of CCl4 treatment, PDGFRα loss in epithelial cells did not affect the development of hepatic fibrosis. Intriguingly, comparably higher levels of PDGFRa were evident in KO and controls after 4 weeks of CCl4. In addition comparable liver injury was evident in KO and controls as assessed by serum biochemistry. Our findings suggest that PDGFRα in hepatic parenchymal cells may not be playing an important role in disease pathogenesis especially at 4 weeks after CCl4. This study also suggests that PDGFRα is primarily expressed in non‐parenchymal cell populations early during chronic liver injury.
The Novel Growth Factor, Progranulin, Regulates Autophagy in a Mouse Model of Cholestasis
Authors: DeMorrow Sharon , Francis Heather
Published: June 2021

Cholestatic liver diseases are characterized by hyperplastic cholangiocyte proliferation followed by ductopenia. We have previously shown that the novel growth factor progranulin (PGRN) is upregulated during, and contributes to, hyperplastic cholangiocyte proliferation. The mechanism by which PGRN triggers cholangiocyte proliferation and associated liver pathology is poorly understood. Autophagy is a self‐degradative process whereby cytoplasmic constituents are delivered to the lysosome and degraded. In cholangiocytes, strategies to induce autophagy increases apoptotic cell death and inhibition of autophagy significantly increased cell proliferation in vitro. Our aim was to define a mechanism by which PGRN may induce cholangiocyte proliferation. After bile duct ligation (BDL), markers of autophagy were increased in cholangiocytes. Strategies to inhibit autophagy (chloroquin) increased intrahepatic biliary mass, whereas strategies to stimulate autophagy (Rapamycin) reduced intrahepatic biliary mass after BDL. Treatment with recombinant PGRN reduced the expression of autophagy markers in cholangiocytes and increased cholangiocyte proliferation in vitro and in vivo. Associated with these effects was a PGRN‐induced suppression of the pro‐autophagic molecule, Sirt1. Indeed, the inhibitory effect of PGRN on autophagy was alleviated in cholangiocytes overexpression Sirt1. Our data suggest that autophagy is upregulated during hyperplastic cholangiocyte proliferation, presumably as a compensatory mechanism to prevent overt proliferation, and that PGRN may induce cholangiocyte proliferation by inhibiting autophagy via the suppression of Sirt1 expression.
How to teach physiology to 4th‐grade children? High Tech PhUn!
Authors: Gurovich Alvaro , Anthis Taylor , Barrett Emily , Brown Carson , Brown Jaylyn , Cole Shelby , Evans LeVisa , Fagg Breanna , Hamilton Shannon , Harpenau Olivia , Hayslip Rachel , Jarrett Steven , Majors Katharyn , Miller Breena , Thomas Destini
Published: June 2021

Physiology Understanding (PhUn) week is the APS K‐12 outreach program that helps increasing awareness about STEM education. Here, we combined PhUn week, health education, and high technology to show 3 physiological systems: cardiovascular system (CV), neuromuscular (NM), and central nervous system (CNS). Three hands‐on activities were designed using a Biopac MP40 system. These activities were integrated into the 4th grade science curriculum. Five different sessions in two different days were completed, and 14 undergraduate students worked as facilitators, reaching 116 elementary school students. Each session was divided in 6 small 4‐student groups with the following general activity set‐up: 1) brief presentation about the activity, 2) measurement of HR during 3 different conditions (CV), reaction time on dominant and non‐dominant forearm (NM), and brain activity during 4 different activities (CNS), 3) analyzing collected data, and 4) discussing obtained results. Two children per group were connected to the Biopac MP40 system, one student per group controlled the computer, and the last member of the group recorded data on a data collection form. Collected data was later used in their science class to plot and compare values. Teaching physiology to 4th‐graders is not an easy task. Here, children had a great time and were able to understand better the effects of, for example, exercise on brain function and heart rate. Finally, we strongly suggest using applied high tech activities to strengthen science curricula while kids have ‘PhUn’.

Supported by IU AHEC 14/15 #PIU081 and APS PhUn week program
Combining blood glucose testing with analysis of a classic paper in an endocrine physiology lab activity
Authors: Walton Kristen
Published: June 2021

Endocrine physiology lab activities can be challenging to do with limited resources, due to the complex nature of hormone regulation and the expense of measuring serum hormone levels. Simulated labs are available from various publishers, but hands‐on labs often require animal models, surgeries, and/or expensive reagents. In contrast, blood glucose testing requires relatively inexpensive equipment and can be performed in a 3‐hour lab period by students with little prior training in lab procedures. Consumption of different beverages (for example, water, orange juice, low‐sugar or high‐sugar nutritional shakes) followed by blood glucose testing at one or more time points allows students to see the effects of different amounts and types of carbohydrates on blood glucose levels. To extend this activity and illustrate the effects of various carbohydrates on insulin production, students read an article (Am. J. Physiol 1963;205:638‐644). This classic paper describes perfusion of isolated rat pancreas with various carbohydrates and measurement of insulin by radioimmunoassay (RIA). Students were asked to diagram the methods and interpret the data from the article. They also had to consider the evidence from the paper on effects of different sugars on insulin secretion when analyzing the class data on blood glucose levels over time after consuming various sugar combinations. Students were enthusiastic about the activity as a whole. The use of the classic paper helped to complete the conceptual framework of blood glucose homeostasis illustrated in part by blood glucose testing. In addition, students responded much more positively to this lab experience than to simulated labs on endocrine physiology offered in a previous semester.
Northwest Biosciences Network: Implementation of Vision and Change in Introductory Biology
Authors: Stavrianeas S. , Baumgartner E. , Brown J. , Duncan J. , Gaiser C , Kayes L. , Kiser S. , Kruchten A , Shriner W.
Published: June 2021

The Northwest Biosciences Consortium (NWBC) is a diverse community of biology educators who embrace Vision and Change to create student‐centered, integrated, and investigative biology experiences for all students.Our faculty‐led approach aims to create introductory courses that train biologically literate students, while simultaneously aligning with upper division courses to ease transfers and improve retention.

The NWBC aims to:

· Develop Student Learning Outcomes (SLOs) that allow students to gain appreciation for the scientific process

· Develop a series of customizable modules that can be incorporated into any introductory biology sequence that reflects our commitment to scientific literacy for all students.

· Develop course descriptions aligned with Vision and Change to facilitate curriculum design and student transition, especially from 2‐ to 4‐year institutions

· Foster professional development and legitimize need for change at our home institutions.

The NWBC supports faculty development and collaborations within and between institutions. We benefit from an excellent working relationship with the NW PULSE Fellows and connections to other groups (i.e. BioQUEST, NABT, etc.) that help shape our efforts. Our learning curve on how to function as a network is leveling off, and we are taking steps to accomplish our goals. We look forward to learning from the experiences of others and share lessons learned with those who have similar aims.

Supported by the NSFRCN‐UBE grant (DBI‐1248121).
TRANSFORMING TEACHING AND LEARNING USING AN ACTIVE LEARNING APPROACH ACROSS AN ENTIRE RESEARCH INTENSIVE FACULTY OF PHARMACY AND PHARMACEUTICAL SCIENCES
Authors: White Paul , Larson Ian , Yuriev Elizabeth , Rangachari Patangi , Malone Daniel , Short Jennifer
Published: June 2021

The conventional lecture has significant limitations, often leading to a passive learning experience for students. This abstract reports a process of transforming teaching and learning with active learning strategies in a research intensive Faculty of 45 academic staff and more than 1000 students. The pilot phase involved 9 staff who developed a common vision and principles. After refinement, an implementation phase involving 12 staff, including three from the pilot group, commenced within all first year subjects. Staff use of active learning strategies in classes increased by 6‐fold and 7‐fold in the pilot and implementation phases respectively. Analysis of exam questions indicated that staff increased their use of questions addressing higher order cognitive skills by 42% (pilot phase) and 51% (implementation phase), compared to exams produced prior to the approach. After the pilot phase, only 3 out of 9 staff agreed that they “understood “what makes for an effective active learning exercise”, which rose to 7 out of 9 staff at the completion of the implementation phase. Deliberate engagement with the student body was effective in overcoming much of the initial resistance to change expressed by students: 53% of students felt they “learnt better” in traditional lectures than with active learning during the pilot phase, and this proportion fell to 34% in year one of implementation and 15% in year two. The development of an explicit, common approach and the evaluation and refinement of active learning approaches were effective elements of our transformational change management strategy.
Fostering Inclusive Education: Intentionally vs. Spontaneously
Authors: Kuang Serena
Published: June 2021

Inclusion has become a mainstream value promoted by educators, curriculum designers, and educational policy makers. To achieve an inclusive classroom environment, a variety of learner‐centered curricula and pedagogies are actively implemented and practiced. These educational efforts are made intentionally to improve the external environment for a learner to bring better learning outcomes. However, creating learner‐centered curricula and implementing pedagogies that promote active learning often requires more educational and technological resources as well as specifically trained personnel and thus may not be cost‐effective. Furthermore, external causes become operative through internal causes, or a learner's internal mind setting. If a learner's internal mind setting does not respond/echo actively to the supportive student‐centered, active learning environment or resistant to it, engagement in the learning process may still remain passive in spite of the favorable external learning settings that have been deliberately and cost‐intensively created and provided. In other words, when a learner's internal mind setting is not actively approaching and engaging, the effectiveness of intentionally prepared and implemented approaches may be discounted. Learners may also be spoiled, taking everything they are provided with for granted with no appreciation. In this presentation, we 1) address the rarely‐studied importance of optimizing a learner's internal mind setting, with which an inclusive classroom environment could be achieved spontaneously rather than intentionally; 2) share our personal experience with this approach; and 3) call for discussions and contributions of more techniques and strategies that may induce, trigger, or shape a learner's self‐inclusion mind setting.
Developing, Testing and Optimising a Mouse Hindlimb Musculoskeletal Model
Authors: Charles James , Cappellari Ornella , Spence Andrew , Wells Dominic , Hutchinson John
Published: June 2021

Stability during locomotion arises from many complex interactions which are not yet fully understood. Studies into how sensory feedback from muscle spindles contributes to this have used neuromechanical simulations, however their accuracy is limited due to the lack of available physiological data. This presentation outlines the methods used to develop a musculoskeletal model of the mouse hindlimb, which will be used to predict responses to perturbations which occur with or without sensory feedback.

The 3D musculoskeletal model, which represents bones, joints and 39 muscles of the mouse hindlimb, was created using SIMM (Musculographics, USA) through a combination of muscle architecture data and I2KI enhanced microCT scanning. Architecture data, such as muscle mass, pennation angle and fibre length were gathered from microdissections, while muscle geometry was determined using I2KI microCT scanning, a non‐destructive method of determining muscle paths and attachment points. Muscle moment arms predicted by the model were found to agree with measured data from previous studies.

In future work, in vivo optogenetics will be used to characterise changes in gait and muscle forces which occur in free running mice in response to induced neural and mechanical perturbations with or without sensory feedback from hindlimb muscles. These physiological data will be used to update and refine the musculoskeletal model.
Renoprotection from Diabetic Complications in OVE Transgenic Mice by Endothelial Cell Specific Overexpression of Metallothionein
Authors: Carlson Edward , Chhoun Jennifer , Laturnus Donna , Young Laurie , Swinscoe John , Epstein Paul , Zheng Shirong , Tan Yi
Published: June 2021

In an effort to test our working hypothesis that diabetes‐induced renal glomerular damage may be the result of oxidative insult, JTMT transgenic mice were produced that overexpress the antioxidant protein metallothionein specifically in endothelial cells. JTMT animals were crossed with severely diabetic OVE transgenic mice to determine whether an endothelial specific antioxidant transgene might provide renoprotection from chronic diabetic complications. In double transgenic 150 day‐old OVE‐JTMT mice, diabetic parameters including blood glucose and HbA1c were indistinguishable from age‐matched OVE mice. However, our data indicate that endothelial‐specific metallothionein overexpression in OVE‐JTMT mice reduced a number of nephropathic complications of diabetes including severe albuminuria. In addition, compared to OVE diabetic mice, double transgenic OVE‐JTMT animals showed significant protection to all major components of the glomerular filtration barrier (i.e. podocyte foot process effacement, glomerular basement membrane thickening, and endothelial damage as evidenced by reduced loss of percent area of glomerular luminal capillary endothelial fenestrations). Moreover, when compared to OVE diabetic animals, OVE‐JTMT mice showed reduced glomerular hypertrophy, lowered mesangial cell density and reduced total glomerular cytoproliferation. These results suggest a direct role of oxidative damage to endothelial cells and indicate that their targeted protection can reduce or delay several features of diabetic nephropathy.
Expression and function of proBDNF in pancreatic cancer
Authors: Liu Shangqing
Published: June 2021

Pancreatic cancer is a common gastrointestinal malignancy, which incidence is almost equivalent to its mortality and the average five‐year survival rate is still less than 5%. There is no specific diagnostic marker or complete cure program for pancreatic cancer so far. Both proBDNF and BDNF are widespread in central nervous system, proBDNF may be cleaved to produce BDNF by several different mechanisms. Several studies confirmed that BDNF also expressed in non‐nervous system malignancies such as pancreatic cancer, but there is no literature suggests that proBDNF also present in pancreatic cancer as well. In terms of biological activity, proBDNF may have the opposite effect with BDNF. BDNF may bind to the receptor Trk B and P75NTR, and play an important role in promoting tumor cell proliferation and differentiation, invasion and metastasis, angiogenesis, tolerating chemotherapy and inhibiting tumor cell apoptosis. ProBDNF also can bind P75NTR and Trk B receptors, but it is unclear whether proBDNF play a role in the pathogenesis, invasion and metastasis of pancreatic cancer. By immunohistochemical study, our project group found that compared with normal pancreas, BDNF, proBDNF, P75NTR and Trk B was significantly higher in cell cytoplasm and membrane of human pancreatic carcinoma, which means proBDNF and its receptors also play a role in the pathogenesis of pancreatic cancer. We will further study the possible regulation mechanisms and signal transduction pathways of proBDNF in pancreatic cancer, and investigate deeply the pathogenesis of pancreatic cancer.
Anatomical Mapping of the Omental Vasculature to Refine its Optimal Use in Free Flap Transfer
Authors: McAndrew Darryl , Buckley Lisa , Ashford Bruce , Clark Jonathan
Published: June 2021

Current clinical practice when harvesting an omental free flap is utilisation of the right gastroepiploic artery. This approach is time consuming and surgically demanding / invasive. The clinical use of omental free tissue transfer for reconstruction is based on arterial dimensions, capabilities of surgical instrumentation and surgeon experience. This study mapped the omental arterial distributions and the diameter of the branching omental arteries to determine the viability of alternative vessels for microvascular anastomosis. By establishing the dimensions, patterns and calibres of omental arcades, disruption to the gastroepiploic arterial distribution could be minimised and allow smaller and simpler omental flaps to be harvested.

Mapping of the pattern of the omental vasculature and physical measurement of the arterial omental branches and primary gastroepiploic arteries occurred within 10 cadavers.

Results indicate average arterial omental branch diameters of 0.71mm, compared to an average gastroepiploic artery diameter of 1.66mm. Vessel diameters do not support the reliable use of omental branches as candidates for microvascular anastomosis, and support the continued use of the larger, more proximal gastroepiploic artery.
Accuracy of Osteophyte Detection in Conventional Computed Tomography and Magnetic Resonance Imaging of Joints
Authors: Al‐Attar N , Venne G , Easteal R , Kunz M
Published: June 2021

Osteophytes are bony spurs on normal bone that develop as an adaptive reparative process due to excessive stress at/near a joint. As osteophytes develop from normal bone, they are not always well depicted in common imaging techniques (e.g. CT, MRI). This creates a challenge for preoperative planning and image‐guided surgical methods that are commonly incorporated in the clinical routine of orthopedic surgery.

The study examined the accuracy of osteophyte detection in clinical CT and MRI scans of varying types of joints.

The investigation was performed on three fresh‐frozen ex‐vivo human resected joints identified as having a high potential for presentation of osteophytes. The specimens underwent varying imaging protocols for CT scanning and clinical protocols for MRI. After dissection of the joint, the specimens were subjected to structured 3D light scanning to establish a reference model of the anatomy. Scans from the imaging protocols were segmented and their 3D models were co‐registered to the light scanner models. The quality of the osteophyte images were evaluated by determining the Root Mean Square (RMS) error between the segmented osteophyte models and the light scan model.

The mean RMS errors for CT and MRI scanning were 1.169 mm and 1.419 mm, respectively. Comparing the different CT parameters, significance was achieved with scanning at 120 kVp and 1.25 mm slice thickness to depict osteophytes; also, significance was also apparent at a lower voltage (100 kVp).

Preliminary results demonstrate that osteophyte detection may be dependent on the degree of calcification of the osteophyte. They also illustrate that while some imaging parameters were more favorable than others, a more accurate osteophyte depiction may result from the combination of both MRI and CT scanning.
Does The Axillary Nerve Play A Role In The Innervation Of The Long Head Of The Triceps Muscle? A Cadaveric Study In A Puerto Rican Population
Authors: Medina Stefan , Mejias Emanuel , Veras Wilson
Published: June 2021

The presence of an unusual innervation to the long head of the triceps brachii muscle, different as described in anatomical textbooks, may have clinical importance. The aim of this cadaveric study is to explore a possible contribution of the axillary nerve to the motor innervation of the long head of the triceps in a Puerto Rican population. We dissected the posterior cord of the brachial plexus in a supine position in embalmed cadavers, and the path of axillary nerve was followed to the quadrangular space. In a prone position, the posterior attachment of the deltoid muscle was cut to expose the long head of the triceps and its relation with the axillary nerve. After the dissection was carried out, many photographs were taken. The objective of this study was to clarify the motor innervation of the long head of the triceps brachii muscle because it has not been fully elucidated. The majority of anatomical textbooks state that the motor branch of the long head of the triceps brachii arises from the radial nerve. In our study, we found some specimens where the axillary nerve was innervating the long head of the triceps. It is very important to be aware about the presence of this variation in case the motor branch of the triceps muscle is used as a donor for nerve transfer. Recognizing this variation may also be important in radial nerve pathologies. In this clinical setting, muscle wasting would presumably be absent in the area innervated by the axillary nerve.
MicroScribe 3D Analysis of the Rotator Cuff Muscles Compared to MRI Reconstruction
Authors: Jorgensen Adam , Avondet McKay , Gardiner Brett , Robison Scott , Wisco Jonathan
Published: June 2021

We mapped and defined the attachments and fiber orientations of the rotator cuff muscles of the right and left shoulders of a 58‐year‐old male cadaveric specimen. A better understanding of the complex attachments and inter‐relationships of these muscles will contribute to improvements in rotator cuff surgery and endoscopic repairs. We performed high‐resolution Magnetic Resonance Imaging (MRI) of the right and left shoulders allowing three‐dimensional (3D) reconstruction of the scapula, humerus, and rotator cuff muscles using the reconstruction software Amira. We then dissected the supraspinatus (SS), infraspinatus (IS), teres minor (TM), subscapularis (SUB), acquired spatial maps of the muscle fibers using the MicroScribe 3D Digitizer, and reconstructed the data into 3D renderings using Autodesk Maya. This data was overlaid onto MRI reconstructions of each muscle, offering complete visualization of muscle fiber attachments on the scapula and humerus. The distal attachments and interactions of SS, IS, and TM muscle fibers on the greater tubercle (GT) were visualized in 3D in near microscopic detail. Microscribe 3D analysis captures a more complete perspective of muscle fiber attachments then does its MRI reconstructed counterpart. Typical MRI reconstructions give a general body to the muscles analyzed, but are not detailed enough to show total attachment of muscle to bone. With this enhanced view of muscle fibers, we observed several unique muscle attachments that should be considered in surgical repair of the rotator cuff. Our rendering of the SS, IS, and TM at the distal attachment point on the GT will be beneficial in endoscopic repair of rotator cuff injuries.
Quantitative Analytics on Educational Value of the Unique Instructional Tools on a New Virtual Histology Laboratory
Authors: Rosenthal Oana , Lee Lisa
Published: June 2021

Virtual histology programs, while widely accepted and increasingly used, have not yet been shown to enhance learning over light microscopy, likely due to lack of interactive educational tools. The objective of the study was to investigate the educational value of the interactive annotations and game‐based quiz tools on the new virtual histology program designed to simulate an in‐class interaction with an expert. Twenty three virtual slides, representing four organ systems were made available on the new virtual platform to the first year, graduate students enrolled in a histology course at University of Colorado School of Medicine. Practical scores were collected for quantitative performance analyses on topics that were available on the new virtual histology program vs. those unavailable. A survey was conducted at the end of the course to gauge students' perceived value of the interactive tools on the website. Four weeks after completion of the course, a comprehensive practical was administered to investigate whether content available on the new program yielded better retention of the material compared to the control content. The results reveal that students consistently performed significantly better on the content available on the new virtual histology lab featuring the unique instructional tools. The survey results reveal that the game‐based quiz function and its leader‐board were perceived as the most educationally valuable and motivating tools for studying histology on the new virtual lab. The innovative learning tools on the new virtual histology program show promise as an effective asynchronous educational tool suitable for the new health science curricula.
The Role of Body Donation Programs in Improving Anatomy Education
Authors: Rocha Andrea , Thomaz Leonardo , Pedron Julia , Simoneti Lucas , Girotto Marina , Bonatto‐Costa João
Published: June 2021

The Body Donation Program (BDP) of the Federal University of Health Sciences of Porto Alegre was created in 2008 to supply the lack of bodies available for the study of human anatomy in the University. The Program was pioneer in Brazil and allowed the development of several other activities by the discipline of Anatomy. This study aims to evaluate the improvement of anatomy education through the BDP and the activities introduced after its creation: the Dissection Workshop, the Museum of Anatomy and the Ceremony in Honor to the Body Donors. The information in BDP's database and the results of the activities related to the Program since 2008 were analyzed. Since the BDP was created, 297 people registered as body donors and 48 bodies were donated to the University compared to 23 bodies received between 2001‐2007. This increase in the number of bodies allowed the implementation of the Dissection Workshop, in which students prepare high quality anatomical specimens to be displayed at the Museum of Anatomy. The Museum, an annual and temporary exhibition also held since 2008, received 2.416 visitors in 2014 compared to 1.146 in 2013. In addition, 81 students acted as guides to visitors and shared their knowledge about Anatomy. At the end of each year, first year students organize the Ceremony in Honor of the Body Donors to thank the families for their altruistic gesture. The increased number of bodies received through the BDP allowed the discipline to offer a larger number of activities, which enhanced the students'interest and participation. Thus, we concluded that the BDP improved the quality of anatomy education and benefited the ethical and professional education of students as a whole.
Using the Brains We Have: Dissection of the human brain assists the medical student in learning and retaining neuroanatomy
Authors: Rae Guenevere , Cork R John , Karpinski Aryn , Farris Hamilton , Swartz William
Published: June 2021

The purpose of this study was to evaluate short and long‐term effects of adding a brain dissection activity to a medical neuroscience course. First‐year medical students participated in a brain dissection activity that included dissection of the basal nuclei and associated deep brain structures. Short‐term retention was assessed by administering identical pre and post‐activity tests involving identification of brain structures. The assessment consisted of items that were included in the brain dissection protocol (deep structures), and also items that were not part of the dissection protocol (superficial structures). Following the brain dissection, the students' ability to identify deep brain structures increased significantly (mean score: 72.0%±20.8%), while their ability to identify superficial structures remained the same (64.25%±16.25%). Long‐ term retention was evaluated by conducting an identical assessment five months after completion of the course. Students who participated in the dissection activity (n= 81) had significantly higher scores (49.31%± 20.6%) than the students who did not participate in the dissection activity (n=86) (40.5%± 19.2%) (p 蠄 0.01). In addition to the long‐term retention assessment, the NMBE subject examination scores of students who participated in the dissection activity were significantly higher than the students who did not participate in the dissection activity (p 蠄 0.01). A short brain dissection activity may improve students' ability to learn neuroanatomy. This effect may have long‐term benefits on knowledge retention and may be correlated with performance level on standardized subject exams.