bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemical Analysis of LGR5 Expression in Pediatric Liver Disease
Authors: Khan Zahida , Orr Anne , Michalopoulos George , Ranganathan Sarangarajan 
Published: June 2021

BACKGROUNDIn regenerating liver, hepatic progenitor cells (HPCs) are recruited in response to liver injury; however, there is a lack of highly specific human HPC markers for the hepatocyte lineage. LGR5, a Wnt‐associated adult stem cell marker, has been extensively studied in intestinal stem cells. Although LGR5 appears to be exclusively expressed by HPCs in mice, little is known about its expression in human liver. We hypothesized that LGR5+ cells are induced in the regenerative response to liver injury to potentially rescue dysfunctional hepatocytes.METHODSUsing immunohistochemistry, we characterized LGR5 expression in pediatric liver diseases, using mainly liver explants (n=36 cases total).RESULTSWe found cytoplasmic LGR5 over‐expression in all 36 pediatric cases, including acute hepatic necrosis and cholestatic liver diseases. In 44% of cases, >50% of hepatocytes were LGR5+, signifying a robust regenerative response. In contrast, there was only weak staining in bile ducts, suggesting hepatocyte‐specific expression. Marked peri‐portal expression was prominent in cholestatic diseases, consistent with known patterns of regeneration. Comparison to other regeneration markers will further characterize this hepatocyte progenitor cell phenotype.CONCLUSIONSAlthough we observed some degree of regenerative response in all cases examined, LGR5 was highly expressed in cholestatic liver diseases, possibly due to alternate regeneration pathways. These studies are the first to support a unique role for LGR5 in human hepatocyte regeneration and as a potential predictive marker for recovery of liver function in children.

LGR5 INTENSITY
TOTAL CASES
WEAK +
1+
2+
3+

A1AT Deficiency (ATD)
15
0
2
5
8

Biliary Atresia (BA)
5
0
0
2
3

PFIC
10
1
1
5
3

Acute Hepatic Necrosis (ALF)
6
1
4
1
0

TOTAL CASES
36
2
7
13
14

imageimage
“Dialogical Story‐Telling” Approach to Enhance Analytical Thinking and Student Engagement During Lecture‐Based Classes
Authors: ElSayed Suzan , Loftus Stephen 
Published: June 2021

The “Dialogical Story‐Telling” approach is an interactive method to teach physiology for health professional students during didactic lectures. This interactive method integrates an interactive conversational style within a story‐telling method. The story telling incorporates dialogue with the students, which is in a question‐answer format that not only creates a motivating learning context but also builds an educationally safe and supportive environment.A week before the lecture, students are provided with copies of the PowerPoint slides to be used. The students are required to review all the slides. During the lecture, the instructor guides the students through the material using story‐telling and question‐answer styles. The instructor also uses questions related to the material that encourage analytical thinking.There is an emphasis on building an educational relationship between students and teachers. Relationship‐centered learning goes beyond student‐centered learning, in recognizing and rehabilitating the role of the teacher. There are strong theoretical foundations for relationship‐centered learning. There is the dialogism of Bakhtin, with the recognition of the importance of interactivity. There is also social constructionism where it is accepted that meaning, knowledge and understanding are jointly constructed with others.
Changes of Chemical Elements in the Special Embalming Fluid after Immersed in Human Fresh Amputated Remains
Authors: Luo Jia , Liu Tianxiong , Liu Lian , Hu Tu , Wang Jianlong , Chen Yanliang , Zeng Leping , Huang Jufang 
Published: June 2021

ObjectivesTo evaluate the effect of the special embalming fluid preserved on the human fresh amputated remains at a micro level, and to find out the temporal and spatial changes of chemical elements leaching from tissues.MethodsThe whole remains and tissues (skin, muscle, nerve, artery) cut off from the remains were immersed into the special embalming fluid for 6, 12 and 24 months. After paraffin embedding, H&E staining was performed, and the concentrations of chemical elements in embalming fluid were determined by ICP‐AES.ResultsThe morphological structure of tissues was preserved well in 6 and 12 months, and the chemical elements, especially the trace elements leached few into the embalming fluid. The common elements leached earlier than the trace elements. As the time passing, the type and the concentrations of chemical elements were increased. The trace elements in the whole remains were preserved better than the removed tissues, so were that in muscle and artery better than in skin and nerve.ConclusionThe embalming fluid preserved the fresh amputated remains well in short time. Specific embalming fluid should be developed to preserve different tissues better and longer.This work was supported by the National Key Technology Support Program (No.2012BAK14B03), Chinese postdoctoral Science Foundation (No. 2014M562136) and Hunan Provincial Innovation Foundation For Postgraduate(No.1145‐71380100001)
Codistribution of Collagens V and VI with Collagens I and III in Hepatic Fibrosis of Elderly Cadavers
Authors: Mak Ki 
Published: June 2021

Collagen V is a fibrillar collagen of the extracellular matrix (ECM). It forms heterotypic fibrils with collagen I and regulates the growth of collagen I fibrils. Collagen VI is a microfilamentous collagen that forms a network in the ECM, linking matrix components and cells. In the liver, collagens V and VI are minor ECM proteins, but their levels are significantly elevated in cirrhosis. Fibrosis is often seen in aged livers and is prevalent in elderly cadavers. Using immunoperoxidase staining in paraffin sections, this study assessed collagens V and VI expression and their association with fibrillar collagens I and III in progressive stages of liver fibrosis of elderly embalmed cadavers. In liver with minimal fibrosis, staining for collagens V and VI was uniform in the perisinusoidal space of the lobules, stroma and vessel walls of portal tracts, and rims of central veins. Perisinusoidal hepatic stellate cells (HSCs) expressed collagens V and VI, revealing the cellular source of these collagens. In foci of severe perisinusoidal fibrosis, collagens V and VI staining was enhanced, codistributing with the increased presence of collagens I and III. Collagens V, VI, I, and III were abundant in the ECM of fibrotic portal tracts, fibrous septa of sepal fibrosis and cirrhosis. In sections post‐stained with Sirius red for collagen fibers—mainly collagens I and III—the immunoreactivity of collagens V and VI was seen localized to the fiber bundles.ConclusionThe association of collagen V with collagen I in fibrotic foci is in accord with its regulatory role for fibrillogenesis of collagen I, while collagen VI—a connecting protein—links fibrillar collagens to the surrounding ECM. Thus, collagens V and VI could serve as biomarkers of liver fibrogenesis.
Extracellular Matrix Proteins of Fibrous Septa in Elderly Cadaveric Livers
Authors: Mak Ki 
Published: June 2021

The formation of fibrous septa in the liver is a histological hallmark of advanced liver fibrosis that can progress to cirrhosis, the end stage of fibrosis. Liver fibrosis has been shown to be associated with aging and was found to be prevalent in elderly cadavers with a high incidence of septal fibrosis. Using immunoperoxidase staining in paraffin sections, this study assessed the extracellular matrix (ECM) protein constituents of the fibrous septa accompanying septal fibrosis and cirrhosis in the liver of elderly embalmed cadavers. In the developing short septa extending from portal tracts or central veins, the ECM was positively stained for collagens I, III, V, and VI. Elastic fibers—identified by resorcin fuchsin stain—were also present. The staining for these collagens and elastin became more prominent in the bridging septa that link portal tract to portal tract or portal tract to central vein. Some of these septa also contained bile ductules and venules, marked by immunostaining for collagen IV and laminin, two major basement membrane (BM) proteins. Additionally, the venous endothelium expressed factor VIII‐related antigen (FVIIIRAg). In cirrhosis, the fibrotic bands showed conspicuous staining for all these collagens and proteinsConclusionThere are at least eight proteins present in the septa: fibrillar collagens I, III, and V, microfilamentous collagen VI, elastin, BM collagen IV and laminin, and vascular endothelial phenotypic marker FVIIIRAg. Thus, while collagen V regulates the growth of collagen I fibrils, collagen VI—a connecting protein—links fibrillar collagens to the septal ECM, giving the septa their tensile strength and rigidity. Elastin imparts elasticity to the septa. Collagen IV and laminin support the growth of ductules and venules in the septa.
May anatomy explain the origin of the leak after gastrectomy Sleeve?
Authors: PEREZ Manuela , BRUNAUD Laurent , KEDAIF Sabrina , GUILLOTIN Cyril , GERARDIN Alexandre , QUILLOT Didier , GROSDIDIER Gilles , REIBEL Nicolas 
Published: June 2021

The aim of this study was to realize cartography of the arterial gastric vascular supply on fresh cadaver after performing a sleeve gastrectomy to evaluate the rule of potential vascular changes on the gastric leak.Sleeve Gastrectomy is a bariatric surgical procedure with a specific morbi‐mortality due to gastric fistula in the upper part of the gastric tube. Two theories are currently proposed to explain this specific leak location: a vascular one and a mechanical one.We performed a sleeve gastrectomy on 11 cadaveric trunks and achieved a detailed anatomical study of the gastric vascular supply after latex injection.In 55% of cases, sleeve procedure induced a change in the gastric vascular supply and in 9,1%, it lead the section of the three left gastric artery branches arising the lesser curvature. Few changes were noticed in the antrum and pylorus area.This anatomical study allowed to demonstrate that the vascular supply of the upper part of the gastric tube could be damaged by a Sleeve procedure, severing one or more of the branches arising from the left gastric artery. The antrum and pyloric area get an invariable vascular supply. It could explain the preferential localization of the fistula to the upper part of the gastric tube.
Influence of the torsion of femur and tibia on the torsion of the calcaneal tendon.
Authors: Hirtler Lena , Hadrovic‐Avdic Merisa , Kainberger Franz 
Published: June 2021

IntroductionThe vulnerability of the calcaneal tendon is favoured by pulling forces of different strengths within the calcaneal tendon, which result from its anatomical torsion. This trial tries to determine whether the torsion of femur and tibia influence the amount torsion of the Achilles tendon.Methods40 lower extremities were measured. The torsion angle of femur and tibia and calcaneal tendon was measured. Descriptive data on the calcaneal tendon were gathered.ResultsThe length of the Achilles tendon is 6,9 ± 2,6 cm, its diameter at the beginning of the insertion site is 2,8 ± 0.5 cm, compared to 3,8 ± 0.6 cm at the end of the insertion site. The overal mode of torsion of the calcaneal tendon was classified into 4 types. The torsion of the calcaneal tendon was positively correlated to the torsion of the femur (p<0.05, R=0.37). The tibial torsion did not influence the morphology of the calcaneal tendon significantly (p>0.05).ConclusionGenerally, the torsion of the bones of the lower extremity as well as the torsion of the calcaneal tendon show a great amount of variation. But it seems, that the amount of femoral torsion influences the degree of torsion of the calcaneal tendon. Therefor not only the length of the calcaneal tendon, as already shown in literature, but also the bony configuration of the lower extremity influence the morphology of the calcaneal tendon. Based on the results of this study, a morphological analysis of the torsion of the calcaneal tendon and bone torsion could indicate higher or lesser risks of calcaneal tendon rupture.
A proposal for ethical guidelines in anatomical education
Authors: Hildebrandt Sabine 
Published: June 2021

While ethical body procurement in the form of willed body donation programs has become the norm at medical schools in the US, the recent report of disturbing incidences in an anatomical dissection course underline the importance of ethical guidelines for anatomical education. This proposal argues that ethical body procurement and ethical anatomical education are the foundation for humanism‐based professional training of students in medicine. As the dissection course presents an exceptional situation for all involved, anatomists need to be trained in professional ethics, and students should receive an education that is founded on ethical considerations, including the following:1. a preparatory phase before the start of the course, in which students are asked about their expectations and fears concerning anatomical dissection2. an introduction to the history and ethics of anatomy3. a chance for reflection in the dissection room before the start of dissection4. a regular opportunity for reflections on dissection in parallel to the course with students and faculty5. a memorial service for the donors organized by students for faculty, students and donor families.Some anatomy programs have incorporated these ideas, while others are clearly lacking. Ethical guidelines in anatomical dissection can strengthen the foundation of a humanistic approach to medicine in future physicians and health care workers.
Course Remediation Within a First‐Year Integrated Medical Curriculum
Authors: Mork Amy Lovejoy , Klement Brenda , Paulsen Douglas , Wineski Lawrence 
Published: June 2021

The integration of basic science courses throughout the first two years of medical education has introduced complications to assisting students who struggle academically within a program comprised of intensely interwoven topics. Course remediation has been a long standing practice within medical school curricula, providing students with additional opportunities for success and advancement. At Morehouse School of Medicine, the first‐year integrated curriculum is built around a gross anatomy template, and is composed of gross anatomy, embryology, cell biology, histology, neurobiology, biochemistry, and physiology. The first year curriculum is separated into the following courses; Basic Principles and Organ Systems I, II and III. These divisions enable students who underperform in one of these courses, a grade of 60‐69.4%, to be allowed to advance to the next course, with the understanding that they must remediate the course within a set schedule. Course remediation consists of a detailed self directed study plan that is developed and submitted by the student, and culminates in a comprehensive multiple choice exam. Students who pass the remediation exam (蠅 70%) receive a “C” for the course. Students who fail the remediation exam repeat the course the subsequent year. Current remediation guidelines have evolved over the past six years of the integrated first year curriculum. With an average of three students remediating per year, 68% are successful, and only 32% must retake the course. Thus, we regard course remediation as a successful means of aiding students who underperform in the first year of medical school.Sponsored in part by NIH PO31B04017 and G12RR003034
Development of the Ventricular Conduction System of the Crocodilian Heart
Authors: Kvasilova Alena , Jensen Bjarke , Christoffels Vincent , Sedmera David 
Published: June 2021

Unlike other cold‐blooded vertebrates, crocodilians have a fully septated heart, similar to birds and mammals. It is not known whether they have a ventricular conduction system (VCS) as wellWe studied a group of 8 embryos of the Siamese and Mugger Crocodile between 3 and 84 days of incubation, and serial early embryo sections with HNK‐1/Hematoxylin staining of the Nile Crocodile. We employed optical mapping, ultrasound biomicroscopy, histo‐ and immunohistochemistry, in situ hybridization and 3D reconstructionAt the pre‐septation stage (12 days of incubation), the ventricular activation pattern progressed in a left‐to‐right sweep, similar to that observed at early stages of avian and mammalian cardiogenesis. At two post‐septation stages investigated (45 and 84 days) , epicardial activation patterns showed dual apical breakthroughs on either side of the interventricular septum. Immunohistochemistry using smooth muscle actin (SMA), sarcomeric actin, periostin and HNK‐1 antibodies showed that myocardial SMA staining was present even after septation, while it disappears in comparable chick or mouse hearts. HNK‐1 staining was prominent in the interventricular septum, similar to the situation in the chick and rat where it is considered a marker of the developing ventricular conduction system. In situ hybridization for Cx40 (VCS marker) showed a uniform expression in the entire trabeculated myocardiumWe conclude that this is an evidence of evolutionary correlation between ventricular septation and presence specialized VCS in vertebratesSupported by PRVOUK P35/LF1/5.
Analysis of SM22 at Enteropathogenic Escherichia coli Induced Pedestals
Authors: Chua Michael , Hipolito Kevin , Guttman Julian 
Published: June 2021

Disease caused by enteropathogenic Escherichia coli (EPEC) is initiated when these extracellular bacteria attach onto host epithelial cells and secrete disease‐causing proteins to control the host cell machinery. Morphological actin‐rich structures, called pedestals, are formed within the host cells at sites of bacterial attachment. These structures are needed for disease to occur and are known to confer motility to the bacteria, enabling the microbes to “surf” atop the infected cells. SM22 is an actin‐associated protein that stabilizes cellular actin filament bundles. To further characterize the protein make‐up of pedestals and understand the functions of those proteins in the infectious process, we hypothesized that SM22 would be present at EPEC pedestals and would play a crucial role in forming or stabilizing these actin‐rich structures. To test this hypothesis, we immunolocalized SM22 in EPEC‐infected HeLa cells and found that SM22 localized along the entire length of the pedestals. To determine the functional role of SM22, we knocked‐down protein levels of SM22 using small interfering RNA. On cells with reduced or undetectable levels of SM22, significantly less pedestals were observed. Our data demonstrates that SM22 contributes to the formation or stability of EPEC‐induced pedestals and provides a novel target for the development of future therapeuticsThis study was funded through NSERC.
Design and Implementation of a Professional Master of Science in Biotechnology Innovation and Regulatory Science with Global Impact
Authors: Clase Kari , Byrn Stephen 
Published: June 2021

Biotechnology is one of the fastest growing industry sectors and demands graduates equipped to become innovative researchers, problem solvers and leaders in biotechnology organizations. Demand has increased for degrees that blend scientific content knowledge with professional skills and competencies in understanding of regulatory issues, project management, strategy and global leadership.In response to this need, we developed a Master of Science in Biotechnology Innovation and Regulatory Science (BIRS). BIRS M.S. provides a thorough understanding of the entire process of biotechnology innovation: from early discovery and toxicology research, through clinical trials and manufacturing, and finally registration of a drug or medical product. Individuals completing this program are qualified for employment in regulatory affairs, quality control, and regulatory assurance departments within industry.The competencies and learning outcomes for the BIRS program align with those identified by an academic consortium with guidance from both regional and national reports. Program curriculum was developed by academic faculty with input from key industry stakeholders using a backwards design approach. Course topics include principles of drug discovery and development, biologics, statistical analysis, good regulatory practices, quality systems management, patenting and commercialization. Current enrollment in BIRS MS includes approximately 20 students from the US and 50 students from Africa, most working professionals within industry.This program has received funding from Merck, Roche and UNIDO.
Confirmation and Characterization of Lin‐/Sca‐1+/CD45‐ Very Small Embryonic‐Like Cells (VSELs) Purified from Bone Marrow
Authors: Shin Ellie , Truman Alisha , Woods Dori , Tilly Jonathan 
Published: June 2021

Previously published studies have identified the presence of a rare population of very small cells (< 5.0 microns in diameter) in the bone marrow of mice (Leukemia 2006 May;20(5):857‐69). In addition to size, these cells are characterized by a gene expression profile consistent with pluripotent embryonic stem cells and can differentiate into multiple cell lineages. While the discovery of these cells, termed 'very small embryonic like' (VSEL) cells, generated much enthusiasm in the field, it was not without controversy. Most recently, a failed attempt at repeating the published protocol that was used to isolate VSEL cells from murine bone marrow concluded that “the existence of adult mouse VSELs in the bone marrow remains dubious.” (Stem Cell Reports 2013 Jul 24;1(2):198‐208). However, close inspection of the methodology employed in this attempt reveals key missteps that may have led to this conclusion. Accordingly, we repeated the protocol as published to determine whether cells with features consistent with VSEL cells could be isolated (Stem Cells Dev. 2014 Apr 1;23(7):702‐13).Bone marrow was flushed from the tibiae and femurs of 10 5‐week female C57BL/6 mice. Following lysis of red blood cells, the bone marrow preparation was incubated with antibodies targeting the following cell surface markers: stem cell antigen 1 (Sca‐1), protein tyrosine phosphatase receptor type C (CD45), and lineage (Lin). The labeled sample was subjected to fluorescence activated cell sorting (FACS), using a gating strategy that employs both size (2–10µm) and fluorescence to determine the appropriate gates. Putative VSEL cells (Lin‐/Sca‐1+/CD45‐) and hematopoietic cells (Lin‐/Sca‐1+/CD45+) were collected for downstream analysis.Using the FACS gating strategy described above, Lin‐/Sca‐1+/CD45‐ cells approximately 3‐5 µm in diameter were successfully identified, lending further support to the existence of VSEL cells in bone marrow of mice.Source of Research Support: Schafer Co‐op Research Scholarship