bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue‐engineered Vascular Grafts for Congenital Heart Surgery
Authors: Breuer Christopher 
Published: April 2020

ObjectiveWe developed a tissue engineered vascular graft (TEVG) formed by seeding autologous bone marrow‐derived mononuclear cells onto a biodegradable tubular scaffold fabricated from a knitted polyglycolic acid core and coated with a 50:50 copolymer of poly lactic acid and polycaprolactone. Once implanted, the scaffold degrades and neotissue forms giving rise to neovessel which is structurally and functionally similar to the native vessel into which it was implanted. Herein we will describe the natural history of the evolution of the mechanical properties of the TEVG after implantation and evaluate the impact of the mechanical properties of the TEVG on graft performance.MethodsWe utilized an ovine intrathoracic inferior vena cava model in order to evaluate the evolving mechanical properties of the TEVG and determine their impact on graft performance. We implanted TEVG into 24 juvenile lambs and serially assessed graft morphometry and function using serial angiography and intravascular ultrasound (IVUS) over a 6 ‐month to 1‐year period. We serially measured changes in graft size using both angiography and IVUS. We also assessed the graft hemodynamics at angiography. We measured graft displacement over both the cardiac and respiratory cycle. Finally, a subset of TEVGs were harvested and underwent biaxial mechanical testing.ResultsThe TEVG undergoes significant remodeling when after implantation. As the scaffold degrades, the TEVG transforms from a relatively stiff conduit to a highly compliant neovessel with growth capacity.ConclusionsThe transformation of the TEVG from a relatively stiff vascular conduit to a more compliant neovessel enables the graft to function as a capacitance vessel improving its performance when used in the venous circulation.Support or Funding InformationNIH R01HL139796
Students as Evaluators of their Learning Experience
Authors: Rosenberg Martina 
Published: April 2020

Student evaluations of teaching (SET) have been an evergreen topic of passionate debates in higher education. Concerns have been raised about use student feedback in the form of SETs for administrative purposes. Nevertheless, they remain a reality at most institutions and are frequently the sole or key metric on which teaching excellence is evaluated.This session will provide an overview of national trends with the struggle to define teaching excellence in context and the current discussion on what aspects of the teaching and learning can be evaluated with different SET formats. Viewed through the lens of academic development, participants will examine why SETs are so pervasive, how to mitigate the emotional charge that is a barrier to individual growth of instructors within their professional setting, and how students can act as productive partners in institutional learning.
Weaving Histology into the Fabric of Medical Education: Histology as a Foundation for Integration and Application
Authors: Goldman Haviva M 
Published: April 2020

Over the past two decades, histology education in the health sciences has undergone a dramatic shift both in method (use of virtual microscopy) and curricular focus (decrease in hours; increased integration). While this new landscape introduced challenges for histology teaching, histology’s strengths as a conceptual link between molecular/cellular level mechanisms and organismal structure and function make it an ideal springboard for integrating multiple disciplines in creative ways, allowing the discipline to play a key role in building both foundational knowledge and clinical diagnostic skills.At Drexel University College of Medicine, histology is taught as part of an integrated curriculum that takes a sequenced normal (yr 1)/abnormal (yr 2) approach. Content delivery utilizes a flipped‐classroom approach, and histology is integrated within four different types of delivery methods including integrated online ‘Independent Learning Modules’; Histology focused (but integrated) ‘Laboratory Reviews’ including scavenger hunt and mystery slide exercises; multidisciplinary ‘Think‐Pair‐Share’ sessions; and multidisciplinary ‘Team Based Learning’ sessions that focus on clinical application. Specific examples of each of these integrated modalities will be presented with a focus on highlighting the challenges and opportunities these approaches afford from the perspective of the discipline, the educator, the student, and ultimately the clinician.
Early Signals in Wound Healing
Authors: Niethammer Philipp 
Published: April 2020

Reactive oxygens species (ROS) and polyunsaturated fatty acids (PUFAs) are conserved wound signals throughout phylae. In zebrafish larvae, ROS gradients and osmotically released arachidonic acid mediate rapid wound detection by afar leukocytes. But it is unclear, whether these cues initiate de novo leukocyte recruitment like alarmins or rather amplify responses to other initiating signals. This talk will summarize our recent progress on this question, outlining a novel role for lipid peroxidation gradients as physiological integrators of ROS‐ and PUFA‐mediated early wound cues.Support or Funding InformationNIH‐R21AI139986NIH‐R01GM099970NIH‐R01GM127356
Developing Novel Means to Inhibit Metastasis Through Targeting Tumor Heterogeneity and EMT
Authors: Ford Heide L. , Kong Deguang , Neelakantan Deepika , Zhou Hengbo , Hughes Connor , Lewis Michael , Marugan Juan , Patnaik Samarijit , Zhao Rui 
Published: April 2020

It is well established that a subset of cells within primary breast cancers can undergo an epithelial to mesenchymal transition (EMT), although the role of EMT in metastasis remains controversial. We previously demonstrated a novel mechanism by which EMT contributes to metastasis, via mediating tumor cell crosstalk. In this seminar, I will discuss how breast cancer cells that have undergone an oncogenic EMT can increase metastasis of neighboring epithelial cancer cells via non‐canonical paracrine‐mediated activation of GLI activity that is dependent on Six1 expression in the EMT cancer cells. I will discuss how VEGF‐C, secreted by breast cancer cells that have undergone an EMT, promotes paracrine‐mediated increases in proliferation, migration, invasion, and metastasis of epithelial breast cancer cells, via non‐canonical activation of GLI‐signaling. Importantly, the aggressive phenotypes imparted by EMT cells on adjacent epithelial cancer cells can be disrupted by either inhibiting VEGF‐C in EMT cells or by knocking down NRP2, which interacts with VEGF‐C, in neighboring epithelial cancer cells both in vitro and in vivo. Interrogation of TCGA and GEO public datasets supports the relevance of this pathway in human breast cancer, as VEGF‐C and GLI pathway genes significantly positively correlate. Our study suggests that the VEGF‐C/NRP2/GLI axis may be a novel and conserved paracrine means by which EMT cells enhance metastasis, and provides potential targets for therapeutic intervention in this heterogeneous disease. In addition, because SIX1 activates VEGF‐C expression which leads to enhancement of metastasis via cell autonomous and non‐cell autonomous means, we have developed an inhibitor that targets SIX1 action and thereby inhibits metastatic disease. We describe results using this inhibitor in cell culture, where it inhibits SIX1 function and EMT, and in animals, where it inhibits metastasis without an effect on primary tumor growth.Support or Funding InformationColorado Cancer Translational Research Accelerator (CCTRA) PI Heide L. Ford, Co‐I Rui ZhaoNCI R01 CA224867 PIs Heide L. Ford and Michael T. Lewis
The Development of Appendicular joint cartilages in Alligator mississippiensis: Evolutionary and Biomechanical Implications for Archosauria
Authors: Tsai Henry P. 
Published: April 2020

Crocodylians and birds are the two surviving lineages within Archosauria, a clade of morphologically and ecologically diverse vertebrates that evolved highly disparate locomotor postures. The appendicular joints of crocodylians and birds differ substantially, thus complicating inferences of ancestral morphology and evolutionary transitions. Recent studies have indicated that the American alligator, an extant crocodylian, use a wide spectrum of cartilaginous and other connective tissues to construct the hip joint. However, little is known about the distribution and use of cartilage throughout other appendicular joints, as well the ontogenetic transition of the crocodilian chondro‐osseous interface during early development. In particular, the hyaline cartilage on the proximal femur of late embryonic alligators possesses a convex, cone‐like extension that inserts deep into the metaphysis. This morphology is not seen in juvenile and adults, but is superficially similar to the cartilage cone‐metaphyseal trough articulation inferred in early members of multiple archosaurian groups. The method by which alligators and other archosaurs reduced the cartilage cone during ontogeny and evolution, as well as the functional significance of the cartilage cone itself, are poorly understood.This study examined the ontogenetic transitions of proximal appendicular joints in the American alligator, spanning from in ovo stages to the first year of life. We used dissection, histology, and imaging techniques to assess the articular soft tissue anatomy at the chondro‐osseous junction of the proximal‐ and distal epiphyses of the femur and humerus. Additionally, osteological correlates for joint cartilage were identified on fully skeletonized limb bone elements and compared with bony morphology seen in fossil archosauromorphs.At the onset of hatching, the alligator did not reduce the cartilage cone via decreasing the “depth” of cartilaginous extension into the metaphysis, as inferred for early archosaurs. Instead, neonatal alligators regress the cartilage cone via multiple invasion fronts of trabecular bones, such that the subchondral growth plate of hatchlings presents a convex surface perforated by numerous cartilage canals, similar to those found in young birds. These results suggest that the ontogenetic loss of cartilage cone in the alligator is different from the evolutionary loss of cartilage cone hypothesized for early archosaurs. Instead, the role of cartilage thinning, fibrocartilage sleeve development and calcified epiphyseal cartilage may be highly associated within different sauropsid lineages in response to evolutionary changes in joint loading regimes.Support or Funding InformationThis research is supported by the Missouri State University Faculty Research Grant
Incorporating Trace Fossils when Exploring the Interplay of Form and Function in the Crocodyliform Feeding Apparatus
Authors: Drumheller Stephanie K. 
Published: April 2020

Many crocodylians, both living and extinct, fill the semi‐aquatic ambush predator niche, and their prey preferences roughly can be predicted based on a combination of snout shape, tooth morphology, and body size. Among extant crocodylians, slender‐snouted taxa such as Gavialis gangeticus and Tomistoma schlegelii generally prefer smaller‐bodied prey, whereas the broader‐snouted taxa divide into generalists like Crocodylus niloticus and macro‐generalists like Alligator mississippiensis, who will eat a diversity of prey items including animals that are as big or even bigger than themselves. Large‐bodied members of these generalist ecomorphotypes generate the highest bite forces observed in modern taxa and are often apex predators in their ecosystems. The availability of a robust phylogenetic hypothesis for crocodylians makes them an excellent clade with which to explore these types of ecomorphological hypotheses, which link form and function in the feeding apparatus within an evolutionary framework. The resulting synthesis of extant and extinct datasets has provided both exciting new insights, but also some complications. The addition of extinct taxa into studies of morphological disparity, both within the crown group and deeper in the crocodyliform evolutionary tree, introduce a diverse array of snout shapes and associated niches that are not represented in the surviving members of the clade (e.g. fully marine, fully terrestrial, durophagous, omnivorous, and even possibly herbivorous forms). Though hypotheses regarding diet in these diverse groups are based on craniodental morphology, indirect evidence, in the form of trace fossils, provides an independent means of testing those predictions. Gut contents are extremely rare in this clade because of the highly destructive digestion of crocodyliforms, and coprolites, though comparatively common, contain remains that are so degraded as to be largely unidentifiable and uninformative. Isotopic and dental microwear studies can provide broad patterns of diet. However, for detailed, direct evidence of crocodyliform feeding, bite marks are a particularly useful source of direct evidence with which to explore patterns of diet in this clade. A recent, concentrated effort to characterize modern crocodylian bite marks has resulted in the identification of novel patterns and diagnostic traces associated with feeding behavior in that clade. These trace fossils provide critical insights into diet, feeding strategy, and even intraspecific competition in crocodyliforms and their extinct relatives. By integrating these ichnological data with traditional dietary hypotheses based on morphology and phylogeny of extinct groups, a more complete, and oftentimes more complex and realistic, concept of past ecosystems and trophic structures can be explored.Support or Funding InformationFunding provided by the National Science Foundation, the Leakey Foundation, and National Geographic.
Illuminating the Biochemical Activity Architecture of the Cell
Authors: Zhang Jin 
Published: April 2020

The complexity and specificity of many forms of signal transduction are widely suspected to require spatial microcompartmentation and dynamic modulation of the activities of signaling molecules, such as protein kinases, phosphatases and second messengers. We have developed a series of fluorescent biosensors to probe the compartmentalized signaling activities in living cells. In this talk, I will focus on cAMP/PKA and PI3K/Akt/mTORC1 signaling pathways and present studies where we combined genetically encoded fluorescent biosensors, superresolution imaging, targeted biochemical perturbations and mathematical modeling to probe the biochemical activity architecture of the cell.Support or Funding InformationThe work is supported by NIH
Sex as a Biological Variable in Bronchopulmonary Dysplasia
Authors: Lingappan Krithika 
Published: April 2020

The incidence of bronchopulmonary dysplasia (BPD) is higher among premature male neonates even after adjusting for other confounders. Despite the well‐established sex‐specific differences in the incidence of BPD and impaired lung function in males, the molecular mechanism(s) behind this are poorly understood. Mammalian cells have intrinsic differences based on sex and respond differently to stressors irrespective of the past or current concentrations of sex hormones. Our research investigates the effect of sex on neonatal hyperoxic lung injury and the mechanisms underlying these differences. Alveolarization and angiogenesis is preserved in female neonatal mice exposed to hyperoxia compared to males. Differences in the lung transcriptome and the epigenome may contribute to these sex‐specific differences. We have shown that differential expression of miRNA (miR‐30a) and their downstream targets have also been shown to modulate this process. Sex‐specific differences at the cellular level in the pulmonary endothelial cells and fibroblasts will also be discussed. To distinguish sex differences caused by gonadal hormones versus sex chromosome complement (XX versus XY), we used the four Core Genotype mice (FCG). The FCG model can discriminate between sex differences determined by gonadal type (versus those determined by the effects of sex chromosomes). Sex‐specific transcriptomic changes were observed in numerous genes for each genotype at in room air and after hyperoxia exposure. Sex‐hormones and sex chromosomes may cause sex‐specific differences in the pathogenesis of BPD in premature neonates. The presentation will address knowledge gaps in the molecular mechanisms behind the sexually divergent incidence of BPD and will discuss novel molecular pathways for future therapeutic interventional strategies to combat BPD.Support or Funding InformationThis work was supported by grants from NIH: K08‐HL127103; R03‐HL141572 and R01‐HL14775 to KL.
Current Progress of hiPSCs‐based Therapy in non‐human Primates and Human Clinical Trials
Authors: He Jia-Qiang 
Published: April 2020

Since the first successful creation of mouse induced pluripotent stem cells (miPSCs) in 2006 by Dr. Shinya Yamanaka and the subsequent generation of human iPSC (hiPSCs) in 2007, independently, by Dr. Yamanaka and Dr. James Thomas, iPSCs have been drawing exceptional attention compared to human embryonic stem cells (hESCs), mainly because hiPSCs can be easily generated from virtually any embryonic or adult somatic cells of the body without demolishing human embryos, thus offering an immense promise for personalized regenerative medicine; In contrast to the fetal or adult stem cells (FSCs, ASCs), hiPSCs demonstrate unlimited abilities of self‐renewal and differentiation potency to become almost all somatic cells in the body. Over the past 14 years, about 17,364 papers regarding iPSCs have been published (PubMed search between 2006/01/01 and 2019/11/12), which cover a wide spectrum ranging from in vitro basic researches, computer modeling, in vivo animal and non‐human primate studies to human clinical trials. Up to the present, systemic protocols involving iPSC reprogramming, purification, large‐scale culture expansion, and lineage‐specific differentiation have been successfully developed or optimized to increase the efficiencies of production. Meanwhile, iPSCs and its derivatives have also been widely utilized for mechanistic studies of cellular and molecular development, disease modeling, new drug discovery and toxicity testing. Along with it, a vast type of small‐, large‐animals, and non‐human primate‐models have been exploited to test the therapeutic potentials of these cells in treatments of numerous human diseases. More excitingly, 53 clinical trials of iPSC‐based therapy have been registered in the https://clinicaltrials.gov as of today. Although most of them are still in the “Recruiting” stage, the substantial increase of the registered trials signifies a critical movement towards future clinical practice in all aspects, such as ethical and regulatory compliance under surveillance of U.S. Food and Drug Administration (FDA), quality control of cell products, current good manufacturing practice (cGMP)‐guided cell storage, culture, purification, and lineage‐specific differentiation as well as in vivo assessments of efficacy and safety in a short and long‐term follow‐up. In this talk, we will present an overview of the current progresses, challenges, and concerns of hiPSC‐based treatments for various major diseases (e.g. neural disorders, cardiovascular diseases, and diabetes) using animal models; especially, we will focus on the recent progress acquired from the studies of non‐human primates and human subjects.Support or Funding InformationThis work was supported by the National Institute of Health (NIH 1R15HL140528), the Virginia Tech Commonwealth Health Research Board (CHRB, HE208‐09‐16), and the IRC seed grant from the College of Veterinary Medicine at Virginia Tech.
Regulatory Dynamics of Midfacial Growth in Evolution and Disease
Authors: Selleri Licia , Welsh Ian , Hansen Karissa , Osterwalder Marco , Losa-Llabata Marta , Wells Julie , Bult Carol , Mohun Timothy , Hu Diane , Marcucio Ralph , Visel Axel , Swigut Tomek 
Published: April 2020

Craniofacial morphogenesis demands coordinated outgrowth of spatially‐separated facial prominences. Underscoring this complex choreography, 1/3 of all human birth defects affect craniofacial development. Both orofacial clefting and malocclusions are common birth abnormalities that affect the midface. During midfacial development, regulatory genes control the dynamics of transcriptional activity, tissue patterning, and intercellular signaling to modulate the timing of morphogenetic and growth processes. Variation in these dynamics underlies both evolutionary divergence in midfacial outgrowth and the etiology of craniofacial birth defects. In non‐avians, the main variable driving species‐specific midfacial length is the maxilla of the upper jaw, while in avians it is the premaxilla. Also, avians have cleft palate in physiological conditions. Despite the availability of datasets of regulatory elements from craniofacial tissues and cranial neural crest cells, the majority of regulatory networks that control embryonic midfacial outgrowth are unknown with respect to their in vivo spatiotemporal context‐dependence. We are establishing regulatory landscapes that control different morphogenetic and outgrowth characteristics of midfacial elements at the organismal level in chick, mouse, and pig embryos, species characterized by remarkably different midfacial lengths. To this end, we are combining 3D gene expression profiles obtained via High Resolution Episcopic Microscopy (HREM) of embryos processed by whole mount in situ hybridization as well as genome‐wide transcriptional regulatory activity and epigenetic regulation assessed by RNA Seq, ATAC‐Seq, and chromatin mark ChIP‐Seq of embryonic midfacial anlagen. By this approach, we have identified candidate genes that regulate maxillary‐specific morphogenetic programs in avians versus mammals. One of these genes, which encodes a transcription factor (TF) bearing zinc finger motifs and a homeobox motif, is expressed meristically along the AP palatal shelf of mouse embryos at E11.5–14.5, but is not expressed in the palatal shelves of avian embryos at the corresponding developmental stages. Mice we generated with CRISPR/Cas‐mediated loss‐of‐function of this TF show cleft palate and stunted snout. Strikingly, children with a deletion of this TF exhibit high‐arched palate and cleft palate. These findings establish mechanisms underlying tolerance to morphological variation that separate normal development and evolution of craniofacial features from malformations associated with birth defects.Support or Funding InformationUCSF Recruitment Funds