bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tracing the Cellular “Life Cycle” of Medical Education: Histology as a Theme in Medical Education
Authors: Macnow Alexander Stone Renner 
Published: April 2020

As students pass through the various phases of their “life cycle” in medical education—from undergraduate or post‐baccalaureate student to medical student to residency training and beyond as a healthcare practitioner—cellular structure and function underlie a thorough understanding of mechanisms of disease and are recognized as appropriate launching‐off points to explore the subjects of pathology and therapeutic interventions.Starting in undergraduate and post‐baccalaureate education, students are exposed to cellular structure and function as a corollary to physiology. Research conducted by the Association of American Medical Colleges (AAMC) in anticipation of the Medical Colleges Admissions Test (MCAT®) redesign in 2015 highlighted the importance of histology, cellular physiology, and molecular biology—and the connections between these disciplines—as necessary for success in medical curricula of the twenty‐first century (AAMC MR5 Committee, November 2011).So what role does histology play, then, in medical curricula themselves? As also discussed by the other members of this panel, recognition of histology as a physical correlate of proper cellular function permits the identification of morphologic changes as correlates of cellular dysfunction. Indeed, it is only through the assimilation of a paradigm of “normal” that the student can distinguish “abnormal” and apply or infer the effects of disease states in tissues.Finally, as only a small minority of graduating medical students will select the fields of Anatomic or Clinical Pathology as their career paths, how does histology remain relevant for practitioners during and after graduate medical training? Exploration of analytical and post‐analytical communication between diagnostician and clinician highlights several of these key roles of histology (and pathology) in medical communication and in the discourse of disease. These include improving classification and nomenclature of neoplasms; providing rapid on‐site cytologic diagnoses; and carefully choosing language to trigger or eschew specific interventions, improving patient safety. In these myriad ways, cellular histology (though perhaps often “hidden” behind the microscope) remains relevant throughout the life cycle from student to practitioner.
A new approach for preparing SC‐514 loaded PLGA particles by single emulsion method
Authors: Famuyiwa Toluleke Oloruntobi , Diaka James Kumi , Asghar Waseem , Bowers Zoey , Jebelli Joubin , Bentley Austin , Subtil Paulynice 
Published: April 2020

Poly (lactic‐co‐glycolic acid) (PLGA) is a non‐toxic or non‐injurious subdivision of biodegradable polymer that is not capable of causing immunological rejection. PLGA has been successfully used to encapsulate drugs and deliver drugs in various applications. This high success rate can be linked to the fact that PLGA has been approved by FDA (Food and Drug Administration). SC‐514 is a relatively new hydrophobic dug, which has been shown to have anti‐cancer effects via inhibition of NF‐KB dependent gene expression in cancer cells. SC‐514 was encapsulated in PLGA nanoparticles via single‐emulsion method. The SC‐514 loaded PLGA nanoparticles (diameter=49.4nm) synthesized has the potential to increase the bioavailability of SC‐514 drug in prostate cancer treatment. Hence, increasing the therapeutic effect of SC‐514 in prostate cancer treatment.Support or Funding InformationFellowships and Scholarships from FAU
Endothelial Dysfunction is Transferable from Humans to Germ‐Free Mice via Fecal Microbiota Transplantation
Authors: Trikha Raj , Lee Dustin M. , Ecton Kayl E. , Wrigley Scott D. , Vazquez Allegra R. , Litwin Nicole S. , Thomas Keely N. , Battson Micah L. , Johnson Sarah A. , Weir Tiffany L. , Gentile Christopher L. 
Published: April 2020

IntroductionEndothelial dysfunction and arterial stiffness are commonly observed in obese individuals and are both independent risk factors for cardiovascular disease. Recent preclinical data from our laboratory suggest that alterations in the gut microbiota may be an important factor linking obesity to endothelial dysfunction and arterial stiffness. The purpose of this study was to begin to translate these preclinical data to a human population by examining whether vascular phenotypes in humans are transmissible by fecal microbiota transplantation to germ‐free mice. We hypothesized that germ‐free mice receiving transplantation of an obesity‐associated microbiota would display impaired vascular function compared to germ free mice receiving transplantation of a lean microbiota.MethodsTwenty lean and obese participants were screened for vascular dysfunction and stool samples were collected. One representative obese and one lean age‐ and sex‐matched participant with disparate vascular function were selected as donors for fecal microbiota transplantation. Following transplantation, mice consumed a maintenance diet for 12 weeks. During weeks 11 and 12, mice underwent a glucose tolerance test and a FITC‐dextran test to assess intestinal permeability. After 12 weeks, vascular phenotypes were determined via in vivo aortic pulse wave velocity and ex vivo endothelium‐dependent and ‐independent dilation. 16S rRNA sequencing was used to analyze the microbiota in all samples and sequence data was analyzed using QIIME2 and myPhyloDB.ResultsPrincipal Component Analysis of mouse and donor samples revealed separation of global microbiota profiles with species (human vs mouse) being the factor accounting for the greatest variability (Axis 1; ~24%) in the microbiota, followed by vascular phenotype of the donor (Axis 2; ~19%).Endothelium‐dependent dilation was significantly impaired (p<0.05) in mice receiving microbiota from the obese donor relative to those with lean donor microbiota (maximal dilation to ACH: 50.1% vs 76.9%, p=0.013). Glucose tolerance was also impaired in mice receiving the obese microbiota (AUC: 1577.3 vs 1168.13 mg/dL, p=0.064; minute 90: 372.0 vs 219.2 mg/dL, p=0.043; minute 120: 371.7 vs 211.5 mg/dL, p=0.032). No significant differences were seen with endothelium‐independent dilation, aortic pulse wave velocity, or body weight.ConclusionsThese data provide further evidence that the gut microbiota is an important regulator of vascular function, and suggest that directly targeting the microbiota may be a novel therapeutic strategy for altering vascular phenotypes.Support or Funding InformationNIH R01 HL14411; American Heart Association #18TPA34170585; NIFA AES COL00766
A Randomized, Placebo‐Controlled, Double‐Blind Clinical Investigation on a Patent‐Pending KD120 Metabolically Activated Enzyme Formulation, N‐SORB, in Healthy Young Volunteers
Authors: Nair Sreejayan , Smith Derek , Nair Rama , Downs Berrnard W. , Kushner Steve W. , Bagchi Debasis , Bagchi Manashi 
Published: April 2020

Impaired digestive competence and consequential sluggish immune and metabolic sequela are epidemic‐sized health problems in modern cultures. Since digestion is the first step of metabolism, implementing novel strategies to restore digestive and metabolic competence are important health priorities. N‐SORB is a patent‐pending KD120 multienzyme complex composed of metabolically activated natural digestive‐type enzymes encapsulated in a high‐potency phosphatidylcholine non‐GMO soy lecithin SK713 SLP absorption technology (Prodosome®). A randomized, double‐blind placebo‐controlled study was conducted in 46 male and female healthy volunteers (age: 25.8 ± 12.1 years) to assess the safety and efficacy of N‐SORB. Subjects received either N‐SORB (1 mL, twice daily) or the same amount of placebo for 90 consecutive days. Body weight, blood pressure, physical health, and complete blood chemistries including blood glucose, liver enzymes, and lipid profiles; and immune health, physical health, sleep quality and quality of life parameters were assessed pre‐ and post‐intervention. Serum cytokine levels were determined by using a Bio‐Plex Pro Human Cytokine 8‐plex assay and ELISA. Whole body composition analysis was performed by dual‐energy X‐Ray absorptiometry (DEXA) to determine body fat mass, lean mass and android and gynoid fat. Quality of life (QOL) and sleep quality were assessed using WHOQOL‐BREF and Pittsburgh Sleep Quality Index (PSQI) questionnaire. Adverse events were strictly monitored. 40 subjects completed the study. Hematocrit, hemoglobin, mean corpuscular volume, platelets and lymphocytes provide evidence indicating consistent trends of improvement in the N‐SORB group. QOL parameters showed a small but significant improvement in the N‐SORB group. A significant increase was observed in AST levels in the placebo group at the end of 90 days of treatment, indicating increased liver distress. However, no increase was observed in the N‐SORB group. No significant changes in BUN, serum creatinine, ALP, ALT, and lipid profile were observed between the placebo and treatment groups before and after the 90‐day intervention. No adverse effects were reported. This 90‐day intervention study with N‐SORB clearly exhibited trends of improvement in RBC and immune parameters and found improvements in QOL and sleep quality scivnin already healthy volunteers. The N‐SORB treatment group experienced significant improvement in gastrointestinal functions, immune and metabolic parameters and other systemic improvements. No adverse events were reported.Support or Funding InformationThe Project was partially sponsored by VNI Inc, Lederach, PA
Vacuole Membrane Protein 1 Deficiency Promotes the Development of Pancreatitis Through Autophagy Impairment and Endoplasmic Reticulum Stress
Authors: Wang Shaogui , Chao Xiaojuan , Ma Xiaowen , Ni Hong-Min , Ding Wen-Xing 
Published: April 2020

Pancreatitis is a potentially fatal inflammatory disease with significant morbidity and mortality but the exact molecular mechanisms remain largely obscure. We investigated the role of vacuole membrane protein 1 (VMP1), an endoplasmic reticulum (ER) resident protein, in the pathogenesis of pancreatitis. We examined VMP1 expression and ER stress in human pancreatitis samples. We also determined VMP1 level and ER stress in experimental pancreatitis induced by cerulein as well as in pancreatic acinar cell‐specific VMP1 knockout (VMP1Δacinar) mice. We found that VMP1 expression was significantly lower in human pancreatitis samples associated with extensive ER stress. In a mouse experimental pancreatitis model, treatment with ceruleint markedly decreased VMP1 expression but increased levels of several ER stress markers such as p‐elf2α, XBP1s and CHOP. Western blot and immune histochemical analysis of human and experimental mouse pancreatitis samples showed impaired autophagy with accumulation of p62, an autophagy substrate protein that generally is degraded by autophagy. Intriguingly, VMP1Δacinar mice developed spontaneous pancreatitis with pathological features of chronic pancreatitis. In addition, VMP1Δacinar caused accumulation of p62 as well as selective ER‐phagy receptor FAM134B. Moreover, VMP1Δacinar mice had increased ER tress accompanied with massive cell death, suggesting VMP1 may serve as a key mediator of pancreatic ER homeostasis. Collectively, these data indicate a critical role of VMP1 in maintaining ER homeostasis in acinar cells and decreased VMP1 expression may contribute to the development of pancreatitis.Support or Funding InformationR01 AA020518, R01 DK102142, U01 AA024733 and P30GM118247 (W.X.D).
Hemodynamic Effects of Acute Over‐Ventilation in a Swine Hemorrhage Model
Authors: Blackburn Megan B. , Hudson Ian L. , Rodriguez Cassandra M. , Ryan Kathy L. 
Published: April 2020

IntroductionAirway compromise is the second leading cause of potentially survivable death on the battlefield, indicating a need for improved airway management approaches. Over‐ventilation of the lungs is a complication associated with prolonged use of mechanical ventilation, but few studies have examined the consequence of acute, pre‐hospital over‐ventilation. Therefore, the goal of this study was to determine the effect of acute hyperventilation on the morbidity of hemorrhaged swine.Materials and MethodsFemale Yorkshire pigs (40–50 kg) were anesthetized with isoflurane, instrumented for hemodynamic measurements and blood draws, and switched to IV anesthesia with midazolam and ketamine. Following baseline recording, 25% blood volume by weight was removed, followed by 1 hour of: spontaneous breathing (n=8), “normal” bag ventilation (6 L minute volume, n=9), bag hyperventilation (20 L minute volume, n=8), or mechanical ventilation (n=8). The pigs were then allowed to wake up from anesthesia, recovered for 24 hours, and euthanized for blood and tissue collections.ResultsHemorrhage significantly decreased mean arterial pressure (P<0.001), cardiac output (P<0.001), and stroke volume (P=0.004), but increased heart rate (P<0.001). Ventilation following hemorrhage did not have any further impact on hemodynamic variables, except a significant increase in heart rate in those that underwent bag hyperventilation as compared to spontaneous breathing, normal bag ventilation, and mechanical ventilation groups (24±5 bpm, vs −7±7, 9±11, and 2±2 bpm), respectively. Following ventilation, blood lactate levels were significantly elevated compared to baseline in all groups. The change was significantly greater in those that underwent hyperventilation than in spontaneous breathing, normal bag ventilation, and mechanical ventilation groups (7.9±0.7 mmol/L, vs 4.1±0.6, 5.9±0.4, and 5.4±1 mmol/L), respectively. Blood lactate levels returned to baseline levels by 24 h in all groups. Wet to dry lung weight ratios were also not significantly different between groups, an indication that any edema caused by over‐inflation dissipates by 24 hours.DiscussionThis study was undertaken on the premise that over‐inflation of the lungs, even acutely, would result in significant barotrauma and negative downstream physiological effects. Preliminary results, however, indicate that hemorrhage followed by acute hyperventilation does not affect hemodynamic variables or increase morbidity in mildly hemorrhaged swine. Ongoing studies include histological evaluation of tissue samples, assessment of blood markers for tissue damage, and measurement of plasma cytokine levels to more fully discern the presence of any lasting detrimental physiological effects to the lung or to systemic physiology.Support or Funding InformationUSAMRDC Tactical Combat Casualty Care Research Program
Recombinase‐mediated Method for Multi‐scale Genomic Rearrangements
Authors: Ahmed Haidar S , O’Connell Ronan , Bashor Caleb 
Published: April 2020

With the widespread use of genomic editing tools like CRISPR/Cas9, scientists have gained the ability to modify a host genome with high precision. Although these technological advancements have improved throughout the years, there is still a need for better methods to build more sophisticated multi‐part biological circuits. For this reason, we have employed the use of a genomic integration technique, landing pads, which utilized site‐specific recombinases to insert relatively large DNA assemblies into a well‐defined location the host genome. Using the CRISPR/Cas9 system, we knocked‐in an 8kb landing pad repair template into the AAVSl safe harbor locus of HEK293T cells. After single‐cell sorting and verifying the genotype of our clonal cell line, we used the BxB1 recombinase to integrate a destination plasmid into the landing pad site. Using microscopy, flow cytometry, and PCR genotyping, we demonstrate almost complete replacement of the original landing pad template with our destination vector species within 12 days. Here we present an approach that enables the rapid creation of mammalian cell lines harboring complex, multi‐part regulatory circuits at single copy. This platform allows for precise and tunable control of gene expression profiles, providing an excellent opportunity to engineer safer and more sophisticated cell‐‐based therapies.Support or Funding InformationNational Institute of General Medical Sciences of the National Institutes of Health under linked Award Numbers SC1GM111172, RL5GM118969, TL4GM118971, UL1GM118970, and 5G12MD007592.
Elevated Phosphate Levels Induce Markers of Systemic Inflammation and Anemia in Murine Hepatocytes
Authors: Cunningham Stephen Eric , Czaya Brian Eric , Faul Christian 
Published: April 2020

In chronic kidney disease (CKD), elevated serum levels of fibroblast growth factor 23 (FGF23) and phosphate are associated with various pathologies, including systemic inflammation and anemia. Experimental studies have shown that high phosphate can accelerate CKD‐associated pathologies, but direct effects of circulating phosphate on tissues are not well described. Our objective was to compare the effects of phosphate versus FGF23 on primary murine hepatocytes and to determine their respective contributions to systemic inflammation and anemia in the context of CKD. We postulate that in CKD, elevations in serum phosphate levels contribute to systemic inflammation and anemia by directly targeting the liver and inducing gene programs in hepatocytes, which systemically regulate the inflammatory response and iron metabolism. Our study does not only provide novel insights into the basic pathophysiology of CKD, but might also suggest novel therapeutic strategies to block hepatic effects of phosphate in order to tackle CKD‐associated injuries.Support or Funding InformationPROmoTE R25 DK 112731
Cardiomyocyte‐Specific Deletion of GCN5L1 Limits Cardiac Contractile Decline in High Fat Diet Fed Mice
Authors: Scott Iain , Thapa Dharendra , Manning Janet R. , Stoner Michael W. , Zhang Manling , Xie Bingxian 
Published: April 2020

Healthy hearts use several fuel substrates for energy metabolism, with fatty acid oxidation (FAO) accounting for ~70% of total ATP production. Reduced substrate flexibility, and a shift towards increased fatty acid utilization, is a key feature of obesity and diabetes. We previously reported that increased acetylation of several mitochondrial FAO enzymes, regulated in part by increased abundance of the mitochondrial acetyltransferase GCN5L1, correlated with increased FAO enzyme activity in the heart. The focus of the current study was to investigate whether decreased acetylation, via cardiomyocyte‐specific deletion of GCN5L1 (GCN5L1 cKO), regulates cardiac energy metabolism following exposure to a high fat diet (HFD). Excess dietary fat led to similar cardiac hypertrophy in wildtype and GCN5L1 cKO mice, however animals lacking cardiac GCN5L1 expression were protected from a reduction in cardiac workload. We found that GCN5L1 deletion led to decreased acetylation and FAO activity following a HFD. Furthermore, we found that acetylation of pyruvate dehydrogenase (PDH) was significantly reduced in HFD GCN5L1 cKO animals, which resulted in its increased enzymatic activity relative to HFD wildtype controls. Finally, the acetylation of both electron transport chain Complex I protein NDUFB8 and manganese superoxide dismutase 2 (SOD2) was significantly reduced by cardiac GCN5L1 deletion in HFD animals, resulting in decreased lipid peroxidation. In summary, we demonstrate that GCN5L1 deletion in the heart limits cardiac contractile decline observed in HFD mice, through increased glucose oxidation potential and decreased reactive oxygen species damage.Support or Funding InformationThis work was supported by NIH T32HL110849 to D.T. and J.R.M., and by NIH K22HL116728, R56HL132917, R01HL132917 to I.S.
Cognitive Integration: The Value of Explicitly Communicating the Connections Between Anatomy and Clinical Science
Authors: Lisk Kristina 
Published: April 2020

BackgroundIntegration of basic and clinical sciences is a central component of ongoing curricular reform discussions within health professions education. Despite focused efforts, successfully supporting the development of learners’ integrated knowledge remains an educational challenge. A growing number of experimental studies suggest that learners can benefit when instruction is designed to support cognitive integration; this type of integration is supported through micro‐level teaching activities that present the basic and clinical sciences in a causal network. In this research, I examine the effect of different instructional and learning strategies on supporting cognitive integration of anatomy and clinical science in novice learners using diagnostic performance measures.MethodsIn each study, allied health students were taught four musculoskeletal hand pathologies using different instructional approaches (integrated, segregated, or clinical science only) and learning strategies (self‐explanation or feature counting). Integrated instruction involved explicitly linking the clinical features of each disease with its underlying anatomical pathology, whereas in segregated instruction the anatomy and clinical features were separated. In clinical science only instruction, the general anatomy and anatomical pathology was excluded. Diagnostic performance was measured immediately after instruction, and one‐week later.ResultsThe findings of these studies show that students who were taught the musculoskeletal pathologies with integrated causal mechanisms had superior diagnostic accuracy and a better understanding of the relative importance of key clinical features of disease categories. The application of additional learning strategies, including self‐explanation or feature counting, combined with integrated or segregated instruction did not result in superior diagnostic performance.ConclusionsThis research highlights the value of designing instruction that supports cognitive integration and emphasizes the importance of explicitly communicating the link between anatomy and clinical science during individual teaching sessions. These findings suggest that educators need to carefully consider not only the structure of a learning strategy, but also the extent to which any given learning tool fosters a holistic understanding of clinical signs and symptoms with causal mechanisms.Support or Funding InformationFunding for this research was provided by Humber College Institute of Technology & Advanced Learning.