bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isopropyl Alcohol and Methylene Chloride as Alternatives for pre‐plastination Dehydration and Defatting processes
Authors: Lopez-McCormick Juan Sebastian , Pedraza Juan Daniel , Rueda-Esteban Roberto Javier 
Published: April 2020

Plastination as a technique creates durable, long lasting, realistic specimens with a high value in anatomy teaching and research. While the original protocol using Acetone has shown great results, the use of this substance is restricted in some countries due to socioeconomical or governmental limitations. The aim of this work is to develop a protocol in which acetone has been replaced as a dehydration and defatting medium.Three groups of specimens were procured. Each of them had a sample of abdominal organs with varying fragility (kidney‐liver‐small intestine), skeletal muscle and brain tissue. Group 1 and 2 (G1–G2) were previously fixated with formaldehyde 4%, while group 3 (G3) was preserved in a glycerin‐based formaldehyde free solution. A conventional plastination technique was carried out including fixation, dehydration, defatting, forced impregnation and curing.All groups were fixated with formaldehyde 10%, although G3 required cleansing with a 50% ethylic alcohol (EA) solution to remove the glycerin. G1 was dehydrated and defatted with EA. G2 & G3 were dehydrated with isopropyl alcohol (IA), and defatted with methylene chloride (MC). All groups were impregnated in low temperatures with 1% S3–S10 Biodur silicone‐cross linker mixture. Finally, curing was divided in two steps, passive curing for 6 months and S6 cross linking. The specimens were analyzed based on tissue retraction, color degradation, morphological alterations and final specimen pliability.G1 showed maximum tissue shrinkage, morphological alteration and color degradation acquiring a brownish tone. G2 & G3 suffered less tissue retraction, color degradation was minimal, morphological alteration was not observed. Specimen pliability remained the same across the three groups, specific tissues such as skeletal muscle, blood vessels and intestine were more pliable.Lesser tissue retraction and increased color preservation were obtained with the use of IA and MC for dehydration and defatting, compared with exclusive use of EA for both steps. Specimens previously preserved with glycerin‐based formaldehyde free solutions where successfully plastinated with this technique.While this study serves as a proof of concept that IA and MC are viable substitutes for Acetone in the dehydration and defatting steps, the lack of objective measurements and a control group with acetone are strong limitations of this study. Future studies with a higher number of standardized specimens and controls are needed to determine the impact of the proposed replacement in the plastination protocol.
Effect of Prostate Cancer and Endurance Exercise Training on Aerobic Capacity
Authors: Baumfalk Dryden R. , Colburn Trenton D. , Horn Andrew G. , Kunkel Olivia N. , Weber Ramona E. , Musch Timothy I. , Behnke Bradley J. 
Published: April 2020

BackgroundProstate cancer is the most commonly diagnosed non‐skin cancer in men accounting for 20% of all diagnoses. Exercise intolerance is common in cancer patients, in particular, in those undergoing adjuvant therapies (i.e., androgen deprivation therapy) that leads to reductions in quality of life. Recent evidence suggests prostate cancer, independent of treatment, hastens fatigue (i.e., reduces time to exhaustion) which is associated with atrophic effects on whole heart and left ventricular (LV) mass. However, moderate‐intensity endurance training mitigates cardiac mass loss in prostate tumor‐bearing rats. Using a pre‐clinical orthotopic model of prostate cancer, we tested the hypothesis that prostate cancer would reduce aerobic capacity, assessed as maximal oxygen consumption (V̇o2max). We also investigated whether moderate‐intensity endurance training would mitigate any loss of aerobic capacity associated with prostate cancer.MethodsDunning R‐3327 MatLyLu prostate adenocarcinoma cells (2×105) in 0.1ml of physiological saline solution were injected in the ventral lobe of 4–5‐month‐old male RNU (NIH nude) rat (n=10). These animals were randomized into 2 groups, Tumor Bearing Exercise (TBEX, n=6) or Tumor Bearing Sedentary (TBS, n=4). After ~5 days of recovery, TBEX animals began progressive exercise training on a motorized treadmill at 25 m/min with a 5% incline for 10 minutes a day progressing to 60 min/day for a ~5 week period. Pre‐injection (Pre) and post‐exercise training (Post) animals performed V̇o2max testing at least twice to verify attainment of maximal value (i.e validation test), with a minimum of 24 h of recovery between bouts to ensure reproducibility.ResultsThere were no significant differences (all p>0.05) in tumor mass between groups (TBEX 6.4±1.1; TBS 7.6±1.2 g), body mass (TBEX 322±15; TBS 361±16 g), or Pre‐injection V̇o2max (TBEX 82.2±2.1; TBS 78.5±2.5 ml·min−1·kg−1). Heart to body mass ratio was lower in TBS group compared to TBEX (2.9±0.1 vs. 3.3±0.1 mg/g, p<0.05). Following training, TBEX had increases in V̇o2max (6.4±1.3 ml·min−1·kg−1, p<0.05) whereas TBS had a decrease in aerobic capacity
(
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5.6±2. ml·min−1·kg−1, p<0.05).ConclusionThis study suggests that prostate cancer, independent of treatment significantly diminishes maximal aerobic capacity. Further, moderate‐ intensity exercise training not only mitigates this cancer‐associated loss, but effectively improves aerobic capacity vs. values obtained prior to cancer development. Given prostate cancer patients often present fatigue and loss of quality of life, moderate‐ intensity exercise training may be useful to improve both facets via maintaining or improving aerobic capacity.Support or Funding InformationNIH HL137156‐01A1ACS RSG‐14‐150‐01‐CCE
The effect of hand preference on skeletal asymmetry in human limbs
Authors: Eriksen Amandine B. , von Cramon-Taubadel Noreen 
Published: April 2020

The study of asymmetry offers valuable insight into the biomechanical factors, such as hand preference, that influence development of the human body. Previous studies of human skeletal asymmetry often lack known handedness data and tend to presume right‐handedness without specifically analyzing upper limb elements. Here, we investigate differences in individual asymmetry (IA) in elements of the upper limb (i.e. humerus, radius) and lower limb (i.e. femur, tibia) from a modern sample of 40 males and females for whom hand preference was documented. The shape of these four bones was quantified using landmark configurations on 3D bone models. All possible distances between landmarks were calculated for the left and right sides of each bone and were used to calculate average IA for each individual bone. The results found that IA for the four bones was only correlated between the humerus and radius (r = 0.33, p = 0.038), suggesting that the upper limb does not always correlate with the lower limb as previously thought. Kruskal‐Wallis and Mann‐Whitney U tests found no significant differences in IA across sex or handedness groups for the limb bones but left‐handed males and females had higher left‐side dominance in the radius and tibia as compared to right‐handed individuals. Thus, the results suggest that handedness can affect asymmetry in the lower limb. Further addition of specimens, particularly left‐handed individuals, will elucidate the relative effects of handedness in shaping human skeletal asymmetry patterns.Support or Funding InformationThis was supported by funding from the Wenner‐Gren Dissertation Fieldwork Grant (Grant #9641), the Mark Diamond Research Fund (SP‐18‐19), and the 2017 Morris E. and Lucille R. Opler Dissertation Research Scholarship.
Essential Anatomy for General Surgery in the Undergraduate Medical Curriculum
Authors: Keim Sarah , Topping Daniel , Zumwalt Ann , McNary Thomas , Farias Anna , Granite Guinevere , Notebaert Andrew , Sanky Charles , Laitman Jeffrey , Reidenberg Joy S. , Lewis Steven , Brooks William , Royer Danielle , Martindale Jim , Harmon Derek , Hankin Mark 
Published: April 2020

IntroductionTo prepare medical students for clinical training and practice, it is critical to understand the anatomical knowledge considered most important for different clinical specialties.AimTo address this issue, a consortium of anatomists in the US and Canada is collecting data from clinical educators in General Surgery clerkships and electives to identify the anatomy they consider essential.MethodsAn IRB‐approved, online survey (Qualtrics, Seattle, WA) was used to assess the importance of 98 anatomical topics in seven body regions. The study first examined the percentage of General Surgery clinical educators (clerkship/elective directors and attending physicians) that considered each anatomical region important to their specialty. Second, the study examined the rank assigned to each anatomical topic using an ordinal scale from 1 (not important) to 4 (essential).ResultsAt the time of abstract submission, data had been collected from 40 General Surgery clinical educators at 14 medical schools. The percentage of General Surgery clinical educators that considered each anatomical region important to their specialty were (highest‐to‐lowest): Abdomen (100%), Pelvis & Perineum (89.7%), Thorax (82.5%), Head & Neck (71.8%), Upper Limb (61%), Lower Limb (59%), and Back (51.2%). Further data analysis has identified the highest ranked anatomical topics in each body region for the General Surgery clerkship/elective.Discussion and ConclusionThis database provides detailed information regarding the most clinically relevant anatomical topics as identified by General Surgery clinical educators. This information can aid in focusing preclinical learning to best prepare medical students for success in their undergraduate and graduate clinical experiences.
Comparison between Supplementation and a Diet High in Vitamins A, C, E on Inflammation and Oxidative Stress in Patients with Cardiometabolic Risk
Authors: Ortiz-Avila Omar , Campos-Arroyo Ana Gabriela , del Carmen López-Miranda María 
Published: April 2020

Cardiometabolic risk refers to interrelated traditional risk factors for metabolic syndrome such as dyslipidemia, hypertension, obesity, insulin resistance, and hyperglycemia as well as behavioral factors such as physical inactivity, smoking, and unhealthy eating patterns. Family history, age, sex, and race/ethnicity also contribute to cardiometabolic risk. Currently Mexico has presented an increase in cases of obesity, according to the OCDE, Mexico is the second country, after the United States, with higher degree of obesity in the adult population. Oxidative stress and inflammation play a central role in the onset and development of many of the diseases that appear in patients with cardiometabolic risk, due to this an alternative in the treatment would be the use of antioxidants such as vitamins A, C and E. High dietary intake of vitamin C, carotenoids, and vitamin E have been associated with reduced risk of cardiovascular disease, cancer, and mortality, but these associations have not shown conclusive results. In addition, there is controversy between whether it is better to supplement these vitamins or include them in diet foods.Therefore, the objective of this work was to compare the effect between foods and supplements with a high contribution of vitamin C, A and E on markers of inflammation and oxidative stress in patients with cardiometabolic risk. The sample selection is from voluntary subjects and consists of 30 people between 30 and 60 years of age who present cardiometabolic risk factors, which were divided into two groups, one received the vitamins in supplements and the other in the food of the diet for 90 days. At the beginning and the end of the treatment, anthropometric measurements, biochemical determinations such as glucose and lipid profile, as well as markers of inflammation (IL‐6 and TNF‐α) and oxidative stress (TBARS and Glutathione) were performed.On average the patients was 33.4 years old and they had a BMI of 34.5. Women had a waist circumference of 88 cm and 102 cm for men which most were obese. In addition, patients had impaired fasting glucose levels (105.4 mg/dL) and low HDL levels (Men: 31.3 mg/dL; Women: 42 mg/dL). As they were patients with cardiometabolic risk presented oxidative stress and inflammation. The consumption of supplements showed a greater effect in reducing these parameters since were higher doses that can’t be achieved with diet foods. The results indicate that consumption of vitamins A, C and E in patients with cardiometabolic risk is a tool that can complement the treatment of these patients because it helps reduce oxidative stress and inflammation due to its antioxidant effects.Support or Funding InformationThis project was sponsored by the Instituto de Investigaciones de la Universidad de Morelia S.C.
Effect of Chronic Temperature Acclimation on the Liver Proteome of Threespine Sticklebacks (Gasterosteus aculeatus)
Authors: Levitan Bryn Bo , Bates Alexandria Nicole , Kültz Dietmar 
Published: April 2020

This study investigated the liver molecular phenotypes of two different populations of first generation lab‐reared threespine sticklebacks (Gasterosteus aculeatus) from northern California: a fully plated population from the Klamath River in Klamath, CA and a low plated population from Big Lagoon in Trinidad, CA. Temperature is one of the most influential abiotic factors affecting fish and this study gives insight into the molecular changes used to offset temperature stress in the liver. We constructed an assay library for the liver that consisted of 1,715 proteins, 5,897 peptides, 6,995 precursors, and 40,999 transitions with Skyline (MacCoss Lab). The assay library was constructed with samples from fish (N=22) of both populations after chronic warm, chronic cold, acute warm, and acute cold (Klamath population only) temperature stress experiments using data dependent acquisition (DDA) shotgun proteomics. This assay library was then used to compare the molecular phenotypes of Klamath and Big Lagoon stickleback livers after a three‐week exposure to either 7°C (cold), 15°C (control), or 25°C (warm). It will also be used to analyze acute temperature stress experiments in the future. Liver proteomes were extracted, trypsinized, and analyzed by gel‐free quantitative proteomics using liquid chromatography‐mass spectrometry (LC‐MS/MS). There were only 6 proteins with significantly different abundances between the Klamath and Big Lagoon populations (p < 0.05, fold change ± 2), suggesting similar molecular phenotypes between the two groups. There were 8, 141, and 234 proteins with significantly different protein abundances for comparisons of 7°C and 15°C, 15°C and 25°C, and 7°C and 25°C respectively (across both populations combined). Our results suggest that gradual acclimation to a warmer temperature, as opposed to a colder temperature, results in larger changes in relative protein abundance and gives insight into potential liver adaptations to sustained warmer temperatures.Support or Funding InformationThis study was funded by a grant from NSF (IOS‐1656371).
In Silico Prediction of Cytochrome P450‐Based Drug‐Drug Interactions in Breast Cancer Treatment Regimens
Authors: Arrighi Scott , Hernandez Layrette , Deb Subrata 
Published: April 2020

IntroductionBreast cancer is one of the most frequently diagnosed cancers in US. Its treatment regimens are complex as they involve premedications and concomitant medications, and can result in drug‐drug interactions (DDI). There are limited data available on cytochrome P450 (CYP)‐based drug interactions within the breast cancer regimens. The goal of the current study was to predict DDI between the drugs in the breast cancer treatment regimens.MethodsUsing the National Comprehensive Cancer Network (NCCN) guidelines the treatment regimens for breast cancer were identified. In silico DDI predictions were performed at steady state simulation using DDI module of the GastroPlus software provided by Simulation Plus Inc. The premedication and concomitantly administered drugs were evaluated as combinations with chemotherapeutic agents. Various enzyme inhibition kinetics parameters (e.g., Ki and EC50) required for simulation were obtained from the recent literature.ResultsUsing the simulated and calculated gut and liver unbound perpetrator concentration during the steady state simulation, combinations of drugs showed differential DDI potential. Aprepitant, an antiemetic agent, showed moderate to strong inhibition when used with docetaxel, paclitaxel, abemaciclib and olaparib. In certain cases calculated liver perpetrator concentration showed a stronger inhibitory prediction of chemotherapeutic agents compared to simulated liver perpetrator concentration. Results obtained with netupitant varied from weak to strong inhibitory interactions with chemotherapeutic agents.ConclusionsIn silico analyses appear to confirm that breast cancer treatment regimens may interact with each other and influence plasma concentrations of chemotherapeutic agents. We conclude that toxicity or therapeutic failure from anticancer agents could be due to interactions within the breast cancer treatment regimens.Support or Funding InformationThe GastroPlus software 9.5 version was provided by Simulations Plus, Inc. (Lancaster, CA)
Protein Kinase C Activity is Increased in Human Coronary Smooth Muscle Cells following Exposure to 5‐FU Chemotherapy
Authors: Parr Shannon K. , Hammond Stephen T. , Baumfalk Dryden R. , Kunkel Olivia N. , Steele Catherine C. , Behnke Bradley J. , Ade Carl J. 
Published: April 2020

Background5‐Fluorouracil (5‐FU) is the third most commonly used chemotherapeutic agent used to treat cancer but is strongly associated with a dose‐limiting cardiotoxicity. Cancer patients treated with 5‐FU chemotherapy are at risk of cardiotoxicity that manifests as alterations in the myocardial circulation such as resting or exertional angina, arrhythmias, myocardial infarction, and coronary vasospasm. However, little is known about the primary signaling mechanisms that contribute to cardiotoxicity with 5‐FU. Recent work has suggested that the Protein Kinase C (PKC) family of kinases plays a role in altered vasoconstrictive responses in vascular smooth muscle following exposure to 5‐FU. Further, PKC signaling in other pathologies is known to be influenced by reactive oxygen species (ROS) and 5‐FU chemotherapy is known to promote the production of ROS. Therefore, we hypothesized that 5‐FU administration would increase PKC activity in human coronary smooth muscle cells (HCSMCs).MethodsIn vitro, HCSMCs were incubated with 5‐FU (7×10−3M) for 3h, 1h, and 10 minutes. Following the respective incubation periods, media was aspirated in control and 5‐FU groups and the HCSMCs were scraped, homogenized in lysis buffer, and analyzed for protein content. The activity of PKC was assessed by a PKC activity assay kit.ResultsAnalysis revealed relative PKC activity was significantly increased in HCSMCs following 10 minutes of exposure to 5‐FU chemotherapy (6.52±0.36 versus 4.84±0.36; p=0.02) and was not different at 1 hour versus control and 3 hours versus control (1h 5.28±0.356 versus 4.84±0.36; p=0.82, 3h 5.67±0.36 versus 4.84±0.36; p=0.37).ConclusionsOur findings suggest 5‐FU exposure acutely upregulates PKC activity in coronary smooth muscle cells immediately following drug administration and the PKC pathway may have a mechanistic role in the altered vasoconstrictive response to 5‐FU as previously shown. These findings are imperative given the limited knowledge of mechanistic pathways that lead to vascular damage following 5‐FU exposure. Future studies will focus on reactive oxygen species as a regulator of PKC activity and specific isoforms involved in this pathway.
Hepatocyte specific ablation of β and γ‐catenin leads to altered hepatocyte polarity and EMT induction
Authors: Pradhan-Sundd Tirthadipa , Singh Sucha , Bell Aaron , Monga Satdarshan Pal 
Published: April 2020

A hallmark of epithelial cells is polarization. Like any other epithelial cell, hepatocytes in the liver show a unique polarity by forming several apical and basolateral poles within a cell. Polarization of hepatocytes is necessary for many functions and requires carefully orchestrated cooperation between cell adhesion molecules, extracellular matrix, cell junctions, cytoskeleton, and intracellular trafficking machinery. Loss of hepatocyte polarity is associated with various liver diseases including cholestasis.Previously, we discovered that simultaneous deletion of adherens junction protein β and γ catenin in the mice liver led to cholestasis (Hepatology, 2017). However, the molecular mechanism that led to cholestasis in the absence of β‐ γ‐catenin remained unclear. To address this, we have developed a hepatocyte specific β and γ catenin conditional double‐knockout mice. Electron microscopy revealed dilation of bile canaliculi with significant reduction in microvilli in the liver of double knock out mice. IHC, protein and RT‐PCR analysis revealed loss of several hepatocyte polarity markers including CD10, ZO‐2, BSEP, and MRP2, increased fibrosis and epithelial‐mesenchymal transition in the liver. Remarkably, RNA‐seq analysis revealed over activation of TGFβ pathway in double knock out liver and blocking TGFβ pathway led to partial rescue of tight‐junctional proteins and cholestasis. Taken together, our findings suggest that β; γ‐catenin are critical to the maintenance of hepatocyte polarity and cholestasis development by regulating TGFβ signaling in hepatocytes. Profound understanding of the regulation of hepatocyte polarity by both β ‐and γ‐ catenin will be useful not only in understanding cholestasis but also in the context of liver development and pathophysiology.