bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renal‐derived human sPRR increases blood pressure in female but not male mice
Authors: Arthur Gertrude , Poupeau Audrey , Nichols Kellea , Leachman Jacqueline , Loria Analia , Osborn Jeffrey , Yiannikouris Frederique 
Published: May 2022

Previous studies showed that soluble prorenin receptor (sPRR) plays an important role in blood pressure regulation. In rodent models, sPRR contributes to AngII production by increasing renin activity and systolic blood pressure (SBP). Moreover, reducing sPRR release into plasma decreased blood pressure and attenuated angiotensin II (AngII) induced hypertension. However, there is a gap of knowledge concerning the functional role of locally produced sPRR from the kidney in blood pressure regulation. Additionally, the role of human sPRR in blood pressure regulation has not been delineated. Therefore, we evaluated the renal derived human sPRR role in SBP control.Human sPRR‐Myc‐tag transgenic mice were bred with mice expressing Hoxb7/Cre to selectively express human sPRR in the collecting duct (RHsPRR). RHsPRR and control (CTL) male and female mice were fed a standard diet for 10 months (n=8‐11/group). Body weight and urine flow rate were examined and SBP measured by radiotelemetry. Western blot analysis depicted the presence of human sPRR‐Myc‐tag (28 KDa) in the cortex and medulla of RHsPRR male mice which validated the humanized mouse model.Male mice have higher body weights than female mice but renal derived human sPRR did not influence body weights (M: 34.1±0.8 and 32.9±0.8g, F: 28.4±0.8 and 29.6±0.5g, P<0.05). Circulating sPRR was unchanged between male and female mice (M: 3995±643 and 4342±500pg/ml, F: 3479±194 and 3948±238pg/ml). SBP increased significantly in female RHsPRR mice compared to CTL (F: 118.7±2 and 127.2±3 mmHg, P<0.05) but not in male mice (M: 123.8±2 and 119.9±6 mmHg). The SBP response to losartan, an AT1R antagonist, was unchanged in females but was impaired in males (M: ‐7.6±1.2 and ‐5.5±0.8 mmHg, F: ‐6.5±1.2 and ‐7.9±1.5 mmHg, P<0.05). Renal derived human sPRR significantly increased AT1R gene expression in females but not in males (M: 1.8±0.6 and 1.2±0.3 2‐ΔΔCT, F: 1.6±0.5 and 3.8±0.9 2‐ΔΔCT, P<0.05). Moreover, renal derived human sPRR decreased the gene expression of renin and angiotensinogen in female mice (Renin: 1.5±0.5 and 0.4±0.1 2‐ΔΔCT, Angiotensinogen: F: 0.9±0.1 and 0.6±0.1 2‐ΔΔCT, P<0.05) suggesting a negative feedback loop involving Angiotensin II‐AT1R pathway. These effects were not observed in males (Renin: 3.3±1.2 and 4.1±1.2 2‐ΔΔCT; Angiotensinogen: M: 1.4±0.4 and 1.4±0.4 2‐ΔΔCT).Overall, our data suggest that renal‐derived human sPRR increases blood pressure in female mice likely via the activation of renal AT1R expression. In contrast, renal‐derived human sPRR expression impaired the blood pressure response to Losartan in male mice. In conclusion, our data support renal derived human sPRR as a promising therapeutic target in hypertension in humans.
Role of Stress Granules in the Pathogenesis of Pulmonary Hypertension Kosmas Kosmas 1,2, Fotios Spyropoulos1,2,Helen Christou 1,21Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA 2Harvard Medical School, Boston, MA 02215, USA
Authors: Kosmas Kosmas , Spyropoulos Fotios , Christou Helen 
Published: May 2022

BackgroundPAH is a devastating and incurable disease characterized by abnormal pulmonary vascular phenotypes and progressive right ventricular failure, but the underlying mechanisms are incompletely understood. There is an urgent need of new therapeutic approaches, and a better understanding of disease pathogenesis is essential in identifying novel pathways that can be therapeutically targeted. Stress granules (SGs) are small intracellular structures that form in response to stress and contain mRNA molecules and mRNA‐binding proteins. These granules allow cells to temporarily halt translation by “parking” or sequestering certain mRNAs in a protected zone (the stress granule) and this allows the cells to survive in conditions of stress. The role of SGs in abnormal vascular and cardiac homeostasis in PAH is not known.HypothesesWe hypothesized that increased SG formation may contribute to both abnormal vascular cellular phenotypes and cardiac failure in human and experimental PAH. Further, we examined whether treatment with the carbonic anhydrase Acetazolamide (ACTZ) which is known to ameliorate experimental PAH, would alter SG tissue abundance in the lungs and heart.MethodsWe used the adult rat (Sprague Dawley) sugen/hypoxia (Su/Hx) model of severe pulmonary hypertension and studied tissue sections from lungs, heart and skeletal muscle as well as isolated primary pulmonary artery smooth muscle cells (PASMCs). We also used PASMCs from patients with PAH. We applied a combination of immunofluorescence and protein expression studies as well as drug (ACTZ) treatment and in vitro induction of oxidative stress (arsenite) to assess SG formation and SG related markers in experimental PAH and the effect of ACTZ.ResultsWe have discovered that PASMCs from patients with PAH have a higher number of stress granules in response to oxidative stress than cells from normal individuals. We also found that PASMCs from a preclinical model of PAH (Sugen/Hypoxia) have more stress granules and increased SG components in response to oxidative stress compared to normal animals. Further, we found that treatment of PASMCs with ACTZ resulted in lower number of stress granules after cell stress. In addition, we found increased G3BP1 (key component of SG assembly) puncta in alveoli and bronchi and sarcoplasmic G3BP1 puncta in cardiac and soleus muscles from the rat sugen/hypoxia (Su/Hx) model compared to controls and with ACTZ treatment.ConclusionsWe conclude that there is increased SG formation in PASMCs and tissues in experimental PAH and acetazolamide inhibits stress granule assembly in response to oxidative stress. Further studies are needed to define the role of SG in disease pathogenesis, and evaluate whether targeting stress granules may be effective in restoring normal cellular function and improving PAH.
Evaluating Cybersickness in Virtual 3D Models for Anatomy Learning
Authors: Ives Rowan , Lohit Simran , Touliopoulos Evangelea , Reis Isabella R. , Chan Sachi , Sinha Sakshi , Nehru Amit , DeYoung Veronica , Mitchell Josh P. , Brewer‐Deluce Danielle , Sonnadara Ranil , Wainman Bruce C. 
Published: May 2022

IntroductionCybersickness is an array of symptoms associated with exposure to three‐dimensional visualization technology (3DVT) environments, such as virtual reality (VR). It is thought that cybersickness is a type of motion sickness caused by a mismatch in sensory and vestibular input when using these modalities. Symptoms of cybersickness are often akin to those of traditional motion sickness, such as headache and nausea. In the literature, as many as 40‐60% of VR users report symptoms of cybersickness, though in our laboratory approximately 20% of users report symptoms of cybersickness. Our past research has shown that the physical environment is often preferred by students, and more effective for learning anatomy, compared to 3DVT environments. We hypothesize that the preference for, and effectiveness of, the physical environment over 3DVT may be a result of cybersickness due to the isolation of the learner from the physical environment. However, no direct measurements of cybersickness or comparisons between 3DVT environments in anatomy are available.MethodsOur study involves comparisons of cybersickness during anatomy learning between three 3D modalities: a VR Oculus Quest 2TM headset, an autostereoscopic screen (AlioscopyTM), and a 3D‐printed physical model. Undergraduate students, with no formal anatomy training, will be randomized via a Latin square design to view one of three skeletal models (human hemipelvis, zygomatic bone, or calcaneus) in each of the modalities. Participants may not touch the model but may rotate it along the horizontal plane using an XboxTM controller. Participants will have four minutes to learn ten bony landmarks on the viewed model and will then take an untimed, recognition‐based test for landmarks learned before progressing onto the next modality. Cybersickness will be assessed following testing in each modality, via self‐reports on the simulation sickness questionnaire (SSQ).ResultsWe hypothesise that reported cybersickness will be highest for the VR displayed on the head‐mounted display of the Oculus Quest 2TM which entirely covers the visual field, compared to learning through the AlioscopyTM screen or the physical model due to the relative lack of isolation of the learner from the physical environment in the last two treatment groups.ConclusionWith the rapid development of 3DVT for use in anatomical education, cybersickness is an important issue in evaluating the quality of 3D modalities. The results of this study will allow educators and students to make informed decisions about the use of 3DVT in anatomy thus preventing uncomfortable physical symptoms associated with learning using 3DVT and improving learning as a result.
Virtual Reality, Autostereoscopy, and Physical Models for Learning Anatomy: Performance Comparisons
Authors: Lohit Simran , Reis Isabella R. , Ives Rowan , Chan Sachi , Touliopoulos Evangelea , Sinha Sakshi , Nehru Amit , DeYoung Veronica , Mitchell Josh P. , Brewer‐Deluce Danielle , Sonnadara Ranil , Wainman Bruce C. 
Published: May 2022

IntroductionTraditional anatomical education relies on textbooks, physical models, and cadaveric specimens. Advances in technology have provided other display modalities including virtual reality (VR), and autostereoscopic displays. VR uses head‐mounted displays (HMDs) for an interactive experience and autostereoscopic screens, like AlioscopyTM, offer a stereoscopic but HMD‐free environment. Current research shows contradictory results on the efficacy of VR compared to physical models, and there appears to be no data on the efficacy of autostereoscopic displays in learning anatomy. The purpose of this study is to determine whether VR, AlioscopyTM, or physical models yield the best performance for anatomical education.MethodsStudents at McMaster University without prior anatomy training will learn nominal skeletal anatomy in three different modalities: VR (Oculus Quest 2TM), AlioscopyTM, or a physical 3D‐printed bone model. Each of the environments will be as identical as possible (i.e, the VR environment is a rendering of the exact room and set‐up used for testing the physical bone models). Participants will be randomized to one of three interventions where they will study ten bony landmarks on either the human hemipelvis, zygomatic bone, or calcaneus in a distinct modality. Participants will be seated and use an XboxTM controller to rotate the bone along the vertical axis of rotation. After four minutes, an untimed, recognition‐based test will be administered, where participants will be given a 3D‐printed bone identical to the one used in the learning phase, with randomized landmarks and word bank of landmarks learnt. Performance will be evaluated based on landmarks correctly identified on the recognition‐based test.ResultsBased on the current literature, we hypothesize that the physical models will be a superior learning environment compared to the VR environment. However, significant improvements in the HMD of the Oculus Quest 2 may have ameliorated previous issues with the VR environment. There is no data available on the efficacy of AlioscopyTM and while the absence of an HMD is appealing, its narrow viewing angle compared to the immersive VR environment may be problematic.ConclusionWith the push to increase accessibility and decrease costs associated with anatomical education with the help of digital modalities, the findings from this study are critical to informing teaching practices, and technology use in anatomy education.
Minigames for Teaching the Cardiovascular System to Students of Human Anatomy
Authors: Naples Virginia , Sullivan Ian , LaBarbera Dean , Kluga Ben , Edwards Lucas , Freedman Reva 
Published: May 2022

We are building a series of cell‐phone based minigames as a new approach to teaching cardiovascular concepts. The minigames belong to the first iteration of our intelligent textbook, Cardiovascular and Respiratory Anatomy Map (CRAM). They are part of a larger suite of games under a common umbrella that teach students the key concepts in human anatomy. Playing games engages student interest and enables students to learn at a lower stress level. Our goal is to enable students to master this material without getting distracted by different but related concepts in the cardiovascular system.The purpose of this game is to demonstrate that oxygenated and deoxygenated blood flow patterns in the pulmonary circuit are different than in the systemic circuit. We ask students to learn the names of the arteries and veins that supply and drain the heart and lungs. In the first stage of the game, students just need to identify correctly which vessels contain oxygenated and deoxygenated blood and the direction of blood flow.Students run this game on a cell phone or laptop. The screen shows the main organs involved in this process, namely the heart, the two lungs (one on each side of the screen), and a stick‐figure representation of the body. The organs are connected by the great vessels that transport blood to and from the heart and lungs. Students click on the arrows representing the vessels and color them red or blue. When they color a vessel incorrectly, the system responds with information to correct their misconception. For example, if the student colors the pulmonary arteries red, they are informed that the pulmonary arteries carry deoxygenated blood to the heart.This game is the first of a series of games teaching students the fundamentals of cardiac anatomy and function. Different from other materials that teach cardiovascular function, the first game does not make students memorize the chambers of the heart and their relationship to the great vessels. We believe that separating this issue from understanding the higher level relationship between the organs reduces the initial cognitive load on students and streamlines their ability to attain mastery of the entire system. A typical human anatomy book requires 30–40 pages of text to cover the material we present in a series of minigames. This approach appeals to contemporary students who prefer to use their cell phones for learning and are reluctant to read the assigned text.The system has two take‐home messages. In mammals, the pulmonary arteries are the exception to the rule that an artery always carries oxygenated blood because they receive deoxygenated blood from the heart. In addition, the lungs only provide oxygen to body tissues via the heart, which is a double‐circuit pump. In this game, students assimilate this information via active participation rather than by rote memorization.
Metabolomic characterization of Pseudomonas protegenssecretions for identification of biopesticides against Bacterial Panicle Blight of rice
Authors: Balboa Samantha J. , Vierengel Maia , Gates Kristen , Rojas Clemencia , Hicks Leslie 
Published: May 2022

Bacterial Panicle Blight (BPB) is a rice disease caused by Burkholderia glumae that has become a global concern in reducing rice yields. Currently, there are no effective chemical treatments or resistant cultivars to control BPB. We have observed that bacterial secreted fractions from the antagonistic microorganism Pseudomonas protegens PBL3 inhibits B. glumae infections in rice plants. However, the responsible antimicrobial molecules are unknown. Genome comparison between P. protegens PBL3 and the reference strain P. protegensCHA0, a well‐characterized microbial biological control agent, revealed the presence of 14 known biosynthetic gene clusters (BGCs) in P. protegensPBL3. From this genomic data, it is likely that P. protegensPBL3 secretes metabolites with activity against BPB that are not produced by P. protegensCHA0.Cultures of P. protegensPBL3 and the reference strain, P. protegensCHA0, were grown in M9 minimal media supplemented with 1% myo‐inositol. The metabolite secretome of P. protegens PBL3 and CHA0 were harvested in log phase and analyzed with a Waters Acquity H‐Class HPLC coupled to a Thermo Q‐Exactive HF‐X. In addition, active PBL3 fractions against B. glumaewere analyzed via LC‐MS to confirm the presence of bioactive compounds. The resulting data were searched against the Global Natural Products Social Molecular Networking (GNPS) spectral library. For potential antimicrobial peptide identification, data were searched against the Mascot database. To validate these results, known bioactive metabolites in P. protegensCHA0 were identified. By utilizing LC‐MS/MS based metabolomics, several compounds were uniquely identified in P. protegensPBL3 that could be used as biocontrol agents against BPB in rice.
Core Concepts as a Framework to Assess the Progression of Student Learning in a Ume Curriculum
Authors: Averill David , Waite Gabi N. , Sharma Prerna , Mamillapalli Sireesha , Carbe Christian 
Published: May 2022

PURPOSEConceptual frameworks have demonstrated better learning outcomes in undergraduate medical education (UME). We propose developing a conceptual framework based upon core concepts (CCs) in biomedical sciences to link the progression of student learning to program objectives of a recently revised UME curriculum.METHODSOur project involves three steps. Step 1 identifies clinically relevant CCs pertinent to learning objectives of basic science disciplines. Step 2 tags multiple choice questions (MCQs) allowing us to follow students’ progression of conceptual learning across formative and summative assessments and to identify conceptual learning gaps for continuous program improvement. Step 3 will develop enterprise‐grade dashboards to monitor the learner’s conceptual understanding across UME.RESULTSFor Step 1, we identified 7‐10 clinically relevant CCs in the disciplines of physiology, biochemistry, and genetics. We adapted CCs published by discipline‐specific organizations and by Aquifer, Inc. to our clinical presentation‐based curriculum. The selection process and outcomes will be presented at the meeting. For step 2, we established concept categories in Examsoft™ where our MCQs are housed and are already tagged by discipline and clinical presentation. We will present results of ANOVA‐based analysis of student performance data. For Step 3, we will incorporate CCs with One45 Analytics‐based dashboards which draw upon data from Examsoft™ and our Learning Management System. This is a collaboration with our Department of Assessment and Evaluation. A beta version of the dashboard will be presented at the meeting.CONCLUSIONSThis study presents student performance data on concept tagged MCQs. These data will track student learning as well as the efficacy of conceptual clinical presentation frameworks implemented in our revised curriculum. Together with high‐quality systemic dashboards, we can monitor conceptual learning and basic science application in our UME curriculum.
Cord Blood Metabolomics and Autism Spectrum Disorder
Authors: Schickling Brandon , Gumusoglu Serena , Santillan Donna A. , Santillan Mark K. 
Published: May 2022

IntroductionAutism spectrum disorder (ASD) has increased dramatically in prevalence and incidence in recent years (1:59 in the US, CDC). With prenatal and/or genetic origins, early detection and intervention are critical to improve outcomes. Few studies have assessed perinatal biomarkers for later development of ASD. We hypothesize that cord blood plasma‐based metabolomics will differentiate infants who would later be diagnosed with ASD and typically developing (TD) controls.MethodsBanked cord blood plasma samples and clinical data from the Iowa Maternal Fetal Tissue Bank were used. Samples were analyzed via gas chromatography and mass spectrometry (GC‐MS) and relative MS signal intensity of a maximum of was quantified ratiometrically. All metabolites were normalized to internal controls (succinate) to account for effects of extraction, derivatization, and/or loading. Ratiometric levels of each metabolite were compared by t‐test between ASD and control groups. Results P<0.01 are reported given the pilot nature of this small study. Metabolite set enrichment analysis (MSEA) was performed against human libraries. Significantly altered metabolites were compared to a tertiary sample of cord blood from individuals later diagnosed with attention deficit hyperactivity disorder (ADHD) to determine specificity for ASD.Results91 metabolites were detected and analyzed. Homocysteine (fold change [FC]: 1.411; p=0.017), Myristic acid (FC: 1.221; p=0.084), Pentadecanoic acid (FC: 1.256; p=0.093) were increased in ASD samples, while L‐Isoleucine (FC: 0.858; p=0.047), L‐Threonine (FC: 0.7131; p=0.068), O‐Phosphoethanolamine (FC: 0.704; p=0.070), and 2‐Hydroxybutyric acid (FC: 0.615; p=0.073) were decreased. Of these, only pentadecanoic was also significantly changed in ADHD samples (FC: 1.514; p=0.002). MSEA revealed enrichment of homocysteine degradation (p=0.017), catecholamine biosynthesis (p=0.048), threonine and 2‐Oxobutanoate degradation (p=0.068), Phosphatidylcholine Biosynthesis (p=0.070), and Phosphatidylethanolamine Biosynthesis (p=0.070) in ASD cord blood samples.ConclusionWe found that cord blood plasma metabolomics reveals intriguing and specific differences between ASD and control samples. While some of differences are supported by evidence, these alterations have not previously been extended to the prenatal period. Future work will investigate concordance with maternal blood metabolomics to determine maternal‐fetal pathways.
Short‐duration Aerobic Exercise Improves Chemotherapy Induced Physical Dysfunction in Mice
Authors: Halle Jessica L. , Counts Brittany R. , Carson James A. 
Published: May 2022

Chemotherapy regimens for colorectal cancer cause body weight loss, fatigue, and weakness that may persist long after treatment completion. While increased physical activity can help to mitigate these effects, low adherence to standard exercise prescriptions limits the therapeutic potential. Therefore, it is necessary to determine if an exercise threshold is required to improve chemotherapy toxicity. Gaps remain in our understanding of the extent of chemotherapy toxicities after treatment completion, and if a low dose of exercise is sufficient to improve chemotherapy‐induced dysfunction.PurposeTo examine the effects of exercise dose on body composition and physical function in mice during the recovery from Folfox chemotherapy.MethodsMale C57BL/6J mice (12wks) were injected with 4 cycles (1 cycle= 1 injection every other wk) of Folfox (FOL; 5FU 30mg/kg, Oxaliplatin 6mg/kg, Leucovorin 90mg/kg) or PBS. Mice were sacrificed 0wks (n=8) or 4wks (n=16) after the 4th cycle. Subsets of mice performed 14 sessions (6d/wk, 5% grade) of short‐ (15min/d; n=10) or long‐duration (60min/d; n=10) treadmill exercise during recovery. Body composition by MRI, treadmill run time to fatigue (RTF), and grip strength tests were performed pre, post, and after 4wks recovery.ResultsFOL treatment attenuated body mass gain (PBS 10%, FOL 3%) independent of food intake (p=0.586) or cage activity (p=0.801). Fat mass accumulation was decreased (PBS: 56%, FOL: ‐3%) with no changes in lean mass during treatment. During recovery, body mass remained suppressed (‐8%; p=0.022), and RTF (‐43%; p<0.01) and grip strength were reduced (‐9%; p=0.045) in FOL mice compared to PBS. Treadmill exercise improved body weight loss (3%; p=0.041) independent of fat mass. Long‐ compared to short‐duration exercise increased lean mass (p<0.01) in both treatment groups. Both short‐ and long‐duration exercise improved RTF (93%; p<0.01) without improving grip strength.ConclusionRepeated cycles of Folfox chemotherapy can induce persistent deficits in physical function and fat mass. Two weeks of short‐duration aerobic exercise was sufficient to reverse chemotherapy induced fatigue without improving strength. Future studies should examine if the combined effects of aerobic and resistance exercise can improve strength.