bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of game-based learning strategies in student engagement in Health Professions education
Authors: Alarcon Fortepiani Maria 
Published: May 2023

Learning is enhanced when students are involved and engaged. However, in the past years there has been an increase in student disengagement. Class attendance is decreasing and students do not complete their assignments or turn work on time. Research has demonstrated that engagement allows the student to develop higher-level critical thinking, which is essential in Health Professions. Providing opportunities for this intellectual engagement is necessary to capture the student’s attention and numerous technologies have surged to meet this goal. One of the teaching resources utilized as an engagement tool in the classroom is gamification and game-based learning strategies. In this study, we developed game based educational resources and assessed their impact in student engagement and learning in Optometry students. A total of 66 students were enrolled in a Systemic Pathology course. The course used flipped instruction and students were asked to watch pre-recorded lectures or videos on a topic before the on-site session, where they worked in groups on a case based on that topic. The game-based learning approach was used for some of the course cases and consisted in using multiple games provided by the instructor to provide a short answer for the case questions. At the end of the semester, all the students completed a feedback questionnaire. The students reported that solving cases during class, independent of the use of games, was beneficial to their learning (79%). They perceived the use of games as enjoyable (68%) and reported an improvement in their learning (69% reporting from beneficial sometimes to very often) when compared to the traditional cases without the game component. Furthermore, we compared this cohort to the same course offered the previous year with no game-based activities to determine the impact on student performance. We found that the two groups obtained similar scores in the quizzes, final exam, and course average. In conclusion, the use of game-based learning strategies increased the engagement of the students and their perception of what they learned, however, it did not seem to improve their academic performance in the course. APS Teaching Career Enhancement Award This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Microvascular constriction via fatty acid-mediated oxidative stress in humans
Authors: David Hannah , Holwerda Seth 
Published: May 2023

Purpose: Excess plasma lipids promote oxidative stress and impair vascular function. Herein, we examined microcirculatory blood flow and tested the hypothesis that a co-infusion of a water-soluble antioxidant (ascorbic acid, AA) would attenuate reductions in retinal arteriole lumen diameter and increase resistance resulting from acutely elevated plasma lipids in healthy adults. Methods: A 20% IV fat emulsion (Intralipid) was administered for 2 hours to 8 healthy, middle-aged adults (2 men/6 women) with and without co-infusion of ascorbic acid (separate visits) in a double-blinded, crossover study design. Co-infusion of AA was administered at 0.06g/kg fat free mass in 100 ml saline at 5 mL/min over 20 min (bolus) followed by a drip infusion at 0.02 g/kg fat-free mass in 30 ml saline at 0.33 mL/min over 90 min. Retinal arteriole lumen diameter and resistance were assessed via Laser Speckle Flowgraphy at baseline and after infusion. Results: Lipid infusion significantly increase plasma fatty acid concentrations (lipid w/o AA: +36 ± 18 vs. lipid with AA: +41 ± 13 vs. μmol/L, P=0.84). AA infusion significantly increased plasma ascorbic acid concentrations (lipid w/o AA: -1 ± 7 vs. lipid with AA: +26 ± 11 μmol/L, P=0.04). A significant increase in retinal arteriole resistance was observed following lipid infusion (lipid w/o AA: +20 ± 8 %, vs. lipid with AA: +17 ± 8 %, P=0.40). In accordance, lipid infusion significantly reduced retinal arteriole lumen diameter; however, co-infusion of AA reversed the lipid-mediated decrease in retinal arteriole diameter (lipid w/o AA: -3 ± 1 % vs. lipid with AA: +3 ± 2 %, P=0.01). Conclusions: Although microvascular resistance was increased, co-infusion of the antioxidant (ascorbic acid) reversed the fatty acid-mediated reduction in arteriole lumen diameter. Therefore, these preliminary findings suggest that acute elevations in plasma fatty acids induce microvascular constriction via an oxidative stress pathway. Funding and support: R01HL159370-01 (S.W.H.). This work was also supported by a CTSA grant from NCATS awarded to the University of Kansas for Frontiers: University of Kansas Clinical and Translational Science Institute (# UL1TR002366). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or CTSA. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Addressing underrepresentation in physiology research through internship opportunities
Authors: Barnett Vincent , Wu Steven , Metzger Joseph , Anderson Lisa 
Published: May 2023

A challenge in the undergraduate physiology landscape is that some students who are underrepresented in the biomedical sciences are not aware of or are unable to take advantage of laboratory research opportunities. This is unfortunate because lab research can provide students with unique skill sets that are beneficial for future success, whether the students remain in research or move on to other careers. These skills include opportunities for critical thinking, improvement of oral and written communication skills, development of teamwork and leadership skills, learning about ethics in biomedical decision making and enhancement of digital literacy among others. As a program that sponsors an undergraduate Human Physiology major that has been successful in attracting underrepresented students (>40% students of color and >60% female) for a major Land-grant university, we challenged ourselves to consider how we might help our students make the most of their physiological interests and potentially improve the demographics of representation in our discipline. Starting in the summer of 2020, a group of faculty began a series of meetings to define an undergraduate program that would attract underrepresented students to lab-based internships, minimize the need for outside work by providing stipends and nurture their academic progress through informal student-faculty interactions. Though delayed by the Covid-19 pandemic, this framework has been used to initiate two new outreach programs. In the summer of 2021, we used this framework to initiate an American Heart Association sponsored research internship opportunity for 3rd and 4th year students. This program which we have named UPRIME is the focus of another abstract at this meeting. The INPUT (INtegrative biology and Physiology Undergraduate Training) program was started in fall of 2022. The program is internally supported and targets 1st and 2nd year undergraduates who represent populations that have been underrepresented in biomedical sciences. These students will be provided laboratory research experiences coupled with opportunities for educational support. A stipend of $3000 per student per semester is offered with the prospect of renewal dependent on a post-semester review. A cohort of six students were selected from a campus wide solicitation for applications into the inaugural INPUT class. These students will begin their projects in January 2023. We look forward to contributing to the scientific growth and development of these students. Perceptions of lab-based research and academic progress will be tracked along with career aspirations as the program progresses. Department of Integrative Biology and Physiology, University of Minnesota Medical School This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
In vitro differences analysis in proliferation and drug sensitivity of tumor-associated fibroblasts from different regions of FDG metabolism to non-small-cell lung carcinoma
Authors: Hu Yiyi , Jian Shaojie , Yang Weihua , Wu Zhifang 
Published: May 2023

Objective: 18F-FDG PET can directly reflect the glucose metabolism level of cells from the molecular level. Tumor-associated fibroblasts, as the natural physiological barrier of tumors, support and protect the survival of non-small cell lung cancer cells. This study will further observe the differences in the supporting effects of CAFs from different regions of 18F-FDG PET metabolism on cancer cells. Methods: Biopsy tissues were collected from PET/CT patients diagnosed with NSCLC for the first time in the Department of Nuclear Medicine, The First Hospital of Shanxi Medical University. The locations of puncture were all selected in areas with high metabolism of tumor. Primary CAFs were cultured by tissue adhesion method. A549 acts as EGFR (-) tumor cells, while PC9 acts as EGFR (+) tumor cells. CAFs conditional medium was collected to induce the culture of A549 and PC9 cells, labeled as A549high/low and PC9high/low, respectively. CCK was used to measure cancer cell proliferation rate, Transwell was used to measure cancer cell invasiveness, and scratch assay was used to measure cancer cell migration. The cells were treated with cisplatin and gefitinib respectively to observe the resistance of the cells. Results: Tissues of two NSCLC patients with SUVmax were 1.25 and 11.15, respectively. The conditioned medium induced cancer cells for 48 hours. CCK (48h) results showed that SUVhigh-derived CAFs could promote the proliferation of two types of cancer cells more than SUVlow-derived CAFs. The wound healing experiment showed that A549high had completed the healing at 72h, followed by low metabolism area, and A549 was the worst. The results for PC9 cells were similar to those for A549. Transwell experiment showed that PC9high/ low showed obvious difference in invasiveness at 24 hours, and the difference was more significant at 48 hours. A549 also showed difference in invasiveness, but the difference was relatively weak. When the corresponding cells were further treated with cisplatin or gefitinib, the proliferation rate of A549high/low cells was significantly different in the gradient range of high cisplatin concentration, while the proliferation rate of PC9high/low cells was significantly different in the low-medium gefitinib concentration. Conclusion: The regions of FDG metabolism difference shown in PET support the reverse warburg effect. As a physiological barrier to tumors, CAFs is one of the key factors that promote the occurrence, metastasis and drug resistance of lung cancer. National Natural Science Foundation of China (Grant number:81971655) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Alveolar macrophage-derived secretory autophagosomes exacerbate inflammation in lipopolysaccharide-induced acute respiratory distress syndrome
Authors: Xu Xinyi 
Published: May 2023

Background: Acute respiratory distress syndrome (ARDS) has a high incidence among patients in intensive care units. Extracellular vesicles and particles released from activated alveolar macrophages (AMs) contribute to ARDS-associated lung injury; however, the mechanisms underlying the inflammatory process remain unclear. Purpose: This study investigated the effects and the mechanisms through which AM-derived secretory autophagosomes (SAPs) contribute to ARDS-associated lung injury. Methods: SAPs were isolated from cell culture supernatants of AMs treated or untreated with lipopolysaccharide (LPS) and intratracheally injected to determine whether SAP exacerbated lung injury in mice with ARDS. The SAP proteome was analysed using mass spectrometry. Lung fibroblasts were treated with SAPs and collected for transcriptome sequencing. A transwell assay was conducted to study the chemotactic activity of fibroblasts induced by SAPs. Results: We found that AMs contributed to ARDS-associated lung injury by releasing a novel type of pro-inflammatory vesicles named SAPs, which were characterised as double-membraned vesicles approximately 200 nm in diameter and light-chain-3 expression. Proteomic analysis of SAPs and gene ontology (GO) enrichment analysis revealed that LPS-SAPs contain several differentially expressed proteins involved in effecting an inflammatory response, including interleukin (IL)-1β. We confirmed this result by quantifying IL-1β in SAPs using ELISA. Moreover, administering SAPs from LPS-stimulated macrophages to mice with ARDS exacerbated lung injury, whereas IL-1 receptor antagonist (IL-1RA) pre-treatment significantly ameliorated SAP-induced lung injury. In addition, we conducted transcriptome sequencing of lung fibroblasts treated with SAPs to explore the effect of SAPs on fibroblasts in ARDS, which demonstrated that the expression of several chemokines (CXCL2, CXCL15, and so forth) significantly increased with SAP stimulation. Furthermore, the transwell assay indicated that SAPs could enhance the chemotactic activity of fibroblasts, suggesting that SAPs may exacerbate inflammation in ARDS by promoting neutrophil or monocyte recruitment. Conclusion: This is the first study to show that AM-derived SAPs contribute significantly to ARDS by secreting pro-inflammatory cytokines and promoting inflammatory cell recruitment by activating fibroblasts, which may be beneficial for therapeutic development of ARDS. National Natural Science Foundation of China (Grant numbers 81870066, 81670074, 81930058, 82270083 and 81971888), Six Talent Peaks Project in Jiangsu Province(Grant numbers TD-SWYY-003), and Social Development Specifc Projects of Jiangsu Province [Grant number BE2020786]. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Dicarbonyl Stress Aggravates De Novo Fatty Acid Synthesis of Renal cells of Diabetes Mellitus via SREBP-1 /LDL-R Axis
Authors: Chen Eugene Chang-Yu 
Published: May 2023

Introduction & Objectives: In diabetic patients, the excess blood glucose is autooxidized to produce methylglyoxal (MG), eliciting dicarbonyl stress, alteration of cellular proteins. MG was reported to play the role in the pathogenesis of renal microvascular complications. The storage of lipid droplets in nonadipose tissues is called ectopic lipid accumulation, which would induce cellular dysfunction. Literature indicated that renal lipid accumulation is associated with diabetic nephrodamage. Sterol regulatory-element binding proteins (SREBPs) regulate lipid homeostasis and cellular metabolism by controlling the expression of genes required for the uptake and synthesis of fatty acid, cholesterol, triglycerides. Considering MG to be the precursor of advanced glycation end products, whether the elevated dicarbonyl stress in DM patients can lead to renal lipotoxicity is still unclear. The aim of this project is to investigate the mechanisms of MG induced renolipotoxicity. Hypothesis: MG dysregulates fatty acid homeostasis in renal tubular cells to elicit lipotoxic complications with DM. Materials & Methods: In vitro NRK52E renal tubular cells and in vivo high-fat-diet induced diabetic mice models were treated with MG to verify this hypothesis. The 3D live cell imaging and Nile red staining were used to confirm the lipid deposition in the renal cells. The signaling proteins related to MG-induced fatty acid homeostasis were investigated by Western blot and immunohistochemistry. The renal lipotoxicity was analyzed by flowcytometry in vitro and hematoxylin-eosin stain in vivo. All data were statistically analyzed by the one-way AVOVA and the significance of confidence level was p< 0.05. Results: In vitro, severe lipid droplet deposition was found in the MG-treated renal tubular cells as revealed by the 3D live cell imaging. MG activated the SREBP1, resulting in stimulated expression of key regulators of fatty acid synthesis and LDLR-mediated lipid uptake. In parallel, in vivo fatty kidney and associated pathological severity in tubular cells under MG treatment were also evidenced. Conclusions: Our studies have revealed the molecular mechanism of reno-lipotoxicity caused by dicarbonyl stress in DM. Suggestively, to target on such early dicarbonyl stress may become a useful future therapeutic strategy for clinical treatment of delaying diabetic kidney disease. This research received funding from the Ministry of Science and Technology, Taiwan. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
The role of type I interferon on trisomy 21 endothelial angiogenesis
Authors: Frauenpreis Andrew , Hoarau Antony , Bhattacharya Soumyaroop , Glass Ian , Deutsch Gail , Mariani Thomas , Al Alam Denise , Danopoulos Soula 
Published: May 2023

Rationale: Down syndrome (DS), resulting from Trisomy 21 (T21), is the most common chromosomal disorder worldwide. Cardiopulmonary complications are a leading cause of morbidity and mortality in DS. Pulmonary disorders include pulmonary hypertension and pulmonary capillaritis, which can result from a dysregulated lung endothelium. One of the major pathways consistently activated in DS is the type I interferon (IFN-I) pathway. High IFN-I inhibits VEGF induced development of capillary like structures, thus playing an anti-angiogenic role. Therefore, we aim to characterize the effects of IFN-I on T21 and euploid iPSC-derived endothelial cells (iPSC-ECs). Methods: Endothelial cell populations from single cell sequencing data of age matched T21 and Non-T21 prenatal lungs were carefully analyzed. Four iPSC lines were derived from age and sex matched T21 and non-T21 human fetal lung fibroblasts and used for endothelial cell differentiation using standardized kits and protocols from Stem Cell Technologies. FACs analysis confirmed endothelial cell purity and differentiation success: CD31+CD34+CD144+CD45-. For angiogenesis assays, endothelial cells were plated onto Cultrex in Ibidi angiogenesis 96-well plates with varying concentrations (0 to 104 pM) of IFNβ for 24 hours. Phase contrast images were taken with a 2.5X lens and analyzed in FIJI with the polygon shape tool to measure continuous mesh areas (CMA), defined here as a continuous endothelial cell layer undisrupted by branching structures. Results: Pathway analysis from our scRNAseq data demonstrated an upregulation of the IFN-I pathway across T21 endothelial clusters. T21 and non-T21 iPSC lines exhibited markers of pluripotency (OCT4, NANOG, SOX2, LIN28) and successfully generated pure populations of endothelial cells (~98% CD31+CD34+CD144+CD45-) by passage 2. Quantification demonstrated that at baseline T21 iPSC-ECs consistently had a significantly larger mean CMA than that of non-T21 iPSC-ECs (p< 0.01, n=4). High concentrations of IFN treatment (104 pM) resulted in an increased CMA in non-T21 cultures (p=0.14; n=4), trending towards baseline T21 cultures (p=0.28, n=4). Additionally, we observed a significant increase in the CMA of T21 cultures treated with 104 pM IFNβ (p=0.04, n=4). Conclusion: Our data suggest decreased angiogenesis in T21 iPSC-ECs may be caused by hyperactive IFN-I signaling. Further studies are needed to determine the mechanisms by which IFN-I regulates angiogenesis in T21 lungs. NIH/NHLBI/OD HL155104-01A1, NIH/NHLBI HL141856, NIH/NHLBI R21HL165411-01, NIH/NICHD 2R24HD000836-52 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Constitutive knock-in of MnSODK68R causes dilated cardiomyopathy and senescence in mice
Authors: Schell Joseph , Chocron E. Sandra , Wei Sung-Jen , Zhang Jun , Jiang Haiyan , Horikoshi Nobuo , Gius David 
Published: May 2023

The mitochondrial superoxide dismutase (SOD2 or MnSOD) is an essential enzyme for managing oxidative stress, particularly by removing the highly reactive superoxide generated during the normal functioning of the electron transport chain. The activity of MnSOD is regulated post-translationally by acetylation, specifically at lysine 68. The deacetylated form of MnSOD is catalytically active, and it has been shown that the deacetylation mimic, MnSODK68R in which lysine 68 has been replaced with arginine, has upregulated dismutase activity in MCF7 and T47D human breast cancer cells. Overexpression of MnSOD has been shown to increase lifespan and protect against oxidative stress in the aging heart. We investigated a MnSODK68R knock-in mouse with ubiquitous expression of the mutant enzyme and expected similar effects as the MnSOD overexpressing mice. However, we have found that MnSODK68R homozygous knock-in mice develop dilated cardiomyopathy and have significantly decreased ejection fraction as evidenced by echocardiography at a young age. These mice also exhibit lower blood pressure compared to wild-type mice. Strikingly, these mice exhibit higher body weight, with increased lean mass and food consumption. Mitochondria isolated from MnSODK68R knock-in mouse hearts showed higher respiratory capacity than WT counterparts. Biochemical analysis revealed increased lipid peroxidation, oxidized peroxiredoxin and senescence markers, possibly indicative of a premature aging phenotype. We conclude that MnSOD constitutive function upregulation may produce a sustained increase in hydrogen peroxide levels that could cause senescence and lead to dilated cardiomyopathy. This research was funded by NCI grant R01CA152601 and, R01CA214025, and the Cancer Prevention and Research Institute of Texas grant number RR20012. JS is supported by T32 AG 021890. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.