bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using digital innovation to support anatomy and surgical education during the pandemic
Authors: Jayanth Aiden , Stone Danya , Dhanda Jagtar , Smith Claire F 
Published: May 2022

The COVID‐19 pandemic has had a detrimental impact on healthcare education. With restricted access to traditional teaching aids such as the cadaver, educators had to adapt their teaching practise to minimise disruptions to students’ educational process. However, cadaveric dissection is highly regarded as a key component of anatomical and surgical education. This was particularly challenging when teaching was purely online due to pandemic restrictions. To accommodate the shift to online delivery only, the Anatomy Department at Brighton and Sussex Medical School (BSMS) adopted a variety of synchronous and asynchronous teaching methods. As part of this strategy, the department extended its provision of anatomy teaching by live streaming cadaver dissections to first year medical students (n=220). BSMS was the first UK medical school to use this innovative digital tool. A Virtual Reality in Medicine and Surgery (VRiMS) course was also developed to provide training to surgeons worldwide. This work explores the place of cadaver‐based education in a true blended learning provision.Cadaver dissections were live streamed from the dissection room using operating theatre lights and a 4K camera via Microsoft Teams. These sessions were also interactive in nature, allowing students to ask questions throughout the dissection. Student feedback was collected through module and end of year evaluations. The VRiMS course provided a platform to demonstrate surgical procedures on cadavers using live streaming with virtual reality or 360 cameras. Surgeons were able to choose multiple camera angle perspectives through virtual reality headsets. Course participation data was used to determine the useability of this novel method of teaching and training.Module evaluation showed that the overall quality of delivery for anatomy practical sessions was rated as good and very good by 86% of the cohort. Moreover, 93% of students found the material to be just right. In the end of year evaluation, students have indicated that live streamed dissection sessions were one of their favourite aspects and has had a positive impact on their time at BSMS. In total, 1354 participants from around the world have watched 923 hours of live broadcasted content across four VRiMS courses to date. The course has seen a 52% increase in participation rate since its launch.The evaluation findings suggest that a hybrid learning approach with the use of live streaming for anatomical education has had a positive outcome on student satisfaction. Furthermore, VRiMS course participation data indicates that virtual reality has a promising future in surgical training. Live streaming and virtual reality have proved successful in bringing the dissection room to medical students and surgical trainees during unprecedented circumstances. This approach has the potential to prevent the complete loss of interactive cadaver‐based education and a probable solution to cadaver scarcity.
Effect of di‐ethylhexyl phthalate (DEHP) on androgen related proteins in JEG‐3 placental cells
Authors: Kruger Laken , Prasad Bhagwat 
Published: May 2022

The placenta is a critical fetal endocrine organ that plays an important role in fetal development, xenobiotic detoxification, and sex steroid homeostasis. Although the importance of the placenta in endocrine homeostasis is known, the effect of endocrine disruptors, like phthalates, on placental endocrine function needs further exploration. A common phthalate that expectant mothers can be exposed to is di‐ethylhexyl phthalate (DEHP) which is used to make flexible plastics. We aim to determine the effect of DEHP on the androgen related proteome in JEG‐3 placental cell model.JEG‐3 cells were seeded in 6‐well plates at 100,000 cells per well and treated with 0 (vehicle control), 1, 10, and 100 mM DEHP for 72 hours. The cells were harvested, homogenized, and protein sample was digested using an optimized protocol. Global proteomics data were acquired using a Q‐Exactive HF Quadrupole‐Orbitrap mass spectrometer (Thermo Fisher Scientific, Waltham, MA). The data were processed with MaxQuant (version 1.6.8.0) using the Andromeda search engine to search the high‐resolution MS/MS spectra against the human proteome database curated from Uniprot. Label‐free quantification (LFQ) intensities of androgen related proteins were compared across control and treatment groups.Out of the total 2368‐ 2530 proteins detected, 2085 proteins were common in control and all treatment groups. The control group had 49 unique proteins and DEHP treatment showed 63, 42, and 119 unique proteins to 1, 10 and 100 mM, respectively. ABCG2 was uniquely identified in the higher DEHP treatment group. DEHP treatment elevated the levels of aromatase (CYP19A1) and aldo‐keto reductase 1B1 (AKR1B1) in a dose‐dependent manner with a 291% and 59% increase in the 100 mM treatment, respectively. Steryl‐sulfatase (STS), estradiol 17‐beta‐dehydrogenase 11, and aldehyde dehydrogenase 3A2levels were unaltered by the DEHP treatments.Determining how environmental endocrine disruptors, like DEHP, affects the placental endocrine pathways is vital to mitigating the toxicity. The elevation of aromatase with DEHP treatment may lead to estrogenic effects as CYP19A1 converts androstenedione and testosterone to estrogens, resulting in hormone imbalance which can cause adverse fetal outcomes both physically and neurodevelopmentally.
Metabolomic Kidney Input and Output Analyses in Salt‐Sensitive Hypertension
Authors: Hoffmann Brian R. , Shimada Satoshi , Greene Andrew S. , Liang Mingyu , Dash Ranjan , Cowley Allen 
Published: May 2022

RationaleSalt‐sensitive hypertension is globally widespread and associated with increased risk of cardiovascular eventsand kidney disease. Although excess dietary salt intake is a major cause of these damaging effects, many of the underlying mechanisms remain poorly defined. Specifically, it is not understood how the critical energy needs of the kidney are met in face of constantly changing environmental nutrients and how this affects metabolic homeostasis in the kidney.MethodsWe hypothesized that a high salt diet in normal salt‐insensitive Sprague Dawley rat would lead to alterations of renal tubular bioenergetics and substrate metabolism. To test this, metabolomic analysis of arterial plasma (input) and renal venous plasma (filtered output) obtained from unanesthetized instrumented rats was performed using tandem mass spectrometry for comparison on a Q‐Exactive Orbitrap mass spectrometer coupled to a dual‐channel Vanquish Ultra‐Performance Liquid Chromatography system. Plasma metabolites were extracted from 20 µL of plasma from SD rats consuming low salt (0.4% NaCl) or high salt (4% NaCl) for 7, 14, or 21 days. These samples were then analyzed with separation over a hydrophobic (C18) and hydrophilic (HILIC) column under both positive and negative polarity to maximize identification of metabolites identified. Varying amounts of quality control plasma sample pools were used to determine injection sample concentration to analyze for each sample and remaining pools were used for normalization of the runs over time.ResultsA total of 4,603 metabolite features were detected, with 1,205 being identified named compounds. After applying further stringency filters to these named metabolites, 350 were significantly different in response to the varying high salt diets (p <0.05; Benjamini‐Hochberg correction) in at least one of the group comparisons performed (versus low salt and artery versus vein). Differential metabolites include numerous lipids, amino acids, and bioenergetic compounds, among others. There appeared to be a shift in these differential compounds between 14 and 21 days of high salt diet, suggesting a potential metabolic shift between initial responses and prolonged high salt responses. Complementary studies are also underway to compare urine metabolite flux, outer medulla, and cortex in conjunction with the plasma analysis to produce a complete computational prediction model.ConclusionTogether, implementation of this methodology will provide key insights and be valuable in further predicting the emergent properties of complex metabolic interactions in the kidney of rats during the development of salt‐induced hypertension.
The Role of Endothelin Receptors on Sensory Nerve Mediated Dilation in Postmenopausal Women
Authors: Del Vecchio Angelica R. , Welti Laura M. , Kuczmarski Andrew V. , McGinty Shane J. , Wong Brett J. , Wenner Megan M. 
Published: May 2022

Rapid local heating of the skin elicits biphasic vasodilation. The initial peak in skin blood flow (SkBF) is mediated by sensory nerves (i.e., the axon reflex). Both endothelin (ETA and ETB) receptors are located on axon terminals on nociceptor fibers, and therefore may be involved in the sensory nerve mediated vasodilation. Although prior work shows a blunted axon reflex with aging, this has yet to be examined in women, and the role of ETA and ETB receptors in this initial sensory nerve‐mediated vasodilatory response remains unclear.PURPOSEWe tested the hypothesis that the initial peak is blunted in postmenopausal women (POST) compared to young women (YW), and that blockade of ETA and ETB receptors would improve sensory nerve‐mediated dilation in POST.METHODSWe retrospectively analyzed data in 25 healthy YW (27±10 yr) and 16 healthy POST (56±1 yr). Cutaneous vasodilation to local heating was measured using laser doppler flowmetry during microdialysis perfusions of lactated Ringer’s (control), ETA receptor blockade (BQ‐123, 500nM), and ETB receptor blockade (BQ‐788, 300nM). Cutaneous vascular conductance (CVC) was calculated as SkBF/MAP at baseline and during the initial peak of local heating (42°C); CVC were normalized to maximal vasodilation achieved by perfusion of sodium nitroprusside (28mM) and heating to 43°C.RESULTSAll women were normotensive (MAP: YW 83±8 mmHg; POST 94±2 mmHg, p < 0.001) and not obese (YW 23±3 kg/m2; POST 24±1 kg/m2, p = 0.153). Sensory nerve‐mediated dilation at the control site was reduced in POST (YW 63 ±14 vs POST 49 ±17 %CVCmax, p=0.004). Blockade of ETA (YW 54 ±10 vs POST 55 ±9 %CVCmax, p=0.579) and ETB (YW 62 ±17 vs POST 59 ±13 %CVCmax, p=0.476) receptors did not impact the initial peak of local heating in either group.CONCLUSIONSThese preliminary data suggest the sensory nerve‐mediated vasodilation during local heating is attenuated with aging in women, but endothelin receptors do not contribute to this age‐related decrease. Additional research is needed to further understand the interactions between sex hormones and aging in regulating sensory nerve mediated vasodilation.
Cochlear Duct Abnormalities in Mice With Osteogenesis Imperfecta
Authors: Huston Lila A. , Menegaz Rachel , Handler Emma , Organ Jason , Gonzales Lauren 
Published: May 2022

Osteogenesis imperfecta (OI), a developmental disorder of type I collagen, is known to cause hearing loss in ~ 60% of the diseased population. Identified forms include conductive hearing loss (17.4% of OI patients), involving loss of function within the ossicular chain, and sensorineural hearing loss (25.8%), resulting from damage to the cochlea, with the most predominant form being mixed hearing loss (56.8%), involving damage to both the cochlea and ossicles. While OI‐related pathologies have largely focused on the middle ear, the pathological appearance of the cochlea (the organ most often compromised in OI‐related hearing loss) has gained little focus. In this study, we examine OI‐related pathologies on the cochlea in a mouse model for the severe type III OI, to document 1) any visible variation between WT and OI variants, and 2) assess the encroachment of the otic capsule onto the cochlea by analyzing differences in duct volumes. We hypothesize that cochlea in mice with OI will have less consistent morphology overall than their WT counterparts due to abnormal growth of the bony capsule.16 week old OIM mice (B6C3Fe a/a‐Col1a2oim/J) (n=6) were compared to unaffected wildtype (WT) littermates (n=6) with no known hearing defects. High‐resolution micro‐CT scans were created for all specimens and 3D models and volumes of the cochlea were generated using 3D Slicer software. Two‐tailed Mann‐Whitney U‐tests were used to investigate differences between 1) right and left ears of the same mouse to examine intraindividual symmetry and 2) differences in volumes between WT and OI cochlea.No major morphologic differences between OI and WT were observed, except for minor areas of higher ossification at the base of the cochlea, mostly within the OI sample. Within WT specimens, we observed little intraindividual difference in the cochlear volume (0‐3%). Within OI specimens, significant differences were observed in cochlear volume between right and left ears in the same animal (4‐15%; p<0.05), indicating potential unilateral effects. When average WT and OI volumes were compared, there was much overlap between the two samples although the OI volumes had a significantly larger range than the WT range (Mann‐Whitney U, p<0.05).Overall, our results indicate that mice with OI are much more likely to have evidence of unilateral cochlear volume losses, despite very little difference in overall shape appearance, possibly due to bony capsule encroachment. This find indicates an extremely high potential for sensorineural and mixed hearing loss in OI‐bred mice and elucidates at least one mechanism behind how this type of hearing loss might be occurring.Little is known about the pathological appearance of the cochlea in OI, leading to difficulty in managing hearing loss. Further investigation of the etiology and progression of cochlear pathologies will allow for better outcomes in hearing for those patients afflicted with OI‐related hearing loss.
Time‐dependent Characterization of Respiratory Parameters post Bleomycin‐induced Lung Injury
Authors: Karpuk Nikolay , Kamra Kajal , Lisco Steven J. , Zucker Irving H. , Wang Hanjun 
Published: May 2022

Background‐Acute lung injury (ALI) induces inflammation that disrupts the normal alveolar‐capillary endothelial barrier which impairs gas exchange to induces hypoxemia that reflexively increases respiration. Increased respiratory rate (RR) usually develops within a few hours to a few days after ALI. The bleomycin (Bleo)‐induced lung injury rat model has been one of the most widely used animal models to study the mechanisms of respiratory failure post ALI. However, systemic and time‐dependent characterization of respiratory parameters in this model has not been done. In the current study, we aimed to use the plethysmography (DSI system) to characterize the changes in variable respiratory parameters at different stages of lung injury in the bleomycin‐induced ALI rat model.Methods and Results‐ALI was induced in male SD rats (200‐250g) using a single intra‐tracheal injection of Bleo (day 0) and respiratory variables‐ Respiratory rate (RR), Tidal Volume (TV), Minute Ventilation (MV), enhanced pause (Penh), pause (PAU), ratio rate of achieving peak expiatory flow (Rpef), peak inspiratory flow (box) (PIFb), peak expiratory flow box (PEFb), inspiratory time (Ti), expiratory time (Te), expiratory flow at the point of 50%TV (EF50), end inspiratory pause (EIP), end expiratory pause (EEP), relaxation time (Tr) and time of brake (TB) were measured at room air for one hour weekly from W1 (acute phase of ALI) to W4 (recovery phase of ALI) using whole‐ body plethysmography (WBP). Our data showed that MV and RR were significantly elevated from baseline (W0) to W1‐W4 in Bleo‐treated rats whereas TV was decreased from baseline to W1‐W3 post Bleo (p≤0.01 compared to W0). Associated with increased RR, Ti, Te and Tr were significantly shorter at W1‐W4 post Bleo compared to baseline (W0). Penh and Rpef, measures of airway obstruction, were significantly increased at W2 and W1‐W4 post Bleo, respectively. PIFb and PEFb were significantly increased whereas EIP and EEP were significantly decreased in W1‐W4 post Bleo. EF50, a measurement of exhalation flow rate, was significantly increased at W1‐W4 post Bleo.Conclusions‐These data suggest that a single intratracheal instillation of Bleo induced long‐lasting changes in respiratory function from acute to recovery phase of lung injury. Although blood gas returned to the normal level at W4 post Bleo, many respiratory parameters remained abnormal, indicating that pulmonary function might require a longer time to recover in this model.
Role of Neuregulin 3‐ErbB4 Signaling in a Murine Model of Co‐Morbid Nicotine Dependence and Schizophrenia
Authors: Prantzalos Emily , Turner Jill 
Published: May 2022

According to the NIH, rates of nicotine dependence among patients with schizophrenia are at nearly 90%, compared to smoking rates of approximately 12% in the general population. Current research shows that variations in the gene for Neuregulin 3 (NRG3), a member of the EGF superfamily and the cognate ligand for ErbB4 receptors, are considered some of the strongest genetic links contributing to schizophrenia risk. Additionally, NRG3 protein and mRNA have been found to be highly enriched following chronic nicotine exposure and withdrawal. However, specific mechanisms underpinning NRG3’s association with both increased schizophrenia risk and increased nicotine withdrawal symptomology are unknown. In this ongoing experiment, we are testing the overall hypothesis that NRG3‐ErbB4 signaling effects on NMDA receptor function may provide a discrete, mechanistic link between nicotine dependence and schizophrenia.We plan to utilize a novel genetic mouse model of both nicotine dependence and schizophrenia in a multidimensional approach to study how NRG3 mediates nicotine withdrawal‐induced alterations on behavioral and molecular levels and how the alterations relate to schizophrenic‐like dysfunction. To first begin these investigations, we examined the behavioral and molecular baseline effects of nicotine and aripiprazole, a long‐acting atypical antipsychotic used to treat schizophrenia, in wildtype littermates. Animals treated chronically for nicotine and then undergoing spontaneous nicotine withdrawal were examined in the alternating Y‐maze, social interaction test, and open field test for efficacy in reducing behavioral endophenotypes common to both nicotine withdrawal and schizophrenia in our model. Following behavioral testing, PFC tissues were analyzed to determine mRNA and protein expression of factors in the NRG3 signaling pathway. Preliminary results show differential changes in mRNA expression associated with glutamatergic and serotonergic transmission in the mPFC, OFC, and hippocampus. Ongoing experiments will extend these studies to include time‐ and site‐specific genetic deletion of NRG3 in the PFC and compare these results to those derived in wildtype littermates. Our findings will provide insight into the underlying mechanisms linking the NRG3 signaling pathway and nicotine dependence, and may provide a novel link between nicotine use and its highly co‐morbid psychiatric disorder, schizophrenia. Findings from these highly translational studies may lead to novel therapeutic development for both nicotine dependence and schizophrenia.
Circulating human sPRR increased blood pressure in female mice fed a low‐fat diet
Authors: Nichols Kellea , Poupeau Audrey , Arthur Gertrude , Yiannikouris Frederique 
Published: May 2022

Essential hypertension and obesity‐hypertension have been associated with elevated plasma soluble prorenin receptor (sPRR) in men. Additionally, our laboratory previously found that the infusion of mouse sPRR elevates systolic blood pressure (SBP) in high‐fat (HF) fed male mice through activation of the sympathetic nervous system but did not elevate SBP in HF‐fed female mice. Interestingly, the infusion of mouse sPRR increased renal and hepatic angiotensinogen (AGT) and plasma renin concentration in female mice fed a standard diet. However, the mechanistic role of sPRR on the renin angiotensin system (RAS) to regulate blood pressure in lean female mice remains to be investigated. Moreover, there is critical gap concerning the functional role of human sPRR on blood pressure in women. Therefore, in the present study, we aim to determine whether human sPRR participates to blood pressure control in lean female mice.A transgenic mouse model expressing the human form of the soluble prorenin receptor (HsPRR‐Myc‐tag) was developed. Human sPRR‐transgenic female mice were bred with male mice expressing Alb/Cre recombinase to generate mice selectively expressing human sPRR (Alb‐HsPRR) in the liver and control littermates (CTL). Control and Alb‐HsPRR female mice were fed a LF‐diet for 8 months (n=11/groups). Body weight was assessed weekly and body composition was examined monthly. Blood pressure was assessed by radiotelemetry. Human sPRR‐Myc‐tag was detected in the liver of Alb‐HsPRR female mice and plasma sPRR levels increased by 50‐fold (CTL: 3.6±0.5 ng/ml, Alb‐HsPRR: 190.5±24.4 ng/ml; P<0.05), which validated the humanized mouse model.Elevated circulating human sPRR did not change body weight (CTL: 22.2±0.4g, Alb‐HsPRR: 23.0±0.3g) or fat mass (CTL: 2.5±0.2, Alb‐HsPRR:3.1±0.2g). Liver‐derived human sPRR significantly elevated SBP in Alb‐HsPRR compared to control female mice (Night SBP: CTL, 130.5±1.2 mmHg; Alb‐HsPRR, 135.9±2 mmHg; P<0.05) and acute injection of Angiotensin II exacerbated the SBP elevation. Interestingly, the decrease in blood pressure mediated by Losartan was not different between Alb‐HsPRR and control female mice (Night □SBP: CTL, ‐13.1±2.2 mmHg; Alb‐HsPRR, ‐14.8±2.7 mmHg; P>0.05). Plasma AGT and renin activity were similar between Alb‐HsPRR and control littermate female mice suggesting that the elevation of SBP was not mediated by the circulating renin angiotensin system. Therefore, whether the sympathetic nervous system is involved in human sPRR‐mediated increase of SBP remains to be examined. Altogether, these results support an important role of circulating human sPRR in blood pressure control in women.