bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Impact of JUUL Electronic Cigarette use on Cerebral Vascular Vasodilator Responsiveness
Authors: Campbell Jeremiah C. , Akins John D. , Dabroy Danny M. , Yesmin Farjana , Nelson Michael D. , Ben Taleb Ziyad , Brothers R. Matthew 
Published: May 2022

BackgroundCardiovascular disease is a major cause of death among cigarette smokers and is responsible for ~30% of heart disease related mortality in the U.S each year. Although cigarette smoking rates have declined in recent years, the use of electronic cigarettes (e‐cigarettes) continues to gain popularity in the U.S. and have generated widespread debate within the public health community, mostly due to the lack of scientific evidence regarding their safety and impact on health and behavior. The increasing rates of e‐cigarette use in the U.S have been largely attributed to the recent emergence of the high‐nicotine‐delivery pod‐based devices such as JUUL. Unlike e‐cigarettes, the literature surrounding the health impact of combustible cigarette smoking is well developed with overwhelming evidence of an adverse impact on various cardiovascular outcomes including impaired cerebral perfusion/vascular function. However, the impact of e‐cigarettes on cerebral vascular function remains to be elucidated, representing a major knowledge gap and research priority.HypothesisThis study tested the hypothesis that acute e‐cigarette vaping (JUUL) will impair cerebral vascular function as indexed by the cerebral vasodilatory responsiveness to a hypercapnic stimulus.MethodsA total of 16 adult smokers (mean age=25±5 yrs.) participated in this pilot study which occurred following an overnight fast. Cerebral vascular function was assessed as the hyperemic response to rebreathing‐induced hypercapnia before and ~45 min following a vaping session (10 puffs; 3s each, separated by 30s intervals). Heart rate (ECG), respiration (Pneumotrace), beat‐to‐beat blood pressure (Finometer), middle cerebral artery mean blood velocity (MCAv ‐ transcranial Doppler) and breath‐by‐breath end‐tidal carbon dioxide concentration (PETCO2‐ capnograph) were continuously measured. Cerebral vascular conductance index (CVCi) was calculated as MCAv / mean arterial pressure. Cerebral vasodilatory responsiveness was assessed as % increase in CVCi (%CVCi) during the highest common magnitude of hypercapnia achieved during the pre‐ and post‐vaping trials.ResultsAll CVCi data are reported at the highest common magnitude of hypercapnia achieved during the pre‐ and post‐vaping sessions (ΔPETCO2Pre: 13±2 mmHg, ΔPETCO2 Post: 12±2 mmHg; P=0.11). Cerebral vascular function/vasodilatory responsiveness, as assessed by the CVCi response to the hypercapnic challenge was significantly blunted following the vaping session (Pre: +52±25%, Post: +42±14%; P=0.04).ConclusionsOur preliminary results suggest that e‐cigarette vaping using JUUL acutely impairs cerebral vascular function as indexed by cerebral vasodilatory responsiveness to a hypercapnic challenge. These findings highlight the need for longitudinal studies to assess the long‐term impact of JUUL use on cerebral vascular function as well as other indices of cardiovascular health.
Elucidating the Bitter Taste Signaling Paradox in Airway Smooth Muscle Relaxation
Authors: Conaway Stanley , Huang Weiliang , Kane Maureen , Shapiro Paul , Deshpande Deepak A. 
Published: May 2022

RATIONALEAirway smooth muscle (ASM) hypersensitivity and hypercontractility play a pivotal role in the pathophysiology of obstructive airway diseases such as asthma. Furthermore, over half of affected individuals are unable to reliably control these disorders using the current standard of care, β‐(adrenergic) agonists. Previously, our group discovered the expression of a novel group of G protein‐coupled receptors (GPCRs), type 2 taste receptors (TAS2Rs), in the human airway which evoke ASM relaxation. Previous work in our lab suggests that TAS2R agonists evoke relaxation in a G protein beta‐gamma subunit‐, phospholipase C beta‐ and calcium‐dependent manner. We hypothesized that the downstream molecular targets of contractile‐related signaling components are differentially regulated by TAS2Rs compared to other GPCRs. The goal of this study was to establish the molecular mechanism by which TAS2Rs induce ASM relaxation.METHODSWe employed a phosphoproteomic approach, involving dual‐mass spectrometry, to determine differences in the phosphorylation status of contractile‐related proteins in ASM following the stimulation of TAS2Rs and other GPCRs. Healthy human ASM cells were treated with the TAS2R agonist chloroquine or β‐agonist isoproterenol alone or in combination with the bronchoconstrictive agonist histamine to study the ability of each relaxant compound to attenuate the histamine‐mediated phosphorylation profile of contractile‐related proteins. These phosphoproteomic profiles were compared and a select set of targets were validated using western blot analysis.RESULTSOur phosphoproteomic data demonstrated that histamine stimulation results in increased phosphorylation of Ras homolog family member A (RhoA) guanine nucleotide exchange factor (ARHGEF) 12 and A kinase anchoring proteins (AKAP) 2 and 12, as well as decreased phosphorylation of RhoA GTPase‐activating protein (ARHGAP) 6. Furthermore, chloroquine treatment attenuated histamine‐induced phosphorylation of ARHGEF12 but not AKAP2 or AKAP12. Interestingly, isoproterenol attenuated histamine‐induced phosphorylation of AKAP2 and AKAP12 but not ARHGEF12. Validation studies using western blot analysis revealed chloroquine mediated inhibition of histamine‐induced RhoA activation and myosin phosphatase target subunit 1 (MYPT1) phosphorylation at the T853 residue, which was not observed with isoproterenol.CONCLUSIONOur findings were able to show that contractile‐related proteins are phosphorylated differentially by chloroquine and isoproterenol to elicit ASM relaxation. Furthermore, our studies strongly suggest the importance of RhoA and the T853 residue on MYPT1 as points of mechanistic divergence between TAS2R and other GPCR pathways. These findings provide further insight into the mechanism by which TAS2R signaling reduces airway contractility and its potential as a novel therapy for obstructive airway disease.
Maternal adiposity inversely associates with physical activity in 2‐year‐old girls
Authors: Diaz Eva C. , Williams David K. , Howie Erin K. , Borsheim Elisabet , Andres Aline 
Published: May 2022

BackgroundAnimal studies suggest that maternal obesity and high fat diet during pregnancy program physical activity (PA) patterns in the offspring. However, such nexus has not been established in humans. The purpose of this study was to evaluate the association of maternal adiposity measured early in pregnancy with offspring PA at age 2 years while taking into consideration confounding and modifying factors.MethodsWomen (n=152) were enrolled early in pregnancy (<10 weeks). At enrollment, maternal adiposity [air displacement plethysmography, fat mass index (FMI, kg/m2] was measured, and maternal dietary quality (Healthy Eating Index), age, race, and education level were assessed. Gestational weight gain was measured at the research facility. Offspring birthweight and sex were self‐reported. At age 2 years, parental feeding practices (child feeding questionnaire) were assessed whereas anthropometrics (length and weight) and physical activity (ankle worn accelerometers) were objectively measured. Offspring body mass index z‐scores were calculated. Generalized linear regression analysis with a natural log link was done to model the association of maternal FMI and offspring PA. The interaction between maternal FMI and covariates (i.e., all variables listed above) was assessed. Our final model was created using principles of purposeful selection. The best subset of these terms was identified by observation of minimum model AIC statistic.ResultsThere was interaction between maternal FMI and offspring sex in association with offspring total PA [average activity counts (AC)/day] at 2 years of age. Specifically, PA decreased with increasing maternal FMI but only in girls (β=‐0.02, p=0.0470). In addition, total PA was higher in children born to women with college education compared to children born to women without college education (β=0.09, p=0.0369). Minutes spent in sedentary time increased (β= 0.01, p=0.0422) while minutes spent in light PA tended to decrease (β=‐0.01, p=0.0536) with increasing maternal FMI in girls compared to boys.ConclusionsThere is sexual dimorphism in the association of maternal adiposity measured early in pregnancy with offspring PA at age 2 years. PA levels in 2‐year‐old girls was negatively associated with increasing maternal adiposity.
A Consideration for Intersectional Framing Within Physiological Training
Authors: Cisneros Marissa , McNeely Andrew , Quick Christopher M. , Gatson Sarah 
Published: May 2022

ObjectivesPrevious scholars have identified the need to increase diversity in medical education in terms of diversifying the student base, cultural competency curricula, and increasing health equity (Awosogba et al 2015; Sharma 2019; Hordjik 2019; Muntinga et al 2016). Establishing an intersectional theoretical framework, and other feminist theoretical frameworks, within medical education has been put forth, however literature indicates there are many obstacles in optimizing this implementation (Sharma 2019). In line with Bentabos et al (2014), we argue that much can be gained from addressing health equity at the biomedical undergraduate level, as healthcare is an institution of workers beyond the medical field (e.g. clinical research). Further, we posit that, given AAMC data points (AAMC Diversity in Medicine: Facts and Figures 2019), addressing diversity at the medical education level addresses the problem too late. Finally, the traditional medical education environment likely does not provide space to adequately develop a critical framing of cultural competency (Moore 2007; Muntinga et al 2016). As such, the purpose is to demonstrate how intersectional framing embedded within the Health Disparities track of a Biomedical Research Certificate provides a multidimensional analytical tool able to equip health & care workers, including future medical students to: (1) Increase a diversity minded environment in medical education. (2) Apply reflective and reflexive tools to professional and graduate biomedical aimed curricula thus impacting the organizational discourse overall.MethodsThematic analysis applied to Intersectional Methodology to identify the interaction of curricula content and scaffolded collaborative learning through the Research‐Intensive Community (RIC) Model (Desai et al 2008). The major themes we seek to identify and reflect upon are the Guideposts of Intersectionality laid out by Collins and Bilge (2016). The research question we seek to answer is: how does intersectional curricula within the RIC model interact to create a reflexive lens that can identify and act on inequity at the micro, macro and meso level. Practical Implications:The framework provided here can supply a starting point of implementation that goes beyond an additive framework or simple gesture to intercategorization.
Effect of a single individualized precise constant power exercise on pulse wave in patients with new‐onset chronic disease
Authors: Tai Wenqi , Sun Xingguo 
Published: May 2022

ObjectiveTo observe the changes of pulse wave after exercise and to explore the effect of a single individualized precise constant power exercise on pulse wave in patients with new‐onset chronic disease.Methods13 patients with new‐onset chronic disease, 16 normal persons and 16 patients with long‐term chronic disease were selected, all subjects were tested for symptom‐limited maximal cardiopulmonary exercise test (CPET), and individualized exercise prescriptions were formulated based on Δ50% power. First, the 50s pulse wave data in the resting state was measured and recorded. The subjects exercised for 30 minutes according to the established exercise intensity, and then measured and recorded the pulse wave data at 10, 20, and 30 minutes after the exercise, next analyzed and compared the pulse wave changes between patients and normal people.Results10min after exercise in newly‐onset chronic patients, YPL (the amplitude of the trough of a pulse wave notch), ΔPL (the amplitude difference between the trough of a pulse wave notch and the starting point of a pulse wave), TPL (the time of trough of a pulse wave notch), TE (time at the end of the pulse wave), and TE‐TPL (the duration of a pulse wave notch) were all reduced, while ΔTP2′(TP2‐TPL, the duration of trough to peak of a pulse wave notch) and notched pulse wave ratio increased. In other words, the pulse wave notch was more obvious, and the duration of a single pulse wave was shortened. This trend was maintained at 20min and 30min after exercise, but the duration of a single pulse wave increased with time. After exercise, the occurrence rate and apparent degree of the pulse wave notch in new‐onset chronic disease patients are not as good as those of normal people, but they are better than those of long‐term chronic disease patients.ConclusionA single individualized precise constant power exercise makes the pulse wave of patients with new‐onset chronic disease tend to be normal, but it is still worse than that of normal people, which prompts us to further explore the impact of long‐term exercise strengthening control on the pulse wave of patients with new‐onset chronic disease.
Addressing Race, Ethnicity, and Structural Inequality in Pharmacology Education and Assessment
Authors: Blumer Joe B. , Szarek John L. , Lee Michael W. , Zaveri Naunihal T. , Schneid Stephen D. , Kruidering Marieke , Quesnelle Kelly M. 
Published: May 2022

OBJECTIVESocial determinants of health, including race, ethnicity, and gender, represent important factors in health care delivery and patient outcomes, and contribute to health disparities. Pharmacology, as an integrated discipline, lies at the nexus between foundational science and clinical practice, providing a platform for educators to discuss the impact of social determinants on patient outcomes. Our goal is to create a framework that provides guidance for topics in pharmacotherapeutics for educators, learners, and providers to use in promoting antiracism in medical curricula.METHODSThrough iterative discussions, we developed a conceptual framework that includes topics taught across medical schools, such as drug metabolism, pharmacogenomics, adverse drug reactions, prescribing guidelines, factors affecting medication adherence, pain management, and therapeutic outcomes. Under each topic, we describe how social constructs such as race, ethnicity, and gender can impact pharmacology and therapeutic outcomes.RESULTSLiterature reports show that some topics in pharmacology education have already established cultural competency and should be adopted widely by all pharmacology educators, e.g., using more appropriate terminology for drug reactions such as vancomycin‐infusion reaction. Other topics are less established, so a more nuanced discussion with students is required. Society guidelines for managing diseases such as hypertension include prescribing recommendations based on race, with which learners are expected to be familiar as they enter clinical training but are actively being debated. Similarly, inter‐ethnic differences in drug metabolism are often reported as a function of genetic polymorphisms without considering non‐genetic factors.CONCLUSIONSWe have developed a conceptual framework for promoting antiracism in pharmacology education by categorizing topics based on those where cultural competencies are clearly established and those where a more nuanced discussion is required with learners, as well as identifying and reducing bias in assessment. These are generalizable across health professions in which pharmacology education is a discipline in the curriculum.
Multi‐omics Sample Preparation Workflow for Proteins and DNA Using the Reversible Protein Tag ProMTag
Authors: Biedka Stephanie , Minden Jonathan S. , Lucas Amber 
Published: May 2022

Sample preparation is a crucial first step for both genomics and proteomics workflows. Removal of contaminants such as salts, detergents, and other biologics while maintaining high yields of the desired product is key to reproducible and informative results from these analyses. More and more frequently, these ‐omics technologies are being used in tandem to gain deeper insights into biological processes. However, multi‐omics sample preparation remains tedious and usually requires many steps in multiple different sample preparation workflows.In this study, we present a new multi‐omics workflow for the simultaneous preparation of DNA and protein samples from a single starting cell lysate. We accomplished this using the ProMTag reversible click chemistry technology that allows for reversible modification of the surface of proteins. Using ProMTag we were able to tag proteins in a cell lysate, bind them to ProMTag capture resin, and then precipitate nucleic acids so they also stay with the resin. With the nucleic acids and proteins bound to the resin, we were then able to wash away detergents, salts, and other contaminants. We then eluted the nucleic acids by resolubilizing in a nucleic acid elution buffer. We then were able to reverse the ProMTag by adding the protein elution buffer and eluted the sample in a mass spectrometry (MS) compatible buffer ready for proteomic analysis. Using this workflow we got yields >75% for protein and >90% for DNA. Gel electrophoresis showed a genomic DNA band free of degradation and the 260/280 absorption ratio indicated a pure DNA sample. Whole genome sequencing and MS proteomics analysis were performed and compared to traditional separate sample preparation workflows for DNA and proteins. This work establishes a new, high yield, reproducible workflow for the simultaneous preparation of DNA and proteins for genomics and proteomic analysis from a single starting sample.
Glutathione Regulates Endothelial Cell Function and VEGFR2 Signaling
Authors: Rashdan Nabil A. , Mackay Ryan P. , Delgadillo Luisa F. , Pattillo Christopher B. 
Published: May 2022

Under physiological and pathological conditions angiogenesis progresses in an idealized window of reactive oxygen species. Mice heterozygous for the Glutamate cysteine ligase modifier subunit knockout have augmented ischemic remodeling. During occlusion the ensuing ischemic milieu and accompanying vascular changes regulate the activity of vascular endothelial receptor 2 (VEGFR2). We hypothesized that cellular GSH concentration regulates endothelial cell function via altered VEGFR2 signaling.MethodsTo test this hypothesis, we first preformed mouse aortic endothelial cell (MAEC) outgrowth assays on aortic segments dissected from mice homozygous (KO) and heterozygous (Het) for GCLm knockout as well as wildtype controls (WT). VEGF stimulated chemotaxis was determined using the under‐agarose migration assay. Primary human aortic endothelial cells (HAEC) were purchased from Lonza and cultured following suppliers’ recomendations. Phospho‐Y1175 VEGFR2/total VEGFR2 and phospho‐Y416 proto‐oncogene c‐Src (Src)/total Src were determined by western blotting.ResultsOutgrowth area in the Het group was significantly larger than WT and KO at day 7 (2.15 fold, n=4, P<0.001). Het MAECs were 1.25 fold faster (n=4 p<0.001) while KO MAECs were 0.90 fold slower than WT (n=3, p<0.05) migrating towards VEGF‐A. Concurrently, we inhibited glutathione reductase in HAECs using 2‐acetylamino‐3‐[4‐(2‐acetylamino‐2‐carboxyethylsulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2‐AAPA). 2‐AAPA (75 µM) alone didn’t significantly activate VEGFR2. However, 2‐AAPA (75 µM) in combination with H2O2 (100 µM) induced a 5.5 fold (p<0.01, n=4) increase in the relative amount of active VEGFR2 compared to vehicle treated HAECs. 2‐AAPA both with and without H2O2 induced a significant increase in active Src, 5.3 and 9.0 fold (p<0.05, p<0.01, n=6) respectively. This effect was attenuated by the addition of Dithiothreitol (1mM). Furthermore, Src kinase inhibitor 1 (SKI) (200 nM) attenuated the effect of 2‐AAPA + H2O2 on VEGFR2. While the VEGFR2 kinase inhibitor SU1948 inhibited activation of VEGFR2, it had no significant effect on the 2‐AAPA + H2O2 mediated activation of Src. Glutathione S‐transferase P1 (GSTP1) catalyzes the enzymatic glutathionylation of proteins, The GSTP1 inhibitor TLK199 (50 µM) abrogated the effects of 2‐AAPA + H2O2 on VEGFR2.ConclusionCombined these data suggest Src mediates the 2‐AAPA + H2O2 activation of VEGFR2. And that glutathionylation is necessary for this effect, co‐immunoprecipitation experiments are underway to determine the glutathionylation status of Src in our system and its effect on the interaction of Src and VEGFR2.
A Closed Loop Feature Detection Platform for Automated Neonate Cardio‐Respiratory Measurements and Data Analysis
Authors: Ward Christopher S. , Aissi Eunice , Patel Dipak , Ruiz Brandon , Garcia Acosta Mariana , Ray Russell S. 
Published: May 2022

BackgroundSudden Infant Death Syndrome is thought to partly result from unseen brain abnormalities affecting cardio‐respiratory function, but for which no clear genetic or environmental mechanisms are known. Mouse genetic and exposure models present an opportunity to uncover molecular and environmental mechanisms. However, measuring cardio‐respiratory function in neonate mice is expensive, difficult, and inefficient. One major challenge is the time needed to carry out such measurements. The neonate autoresuscitation assay, consisting of repeated anoxic exposures followed by recovery, requires the full attention of an observer for the multi‐hour duration of a single‐subject assay, limiting throughput. To address this, we developed a closed‐loop feature detection platform for automated neonate cardio‐respiratory measurements.MethodsOur platform design consists of:1) a pneumotachograph face‐mask for precise respiratory measurements. 2) a micro‐controller automated bell‐housing gas switching system for rapid induction of respiratory challenges. 3) a micro‐computer‐based data‐acquisition system with real‐time feature detection and outputs for controlling gas exposure. 4) a data analysis suite that assists with study recordkeeping and provides a facile method to extract key outcome measures from acquired data.ResultsGas challenges are administered via the rotating bell housing system. A python program detects waveform features in real‐time, such as apnea and bradycardia. Upon apnea detection, the system switches to a rescue gas. Resumption of normal breathing and heart rate can also be detected and incorporated into criteria for automated initiation of the next anoxic exposure trial. Data is stored for later offline automated analysis using the data analysis suite.ConclusionsThe system offers a relatively inexpensive approach for automated high throughput neonate cardio‐respiratory assessment for facile screening to yield important clues in developmental pathophysiology.