bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decentering, Aortic Wave Reflection, and Arterial Stiffness
Authors: LewAllen Sarah E. , Vyas Aditi , Thivierge Grant S. , Morin Brigitte E. , Durocher John J. 
Published: April 2020

Decentering, a mindfulness‐related quality, involves an individual’s inherent ability to recognize thoughts as simply psychological stimuli and accept a distant perspective. This includes understanding that thoughts and emotions are transient, rather than permanent associations of the individual. Previous studies have concluded that improvements in anxiety following an MBSR protocol were related to an increased ability to decenter. However, it is currently unknown how the ability to decenter might influence wave reflection and arterial stiffness. Therefore, the purpose of this study was to determine if a higher ability to decenter would be associated with lower arterial stiffness. Twenty‐eight individuals (23±6 years) volunteered to participate in this study. All participants had a BMI less than 30 kg/m2, and reported no history of smoking, taking cardiovascular medication, or having diabetes. Subjects were instructed not to consume alcohol, caffeine, or exercise for 12 hours before, and to abstain from food three hours before testing. We performed applanation tonometry with a SphygmoCor system for pulse wave analysis (PWA) at the radial artery, and carotid‐femoral pulse wave velocity (cfPWV) at the respective arteries to estimate arterial stiffness. Participants also completed an 11‐item decentering questionnaire to objectify their ability to disconnect from their emotions. The Spielberger state‐trait anxiety inventory and the Five Facets of Mindfulness Questionnaire (FFMQ) were also completed. Data were analyzed using IBM SPSS statistical software for a median analysis on the ability to decenter, and for independent‐samples t‐tests. Means were considered significantly different when p<0.05. A higher ability to decenter was associated with a significantly lower aortic augmentation index (AIx, 8 ± 4 vs. −1 ± 3%, p<0.05), while cfPWV tended to be lower in those who scored higher on the decentering questionnaire (p=0.07). Our results in a small cross‐sectional sample indicate that the ability to decenter may be associated with lower cardiovascular risk factors such as AIx. Previous studies with very large sample sizes indicate that there is a moderate correlation between AIx and cardiovascular disease risk factors. Our preliminary results are promising in regard to how the ability to decenter may reduce cardiovascular risk.Support or Funding InformationThis project was partially supported by a National Heart, Lung, and Blood Institute award to John J. Durocher (1R15HL140596‐01).
Differential Expression of Inflammatory Response Genes During Acute High‐Altitude Exposure
Authors: Pham Kathy , Heinrich Erica C. 
Published: April 2020

Inflammatory signaling and hypoxia responses are linked via HIF and NF‐kB crosstalk. Upon high‐altitude exposure, the inflammatory profile adapts to the hypoxic environment. However, these evolutionarily conserved inflammatory responses to oxygen limitation likely contribute to pathologies such as Acute and Chronic Mountain Sickness, a progressive fatal disease characterized by excessive erythrocytosis. We hypothesize that pro‐inflammatory gene expression will increase upon acute high‐altitude exposure. We compared the inflammatory profiles in whole blood samples collected in the morning during fasting at sea level and after one night at high altitude (3800 m elevation) in 14 healthy sojourners (4 women, 10 men). Expression of 255 inflammation‐related genes was determined via the NanoString Inflammation panel. 15 genes showed significant differential expression at altitude. These include upregulation of LY96, TGFBR1, HSPB2, IL13, IL9, as well as multiple chemokines (p < 0.0003 for all). Additionally, HIF1A expression was significantly correlated with the expression of multiple genes including TLR4 (R = 0.66, p=0.0003), IL6R (R = 0.68, p=0.001), and IFNG (R = −0.71, p = 0.001). The upregulation of chemotactic proteins provides evidence that acute high‐altitude exposure induces pro‐inflammatory signaling. Furthermore, LY96 encodes MD2, a coreceptor with toll‐like receptor 4, which is upregulated in macrophages via HIF and involved in modulating the inflammatory response to lipopolysaccharide. Therefore, this data suggests that at high‐altitude, hypoxic stress may increase susceptibility to subsequent infection.Support or Funding InformationThis work was supported by the University of California, Riverside, School of Medicine.
Application of Machine Learning Techniques for Testing Sensitivity of Cardiac Dynamics to Arrhythmia Vulnerability Parameters
Authors: Aghasafari Parya , Yang Pei-Chi , Clancy Colleen 
Published: April 2020

In this study, we developed a new approach to address the importance of arrhythmia vulnerability parameters for cardiac dynamics prediction in response to autonomic stimulation. We generated various case studies using a series of complex electrophysiology protocols for control versus stimulated single cardiac myocytes by autonomic nervous system (ANS). We collected the “TRiAD” related parameters (triangulation (APD TRI), reverse use dependence (RUD), beat‐to‐beat (bTb) instability of action potential duration and spatial APD dispersion (T‐wave area)). We used collected data to train different machine learning algorithms for classifying control versus ANS case studies. We used artificial neural network (ANN), support vector machine (SVM) with Gaussian kernels and random forest (RF) algorithms and observed that RF outperformed the other two algorithms with higher model accuracy for output prediction. Our results illustrated that bTb instability, APD TRI, RUD and T‐wave area are respectively the most important parameters for our classification problem. We also studied the sensitivity of cardiac dynamics to the listed TRiAD parameters. We observed that increase in bTb instability values leads to higher probability of case study being classified into control group while increase in RUD and TRI values result into higher probability of case study being classified into ANS group. Whereas T‐wave area values illustrated different trend compared to three other parameters, where low values could be misleading in decision making about the group that the case study will belong to and higher T‐wave values mostly belong to ANS classified case studies. Therefore, our study suggests the advantages of data analytics techniques for discoveries that may not have been evident.Support or Funding InformationThis study was funded by National Institutes of Health (Grant OT2OD026580).
Visualizing Arc mRNA transfer using single molecule fluorescence assays
Authors: Little Saffron R. , Walter Nils G. 
Published: April 2020

The transfer of genetic material between cells has been implicated in both maintaining neuronal function as well as the proliferation of many diseases and disorders, especially neurodegenerative disorders. Regulation of mRNA transfer through transport and localization is conducted by RNA binding proteins (RBPs), making RBPs responsible for control of gene expression. The activity‐regulated cytoskeleton‐associated protein, Arc, is an important component of maintaining neuronal synaptic plasticity which ensures the proper flow of cognitive information. In Alzheimer’s disease, an increase of Arc protein expression and localization in synaptic activity areas has been observed in compensating for memory and cognition loss. Although Arc is thought to be released from the synaptic cleft through Arc‐formed capsids to transfer Arc mRNA into new target cells, the mechanism of action is unknown. This project uses single molecule fluorescence methods to interrogate the dynamics of Arc allowing for visualization of the potential movement of Arc capsids/Arc mRNA and the transfer of this genetic information in human cells. Preliminary studies of the Arc using single molecule fluorescence in situ hybridization (smFISH) and live cell imaging techniques has shown a static trajectory of Arc diffusion. Further studies of the transport and transfer of mRNA from Arc capsids will allow for an understanding how this machinery works that can be the basis for the development of new drug delivery methods for diseases with RNA targets.Support or Funding InformationNIH grant number: 1T32GM1320461
Spontaneous Splenic Rupture Case Report: an Approach to Anatomy Importance for Radiological Correlation
Authors: Esteban Roberto Javier Rueda , Pedraza-Rodriguez Juan Daniel , Ramirez Daniela Paola , Perdomo Felipe 
Published: April 2020

Spontaneous splenic rupture (SSR) is a rare entity
1, usually associated with hematologic malignancies, infectious processes or inflammatory diseases. Timely diagnosis by ultrasound and/or computed tomography
1 allows early clinical and/or surgical management
2, reducing the mortality
1.Our aim is to expose, through a clinical case of SSR, the importance of anatomy knowledge and its radiological correlation in medical education.A 26‐year‐old man, diagnosed with chronic myeloid leukemia (CML) without chemotherapy treatment, attends to the emergency department for 10/10 (VAS) colic pain in the right inferior abdominal quadrant, irradiated to the ipsilateral inguinal region, associated with non‐emetic nauseas, abdominal distention and dysuria. At presentation, heart rate was 80 beats/minute, respiratory rate 18 breaths/minute, blood pressure 123/71 mmHg, temperature 36.0 ° C and SatO2 87%.Initial workup positive findings were leukocytosis (270.000/mm3), low hemoglobin (11.2 g/dL) and hematocrit (33.3%), thrombocytosis (925.000 platelets), and Hypokalemia (2,96 mEq/L). Abdominal computed tomography showed hepato‐splenomegaly and a poorly defined lesion with irregular borders, infiltration and vascular tracts on the spleen inferior segment. Considerable accumulation of free liquid in the abdominal cavity was present.After 2 hours the patient reported an increase in pain, associated to abdominal guarding and rebound tenderness. Heart rate of 134 beats/minute, respiratory rate 30 breaths/minute, blood pressure 150/70 mmHg, SatO2 84% and metabolic acidosis (pH 7.0).Based on the suspicion of hypovolemic shock, an emergency xipho‐pubic laparotomy was performed, finding a 1500cc hemoperitoneum, active bleeding, clots and splenic segments. Complete splenectomy was selected obtaining a surgical specimen (spleen) of 2 Kg, 32 cm in cephalo‐caudal length, and a lower pole rupture. Patient’s postoperative evolution was satisfactory, specific treatment for CML was initiated and he was discharged 14 days after the surgical procedure.An early diagnosis is crucial for the reduction of morbidity and mortality in patients suffering a SSR. This is carried out through the proper interpretation of diagnostic images. This clinical approach requires a broad body anatomy knowledge, and the capacity to extrapolate it to a bidimensional representation. Several researchers confirm that the inclusion of diagnostic‐images in the anatomy curriculum leads to an early exposure of medical student to these tools, which improves their imaging interpretation and diagnostical skills
2. Finally, the implementation of these diagnostic tools in the anatomy program could lead to better medical practice and, as seen in this case, to a reduction on mortality.
Impact of Immune Function on Aerobic Capacity in Rats
Authors: Baumfalk Dryden R. , Colburn Trenton D. , Horn Andrew G. , Kunkel Olivia N. , Musch Timothy I. , Behnke Bradley J. 
Published: April 2020

BackgroundThe use of immunocompromised animals has been indispensable in cancer and immunology research. The use of exercise with these models in these areas of research has increased dramatically over the past decade, with little to no evidence of how immune modification of strains of animals is impacting exercise capacity and/or responses to training. This data is critical for extrapolation to exercise recommendations in humans as the majority of cancer patients do not present with primary immunodeficiency diseases. Recently, observations of lower skeletal muscle oxidative capacity between RNU (NIH Nude, immunocompromised) and Copenhagen rats (immunocompetent) have been speculated to result from possible differences between immune function in animals. The purpose of this study was to determine if there are differences in maximal aerobic capacity, through assessment of V̇o2max, between immune‐competent and ‐compromised animals of the same strain. We tested the hypothesis that immunocompromised animals would have a lower aerobic capacity than their immunocompetent counterparts.MethodsRNU 316 (NU−/−, T‐cell deficient; n=10) and RNU 118 (NU+/−, no deficiency; n=10) male rats (~4 months old) were obtained from Charles River. Both groups were acclimated to motorized treadmill running at varying speeds (20–40 m/min) for 3–5 sessions before beginning V̇o2max assessment. V̇o2max graded treadmill testing consisted of a 2‐minute warm‐up at 25 m/min at a 5% incline followed by 2 minutes at 35 m/min, and subsequent increases in speed of 5 m/min every minute after until a plateau was seen in oxygen consumption with increased speed, or test termination was required for safety of the animal. Tests were repeated a minimum of two times (3 maximally) per animal to verify maximum values were achieved.ResultsThere were no significant differences in body mass (NU−, 347±12 g, NU+, 321±8 g; p=0.17). V̇o2max was lower in NU− vs NU+ animals (80.0±1.5 vs. 88.4±1.9 ml·min−1·kg−1; p<0.01). There was a significant difference in respiratory exchange ratio (RER) at V̇o2max (NU−, 1.05±0.01 vs. NU+, 0.98±0.01; p<0.05), but no difference in CO2 production (NU−, 83.7±1.3 vs. NU+, 86.7±1.5 ml·min−1·kg−1; p>0.05).ConclusionThis study suggests that immunocompromised animals have a decreased aerobic capacity compared to immunocompetent counterparts. This should be considered when both designing exercise interventions in immunedeficient/compromised animals as well as interpretations derived from such studies.Support or Funding InformationNIH HL137156‐01A1ACS RSG‐14‐150‐01‐CCE
Regulation of neutrophil secretion by the lysosomal amino acid transporter, cystinosin
Authors: Carvalho-Gontijo Raquel D. , Johnson Jennifer L. , Catz Sergio D. 
Published: April 2020

Neutrophil exocytosis is an important immune response, but secretion must be tightly regulated because exacerbated release of the neutrophil toxic mediators is injurious to the host and mediates inflammation. Here we show that neutrophil exocytosis of azurophilic granules is regulated by the cystine lysosomal transporter cystinosin. Cystinosin localized at azurophilic granules and lysosomes in neutrophils. Isolated bone‐marrow‐derived Ctns−/− neutrophils showed exacerbated azurophilic granule secretion under unstimulated conditions, suggesting dysregulation of a cell‐intrinsic mechanism. The defect was specific for azurophilic granules because secretion of gelatinase granules was not affected. Using phalloidin staining, we show that Ctns−/− neutrophils have decreased F‐actin, suggesting disruption of the azurophilic granule‐specific actin barrier. In addition, phalloidin‐based staining showed increased filopodial protrusion formation in Ctns−/− neutrophils, thus affecting cell morphology. Induction of either actin polymerization or depolymerization by jasplakinolide (JK) or cytochalasin, respectively, followed by stimulation with the bacteria‐derived peptide, fMLF, showed that secretion was still significantly increased in Ctns−/− neutrophils, suggesting mechanistic defects beyond impaired actin remodeling. Using Total Internal Reflection Fluorescence Microscope (TIRFM) and Super‐Resolution Radial Fluctuations (SRRF), we show increased numbers of docked granules at the exocytic actin zone in Ctns−/− neutrophils. Immunofluorescence analysis showed increased colocalization of the small GTPase Rab27a with its effector JFC1 in Ctns−/− neutrophils, suggesting that Rab27a drives the increased exocytosis observed in Ctns−/− neutrophils. This was confirmed by treatment with the Rab27a‐JFC1 binding‐specific inhibitor Nexinhib20 (NEI20), which decreased granule docking and impaired secretion of the azurophilic granule marker myeloperoxidase (MPO) in unstimulated and stimulated Ctns−/− neutrophils. Combined treatment with NEI20 and JK further decreased MPO secretion in Ctns−/− neutrophils suggesting the uncoupling of Rab27a activation and actin depolymerization in Ctns−/− neutrophils. This was confirmed by the observation that the number of docking granules decreases in response to the combined treatment. Blocking ERM (Ezrin/Radixin/Moesin) also decreased the number of docked azurophilic granules at the exocytic active zone and impaired MPO secretion in Ctns−/− neutrophils, suggesting the participation of ERM on azurophilic granule exocytosis. In vivo, we found elevated levels of azurophilic granule cargo in plasma from cystinosin‐deficient mice, and Ctns−/− mice showed increased neutrophilic tissue infiltration, denoting systemic activation. Our data suggest that cystinosin is a negative regulator of exocytosis and that neutrophil‐mediated inflammation may play a significant role in disease progression in cystinosis.Support or Funding InformationCRFNIH
Innate Immunity in Cutaneous Lupus Erythematosus
Authors: Calderon Irene 
Published: April 2020

BackgroundCutaneous Lupus Erythematosus (CLE) is an autoimmune skin disorder. The adaptive immune system is involved in the etiology of CLE. CLE lesions respond to inhibition of endosomal toll like receptors, hence supporting other disease mechanisms in its pathogenesis.HypothesisGenes associated with defects in the innate immune system would be differentially expressed in CLE skin compared to normal controls.MethodUsing the Gene Expression Omnibus, gene expression data from skin biopsies of patients with cutaneous and normal controls were compared. Data sets selected included: GSE109248, GSE81071, GSE52417, and GSE95474, including acute lupus, subacute lupus, discoid lupus, and normal skin samples. GEO2R was used to analyze the gene expressions between the two sample groups for each data set. STRING (Search Tool for the Retrieval of Interacting Genes/Proteins), GeneCard, and KEGG (Kyoto Encyclopedia of Genes and Genomes Pathway) analysis were used to identify the interaction and function of specific genes.ResultsGenes associated with the NOD like receptor (NLR) signaling pathway were consistently differentially expressed in discoid lupus skin samples in all data sets (p‐value < 8.74e‐05). Five genes associated with the NLR signaling pathway were found to be upregulated in skin samples of discoid lupus patients in all datasets compared to normal controls. These included: STAT1 (signal transducer and activator of transcription 1), Oligoadenylate Synthetases (OAS1, OAS2, OAS3), and AIM2 (absent in melanoma 2). These five genes are known to be involved with transcription activation, regulation of viral infection, and interferon response.ConclusionGenes associated with the NLR signaling pathway are differentially expressed in the skin lesions of lupus patients, specifically discoid lupus, compared to normal controls, supporting the role of the innate immune system in its pathogenesis. Further validation studies using experimental methods such as polymerase chain reaction are needed.
Ethanol Extract of Euonymus alatus Leaf Prevents Scopolamine‐Induced Learning and Memory Impairment in Mice
Authors: Woo Yunju , Lim Ji sun , Oh Jisun , Kim Jong-Sang 
Published: April 2020

Our previous in vitro study demonstrated that the ethanol extract from young leaves of Euonymus alatus (so‐called burning bush spindle tree) had antioxidant and neuroprotective activities. In the present study, we examined whether oral supplementation of the extract recovers learning and memory capabilities in a scopolamine‐induced acute hypomnesic mouse model. Behavioral tests showed that spatial learning and memory were improved by the extract treatment in scopolamine‐treated mice. Histological damage observed in the hippocampal region of the scopolamine‐treated mouse brain was attenuated by oral administration of the extract. Oxidative stress markers, including plasma 8‐hydroxy‐2′‐deoxyguanosine and hepatic malondialdehyde increased in scopolamine‐injected mice were decreased by the extract treatment. The expression levels of antioxidant proteins such as heme oxygenase‐1 and nuclear factor (erythroid‐derived 2)‐like 2 in the hippocampal tissue homogenates were decreased in group treated with scopolamine alone while the expression of those proteins was restored by the extract treatment. In addition, synaptic plasticity biomarkers such as neurotrophic factors, including postsynaptic density protein‐95, brain‐derived neurotrophic factor and N‐methyl‐D‐aspartate receptor, were enhanced in the extract‐treated mouse hippocampal tissue compared to the group exposed to scopolamine alone. These findings indicate that Euonymus alatus leaf extract could rescue learning and memory impairment caused by oxidative stress‐dependent hippocampal damage through upregulated antioxidant response and strengthened synaptic function of neuronal circuits particularly in the hippocampus.Support or Funding InformationThis study was funded by the Forest Resources Development Institute of Gyeongsanbuk‐do, Andong, Republic of Korea.
A comparison of mitochondrial respiratory function in adult and fetal sheep pulmonary arteries.
Authors: Hanson Shawn F. L. , Murray Samuel T. , Wilson Sean M. , Blood Arlin B. 
Published: April 2020

Neonatal pulmonary hypertension (PH) occurs in approximately 6/1000 term infants. It results from insufficient vasodilation of the pulmonary arteries at birth, although the underlying etiology is not well understood. This increase in pulmonary arterial pressure can lead to severe systemic hypoxia due to redirection of blood flow away from the lungs via ductus arteriosus, resulting in systemic hypoxia. PH is more common in human fetuses exposed to chronic hypoxia during gestation, a phenomenon that is also demonstrated in our high‐altitude fetal sheep model.There is growing evidence that the mitochondria of pulmonary artery smooth muscle cells (PASMCs) play a key role in establishing vascular tone. Mitochondria are exposed to profound changes in oxygen and substrate availability in the transition from fetus to newborn. To gain a better understanding of the developmental changes in mitochondrial function in PASMCs, we tested the hypothesis that mitochondria from fetal vs adult PASMCs would display different substrate‐dependent rates of oxygen consumption and energy production.Lungs were surgically removed from adult non‐pregnant ewes or near‐term fetuses following greater than 100 days of residing at an altitude of over 3801 meters using protocols approved by the Loma Linda University IACUC. 4th–6th generation intrapulmonary pulmonary arteries were isolated, and denuded of endothelium. The metabolic activity of the arterial segments was analyzed in a Seahorse XFe 24 Analyzer that measures the oxygen consumption rate (OCR) with values being normalized to the arterial segment dry weight. These experiments were conducted in the presence of selective antagonists to enable determination of proton leak, non‐mitochondrial oxygen consumption, basal respiration, ATP‐linked respiration, maximal respiration, and spare capacity.Four adults and six fetuses were studied. Compared to adults, fetal PASMCs demonstrated a greater maximal respiratory capacity [813.99 +/− 73.20 (pmol/min) vs. 601.64 +/− 58.09 (pmol/min)] and spare‐capacity [593.28+/− 48.56 (pmol/min) vs. 353.74 +/− 40.39 (pmol/min)] for oxygen consumption while using carbohydrates and amino acids as substrates (p≤ 0.003, ANOVA). Other parameters of OCR were not different between fetuses and adults.These experiments provide initial evidence that there are maturational changes in mitochondrial function. Ongoing studies are evaluating the contribution of long‐term high altitude exposure to these differences in mitochondrial respiration and their importance to phenotypic and functional aberrations in lung function.Support or Funding Information(Supported in part by NIH grant HD083132 (ABB), HD098477 (SMW))