bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient and bright phosphorescent organic light-emitting diodes adopting MoO3/PEDOT:PSS as dual hole injection layers
Authors: Zhang Nan , Chen Yang , Wang Yan-Hui 
Published: September 2019

It has been demonstrated that high efficiency and brightness can be achieved in phosphorescent organic light-emitting diodes (PHOLEDs) by using molybdenum oxide (MoO3)/poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS) as dual hole injection layers (HILs) on indium tin oxide (ITO) substrate. The dual HILs were simply fabricated by spin-coating PEDOT:PSS solution on a thin MoO3layer deposited by vacuum thermal evaporation. This work reveals that PEDOT:PSS coating on MoO3resulted in a smoother surface, simultaneously MoO3lamella prevented acid corrosion of PEDOT:PSS on ITO. Meanwhile, with the insertion of PEDOT:PSS and MoO3as HILs between anode and hole transporting layer (HTL), the energy barrier has been reduced and gave rise to effective hole injection. OLEDs with dual HILs resulted in the maximum current efficiency (CE) of 61.3 cd A[Formula: see text] and maximum luminance of 112200 cd cm[Formula: see text], which showed a superior performance compared to those devices with single HIL of PEDOT:PSS or MoO3. Our results proved the composition of PEDOT:PSS and MoO3as HILs were beneficial for high performance OLEDs.
HEMODYNAMIC INVESTIGATION OF SUBCLAVIAN-CORONARY STEAL SYNDROME IN DIALYSIS PATIENTS WITH CORONARY ARTERY OCCLUSION AND DIFFERENT STENOSIS PERCENTAGES IN SUBCLAVIAN ARTERY
Authors: RAHMANI SHAHROKH , EBRAHIMI BEHDAD SHAARBAF , HEIDARI ALIREZA , NAVIDBAKHSH MAHDI , ALIZADEH MANSOUR , TAFTI HOSSEIN AHMADI 
Published: September 2019

Purpose: Diseases of the coronary arteries represent critical cardiovascular bleakness and mortality around the world. The main focus of this study is to simulate hemodialysis patients undergoing Coronary Artery Bypass Graft (CABG) surgery by the left internal mammary artery. The survey is to investigate whether subclavian-coronary steal syndrome will occur in patients with stenosis in their left subclavian. Methods: A three-dimensional model of Brachial—Radial—Ulnar tree arterial system and dialysis graft are constructed and then simulated by the implementation of fluid–structure interaction (FSI) and non-FSI models. After consent was obtained, data attributed to dialysis patients who had undergone coronary bypass surgery at the Tehran Heart Center (THD) was collected. Results: Stenosis in the subclavian artery causes the left internal mammary artery (LIMA) graft to lack flow that, in CABG cases, is supplying the heart muscle. With the increase of stenosis from zero to 54%, the flow results show a negative flow indicating reversed flow in the artery. Meanwhile, the comparison between flow quantity of a normal Left Anterior Descending (LAD) and LIMA in case of 38% stenosis in subclavian shows that the amount of flow reaching the heart is less than standard. The threshold stenosis in the subclavian artery for which subclavian-coronary steal phenomena occurs is simulated to be around 54%. Furthermore, investigation of the effect of flow quantity in cases of hemodialysis versus nonhemodialysis shows that the flow is lessened in case of hemodialysis. Conclusions: In hemodialysis patients with more than 38% stenosis in left subclavian, it is well advised that LIMA bypass graft is not the preferred graft choice, and at 54% of subclavian stenosis, the steal phenomenon occurs.
Proteomics in gastroparesis: unique and overlapping protein signatures in diabetic and idiopathic gastroparesis
Authors: Grover Madhusudan , Dasari Surendra , Bernard Cheryl E. , Chikkamenahalli Lakshmikanth L. , Yates Katherine P. , Pasricha Pankaj J. , Sarosiek Irene , McCallum Richard , Koch Kenneth L. , Abell Thomas L. , Kuo Braden , Shulman Robert J. , Gibbons Simon J. , McKenzie Travis J. , Kellogg Todd A. , Kendrick Michael L. , Tonascia James , Hamilton Frank A. , Parkman Henry P. , Farrugia Gianrico 
Published: September 2019

Macrophage-based immune dysregulation plays a critical role in development of delayed gastric emptying in diabetic mice. Loss of anti-inflammatory macrophages and increased expression of genes associated with pro-inflammatory macrophages has been reported in full-thickness gastric biopsies from gastroparesis patients. We aimed to determine broader protein expression (proteomics) and protein-based signaling pathways in gastric biopsies of diabetic (DG) and idiopathic gastroparesis (IG) patients. Additionally, we determined correlations between protein expressions, gastric emptying, and symptoms. Full-thickness gastric antrum biopsies were obtained from nine DG patients, seven IG patients, and five nondiabetic controls. Aptamer-based SomaLogic tissue scan that quantitatively identifies 1,305 human proteins was used. Protein fold changes were computed, and differential expressions were calculated using Limma. Ingenuity pathway analysis and correlations were carried out. Multiple-testing corrected P < 0.05 was considered statistically significant. Seventy-three proteins were differentially expressed in DG, 132 proteins were differentially expressed in IG, and 40 proteins were common to DG and IG. In both DG and IG, “Role of Macrophages, Fibroblasts and Endothelial Cells” was the most statistically significant altered pathway [DG false discovery rate (FDR) = 7.9 × 10−9; IG FDR = 6.3 × 10−12]. In DG, properdin expression correlated with GCSI bloating ( r = −0.99, FDR = 0.02) and expressions of prostaglandin G/H synthase 2, protein kinase C-ζ type, and complement C2 correlated with 4 h gastric retention ( r = −0.97, FDR = 0.03 for all). No correlations were found between proteins and symptoms or gastric emptying in IG. Protein expression changes suggest a central role of macrophage-driven immune dysregulation in gastroparesis, specifically, complement activation in diabetic gastroparesis. NEW & NOTEWORTHY This study uses SOMAscan, a novel proteomics assay for determination of altered proteins and associated molecular pathways in human gastroparesis. Seventy-three proteins were changed in diabetic gastroparesis, 132 in idiopathic gastroparesis compared with controls. Forty proteins were common in both. Macrophage-based immune dysregulation pathway was most significantly affected in both diabetic and idiopathic gastroparesis. Proteins involved in the complement and prostaglandin synthesis pathway were associated with symptoms and gastric emptying delay in diabetic gastroparesis.
PD-1 and LAG-3 Dominate Checkpoint Receptor–Mediated T-cell Inhibition in Renal Cell Carcinoma
Authors: Zelba Henning , Bedke Jens , Hennenlotter Jörg , Mostböck Sven , Zettl Markus , Zichner Thomas , Chandran Anoop , Stenzl Arnulf , Rammensee Hans-Georg , Gouttefangeas Cécile 
Published: September 2019

Abstract
Drugs targeting the programmed cell death protein 1 (PD-1) pathway are approved as therapies for an increasing number of cancer entities, including renal cell carcinoma. Despite a significant increase in overall survival, most treated patients do not show durable clinical responses. A combination of checkpoint inhibitors could provide a promising improvement. The aim of the study was to determine the most promising checkpoint blockade combination for renal cell carcinoma patients. Tumor-infiltrating lymphocytes (TIL) and autologous peripheral blood mononuclear cells (PBMC) were isolated from patients undergoing surgery for primary tumors. Cells were stained for multicolor flow cytometry to determine the (co)expression of five inhibitory receptors (iR), PD-1, LAG-3, Tim-3, BTLA, and CTLA-4, on T-cell populations. The function of these TILs was assessed by intracellular cytokine staining after in vitro stimulation in the presence or absence of PD-1 ± LAG-3 or Tim-3–specific antibodies. Although the percentage of iR+ T cells was low in PBMCs, both CD4+ and CD8+ T cells showed increased frequencies of PD-1+, LAG-3+, and Tim-3+ cells on TILs. The most frequent iR combination was PD-1 and LAG-3 on both CD4+ and CD8+ TILs. Blockade of PD-1 resulted in significant LAG-3, but not Tim-3, upregulation. The dual blockade of PD-1 and LAG-3, but not PD-1 and Tim-3, led to increased IFNγ release upon in vitro stimulation. Together, these data suggest that dual blockade of PD-1 and LAG-3 is a promising checkpoint blockade combination for renal cell carcinoma.
Single-Cell Transcriptome Analysis Reveals Gene Signatures Associated with T-cell Persistence Following Adoptive Cell Therapy
Authors: Lu Yong-Chen , Jia Li , Zheng Zhili , Tran Eric , Robbins Paul F. , Rosenberg Steven A. 
Published: September 2019

Abstract
Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) can mediate responses in some patients with metastatic epithelial cancer. Identifying gene signatures associated with successful ACT might enable the development of improved therapeutic approaches. The persistence of transferred T cells in the peripheral blood is one indication of clinical effectiveness, but many T-cell and host factors may influence T-cell persistence. To limit these variables, we previously studied a patient with metastatic colorectal cancer treated with polyclonal TILs targeting the KRAS(G12D) hotspot mutation, who experienced a partial response for 9 months. Three dominant clonotypes specifically recognizing KRAS(G12D) epitopes were identified, but we found that only two clonotypes persisted 40 days after ACT. Because of these findings, in this study, we performed the single-cell transcriptome analysis of the infused TILs. The analysis revealed a total of 472 genes that were differentially expressed between clonotypes 9.1-NP and 9.2-P single cells, and 528 genes between 9.1-NP and 10-P. Following these clonotypes in the peripheral blood after ACT, the gene expression patterns changed, but IL7R, ITGB1, KLF2, and ZNF683 remained expressed in the persistent 9.2-P and 10-P cells, compared with the nonpersistent 9.1-NP cells. In addition, four autologous TILs, which were used for treatment but persisted poorly 1 month after ACT, did not express the gene profiles associated with persistence. These results suggest that certain TIL populations possess a unique gene expression profile that can lead to the persistence of T cells. Thus, this single-patient study provides insight into how to improve ACT for solid cancer.
Abstract 037: Monogenic Hypertension Associated With a Pathogenic STX16 Mutation
Authors: Wan Elizabeth , Sofat Reecha , Cross Jennifer , Walsh Stephen B 
Published: September 2019

Hypertension is the most important modifiable risk factor for death worldwide. Finding novel model mechanisms for blood-pressure (BP) regulation is an important goal and Mendelian syndromes have been very helpful in that regard.
Pseudohypoparathyroidism type 1B (PHP1B) is an example in which affected individuals are invariably hypertensive for unknown reasons.

We encountered a 48 year-old woman with severe, five-drug-resistant, hypertension. Her father and two aunts were also severely hypertensive. Her two young sons have developed drug-dependent hypertension before age 20 years. We measured 24-h ambulatory blood pressure and excluded all known secondary causes. However, the proband’s sons and their grandfather have the PHP1B phenotype, while our index patient and her two hypertensive aunts do not. The blood pressure phenotype in this pedigree suggested autosomal dominant inheritance. The Syntaxin 16 (STX16) gene encodes a snare protein and mutations cause PHP1B. Mutated STX16 causes methylation defects of Guanine Nucleotide Binding Protein, Alpha Stimulating (GNAS), a G protein regulator. Since GNAS is an imprinted gene, only inheritance from the mother causes the PHP1B phenotype. Subsequently, we sequenced
STX16
in our kindred. We found a heterozygous deletion involving exons 5 and 6. We were also able to show complete loss of methylation in
GNAS
exon 1A. All hypertensive persons in our kindred have the
STX16
mutation and are hypertensive. However, only those with maternal inheritance show the PHP1B phenotype. The methylation target region influenced by
STX16
encompasses 7 genes. Our candidate is endothelin-3 encoded by
EDN3
. Our data separate the hypertension-PHP1B phenotypes. We imply separate mechanisms are involved. We suggest new targets of blood pressure-raising relevance.
Abstract P3021: Trimethylamine but Not Trimethylamine N-Oxide Increases Blood Pressure in Rats, Affects Viability of Vascular Smooth Muscle Cells and Degrades Protein Structure
Authors: Konop Marek , Jaworska Kinga , Bielinska Klaudia , Bielak-Zmijewska Anna , Mosieniak Grazyna , Sikora Ewa , Pilz Marta , Derzsi Ladislav , Sozanski Krzysztof , Holyst Robert , Ufnal Marcin 
Published: September 2019

Increased plasma level of trimethylamine N-oxide (TMAO), a liver metabolite of gut bacteria-produced trimethylamine (TMA), has been suggested to increase cardiovascular risk. Mechanisms of TMAO increase in plasma and biological effects of TMAO are obscure. We evaluated the impact of heart failure (HF) on plasma levels of TMA and TMAO, and biological effects of the molecules.
Gut permeability was evaluated in male, 58-week-old Spontaneously Hypertensive Heart Failure (SHHF) and Wistar-Kyoto (WKY) rats. TMA and TMAO levels were assessed using LC-MS. Mean arterial blood pressure (MABP) was measured in anaesthetized, male, 16-week-old WKY treated intravenously with either 0.9% NaCl (vehicle), TMA or TMAO. The cytotoxicity of TMA and TMAO in human vascular smooth muscle cells (hVSMCs) was evaluated using MTT assay. The effect of TMA and TMAO on protein structure of bovine albumin was assessed by fluorescence correlation spectroscopy.
WKY showed no pathological changes in the circulatory system. SHHF showed HF with reduced ejection fraction. In comparison to WKY, SHHF had a significantly higher plasma level (μM) of TMA (99.05±6.40 vs 149.30±21.87) and TMAO (5.22±0.61 vs 6.69±0.67). SHHF had a significantly higher plasma-to-stool ratio of TMA, decreased intestinal blood flow and morphological alterations in the colon indicating the increased gut-to-blood penetration of TMA due to HF-induced leaky gut.
In WKY treatment with the vehicle and TMAO did not affect MABP. In contrast, TMA (at equimolar doses to TMAO) significantly increased MABP by 5-40 mmHg in a dose dependent manner. In vitro, TMA at a concentration of 500μM reduced hVSMCs viability. TMAO at a concentration of 100mM was not cytotoxic whereas TMA at the same concentration killed cells within 24h. Finally, the incubation of albumin with TMA but not with TMAO resulted in the degradation of the protein structure.
In conclusion, HF rats show increased plasma TMA and TMAO, which results from increased gut-to-blood penetration of TMA, a TMAO precursor. TMA but not TMAO affects hemodynamics in rats, reduces viability of cells and degrades protein structure. Therefore, TMA but not TMAO may exert deleterious effects on the circulatory system. Further clinical studies should evaluate not only TMAO but also TMA.
Central Nervous System Electrical Stimulation for Neuroprotection in Acute Cerebral Ischemia
Authors: Bahr Hosseini Mersedeh , Hou Jesse , Bikson Marom , Iacoboni Marco , Gornbein Jeffrey , Saver Jeffrey L. 
Published: September 2019

Background and Purpose—
Brain electrical stimulation, widely studied to facilitate recovery from stroke, has also been reported to confer direct neuroprotection in preclinical models of acute cerebral ischemia. Systematic review of controlled preclinical acute cerebral ischemia studies would aid in planning for initial human clinical trials.

Methods—
A systematic Medline search identified controlled, preclinical studies of central nervous system electrical stimulation in acute cerebral ischemia. Studies were categorized among 6 stimulation strategies. Three strategies applied different stimulation types to tissues within the ischemic zone (cathodal hemispheric stimulation [CHS], anodal hemispheric stimulation, and pulsed hemispheric stimulation), and 3 strategies applied deep brain stimulation to different neuronal targets remote from the ischemic zone (fastigial nucleus stimulation, subthalamic vasodilator area stimulation, and dorsal periaqueductal gray stimulation). Random-effects meta-analysis assessed electrical stimulation modification of final infarct volume. Study-level risk of bias and intervention-level readiness-for-translation were assessed using formal rating scales.

Results—

Systematic search identified 28 experiments in 21 studies, including a total of 350 animals, of electrical stimulation in preclinical acute cerebral ischemia. Overall, in animals undergoing electrical stimulation, final infarct volumes were reduced by 37% (95% CI, 34%–40%;
P
<0.001), compared with control. There was evidence of heterogeneity of efficacy among stimulation strategies (
I
2
=93.1%,
P
heterogeneity
<0.001). Among the within-ischemic zone stimulation strategies, only CHS significantly reduced the infarct volume (27 %; 95% CI, 22%–33%;
P
<0.001); among the remote-from ischemic zone approaches, all (fastigial nucleus stimulation, subthalamic vasodilator area stimulation, and dorsal periaqueductal gray stimulation) reduced infarct volumes by approximately half. On formal rating scales, CHS studies had the lowest risk of bias, and CHS had the highest overall quality of intervention-level evidence supporting readiness to proceed to clinical testing.

Conclusions—
Electrical stimulation reduces final infarct volume across preclinical studies. CHS shows the most robust evidence and is potentially appropriate for progression to early-stage human clinical trial testing as a promising neuroprotective intervention.
Generation Mechanism of Tropical Instability Waves in the Equatorial Pacific Ocean
Authors: Tanaka Yuki , Hibiya Toshiyuki 
Published: September 2019

AbstractTropical instability waves (TIWs) are prominent features in the equatorial Pacific, propagating westward at a speed of ~0.5 m s−1 with a wavelength of ~1000 km. In this study, we show that a linear stability analysis using a 1.5-layer shallow water model can predict successfully an unstable mode whose wavelength, phase speed, growth rate, and meridional structure are all consistent with those of the TIWs simulated by an eddy-resolving ocean general circulation model (OGCM). This unstable mode can be interpreted as resulting from the coupling of two Rossby waves, namely, one trapped just north of the equator (~1°–3.5°N) and the other trapped farther north (~3.5°–8°N). Although these two Rossby waves have opposite intrinsic phase propagation directions reflecting the negative and positive local meridional potential vorticity (PV) gradients, respectively, their actual propagation direction can be adjusted through the advection by the South Equatorial Current and the North Equatorial Countercurrent such that they might propagate westward at the same speed and with the same zonal wavenumber yielding the largest growth rate of TIWs. The unstable mode does not appear during the period in which the negative PV gradient is absent, which demonstrates its essential role in generating TIWs. Indeed, the seasonal and interannual variability of the TIWs simulated by the OGCM is shown to be significantly controlled by the strength of the negative PV gradient just north of the equator, suggesting that it could be a key parameter toward a dynamically based parameterization of the heat and momentum transfer associated with TIWs in coarse-resolution OGCMs.
Frequency of Persistent Blocking and Ridge Events Related to Precipitation over Eastern China during August and Its Preceding Atmospheric Signals
Authors: Zhang Bo , Liu Ge , Zhu Yuejian , Shi Ning 
Published: September 2019

Abstract
Based on a recently developed approach that can recognize both persistent blocking and ridge events effectively, the contributions of the frequency of these persistent events (FOPE) over different regions in Eurasia to precipitation over eastern China were investigated. The results reveal that, the FOPE over the longitudinal range of 110°–130°E, near the Stanovoy Mountains and the Okhotsk Sea, is significantly correlated with precipitation over the middle and lower reaches of the Yangtze River (MLRYR) during summer, particularly in August. The preceding full July (or 1–20 July) mean Balkhash Lake–Caucasus geopotential height index, which measures the combined effect of the Balkhash Lake and Caucasus geopotential height anomalies, is closely related to the August geopotential height anomaly around the Stanovoy Mountains and the Okhotsk Sea, and can therefore reflect the August 110°–130°E FOPE. The predictability based on this preceding atmospheric signal seems to be attributable to slow-varying atmospheric processes on a subseasonal (20-day mean) time scale. On this time scale, the Balkhash Lake and Caucasus geopotential height anomalies occur prior to, and seem to modulate, the geopotential height anomaly around the Stanovoy Mountains and the associated 110°–130°E FOPE through an eastward extension and through exciting a positive–negative–positive pattern in 500-hPa geopotential heights, respectively. As a result of the slow-varying atmospheric processes, this preceding atmospheric signal performs well in predicting the August 110°–130°E FOPE, which also facilitates the prediction of the MLRYR precipitation.
Effectiveness of spinal cord Injury Rehabilitation
Authors: Inman Clive 
Published: September 2019

As in other areas of rehabilitation, relatively small numbers and diversity –both of condition and of patients' goals – hinder the assimilation of robust evidence for the effectiveness of rehabilitation. Patients with spinal cord injury (SCI) tend to be gathered together in a small number of regional services, each with their own philosophy and each with different attitudes to outcome measurement, and thus collection of the existing trials for meta-analysis is problematic. The marked improvement in outcome from SCI that has occurred with the development of specialist rehabilitation programmes argues strongly for the effectiveness of rehabilitation, and we have progressed beyond the point where randomized controlled trials that deny a group such intervention could be considered ethical. Current research is aimed at teasing apart the aspects of different care models that are most effective, or the evidence for the usefulness of interventions for control of symptoms such as spasticity and pain. This evidence is reviewed and discussed.