bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomised cross-over study of automated oxygen control for preterm infants receiving nasal high flow
Authors: Reynolds Peter R , Miller Thomas L , Volakis Leonithas I , Holland Nicky , Dungan George C , Roehr Charles Christoph , Ives Kevin 
Published: November 2018

ObjectiveTo evaluate a prototype automated controller (IntellO2) of the inspired fraction of oxygen (FiO2) in maintaining a target range of oxygen saturation (SpO2) in preterm babies receiving nasal high flow (HF) via the Vapotherm Precision Flow.DesignProspective two-centre order-randomised cross-over study.SettingNeonatal intensive care units.PatientsPreterm infants receiving HF with FiO2 ≥25%.InterventionAutomated versus manual control of FiO2 to maintain a target SpO2 range of 90%–95% (or 90%–100% if FiO2=21%).Main outcome measuresThe primary outcome measure was per cent of time spent within target SpO2 range. Secondary outcomes included the overall proportion and durations of SpO2 within specified hyperoxic and hypoxic ranges and the number of in-range episodes per hour.ResultsData were analysed from 30 preterm infants with median (IQR) gestation at birth of 26 (24–27) weeks, study age of 29 (18–53) days and study weight 1080 (959–1443) g. The target SpO2 range was achieved 80% of the time on automated (IntellO2) control (IQR 70%–87%) compared with 49% under manual control (IQR 40%–57%; p<0.0001). There were fewer episodes of SpO2 below 80% lasting at least 60 s under automated control (0 (IQR 0–1.25)) compared with manual control (5 (IQR 2.75–14)). There were no differences in the number of episodes per hour of SpO2 above 98% (4.5 (IQR 1.8–8.5) vs 5.5 (IQR 1.9–14); p=0.572) between the study arms.ConclusionsThe IntellO2 automated oxygen controller maintained patients in the target SpO2 range significantly better than manual adjustments in preterm babies receiving HF.Trial registration numberNCT02074774.
Inhibitory effects of growth differentiation factor 11 on autophagy deficiency-induced dedifferentiation of arterial smooth muscle cells
Authors: Yuan Xinxu , Bhat Owais M. , Lohner Hannah , Li Ningjun , Zhang Yang , Li Pin-Lan 
Published: November 2018

Growth differentiation factor (GDF)11 has been reported to reverse age-related cardiac hypertrophy in mice and cause youthful regeneration of cardiomyocytes. The present study attempted to test a hypothesis that GDF11 counteracts the pathologic dedifferentiation of mouse carotid arterial smooth muscle cells (CASMCs) due to deficient autophagy. By real-time RT-PCR and Western blot analysis, exogenously administrated GDF11 was found to promote CASMC differentiation with increased expression of various differentiation markers (α-smooth muscle actin, myogenin, myogenic differentiation, and myosin heavy chain) as well as decreased expression of dedifferentiation markers (vimentin and proliferating cell nuclear antigen). Upregulation of the GDF11 gene by trichostatin A (TSA) or CRISPR-cas9 activating plasmids also stimulated the differentiation of CASMCs. Either GDF11 or TSA treatment blocked 7-ketocholesterol-induced CASMC dedifferentiation and autophagosome accumulation as well as lysosome inhibitor bafilomycin-induced dedifferentiation and autophagosome accumulation. Moreover, in CASMCs from mice lacking the CD38 gene, an autophagy deficiency model in CASMCs, GDF11 also inhibited its phenotypic transition to dedifferentiation status. Correspondingly, TSA treatment was shown to decrease GDF11 expression and reverse CASMC dedifferentiation in the partial ligated carotid artery of mice. The inhibitory effects of TSA on dedifferentiation of CASMCs were accompanied by reduced autophagosome accumulation in the arterial wall, which was accompanied by attenuated neointima formation in partial ligated carotid arteries. We concluded that GDF11 promotes CASMC differentiation and prevents the phenotypic transition of these cells induced by autophagosome accumulation during different pathological stimulations, such as Western diet, lysosome function deficiency, and inflammation.NEW & NOTEWORTHY The present study demonstrates that growth differentiation factor (GDF)11 promotes autophagy and subsequent differentiation in carotid arterial smooth muscle cells. Upregulation of GDF11 counteracts dedifferentiation under different pathological conditions. These findings provide novel insights into the regulatory role of GDF11 in the counteracting of sclerotic arterial diseases and also suggest that activation or induction of GDF11 may be a new therapeutic strategy for the treatment or prevention of these diseases.
Downregulation of GATA6 in mTOR-inhibited human aortic endothelial cells: effects on TNF-α-induced VCAM-1 expression and monocytic cell adhesion
Authors: Fan Xing , Chen Xiaolin , Feng Qi , Peng Kai , Wu Qianqian , Passerini Anthony G. , Simon Scott I. , Sun ChongXiu 
Published: November 2018

Increased expression of vascular cell adhesion molecule 1 (VCAM-1) on the aortic endothelium is an early marker of atherogenesis, promoted in part by elevated levels of inflammatory cytokines such as TNF-α. Mammalian target of rapamycin (mTOR) is a ubiquitous signaling molecule that has been considered to contribute to diverse cellular processes through mTOR complex 1 (mTORC1) or complex 2 (mTORC2). This study aimed to elucidate the role of mTOR signaling in TNF-α-induced VCAM-1 expression by the arterial endothelium. Primary human aortic endothelial cells (HAECs) were treated with low-dose (0.1 ng/ml) TNF-α, and VCAM-1 expression was measured by real-time quantitative PCR, Western blot analysis, and flow cytometry. Inhibition of mTOR through siRNA-mediated depletion or treatment with chemical inhibitors rapamycin or torin 1 suppressed VCAM1 transcription, which translated to inhibition of VCAM-1 surface expression by HAECs and concomitant decreased adhesion of monocytes. A promoter luciferase assay and chromatin immunoprecipitation indicated that mTOR regulated VCAM1 transcription through a mechanism involving transcription factor GATA6. Activation of PKC-α and an increase in miR-200a-3p expression, caused by mTOR inhibition but not disruption of mTORC1 or mTORC2 singly or together, decreased TNF-α-induced GATA6 expression and its enrichment at the VCAM1 promoter. In conclusion, mTOR inhibition activates PKC-α independently of disruption of mTORC1 and/or mTORC2, which challenges the conventional wisdom regarding mTOR signaling. Moreover, mTOR signals through transcriptional and posttranscriptional mechanisms to elicit maximal cytokine-induced endothelial inflammation that precedes atherosclerosis. NEW & NOTEWORTHY Both mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and mTORC2 contribute to PKC-α activation in the human aortic endothelium. Inhibition of mTOR is not equivalent to disruption of mTORC1 and/or mTORC2 in affecting human aortic endothelial cell signaling. Specifically, inhibition of mTOR causes PKC-α activation and miR-200a-3p upregulation, which independently suppresses TNF-α-induced transcription factor GATA6 expression and subsequently inhibits VCAM-1 expression and monocytic cell adhesion onto the aortic endothelium.
Curcumin improves exercise performance of mice with coronary artery ligation-induced HFrEF: Nrf2 and antioxidant mechanisms in skeletal muscle
Authors: Wafi Ahmed M. , Hong Juan , Rudebush Tara L. , Yu Li , Hackfort Bryan , Wang Hanjun , Schultz Harold D. , Zucker Irving H. , Gao Lie 
Published: November 2018

A hallmark of chronic heart failure (HF) with low ejection fraction (HFrEF) is exercise intolerance. We hypothesized that reduced expression of nuclear factor E2-related factor 2 (Nrf2) in skeletal muscle contributes to impaired exercise performance. We further hypothesized that curcumin, a Nrf2 activator, would preserve or increase exercise capacity in HF. Experiments were carried out in mice with coronary artery ligation-induced HFrEF. Curcumin was deliveried by a subcutaneous osmotic minipump at a dose of 50 mg·kg−1·day−1 for 8 weeks. In vivo, in situ, and in vitro experiments were employed to evaluate exercise capacity, muscle function, and molecular mechanisms. We found that: 1) the maximal speed, running distance to exhaustion, and limb grip force were significantly lower in HFrEF mice compared with sham. Curcumin-treated HF mice displayed enhanced exercise performance compared with vehicle-treated HF mice; 2) both soleus (Sol) and extensor digitorum longus (EDL) muscles of HFrEF mice exhibited reduced force and rapid fatigue, which were ameliorated by curcumin; and 3) protein expression of Nrf2, hemeoxygenase-1, SOD2, myogenin, and MyoD were significantly lower, but total ubiquitinated proteins, MURF1, and atrogen-1 were higher in Sol and EDL of HFrEF compared with sham mice, whereas these alterations in Nrf2 signaling and antioxidant defenses in HFrEF were attenuated by curcumin, which had no effect on cardiac function per se in mice with severe HFrEF. These data suggest that impaired Nrf2 signaling intrinsic to skeletal muscle contributes to exercise intolerance in HFrEF. Skeletal muscle Nrf2 should be considered as a novel therapeutic target in severe HF. NEW & NOTEWORTHY These studies suggest that impaired nuclear factor E2-related factor 2 (Nrf2) signaling is a critical mechanism underlying the enhanced oxidative stress in skeletal muscle in heart failure with low ejection fraction (HFrEF). Curcumin prevents the decline in running performance in HFrEF mice by upregulating antioxidant defenses in skeletal muscle, likely mediated by activating Nrf2 signaling. These findings suggest a novel therapeutic target for the improvement of exercise capacity and quality of life in HFrEF patients.
Colocalization of distinct NMDA receptor subtypes at excitatory synapses in the entorhinal cortex
Authors: Beesley Stephen , Sullenberger Thomas , Pilli Jyotsna , Abbasi Saad , Gunjan Akash , Kumar Sanjay S. 
Published: November 2018

The subunit composition of N-methyl-d-aspartate receptors (NMDARs) at synaptic inputs onto a neuron can either vary or be uniform depending on the type of neuron and/or brain region. Excitatory pyramidal neurons in the frontal and somatosensory cortices (L5), for example, show pathway-specific differences in NMDAR subunit composition in contrast with the entorhinal cortex (L3), where we now show colocalization of NMDARs with distinct subunit compositions at individual synaptic inputs onto these neurons. Subunit composition was deduced electrophysiologically based on alterations of current-voltage relationship ( I–V) profiles, amplitudes, and decay kinetics of minimally evoked, pharmacologically isolated, NMDAR-mediated excitatory postsynaptic currents by known subunit-preferring antagonists. The I–Vs were outwardly rectifying in a majority of neurons assayed (~80%), indicating expression of GluN1/GluN2/GluN3-containing triheteromeric NMDARs ( t-NMDARs) and of the conventional type, reversing close to 0 mV with prominent regions of negative slope, in the rest of the neurons sampled (~20%), indicating expression of GluN1/GluN2-containing diheteromeric NMDARs ( d-NMDARs). Blocking t-NMDARs in neurons with outwardly rectifying I–Vs pharmacologically unmasked d-NMDARs, with all responses antagonized using D-AP5. Coimmunoprecipitation assays of membrane-bound protein complexes isolated from the medial entorhinal area using subunit-selective antibodies corroborated stoichiometry and together suggested the coexpression of t- and d-NMDARs at these synapses. Colocalization of functionally distinct NMDAR subtypes at individual synaptic inputs likely enhances the repertoire of pyramidal neurons for information processing and plasticity within the entorhinal cortex. NEW & NOTEWORTHY The subunit composition of a N-methyl-d-aspartate (NMDA) receptor, which dictates most aspects of its function, can vary between neurons in different brain regions and/or between synaptic inputs onto single neurons. Here we demonstrate colocalization of tri- and diheteromeric-NMDA receptors at the same/single synaptic input onto excitatory neurons in the entorhinal cortex. Synaptic colocalization of distinct NMDAR subtypes might endow entorhinal cortical neurons with the ability to encode distinct patterns of neuronal activity through single synapses.
Vigorous Physical Activity Is Associated with Lower Risk of Metastatic–Lethal Progression in Prostate Cancer and Hypomethylation in the CRACR2A Gene
Authors: Dai James Y. , Wang Bo , Wang Xiaoyu , Cheng Anqi , Kolb Suzanne , Stanford Janet L. , Wright Jonathan L. 
Published: November 2018

Abstract

Background:
There is preliminary evidence linking physical activity to better prostate cancer outcomes, though the molecular mechanisms underlying this association are not clear.

Methods:
In a Seattle-based cohort of patients diagnosed with clinically localized prostate cancer and prospective follow-up for outcomes (n = 1,354), we studied the association between self-reported vigorous physical activity and prostate cancer progression to a metastatic–lethal phenotype. A subset of patients had prostate cancer tissue samples available for investigating DNA methylation (Infinium HumanMethylation450 BeadChip array) and exercise (n = 524).

Results:
Patients who had vigorous physical activity at least once per week during the year before diagnosis (∼79% of the cohort) were significantly less likely to progress to metastatic–lethal prostate cancer compared with those who had vigorous physical activity less frequently (adjusted hazard ratio = 0.63; P = 0.029). Among the subset of men who had radical prostatectomy as primary treatment and tumor tissue available, a differentially methylated region (DMR) was identified (family-wise error rate = 0.03, hypomethylated in the weekly exercise group), with 9 methylation probes located in the promoter region of CRACR2A. This gene encodes a calcium binding protein involved in innate immune response. The methylation level of the nine CpGs was inversely correlated with CRACR2A gene expression (average correlation coefficient = –0.35).

Conclusions:
Vigorous physical activity before diagnosis is associated with epigenetic alterations of CRACR2A and prostate cancer metastatic–lethal progression.

Impact:
This analysis provides strong evidence for the association between vigorous physical activity and a less likelihood to develop metastatic–lethal progression, and a suggestive link between exercise and DNA methylation in the CRACRA2A gene.
Human Epidermal Growth Factor Receptor 2 in Non-Muscle Invasive Bladder Cancer: Issues in Assessment Methods and Its Role as Prognostic/Predictive Marker and Putative Therapeutic Target: A Comprehensive Review
Authors: Sanguedolce Francesca , Russo Davide , Mancini Vito , Selvaggio Oscar , Calò Beppe , Carrieri Giuseppe , Cormio Luigi 
Published: November 2018

Although human epidermal growth factor receptor 2 (HER2) plays a prognostic and predictive role in breast and gastric cancer, its function in bladder cancer (BC) is still controversial. A comprehensive review of the literature has been carried out. An electronic search of databases from PubMed, Scopus, Google Scholar was implemented. The search terms were: “BC,” “bladder carcinoma,” “bladder neoplasm,” “human epidermal growth factor 2,” “HER2,” “HER-2,” “c-erbB-2,” “c-erbB2,” “erbB-2,” “erbB2,” “neu,” “marker,” “biomarker,” and “prognosis”. Results of the review consented to (a) summarize the available data on HER2 a predictor of recurrence and/or progression free survival on univariate and multivariate analysis, (b) explore the related issues in assessing HER2 status on these tumor samples, since they may severely impair its predictive function, and (c) report the state-of-the art of HER2 as a putative therapeutic target in BC and especially non-muscle invasive BC. HER2 stands out for being a prognostic factor as well as a therapeutic target in various cancers. Data from the literature concerning its use in BC provide conflicting results, probably due to the inherent complexity of BC biology. Efforts should be made to establish a suitable tumor-specific scoring system, and to assess single drugs’ efficacy in well-designed clinical trials.
The Association of Longitudinal Serum Uric Acid and All-Cause Mortality in Incident Peritoneal Dialysis Patients
Authors: Chang Wenxiu , Zhang Wenyu , Wang Xichao , Liu Ying , Han Yingying , Tu Yangke , Uchida Shunya 
Published: November 2018

<b><i>Background:</i></b> Time-averaged uric acid (TA-UA) value was calculated to investigate the association of longitudinal UA and all-cause mortality in incident peritoneal dialysis (PD) patients. <b><i>Methods:</i></b> Three hundred PD patients were divided into 3 groups based on the serum TA-UA level (Group 1: &#x3c; 6 mg/dL; Group 2: 6–8 mg/dL; Group 3: ≥8 mg/dL). Hazards ratio (HR) of all-cause mortality was calculated. Logistic regression was conducted to identify the associated clinical factors of lower and higher TA-UA level. <b><i>Results:</i></b> Increased HRs for death existed in Group 1 and Group 3 compared with Group 2 (HR 3.24, 95% CI 1.25–8.39, <i>p</i> = 0.016; HR 4.69, 95% CI 1.24–17.72, <i>p</i> = 0.023). Lower residual renal function, lower albumin, and higher high-density lipoprotein cholesterol were related to the lower serum TA-UA. Higher body mass index and higher C-reactive protein were associated with higher serum TA-UA in PD patients. <b><i>Conclusion:</i></b> Both TA-UA &#x3c; 6 and ≥8 mg/dL increased the all-cause mortality in incident PD patients.
A Unified Model Spectrum for Anisotropic Stratified and Isotropic Turbulence in the Ocean and Atmosphere
Authors: Kunze Eric 
Published: November 2018

AbstractIn the decade or so below the Ozmidov wavenumber (N3/ε)1/2, that is, on scales between those attributed to internal gravity waves and isotropic turbulence, ocean and atmosphere measurements consistently find k1/3 horizontal wavenumber spectra for horizontal shear uh and horizontal temperature gradient Th and m−1 vertical wavenumber spectra for vertical shear uz and strain ξz. Dimensional scaling is used to construct model spectra below as well as above the Ozmidov wavenumber that reproduces observed spectral slopes and levels in these two bands in both vertical and horizontal wavenumber. Aspect ratios become increasingly anisotropic below the Ozmidov wavenumber until reaching ~O(f/N), where horizontal shear uh ~ f. The forward energy cascade below the Ozmidov wavenumber found in observations and numerical simulations suggests that anisotropic and isotropic turbulence are manifestations of the same nonlinear downscale energy cascade to dissipation, and that this turbulent cascade originates from anisotropic instability of finescale internal waves at horizontal wavenumbers far below the Ozmidov wavenumber. Isotropic turbulence emerges as the cascade proceeds through the Ozmidov wavenumber where shears become strong enough to overcome stratification. This contrasts with the present paradigm that geophysical isotropic turbulence arises directly from breaking internal waves. This new interpretation of the observations calls for new approaches to understand anisotropic generation of geophysical turbulence patches.
A specific immunoassay for detection of feline kidney injury molecule 1
Authors: Bland S Karlyn , Clark Mary Ellen , Côté Olivier , Bienzle Dorothee 
Published: November 2018

Objectives The aim of this study was to design and carry out a preliminary evaluation of a urine point-of-care test for kidney injury molecule 1 (KIM-1) in healthy and diseased cats. Methods Part of the feline KIM-1 gene was amplified, ligated into a plasmid with a signal peptide and monomeric human IgGFc, and transfected into a mammalian cell line. Supernatant was purified and tested for the fusion protein by gel electrophoresis and Western blot. Mice were immunized three times with purified proteins, and hybridomas were generated from splenocytes. Antibodies were tested by ELISA for detection of recombinant KIM-1 and naturally occurring KIM-1 in disease-state urine. Next, a lateral flow assay (LFA) with capture and detection antibodies was constructed, and tested with 34 urine samples from healthy and diseased cats. Antibodies were also tested for reactivity with formalin-fixed paraffin-embedded kidney tissue. Results Three antibodies were assessed. Antibodies detected between 0.4 and 60 ng/ml feline KIM-1 fusion protein in the LFA. Urine samples from healthy cats yielded faint bands in the LFA corresponding to optical density (OD) values of 4.8–8.8. Samples from cats with suspected or confirmed acute kidney injury (AKI) had OD values ranging from 1.6–20.5. Urine KIM-1 varied over multiple days in cats with sepsis or urethral obstruction despite normalizing serum creatinine concentration. In tissue sections, KIM-1 antibodies labeled tubular cells with morphological features of injury. Conclusions and relevance A practical patient-side assay for detection of KIM-1 in feline urine has been developed. Preliminary results show marked though transient increases in cats with sepsis and urethral obstruction-associated AKI, and expression in injured tubules. Although initial data indicating that the LFA is sensitive and specific for KIM-1 in cats with AKI are promising, values associated with different types of injury, urine collection, urine storage and specific gravity need to be investigated.
Shape shifters: Racialized and gendered crossings in Piccadilly (1929) and Shanghai Express (1932)
Authors: Li Yumin 
Published: November 2018

The Chinese American actress Anna May Wong (1905–1961) is today considered an ambivalent icon who, on the one hand, was the first Asian American film star to gain international recognition, and on the other hand, became a symbol of the hypersexualized Asian woman in film. In this article, I will analyse the crossing of racial and sexual boundaries in two of her films, Piccadilly (1929) and Shanghai Express (1932). The comparison of Piccadilly with Shanghai Express reveals the journey not only of transatlantic agents, like Anna May Wong, but also the simultaneous trajectory of sets of interrelated motifs, narratives, and aesthetic tropes. As discourses of gender and race converge into the figure of the transnational Asian American actress, Anna May Wong offers a key and privileged site to unpack and discuss them. The relationship between sexuality and race in these films has often been reduced to processes of exoticization. However, I will show that this relationship ought instead to be understood as interrelated through practices of appropriation, subversion, and cross-dressing. By applying the term ‘exotic’ to the analysis of Anna May Wong’s performances, I aim to foreground the entangled processes of sexualization and exoticization in order to reveal that the delineation of the ‘other’ is more ambivalent than clear. The films are particularly interesting in the context of ‘sexoticization’ because they do not construct a gendered and racialized ‘other’ that is clearly distinct to a western ‘us’. Modes of appropriation and masquerade complicate the representation of the ‘sexotic’, non-European ‘other’.