bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of thalidomide on Th17, Treg cells and TGF‐β1/Smad3 pathway in a mouse model of systemic sclerosis
Authors: Lu Yi , Zhao Cheng , Lei Ling , Tao Zhiqing , Zheng Leting , Wen Jing , Li Xi 
Published: December 2019

AbstractObjectiveTo evaluate the immune regulatory and anti‐fibrosis function of thalidomide (Thal) in systemic sclerosis (SSc), we investigated the effects of Thal on: (a) Th17 and Treg cell production; (b) related factors expression; and (c) transforming growth factor (TGF)‐β1/Smad3 pathway, using a mouse model of SSc.MethodsForty female BALB/c mice were randomly divided into a normal control (NC) group, SSc group (bleomycin [BLM]‐induced experimental SSc), BLM + Thal (10 mg/kg/day) group, BLM + Thal (20) group, and BLM + Thal (30) group. Thal was administered a day after BLM. At the end of the animal experiments, mouse tissues were collected for detection of pathological changes and hydroxyproline content. Flow cytometry, real‐time polymerase chain reaction, enzyme‐linked immunosorbent assay, immunohistochemistry, Western blot and other methods were used to measure Th17, Treg cell population and their related factors, as well as TGF‐β1/Smad3 pathway expression.ResultsThal treatment: (a) reduced skin, and pulmonary tissue fibrosis, inflammation score, and hydroxyproline content (P < .001) in BLM‐induced SSc mice; (b) reduced the percentages of Th17 cells and associated interleukin (IL)‐17A expression (both P < .05) but increased the percentages of Treg cells and its transcription factor Foxp3 expression (both P < .05); (c) correlation analysis found positive correlations between Th17/Treg ratio, the inflammatory score of the skin and pulmonary tissues, hydroxyproline content, and type I collagen messenger RNA expression (r = .8546, .8656, .6902, .6807, .8118, and .8424, respectively, P < .01); (d) Thal inhibited TGF‐β1 expression and Smad3 phosphorylation (both P < .05); (e) TGF‐β1 was positively correlated with the IL‐17A and Th17/Treg ratio (r = .5856, P = .005; r = .6684, P = .0107, respectively).ConclusionThal can effectively prevent skin and pulmonary tissue fibrosis in a mouse model of SSc through the TGF‐β1/Smad3 signaling pathway and can rectify the distortion of the Th17/Treg balance in SSc by potentially regulating Th17 and Treg cell production, as well as their related factors expression.
Downregulation of Rab17 promotes cell proliferation and invasion in non‐small cell lung cancer through STAT3/HIF‐1α/VEGF signaling
Authors: Wang Mingliang , Wang Wendong , Ding Jingmin , Wang Jiashun , Zhang Jun 
Published: December 2019

BackgroundRab GTPases play a key role in regulating intercellular vesicle trafficking in both exo‐ and endocytic pathways. Recent studies have reported that Rab small GTPases and the associated regulatory proteins and effectors are involved in many cancers. The purpose of this study was to investigate the biological role of Rab17 in non‐small cell lung cancer (NSCLC) and the relative mechanism.MethodsRab17 expression in human NSCLC cell lines and tissues was evaluated using real‐time PCR (RT‐PCR), western blot and immunohistochemical (IHC) staining. NSCLC cell lines with RAB17 stable knockdown were generated to explore its function in vitro and in vivo. Additionally, we investigated the potential mechanism of Rab17 by identifying the expression levels of STAT3/HIF‐1α/VEGF pathway using western blot analysis.ResultsDecreased Rab17 expression was correlated with poor overall survival in NSCLC patients. The functional assays showed that knockdown of Rab17 could promote tumorigenic properties of NSCLC cells in vitro and in vivo, including enhanced cell proliferation, colony formation, invasion and migration, angiogenesis and tumor xenograft growth, and suppressed apoptosis. Moreover, Rab17 downregulation decreased epithelial marker E‐cadherin and increased mesenchymal markers Vimentin and β‐catenin, suggesting knockdown of Rab17 induced epithelial‐mesenchymal transition (EMT).ConclusionDownregulation of Rab17 promotes cell invasion and enhances tumorigenicity in part through the STAT3/HIF‐1α/VEGF pathway, which may represent a novel potential therapeutic target.
Compromised steady‐state germinal center activity with age in nonhuman primates
Authors: Shankwitz Kimberly , Pallikkuth Suresh , Sirupangi Tirupataiah , Kirk Kvistad Daniel , Russel Kyle Blaine , Pahwa Rajendra , Gama Lucio , Koup Richard A. , Pan Li , Villinger Francois , Pahwa Savita , Petrovas Constantinos 
Published: December 2019

AbstractAge‐related reductions in vaccine‐induced B cells in aging indicate that germinal centers (GCs), the anatomical site where the development of humoral responses takes place, may lose efficacy with age. We have investigated the baseline follicular and GC composition in nonhuman primates (NHPs) with respect to their age. There was a marked reduction in follicular area in old animals. We found significantly lower normalized numbers of follicular PD1hi CD4 T (Tfh) and proliferating (Ki67hi) GC B cells with aging, a profile associated with significantly higher numbers of potential follicular suppressor FoxP3hiLag3hi CD4 T cells. Furthermore, a positive correlation was found between Tfh and follicular CD8 T cells (fCD8) only in young animals. Despite the increased levels of circulating preinflammatory factors in aging, young animals had higher numbers of monocytes and granulocytes in the follicles, a profile negatively associated with numbers of Tfh cells. Multiple regression analysis showed an altered association between GC B cells and other GC immune cell populations in old animals suggesting a differential mechanistic regulation of GC activity in aging. Our data demonstrate defective baseline GC composition in old NHPs and provide an immunological base for further understanding the adaptive humoral responses with respect to aging.
Chronic Voluntary Ethanol Drinking in Cynomolgus Macaques Elicits Gene Expression Changes in Prefrontal Cortical Area 46
Authors: Walter Nicole A. R. , Zheng Christina L. , Searles Robert P. , McWeeney Shannon K. , Grant Kathleen A. , Hitzemann Robert 
Published: December 2019

BackgroundGenome‐wide profiling to examine brain transcriptional features associated with excessive ethanol (EtOH) consumption has been applied to a variety of species including rodents, nonhuman primates (NHPs), and humans. However, these data were obtained from cross‐sectional samples which are particularly vulnerable to individual variation when obtained from small outbred populations typical of human and NHP studies. In the current study, a novel within‐subject design was used to examine the effects of voluntary EtOH consumption on prefrontal cortex (PFC) gene expression in a NHP model.MethodsTwo cohorts of cynomolgus macaques (n = 23) underwent a schedule‐induced polydipsia procedure to establish EtOH self‐administration followed by 6 months of daily open access to EtOH (4% w/v) and water. Individual daily EtOH intakes ranged from an average of 0.7 to 3.7 g/kg/d. Dorsal lateral PFC area 46 (A46) brain biopsies were collected in EtOH‐naïve and control monkeys; contralateral A46 biopsies were collected from the same monkeys following the 6 months of fluid consumption. Gene expression changes were assessed using RNA‐Seq paired analysis, which allowed for correction of individual baseline differences in gene expression.ResultsA total of 675 genes were significantly down‐regulated following EtOH consumption; these were functionally enriched for immune response, cell adhesion, plasma membrane, and extracellular matrix. A total of 567 genes that were up‐regulated following EtOH consumption were enriched in microRNA target sites and included target sites associated with Toll‐like receptor pathways. The differentially expressed genes were also significantly enriched in transcription factor binding sites.ConclusionsThe data presented here are the first to use a longitudinal biopsy strategy to examine how chronic EtOH consumption affects gene expression in the primate PFC. Prominent effects were seen in both cell adhesion and neuroimmune pathways; the latter contained both pro‐ and antiinflammatory genes. The data also indicate that changes in miRNAs and transcription factors may be important epigenetic regulators of EtOH consumption.
Sex Differences in the Expression of the α5 Subunit of the GABAA Receptor in Alcoholics with and without Cirrhosis of the Liver
Authors: Janeczek Paulina , Colson Natalie , Dodd Peter R. , Lewohl Joanne M. 
Published: December 2019

BackgroundAlcohol exposure alters the expression of a large number of genes, resulting in neuronal adaptions and neuronal loss, but the underlying mechanisms are largely unknown. miRNAs are gene repressors that are abundant in the brain. A recent study identified ~ 35 miRNAs that are up‐regulated in the prefrontal cortex of human alcoholics and predicted to target genes that are down‐regulated in the same region. Although interactions between alcohol‐responsive miRNAs and their target genes have been predicted, few studies have validated these predictions.MethodsWe measured the expression of GABAAα5 mRNA in the prefrontal and motor cortices of human alcoholics and matched controls using real‐time PCR. The expression of miR‐203 was measured in a subset of these cases. The predicted interaction of miR‐203 and GABRA5 was validated for miR‐203 using a luciferase reporter assay.ResultsIn both frontal and motor cortices, the expression of GABAAα5 was significantly lower in cirrhotic alcoholics compared with controls. Further, the pattern of expression between the groups was significantly different between males and females. The expression of miR‐203 was higher in the prefrontal cortex of cirrhotic alcoholics compared with controls and uncomplicated alcoholics. These differences were particularly marked in female cases. Cotransfection of GABRA5 with miR‐203 in HEK293T cells reduced luciferase reporter activity.ConclusionThere are sex differences in the expression of GABAAα5 and miR‐203 in the brain of human alcoholics which are particularly marked in alcoholics with cirrhosis of the liver. Further, miR‐203 may mediate the changes in expression of this GABAA receptor isoform that is brought about by alcohol exposure.
Impact of hospital resection volume and service capability on post‐operative mortality following gastrectomy
Authors: Narendra Aaditya , Baade Peter D. , Aitken Joanne F. , Fawcett Jonathan , Smithers B. Mark 
Published: December 2019

AbstractBackgroundImproved post‐operative mortality following gastrectomy for cancer in hospitals with higher resection volumes has not been reported in Australia. Using a population‐based study in Queensland, we aimed to compare post‐operative mortality following gastrectomy between high‐ and low‐volume hospitals stratified by their service capability.MethodsAll patients undergoing gastrectomy for adenocarcinoma in Queensland between 2001 and 2015 were obtained from the Queensland Oncology Repository. Hospital service capability was defined using the 2015 Australian Institute of Health and Welfare hospital peer groupings. Hospitals were grouped into ‘high‐volume (≥5 gastrectomies annually), high service capability’ (HVHS); ‘low‐volume (<5), high service capability’; and ‘low‐volume, low service capability’ (LVLS). Negative binomial regression models were used to compare 30‐ and 90‐day mortality rates between hospital groups adjusting for age, sex, socio‐economic status, Charlson and American Society of Anesthesiologists scores, treatment regimen, stage and time‐period. Potential mediation of mortality differences between hospital groups due to differences in the type of gastrectomy performed was also examined.ResultsLVLS hospitals have higher adjusted 30‐day (incidence rate ratio (IRR) 2.97, 95% confidence interval (CI) 1.65–5.35) and 90‐day (IRR 1.95, 95% CI 1.23–3.09) mortality rates compared with HVHS hospitals. There is no significant difference in adjusted 30‐day (IRR 1.16, 95% CI 0.48–2.79) and 90‐day (IRR 1.12, 95% CI 0.59–2.13) mortality rates comparing low‐volume, high service capability hospitals with HVHS hospitals. The type of gastrectomy performed did not significantly influence differences in mortality compared between hospital groups.ConclusionIn the Australian environment, post‐operative mortality following gastric cancer surgery may be optimized by centralizing gastrectomy away from hospitals characterized by LVLS.
Mitochondrial fusion promoter restores mitochondrial dynamics balance and ameliorates diabetic cardiomyopathy in an optic atrophy 1‐dependent way
Authors: Ding Mingge , Liu Chaoyang , Shi Rui , Yu Mingzhe , Zeng Ke , Kang Junjun , Fu Feng , Mi Mantian 
Published: December 2019

AbstractAimImbalanced mitochondrial dynamics including suppressed mitochondrial fusion has been observed in diabetic hearts. However, it is still unknown whether mitochondrial fusion promoter is an effective protection to diabetic hearts. This study was designed to explore the efficacy of mitochondrial fusion promoter on diabetic cardiomyopathy (DCM).MethodsMale Sprague‐Dawley rats were injected with streptozotocin (STZ, 65 mg/kg/d) intraperitoneally to induce diabetes. Seven weeks after vehicle or STZ injection, control or diabetic rats were treated with the vehicle or a mitochondrial fusion promoter‐M1 (2 mg/kg/d) intraperitoneally for 6 weeks. Moreover, M1 was administrated to the primary cardiomyocytes cultured in normal glucose medium (NG, 5.5 mmol/L) or high glucose (HG, 33 mnol/L).ResultsAdministration of M1 significantly promoted mitochondrial fusion and attenuated the reduction in optic atrophy 1 (Opa1) expression in diabetic hearts. Importantly, M1 treatment attenuated oxidative stress, improved mitochondrial function and alleviated DCM in diabetic rats. In HG‐treated cardiomyocytes, M1 treatment consistently increased the expression of Opa1, promoted mitochondrial fusion, enhanced mitochondrial respiratory capacity and reduced mitochondria‐derived superoxide production, all of which were blunted by Opa1 siRNA knockdown. In addition, selective upregulation of Opa1 alone can also promote mitochondrial fusion, improve mitochondrial function and inhibit mitochondria‐derived superoxide production in HG‐cultured cardiomyocytes.ConclusionOur findings show for the first time that mitochondrial fusion promoter M1 effectively balances mitochondrial dynamics and protects against diabetic cardiomyopathy (DCM) via an Opa1‐dependent way, suggesting that promoting mitochondrial fusion might be a potential therapeutic strategy for DCM.
Clothing color mediates lizard responses to humans in a tropical forest
Authors: Fondren Andrea , Swierk Lindsey , Putman Breanna J. 
Published: December 2019

AbstractIdentifying how ecotourism affects wildlife can lower its environmental impact. Human presence is an inherent component of ecotourism, which can impact animal behavior because animals often perceive humans as predators and, consequently, spend more time on human‐directed antipredator behaviors and less on other fitness‐relevant activities. We tested whether human clothing color affects water anole (Anolis aquaticus) behavior at a popular ecotourism destination in Costa Rica, testing the hypothesis that animals are more tolerant of humans wearing their sexually selected signaling color. We examined whether clothing resembling the primary signaling color (orange) of water anoles increases number of anole sightings and ease of capture. Research teams mimicked an ecotourism group by searching for anoles wearing one of three shirt treatments: orange, green, or blue. We conducted surveys at three different sites: a primary forest, secondary forest, and abandoned pasture. Wearing orange clothing resulted in more sightings and greater capture rates compared with blue or green. A higher proportion of males were captured when wearing orange whereas sex ratios of captured anoles were more equally proportional in the surveys when observers wore green or blue. We also found that capture success was greater when more people were present during a capture attempt. We demonstrate that colors “displayed” by perceived predators (i.e., humans) alter antipredator behaviors in water anoles. Clothing choice could have unintended impacts on wildlife, and wearing colors resembling the sexually selected signaling color might enhance tolerance toward humans.Abstract in Spanish is available with online material.
Changes in young children's oral health‐related behaviours and caregiver knowledge: A cluster randomized controlled trial in Brazil
Authors: Menegaz Aryane Marques , Quevedo Luciana de Ávila , Muniz Ludmila Correa , Finlayson Tracy L. , Ayala Guadalupe X. , Cascaes Andreia Morales 
Published: December 2019

AbstractObjectiveTo evaluate the effectiveness of an intervention to improve young children's oral health‐related behaviours and caregiver knowledge.MethodsThis paper reports on findings from a cluster randomized controlled trial, 12 months after of baseline, conducted in Pelotas, Southern Brazil. Two Primary Healthcare Centers (PHCs) and 170 caregiver‐child dyads were assigned to an intervention group, and two PHCs and 174 dyads were assigned to a control group. Children's oral hygiene behaviours, sugar consumption and use of dental services were the outcomes analysed as well as changes in caregiver knowledge. The impact of the intervention was assessed using multilevel mixed‐effects model regressions and the change rate ratios (IRR) were expressed.ResultsThere were positive and significant changes in favour of the intervention group in children's oral hygiene behaviours, use of dental services, and caregivers’ knowledge of oral health. For example, children in the intervention group were more likely to have brushed with fluoride toothpaste at least two times a day (IRR 1.43, 95% CI 1.06‐1.92), to have brushed their teeth before bedtime (IRR 1.37, 95% CI 1.02‐1.84), and to have used dental services for preventive care (IRR 2.54, 95% CI 2.02‐3.19) than children in the control group.ConclusionThis intervention had positive effects on children's oral health‐related behaviours and caregivers’ oral health knowledge.
Conservation enforcement: Insights from people incarcerated for wildlife crimes in Nepal
Authors: Paudel Kumar , Potter Gary R. , Phelps Jacob 
Published: December 2019

ABSTRACTThere are long‐standing debates about the effectiveness and social impacts of enforcement‐based conservation, particularly as investments into enforcement increase in response to growing alarm about Illegal Wildlife Trade (IWT). However, there is little data on the people subject to this enforcement, including prison sentences, species targeted, what motivates and deters them, and the social impacts of enforcement. This study identified 384 individuals across Nepal who were in prison for IWT offences in late 2016, and involved interviews (n = 116) focused on respondents' trade practices, economic circumstances and motivations. IWT prisoners represented 10–20% of the total prison populations in two regions and often received stiff sanctions, with a range of downstream impacts on respondents' families. Most respondents were arrested for their involvement in the rhinoceros trade (61%). Most were poor (56%) and from indigenous communities (75%), highlighting potentially inequitable impacts of enforcement. Despite common assumptions about the links between IWT, poverty and organized crime, most respondents were motivated by the desire to earn extra income and by the ease of IWT compared to other employment. IWT was neither a primary livelihood strategy, nor had the attributes for formal organized crime. Respondents, particularly poor respondents, seemed to underestimate the risks of detection and incompletely understood the scale of sanctions. Improved public awareness about the scale and social impacts of sanctions could help increase deterrence effects while reducing unintended social harms of enforcement.
Detection of LV apical thrombus by three‐dimensional transesophageal echocardiography
Authors: Fazlinezhad Afsoon , Narayanasamy Hemalatha , Wilansky Susan , Naqvi Tasneem Z. 
Published: December 2019

AbstractIntroductionPatients with apical myocardial infarction are at higher risk of developing left ventricular (LV) thrombi. Standard transesophageal echocardiography (TEE) is commonly used in assessing cardiac source of embolic cerebrovascular accident (CVA). Contrast‐enhanced transthoracic echocardiography (TTE) improves sensitivity for thrombus detection compared with noncontrast TTE, and however for LV apical thrombi, contrast‐enhanced magnetic resonance imaging (MRI) and/or contrast‐enhanced computed tomography (CT) outperform both TTE and TEE in some studies.CaseA 67‐year‐old man with history of prior myocardial infarction (MI), four‐vessel coronary artery bypass surgery, congestive heart failure with LV ejection fraction of 30%, and diabetes mellitus presented to our facility with acute right occipital‐parietal stroke and recent history of left lower extremity ischemia. Head and neck MRI and MR angiography found multiple posterior circulation infarcts suggestive of cardio‐embolic etiology. TTE image quality was suboptimal even after contrast use to evaluate for LV thrombus, and due to renal insufficiency, MRI or CT was precluded and 3DTEE identified large LV apical thrombus with mobile components.Conclusion3DTEE may increase the detection of LV apical thrombi as well as evaluating its characteristics by live imaging as well as by offline reconstruction. TEE may be a useful diagnostic modality, especially in patients with decreased renal function, where iodinated contrast for cardiac CT or Gadolinium for MRI may be contraindicated. Multimodality imaging studies may further prove the utility of 3D echocardiographic imaging in the detection of LV apical thrombus.
Framework and operationalisation challenges for quantitative comparative research in higher education
Authors: Seeber Marco 
Published: December 2019

AbstractThe increasing availability of data on higher education systems, institutions and their members creates new opportunities for comparative research adopting a quantitative approach. The value of future studies crucially depends on the capability to recognise and address some major methodological challenges existing in quantitative comparative research in higher education. The higher education context presents in fact specific features that can hinder comparisons, and political and social processes occurred in recent decades further enhanced complexity. This article aims to discuss key challenges that are currently met in quantitative comparative research in higher education while developing the conceptual framework and in research operationalisation, to discuss possible solutions and the value of configurational and multilevel analytical approaches in identifying meaningful objects of comparisons, to take into account the complexity of the higher education context and in identifying causal relationships.