bluuebunny/crossref_metadata_2025_split huggingface dataset:
A survey of ENT experience in South West Peninsula general practitioner trainees: how can post-graduate ENT training be improved?
Authors: Easto R H , Reddy V 
Published: September 2016

AbstractObjectives:To assess how much ENT experience regional general practitioner trainees received, both in their undergraduate and post-graduate training, and to establish if trainees felt they required further ENT training to manage ENT complaints.Methods:An online survey was emailed to general practitioner trainees in Cornwall and Devon.Results:Of 200 general practitioner trainees, 121 (60.5 per cent) responded to the survey. Of these respondents, 95.9 per cent felt ENT experience was important as a general practitioner; however, 59.5 per cent had no ENT experience in their post-graduate training. Sixty-five per cent of trainees had not had any formal ENT teaching since leaving medical school; however, 93.4 per cent would attend a 1-day course if offered the opportunity locally. Finally, 75.8 per cent of trainees would have liked an ENT post during their post-graduate training.Conclusion:Further ENT training is required for doctors in general practitioner training schemes to aid improvement of patient care. The most logical way to enhance ENT training in a post-graduate setting is through up-to-date courses held locally with a faculty made up of experts working within the specialty.
Autologous fat injection therapy including a high concentration of adipose-derived regenerative cells in a vocal fold paralysis model: animal pilot study
Authors: Nishio N , Fujimoto Y , Suga K , Iwata Y , Toriyama K , Takanari K , Kamei Y , Yamamoto T , Gotoh M 
Published: September 2016

AbstractObjectives:To verify the effectiveness and safety of the addition of adipose-derived regenerative cells to autologous fat injection therapy.Methods:Unilateral vocal fold paralysis models were made by cutting the right recurrent laryngeal nerve in two pigs. At day 30, 0.5 ml adipose-derived regenerative cells mixed with 1 ml autologous fat was injected into the right vocal fold of one pig, with the other receiving 0.5 ml Ringer's solution mixed with 1 ml autologous fat. At day 120, fibrescopy, laser Doppler flowmeter, computed tomography, vocal function evaluation and histological assessment were conducted.Results:Although histological assessment revealed atrophy of the thyroarytenoid muscle fibre in both pigs, there was remarkable hypertrophy of the thyroarytenoid muscle fibre in the area surrounding the adipose-derived regenerative cells injection site.Conclusion:The addition of a high concentration of adipose-derived regenerative cells to autologous fat injection therapy has the potential to improve the treatment outcome for unilateral vocal fold paralysis.
A systematic review with meta-analysis of the role of anxiety and depression in irritable bowel syndrome onset
Authors: Sibelli A. , Chalder T. , Everitt H. , Workman P. , Windgassen S. , Moss-Morris R. 
Published: September 2016

BackgroundIt is well established that people with irritable bowel syndrome (IBS) have higher levels of anxiety and depression compared with controls. However, the role of these as risk factors is less clearly established. The aims of this systematic review were to investigate: (1) whether anxiety and/or depression predict IBS onset; (2) the size of the relative risk (RR) of anxiety versus depression in IBS onset. Subgroup analyses explored if methodological factors affected the overall findings.MethodProspective cohort or case–control studies were included if they: (1) focused on the development of IBS in population-based or gastroenteritis cohorts; (2) explored the effects of anxiety and/or depression at baseline as predictors of IBS onset at a future point. In all, 11 studies were included of which eight recruited participants with a gastrointestinal infection. Meta-analyses were conducted.ResultsThe risk of developing IBS was double for anxiety cases at baseline compared with those who were not [RR 2.38, 95% confidence interval (CI) 1.58–3.60]. Similar results were found for depression (RR 2.06, 95% CI 1.44–2.96). Anxiety and depression seemed to play a stronger role in IBS onset in individuals with a gastrointestinal infection although this could be attributed to other differences in methodology, such as use of diagnostic interviews rather than self-report.ConclusionsThe findings suggest that self-reported anxiety and depression provide a twofold risk for IBS onset. There is less support for the role of anxiety or depressive disorder diagnosed using clinical interview. These findings may have implications for the development of interventions focused on IBS prevention and treatment.
VARIÉTÉS DE KISIN STRATIFIÉES ET DÉFORMATIONS POTENTIELLEMENT BARSOTTI-TATE
Authors: Caruso Xavier , David Agnès , Mézard Ariane 
Published: September 2016

Let $F$ be a unramified finite extension of $\mathbb{Q}_{p}$ and $\overline{\unicode[STIX]{x1D70C}}$ be an irreducible mod $p$ two-dimensional representation of the absolute Galois group of $F$. The aim of this article is the explicit computation of the Kisin variety parameterizing the Breuil–Kisin modules associated to certain families of potentially Barsotti–Tate deformations of $\overline{\unicode[STIX]{x1D70C}}$. We prove that this variety is a finite union of products of $\mathbb{P}^{1}$. Moreover, it appears as an explicit closed connected subvariety of $(\mathbb{P}^{1})^{[F:\mathbb{Q}_{p}]}$. We define a stratification of the Kisin variety by locally closed subschemes and explain how the Kisin variety equipped with its stratification may help in determining the ring of Barsotti–Tate deformations of $\overline{\unicode[STIX]{x1D70C}}$.
Clearance of autophagy-associated dying retinal pigment epithelial cells – a possible source for inflammation in age-related macular degeneration
Authors: Szatmári-Tóth M , Kristóf E , Veréb Z , Akhtar S , Facskó A , Fésüs L , Kauppinen A , Kaarniranta K , Petrovski G 
Published: September 2016

AbstractRetinal pigment epithelial (RPE) cells can undergo different forms of cell death, including autophagy-associated cell death during age-related macular degeneration (AMD). Failure of macrophages or dendritic cells (DCs) to engulf the different dying cells in the retina may result in the accumulation of debris and progression of AMD. ARPE-19 and primary human RPE cells undergo autophagy-associated cell death upon serum depletion and oxidative stress induced by hydrogen peroxide (H2O2). Autophagy was revealed by elevated light-chain-3 II (LC3-II) expression and electron microscopy, while autophagic flux was confirmed by blocking the autophago-lysosomal fusion using chloroquine (CQ) in these cells. The autophagy-associated dying RPE cells were engulfed by human macrophages, DCs and living RPE cells in an increasing and time-dependent manner. Inhibition of autophagy by 3-methyladenine (3-MA) decreased the engulfment of the autophagy-associated dying cells by macrophages, whereas sorting out the GFP-LC3-positive/autophagic cell population or treatment by the glucocorticoid triamcinolone (TC) enhanced it. Increased amounts of IL-6 and IL-8 were released when autophagy-associated dying RPEs were engulfed by macrophages. Our data suggest that cells undergoing autophagy-associated cell death engage in clearance mechanisms guided by professional and non-professional phagocytes, which is accompanied by inflammation as part of an in vitro modeling of AMD pathogenesis.
MiR-182-5p protects inner ear hair cells from cisplatin-induced apoptosis by inhibiting FOXO3a
Authors: Li Yimeng , Li Ao , Wu Jingfang , He Yingzi , Yu Huiqian , Chai Renjie , Li Huawei 
Published: September 2016

AbstractCisplatin is widely used for chemotherapy of a variety of malignancies. However, the clinical application of cisplatin is hampered by the resultant irreversible hearing loss due to hair cell apoptosis. To date, no practical regimen to resolve this has been developed. Meanwhile, the role of microRNA in protecting hair cells from cisplatin-induced apoptosis in the inner ear has not been extensively investigated. In this study, we monitored miR-183, -96, and -182 turnover in the cochlea during cisplatin treatmentin vitro. We found that overexpression of miR-182, but not miR-183 and -96, improved hair cell survival after 3 μM cisplatin treatmentin vitro. We demonstrated that overexpression of miR-182 repressed the intrinsic apoptotic pathway by inhibiting the translation of FOXO3a. Our study offers a new therapeutic target for alleviating cisplatin-induced hair cell apoptosis in a rapid and tissue-specific manner.
Ret is essential to mediate GDNF’s neuroprotective and neuroregenerative effect in a Parkinson disease mouse model
Authors: Drinkut Anja , Tillack Karsten , Meka Durga P , Schulz Jorg B , Kügler Sebastian , Kramer Edgar R 
Published: September 2016

AbstractGlial cell line-derived neurotrophic factor (GDNF) is a potent survival and regeneration-promoting factor for dopaminergic neurons in cell and animal models of Parkinson disease (PD). GDNF is currently tested in clinical trials on PD patients with so far inconclusive results. The receptor tyrosine kinase Ret is the canonical GDNF receptor, but several alternative GDNF receptors have been proposed, raising the question of which signaling receptor mediates here the beneficial GDNF effects. To address this question we overexpressed GDNF in the striatum of mice deficient for Ret in dopaminergic neurons and subsequently challenged these mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Strikingly, in this established PD mouse model, the absence of Ret completely abolished GDNF’s neuroprotective and regenerative effect on the midbrain dopaminergic system. This establishes Ret signaling as absolutely required for GDNF’s effects to prevent and compensate dopaminergic system degeneration and suggests Ret activation as the primary target of GDNF therapy in PD.
Omentin protects against LPS-induced ARDS through suppressing pulmonary inflammation and promoting endothelial barrier via an Akt/eNOS-dependent mechanism
Authors: Qi Di , Tang Xumao , He Jing , Wang Daoxin , Zhao Yan , Deng Wang , Deng Xinyu , Zhou Guoqi , Xia Jing , Zhong Xi , Pu Shenglan 
Published: September 2016

AbstractAcute respiratory distress syndrome (ARDS) is characterized by increased pulmonary inflammation and endothelial barrier permeability. Omentin has been shown to benefit obesity-related systemic vascular diseases; however, its effects on ARDS are unknown. In the present study, the level of circulating omentin in patients with ARDS was assessed to appraise its clinical significance in ARDS. Mice were subjected to systemic administration of adenoviral vector expressing omentin (Ad-omentin) and one-shot treatment of recombinant human omentin (rh-omentin) to examine omentin’s effects on lipopolysaccharide (LPS)-induced ARDS. Pulmonary endothelial cells (ECs) were treated with rh-omentin to further investigate its underlying mechanism. We found that a decreased level of circulating omentin negatively correlated with white blood cells and procalcitonin in patients with ARDS. Ad-omentin protected against LPS-induced ARDS by alleviating the pulmonary inflammatory response and endothelial barrier injury in mice, accompanied by Akt/eNOS pathway activation. Treatment of pulmonary ECs with rh-omentin attenuated inflammatory response and restored adherens junctions (AJs), and cytoskeleton organization promoted endothelial barrier after LPS insult. Moreover, the omentin-mediated enhancement of EC survival and differentiation was blocked by the Akt/eNOS pathway inactivation. Therapeutic rh-omentin treatment also effectively protected against LPS-induced ARDS via the Akt/eNOS pathway. Collectively, these data indicated that omentin protects against LPS-induced ARDS by suppressing inflammation and promoting the pulmonary endothelial barrier, at least partially, through an Akt/eNOS-dependent mechanism. Therapeutic strategies aiming to restore omentin levels may be valuable for the prevention or treatment of ARDS.
Distal regulation of c-myb expression during IL-6-induced differentiation in murine myeloid progenitor M1 cells
Authors: Zhang Junfang , Han Bingshe , Li Xiaoxia , Bies Juraj , Jiang Penglei , Koller Richard P , Wolff Linda 
Published: September 2016

AbstractThe c-Myb transcription factor is a major regulator that controls differentiation and proliferation of hematopoietic progenitor cells, which is frequently deregulated in hematological diseases, such as lymphoma and leukemia. Understanding of the mechanisms regulating the transcription of c-myb gene is challenging as it lacks a typical promoter and multiple factors are involved. Our previous studies identified some distal regulatory elements in the upstream regions of c-myb gene in murine myeloid progenitor M1 cells, but the detailed mechanisms still remain unclear. In the present study, we found that a cell differentiation-related DNase1 hypersensitive site is located at a −28k region upstream of c-myb gene and that transcription factors Hoxa9, Meis1 and PU.1 bind to the −28k region. Circular chromosome conformation capture (4C) assay confirmed the interaction between the −28k region and the c-myb promoter, which is supported by the enrichment of CTCF and Cohesin. Our analysis also points to a critical role for Hoxa9 and PU.1 in distal regulation of c-myb expression in murine myeloid cells and cell differentiation. Overexpression of Hoxa9 disrupted the IL-6-induced differentiation of M1 cells and upregulated c-myb expression through binding of the −28k region. Taken together, our results provide an evidence for critical role of the −28k region in distal regulatory mechanism for c-myb gene expression during differentiation of myeloid progenitor M1 cells.
Unconventional charge order in a co-doped high-Tc superconductor
Authors: Pelc D. , Vučković M. , Grafe H. -J. , Baek S. -H. , Požek M. 
Published: September 2016

AbstractCharge-stripe order has recently been established as an important aspect of cuprate high-Tcsuperconductors. However, owing to the complex interplay between competing phases and the influence of disorder, it is unclear how it emerges from the parent high-temperature state. Here we report on the discovery of an unconventional ordered phase between charge-stripe order and (pseudogapped) metal in the cuprate La1.8−xEu0.2SrxCuO4. We use three complementary experiments—nuclear quadrupole resonance, nonlinear conductivity and specific heat—to demonstrate that the order appears through a sharp phase transition and exists in a dome-shaped region of the phase diagram. Our results imply that the new phase is a state, which preserves translational symmetry: a charge nematic. We thus resolve the process of charge-stripe development in cuprates, show that this nematic phase is distinct from high-temperature pseudogap and establish a link with other strongly correlated electronic materials with prominent nematic order.
Independent effect of prior exacerbation frequency and disease severity on the risk of future exacerbations of COPD: a retrospective cohort study
Authors: Margüello Miguel Santibañez , Garrastazu Roberto , Ruiz-Nuñez Mario , Helguera Jose Manuel , Arenal Sandra , Bonnardeux Cristina , León Carlos , Miravitlles Marc , García-Rivero Juan Luis 
Published: September 2016

AbstractFew studies have researched the independent effect of COPD severity on the risk of future exacerbations adjusted by previous exacerbation frequency. We aimed to analyse the independent effect of COPD severity on the risk of exacerbations in the following year, and whether this effect was stronger or not than the effect of a previous history of exacerbations. We conducted a retrospective population-based cohort study including 900 patients with confirmed COPD. Exacerbation frequency was observed for the previous year and for the following year. Patients were defined as ‘Frequent Exacerbator’ (FE) phenotype if they suffered ⩾2 exacerbations in a year, and were categorised according to the severity of COPD (GOLD Grades 1–4). Odds ratios (ORs) were estimated by logistic regression adjusting for age, gender, smoking status, severity of COPD and being FE in the previous year. The main predictor of being FE among all grades of COPD severity was a history of frequent exacerbations in the previous year: adjusted OR 4.97; 95% confidence interval (CI) (3.54–6.97). COPD severity was associated with a higher risk of being FE: Crude OR GOLD Grade 4 3.86; 95% CI (1.50–9.93). However, this association diminished after adjusting for being FE in the previous year: adjusted OR 2.08; 95% CI (0.75–5.82). Our results support that a history of frequent exacerbations in the previous year is the most important independent predictor of exacerbations in the following year, also among the most severe COPD patients. Severity of COPD would be associated with a higher risk of exacerbations, but this effect would be partly determined by the exacerbations suffered in the previous year.
Screening of SOD1, FUS and TARDBP genes in patients with amyotrophic lateral sclerosis in central-southern China
Authors: Hou Lihua , Jiao Bin , Xiao Tingting , Zhou Lu , Zhou Zhifan , Du Juan , Yan Xinxiang , Wang Junling , Tang Beisha , Shen Lu 
Published: September 2016

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons of the brain, brainstem and spinal cord. To date, mutations in more than 30 genes have been linked to the pathogenesis of ALS. Among them, SOD1, FUS and TARDBP are ranked as the three most common genes associated with ALS. However, no mutation analysis has been reported in central-southern China. In this study, we sequenced SOD1, FUS and TARDBP in a central-southern Chinese cohort of 173 patients with ALS (15 familial ALS and 158 sporadic ALS) to detect mutations. As a result, five missense mutations in SOD1, namely, p.D101N, p.D101G, p.C111Y, p.N86S and p.V87A, were identified in three unrelated familial probands and three sporadic cases; two mutations in FUS were found in two unrelated familial probands, including an insertion mutation (p.P525_Y526insY) and a missense mutation (p.R521H); no variants of TARDBP were observed in patients. Therefore, SOD1 mutations were present in 20.0% of familial ALS patients and 1.9% of sporadic ALS patients, while FUS mutations were responsible for 13.3% of familial ALS cases and TARDBP mutations were rare in either familial or sporadic ALS cases. This study broadens the known mutational spectrum in patients with ALS and further demonstrates the necessity for genetic screening in ALS patients from central-southern China.
Glucose-dependent anaplerosis in cancer cells is required for cellular redox balance in the absence of glutamine
Authors: Cetinbas Naniye Mallı , Sudderth Jessica , Harris Robert C. , Cebeci Aysun , Negri Gian L. , Yılmaz Ömer H. , DeBerardinis Ralph J. , Sorensen Poul H. 
Published: September 2016

AbstractCancer cells have altered metabolism compared to normal cells, including dependence on glutamine (GLN) for survival, known as GLN addiction. However, some cancer cell lines do not require GLN for survival and the basis for this discrepancy is not well understood. GLN is a precursor for antioxidants such as glutathione (GSH) and NADPH, and GLN deprivation is therefore predicted to deplete antioxidants and increase reactive oxygen species (ROS). Using diverse human cancer cell lines we show that this occurs only in cells that rely on GLN for survival. Thus, the preference for GLN as a dominant antioxidant source defines GLN addiction. We show that despite increased glucose uptake, GLN addicted cells do not metabolize glucose via the TCA cycle when GLN is depleted, as revealed by 13C-glucose labeling. In contrast, GLN independent cells can compensate by diverting glucose-derived pyruvate into the TCA cycle. GLN addicted cells exhibit reduced PDH activity, increased PDK1 expression, and PDK inhibition partially rescues GLN starvation-induced ROS and cell death. Finally, we show that combining GLN starvation with pro-oxidants selectively kills GLN addicted cells. These data highlight a major role for GLN in maintaining redox balance in cancer cells that lack glucose-dependent anaplerosis.
Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo
Authors: Greening David W. , Ji Hong , Chen Maoshan , Robinson Bruce W. S. , Dick Ian M. , Creaney Jenette , Simpson Richard J. 
Published: September 2016

AbstractMalignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets.
Synthesis of semicrystalline nanocapsular structures obtained by Thermally Induced Phase Separation in nanoconfinement
Authors: Torino Enza , Aruta Rosaria , Sibillano Teresa , Giannini Cinzia , Netti Paolo A. 
Published: September 2016

AbstractPhase separation of a polymer solution exhibits a peculiar behavior when induced in a nanoconfinement. The energetic constraints introduce additional interactions between the polymer segments that reduce the number of available configurations. In our work, this effect is exploited in a one-step strategy called nanoconfined-Thermally Induced Phase Separation (nc-TIPS) to promote the crystallization of polymer chains into nanocapsular structures of controlled size and shell thickness. This is accomplished by performing a quench step of a low-concentrated PLLA-dioxane-water solution included in emulsions of mean droplet size <500 nm acting as nanodomains. The control of nanoconfinement conditions enables not only the production of nanocapsules with a minimum mean particle diameter of 70 nm but also the tunability of shell thickness and its crystallinity degree. The specific properties of the developed nanocapsular architectures have important implications on release mechanism and loading capability of hydrophilic and lipophilic payload compounds.