bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highly expressed long non‐coding RNA CRNDE promotes cell proliferation through PI3K/AKT signalling in non‐small cell lung carcinoma
Authors: Liu Xiao‐Xiong , Xiong Han‐Peng , Huang Jiu‐Sheng , Qi Kai , Xu Jian‐Jun 
Published: May 2017

SummaryRecently, numerous studies have revealed that long non‐coding RNAs (lncRNAs) play complex roles in various lung diseases, while the colorectal neoplasia differentially expressed (CRNDE) functions in non‐small cell lung carcinomas (NSCLC) remain largely unknown. In the present study, we investigate the role and mechanism of CRNDE in the progression of NSCLC. The mRNA level of CRNDE in NSCLC patients and cells was detected by qRT‐PCR. The influence of CRNDE silencing or over‐expression on NSCLC cell proliferation and growth were assessed by MTT and flow cytometry, respectively. We also investigated the effect of abnormal CRNDE expression on cyclins and PI3K/AKT pathway. Furthermore, si‐CRNDE NSCLC cell lines were injected subcutaneously into nude mice to explore tumour formation in vivo. The expression of CRNDE was significantly upregulated in NSCLC patients and cells. In addition, both loss and gain function assays revealed that CRNDE promoted NSCLC cell proliferation and growth both in vitro and in vivo. Moreover, CRNDE regulated the cell cycle transition from G0/G1 stage to S stage and modulated the expression of CDK4, CDK6 and CCNE1. We further illustrated that CRNDE activated PI3K/AKT signalling in NSCLC cell lines. In conclusion, CRNDE was highly expressed in NSCLC malignant tissues and the heightened CRNDE strongly promoted NSCLC cell proliferation and growth through activating PI3K/AKT signalling; our results shed a light on utilizing CRNDE as a potential novel therapeutic target for the treatment of NSCLC.
Dose discrepancy between planning system estimation and measurement in spine stereotactic body radiation therapy: A case report
Authors: Arumugam Sankar , Berry Megan , Ochoa Cesar , Xing Aitang , Beeksma Bradley , Vial Philip 
Published: May 2017

SummaryStereotactic body radiation therapy (SBRT) to treat spinal metastases has shown excellent clinical outcomes for local control. High dose gradients wrapping around spinal cord make this treatment technically challenging. In this work, we present a spine SBRT case where a dosimetric error was identified during pre‐treatment dosimetric quality assurance (QA). A patient with metastasis in T7 vertebral body consented to undergo SBRT. A dual arc volumetric modulated arc therapy plan was generated on the Pinnacle treatment planning system (TPS) with a 6 MV Elekta machine using gantry control point spacing of 4°. Standard pre‐treatment QA measurements were performed, including ArcCHECK, ion chamber in CTV and spinal cord (SC) region and film measurements in multiple planes. While the dose measured at CTV region showed good agreement with TPS, the dose measured to the SC was significantly higher than reported by TPS in the original and repeat plans. Acceptable agreement was only achieved when the gantry control point spacing was reduced to 3°. A potentially harmful dose error was identified by pre‐treatment QA. TPS parameter settings used safely in conventional treatments should be re‐assessed for complex treatments.
Comparative analysis of DNA extraction methods to study the body surface microbiota of insects: A case study with ant cuticular bacteria
Authors: Birer Caroline , Tysklind Niklas , Zinger Lucie , Duplais Christophe 
Published: May 2017

AbstractHigh‐throughput sequencing of the 16S rRNA gene has considerably helped revealing the essential role of bacteria living on insect cuticles in the ecophysiology and behaviour of their hosts. However, our understanding of host‐cuticular microbiota feedbacks remains hampered by the difficulties of working with low bacterial DNA quantities as with individual insect cuticle samples, which are more prone to molecular biases and contaminations. Herein, we conducted a methodological benchmark on the cuticular bacterial loads retrieved from two Neotropical ant species of different body size and ecology: Atta cephalotes (~15 mm) and Pseudomyrmex penetrator (~5 mm). We evaluated the richness and composition of the cuticular microbiota, as well as the amount of biases and contamination produced by four DNA extraction protocols. We also addressed how bacterial community characteristics would be affected by the number of individuals or individual body size used for DNA extraction. Most extraction methods yielded similar results in terms of bacterial diversity and composition for A. cephalotes (~15 mm). In contrast, greater amounts of artefactual sequences and contaminations, as well as noticeable differences in bacterial community characteristics were observed between extraction methods for P. penetrator (~5 mm). We also found that large (~15 mm) and small (~5 mm) A. cephalotes individuals harbour different bacterial communities. Our benchmark suggests that cuticular microbiota of single individual insects can be reliably retrieved provided that blank controls, appropriate data cleaning, and individual body size and functional role within insect society are considered in the experiment.
Sound levels in a neonatal intensive care unit significantly exceeded recommendations, especially inside incubators
Authors: Parra Johanna , de Suremain Aurelie , Berne Audeoud Frederique , Ego Anne , Debillon Thierry 
Published: May 2017

AbstractAimThis study measured sound levels in a 2008 built French neonatal intensive care unit (NICU) and compared them to the 2007 American Academy of Pediatrics (AAP) recommendations. The ultimate aim was to identify factors that could influence noise levels.MethodsThe study measured sound in 17 single or double rooms in the NICU. Two dosimeters were installed in each room, one inside and one outside the incubators, and these conducted measurements over a 24‐hour period. The noise metrics measured were the equivalent continuous sound level (Leq), the maximum noise level (Lmax) and the noise level exceeded for 10% of the measurement period (L10).ResultsThe mean Leq, L10 and Lmax were 60.4, 62.1 and 89.1 decibels (dBA), which exceeded the recommended levels of 45, 50 and 65 dBA (p < 0.001), respectively. The Leq inside the incubator was significantly higher than in the room (+8 dBA, p < 0.001). None of the newborns’ characteristics, the environment or medical care was correlated to an increased noise level, except for a postconceptional age below 32 weeks.ConclusionThe sound levels significantly exceeded the AAP recommendations, particularly inside incubators. A multipronged strategy is required to improve the sound environment and protect the neonates’ sensory development.
The pharmacokinetic interaction between ivacaftor and ritonavir in healthy volunteers
Authors: Liddy Anne Marie , McLaughlin Gavin , Schmitz Susanne , D'Arcy Deirdre M. , Barry Michael G. 
Published: May 2017

AimsThe aim of this study was to determine the pharmacokinetic interaction between ivacaftor and ritonavir.MethodsA liquid chromatography mass spectrometry (LC–MS) method was developed for the measurement of ivacaftor in plasma. An open‐label, sequential, cross‐over study was conducted with 12 healthy volunteers. Three pharmacokinetic profiles were assessed for each volunteer: ivacaftor 150 mg alone (study A), ivacaftor 150 mg plus ritonavir 50 mg daily (study B), and ivacaftor 150 mg plus ritonavir 50 mg daily after two weeks of ritonavir 50 mg daily (study C).ResultsAddition of ritonavir 50 mg daily to ivacaftor 150 mg resulted in significant inhibition of the metabolism of ivacaftor. Area under the plasma concentration–time curve from time 0 to infinity (AUC0‐inf obv) increased significantly in both studies B and C compared to study A (GMR [95% CI] 19.71 [13.18–31.33] and 19.77 [14.0–27.93] respectively). Elimination half‐life (t1/2) was significantly longer in both studies B and C compared to study A (GMR [95% CI] 11.14 [8.72–13.62] and 9.72 [6.68–12.85] respectively). There was no significant difference in any of the pharmacokinetic parameters between study B and study C.ConclusionRitonavir resulted in significant inhibition of the metabolism of ivacaftor. These data suggest that ritonavir may be used to inhibit the metabolism of ivacaftor in patients with cystic fibrosis (CF). Such an approach may increase the effectiveness of ivacaftor in ‘poor responders’ by maintaining higher plasma concentrations. It also has the potential to significantly reduce the cost of ivacaftor therapy.
Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition
Authors: Bast Tobias , Pezze Marie , McGarrity Stephanie 
Published: May 2017

We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, that is, deficient GABA transmission, within the prefrontal cortex and the hippocampus, for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunction has been implicated in cognitive deficits characterizing neuropsychiatric disorders. GABAergic inhibition shapes cortico‐hippocampal neural activity, and, recently, prefrontal and hippocampal neural disinhibition has emerged as a pathophysiological feature of major neuropsychiatric disorders, especially schizophrenia and age‐related cognitive decline. Regional neural disinhibition, disrupting spatio‐temporal control of neural activity and causing aberrant drive of projections, may disrupt processing within the disinhibited region and efferent regions. Recent studies in rats showed that prefrontal and hippocampal neural disinhibition (by local GABA antagonist microinfusion) dysregulates burst firing, which has been associated with important aspects of neural information processing. Using translational tests of clinically relevant cognitive functions, these studies showed that prefrontal and hippocampal neural disinhibition disrupts regional cognitive functions (including prefrontal attention and hippocampal memory function). Moreover, hippocampal neural disinhibition disrupted attentional performance, which does not require the hippocampus but requires prefrontal‐striatal circuits modulated by the hippocampus. However, some prefrontal and hippocampal functions (including inhibitory response control) are spared by regional disinhibition. We consider conceptual implications of these findings, regarding the distinct relationships of distinct cognitive functions to prefrontal and hippocampal GABA tone and neural activity. Moreover, the findings support the proposition that prefrontal and hippocampal neural disinhibition contributes to clinically relevant cognitive deficits, and we consider pharmacological strategies for ameliorating cognitive deficits by rebalancing disinhibition‐induced aberrant neural activity.Linked ArticlesThis article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc
α‐Conotoxins active at α3‐containing nicotinic acetylcholine receptors and their molecular determinants for selective inhibition
Authors: Cuny Hartmut , Yu Rilei , Tae Han‐Shen , Kompella Shiva N , Adams David J 
Published: May 2017

Neuronal α3‐containing nicotinic acetylcholine receptors (nAChRs) in the peripheral nervous system (PNS) and non‐neuronal tissues are implicated in a number of severe disease conditions ranging from cancer to cardiovascular diseases and chronic pain. However, despite the physiological characterization of mouse models and cell lines, the precise pathophysiology of nAChRs outside the CNS remains not well understood, in part because there is a lack of subtype‐selective antagonists. α‐Conotoxins isolated from cone snail venom exhibit characteristic individual selectivity profiles for nAChRs and, therefore, are excellent tools to study the determinants for nAChR‐antagonist interactions. Given that human α3β4 subtype selective α‐conotoxins are scarce and this is a major nAChR subtype in the PNS, the design of new peptides targeting this nAChR subtype is desirable. Recent studies using α‐conotoxins RegIIA and AuIB, in combination with nAChR site‐directed mutagenesis and computational modelling, have shed light onto specific nAChR residues, which determine the selectivity of the α‐conotoxins for the human α3β2 and α3β4 subtypes. Publications describing the selectivity profile and binding sites of other α‐conotoxins confirm that subtype‐selective nAChR antagonists often work through common mechanisms by interacting with the same structural components and sites on the receptor.Linked ArticlesThis article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc
Do glycoalbumin levels preferentially reflect changes in postprandial glucose excursions?
Authors: Paul S. K. , Holman R. R. 
Published: May 2017

AbstractAimsTo evaluate whether plasma glycated albumin, which provides an integrated measure of plasma glucose levels over the preceding 2–4 weeks, better reflects changes in postprandial glucose excursions than HbA1c.MethodsPeople with suboptimum glycaemic control on dual oral therapy were enrolled in the Treating‐to‐Target‐in‐Type 2 diabetes (4‐T) trial, in which participants were randomized to the addition of once‐daily basal insulin, twice‐daily biphasic insulin or thrice‐daily prandial insulin. Glycated albumin levels were assayed enzymatically from baseline and 1‐year fasting plasma samples. We evaluated robust correlations of glycated albumin and HbA1c both with fasting and postprandial glucose levels at these two time points, and with insulin‐induced changes in the postprandial excursion.ResultsRequisite data were available for 625 of the participants in the 4‐T trial. Their mean (±sd) age was 62 ± 10 years and body weight was 85.8 ± 15.9 kg, and their median (interquartile range) diabetes duration was 9 (6, 13) years. Partial correlations at baseline and 1 year between postprandial glucose excursions and glycated albumin/HbA1c, after adjusting for fasting glucose, were 0.27/0.15 and 0.22/0.18, respectively. Glycated albumin, compared with HbA1c, explained 66% more of the variation in postprandial glucose excursions at baseline. At 1 year, postprandial glucose excursions on basal, biphasic and prandial and insulin therapy were reduced by 0.43, 0.78 and 1.88 mmol/l, respectively. These reductions were associated with changes in both glycated albumin and HbA1c (P < 0.01), with a stronger association for glycated albumin.ConclusionChanges in glycated albumin and HbA1c reflect changes in postprandial glucose excursions to a similar extent.
Developing preference‐based measures for diabetes: DHP‐3D and DHP‐5D
Authors: Mulhern B. , Labeit A. , Rowen D. , Knowles E. , Meadows K. , Elliott J. , Brazier J. 
Published: May 2017

AbstractAimsThe aim of this study was to develop two diabetes‐specific preference‐based measures [the Diabetes Health Profile–3 Dimension (DHP‐3D) and the Diabetes Health Profile–5 Dimension (DHP‐5D)] for use in the calculation of Quality Adjusted Life Years, a key outcome in economic evaluation. These measures were based on the non‐preference‐based instrument the Diabetes Health Profile.MethodsFor DHP‐3D, psychometric and Rasch analyses were used to develop a health state classification system based on the Diabetes Health Profile–18 (DHP‐18). The DHP‐5D added two dimensions to the DHP‐3D to extend the range of impacts measured. Each classification system was valued by 150 general public respondents in the United Kingdom using Time Trade Off (TTO). Multivariate regression was used to estimate utility value sets. The matched dimensions across each measure were compared using z‐score tests.ResultsThe DHP‐3D included three dimensions defined as mood, eating and social limitations, and the DHP‐5D added dimensions defined as hypoglycaemic attacks and vitality. For both, the random effects generalized least squares regression model produced consistent value sets, with the DHP‐3D and DHP‐5D ranging from 0.983 (best state) to 0.717 (worst state), and 0.979 to 0.618 respectively. The addition of the two extra dimensions leads to significant differences for the more severe levels of each matched dimension.ConclusionsWe have developed two diabetes‐specific preference‐based measures that, subject to psychometric assessment, can be used to provide condition‐specific utility values to complement generic utilities from more widely validated measures such as the EuroQol‐5 Dimension.
Adiposity and incident diabetes within 4 years of follow‐up: the Guangzhou Biobank Cohort Study
Authors: Xu L. , Lam T. H. , Jiang C. Q. , Zhang W. S. , Jin Y. L. , Zhu T. , Zhu F. , Thomas G. N. , Cheng K. K. 
Published: May 2017

AbstractAimWhether different adiposity measures predict incident diabetes differentially in general Chinese populations is unclear. We investigated this in Chinese people aged 50+ years in the Guangzhou Biobank Cohort Study.MethodsWaist circumference and BMI were measured at baseline, and fasting glucose was measured at both baseline and follow‐up examinations. Incident diabetes was defined as fasting glucose ≥ 7.0 mmol/l, glucose after 2‐h oral glucose tolerance test ≥ 11.1 mmol/l, and/or self‐reported physician‐diagnosed diabetes during the follow‐up period.ResultsOf 15 752 people without diabetes at baseline from 2003 to 2008, 1779 (11.3%) developed incident diabetes during the follow‐up from 2008 to 2012 (mean = 3.6 years, sd = 1.0). After mutually adjusting each other and adjusting for other potential confounders, waist circumference showed a higher predictive value than BMI. The odds ratio (OR) (95% confidence interval (CI) was 1.50 (95% CI 1.37–1.64) for a 1 sd increment in waist circumference and 1.21 (95% CI 1.11–1.33), for a 1 sd increment in BMI. Similarly, after mutual adjustment, abdominal obesity was associated with an almost twofold odds of incident diabetes (OR 1.93, 95% CI 1.71–2.17), which was higher than that for general obesity (OR 1.76, 95% CI 1.50–2.06). The area under receiver operating characteristic curve (AUC) for waist circumference was higher than that for BMI [AUC = 0.676 (95% CI 0.660–0.686) vs. 0.665 (95% CI 0.651–0.678), P = 0.02].ConclusionAbdominal obesity predicted incident diabetes in older people better than general obesity. Our findings may be an early warning signal for local government or public health practitioners to develop and investigate more effective intervention programmes for diabetes, and should also be disseminated to the public to pay more attention to this important public health issue.
Emergency treatment of hypoglycaemia: a guideline and evidence review
Authors: Villani M. , de Courten B. , Zoungas S. 
Published: May 2017

AbstractAimTo examine the current treatment guidelines for the emergency management of hypoglycaemia and the evidence underpinning recommendations.MethodsInternational diabetes agencies were searched for hypoglycaemia treatment guidelines. Guidelines were assessed using the Appraisal of Guidelines Research and Evaluation II (AGREE II) instrument. An electronic database search was conducted for evidence regarding emergency treatment of hypoglycaemia in adults, and relevant articles were critically appraised.ResultsOf the international diabetes agencies, six sets of guidelines were deemed relevant and of sufficient detail for appraisal by AGREE II. The evidence search returned 2649 articles, of which 17 pertaining to the emergency management of hypoglycaemia were included. High‐quality evidence for the management of hypoglycaemia was lacking, limiting treatment recommendations. In general, guidelines and studies were somewhat concordant and recommended 15–20 g of oral glucose or sucrose, repeated after 10–15 min for treatment of the responsive adult, and 10% intravenous dextrose or 1 mg intramuscular glucagon for treatment of the unresponsive adult. No evidence was found for other treatment approaches.ConclusionEvidence for the emergency treatment of hypoglycaemia in adults is limited, is often low grade and mostly pre‐dates contemporary management of diabetes. Guideline recommendations are limited by the lack of randomized trials. Further high‐quality studies are required to inform the optimum management of this frequently occurring emergency condition.
European consensus for starting and stopping enzyme replacement therapy in adult patients with Pompe disease: a 10‐year experience
Authors: van der Ploeg A. T. , Kruijshaar M. E. , Toscano A. , Laforêt P. , Angelini C. , Lachmann R. H. , Pascual Pascual S. I. , Roberts M. , Rösler K. , Stulnig T. , van Doorn P. A. , Van den Bergh P. Y. K. , Vissing J. , Schoser B. ,   the European Pompe Consortium
Published: May 2017

Background and purposePompe disease is a rare inheritable muscle disorder for which enzyme replacement therapy (ERT) has been available since 2006. Uniform criteria for starting and stopping ERT in adult patients were developed and reported here.MethodsThree consensus meetings were organized through the European Pompe Consortium, a network of experts from 11 European countries in the field of Pompe disease. A systematic review of the literature was undertaken to determine the effectiveness of ERT in adult patients on a range of clinical outcome measures and quality of life. A narrative synthesis is presented.ResultsConsensus was reached on how the diagnosis of Pompe disease should be confirmed, when treatment should be started, reasons for stopping treatment and the use of ERT during pregnancy. This was based on expert opinion and supported by the literature. One clinical trial and 43 observational studies, covering a total of 586 individual adult patients, provided evidence of a beneficial effect of ERT at group level. At individual patient level, the response to treatment varied, but factors associated with a patient's response to ERT were not described in many studies. Eleven observational studies focused on more severely affected patients, suggesting that ERT can also be beneficial in these patients. There are no studies on the effects of ERT in pre‐symptomatic patients.ConclusionsThis is the first European consensus recommendation for starting and stopping ERT in adult patients with Pompe disease, based on the extensive experience of experts from different countries.
Etiologies of acute demyelinating optic neuritis: an observational study of 110 patients
Authors: Deschamps R. , Lecler A. , Lamirel C. , Aboab J. , Gueguen A. , Bensa C. , Vignal C. , Gout O. 
Published: May 2017

Background and purposeNew criteria for the diagnosis of multiple sclerosis (MS) and discovery of myelin oligodendrocyte glycoprotein (MOG) or aquaporin‐4 (AQP4) antibodies (Abs) have changed the management of optic neuritis (ON). Our aim was to specify, in view of these recent advances, the etiologies of acute demyelinating ON for consecutive patients.MethodsRetrospective database analysis was undertaken of consecutive adult patients with acute ON admitted from 1 December 2014 to 31 January 2016. Diagnosis of MS was made according to the 2010 McDonald criteria. Patients with Abs to AQP4 or MOG were classified as ON‐AQP4 and ON‐MOG, respectively. Patients who did not fulfill the diagnostic criteria and were negative for AQP4 and MOG Ab tests were classified as having idiopathic ON.ResultsOf 110 patients assessed, 78 had ON related to MS (70.9%). All patients without MS were tested for AQP4 and MOG Abs: 11 had MOG Ab (10%), 5 had AQP4 Ab (4.5%) and 16 were considered as having idiopathic ON (14.5%). Presence of intrathecal IgG oligoclonal bands was strongly associated with MS (mean, 88.4% vs. 34.4% in patients without MS; after Bonferroni correction, P < 0.0001).ConclusionsOptic neuritis related to MOG Ab was the second cause identified of demyelinating ON in our center. Idiopathic ON was as frequent as both ON‐AQP4 and ON‐MOG combined.