bluuebunny/crossref_metadata_2025_split huggingface dataset:
The risk of community‐acquired pneumonia among 9803 patients with coeliac disease compared to the general population: a cohort study
Authors: Zingone F. , Abdul Sultan A. , Crooks C. J. , Tata L. J. , Ciacci C. , West J. 
Published: May 2016

SummaryBackgroundPatients with coeliac disease are considered as individuals for whom pneumococcal vaccination is advocated.AimTo quantify the risk of community‐acquired pneumonia among patients with coeliac disease, assessing whether vaccination against streptococcal pneumonia modified this risk.MethodsWe identified all patients with coeliac disease within the Clinical Practice Research Datalink linked with English Hospital Episodes Statistics between April 1997 and March 2011 and up to 10 controls per patient with coeliac disease frequency matched in 10‐year age bands. Absolute rates of community‐acquired pneumonia were calculated for patients with coeliac disease compared to controls stratified by vaccination status and time of diagnosis using Cox regression in terms of adjusted hazard ratios (HR).ResultsAmong 9803 patients with coeliac disease and 101 755 controls, respectively, there were 179 and 1864 first community‐acquired pneumonia events. Overall absolute rate of pneumonia was similar in patients with coeliac disease and controls: 3.42 and 3.12 per 1000 person‐years respectively (HR 1.07, 95% CI 0.91–1.24). However, we found a 28% increased risk of pneumonia in coeliac disease unvaccinated subjects compared to unvaccinated controls (HR 1.28, 95% CI 1.02–1.60). This increased risk was limited to those younger than 65, was highest around the time of diagnosis and was maintained for more than 5 years after diagnosis. Only 26.6% underwent vaccination after their coeliac disease diagnosis.ConclusionsUnvaccinated patients with coeliac disease under the age of 65 have an excess risk of community‐acquired pneumonia that was not found in vaccinated patients with coeliac disease. As only a minority of patients with coeliac disease are being vaccinated there is a missed opportunity to intervene to protect these patients from pneumonia.
Glucagon‐related peptides and the regulation of food intake in chickens
Authors: Honda Kazuhisa 
Published: May 2016

AbstractThe regulatory mechanisms underlying food intake in chickens have been a focus of research in recent decades to improve production efficiency when raising chickens. Lines of evidence have revealed that a number of brain‐gut peptides function as a neurotransmitter or peripheral satiety hormone in the regulation of food intake both in mammals and chickens. Glucagon, a 29 amino acid peptide hormone, has long been known to play important roles in maintaining glucose homeostasis in mammals and birds. However, the glucagon gene encodes various peptides that are produced by tissue‐specific proglucagon processing: glucagon is produced in the pancreas, whereas oxyntomodulin (OXM), glucagon‐like peptide (GLP)‐1 and GLP‐2 are produced in the intestine and brain. Better understanding of the roles of these peptides in the regulation of energy homeostasis has led to various physiological roles being proposed in mammals. For example, GLP‐1 functions as an anorexigenic neurotransmitter in the brain and as a postprandial satiety hormone in the peripheral circulation. There is evidence that OXM and GLP‐2 also induce anorexia in mammals. Therefore, it is possible that the brain‐gut peptides OXM, GLP‐1 and GLP‐2 play physiological roles in the regulation of food intake in chickens. More recently, a novel GLP and its specific receptor were identified in the chicken brain. This review summarizes current knowledge about the role of glucagon‐related peptides in the regulation of food intake in chickens.
The morphology of CLL revisited: the clinical significance of prolymphocytes and correlations with prognostic/molecular markers in the LRF CLL4 trial
Authors: Oscier David , Else Monica , Matutes Estella , Morilla Ricardo , Strefford Jonathan C. , Catovsky Daniel 
Published: May 2016

SummaryHistorically, an increase in the percentage and number of circulating prolymphocytes in chronic lymphocytic leukaemia (CLL) has been associated with strong expression of surface immunoglobulin, trisomy 12 and a poor outcome. This study re‐examines the biological and clinical significance of increased peripheral blood prolymphocytes in 508 patients at entry into the randomized UK Leukaemia Research Fund CLL4 trial. It also investigates the associations between increased prolymphocytes and a comprehensive array of biomarkers. 270 patients (53%) had <5% prolymphocytes, 167 (33%) had 5–9%, 60 (12%) had 10–14% and 11 (2%) had ≥15% prolymphocytes. We show that a higher proportion of prolymphocytes (≥10%) was independently associated with NOTCH1 mutations (P = 0·006), absence of 13q deletion (P = 0·001), high CD38 expression (P = 0·02) and unmutated IGHV genes (P = 0·01). Deaths due to Richter syndrome were significantly more common amongst patients who had ≥10% vs <10% prolymphocytes (13% vs 2%) respectively (P < 0·0001). ≥10% prolymphocytes was also associated with a shorter progression‐free survival (Hazard ratio [HR] 1·50 [95% confidence interval [CI]: 1·16–1·93], P = 0·002) and overall survival (HR 1·99 [95% CI: 1·53–2·59], P < 0·0001). Our data support the routine examination of blood films in CLL and suggest that a finding of an increased proportion of prolymphocytes may be a trigger for further evaluation of clinical and laboratory features of progressive disease.
The geometry of morphospaces: lessons from the classicRaup shell coiling model
Authors: Gerber Sylvain 
Published: May 2016

ABSTRACTMorphospaces are spatial depictions of morphological variation among biological forms that have become an integral part of the analytical toolkit of evolutionary biologists and palaeobiologists. Nevertheless, the term morphospace brings together a great variety of spaces with different geometries. In particular, many morphospaces lack the metric properties underlying the notions of distance and direction, which are, however, central to the analysis of morphological differences and evolutionary transitions. The problem is illustrated here with the iconic morphospace of coiled shells implemented byRaup 50 years ago. The model, which allows the description of shell coiling geometry of various invertebrate taxa, is a seminal reference in theoretical morphology and morphospace theory, but also a morphometric framework frequently used in empirical studies, particularly of ammonoids. Because of the definition of its underlying parameters,Raup's morphospace does not possess aEuclidean structure and a meaningful interpretation of the spread and spacing of taxa within it is not guaranteed. Focusing on the region of the morphospace occupied by most ammonoids, I detail a landmark‐based morphospace circumventing this problem and built from the same input measurements required for the calculation ofRaup's parameters. From simulations and a reanalysis ofPalaeozoic ammonoid shell disparity, the properties of these morphospaces are compared and their algebraic and geometric relationships highlighted. WhileRaup's model remains a valuable tool for describing ammonoid shells and relating their shapes to the coiling process, it is demonstrated that quantitative analyses of morphological patterns should be carried out within the landmark‐based framework. Beyond this specific case, the increasing use and diversity of morphospaces in evolutionary morphology call for caution when interpreting patterns and comparing results drawn from different types of morphospaces.
Novel taxane derivatives from Taxus wallichiana with high anticancer potency on tumor cells
Authors: Wang Yong , Wang Jiaying , Wang Hao , Ye Wencai 
Published: May 2016

Four novel taxane derivatives, N‐debenzoyl‐N‐methyl‐N‐heptanoyl‐taxol (1), N‐debenzoyl‐N‐me‐thyl‐N‐octanoyl‐taxol (2), N‐debenzoyl‐N‐methyl‐N‐(4‐methylhexanoyl)‐taxol (3), and N‐debenzoyl‐N‐methyl‐N‐[(4Z)‐1‐oxo‐4‐tenenoyl]‐taxol (4), were isolated from the ethanol extract of the whole plant of Taxus wallichiana.var.mairer. These structures were identified on the basis of extensive spectroscopic analysis, and their antitumor activity was evaluated against MCF‐7, A549, and 3‐AO cancer cell lines by the MTT method. Compound 3, the most promising one, exhibited encouraging effect with IC50 of 77 nm in MCF‐7 cells, which was almost matching that of positive control Taxol. In further mechanism study, the tubulin polymerization assay demonstrated that four compounds caused shifts from the soluble tubulin (depolymerized tubulin) to the particulate tubulin fraction (polymerized) which was similar to Taxol. These results revealed novel natural products with paclitaxel‐likemicrotu‐bule‐stabilizing activity owned their major importance in the clinical treatment of cancer.
Review of paediatric retinal microvascular changes as a predictor of cardiovascular disease
Authors: Newman Alexander R , Andrew Nicholas H , Casson Robert J 
Published: May 2016

AbstractRecent studies have supported the hypothesis that exposure to established cardiovascular risk factors in early life predisposes to the development of adult cardiovascular disease. Retinal imaging is an emerging technique which facilitates non‐invasive, accurate and reproducible assessment of the retinal microvasculature. The assessment may be in the form of static vascular calibre measurements and assessment of the vascular geometry or dynamic structural and functional assessments. Paediatric retinal microvascular changes are reported in response to elevated blood pressure, type 1 diabetes, increasing adiposity, diet, physical activity, systemic inflammation, metabolic peptides, family history and prenatal factors. The resultant microvascular changes have been linked to sub‐clinical and overt cardiovascular, cerebrovascular and metabolic disease states in the adult population. Still missing however is longitudinal evidence showing the persistence of retinal microvascular alterations into adulthood. Future studies will enable retinal microvascular assessment to further evaluate the pathogenesis of disease states and response to intervention. The data obtained will also aid in expanding the clinical utility of retinal imaging as a cardiovascular risk prediction and monitoring tool and supplement existing recommendations to reduce cardiovascular morbidity and mortality.
Short‐ and long‐term outcomes of metformin compared with insulin alone in pregnancy: a systematic review and meta‐analysis
Authors: Butalia S. , Gutierrez L. , Lodha A. , Aitken E. , Zakariasen A. , Donovan L. 
Published: May 2016

AbstractAimTo assess the short‐ and long‐term maternal and fetal impact of metformin in pregnancy compared with insulin.MethodsWe performed a comprehensive literature search of MEDLINE, EMBASE, BIOSIS, Cochrane Database of Systematic Reviews and ClinicalTrials.gov. Eligible studies were randomized control trials (RCTs) or follow‐up of an RCT that: (1) compared metformin with insulin in pregnancy in women with gestational diabetes mellitus or Type 2 diabetes; and (2) reported maternal or fetal outcomes of interest. Two reviewers extracted the data, evaluated study quality and calculated pooled estimates.ResultsSixteen studies (n = 2165 in quantitative analysis) were included. Metformin lowered the risk of neonatal hypoglycaemia [risk ratio (RR) = 0.63; 95% confidence interval (95% CI), 0.45 to 0.87], large for gestational age babies (RR = 0.80; 95% CI, 0.64 to 0.99), pregnancy‐induced hypertension (RR = 0.56; 95% CI, 0.37 to 0.85) and total maternal pregnancy weight gain [mean difference (MD) –2.07; 95% CI –2.88 to –1.27]. Metformin did not increase preterm delivery (RR = 1.18; 95% CI 0.67 to 2.07), small for gestational age babies (RR = 1.20; 95% CI, 0.67 to 2.14), perinatal mortality (RR = 0.82; 95% CI, 0.17 to 3.92) or Caesarean section (RR = 0.97; 95% CI, 0.80 to 1.19). Long‐term outcome information is limited.ConclusionsOur review found that metformin had no short‐term adverse effects on pregnancy, potential benefits in the neonatal period, but limited long‐term follow‐up information. Prior to routine use, we recommend further follow‐up studies of offspring exposed to metformin in utero.
Sleep duration and quality, and risk of gestational diabetes mellitus in pregnant Chinese women
Authors: Wang H. , Leng J. , Li W. , Wang L. , Zhang C. , Li W. , Liu H. , Zhang S. , Chan J. , Hu G. , Yu Z. , Yang X. 
Published: May 2016

AbstractAimsTo examine the association between sleep disturbances during pregnancy and risk of gestational diabetes mellitus.MethodsFrom 2010 to 2012, 12 506 women in Tianjin, China, were screened using a 50‐g 1‐h glucose challenge test at 24–28 weeks’ gestation. Those with glucose challenge test values of ≥ 7.8 mmol/l were invited to further undergo a 75‐g 2‐h oral glucose tolerance test. Gestational diabetes was determined according to the International Association of Diabetes and Pregnancy Study Group's definition. Self‐reported sleep duration and sleep quality during pregnancy was documented using a modified questionnaire. Logistic regression was used to obtain odds ratios and 95% CIs.ResultsA total of 919 women (7.3%) had gestational diabetes. Sleep duration was found to have an approximate J‐shaped association with gestational diabetes risk after adjusting for covariates. Compared with a sleep duration of 7–9 h/day (43% of 12 506 women), the adjusted odds ratios for sleep duration of ≥ 9 h/day (55%) and < 7 h/day (2%) for gestational diabetes were 1.21 (95% CI 1.03–1.42) and 1.36 (95% CI 0.87–2.14), respectively. Compared with good sleep quality (37.9% of 12 506 women), the adjusted odds ratios of moderate (59.9%) and poor sleep quality (2.2%) for gestational diabetes were 1.19 (95% CI 1.01–1.41) and 1.61 (95% CI 1.04–2.50), respectively.ConclusionIn pregnant Chinese women, poor sleep quality, and shorter and longer duration of sleep during pregnancy were independently associated with an increased risk of gestational diabetes.
Temporal cuing modulates alpha oscillations during auditory attentional blink
Authors: Shen Dawei , Ross Bernhard , Alain Claude 
Published: May 2016

AbstractAttentional blink (AB) refers to the phenomenon whereby the correct identification of a visual or auditory target impairs processing of a subsequent probe. Although it has been shown that knowing in advance, when the probe would be presented, reduces the attentional blink and increases the amplitude of event‐related potential (ERP) elicited by the probe, the neural mechanism by which attention mitigates the AB remains unclear. Here, we used time‐frequency analysis to further explore the mechanism of the auditory attentional blink. Participants were presented a series of rapid auditory stimuli and asked to indicate whether a target and a probe were present in the sequence. In half of the trials, participants were cued to the probe position relative to the target (‘Early’ or ‘Late’). Probe detection and ERP amplitude elicited by the probe decreased when the probe was presented shortly after the target compared to when it was presented later after the target. Importantly, the behavioral and ERP correlates of probe discrimination significantly improved when the ‘Early’ cue was presented. The improvement in processing the probe in the cued condition was accompanied by the decrease in alpha activity (8–13 Hz) after the time when the probe was expected; suggesting that successfully directing attention to time window where the probe would likely occur reduces the processing resources needed to suppress distractors. This in turn freed up available processing resources for the target and probe at the short‐term consolidation stage, which ultimately reduced the auditory attentional blink.
Thalamic amplification of sensory input in experimental diabetes
Authors: Freeman Oliver J. , Evans Mathew H. , Cooper Garth J. S. , Petersen Rasmus S. , Gardiner Natalie J. 
Published: May 2016

AbstractDiabetic neuropathy is a common, and often debilitating, secondary complication of diabetes mellitus. As pain, hypersensitivity and paraesthesias present in a distal–proximal distribution, symptoms are generally believed to originate from damaged afferents within the peripheral nervous system. Increasing evidence suggests altered processing within the central nervous system in diabetic neuropathy contributes towards somatosensory dysfunction, but whether the accurate coding and relay of peripherally encoded information through the central nervous system is altered in diabetes is not understood. Here, we applied the strengths of the rodent whisker–barrel system to study primary afferent‐thalamic processing in diabetic neuropathy. We found that neurons in the thalamic ventral posteromedial nucleus from rats with experimental diabetic neuropathy showed increased firing to precisely graded, multidirectional whisker deflection compared to non‐diabetic rats. This thalamic hyperactivity occurred without any overt primary afferent dysfunction, as recordings from the trigeminal ganglion showed these primary afferents to be unaffected by diabetes. These findings suggest that central amplification can substantially transform ascending sensory input in diabetes, even in the absence of a barrage of ectopic primary afferent activity.
Involvement of oxidative stress and impaired lysosomal degradation in amiodarone‐induced schwannopathy
Authors: Niimi Naoko , Yako Hideji , Tsukamoto Masami , Takaku Shizuka , Yamauchi Junji , Kawakami Emiko , Yanagisawa Hiroko , Watabe Kazuhiko , Utsunomiya Kazunori , Sango Kazunori 
Published: May 2016

AbstractAmiodarone hydrochloride (AMD), an anti‐arrhythmic agent, has been shown to cause peripheral neuropathy; however, its pathogenesis remains unknown. We examined the toxic effects of AMD on an immortalized adult rat Schwann cell line, IFRS1, and cocultures of IFRS1 cells and adult rat dorsal root ganglion neurons or nerve growth factor‐primed PC12 cells. Treatment with AMD (1, 5, and 10 μm) induced time‐ and dose‐dependent cell death, accumulation of phospholipids and neutral lipids, upregulation of the expression of gangliosides, and oxidative stress (increased nuclear factor E2‐related factor in nuclear extracts and reduced GSH/GSSG ratios) in IFRS1 cells. It also induced the upregulation of LC3‐II and p62 expression, with phosphorylation of p62, suggesting that deficient autolysosomal degradation is involved in AMD‐induced IFRS1 cell death. Furthermore, treatment of the cocultures with AMD induced detachment of IFRS1 cells from neurite networks in a time‐ and dose‐dependent manner. These findings suggest that AMD‐induced lysosomal storage accompanied by enhanced oxidative stress and impaired lysosomal degradation in Schwann cells might be a cause of demyelination in the peripheral nervous system.
Multiple asynchronous stimulus‐ and task‐dependent hierarchies (STDH) within the visual brain's parallel processing systems
Authors: Zeki Semir 
Published: May 2016

AbstractResults from a variety of sources, some many years old, lead ineluctably to a re‐appraisal of the twin strategies of hierarchical and parallel processing used by the brain to construct an image of the visual world. Contrary to common supposition, there are at least three ‘feed‐forward’ anatomical hierarchies that reach the primary visual cortex (V1) and the specialized visual areas outside it, in parallel. These anatomical hierarchies do not conform to the temporal order with which visual signals reach the specialized visual areas through V1. Furthermore, neither the anatomical hierarchies nor the temporal order of activation through V1 predict the perceptual hierarchies. The latter shows that we see (and become aware of) different visual attributes at different times, with colour leading form (orientation) and directional visual motion, even though signals from fast‐moving, high‐contrast stimuli are among the earliest to reach the visual cortex (of area V5). Parallel processing, on the other hand, is much more ubiquitous than commonly supposed but is subject to a barely noticed but fundamental aspect of brain operations, namely that different parallel systems operate asynchronously with respect to each other and reach perceptual endpoints at different times. This re‐assessment leads to the conclusion that the visual brain is constituted of multiple, parallel and asynchronously operating task‐ and stimulus‐dependent hierarchies (STDH); which of these parallel anatomical hierarchies have temporal and perceptual precedence at any given moment is stimulus and task related, and dependent on the visual brain's ability to undertake multiple operations asynchronously.
Crystallographic analysis on small fatigue crack propagation behaviour of a nickel‐based single crystal superalloy
Authors: Qiu W. , Ma X. , Rui S. , Shi H.‐J. 
Published: May 2016

AbstractIn situ observations by scanning electron microscopy show that small fatigue cracks in a nickel‐based single crystal superalloy are inclined to the loading direction and propagate in dominant crystallographic manners. In order to evaluate the driving forces for inclined crack propagation, three‐dimensional anisotropic linear elastic finite‐element analysis is conducted. The plastic zone size on the dominant slip plane has been calculated and proposed to correlate the fatigue crack growth. It is shown that this parameter takes into account both material anisotropy and octahedral fracture modes, and it can effectively characterize small crack propagation behaviour.
Fine‐scale climate change: modelling spatial variation in biologically meaningful rates of warming
Authors: Maclean Ilya M. D. , Suggitt Andrew J. , Wilson Robert J. , Duffy James P. , Bennie Jonathan J. 
Published: May 2016

AbstractThe existence of fine‐grain climate heterogeneity has prompted suggestions that species may be able to survive future climate change in pockets of suitable microclimate, termed ‘microrefugia’. However, evidence for microrefugia is hindered by lack of understanding of how rates of warming vary across a landscape. Here, we present a model that is applied to provide fine‐grained, multidecadal estimates of temperature change based on the underlying physical processes that influence microclimate. Weather station and remotely derived environmental data were used to construct physical variables that capture the effects of terrain, sea surface temperatures, altitude and surface albedo on local temperatures, which were then calibrated statistically to derive gridded estimates of temperature. We apply the model to the Lizard Peninsula, United Kingdom, to provide accurate (mean error = 1.21 °C; RMS error = 1.63 °C) hourly estimates of temperature at a resolution of 100 m for the period 1977–2014. We show that rates of warming vary across a landscape primarily due to long‐term trends in weather conditions. Total warming varied from 0.87 to 1.16 °C, with the slowest rates of warming evident on north‐east‐facing slopes. This variation contributed to substantial spatial heterogeneity in trends in bioclimatic variables: for example, the change in the length of the frost‐free season varied from +11 to −54 days and the increase in annual growing degree‐days from 51 to 267 °C days. Spatial variation in warming was caused primarily by a decrease in daytime cloud cover with a resulting increase in received solar radiation, and secondarily by a decrease in the strength of westerly winds, which has amplified the effects on temperature of solar radiation on west‐facing slopes. We emphasize the importance of multidecadal trends in weather conditions in determining spatial variation in rates of warming, suggesting that locations experiencing least warming may not remain consistent under future climate change.