bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are sample sizes of randomized clinical trials in rheumatoid arthritis too large?
Authors: Celik Selda , Yazici Yusuf , Yazici Hasan 
Published: September 2014

AbstractObjectiveWe had the impression that randomized clinical trials (RCTs) frequently over enrolled patients. Thus, we surveyed power calculations in publications of RCTs of biologics in rheumatoid arthritis (RA) to assess over enrollment.MethodsA PubMed search identified 40 reports of original RCTs testing the efficacy of infliximab, etanercept, adalimumab, abatacept, rituximab and tocilizumab in patients with RA. As a first analysis, based on a two equal arms study with an alpha error of 0·05 and a power of 80% and of 90%, recalculation of the sample size was performed using the primary outcome results. In the second analysis, only those studies with equal number of patients in both arms and also in which all elements of a power calculation were given, were considered. New sample sizes were calculated based on the presented power elements in the related publications.ResultsIn the first analysis, when we assigned a power of 80% and of 90%, 32 of 40 (80%) studies enrolled more than required number of patients, with a mean 131 ± 147 (SD), and 31 of 40 (78%) studies having had enrolled extra patients, with a mean 121 ± 147 (SD) in their treatment arms, respectively. Eleven studies qualified for the second analysis. There were still more patients with a mean of 48 ± 30 (SD) extra patients enrolled in the treatment arms.ConclusionMost RCTs in RA enrol more patients than needed. This is costly and has the immediate consequence of exposing needless number of patients to potential harm.
Transition issues for children with diffuse cortical malformations, multifocal postnatal lesions, (infectious and traumatic) and Lennox–Gastaut and similar syndromes
Authors: Camfield Peter R. , Bahi‐Buisson Nadia , Trinka Eugen 
Published: September 2014

SummaryPatients with epilepsy may have diffuse, serious brain disorders including genetically determined, multilobar malformations, traumatic brain injury, encephalitis and meningitis, and the many causes of Lennox‐Gastaut syndrome. Transition to adult care needs to consider concomitant intellectual disability, refractory epilepsy, underlying cause, and other nonneurologic but significant problems, especially for genetic etiologies. Adult epilepsy care coupled with dedicated primary/family care is essential. A multidisciplinary setting may be optimal to address the many issues of clinical care, decision making, custody, and ongoing supervision.
Transition to adult life in the monogenic epilepsies
Authors: Scheffer Ingrid E. , Dravet Charlotte 
Published: September 2014

SummaryThere are many monogenic disorders associated with epilepsy that begin in childhood and persist into adult life. Each of these disorders raises specific issues for transition, in addition to common issues facing this group of patients as they move from pediatric to adult care. Such comorbidities include psychiatric and movement disorders. Epileptic encephalopathies may be caused by monogenic disorders, with Dravet syndrome being the best characterized. Although some patients have a relatively good adult outcome, others have persisting severe epilepsy complicated by autistic spectrum disorder and problems with gait. When reevaluating a patient as they transition to adult care, a thorough reconsideration of the genetic etiology of their epilepsy should be performed. This should be followed by genetic counseling for the patient and their family members.
Forest ecosystem respiration estimated from eddy covariance and chamber measurements under high turbulence and substantial tree mortality from bark beetles
Authors: Speckman Heather N. , Frank John M. , Bradford John B. , Miles Brianna L. , Massman William J. , Parton William J. , Ryan Michael G. 
Published: September 2014

AbstractEddy covariance nighttime fluxes are uncertain due to potential measurement biases. Many studies report eddy covariance nighttime flux lower than flux from extrapolated chamber measurements, despite corrections for low turbulence. We compared eddy covariance and chamber estimates of ecosystem respiration at the GLEES Ameriflux site over seven growing seasons under high turbulence [summer night mean friction velocity (u*) = 0.7 m s−1], during which bark beetles killed or infested 85% of the aboveground respiring biomass. Chamber‐based estimates of ecosystem respiration during the growth season, developed from foliage, wood, and soil CO2 efflux measurements, declined 35% after 85% of the forest basal area had been killed or impaired by bark beetles (from 7.1 ± 0.22 μmol m−2 s−1 in 2005 to 4.6 ± 0.16 μmol m−2 s−1 in 2011). Soil efflux remained at ~3.3 μmol m−2 s−1 throughout the mortality, while the loss of live wood and foliage and their respiration drove the decline of the chamber estimate. Eddy covariance estimates of fluxes at night remained constant over the same period, ~3.0 μmol m−2 s−1 for both 2005 (intact forest) and 2011 (85% basal area killed or impaired). Eddy covariance fluxes were lower than chamber estimates of ecosystem respiration (60% lower in 2005, and 32% in 2011), but the mean night estimates from the two techniques were correlated within a year (r2 from 0.18 to 0.60). The difference between the two techniques was not the result of inadequate turbulence, because the results were robust to a u* filter of >0.7 m s−1. The decline in the average seasonal difference between the two techniques was strongly correlated with overstory leaf area (r2 = 0.92). The discrepancy between methods of respiration estimation should be resolved to have confidence in ecosystem carbon flux estimates.
Pollen‐based quantitative reconstructions of Holocene regional vegetation cover (plant‐functional types and land‐cover types) in Europe suitable for climate modelling
Authors: Trondman A.‐K. , Gaillard M.‐J. , Mazier F. , Sugita S. , Fyfe R. , Nielsen A. B. , Twiddle C. , Barratt P. , Birks H. J. B. , Bjune A. E. , Björkman L. , Broström A. , Caseldine C. , David R. , Dodson J. , Dörfler W. , Fischer E. , van Geel B. , Giesecke T. , Hultberg T. , Kalnina L. , Kangur M. , van der Knaap P. , Koff T. , Kuneš P. , Lagerås P. , Latałowa M. , Lechterbeck J. , Leroyer C. , Leydet M. , Lindbladh M. , Marquer L. , Mitchell F. J. G. , Odgaard B. V. , Peglar S. M. , Persson T. , Poska A. , Rösch M. , Seppä H. , Veski S. , Wick L. 
Published: September 2014

AbstractWe present quantitative reconstructions of regional vegetation cover in north‐western Europe, western Europe north of the Alps, and eastern Europe for five time windows in the Holocene [around 6k, 3k, 0.5k, 0.2k, and 0.05k calendar years before present (bp)] at a 1° × 1° spatial scale with the objective of producing vegetation descriptions suitable for climate modelling. TheREVEALSmodel was applied on 636 pollen records from lakes and bogs to reconstruct the past cover of 25 plant taxa grouped into 10 plant‐functional types and three land‐cover types [evergreen trees, summer‐green (deciduous) trees, and open land]. The model corrects for some of the biases in pollen percentages by using pollen productivity estimates and fall speeds of pollen, and by applying simple but robust models of pollen dispersal and deposition. The emerging patterns of tree migration and deforestation between 6kbpand modern time in theREVEALSestimates agree with our general understanding of the vegetation history of Europe based on pollen percentages. However, the degree of anthropogenic deforestation (i.e. cover of cultivated and grazing land) at 3k, 0.5k, and 0.2kbpis significantly higher than deduced from pollen percentages. This is also the case at 6k in some parts of Europe, in particular Britain and Ireland. Furthermore, the relationship between summer‐green and evergreen trees, and between individual tree taxa, differs significantly when expressed as pollen percentages or asREVEALSestimates of tree cover. For instance, whenPinusis dominant overPiceaas pollen percentages,Piceais dominant overPinusasREVEALSestimates. These differences play a major role in the reconstruction of European landscapes and for the study of land cover–climate interactions, biodiversity and human resources.
Long‐term dexamethasone treatment alters the histomorphology of acinar cells in rat parotid and submandibular glands
Authors: Bighetti Bruna B. , Assis Gerson F. d. , Vieira Danilo C. , Violato Natalia M. , Cestari Tania M. , Taga Rumio , Bosqueiro José R. , Rafacho Alex 
Published: September 2014

SummaryGlucocorticoids (GCs) induce insulin resistance (IR), a condition known to alter oral homeostasis. This study investigated the effects of long‐term dexamethasone administration on morphofunctional aspects of salivary glands. Male Wistar rats received daily injections of dexamethasone [0.1 mg/kg body weight (b.w.), intraperitoneally] for 10 days (DEX), whereas control rats received saline. Subsequently, glycaemia, insulinaemia, insulin secretion and salivary flow were analysed. The parotid and submandibular glands were collected for histomorphometric evaluation and Western blot experiments. The DEX rats were found to be normoglycaemic, hyperinsulinaemic, insulin resistant and glucose intolerant (P < 0.05). DEX rat islets secreted more insulin in response to glucose (P < 0.05). DEX rats had significant reductions in the masses of the parotid (29%) and submandibular (16%) glands (P < 0.05) that was associated with reduced salivary flux rate. The hypotrophy in both glands observed in the DEX group was associated with marked reduction in the volume of the acinar cells in these glands of 50% and 26% respectively (P < 0.05). The total number of acinar cells was increased in the submandibular glands of the DEX rats (P < 0.05) but not in the parotid glands. The levels of proteins related to insulin and survival signalling in both glands did not differ between the groups. In conclusion, the long‐term administration of dexamethasone caused IR, which was associated with significant reductions in both mass and flux rate of the salivary glands. The parotid and submandibular glands exhibited reduced acinar cell volume; however, the submandibular glands displayed acinar hyperplasia, indicating a gland‐specific response to GCs. Our data emphasize that GC‐based therapies and insulin‐resistant states have a negative impact on salivary gland homeostasis.
Creating internal conductivity in dry biological SEM samples by a simple vapour treatment
Authors: ENSIKAT H.‐J. , WEIGEND M. 
Published: September 2014

SummaryInternal sample conductivity in scanning electron microscopy can be a valuable alternative to metal coating. Proton conductivity may be used for this purpose. Many solid materials with active hydrogen atoms, such as hydrogen‐ and ammonium‐salts, organic acids, and even ice, are protonic conductors or semiconductors. Here we present a method to generate proton conductivity in dry biological materials. A simple treatment with hydrogen chloride gas or hydrochloric acid vapour for a few minutes provides sufficient conductivity for many samples. After a removal of excess hydrogen chloride vapour with a vacuum desiccator, the objects may be examined in the SEM without metal coating. The use of internally conductive samples extends the range of easy‐to‐perform SEM preparation techniques. It is advantageous for material contrast imaging of uncoated samples, and it can be used in combination with metal coating to enhance conductivity on difficult samples with complex overlapping surfaces, where simple metal coating does not reliably eliminate charging problems.
The relationship between a night's sleep and subsequent daytime functioning in older poor and good sleepers
Authors: Smith Rashelle A. , Lack Leon C. , Lovato Nicole , Wright Helen 
Published: September 2014

SummaryThose suffering insomnia symptoms generally report daytime impairments. However, research has not assessed whether this relationship holds on a nightly basis, despite the strongly held belief that a night of poor sleep impairs mood and functioning the following day. The objective of this study was to test this relationship in a group of older poor sleepers with insomnia symptoms compared with good sleepers. This study utilized a within‐subjects design to investigate day‐to‐day subjective daytime functioning and its relation to the previous night's sleep. Seventeen older individuals (mean age: 67.5 years) were identified with a retrospective questionnaire and 2 weeks of sleep–wake diary to have poor sleep consistent with insomnia. Seventeen good sleepers (mean age: 67.8 years) were selected using the same measures. Participants reported their beliefs about sleep and daytime functioning on the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS‐16). One week later they commenced a 14‐day period of sleep–wake diaries and concurrent responses to a modified Daytime Insomnia Symptom Scale (DISS). Results showed significant night‐to‐day covariation between sleep efficiency and daytime functioning for individuals with poor sleep (r = 0.34), but not for good sleepers (r = 0.08). Those poor sleepers who held this covariation belief most strongly were those who subsequently showed this night‐to‐day relationship the most strongly (r = 0.56). This was not true for good sleepers. For those suffering insomnia, these findings demonstrate their belief that a poor sleep is followed by an impaired daytime, consistent with their experience.
Is there a species spectrum within the world‐wide leaf economics spectrum? Major variations in leaf functional traits in the Mediterranean sclerophyll Quercus ilex
Authors: Niinemets Ülo 
Published: September 2014

SummaryThe leaf economics spectrum is a general concept describing coordinated variation in foliage structural, chemical and physiological traits across resource gradients. Yet, within this concept, the role of within‐species variation, including ecotypic and plastic variation components, has been largely neglected. This study hypothesized that there is a within‐species economics spectrum within the general spectrum in the evergreen sclerophyll Quercus ilex which dominates low resource ecosystems over an exceptionally wide range. An extensive database of foliage traits covering the full species range was constructed, and improved filtering algorithms were developed. Standardized data filtering was deemed absolutely essential as additional variation sources can result in trait variation of 10–300%, blurring the broad relationships. Strong trait variation, c. two‐fold for most traits to up to almost an order of magnitude, was uncovered. Although the Q. ilex spectrum is part of the general spectrum, within‐species trait and climatic relationships in this species partly differed from the overall spectrum. Contrary to world‐wide trends, Q. ilex does not necessarily have a low nitrogen content per mass and can increase photosynthetic capacity with increasing foliage robustness. This study argues that the within‐species economics spectrum needs to be considered in regional‐ to biome‐level analyses.
Insights from the cold transcriptome of Physcomitrella patens: global specialization pattern of conserved transcriptional regulators and identification of orphan genes involved in cold acclimation
Authors: Beike Anna K. , Lang Daniel , Zimmer Andreas D. , Wüst Florian , Trautmann Danika , Wiedemann Gertrud , Beyer Peter , Decker Eva L. , Reski Ralf 
Published: September 2014

Summary

The whole‐genome transcriptomic cold stress response of the moss Physcomitrella patens was analyzed and correlated with phenotypic and metabolic changes.

Based on time‐series microarray experiments and quantitative real‐time polymerase chain reaction, we characterized the transcriptomic changes related to early stress signaling and the initiation of cold acclimation. Transcription‐associated protein (TAP)‐encoding genes of P. patens and Arabidopsis thaliana were classified using generalized linear models. Physiological responses were monitored with pulse‐amplitude‐modulated fluorometry, high‐performance liquid chromatography and targeted high‐performance mass spectrometry.

The transcript levels of 3220 genes were significantly affected by cold. Comparative classification revealed a global specialization of TAP families, a transcript accumulation of transcriptional regulators of the stimulus/stress response and a transcript decline of developmental regulators.

Although transcripts of the intermediate to later response are from evolutionarily conserved genes, the early response is dominated by species‐specific genes. These orphan genes may encode as yet unknown acclimation processes.
Insect and pathogen attack and resistance in maize and its wild ancestors, the teosintes
Authors: de Lange Elvira S. , Balmer Dirk , Mauch‐Mani Brigitte , Turlings Ted C. J. 
Published: September 2014

SummaryMaize (Zea mays ssp. mays) is one of the most important crops worldwide and there are many reports in the literature on its constitutive and inducible defenses against pathogens and insects. However, research on its wild ancestors, the teosintes, with respect to resistance against these antagonists is limited. Here, we review what is known about the different arthropods and microbes that are associated with maize and teosintes in Mexico and Central America, the area of origin, and evaluate the plants' mechanisms of resistance against biotic stresses. Teosintes appear to have greater resistance against a number of pests than their cultivated counterpart. We therefore highlight the need to study the teosintes in order to identify resistance traits that can be improved in maize. As teosintes are at risk of becoming extinct, there is a need to protect their germplasm for future generations.
Histamine H4 receptor in oral lichen planus
Authors: Salem A , Al‐Samadi A , Stegajev V , Stark H , Häyrinen‐Immonen R , Ainola M , Hietanen J , Konttinen YT 
Published: September 2014

ObjectivesOral lichen planus (OLP) is an autoimmune disease characterized by a band‐like T‐cell infiltrate below the apoptotic epithelial cells and degenerated basement membrane. We tested the hypothesis that the high‐affinity histamine H4 receptors (H4Rs) are downregulated in OLP by high histamine concentrations and proinflammatory T‐cell cytokines.Materials and MethodsImmunohistochemistry and immunofluorescence staining, image analysis and quantitative real‐time polymerase chain reaction of tissue samples and cytokine‐stimulated cultured SCC‐25 and primary human oral keratinocytes.ResultsH4R immunoreactivity was weak in OLP and characterized by mast cell (MC) hyperplasia and degranulation. In contrast to controls, H4R immunostaining and MC counts were negatively correlated in OLP (P = 0.003). H4R agonist at nanomolar levels led to a rapid internalization of H4Rs, whereas high histamine concentration and interferon‐γ decreased HRH4‐gene transcripts.ConclusionHealthy oral epithelial cells are equipped with H4R, which displays a uniform staining pattern in a MC‐independent fashion. In contrast, in OLP, increased numbers of activated MCs associate with increasing loss of epithelial H4R. Cell culture experiments suggest a rapid H4R stimulation‐dependent receptor internalization and a slow cytokine‐driven decrease in H4R synthesis. H4R may be involved in the maintenance of healthy oral mucosa. In OLP, this maintenance might be impaired by MC degranulation and inflammatory cytokines.
Modulation of IL‐33/ST2‐TIR and TLR Signalling Pathway by Fingolimod and Analogues in Immune Cells
Authors: Rüger K. , Ottenlinger F. , Schröder M. , Živković A. , Stark H. , Pfeilschifter J. M. , Radeke H. H. 
Published: September 2014

AbstractFor the immune modulatory drug fingolimod (FTY720), lymphocyte sequestration has been extensively studied and accepted as mode of action. Further, direct effects on immune cell signalling are incompletely understood. Herein, we used the parent drug and newly synthesized analogues to investigate their effects on dendritic cell (DC) calcium signalling and on Th1, Th2 and Th17 responses. DC calcium signalling was determined with a single cell‐based confocal assay and IL‐33/ST2‐TIR Th2‐like response with ST2‐transduced EL4‐6.1 thymoma cells. The Th1/Th17 responses were examined with a LPS/TLR‐enhanced antigen presentation assay with OVA‐TCRtg CD4 and CD8 spleen cells. Our results revealed a comparable influence of fingolimod and S1P on intracellular calcium level in DC, while an oxy‐derivative of fingolimod exhibited an EC50 of 3.3 nm, being 14 times more potent than FTY720‐P. The IL‐33/ST2‐TIR Th2‐like response in ST2‐EL4 cells was inhibited by fingolimod and analogues at varying degrees. Using the OVA‐TCRtg LPS/TLR‐enhanced spleen cell assay, we found that fingolimod inhibited both IL‐17 and IFN‐γ production. In contrast, fingolimod phosphate failed to decrease Th1 cytokines. Interestingly, the effects of the parent compound fingolimod were modulated by the PP2A inhibitor okadaic acid, thus suggesting PP2A as relevant intracellular target. These studies describe detailed immune‐modulating properties of fingolimod, including interference with a prototypical Th2 response via IL‐33/ST2‐TIR. Moreover, differential effects of fingolimod versus its phosphorylated derivative on TLR‐activated and antigen‐dependent Th1 activation suggest PP2A as an additional target of fingolimod immune therapy. Together with the analogues tested, these data may guide the development of more specific fingolimod derivatives.
Optimal and Robust Designs for Estimating the Concentration Curve and the AUC
Authors: Belouni Mohamad , Benhenni Karim 
Published: September 2014

AbstractThe problem of interest is to estimate the concentration curve and the area under the curve (AUC) by estimating the parameters of a linear regression model with an autocorrelated error process. We introduce a simple linear unbiased estimator of the concentration curve and the AUC. We show that this estimator constructed from a sampling design generated by an appropriate density is asymptotically optimal in the sense that it has exactly the same asymptotic performance as the best linear unbiased estimator. Moreover, we prove that the optimal design is robust with respect to a minimax criterion. When repeated observations are available, this estimator is consistent and has an asymptotic normal distribution. Finally, a simulated annealing algorithm is applied to a pharmacokinetic model with correlated errors.
Using genic sequence capture in combination with a syntenic pseudo genome to map a deletion mutant in a wheat species
Authors: Gardiner Laura‐Jayne , Gawroński Piotr , Olohan Lisa , Schnurbusch Thorsten , Hall Neil , Hall Anthony 
Published: September 2014

SummaryMapping‐by‐sequencing analyses have largely required a complete reference sequence and employed whole genome re‐sequencing. In species such as wheat, no finished genome reference sequence is available. Additionally, because of its large genome size (17 Gb), re‐sequencing at sufficient depth of coverage is not practical. Here, we extend the utility of mapping by sequencing, developing a bespoke pipeline and algorithm to map an early‐flowering locus in einkorn wheat (Triticum monococcum L.) that is closely related to the bread wheat genome A progenitor. We have developed a genomic enrichment approach using the gene‐rich regions of hexaploid bread wheat to design a 110‐Mbp NimbleGen SeqCap EZ in solution capture probe set, representing the majority of genes in wheat. Here, we use the capture probe set to enrich and sequence an F2 mapping population of the mutant. The mutant locus was identified in T. monococcum, which lacks a complete genome reference sequence, by mapping the enriched data set onto pseudo‐chromosomes derived from the capture probe target sequence, with a long‐range order of genes based on synteny of wheat with Brachypodium distachyon. Using this approach we are able to map the region and identify a set of deleted genes within the interval.