bluuebunny/crossref_metadata_2025_split huggingface dataset:
Muscle Weakness Predicts Pharyngeal Dysfunction and Symptomatic Aspiration in Long-term Ventilated Patients
Authors: Mirzakhani Hooman , Williams June-Noelle , Mello Jennifer , Joseph Sharma , Meyer Matthew J. , Waak Karen , Schmidt Ulrich , Kelly Emer , Eikermann Matthias 
Published: April 2013

Abstract

Background:
Prolonged mechanical ventilation is associated with muscle weakness, pharyngeal dysfunction, and symptomatic aspiration. The authors hypothesized that muscle strength measurements can be used to predict pharyngeal dysfunction (endoscopic evaluation–primary hypothesis), as well as symptomatic aspiration occurring during a 3-month follow-up period.

Methods:
Thirty long-term ventilated patients admitted in two intensive care units at Massachusetts General Hospital were included. The authors conducted a fiberoptic endoscopic evaluation of swallowing and measured muscle strength using medical research council score within 24 h of each fiberoptic endoscopic evaluation of swallowing. A medical research council score less than 48 was considered clinically meaningful muscle weakness. A retrospective chart review was conducted to identify symptomatic aspiration events.

Results:
Muscle weakness predicted pharyngeal dysfunction, defined as either valleculae and pyriform sinus residue scale of more than 1, or penetration aspiration scale of more than 1. Area under the curve of the receiver-operating curves for muscle strength (medical research council score) to predict pharyngeal, valleculae, and pyriform sinus residue scale of more than 1, penetration aspiration scale of more than 1, and symptomatic aspiration were 0.77 (95% CI, 0.63–0.97; P = 0.012), 0.79 (95% CI, 0.56–1; P = 0.02), and 0.74 (95% CI, 0.56–0.93; P = 0.02), respectively. Seventy percent of patients with muscle weakness showed symptomatic aspiration events. Muscle weakness was associated with an almost 10-fold increase in the symptomatic aspiration risk (odds ratio = 9.8; 95% CI, 1.6–60; P = 0.009).

Conclusion:
In critically ill patients, muscle weakness is an independent predictor of pharyngeal dysfunction and symptomatic aspiration. Manual muscle strength testing may help identify patients at risk of symptomatic aspiration.
A Significant Fraction of 21-Nucleotide Small RNA Originates from Phased Degradation of Resistance Genes in Several Perennial Species
Authors: Källman Thomas , Chen Jun , Gyllenstrand Niclas , Lagercrantz Ulf 
Published: April 2013

Abstract
Small RNAs (sRNAs), including microRNA (miRNA) and short-interfering RNA (siRNA), are important in the regulation of diverse biological processes. Comparative studies of sRNAs from plants have mainly focused on miRNA, even though they constitute a mere fraction of the total sRNA diversity. In this study, we report results from an in-depth analysis of the sRNA population from the conifer spruce (Picea abies) and compared the results with those of a range of plant species. The vast majority of sRNA sequences in spruce can be assigned to 21-nucleotide-long siRNA sequences, of which a large fraction originate from the degradation of transcribed sequences related to nucleotide-binding site-leucine-rich repeat-type resistance genes. Over 90% of all genes predicted to contain either a Toll/interleukin-1 receptor or nucleotide-binding site domain showed evidence of siRNA degradation. The data further suggest that this phased degradation of resistance-related genes is initiated from miRNA-guided cleavage, often by an abundant 22-nucleotide miRNA. Comparative analysis over a range of plant species revealed a huge variation in the abundance of this phenomenon. The process seemed to be virtually absent in several species, including Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa), and nonvascular plants, while particularly high frequencies were observed in spruce, grape (Vitis vinifera), and poplar (Populus trichocarpa). This divergent pattern might reflect a mechanism to limit runaway transcription of these genes in species with rapidly expanding nucleotide-binding site-leucine-rich repeat gene families. Alternatively, it might reflect variation in a counter-counter defense mechanism between plant species.
A Guanine Nucleotide Exchange Factor for Rab5 Proteins Is Essential for Intracellular Transport of the Proglutelin from the Golgi Apparatus to the Protein Storage Vacuole in Rice Endosperm
Authors: Fukuda Masako , Wen Liuying , Satoh-Cruz Mio , Kawagoe Yasushi , Nagamura Yoshiaki , Okita Thomas W. , Washida Haruhiko , Sugino Aya , Ishino Sonoko , Ishino Yoshizumi , Ogawa Masahiro , Sunada Mariko , Ueda Takashi , Kumamaru Toshihiro 
Published: April 2013

AbstractRice (Oryza sativa) glutelins are synthesized on the endoplasmic reticulum as a precursor, which are then transported via the Golgi to protein storage vacuoles (PSVs), where they are proteolytically processed into acidic and basic subunits. The glutelin precursor mutant6 (glup6) accumulates abnormally large amounts of proglutelin. Map-base cloning studies showed that glup6 was a loss-of-function mutant of guanine nucleotide exchange factor (GEF), which activates Rab GTPase, a key regulator of membrane trafficking. Immunofluorescence studies showed that the transport of proglutelins and α-globulins to PSV was disrupted in glup6 endosperm. Secreted granules of glutelin and α-globulin were readily observed in young glup6 endosperm, followed by the formation of large dilated paramural bodies (PMBs) containing both proteins as the endosperm matures. The PMBs also contained membrane biomarkers for the Golgi and prevacuolar compartment as well as the cell wall component, β-glucan. Direct evidence was gathered showing that GLUP6/GEF activated in vitro GLUP4/Rab5 as well as several Arabidopsis (Arabidopsis thaliana) Rab5 isoforms to the GTP-bound form. Therefore, loss-of-function mutations in GEF or Rab5 disrupt the normal transport of proglutelin from the Golgi to PSVs, resulting in the initial extracellular secretion of these proteins followed, in turn, by the formation of PMBs. Overall, our results indicate that GLUP6/GEF is the activator of Rab5 GTPase and that the cycling of GTP- and GDP-bound forms of this regulatory protein is essential for the intracellular transport of proglutelin and α-globulin from the Golgi to PSVs and in the maintenance of the general structural organization of the endomembrane system in rice seeds.
Predicting the development of acute kidney injury in liver cirrhosis – an analysis of glomerular filtration rate, proteinuria and kidney injury biomarkers
Authors: Slack A. J. , McPhail M. J. W. , Ostermann M. , Bruce M. , Sherwood R. , Musto R. , Dew T. , Auzinger G. , Bernal W. , O'Grady J. , Heneghan M. A. , Moore K. , Wendon J. A. 
Published: April 2013

SummaryBackgroundThe timely diagnosis of acute kidney injury (AKI) in liver cirrhosis is challenging.AimTo evaluate whether quantification of glomerular filtration rate (GFR), proteinuria and kidney injury biomarkers can accurately predict the development of AKI.MethodsA prospective cohort analysis of patients with cirrhosis was performed. Measures of baseline kidney function included serum creatinine, iohexol clearance and urine protein:creatinine ratio. Blood and urine samples were collected daily. A retrospective analysis of cystatin C GFR and neutrophil gelatinase‐associated lipocalin (NGAL) measured 48 h prior to the diagnosis of AKI was undertaken to evaluate their ability to predict the development of AKI.ResultsEighteen of the 34 cirrhosis patients studied developed AKI. A GFR <60 mL/min/1.73 m2 was identified in 56% with Iohexol clearance compared to 8% using the four‐variable modified diet in renal disease formula (P < 0.0001). Prediction of AKI, 48 h prior to the development of AKI with cystatin C GFR and serum NGAL concentration were similar; area under the receiver operating curve (AUROC) values 0.74 (0.51–0.97), P = 0.04 and 0.72 (0.52–0.92), P = 0.02 respectively. The development of AKI was strongly predicted by urine protein:creatinine ratio above the cut‐off of >30 (equivalent to 300 mg/day of proteinuria) sensitivity 82% (57–96) and specificity 80% (52–96), AUROC 0.86 (0.73–0.98), P ≤ 0.0001. [OR 21 (3–133), P ≤ 0.002].ConclusionsIn patients with liver cirrhosis a urine protein:creatinine ratio >30 predicts AKI. Iohexol clearance and cystatin C formulae identify a greater proportion of patients with a GFR <60 mL/min/1.73 m2, which also predicts the development of AKI.
Comparison of pollinators and natural enemies: a meta‐analysis of landscape and local effects on abundance and richness in crops
Authors: Shackelford Gorm , Steward Peter R. , Benton Tim G. , Kunin William E. , Potts Simon G. , Biesmeijer Jacobus C. , Sait Steven M. 
Published: April 2013

ABSTRACTTo manage agroecosystems for multiple ecosystem services, we need to know whether the management of one service has positive, negative, or no effects on other services. We do not yet have data on the interactions between pollination and pest‐control services. However, we do have data on the distributions of pollinators and natural enemies in agroecosystems. Therefore, we compared these two groups of ecosystem service providers, to see if the management of farms and agricultural landscapes might have similar effects on the abundance and richness of both. In a meta‐analysis, we compared 46 studies that sampled bees, predatory beetles, parasitic wasps, and spiders in fields, orchards, or vineyards of food crops. These studies used the proximity or proportion of non‐crop or natural habitats in the landscapes surrounding these crops (a measure of landscape complexity), or the proximity or diversity of non‐crop plants in the margins of these crops (a measure of local complexity), to explain the abundance or richness of these beneficial arthropods. Compositional complexity at both landscape and local scales had positive effects on both pollinators and natural enemies, but different effects on different taxa. Effects on bees and spiders were significantly positive, but effects on parasitoids and predatory beetles (mostly Carabidae and Staphylinidae) were inconclusive. Landscape complexity had significantly stronger effects on bees than it did on predatory beetles and significantly stronger effects in non‐woody rather than in woody crops. Effects on richness were significantly stronger than effects on abundance, but possibly only for spiders. This abundance‐richness difference might be caused by differences between generalists and specialists, or between arthropods that depend on non‐crop habitats (ecotone species and dispersers) and those that do not (cultural species). We call this the ‘specialist‐generalist’ or ‘cultural difference’ mechanism. If complexity has stronger effects on richness than abundance, it might have stronger effects on the stability than the magnitude of these arthropod‐mediated ecosystem services. We conclude that some pollinators and natural enemies seem to have compatible responses to complexity, and it might be possible to manage agroecosystems for the benefit of both. However, too few studies have compared the two, and so we cannot yet conclude that there are no negative interactions between pollinators and natural enemies, and no trade‐offs between pollination and pest‐control services. Therefore, we suggest a framework for future research to bridge these gaps in our knowledge.
Ketamine as a Fast Acting Antidepressant: Current Knowledge and Open Questions
Authors: Salvadore Giacomo , Singh Jaskaran B. 
Published: April 2013

SummarySeveral recent studies have shown that a single intravenous subanesthetic dose of ketamine, a NMDA receptor antagonist, exerts rapid antidepressant effects in patients with treatment refractory mood disorders and reduces suicidal ideation. Those insights have fueled tremendous excitement in the efforts to elucidate the mechanism underlying ketamine's antidepressant properties in animal models of depression, as well as in humans through the use of brain imaging as well as peripheral blood measurements. For example, there is emerging evidence that ketamine's antidepressant properties rely on increasing AMPA signaling and rapidly inducing synaptogenesis. While pilot clinical studies are promising, a number of critical questions still remain unanswered. They relate to the safe and effective use of ketamine in patients with mood disorders regarding the optimal dose range, modality and method of administration for acute and long‐term maintenance of effect, and the biomarkers associated with response/nonresponse. In this review article, we first summarize the clinical evidence about the use of ketamine in mood disorders, as well as preclinical and humans studies which investigated the mechanisms of action of ketamine, and predictors of antidepressant response in clinical populations. We then provide a critical overview of the knowledge gaps about the use of ketamine in depression and suggest some future research directions for the investigation of ketamine as a promising tool to develop novel more effective and fast acting antidepressants.
Inhaled fluticasone furoate/vilanterol does not affect hypothalamic‐pituitary‐adrenal axis function in adolescent and adult asthma: randomised, double‐blind, placebo‐controlled study
Authors: Allen Ann , Schenkenberger Isabelle , Trivedi Roopa , Cole Jeremy , Hicks Wesley , Gul Nadeem , Jacques Loretta 
Published: April 2013

AbstractIntroductionFluticasone furoate (FF) is a novel inhaled corticosteroid with 24‐h activity. FF is in development as a once‐daily treatment for asthma as monotherapy and in combination with vilanterol (VI), a long‐acting β2 agonist. Corticosteroids can have systemic effects on hypothalamic‐pituitary‐adrenal (HPA) axis function, potentially resulting in cortisol suppression.ObjectivesTo assess the effect of FF/VI compared with placebo on the HPA axis by evaluating 24‐h weighted mean serum cortisol levels in adolescent and adult patients with persistent asthma.MethodsOne hundred eighty‐five patients with >12 weeks history of asthma were randomised in a 4:4:4:1 ratio to one of two once‐daily FF/VI treatments (100/25 μg or 200/25 μg), placebo or an active control group that received inhaled placebo plus one prednisolone 10 mg capsule daily for the last 7 days of the study. Twenty‐four‐hour serum and urinary cortisol was measured at baseline and on day 42.ResultsNon‐inferiority in 24‐h weighted mean serum cortisol after 6 weeks of treatment with once‐daily FF/VI at either strength was shown. Treatment ratios [95% confidence interval (CI)] to placebo for FF/VI 100/25 μg [0.99 (0.87–1.12)] or FF/VI 200/25 μg [0.97 (0.86–1.10)] indicated non‐inferiority of both FF/VI doses to placebo as the lower limit of the 95% CI was greater than the predefined 0.8. Prednisolone substantially reduced 24‐h weighted mean serum cortisol [treatment ratio to placebo 0.34 (0.28–0.41)]. FF/VI was well‐tolerated, and no safety concerns were identified.ConclusionsFF/VI was found to be non‐inferior to placebo on HPA axis function, with no indication of significant cortisol suppression after 42 days.
Assessing nitrate leaching during the three‐first years of Miscanthus × giganteus from on‐farm measurements and modeling
Authors: Lesur Claire , Bazot Mathieu , Bio‐Beri Fadel , Mary Bruno , Jeuffroy Marie‐Hélène , Loyce Chantal 
Published: April 2013

AbstractMiscanthus × giganteus is often regarded as one of the most promising crops to produce sustainable bioenergy. This perennial crop, renowned for its high productivity associated with low input requirements, in particular regarding fertilizers, is thought to have low environmental impacts, but few data are available to confirm this. Our study aimed at assessing nitrate leaching from Miscanthus × giganteus crops in farmers' fields, thus including a wide range of soil and cropping system conditions. We focused on the first years of growth after planting as experimental studies have suggested that Miscanthus × giganteus, once established, results in low nitrate leaching. We combined on‐farm measurements and modeling to estimate drainage, leached nitrogen, and nitrate concentration in drainage water in 38 fields located in Center‐East France during two winters (November 2010 to March 2011, November 2011 to March 2012).Nitrate leaching and nitrate concentration in drainage water were on average very low. Nitrate leaching averaged 6 kg N ha−1 whereas nitrate concentration averaged 12 mg l−1. These low values are attributable to the low estimates of drainage water (mean = 166 mm) but also to the low soil mineral nitrogen contents measured at the beginning of winter (mean = 37 kg N ha−1). Our results were, however, very variable, mainly due to the crop age: nitrate leaching and nitrate concentration were critically higher during the winter following the first growth year of Miscanthus × giganteus, reflecting the low development of the crop. This variability was also explained by the range of soil and cropping conditions explored in the on‐farm design: shallow and/or sandy soils as well as fields where establishment failed had a higher risk of nitrate leaching.
Combinatorial Composition Films and Dielectric Properties of BaxSr1‐xTiO3 Grown on Two‐Inch p‐Si using PLD Process
Authors: Abdel‐Motaleb Ibrahim M. , Navuduri Praveen , Yoo Young‐Zo , Chmaissem Omar , Song Jeong‐Hwan 
Published: April 2013

Combinatorial composition films of BaxSr1‐xTiO3 were grown on two‐inch p‐Si by pulsed laser deposition. Large areas of six different combinatorial composition films were grown on the same wafer using three primary target materials. Consequently, the deposition of Ba0.5Sr0.5TiO3 films was obtained from targets BaTiO3 and SrTiO3, the deposition of Ba0.3Sr0.7TiO3 films was obtained from targets SrTiO3 and Ba0.6Sr0.4TiO3, and the Ba0.8Sr0.2TiO3 film was obtained from targets Ba0.6Sr0.4TiO3 and BaTiO3. The results indicate that the deposited materials are perovskite structures with high dielectric constants ranging from 49.4 to 193.2 and leakage current densities as low as 1.25 × 10−7 A/cm2 at −2V.
Pathophysiology of asthma: lessons from genetic research with particular focus on severe asthma
Authors: Melén E. , Pershagen G. 
Published: April 2013

Abstract.  Melén E, Pershagen G (Institute of Environmental Medicine and Centre for Allergy Research, Karolinska Institutet; Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden). Pathophysiology of asthma: lessons from genetic research with particular focus on severe asthma (Reveiw). J Intern Med 2012; 272: 108–120.There is good evidence that both inherited and environmental factors influence the risk of developing asthma. Only recently, large well‐designed studies have been undertaken with the power to identify the genetic causes for asthma, and methods developed in parallel with the Human Genome Project, such as gene expression and epigenetic studies, have made large‐scale analyses of functional genetics possible. In this review, we discuss the recent findings from genetic and genomic research studies of asthma, particularly severe asthma, and highlight specific genes for which there are multiple lines of evidence for involvement in asthma pathogenesis. Bio‐ontologic enrichment analyses of the most recently identified asthma‐related genes point to attributes such as ‘molecular and signal transducer activity’ and ‘immune system processes’, which indicates the importance of immunoregulation and inflammatory response in the pathogenesis of asthma. Finally, we discuss how genetic and environmental factors jointly influence asthma susceptibility and summarize how the results may increase understanding of the pathophysiology of asthma‐related diseases.
Allergen‐specific immunotherapy: from therapeutic vaccines to prophylactic approaches
Authors: Valenta R. , Campana R. , Marth K. , van Hage M. 
Published: April 2013

Abstract.  Valenta R, Campana R, Marth K, van Hage M (Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna; Christian Doppler Laboratory for Allergy Research, Medical University of Vienna, Vienna, Austria; and Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden) Allergen‐specific immunotherapy: from therapeutic vaccines to prophylactic approaches (Review). J Intern Med 2012; 272: 144–157.Immunoglobulin E‐mediated allergies affect more than 25% of the population. Allergen exposure induces a variety of symptoms in allergic patients, which include rhinitis, conjunctivitis, asthma, dermatitis, food allergy and life‐threatening systemic anaphylaxis. At present, allergen‐specific immunotherapy (SIT), which is based on the administration of the disease‐causing allergens, is the only disease‐modifying treatment for allergy. Current therapeutic allergy vaccines are still prepared from relatively poorly defined allergen extracts. However, with the availability of the structures of the most common allergen molecules, it has become possible to produce well‐defined recombinant and synthetic allergy vaccines that allow specific targeting of the mechanisms of allergic disease. Here we provide a summary of the development and mechanisms of SIT, and then review new forms of therapeutic vaccines that are based on recombinant and synthetic molecules. Finally, we discuss possible allergen‐specific strategies for prevention of allergic disease.
Soluble urokinase‐type plasminogen activator receptor in patients with suspected infection in the emergency room: a prospective cohort study
Authors: Uusitalo‐Seppälä R. , Huttunen R. , Tarkka M. , Aittoniemi J. , Koskinen P. , Leino A. , Vahlberg T. , Rintala E. M. 
Published: April 2013

AbstractObjectivesThe soluble form of urokinase‐type plasminogen activator (suPAR) was evaluated as an early prognostic marker of sepsis in patients with suspected infection.DesignA single‐centre prospective cohort study.MethodsThe cohort comprised 539 patients in the emergency department with suspected infection: 59 without systemic inflammatory response syndrome (SIRS) and without bacterial infection (group 1), 68 with bacterial infection and withoutSIRS(group 2), 54 withSIRSand without bacterial infection (group 3), 309 with sepsis (SIRSand bacterial infection) and without organ failure (group 4) and 49 with severe sepsis (SIRS, bacterial infection and organ failure) (group 5). suPARwas measured on admission using a commercial solid‐phase enzyme‐linked immunosorbent assay.ResultsThe median soluble form of the receptor (suPAR) concentrations in groups 1–5 were 4.7, 5.0, 4.4, 4.8 and 7.9 ng mL−1, respectively (P < 0.001). The levels were significantly higher in nonsurvivors compared with survivors (8.3 vs. 4.9 ng mL−1,P < 0.001) and in patients with severe sepsis (group 5) compared with those in the other groups (7.9 vs. 4.8 ng mL−1,P < 0.001). Area under the receiver operating characteristics curve (AUCROC) for the prediction of case fatality was 0.79 (95% confidence interval [CI]: 0.72–0.86,P < 0.0001) and 0.75 for severe sepsis (95%CI: 0.68–0.81,P < 0.0001). At a cut‐off level of 6.4 ng mL−1, suPARhad 76% sensitivity and 69% specificity for fatal disease; at a cut‐off level of 6.6 ng mL−1, the sensitivity and specificity for severe sepsis were 67% and 72%, respectively. In multivariate models, high suPARremained an independent predictor of case fatality and severe sepsis after adjusting for potential confounders.ConclusionsA high suPARlevel predicts case fatality and severe sepsis in patients with suspected infection.