bluuebunny/crossref_metadata_2025_split huggingface dataset:
Density parameter estimation for finding clusters of homologous proteins—tracing actinobacterial pathogenicity lifestyles
Authors: Röttger Richard , Kalaghatgi Prabhav , Sun Peng , Soares Siomar de Castro , Azevedo Vasco , Wittkop Tobias , Baumbach Jan 
Published: November 2012

Abstract
Motivation: Homology detection is a long-standing challenge in computational biology. To tackle this problem, typically all-versus-all BLAST results are coupled with data partitioning approaches resulting in clusters of putative homologous proteins. One of the main problems, however, has been widely neglected: all clustering tools need a density parameter that adjusts the number and size of the clusters. This parameter is crucial but hard to estimate without gold standard data at hand. Developing a gold standard, however, is a difficult and time consuming task. Having a reliable method for detecting clusters of homologous proteins between a huge set of species would open opportunities for better understanding the genetic repertoire of bacteria with different lifestyles.
Results: Our main contribution is a method for identifying a suitable and robust density parameter for protein homology detection without a given gold standard. Therefore, we study the core genome of 89 actinobacteria. This allows us to incorporate background knowledge, i.e. the assumption that a set of evolutionarily closely related species should share a comparably high number of evolutionarily conserved proteins (emerging from phylum-specific housekeeping genes). We apply our strategy to find genes/proteins that are specific for certain actinobacterial lifestyles, i.e. different types of pathogenicity. The whole study was performed with transitivity clustering, as it only requires a single intuitive density parameter and has been shown to be well applicable for the task of protein sequence clustering. Note, however, that the presented strategy generally does not depend on our clustering method but can easily be adapted to other clustering approaches.
Availability: All results are publicly available at http://transclust.mmci.uni-saarland.de/actino_core/ or as Supplementary Material of this article.
Contact: roettger@mpi-inf.mpg.de
Supplementary information: Supplementary data are available at Bioinformatics online.
iBAG: integrative Bayesian analysis of high-dimensional multiplatform genomics data
Authors: Wang Wenting , Baladandayuthapani Veerabhadran , Morris Jeffrey S. , Broom Bradley M. , Manyam Ganiraju , Do Kim-Anh 
Published: November 2012

AbstractMotivation: Analyzing data from multi-platform genomics experiments combined with patients’ clinical outcomes helps us understand the complex biological processes that characterize a disease, as well as how these processes relate to the development of the disease. Current data integration approaches are limited in that they do not consider the fundamental biological relationships that exist among the data obtained from different platforms.Statistical Model: We propose an integrative Bayesian analysis of genomics data (iBAG) framework for identifying important genes/biomarkers that are associated with clinical outcome. This framework uses hierarchical modeling to combine the data obtained from multiple platforms into one model.Results: We assess the performance of our methods using several synthetic and real examples. Simulations show our integrative methods to have higher power to detect disease-related genes than non-integrative methods. Using the Cancer Genome Atlas glioblastoma dataset, we apply the iBAG model to integrate gene expression and methylation data to study their associations with patient survival. Our proposed method discovers multiple methylation-regulated genes that are related to patient survival, most of which have important biological functions in other diseases but have not been previously studied in glioblastoma.Availability: http://odin.mdacc.tmc.edu/∼vbaladan/.Contact: veera@mdanderson.orgSupplementary information: Supplementary data are available at Bioinformatics online.
Relationship of circulating matrix biomarkers to myocardial matrix metabolism in advanced heart failure
Authors: Kaye David M. , Khammy Ouda , Mariani Justin , Maeder Micha T. 
Published: November 2012

AimsInterstitial fibrosis is a key component of myocardial remodelling in heart failure (HF). Many studies have measured peripheral blood levels of procollagens and matrix metalloproteinases (MMPs), as a surrogate for myocardial matrix metabolism, particularly to evaluate the effect of interventions and their prognostic relevance. However, the relationship between peripheral biomarker levels and actual cardiac turnover in HF is not known. We aimed to determine whether peripheral levels of relevant biomarkers reflect cardiac release in patients with advanced HF.Methods and resultsWe determined whether the failing human heart releases collagen precursors [procollagen I N‐terminal peptide (PINP) and procollagen III N‐terminal peptide (PIIINP)], or key matrix metalloproteinases (MMP9) and MMP inhibitors [tissue inhibitor of metalloproteinase 1 (TIMP1)] by performing transcardiac blood sampling in healthy controls (n = 9) and in patients with advanced HF (n = 18, left ventricular ejection fraction 22 ± 2%). HF patients had higher arterial levels of PIIINP compared with controls (7.0 ± 0.7 vs. 4.0 ± 0.2 µg/L, P < 0.001). PIIINP was closely correlated with the pulmonary capillary wedge pressure (r = 0.54, P = 0.01) and the estimated glomerular filtration rate (r = –0.50, P = 0.01). Transcardiac blood sampling demonstrated that there was no net release of either PINP or PIIINP in controls or HF patients. The transcardiac MMP9 gradient was significantly lower in HF patients (P < 0.05), and was negatively correlated with left ventricular mass (r = –0.51, P = 0.01).ConclusionsOur study shows that the concentration of circulating levels of PINP, PIIINP, MMP9, and TIMP1 do not accurately reflect cardiac turnover. This study highlights the importance of performing transcardiac blood sampling to validate the utility of emerging cardiac biomarkers.
Heart failure determines the myocardial inflammatory response to injury
Authors: Kortekaas Kirsten A. , Lindeman Jan H. , Versteegh Michel I. , van Beelen Els , Kleemann Robert , Klautz Robert J. 
Published: November 2012

AimsSystemic complications after cardiac surgery are common in heart failure patients. However, the pathophysiological mechanisms, such as a different local inflammatory response of failing hearts, remain in question. This study examines whether failing hearts respond differently to cardioplegic arrest and reperfusion compared with non‐failing hearts (controls).Methods and resultsThe inflammatory response was evaluated in samples collected simultaneously from the radial artery and coronary sinus, and myocardial tissue in 62 patients undergoing cardiac surgery. No myocardial release of inflammatory mediators was observed upon reperfusion in controls (n = 19). In contrast, in patients with heart failure, reperfusion was characterized by a myocardial release of several cytokines. Myocardial interleukin‐6 was 115% increased in non‐ischaemic heart failure (n = 18, P = 0.002) as compared with a 117% increase in patients with ischaemic heart failure (n = 25, P = 0.01). Furthermore, a myocardial release of monocyte chemoattractant protein‐1 was observed in both patient groups: a 109% (P = 0.001) and 114% (P = 0.01) increase in patients with non‐ischaemic heart failure and ischaemic heart failure, respectively. Post‐operative myocardial damage, expression of inflammatory mediators, and p65‐nuclear factor‐κB activity were similar in all patient groups. Inflammatory cell content was increased in early ischaemic myocardial tissue in both heart failure groups compared with controls.ConclusionHeart failure patients show a clear myocardial inflammatory response upon reperfusion, probably explained by degranulation of infiltrated inflammatory cells. Results in controls indicate that they better withstand cardioplegic arrest and reperfusion without an explicit myocardial inflammatory response.
Effect of conspecific and heterospecific urine odors on the foraging behavior of the golden spiny mouse
Authors: BAUDOIN Claude , HAIM Abraham , DURAND Jean‐Luc 
Published: November 2012

AbstractThe common spiny mouse (Acomys cahirinus) inhibits the foraging activity of the golden spiny mouse (A. russatus). These two sympatric species of spiny mice, which are considered habitat competitors, occur in extreme arid environments. To test this theory of competition, the influence of urinary odors of both conspecific and heterospecific mice on the foraging behavior of A. russatus was studied under controlled laboratory conditions. Twenty adult males, born in captivity and unfamiliar to the odors of the donor mice, were tested in 3 experimental conditions choosing between 2 seed patches that were scented with urine of either heterospecifics (A. cahirinus), conspecifics (A. russatus) or controls (odors of the tested individual). Of the 20 males, 12 were also tested with urine of unfamiliar gerbils, bushy‐tailed jird, considered as competitors in the field. Both conspecific and heterospecific urine samples from Acomys significantly reduced foraging behavior of A. russatus when compared to the control odor. The inhibitory effect of the Acomys urine does not result from the novelty of chemical stimuli of the urine because no effect was shown with unfamiliar gerbil urine. The findings are in accordance with the general theory that A. cahirinus dominates the foraging activity of A. russatus. We hypothesize that chemical cues in the urine of Acomys spp. might induce a negative effect on the foraging behavior of A. russatus.
Effect of acute hypoxia on blood flow in vertebral and internal carotid arteries
Authors: Ogoh Shigehiko , Sato Kohei , Nakahara Hidehiro , Okazaki Kazunobu , Subudhi Andrew W. , Miyamoto Tadayoshi 
Published: November 2012

New Findings
What is the central question of this study?Does hypoxia enhance blood flow to all parts of the brain uniformly?
What is the main finding and its importance?During hypoxia, internal carotid artery flow is maintained despite a reduction in (end‐tidal) carbon dioxide tension, while vertebral artery blood flow increases. Only with maintained end‐tidal carbon dioxide tension is there an increase in both vertebral and internal carotid blood flow during hypoxia.
Hypoxia changes the regional distribution of cerebral blood flow and stimulates the ventilatory chemoreflex, thereby reducing CO2 tension. We examined the effects of both hypoxia and isocapnic hypoxia on acute changes in internal carotid (ICA) and vertebral artery (VA) blood flow. Ten healthy male subjects underwent the following two randomly assigned respiratory interventions after a resting baseline period with room air: (i) hypoxia; and (ii) isocapnic hypoxia with a controlled gas mixture (12% O2; inspiratory mmHg). In the isocapnic hypoxia intervention, subjects were instructed to maintain the rate and depth of breathing to maintain the level of end‐tidal partial pressure of CO2 () during the resting baseline period. The ICA and VA blood flow (velocity × cross‐sectional area) were measured using Doppler ultrasonography. The was decreased (−6.3 ± 0.9%, P < 0.001) during hypoxia by hyperventilation (minute ventilation +12.9 ± 2.2%, P < 0.001), while was unchanged during isocapnic hypoxia. The ICA blood flow was unchanged (P= 0.429), while VA blood flow increased (+10.3 ± 3.1%, P= 0.010) during hypoxia. In contrast, isocapnic hypoxia increased both ICA (+14.5 ± 1.4%, P < 0.001) and VA blood flows (+10.9 ± 2.4%, P < 0.001). Thus, hypoxic vasodilatation outweighed hypocapnic vasoconstriction in the VA, but not in the ICA. These findings suggest that acute hypoxia elicits an increase in posterior cerebral blood flow, possibly to maintain essential homeostatic functions of the brainstem.
Immobilization increases interleukin‐6, but not tumour necrosis factor‐α, release from the leg during exercise in humans
Authors: Reihmane Dace , Hansen Andreas Vigelsø , Gram Martin , Kuhlman Anja Birk , Nørregaard Jesper , Pedersen Helene Pape , Lund Michael Taulo , Helge Jørn Wulff , Dela Flemming 
Published: November 2012

New Findings
What is the central question of this study?Does physical inactivity influence the exercise‐induced release of tumour necrosis factor‐α and interleukin‐6 in healthy humans? In young, healthy subjects, we immobilized one leg for 2 weeks, followed by 45 min two‐legged exercise where one leg served as the control and the other was the previously inactive leg.
What is the main finding and its importance?We found that prior physical inactivity enhances interleukin‐6 release during exercise, and it is released in the blood from the legs during exercise much faster than previously known. However, tumour necrosis factor‐α is not released in the blood with exercise, even from a previously inactive leg.
Data on interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α) release during acute exercise are not conclusive, and information is lacking about the impact of physical inactivity. Some studies have shown an increase, but others report no changes in IL‐6 and TNF‐α release during exercise. We have now studied the temporal relationship of leg IL‐6 and TNF‐α release before and during isolated two‐legged exercise after 14 days of one‐leg immobilization (IM) while the other leg served as the control (CON) leg. Fifteen healthy male subjects (mean ± SEM age, 23 ± 1 years; body mass index, 23.6 ± 0.7 kg m−2; and maximal oxygen uptake, 46.8 ± 1.4 ml kg−1 min−1) performed 45 min of two‐legged dynamic knee‐extensor exercise at 19.6 ± 0.8 W. Arterial and femoral venous blood samples from the CON and the IM leg were collected every 15 min during exercise, and leg blood flow was measured with Doppler ultrasound. The arterial plasma IL‐6 concentration increased (P < 0.05) with exercise (rest, 1.3 ± 0.1 pg ml−1; 15 min, 1.9 ± 0.2 pg ml−1; 30 min, 2.4 ± 0.2 pg ml−1; and 45 min, 3.1 ± 0.3 pg ml−1). Interleukin‐6 release occurred after 15 min of exercise, and the release from the IM leg was significantly greater compared with the CON leg after 45 min (1114 ± 152 versus 606 ± 14 pg min−1, respectively, P < 0.05). Tumour necrosis factor‐α release did not differ between the CON and the IM leg, and arterial concentrations remained unchanged during exercise (P > 0.05). In conclusion, prior immobilization enhances release of IL‐6 from the leg during exercise at a moderate workload, and the release is already present in the early phase of exercise. Neither immobilization nor exercise had an effect on TNF‐α release in the working legs.
Deficiency in pulmonary surfactant proteins in mice with fatty acid binding protein 4‐Cre‐mediated knockout of the tuberous sclerosis complex 1 gene
Authors: Xiang Xinxin , Yuan Fang , Zhao Jing , Li Ziru , Wang Xian , Guan Youfei , Tang Chaoshu , Sun Guang , Li Yin , Zhang Weizhen 
Published: November 2012

New findings
What is the central question of this study?Does tuberous sclerosis complex 1–mammalian target of rapamycin (mTOR) signalling regulate the synthesis of surfactant proteins A and B and, if so, can this contribute to the postnatal death of Fabp4‐Tsc1cKO mice?
What is the main finding and its importance?Our study reveals a novel mechanism for the regulation of alveolar surfactant proteins. Tuberous sclerosis complex 1–mTOR signalling contributes to the regulation of synthesis of surfactant proteins A and B. Deficiency of tuberous sclerosis complex 1 in alveolar epithelial cells may contribute to the postnatal death of Fabp4‐Tsc1cKO mice.
Tuberous sclerosis complex 1 (TSC1) forms a heterodimmer with tuberous sclerosis complex 2, to inhibit signalling by the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). The mTORC1 stimulates cell growth by promoting anabolic cellular processes, such as gene transcription and protein translation, in response to growth factors and nutrient signals. Originally designed to test the role of TSC1 in adipocyte function, mice in which the gene for TSC1 was specifically deleted by the fatty acid binding protein 4 (FABP4)‐Cre (Fabp4‐Tsc1cKO mice) died prematurely within 48 h after birth. The Fabp4‐Tsc1cKO mouse revealed a much smaller phenotype relative to the wild‐type littermates. Maternal administration of rapamycin, a classical mTOR inhibitor, significantly increased the survival time of Fabp4‐Tsc1cKO mice for up to 23 days. Both macroscopic and microscopic haemorrhages were observed in the lungs of Fabp4‐Tsc1cKO mice, while other tissues showed no significant changes. Levels of surfactant proteins A and B demonstrated a significant decrease in the Fabp4‐Tsc1cKO mice, which was rescued by maternal injection of rapamycin. Co‐localization of FABP4 or TSC1 with surfactant protein B was also detected in neonatal pulmonary tissues. Our study suggests that TSC1–mTORC1 may be critical for the synthesis of surfactant proteins A and B.
Relationships between black tea consumption and key health indicators in the world: an ecological study
Authors: Beresniak Ariel , Duru Gerard , Berger Genevieve , Bremond-Gignac Dominique 
Published: November 2012

ObjectivesThe aim of this study was to investigate potential statistical relationships between black tea consumption and key health indicators in the world. The research question is: Does tea consumption is correlated with one or more epidemiological indicators?DesignEcological study using a systematic data-mining approach in which the unit of the analysis is a population of one country.SettingSix variables, black tea consumption data and prevalence data of respiratory diseases, infectious diseases, cancer, cardiovascular diseases and diabetes, have been studied at a global level.ParticipantsData from 50 participating countries in the World Health Survey were investigated.Primary and secondary outcomes measuresLevel of statistical relationships between variables.ResultsPrincipal component analysis established a very high contribution of the black tea consumption parameter on the third axis (81%). The correlation circle confirmed that the ‘black tea’ vector was negatively correlated with the diabetes vector and was not correlated with any of the other four health indicators. A linear correlation model then confirmed a significant statistical correlation between high black tea consumption and low diabetes prevalence.ConclusionsThis innovative study establishes a linear statistical correlation between high black tea consumption and low diabetes prevalence in the world. These results are consistent with biological and physiological studies conducted on the effect of black tea on diabetes and confirm the results of a previous ecological study in Europe. Further epidemiological research and randomised studies are necessary to investigate the causality.
A randomised trial comparing the clinical effectiveness of different emergency department healthcare professionals in soft tissue injury management
Authors: McClellan Carey Middleton , Cramp Fiona , Powell Jane , Benger Jonathan Richard 
Published: November 2012

ObjectivesTo evaluate the clinical effectiveness of soft tissue injury management by emergency nurse practitioners (ENPs) and extended scope physiotherapists (ESPs) compared to the routine care provided by doctors in a UK emergency department (ED).DesignRandomised, pragmatic trial of equivalence.SettingOne adult ED in England.Participants372 patients were randomised; 126 to the ESP group, 123 to the ENP group and 123 to the doctor group. Participants were adults (older than 16 years) presenting to the ED with a peripheral soft tissue injury eligible for management by any of the three professional groups. Patients were excluded if they had any of the following: injury greater than 72 hours old; systemic disease; dislocated joints; recent surgery; unable to give informed consent (eg, dementia), open wounds; major deformities; opiate analgesia required; concurrent chest/rib injury; neurovascular deficits and associated fracture.InterventionsPatients were randomised to treatment by ESPs, ENPs or routine care provided by doctors (of all grades).Main outcome measuresUpper-limb and lower-limb functional scores, quality of life, physical well-being, preference-based health measures and the number of days off work.ResultsThe clinical outcomes of soft tissue injury treated by ESPs and ENPs in the ED were equivalent to routine care provided by doctors.ConclusionsAs all groups were clinically equivalent it is other factors such as cost, workforce sustainability, service provision and skill mix that become important. This result validates the role of the ENP, which is becoming established as an integral part of minor injuries care, and demonstrates that the ESP should be considered as part of the clinical skill mix without detriment to outcomes.ISRCTN-ISRCTN trials register number70891354.
Regional and temporal variation in the treatment of rheumatoid arthritis across the UK: a descriptive register-based cohort study
Authors: Edwards Christopher John , Campbell Jennifer , van Staa Tjeerd , Arden Nigel K 
Published: November 2012

ObjectivesTo describe current disease-modifying antirheumatic drugs (DMARDs) prescription in rheumatoid arthritis (RA) with reference to best practice and to identify temporal and regional trends in the UK.DesignDescriptive, register-based cohort study.ParticipantsPermanently registered patients aged ≥18 years with a recorded diagnosis of RA between 1 January 1995 and 31 March 2010 and matched controls. Participants with RA were identified through screening of all patients in the General Practice Research Database (GPRD) with a clinical or referral record for RA and at least 1 day of follow-up.Setting639 general practices in the UK supplying data to the GPRD.Main outcome measuresMedication prescribing between 3 and 12 months of RA diagnosis by region and time period (1995–1999, 2000–2005 and 2006–April 2010).ResultsOf the 35 911 patients in the full RA cohort, 15 259 patients (42%) had incident RA. Analysis of prescribing in incident RA patients demonstrated that between 1995 (baseline) and 2010 there was a substantial increase in DMARD, and specifically methotrexate, prescribing across all regions with a less marked increase in combination DMARD prescribing. Taking 12-month prescribing as a snapshot: DMARD prescribing was 19–49% at baseline increasing to 45–74% by 2006–April 2010; methotrexate prescribing was 4–16% at baseline increasing to 32–60%; combination DMARD prescribing was 0–8% at baseline increasing to 3–17%. However, there was marked regional variation in the proportion of RA patients receiving DMARD regardless of time period.ConclusionsThere has been a substantial increase in prescribing of DMARDs for RA since 1995; however, regional variation persists across the UK with relative undertreatment, according to established best practice. Improved implementation of evidence-based best clinical practice to facilitate removal of treatment variation is warranted. This may occur as a result of the implementation of published national guidance.