bluuebunny/crossref_metadata_2025_split huggingface dataset:
A probabilistic coevolutionary biclustering algorithm for discovering coherent patterns in gene expression dataset
Authors: Joung Je-Gun , Kim Soo-Jin , Shin Soo-Yong , Zhang Byoung-Tak 
Published: December 2012

Abstract

Background
Biclustering has been utilized to find functionally important patterns in biological problem. Here a bicluster is a submatrix that consists of a subset of rows and a subset of columns in a matrix, and contains homogeneous patterns. The problem of finding biclusters is still challengeable due to computational complex trying to capture patterns from two-dimensional features.

Results
We propose a Probabilistic COevolutionary Biclustering Algorithm (PCOBA) that can cluster the rows and columns in a matrix simultaneously by utilizing a dynamic adaptation of multiple species and adopting probabilistic learning. In biclustering problems, a coevolutionary search is suitable since it can optimize interdependent subcomponents formed of rows and columns. Furthermore, acquiring statistical information on two populations using probabilistic learning can improve the ability of search towards the optimum value. We evaluated the performance of PCOBA on synthetic dataset and yeast expression profiles. The results demonstrated that PCOBA outperformed previous evolutionary computation methods as well as other biclustering methods.

Conclusions
Our approach for searching particular biological patterns could be valuable for systematically understanding functional relationships between genes and other biological components at a genome-wide level.
The transcriptomic fingerprint of glucoamylase over-expression in Aspergillus niger
Authors: Kwon Min Jin , Jørgensen Thomas R , Nitsche Benjamin M , Arentshorst Mark , Park Joohae , Ram Arthur FJ , Meyer Vera 
Published: December 2012

AbstractBackgroundFilamentous fungi such asAspergillus nigerare well known for their exceptionally high capacity for secretion of proteins, organic acids, and secondary metabolites and they are therefore used in biotechnology as versatile microbial production platforms. However, system-wide insights into their metabolic and secretory capacities are sparse and rational strain improvement approaches are therefore limited. In order to gain a genome-wide view on the transcriptional regulation of the protein secretory pathway ofA. niger, we investigated the transcriptome ofA. nigerwhen it was forced to overexpression theglaAgene (encoding glucoamylase, GlaA) and secrete GlaA to high level.ResultsAnA. nigerwild-type strain and a GlaA over-expressing strain, containing multiple copies of theglaAgene, were cultivated under maltose-limited chemostat conditions (specific growth rate 0.1 h-1). ElevatedglaAmRNA and extracellular GlaA levels in the over-expressing strain were accompanied by elevated transcript levels from 772 genes and lowered transcript levels from 815 genes when compared to the wild-type strain. Using GO term enrichment analysis, four higher-order categories were identified in the up-regulated gene set: i) endoplasmic reticulum (ER) membrane translocation, ii) protein glycosylation, iii) vesicle transport, and iv) ion homeostasis. Among these, about 130 genes had predicted functions for the passage of proteins through the ER and those genes included target genes of the HacA transcription factor that mediates the unfolded protein response (UPR), e.g.bipA, clxA, prpA, tigAandpdiA. In order to identify those genes that are important for high-level secretion of proteins byA. niger, we compared the transcriptome of the GlaA overexpression strain ofA. nigerwith six other relevant transcriptomes ofA. niger. Overall, 40 genes were found to have either elevated (from 36 genes) or lowered (from 4 genes) transcript levels under all conditions that were examined, thus defining the core set of genes important for ensuring high protein traffic through the secretory pathway.ConclusionWe have defined theA. nigergenes that respond to elevated secretion of GlaA and, furthermore, we have defined a core set of genes that appear to be involved more generally in the intensified traffic of proteins through the secretory pathway ofA. niger. The consistent up-regulation of a gene encoding the acetyl-coenzyme A transporter suggests a possible role for transient acetylation to ensure correct folding of secreted proteins.
Comparison of Optimised MDI versus Pumps with or without Sensors in Severe Hypoglycaemia (the Hypo COMPaSS trial)
Authors: Little Stuart , Chadwick Thomas , Choudhary Pratik , Brennand Cath , Stickland Julia , Barendse Shalleen , Olateju Tolulope , Leelarathna Lalantha , Walkinshaw Emma , Tan Horng K , Marshall Sally M , Thomas Reena M , Heller Simon , Evans Mark , Kerr David , Flanagan Daniel , Speight Jane , Shaw James AM 
Published: December 2012

Abstract

Background
Severe hypoglycaemia (SH) is one of the most feared complications of type 1 diabetes (T1DM) with a reported prevalence of nearly 40%. In randomized trials of Multiple Daily Injections (MDI) and Continuous Subcutaneous Insulin Infusion (CSII) therapy there is a possible benefit of CSII in reducing SH. However few trials have used basal insulin analogues as the basal insulin in the MDI group and individuals with established SH have often been excluded from prospective studies. In published studies investigating the effect of Real Time Continuous Glucose Monitoring (RT-CGM) benefit in terms of reduced SH has not yet been demonstrated. The primary objective of this study is to elucidate whether in people with T1DM complicated by impaired awareness of hypoglycaemia (IAH), rigorous prevention of biochemical hypoglycaemia using optimized existing self-management technology and educational support will restore awareness and reduce risk of recurrent SH.

Methods/design
This is a multicentre prospective RCT comparing hypoglycaemia avoidance with optimized MDI and CSII with or without RT-CGM in a 2×2 factorial design in people with type 1 diabetes who have IAH. The primary outcome measure for this study is the difference in IAH (Gold score) at 24 weeks. Secondary outcomes include biomedical measures such as HbA1c, SH incidence, blinded CGM analysis, self monitored blood glucose (SMBG) and response to hypoglycaemia in gold standard clamp studies. Psychosocial measures including well-being and quality of life will also be assessed using several validated and novel measures. Analysis will be on an intention-to-treat basis.

Discussion
Most existing RCTs using this study’s interventions have been powered for change in HbA1c rather than IAH or SH. This trial will demonstrate whether IAH can be reversed and SH prevented in people with T1DM in even those at highest risk by using optimized conventional management and existing technology.

Trial Registration
ISRCTN52164803 Eudract No: 2009-015396-27
Identification of interdependent variables that influence coreceptor switch in R5 SHIVSF162P3N-infected macaques
Authors: Zhuang Ke , Finzi Andres , Toma Jonathan , Frantzell Arne , Huang Wei , Sodroski Joseph , Cheng-Mayer Cecilia 
Published: December 2012

AbstractBackgroundWe previously reported that adoption of an “open” envelope glycoprotein (Env) to expose the CD4 binding site for efficient receptor binding and infection of cell targets such as macrophages that express low levels of the receptor represents an early event in the process of coreceptor switch in two rapidly progressing (RP) R5 SHIVSF162P3N-infected rhesus macaques, releasing or reducing Env structural constraints that have been suggested to limit the pathways available for a change in coreceptor preference. Here we extended these studies to two additional RP monkeys with coreceptor switch and three without to confirm and identify additional factors that facilitated the process of phenotypic conversion.ResultsWe found that regardless of coreceptor switching, R5 viruses in SHIVSF162P3N-infected RP macaques evolved over time to infect macrophages more efficiently; this was accompanied by increased sCD4 sensitivity, with structural changes in the CD4 binding site, the V3 loop and/or the fusion domain of their Envs that are suggestive of better CD4 contact, CCR5 usage and/or virus fusion. However, sCD4-sensitive variants with improved CD4 binding were observed only in RPs with coreceptor switch. Furthermore, cumulative viral load was higher in RPs with than in those without phenotypic switch, with the latter maintaining a longer period of seroconversion.ConclusionsOur data suggest that the increased virus replication in the RPs with R5-to-X4 conversion increased the rate of virus evolution and reduction in the availability of target cells with optimal CD4 expression heightened the competition for binding to the receptor. In the absence of immunological restrictions, variants that adopt an “open” Env to expose the CD4 binding site for better CD4 use are selected, allowing structural changes that confer CXCR4-use to be manifested. Viral load, change in target cell population during the course of infection and host immune response therefore are interdependent variables that influence R5 virus evolution and coreceptor switch in SHIVSF162P3N-infected rhesus macaques. Because an "open" Env conformation also renders the virus more susceptible to antibody neutralization, our findings help to explain the infrequent and late appearance of X4 virus in HIV-1 infection when the immune system deteriorates.
Reconstruction of genome-scale metabolic models for 126 human tissues using mCADRE
Authors: Wang Yuliang , Eddy James A , Price Nathan D 
Published: December 2012

Abstract

Background
Human tissues perform diverse metabolic functions. Mapping out these tissue-specific functions in genome-scale models will advance our understanding of the metabolic basis of various physiological and pathological processes. The global knowledgebase of metabolic functions categorized for the human genome (Human Recon 1) coupled with abundant high-throughput data now makes possible the reconstruction of tissue-specific metabolic models. However, the number of available tissue-specific models remains incomplete compared with the large diversity of human tissues.

Results
We developed a method called metabolic Context-specificity Assessed by Deterministic Reaction Evaluation (mCADRE). mCADRE is able to infer a tissue-specific network based on gene expression data and metabolic network topology, along with evaluation of functional capabilities during model building. mCADRE produces models with similar or better functionality and achieves dramatic computational speed up over existing methods. Using our method, we reconstructed draft genome-scale metabolic models for 126 human tissue and cell types. Among these, there are models for 26 tumor tissues along with their normal counterparts, and 30 different brain tissues. We performed pathway-level analyses of this large collection of tissue-specific models and identified the eicosanoid metabolic pathway, especially reactions catalyzing the production of leukotrienes from arachidnoic acid, as potential drug targets that selectively affect tumor tissues.

Conclusions
This large collection of 126 genome-scale draft metabolic models provides a useful resource for studying the metabolic basis for a variety of human diseases across many tissues. The functionality of the resulting models and the fast computational speed of the mCADRE algorithm make it a useful tool to build and update tissue-specific metabolic models.
Analysis of benzodiazepine withdrawal program managed by primary care nurses in Spain
Authors: Lopez-Peig Cristina , Mundet Xavier , Casabella Bartomeu , del Val Jose Luis , Lacasta David , Diogene Eduard 
Published: December 2012

Abstract

Background
Benzodiazepine (BZD), the long-term treatment of which is harmful for cognitive function, is widely prescribed by General Practitioners in Spain. Based on studies performed in other countries we designed a nurse-led BZD withdrawal program adapted to Spanish Primary Care working conditions.

Results
A pseudo-experimental (before-after) study took place in two Primary Care Centres in Barcelona. From a sample of 1150 patients, 79 were identified. They were over 44 years old and had been daily users of BZD for a period exceeding six months. Out of the target group 51 patients agreed to participate. BZD dosage was reduced every 2-4 weeks by 25% of the initial dose with the optional support of Hydroxyzine or Valerian. The rating measurements were: reduction of BZD prescription, demographic variables, the Short-Form Health Survey (SF-12) to measure quality of life, the Medical Outcomes Study (MOS) Sleep Scale, and the Goldberg Depression and Anxiety Scale.
By the end of the six-month intervention, 80.4% of the patients had discontinued BZD and 64% maintained abstinence at one year. An improvement in all parameters of the Goldberg scale (p <0.05) and in the mental component of SF-12 at 3.3 points (p = 0.024), as well as in most components of the MOS scale, was observed in the group that had discontinued BZD. No significant differences in these scales before and after the intervention were observed in the group that had not discontinued.

Conclusions
At one year approximately 2/3 of the patients had ceased taking BZD. They showed an overall improvement in depression and anxiety scales, and in the mental component of the quality of life scale. There was no apparent reduction in the sleep quality indicators in most of the analysed components. Nurses in a Primary Care setting can successfully implement a BZD withdrawal program.
Reducing HIV-Related Stigma in Health Care Settings: A Randomized Controlled Trial in China
Authors: Li Li , Wu Zunyou , Liang Li-Jung , Lin Chunqing , Guan Jihui , Jia Manhong , Rou Keming , Yan Zhihua 
Published: December 2012

Objectives. The objective of the intervention was to reduce service providers’ stigmatizing attitudes and behaviors toward people living with HIV. Methods. The randomized controlled trial was conducted in 40 county-level hospitals in 2 provinces of China between October 2008 and February 2010. Forty-four service providers were randomly selected from each hospital, yielding a total of 1760 study participants. We randomized the hospitals to either an intervention condition or a control condition. In the intervention hospitals, about 15% of the popular opinion leaders were identified and trained to disseminate stigma reduction messages. Results. We observed significant improvements for the intervention group in reducing prejudicial attitudes (P < .001), reducing avoidance intent towards people living with HIV (P < .001), and increasing institutional support in the hospitals (P = .003) at 6 months after controlling for service providers’ background factors and clinic-level characteristics. The intervention effects were sustained and strengthened at 12 months. Conclusions. The intervention reduced stigmatizing attitudes and behaviors among service providers. It has the potential to be integrated into the health care systems in China and other countries.
Income Inequality, Alcohol Use, and Alcohol-Related Problems
Authors: Karriker-Jaffe Katherine J. , C. M. Roberts Sarah , Bond Jason 
Published: December 2012

Objectives. We examined the relationship between state-level income inequality and alcohol outcomes and sought to determine whether associations of inequality with alcohol consumption and problems would be more evident with between-race inequality measures than with the Gini coefficient. We also sought to determine whether inequality would be most detrimental for disadvantaged individuals.Methods. Data from 2 nationally representative samples of adults (n = 13 997) from the 2000 and 2005 National Alcohol Surveys were merged with state-level inequality and neighborhood disadvantage indicators from the 2000 US Census. We measured income inequality using the Gini coefficient and between-race poverty ratios (Black–White and Hispanic–White). Multilevel models accounted for clustering of respondents within states.Results. Inequality measured by poverty ratios was positively associated with light and heavy drinking. Associations between poverty ratios and alcohol problems were strongest for Blacks and Hispanics compared with Whites. Household poverty did not moderate associations with income inequality.Conclusions. Poverty ratios were associated with alcohol use and problems, whereas overall income inequality was not. Higher levels of alcohol problems in high-inequality states may be partly due to social context.
Sex, Drugs, and Race: How Behaviors Differentially Contribute to the Sexually Transmitted Infection Risk Network Structure
Authors: adams jimi , Moody James , Morris Martina 
Published: December 2012

Objectives. We examined how risk behaviors differentially connect a population at high risk for sexually transmitted infections. Methods. Starting from observed networks representing the full risk network and the risk network among respondents only, we constructed a series of edge-deleted counterfactual networks that selectively remove sex ties, drug ties, and ties involving both sex and drugs and a comparison random set. With these edge-deleted networks, we have demonstrated how each tie type differentially contributes to the connectivity of the observed networks on a series of standard network connectivity measures (component and bicomponent size, distance, and transitivity ratio) and the observed network racial segregation. Results. Sex ties are unique from the other tie types in the network, providing wider reach in the network in relatively nonredundant ways. In this population, sex ties are more likely to bridge races than are other tie types. Conclusions. Interventions derived from only 1 mode of transmission at a time (e.g., condom promotion or needle exchange) would have different potential for curtailing sexually transmitted infection spread through the population than would attempts that simultaneously address all risk-relevant behaviors.
Cervical Spine Immobilization in Sports Related Injuries: Review of Current Guidelines and a Case Study of an Injured Athlete
Authors: Bhamra JS , Morar Y , Khan WS , Deep K , Hammer A 
Published: December 2012

Cervical spine immobilization is an essential component of the ATLS® system. Inadequate training in the management of trauma calls and failure of early recognition can have disastrous consequences. Pre-hospital personnel are routinely involved more in the assessment and stabilization of patients in comparison to other health care professionals.
This case study and review highlights the importance of early recognition, assessment and correct stabilization of cervical spine injuries both in the field and during the initial assessment in hospital.
Inadequate assessment, immobilization and lack of standard guidelines on the management of suspected cervical spine trauma can result in secondary injury. Regular assessment and training of pre-hospital and medical personnel is essential to the proper management of these potentially devastating injuries.
Tissue Engineered Strategies for Pseudoarthrosis
Authors: Longo Umile Giuseppe , Trovato Ugo , Loppini Mattia , Rizzello Giacomo , Khan Wasim Sardar , Maffulli Nicola , Denaro Vincenzo 
Published: December 2012

Numerous classification systems of non-union have been proposed based on: presence or absence of infection, radiographic features, clinical findings, biologic activity, location and shape. The management of pseudarthrosis is strongly related to the type of non-union (infected versus uninfected, atrophic versus hypertrophic). Surgical management of pseudarthrosis is generally effective with a success rate ranging from 75 to 100%. Nevertheless, in a relatively high number of instances several combined treatments are required for the fracture healing. The current gold standard to stimulate the bone regeneration is represented by the revision surgery with the application of autologous bone grafts. However, several approaches have been described to promote and enhance the bone tissue regeneration, including extracorporeal shock wave therapy (ESWT), ultrasound, electromagnetic, bone morphogenic proteins (BMPs) and platelet-rich-plasma (PRP).The aim of the present study was to perform a systematic review of the literature evaluating the current therapies to promote and enhance the bone tissue healing. The systematic review was performed according to PRISMA guidelines with a PRISMA checklist and algorithm.Limitations of the present systematic review are mainly related to the scanty quality of the studies available in the literature. Although the therapies previously described for the management of patients with non-unions seems to be effective, the limitations of the included studies, especially the extensive clinical heterogeneity, make not possible to provide clear recommendations regarding the application of these approaches. The problems remain the need to better understand the most effective treatment options, subject to surgical stabilization as a first step.
Comparison of Cystic Fibrosis–Related Diabetes With Type 1 Diabetes Based on a German/Austrian Pediatric Diabetes Registry
Authors: Konrad Katja , Thon Angelika , Fritsch Maria , Fröhlich-Reiterer Elke , Lilienthal Eggert , Wudy Stefan A. , Holl Reinhard W. ,   for the German/Austrian Diabetes Prospective Documentation Initiative
Published: December 2012

OBJECTIVE
The prevalence of cystic fibrosis–related diabetes (CFRD) has increased with improved life expectancy of patients. Clinical and care characteristics were compared with type 1 diabetes mellitus (T1DM) in a multicenter analysis of pediatric data.

RESEARCH DESIGN AND METHODS
Auxological and treatment data from 47,227 patients aged younger than 21 years with CFRD or T1DM in the German/Austrian Diabetes Prospective Documentation Initiative registry were analyzed by multivariable mixed regression modeling.

RESULTS
Diabetes onset (mean [interquartile range]) occurred later in individuals with CFRD (14.5 [11.8–16.3] years) than in individuals with T1DM (8.5 [4.9–11.8] years), with female preponderance in CFRD (59.1% vs. 47.5%; P &lt; 0.01). CFRD patients had lower BMI standard deviation scores (−0.85 [−1.59 to −0.12] vs. +0.52 [−0.10 to +1.16]; P &lt; 0.01) and lower HbA1c (6.87% vs. 7.97%; P &lt; 0.01). Self-monitoring of blood glucose was more frequent in patients with T1DM (4.5 vs. 3.5; P &lt; 0.01); 72% of CFRD patients received insulin. In insulin-treated patients, insulin dosage adjusted for age, sex, and diabetes duration differed significantly (T1DM: 0.79 IE per kilogram of body weight; CFRD: 0.83 IE per kilogram of body weight). Use of short-acting and long-acting insulin analogs was significantly more frequent in T1DM (47% vs. 39% and 37% vs. 28%; both P &lt; 0.05). Metabolic control in CFRD patients without insulin was better compared with CFRD on insulin (HbA1c: 6.00 vs. 7.12; P &lt; 0.01), but duration of disease was significantly shorter (0.8 years [0.1–2.4] compared with 2.4 years [0.6–4.6]). There was no significant difference for BMI standard deviations scores between CFRD patients with or without insulin treatment.

CONCLUSIONS
Pediatric patients with CFRD show clear auxological and metabolic differences from those with T1DM, with different treatment choices.
Optimizing composition for (Nd, Pr)–Nb–Fe–B hard magnetic nanocomposites
Authors: Thanh Pham Thi , Huyen Nguyen Thi Thanh , Yen Nguyen Hai , Dan Nguyen Huy 
Published: December 2012

Abstract
The influence of composition and annealing temperature on the magnetic properties of (Nd0.5Pr0.5)6
+

x
Nb1.5Fe88.5
–

x

–

y
B4
+

y
(x = 0–6, y = 0–10) nanocomposites prepared via melt-spinning and subsequent annealing was investigated systematically to obtain their optimal compositions and fabrication conditions. The results show that each of the rare earth concentrations has an appropriate ratio of Fe/B to reveal the best performance of the material. The optimal annealing temperature decreases from 750 to 675°C when concentration of rare earth is increased from 6 to 12 at.%. Coercivity, H
c, and maximum energy product, (BH)max, of these nanocomposites can be regulated up to 14.5 kOe and 16 MGOe, respectively, by suitably choosing their composition.