bluuebunny/crossref_metadata_2025_split huggingface dataset:
A long‐term intensive lifestyle intervention and physical function: The look AHEAD Movement and Memory Study
Authors: Houston Denise K. , Leng Xiaoyan , Bray George A. , Hergenroeder Andrea L. , Hill James O. , Jakicic John M. , Johnson Karen C. , Neiberg Rebecca H. , Marsh Anthony P. , Rejeski W. Jack , Kritchevsky Stephen B. ,   for the Action for Health In Diabetes (Look AHEAD) Movement and Memory Ancillary Study Research Group
Published: November 2014

ObjectiveTo assess the long‐term effects of an intensive lifestyle intervention on physical function using a randomized post‐test design in the Look AHEAD trial.MethodsOverweight and obese (BMI ≥ 25 kg m−2) middle‐aged and older adults (aged 45‐76 years at enrollment) with type 2 diabetes (n = 964) at four clinics in Look AHEAD, a trial evaluating an intensive lifestyle intervention (ILI) designed to achieve weight loss through caloric restriction and increased physical activity compared to diabetes support and education (DSE), underwent standardized assessments of performance‐based physical function including an expanded short physical performance battery (SPPBexp), 20‐m and 400‐m walk, and grip and knee extensor strength 8 years post‐randomization, during the trial's weight maintenance phase.ResultsEight years post‐randomization, individuals randomized to ILI had better SPPBexp scores [adjusted mean (SE) difference: 0.055 (0.022), P = 0.01] and faster 20‐m and 400‐m walk speeds [0.032 (0.012) m s−1, P = 0.01, and 0.025 (0.011) m s−1, P = 0.02, respectively] compared to those randomized to DSE. Achieved weight loss greatly attenuated the group differences in physical function, and the intervention effect was no longer significant.ConclusionsAn intensive lifestyle intervention has long‐term benefits for mobility function in overweight and obese middle‐aged and older individuals with type 2 diabetes.
Capillary‐channeled polymer (C‐CP) fibers for the rapid extraction of proteins from urine matrices prior to detection with MALDI‐MS
Authors: Manard Benjamin T. , Jones Sarah M. H. , Marcus R. Kenneth 
Published: November 2014

PurposeWhile MS is a powerful tool for biomarker determinations, the high salt content and the small molecules present in urine poses incredible challenges. Separation/extraction methods must be employed for the isolation of target species at relevant concentrations. Micropipette tips packed with capillary‐channeled polymer (C‐CP) fibers are employed for the SPE of proteins from a synthetic and a certified urine matrix.Experimental designExtractions are performed utilizing a very simple centrifugation method to spin‐down species through the C‐CP fiber tips. Proteins adsorb to the hydrophobic polypropylene fibers and are eluted in a solvent suitable for MALDI‐MS analysis. Figures of merit are determined for representative compounds β2‐microglobulin, retinol binding protein, and transferrin.ResultsThe optimum protein processing included a 100 μL aqueous rinse and an elution solvent composition was 10 μL of 55:45 ACN:water (with triflouroacetic acid). MALDI‐MS responses for the target proteins are improved from nondetectable levels to eventually yield LOD ranging from 5 to 180 nM in 1 μL aliquots.Conclusion and clinical relevanceC‐CP fiber tips offer a plethora of advantages including low materials costs, high throughput, microvolume processing, and the determination of sub‐nanogram quantities of analyte; allowing determination of biomarkers that are otherwise undetectable in urine matrices.
Network of long‐range concerted chemical shift displacements upon ligand binding to human angiogenin
Authors: Gagné Donald , Narayanan Chitra , Doucet Nicolas 
Published: November 2014

AbstractMolecular recognition models of both induced fit and conformational selection rely on coupled networks of flexible residues and/or structural rearrangements to promote protein function. While the atomic details of these motional events still remain elusive, members of the pancreatic ribonuclease superfamily were previously shown to depend on subtle conformational heterogeneity for optimal catalytic function. Human angiogenin, a structural homologue of bovine pancreatic RNase A, induces blood vessel formation and relies on a weak yet functionally mandatory ribonucleolytic activity to promote neovascularization. Here, we use the NMR chemical shift projection analysis (CHESPA) to clarify the mechanism of ligand binding in human angiogenin, further providing information on long‐range intramolecular residue networks potentially involved in the function of this enzyme. We identify two main clusters of residue networks displaying correlated linear chemical shift trajectories upon binding of substrate fragments to the purine‐ and pyrimidine‐specific subsites of the catalytic cleft. A large correlated residue network clusters in the region corresponding to the V1 domain, a site generally associated with the angiogenic response and structural stability of the enzyme. Another correlated network (residues 40–42) negatively affects the catalytic activity but also increases the angiogenic activity. 15N‐CPMG relaxation dispersion experiments could not reveal the existence of millisecond timescale conformational exchange in this enzyme, a lack of flexibility supported by the very low‐binding affinities and catalytic activity of angiogenin. Altogether, the current report potentially highlights the existence of long‐range dynamic reorganization of the structure upon distinct subsite binding events in human angiogenin.
CD41 Marks the Initial Myelo-Erythroid Lineage Specification in Adult Mouse Hematopoiesis: Redefinition of Murine Common Myeloid Progenitor
Authors: Miyawaki Kohta , Arinobu Yojiro , Iwasaki Hiromi , Kohno Kentaro , Tsuzuki Hirofumi , Iino Tadafumi , Shima Takahiro , Kikushige Yoshikane , Takenaka Katsuto , Miyamoto Toshihiro , Akashi Koichi 
Published: November 2014

Abstract
Previous studies have predicted that reciprocal activation of GATA-1 and PU.1 regulates myelo-erythroid versus myelo-lymphoid lineage commitment in early hematopoiesis. Such PU.1-activating myelo-lymphoid progenitors exist within the lymphoid-primed multipotent progenitor (LMPP) population at the primitive Lineage−Sca-1+c-Kit+ (LSK) stage. We here show that the counterpart of GATA-1-activating myelo-erythroid progenitor resides also at the LSK stage, expressing CD41 at a high level. Purified CD41hi LSK cells showed exceedingly strong and prolonged myelo-erythroid-restricted reconstitution, and primed myelo-erythroid gene expression with a more primitive molecular signature as compared to the original common myeloid progenitor (CMP). The CD41hi LSK cells more strongly contributed to emergent and malignant myelopoiesis than LMPPs, and produced the original CMP by downregulating Sca-1 and CD41, suggesting that they are the earliest CMPs. Thus, the hematopoietic developmental map should be revised by integrating the primary branchpoint comprised of the new, isolatable CD41hi CMP and the LMPP populations. Stem Cells 2015;33:976–987
A prospective open‐label study of home use of mifepristone for medical abortion in Nepal
Authors: Conkling Kathryn , Karki Chanda , Tuladhar Heera , Bracken Hillary , Winikoff Beverly 
Published: November 2014

AbstractObjectiveTo assess the uptake and acceptability of self‐administration of mifepristone at home for medical abortion in Nepal.MethodsA prospective, comparative, non‐randomized, open‐label study was conducted at two hospitals in Kathmandu, Nepal, between November 11, 2009, and January 15, 2011. All women in good health and aged 18 years or older who sought medical abortion after fewer than 64 days of pregnancy were enrolled. Participants were offered the choice of taking 200 mg mifepristone orally in the clinic or at home; all participants self‐administered 400 μg of sublingual misoprostol at home 24–72 hours later. All participants were scheduled to return to the clinic within 14 days of mifepristone administration for follow‐up.ResultsAmong 200 participants, 144 (72.0%) opted to take the mifepristone at home. Medical abortion was successful in 130 (95.6%) of 136 women in the home group who were followed up and 53 (94.6%) of 56 women in the clinic group. Only 4 (2.9%) women in the home group took the mifepristone after the scheduled time. Overall, 133 (97.8%) women in the home group stated that they would recommend home administration of mifepristone if a friend wanted a medical abortion.ConclusionSelf‐administration of mifepristone outside the clinic should be offered to all women as part of routine medical abortion services in Nepal.Clinicaltrials.gov: NCT00994734.
Uptake of a women‐only, sex‐work‐specific drop‐in center and links with sexual and reproductive health care for sex workers
Authors: Kim Soyoun Rachel , Goldenberg Shira M. , Duff Putu , Nguyen Paul , Gibson Kate , Shannon Kate 
Published: November 2014

AbstractObjectiveTo longitudinally examine female sex workers’ (FSWs’) uptake of a women‐only, sex‐work‐specific drop‐in service and its impact on their access to sexual and reproductive health (SRH) services.MethodsFor the present longitudinal analysis, data were drawn from the AESHA (An Evaluation of Sex Workers’ Health Access) study, a community‐based, open, prospective cohort of FSWs from Vancouver, BC, Canada. Data obtained between January 2010 and February 2013 were analyzed. Participants are followed up on a semi‐annual basis. Multivariable logistic regression using generalized estimating equations was used to identify correlates of service uptake.ResultsOf 547 FSWs included in the present analysis, 330 (60.3%) utilized the services during the 3‐year study period. Service use was independently associated with age (adjusted odds ratio [AOR] 1.04; 95% confidence interval [CI] 1.03–1.06), Aboriginal ancestry (AOR 2.18; 95% CI 1.61–2.95), injection drug use (AOR 1.67; 95% CI 1.29–2.17), exchange of sex for drugs (AOR 1.40; 95%CI 1.15–1.71), and accessing SRH services (AOR 1.65; 95% CI 1.35–2.02).ConclusionA sex‐work‐specific drop‐in space for marginalized FSWs had high uptake. Women‐centered and low‐threshold drop‐in services can effectively link marginalized women with SRH services.
Immediate electrical storm of Torsades de Pointes after CRT‐D implantation in an ischemic cardiomyopathy patient
Authors: Kaya Adnan , Sungur Aylin , Tekkesin Ahmet Ilker , Turkkan Ceyhan , Alper Ahmet Taha 
Published: November 2014

AbstractCardiac resynchronization therapy with an implantable cardioverter‐defibrillator (CRT‐D) is the preferred treatment for patients with severe heart failure, dyssynchrony, and an increased risk of sudden cardiac death or for primary ventricular arrhythmia survivors. Rarely, left ventricular epicardial pacing can induce ventricular tachyarrhythmia rather than a beneficial effect. We describe an ischemic cardiomyopathy patient who underwent CRT‐D therapy and developed sustained torsades de pointes (TdP) immediately after switching to biventricular pacing (BVP) mode. Here, TdP possibly developed owing to the change in the dispersion of repolarization of the left ventricle myocardium. The diagnosis and management of BVP‐induced ventricular arrhythmia is discussed.
Prediction of clinical outcome in glioblastoma using a biologically relevant nine‐microRNA signature
Authors: Hayes Josie , Thygesen Helene , Tumilson Charlotte , Droop Alastair , Boissinot Marjorie , Hughes Thomas A. , Westhead David , Alder Jane E. , Shaw Lisa , Short Susan C. , Lawler Sean E. 
Published: November 2014

BackgroundGlioblastoma is the most aggressive primary brain tumor, and is associated with a very poor prognosis. In this study we investigated the potential of microRNA expression profiles to predict survival in this challenging disease.MethodsMicroRNA and mRNA expression data from glioblastoma (n = 475) and grade II and III glioma (n = 178) were accessed from The Cancer Genome Atlas. LASSO regression models were used to identify a prognostic microRNA signature. Functionally relevant targets of microRNAs were determined using microRNA target prediction, experimental validation and correlation of microRNA and mRNA expression data.ResultsA 9‐microRNA prognostic signature was identified which stratified patients into risk groups strongly associated with survival (p = 2.26e−09), significant in all glioblastoma subtypes except the non‐G‐CIMP proneural group. The statistical significance of the microRNA signature was higher than MGMT methylation in temozolomide treated tumors. The 9‐microRNA risk score was validated in an independent dataset (p = 4.50e−02) and also stratified patients into high‐ and low‐risk groups in lower grade glioma (p = 5.20e−03). The majority of the 9 microRNAs have been previously linked to glioblastoma biology or treatment response. Integration of the expression patterns of predicted microRNA targets revealed a number of relevant microRNA/target pairs, which were validated in cell lines.ConclusionsWe have identified a novel, biologically relevant microRNA signature that stratifies high‐ and low‐risk patients in glioblastoma. MicroRNA/mRNA interactions identified within the signature point to novel regulatory networks. This is the first study to formulate a survival risk score for glioblastoma which consists of microRNAs associated with glioblastoma biology and/or treatment response, indicating a functionally relevant signature.
Late Glacial Lake-Level Changes in the Lake Karakul Basin (a Closed Glacierized-Basin), eastern Pamirs, Tajikistan
Authors: Komatsu Tetsuya , Tsukamoto Sumiko 
Published: November 2014

AbstractThe lake-level variations during the Late Glacial in the Lake Karakul basin (a closed glacierized-basin), in the northernmost part of the eastern Pamirs, were reconstructed using geomorphological and sedimentological evidence, with a chronology developed using luminescence ages from sand-sized quartz and K-feldspar in the lake sediments. Lake transgression started before ~ 19 ka, with the peak water level of ~ 35 m above the present elevation occurring at ~ 15 ka. This was synchronous with a significant advance of the glacier in the catchment. Stepwise lake regression, including a rapid lowering of the lake level (~ 13 m at ~ 12 ka), persisted until at least ~ 10 ka. Lake transgression and localized glacier expansion from ~ 19 to ~ 15 ka likely correlate with the more regional Late Glacial glacier advances across the semi-arid western Himalayan–Tibetan orogen and the eastern Pamirs. The longer-term trend of this lake transgression was probably caused by colder and/or wetter climatic conditions, forcing a notable glacier advance.
Use of a Population Pharmacokinetic Approach for the Clinical Development of a Fixed‐Dose Subcutaneous Formulation of Trastuzumab
Authors: Hourcade‐Potelleret F , Lemenuel‐Diot A , McIntyre C , Brewster M , Lum B , Bittner B 
Published: November 2014

A new subcutaneous (s.c.) trastuzumab formulation provides savings in terms of time and is preferred by patients and health care professionals relative to standard intravenous (i.v.) administration due to simpler and more rapid administration (2–5 minutes). Selection of the s.c. dose was based on a pharmacokinetic bridging approach that aimed to achieve noninferior trastuzumab serum trough concentrations (Ctrough) vs. reference i.v. administration. Using population modeling and simulation, we showed that a fixed 600‐mg trastuzumab s.c. dose, administered thrice‐weekly (Q3W) without a loading dose, would provide Ctrough (predose Cycle 8) and area under the time–concentration curve (AUC0–21 days, Cycle 7) at least as high as Q3W i.v. administration. The model was retrospectively validated using observed pharmacokinetic data from an independent phase III study of (neo)adjuvant trastuzumab (HannaH). These results provide a strong pharmacokinetic rationale for the trastuzumab s.c. 600‐mg fixed dose, supported by the noninferior efficacy of this regimen vs. reference i.v. administration.CPT Pharmacometrics Syst. Pharmacol. (2014) 3, e87; doi:10.1038/psp.2013.63; advance online publication 2 January 2014
Faster sequence homology searches by clustering subsequences
Authors: Suzuki Shuji , Kakuta Masanori , Ishida Takashi , Akiyama Yutaka 
Published: November 2014

Abstract
Motivation: Sequence homology searches are used in various fields. New sequencing technologies produce huge amounts of sequence data, which continuously increase the size of sequence databases. As a result, homology searches require large amounts of computational time, especially for metagenomic analysis.
Results: We developed a fast homology search method based on database subsequence clustering, and implemented it as GHOSTZ. This method clusters similar subsequences from a database to perform an efficient seed search and ungapped extension by reducing alignment candidates based on triangle inequality. The database subsequence clustering technique achieved an ∼2-fold increase in speed without a large decrease in search sensitivity. When we measured with metagenomic data, GHOSTZ is ∼2.2–2.8 times faster than RAPSearch and is ∼185–261 times faster than BLASTX.
Availability and implementation: The source code is freely available for download at http://www.bi.cs.titech.ac.jp/ghostz/
Contact: akiyama@cs.titech.ac.jp
Supplementary information: Supplementary data are available at Bioinformatics online.
PEASE: predicting B-cell epitopes utilizing antibody sequence
Authors: Sela-Culang Inbal , Ashkenazi Shaul , Peters Bjoern , Ofran Yanay 
Published: November 2014

Abstract
Summary: Antibody epitope mapping is a key step in understanding antibody–antigen recognition and is of particular interest for drug development, diagnostics and vaccine design. Most computational methods for epitope prediction are based on properties of the antigen sequence and/or structure, not taking into account the antibody for which the epitope is predicted. Here, we introduce PEASE, a web server predicting antibody-specific epitopes, utilizing the sequence of the antibody. The predictions are provided both at the residue level and as patches on the antigen structure. The tradeoff between recall and precision can be tuned by the user, by changing the default parameters. The results are provided as text and HTML files as well as a graph, and can be viewed on the antigen 3D structure.
Availability and implementation: PEASE is freely available on the web at www.ofranlab.org/PEASE.
Contact: yanay@ofranlab.org
Community-associated MRSA strain ST72-SCCmecIV causing bloodstream infections: clinical outcomes and bacterial virulence factors
Authors: Park Ki-Ho , Chong Yong Pil , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Lee Mi Suk , Jeong Jin-Yong , Woo Jun Hee , Kim Yang Soo 
Published: November 2014

Abstract

Objectives
Community-associated MRSA (CA-MRSA) has emerged in the community and has recently been spreading in healthcare settings. The objectives of this study were to evaluate the clinical outcomes and bacterial virulence factors of the Korean CA-MRSA (ST72-SCCmecIV) strain, which causes bloodstream infections.

Methods
All adult patients with MRSA bacteraemia were prospectively enrolled. Clinical outcomes, microbiological characteristics and 40 bacterial virulence factors were evaluated.

Results
Of the 352 typed MRSA isolates, 342 isolates (97.2%) belonged to three Panton–Valentine leucocidin-negative strains: ST5-SCCmecII (70.2%), ST72-SCCmecIV (22.4%) and ST239-SCCmecIII (4.6%). The remaining 10 (2.8%) isolates from minor strains were excluded from the final analysis. After controlling for several confounding factors, ST72-SCCmecIV was associated with the lowest mortality (compared with ST5-SCCmecII, adjusted OR = 0.26; 95% CI = 0.13–0.54). However, MRSA isolates with vancomycin MICs of ≥1.5 mg/L were more common in ST72-SCCmecIV compared with ST5-SCCmecII (84.8% versus 66.7%; P = 0.002). Reduced vancomycin susceptibility and vancomycin heteroresistance were not associated with mortality. Compared with ST5-SCCmecII isolates, ST72-SCCmecIV isolates were less likely to harbour multiple virulence genes. Of these genes, three staphylococcal superantigen genes were associated with mortality: sec (OR = 2.31; P = 0.002), sel (OR = 2.55; P = 0.003) and tst (OR = 2.76; P &lt; 0.001).

Conclusions
After controlling for confounding factors, ST72-SCCmecIV was independently associated with lower mortality compared with ST5-SCCmecII, suggesting this CA-MRSA strain to be of lower virulence. The lack of virulence genes, including staphylococcal superantigen genes, may play a role in the lower virulence of this strain.
Generalised empirical Bayesian methods for discovery of differential data in high-throughput biology
Authors: Hardcastle Thomas J 
Published: November 2014

ABSTRACTMotivationHigh-throughput data are now commonplace in biological research. Rapidly changing technologies and application mean that novel methods for detecting differential behaviour that account for a ‘largeP, smalln’ setting are required at an increasing rate. The development of such methods is, in general, being done on anad hocbasis, requiring further development cycles and a lack of standardization between analyses.ResultsWe present here a generalised method for identifying differential behaviour within high-throughput biological data through empirical Bayesian methods. This approach is based on ourbaySeqalgorithm for identification of differential expression in RNA-seq data based on a negative binomial distribution, and in paired data based on a beta-binomial distribution. Here we show how the same empirical Bayesian approach can be applied to any parametric distribution, removing the need for lengthy development of novel methods for differently distributed data. Comparisons with existing methods developed to address specific problems in high-throughput biological data show that these generic methods can achieve equivalent or better performance. A number of enhancements to the basic algorithm are also presented to increase flexibility and reduce computational costs.AvailabilityThe methods are implemented in theRbaySeq(v2) package, available on Bioconductorhttp://www.bioconductor.org/packages/release/bioc/html/baySeq.html.Contacttjh48@cam.ac.uk
msCentipede: Modeling heterogeneity across genomic sites improves accuracy in the inference of transcription factor binding
Authors: Raj Anil , Shim Heejung , Gilad Yoav , Pritchard Jonathan K. , Stephens Matthew 
Published: November 2014

AbstractMotivation:Understanding global gene regulation depends critically on accurate annotation of regulatory elements that are functional in a given cell type. CENTIPEDE, a powerful, probabilistic framework for identifying transcription factor binding sites from tissue-specific DNase I cleavage patterns and genomic sequence content, leverages the hypersensitivity of factor-bound chromatin and the information in the DNase I spatial cleavage profile characteristic of each DNA binding protein to accurately infer functional factor binding sites. However, the model for the spatial profile in this framework underestimates the substantial variation in the DNase I cleavage profiles across factor-bound genomic locations and across replicate measurements of chromatin accessibility.Results:In this work, we adapt a multi-scale modeling framework for inhomogeneous Poisson processes to better model the underlying variation in DNase I cleavage patterns across genomic locations bound by a transcription factor. In addition to modeling variation, we also model spatial structure in the heterogeneity in DNase I cleavage patterns for each factor. Using DNase-seq measurements assayed in a lymphoblastoid cell line, we demonstrate the improved performance of this model for several transcription factors by comparing against the Chip-Seq peaks for those factors. Finally, we propose an extension to this framework that allows for a more flexible background model and evaluate the additional gain in accuracy achieved when the background model parameters are estimated using DNase-seq data from naked DNA. The proposed model can also be applied to paired-end ATAC-seq and DNase-seq data in a straightforward manner.Availability:msCentipede, a Python implementation of an algorithm to infer transcription factor binding using this model, is made available athttps://github.com/rajanil/msCentipede