bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells
Authors: Amabile Giovanni , Welner Robert S. , Nombela-Arrieta Cesar , D'Alise Anna Morena , Di Ruscio Annalisa , Ebralidze Alexander K. , Kraytsberg Yevgenya , Ye Min , Kocher Olivier , Neuberg Donna S. , Khrapko Konstantin , Silberstein Leslie E. , Tenen Daniel G. 
Published: December 2012

Key Points
Human hematopoietic cells develop within human iPSC-derived teratomas in immunodeficient mice. Co-transplantation of OP9 stromal cells along with human iPSCs increases hematopoietic specification within teratomas.
Some higher order Hardy inequalities
Authors: Kufner Alois , Kuliev Komil , Persson Lars-Erik 
Published: December 2012

Abstract
We investigate the k-th order Hardy inequality (1.1) for functions satisfying rather general boundary conditions (1.2), show which of these conditions are admissible and derive sufficient, and necessary and sufficient, conditions (for 0 < q < ∞, p > 1) on u, v for (1.1) to hold.
Comparative evaluation of set-level techniques in predictive classification of gene expression samples
Authors: Holec Matěj , Kléma Jiří , Železný Filip , Tolar Jakub 
Published: December 2012

Abstract

Background
Analysis of gene expression data in terms of a priori-defined gene sets has recently received significant attention as this approach typically yields more compact and interpretable results than those produced by traditional methods that rely on individual genes. The set-level strategy can also be adopted with similar benefits in predictive classification tasks accomplished with machine learning algorithms. Initial studies into the predictive performance of set-level classifiers have yielded rather controversial results. The goal of this study is to provide a more conclusive evaluation by testing various components of the set-level framework within a large collection of machine learning experiments.

Results
Genuine curated gene sets constitute better features for classification than sets assembled without biological relevance. For identifying the best gene sets for classification, the Global test outperforms the gene-set methods GSEA and SAM-GS as well as two generic feature selection methods. To aggregate expressions of genes into a feature value, the singular value decomposition (SVD) method as well as the SetSig technique improve on simple arithmetic averaging. Set-level classifiers learned with 10 features constituted by the Global test slightly outperform baseline gene-level classifiers learned with all original data features although they are slightly less accurate than gene-level classifiers learned with a prior feature-selection step.

Conclusion
Set-level classifiers do not boost predictive accuracy, however, they do achieve competitive accuracy if learned with the right combination of ingredients.

Availability
Open-source, publicly available software was used for classifier learning and testing. The gene expression datasets and the gene set database used are also publicly available. The full tabulation of experimental results is available at http://ida.felk.cvut.cz/CESLT.
The Genboree Microbiome Toolset and the analysis of 16S rRNA microbial sequences
Authors: Riehle Kevin , Coarfa Cristian , Jackson Andrew , Ma Jun , Tandon Arpit , Paithankar Sameer , Raghuraman Sriram , Mistretta Toni-Ann , Saulnier Delphine , Raza Sabeen , Diaz Maria Alejandra , Shulman Robert , Aagaard Kjersti , Versalovic James , Milosavljevic Aleksandar 
Published: December 2012

Abstract

Background
Microbial metagenomic analyses rely on an increasing number of publicly available tools. Installation, integration, and maintenance of the tools poses significant burden on many researchers and creates a barrier to adoption of microbiome analysis, particularly in translational settings.

Methods
To address this need we have integrated a rich collection of microbiome analysis tools into the Genboree Microbiome Toolset and exposed them to the scientific community using the Software-as-a-Service model via the Genboree Workbench. The Genboree Microbiome Toolset provides an interactive environment for users at all bioinformatic experience levels in which to conduct microbiome analysis. The Toolset drives hypothesis generation by providing a wide range of analyses including alpha diversity and beta diversity, phylogenetic profiling, supervised machine learning, and feature selection.

Results
We validate the Toolset in two studies of the gut microbiota, one involving obese and lean twins, and the other involving children suffering from the irritable bowel syndrome.

Conclusions
By lowering the barrier to performing a comprehensive set of microbiome analyses, the Toolset empowers investigators to translate high-volume sequencing data into valuable biomedical discoveries.
A cross-validation scheme for machine learning algorithms in shotgun proteomics
Authors: Granholm Viktor , Noble William Stafford , Käll Lukas 
Published: December 2012

AbstractPeptides are routinely identified from mass spectrometry-based proteomics experiments by matching observed spectra to peptides derived from protein databases. The error rates of these identifications can be estimated by target-decoy analysis, which involves matching spectra to shuffled or reversed peptides. Besides estimating error rates, decoy searches can be used by semi-supervised machine learning algorithms to increase the number of confidently identified peptides. As for all machine learning algorithms, however, the results must be validated to avoid issues such as overfitting or biased learning, which would produce unreliable peptide identifications. Here, we discuss how the target-decoy method is employed in machine learning for shotgun proteomics, focusing on how the results can be validated by cross-validation, a frequently used validation scheme in machine learning. We also use simulated data to demonstrate the proposed cross-validation scheme's ability to detect overfitting.
An amputation resets positional information to a proximal identity in the regenerating zebrafish caudal fin
Authors: Azevedo Ana Sofia , Sousa Sara , Jacinto António , Saúde Leonor 
Published: December 2012

Abstract

Background
Zebrafish has emerged as a powerful model organism to study the process of regeneration. This teleost fish has the ability to regenerate various tissues and organs like the heart, spinal cord, retina and fins. In this study, we took advantage of the existence of an excellent morphological reference in the zebrafish caudal fin, the bony ray bifurcations, as a model to study positional information upon amputation. We investigated the existence of positional information for bifurcation formation by performing repeated amputations at different proximal-distal places along the fin.

Results
We show that, while amputations performed at a long distance from the bifurcation do not change its final proximal-distal position in the regenerated fin, consecutive amputations done at 1 segment proximal to the bifurcation (near the bifurcation) induce a positional reset and progressively shift its position distally. Furthermore, we investigated the potential role of Shh and Fgf signalling pathways in the determination of the bifurcation position and observed that they do not seem to be involved in this process.

Conclusions
Our results reveal that, an amputation near the bifurcation inhibits the formation of the regenerated bifurcation in the pre-amputation position, inducing a distalization of this structure. This shows that the positional memory for bony ray bifurcations depends on the proximal-distal level of the amputation.
Transcriptome profiling of the demosponge Amphimedon queenslandica reveals genome-wide events that accompany major life cycle transitions
Authors: Conaco Cecilia , Neveu Pierre , Zhou Hongjun , Arcila Mary Luz , Degnan Sandie M , Degnan Bernard M , Kosik Kenneth S 
Published: December 2012

Abstract

Background
The biphasic life cycle with pelagic larva and benthic adult stages is widely observed in the animal kingdom, including the Porifera (sponges), which are the earliest branching metazoans. The demosponge, Amphimedon queenslandica, undergoes metamorphosis from a free-swimming larva into a sessile adult that bears no morphological resemblance to other animals. While the genome of A. queenslandica contains an extensive repertoire of genes very similar to that of complex bilaterians, it is as yet unclear how this is drawn upon to coordinate changing morphological features and ecological demands throughout the sponge life cycle.

Results
To identify genome-wide events that accompany the pelagobenthic transition in A. queenslandica, we compared global gene expression profiles at four key developmental stages by sequencing the poly(A) transcriptome using SOLiD technology. Large-scale changes in transcription were observed as sponge larvae settled on the benthos and began metamorphosis. Although previous systematics suggest that the only clear homology between Porifera and other animals is in the embryonic and larval stages, we observed extensive use of genes involved in metazoan-associated cellular processes throughout the sponge life cycle. Sponge-specific transcripts are not over-represented in the morphologically distinct adult; rather, many genes that encode typical metazoan features, such as cell adhesion and immunity, are upregulated. Our analysis further revealed gene families with candidate roles in competence, settlement, and metamorphosis in the sponge, including transcription factors, G-protein coupled receptors and other signaling molecules.

Conclusions
This first genome-wide study of the developmental transcriptome in an early branching metazoan highlights major transcriptional events that accompany the pelagobenthic transition and point to a network of regulatory mechanisms that coordinate changes in morphology with shifting environmental demands. Metazoan developmental and structural gene orthologs are well-integrated into the expression profiles at every stage of sponge development, including the adult. The utilization of genes involved in metazoan-associated processes throughout sponge development emphasizes the potential of the genome of the last common ancestor of animals to generate phenotypic complexity.
Asymmetric purine-pyrimidine distribution in cellular small RNA population of papaya
Authors: Aryal Rishi , Yang Xiaozeng , Yu Qingyi , Sunkar Ramanjulu , Li Lei , Ming Ray 
Published: December 2012

Abstract

Background
The small RNAs (sRNA) are a regulatory class of RNA mainly represented by the 21 and 24-nucleotide size classes. The cellular sRNAs are processed by RNase III family enzyme dicer (Dicer like in plant) from a self-complementary hairpin loop or other type of RNA duplexes. The papaya genome has been sequenced, but its microRNAs and other regulatory RNAs are yet to be analyzed.

Results
We analyzed the genomic features of the papaya sRNA population from three sRNA deep sequencing libraries made from leaves, flowers, and leaves infected with Papaya Ringspot Virus (PRSV). We also used the deep sequencing data to annotate the micro RNA (miRNA) in papaya. We identified 60 miRNAs, 24 of which were conserved in other species, and 36 of which were novel miRNAs specific to papaya. In contrast to the Chargaff’s purine-pyrimidine equilibrium, cellular sRNA was significantly biased towards a purine rich population. Of the two purine bases, higher frequency of adenine was present in 23nt or longer sRNAs, while 22nt or shorter sRNAs were over represented by guanine bases. However, this bias was not observed in the annotated miRNAs in plants. The 21nt species were expressed from fewer loci but expressed at higher levels relative to the 24nt species. The highly expressed 21nt species were clustered in a few isolated locations of the genome. The PRSV infected leaves showed higher accumulation of 21 and 22nt sRNA compared to uninfected leaves. We observed higher accumulation of miRNA* of seven annotated miRNAs in virus-infected tissue, indicating the potential function of miRNA* under stressed conditions.

Conclusions
We have identified 60 miRNAs in papaya. Our study revealed the asymmetric purine-pyrimidine distribution in cellular sRNA population. The 21nt species of sRNAs have higher expression levels than 24nt sRNA. The miRNA* of some miRNAs shows higher accumulation in PRSV infected tissues, suggesting that these strands are not totally functionally redundant. The findings open a new avenue for further investigation of the sRNA silencing pathway in plants.
Multi-objective dynamic population shuffled frog-leaping biclustering of microarray data
Authors: Liu Junwan , Li Zhoujun , Hu Xiaohua , Chen Yiming , Liu Feifei 
Published: December 2012

Abstract

Background
Multi-objective optimization (MOO) involves optimization problems with multiple objectives. Generally, theose objectives is used to estimate very different aspects of the solutions, and these aspects are often in conflict with each other. MOO first gets a Pareto set, and then looks for both commonality and systematic variations across the set. For the large-scale data sets, heuristic search algorithms such as EA combined with MOO techniques are ideal. Newly DNA microarray technology may study the transcriptional response of a complete genome to different experimental conditions and yield a lot of large-scale datasets. Biclustering technique can simultaneously cluster rows and columns of a dataset, and hlep to extract more accurate information from those datasets. Biclustering need optimize several conflicting objectives, and can be solved with MOO methods. As a heuristics-based optimization approach, the particle swarm optimization (PSO) simulate the movements of a bird flock finding food. The shuffled frog-leaping algorithm (SFL) is a population-based cooperative search metaphor combining the benefits of the local search of PSO and the global shuffled of information of the complex evolution technique. SFL is used to solve the optimization problems of the large-scale datasets.

Results
This paper integrates dynamic population strategy and shuffled frog-leaping algorithm into biclustering of microarray data, and proposes a novel multi-objective dynamic population shuffled frog-leaping biclustering (MODPSFLB) algorithm to mine maximum bicluesters from microarray data. Experimental results show that the proposed MODPSFLB algorithm can effectively find significant biological structures in terms of related biological processes, components and molecular functions.

Conclusions
The proposed MODPSFLB algorithm has good diversity and fast convergence of Pareto solutions and will become a powerful systematic functional analysis in genome research.
Identification and recombinant expression of anandamide hydrolyzing enzyme from Dictyostelium discoideum
Authors: Neelamegan Dhamodharan , Schoenhofen Ian C , Richards James C , Cox Andrew D 
Published: December 2012

Abstract

Background
Anandamide (Arachidonoyl ethanolamide) is a potent bioactive lipid studied extensively in humans, which regulates several neurobehavioral processes including pain, feeding and memory. Bioactivity is terminated when hydrolyzed into free arachidonic acid and ethanolamine by the enzyme fatty acid amide hydrolase (FAAH). In this study we report the identification of a FAAH homolog from Dictyostelium discoideum and its function to hydrolyze anandamide.

Results
A putative FAAH DNA sequence coding for a conserved amidase signature motif was identified in the Dictyostelium genome database and the corresponding cDNA was isolated and expressed as an epitope tagged fusion protein in either E.coli or Dictyostelium. Wild type Dictyostelium cells express FAAH throughout their development life cycle and the protein was found to be predominantly membrane associated. Production of recombinant HIS tagged FAAH protein was not supported in E.coli host, but homologous Dictyostelium host was able to produce the same successfully. Recombinant FAAH protein isolated from Dictyostelium was shown to hydrolyze anandamide and related synthetic fatty acid amide substrates.

Conclusions
This study describes the first identification and characterisation of an anandamide hydrolyzing enzyme from Dictyostelium discoideum, suggesting the potential of Dictyostelium as a simple eukaryotic model system for studying mechanisms of action of any FAAH inhibitors as drug targets.
Percutaneous ultrasonographically guided liver punctures: an analysis of 1961 patients over a period of ten years
Authors: Mueller Michael , Kratzer Wolfgang , Oeztuerk Suemeyra , Wilhelm Manfred , Mason Richard Andrew , Mao Ren , Haenle Mark Martin 
Published: December 2012

Abstract

Background
Ultrasonographically guided punctures of the liver represent a decisive tool in the diagnosis of many diseases of the liver. Objective of the study was to determine the extent to which the complication rate for ultrasonographically guided punctures of the liver is affected by less comprehensively studied risk factors.

Methods
A total of 2,229 liver biopsies were performed in 1,961 patients (55.5% males; 44.5% females). We recorded actual complications and assessed the following risk factors: needle gauge, puncture technique, examiner experience, coagulation status, puncture target (focal lesion versus parenchyma), lesion size, patient sex and age.

Results
he rate of complications stood at 1.2% (n = 27), of which 0.5% (n = 12) were major and 0.7% (n = 15) minor complications. A significant increase in complications involving bleeding was observed with larger-gauge needles compared with smaller-gauge needles and for cutting biopsy punctures compared with aspiration biopsies (Menghini technique). In the bivariate analysis complications were 2.7 times more frequent in procedures performed by experienced examiners compared with those with comparatively less experience. Lower values for Quick’s test and higher partial thromboplastin times were associated with a higher rate of bleeding. Neither the puncture target, lesion size or patient sex exerted any measurable influence on the puncture risk. Advanced patient age was associated with a higher rate of complications involving bleeding.

Conclusions
Our study helps to establish the importance of potential and less comprehensively studied risk factors and may contribute to further reduction in complications rates in routine clinical practice.
LINE-1 methylation shows little intra-patient heterogeneity in primary and synchronous metastatic colorectal cancer
Authors: Matsunoki Aika , Kawakami Kazuyuki , Kotake Masanori , Kaneko Mami , Kitamura Hirotaka , Ooi Akishi , Watanabe Go , Minamoto Toshinari 
Published: December 2012

Abstract

Background
Long interspersed nucleotide element 1 (LINE-1) hypomethylation is suggested to play a role in the progression of colorectal cancer (CRC). To assess intra-patient heterogeneity of LINE-1 methylation in CRC and to understand its biological relevance in invasion and metastasis, we evaluated the LINE-1 methylation at multiple tumor sites. In addition, the influence of stromal cell content on the measurement of LINE-1 methylation in tumor tissue was analyzed.

Methods
Formalin-fixed paraffin-embedded primary tumor tissue was obtained from 48 CRC patients. Matched adjacent normal colon tissue, lymph node metastases and distant metastases were obtained from 12, 18 and 7 of these patients, respectively. Three different areas were microdissected from each primary tumor and included the tumor center and invasive front. Normal mucosal and stromal cells were also microdissected for comparison with the tumor cells. The microdissected samples were compared in LINE-1 methylation level measured by multicolor MethyLight assay. The assay results were also compared between microdissected and macrodissected tissue samples.

Results
LINE-1 methylation within primary tumors showed no significant intra-tumoral heterogeneity, with the tumor center and invasive front showing identical methylation levels. Moreover, no difference in LINE-1 methylation was observed between the primary tumor and lymph node and distant metastases from the same patient. Tumor cells showed significantly less LINE-1 methylation compared to adjacent stromal and normal mucosal epithelial cells. Consequently, LINE-1 methylation was significantly lower in microdissected samples compared to macrodissected samples. A trend for less LINE-1 methylation was also observed in more advanced stages of CRC.

Conclusions
LINE-1 methylation shows little intra-patient tumor heterogeneity, indicating the suitability of its use for molecular diagnosis in CRC. The methylation is relatively stable during CRC progression, leading us to propose a new concept for the association between LINE-1 methylation and disease stage.
Orbital glomus tumor in an Asian patient
Authors: Chang Minwook , Lee Youngseok , Baek Sehyun , Lee Tae Soo 
Published: December 2012

Abstract

Background
This report describes a recurrent orbital glomus tumor in an Asian patient.

Case presentation
A healthy 50-year-old Korean man had progressive right exophthalmos and a soft mass on his right lower lid for 6 months. We evaluated the mass using CT and MRI, and performed excisional biopsy and pathologic examination. Pathologically, the mass was a glomus tumor. Although proptosis of the right eye decreased, one month after surgery it increased to almost the same level as before surgery.

Conclusions
This is the first report of an Asian patient with an orbital glomus tumor that demonstrated rapid re-growth after incision without pain or visual problems.
Elevated serum levels of Chromogranin A in hepatocellular carcinoma
Authors: Biondi Antonio , Malaguarnera Giulia , Vacante Marco , Berretta Massimiliano , D’Agata Velia , Malaguarnera Michele , Basile Francesco , Drago Filippo , Bertino Gaetano 
Published: December 2012

Abstract

Background
During the past three decades, the incidence of hepatocellular carcinoma in the United States has tripled. The neuroendocrine character has been observed in some tumor cells within some hepatocellular carcinoma nodules and elevated serum chromogranin A also been reported in patients with hepatocellular carcinoma. The aim of this work was to investigate the role of serum concentration of chromogranin A in patients with hepatocellular carcinoma at different stages.

Methods
The study population consisted of 96 patients (63 males and 33 females age range 52-84) at their first hospital admission for hepatocellular carcinoma. The control group consisted of 35 volunteers (20 males and 15 females age range 50-80). The hepatocellular carcinoma patients were stratified according the Barcelona-Clinic Liver Cancer classification. Venous blood samples were collected before treatment from each patients before surgery, centrifuged to obtain serum samples and stored at -80° C until assayed.

Results
The chromogranin A serum levels were elevated (> 100 ng/ml) in 72/96 patients with hepatocellular carcinoma. The serum levels of chromogranin A were significantly correlated (p<0.05) with alpha-fetoprotein. In comparison with controls, the hepatocellular carcinoma patients showed a significant increase (p<0.001) vs controls. The chromogranin A levels in the Barcelona staging of hepatocellular carcinoma was higher in stage D compared to stage C (p<0.01), to stage B (p<0.001), and to stage A (p<0.001).

Conclusions
Molecular markers, such as chromogranin A, could be very useful tools for hepatocellular carcinoma diagnosis. However the molecular classification should be incorporated into a staging scheme, which effectively separated patients into groups with homogeneous prognosis and response to treatment, and thus serves to aid in the selection of appropriate therapy.