Twelve-month efficacy of second-generation cryoballoon ablation for atrial fibrillation performed at community hospitals: results of the German register on cryoballoon ablation in local hospitals (regional).

Background: The 12-month follow-up (F/U) efficacy of CBA PVI performed at community hospitals for treatment of symptomatic paroxysmal and persistent atrial fibrillation (AF) is unknown. This study determined the 12-month efficacy of pulmonary vein isolation (PVI) using cryoballoon ablation (CBA) performed at community hospitals with limited annual case numbers.

Methods: This registry study included 983 consecutive patients (pts) from 19 hospitals, each with an annual procedural volume of < 100 PVI procedures/year.

Safety and acute efficacy of cryoballoon ablation for atrial fibrillation at community hospitals.

Aims: Pulmonary vein isolation (PVI) using cryoballoon ablation (CBA) is an established procedure for treating symptomatic paroxysmal and persistent atrial fibrillation (AF). The safety and efficacy of PVI performed at community hospitals are unknown. We aimed to determine the safety and acute efficacy of PVI using CBA performed at community hospitals with limited annual case numbers.

Systems analysis utilising pathway interactions identifies sonic hedgehog pathway as a primary biomarker and oncogenic target in hepatocellular carcinoma.

The development and progression of cancer is associated with disruption of biological networks. Historically studies have identified sets of signature genes involved in events ultimately leading to the development of cancer. Identification of such sets does not indicate which biologic processes are oncogenic drivers and makes it difficult to identify key networks to target for interventions.

Genome-wide transcriptional sequencing identifies novel mutations in metabolic genes in human hepatocellular carcinoma.

We report on next-generation transcriptome sequencing results of three human hepatocellular carcinoma tumor/tumor-adjacent pairs. This analysis robustly examined ∼12,000 genes for both expression differences and molecular alterations. We observed 4,513 and 1,182 genes demonstrating 2-fold or greater increase or decrease in expression relative to their normal, respectively.

Obesity in adults is associated with reduced lung function in metabolic syndrome and diabetes: the Strong Heart Study.

Objective: The purposes of this study were to investigate whether reduced lung function is associated with metabolic syndrome (MS) and diabetes (DM) in American Indians (AIs) and to determine whether lower pulmonary function presents before the development of DM or MS.

Research Design And Methods: The Strong Heart Study (SHS) is a multicenter, prospective study of cardiovascular disease (CVD) and its risk factors among AI adults. The present analysis used lung function assessment by standard spirometry at the SHS second examination (1993-1995) in 2,396 adults free of overt lung disease or CVD, with or without DM or MS.

The PathOlogist: an automated tool for pathway-centric analysis.

Background: The PathOlogist is a new tool designed to transform large sets of gene expression data into quantitative descriptors of pathway-level behavior. The tool aims to provide a robust alternative to the search for single-gene-to-phenotype associations by accounting for the complexity of molecular interactions.

Results: Molecular abundance data is used to calculate two metrics--'activity' and 'consistency'--for each pathway in a set of more than 500 canonical molecular pathways (source: Pathway Interaction Database, http://pid.

Detecting cancer gene networks characterized by recurrent genomic alterations in a population.

High resolution, system-wide characterizations have demonstrated the capacity to identify genomic regions that undergo genomic aberrations. Such research efforts often aim at associating these regions with disease etiology and outcome. Identifying the corresponding biologic processes that are responsible for disease and its outcome remains challenging.

The BioPAX community standard for pathway data sharing.

Biological Pathway Exchange (BioPAX) is a standard language to represent biological pathways at the molecular and cellular level and to facilitate the exchange of pathway data. The rapid growth of the volume of pathway data has spurred the development of databases and computational tools to aid interpretation; however, use of these data is hampered by the current fragmentation of pathway information across many databases with incompatible formats. BioPAX, which was created through a community process, solves this problem by making pathway data substantially easier to collect, index, interpret and share.

Needles in the haystack: identifying individuals present in pooled genomic data.

Recent publications have described and applied a novel metric that quantifies the genetic distance of an individual with respect to two population samples, and have suggested that the metric makes it possible to infer the presence of an individual of known genotype in a sample for which only the marginal allele frequencies are known. However, the assumptions, limitations, and utility of this metric remained incompletely characterized. Here we present empirical tests of the method using publicly accessible genotypes, as well as analytical investigations of the method's strengths and limitations.

The completion of the Mammalian Gene Collection (MGC).

Since its start, the Mammalian Gene Collection (MGC) has sought to provide at least one full-protein-coding sequence cDNA clone for every human and mouse gene with a RefSeq transcript, and at least 6200 rat genes. The MGC cloning effort initially relied on random expressed sequence tag screening of cDNA libraries. Here, we summarize our recent progress using directed RT-PCR cloning and DNA synthesis.

Identification of microbial DNA in human cancer.

Background: Microorganisms have been associated with many types of human diseases; however, a significant number of clinically important microbial pathogens remain to be discovered.

Methods: We have developed a genome-wide approach, called Digital Karyotyping Microbe Identification (DK-MICROBE), to identify genomic DNA of bacteria and viruses in human disease tissues. This method involves the generation of an experimental DNA tag library through Digital Karyotyping (DK) followed by analysis of the tag sequences for the presence of microbial DNA content using a compiled microbial DNA virtual tag library.

PID: the Pathway Interaction Database.

The Pathway Interaction Database (PID, http://pid.nci.nih.

Superposition of transcriptional behaviors determines gene state.

We introduce a novel technique to determine the expression state of a gene from quantitative information measuring its expression. Adopting a productive abstraction from current thinking in molecular biology, we consider two expression states for a gene--Up or Down. We determine this state by using a statistical model that assumes the data behaves as a combination of two biological distributions.

A revision of Neomegalotomus (Hemiptera: Alydidae).

We recognize two species in Neomegalotomus, N. parvus (Westwood), the type species; and N. rufipes (Westwood).

The correct name of the neotropical soybean bug (Hemiptera: Alydidae).

A species of Neomegalotomus is an occasional pest of soybean [Glycine max (L.) Merrill] in the neotropics, including in Brazil. It was known as Neomegalotomus parvus (Westwood); but the discovery of the type specimen of a species described earlier requires that the name be changed to Neomegalotomus simplex (Westwood), which becomes the correct name for the soybean pest.

Identification of key processes underlying cancer phenotypes using biologic pathway analysis.

Cancer is recognized to be a family of gene-based diseases whose causes are to be found in disruptions of basic biologic processes. An increasingly deep catalogue of canonical networks details the specific molecular interaction of genes and their products. However, mapping of disease phenotypes to alterations of these networks of interactions is accomplished indirectly and non-systematically.

Cancers as wounds that do not heal: differences and similarities between renal regeneration/repair and renal cell carcinoma.

Cancers have been described as wounds that do not heal, suggesting that the two share common features. By comparing microarray data from a model of renal regeneration and repair (RRR) with reported gene expression in renal cell carcinoma (RCC), we asked whether those two processes do, in fact, share molecular features and regulatory mechanisms. The majority (77%) of the genes expressed in RRR and RCC were concordantly regulated, whereas only 23% were discordant (i.

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project.

A proteomic characterization of the plasma membrane of human epidermis by high-throughput mass spectrometry.

Membrane proteins are responsible for many critical cellular functions and identifying cell surface proteins on different keratinocyte populations by proteomic approaches would improve our understanding of their biological function. The ability to characterize membrane proteins, however, has lagged behind that of soluble proteins both in terms of throughput and protein coverage. In this study, a membrane proteomic investigation of keratinocytes using a two-dimensional liquid chromatography (LC) tandem-mass spectrometry (MS/MS) approach that relies on a buffered methanol-based solubilization, and tryptic digestion of purified plasma membrane is described.

Pathway databases.

Network representations of biological pathways offer a functional view of molecular biology that is different from and complementary to sequence, expression, and structure databases. There is currently available a wide range of digital collections of pathway data, differing in organisms included, functional area covered (e.g.

Quantitative proteomic analysis of inorganic phosphate-induced murine MC3T3-E1 osteoblast cells.

Cleavable isotope-coded affinity tag (cICAT) reagents were utilized to identify and quantitate protein expression differences in control and inorganic phosphate-treated murine MC3T3-E1 osteoblast cells. Proteins extracted from control and treated cells were labeled with the light and heavy isotopic versions of cICAT reagents, respectively. The cICAT-labeled samples were combined, proteolytically digested, and the cICAT-derivatized peptides isolated using immobilized avidin chromatography.

Proteomic analysis of detergent-resistant membrane rafts.

A combined, detergent- and organic solvent-based proteomic method for the analysis of detergent-resistant membrane rafts (DRMR) is described. These specialized domains of the plasma membrane contain a distinctive and dynamic protein and/or lipid complement, which can be isolated from most mammalian cells. Lipid rafts are predominantly involved in signal transduction and adapted to mediate and produce different cellular responses.

Associations of postmenopausal hormone therapy with markers of hemostasis and inflammation and lipid profiles in diabetic and nondiabetic american Indian women: the strong heart study.

Objectives: To examine the associations of postmenopausal hormone therapy (PHT) with indicators of hemostasis and inflammation and with lipid profiles in American Indian women and to determine if diabetes modifies these associations.

Methods: This report is a cross-sectional analysis of data from 1446 postmenopausal women who were free from cardiovascular disease (CVD) at the second Strong Heart Study examination (1993-1995). Diabetes was diagnosed by WHO criteria.

Direct ampholyte-free liquid-phase isoelectric peptide focusing: application to the human serum proteome.

In this study, we utilized a multidimensional peptide separation strategy combined with tandem mass spectrometry (MS/MS) for the identification of proteins in human serum. After enzymatically digesting serum with trypsin, the peptides were fractionated using liquid-phase isoelectric focusing (IEF) in a novel ampholyte-free format. Twenty IEF fractions were collected and analyzed by reversed-phase microcapillary liquid chromatography (microLC)-MS/MS.

caCORE: a common infrastructure for cancer informatics.

Motivation: Sites with substantive bioinformatics operations are challenged to build data processing and delivery infrastructure that provides reliable access and enables data integration. Locally generated data must be processed and stored such that relationships to external data sources can be presented. Consistency and comparability across data sets requires annotation with controlled vocabularies and, further, metadata standards for data representation.