bluuebunny/crossref_metadata_2025 huggingface dataset:
Sublobar resection for lung cancer
Authors: Rami-Porta R. , Tsuboi M.
Published: January 2009

Sublobar resection for small lung cancers has been debated frequently and is still a controversial issue. The only randomised trial comparing lobectomy with sublobar resections found a significantly higher recurrence rate for the latter, but failed to show significant differences in survival, although survival was better for the lobectomy group. One meta-analysis and several nonrandomised comparisons have confirmed these results. In general, lobectomy and sublobar resections have similar 5-yr survival rates. Local recurrence after wedge resection is higher than after segmentectomy. However, for patients aged >71 yrs, lobectomy and wedge resection are associated with similar survival. For tumours of ≤2 cm, segmentectomy is equivalent to lobectomy, but survival after segmentectomy is worse if performed for larger tumours. For both segmentectomy and wedge resection, tumour margins should be ≥1 cm wide to avoid recurrence. For pure bronchioloalveolar carcinoma of ≤2 cm, diagnosed intraoperatively with certainty, sublobar resection seems equivalent to lobectomy, and because there is no nodal involvement, systematic nodal dissection may not be necessary. In case of doubt, however, lobectomy with systematic nodal dissection will ensure complete resection and adequate staging. More randomised trials are needed to confirm all these issues.
EGFR-TKI and lung adenocarcinoma with CNS relapse: interest of molecular follow-up
Authors: Ruppert A-M. , Beau-Faller M. , Neuville A. , Guerin E. , Voegeli A-C. , Mennecier B. , Legrain M. , Molard A. , Jeung M-Y. , Gaub M-P. , Oudet P. , Quoix E.
Published: January 2009

The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) erlotinib improves survival of lung cancer as second- or third-line therapy. However, after an initial response, most patients will recur, particularly within the central nervous system.

The present study reports the case of a 27-yr-old nonsmoking male presenting with a metastatic lung adenocarcinoma withEGFRexon 19 deletion, associated with sensitivity to EGFR-TKI. Gefitinib, followed by chemotherapy and finally erlotinib resulted in prolonged disease control, until multiple liver metastases were detected. After stopping EGFR-TKI, brain metastases with carcinomatous meningitis were diagnosed. A secondary T790M mutation, associated with resistance to EGFR-TKI, was found on the liver biopsy but not in the cerebrospinal fluid. Erlotinib was reintroduced and allowed a quick neurological improvement, even though the extra-cranial disease remained resistant to erlotinib.

The present report underscores the interest of molecular monitoring in lung cancer. Persistent cerebral tyrosine kinase inhibitor sensitivity should be considered in patients presenting with an early central nervous system relapse after stopping epidermal growth factor receptor tyrosine kinase inhibitor, even with a T790M-resistant mutation in noncerebral metastases. Questions remain concerning the selection of sub-clones during epidermal growth factor receptor tyrosine kinase inhibitor therapy, which could differ according to metastatic sites, especially in the central nervous system.
Serum adipocyte-fatty acid binding protein level is elevated in severe OSA and correlates with insulin resistance
Authors: Lam D. C-L. , Xu A. , Lam K. S-L. , Lam B. , Lam J. C-M. , Lui M. M-S. , Ip M. S-M.
Published: January 2009

Obstructive sleep apnoea (OSA) is associated with insulin resistance and metabolic syndrome. There is evidence that adipocyte-fatty acid binding protein (A-FABP) may be involved in the development of cardiometabolic dysfunction. The present authors hypothesise that A-FABP is upregulated in OSA.

A total of 124 males without hypertension, diabetes mellitus, hyperlipidaemia or cardiovascular disease were recruited and underwent polysomnography. Serum A-FABP levels showed significant positive correlations with duration of oxygen desaturation and minimal oxygen saturation, fasting insulin and insulin resistance index by homeostasis model assessment. When subjects were divided into tertiles according to apnoea/hypopnoea index (AHI), serum A-FABP levels were significantly higher in the group with AHI ≥34.4 events·h−1than the groups with AHI 13.2–34.4 events·h−1or with AHI <13.2 events·h−1. Serum A-FABP levels were significantly higher in the AHI ≥34.4 group than obesity-matched subjects with AHI <34.4 events·h−1.

Serum adipocyte-fatty acid binding protein levels correlated with obstructive sleep apnoea and insulin resistance, independently of obesity, and were significantly higher in severe obstructive sleep apnoea. Adipocyte-fatty acid binding protein may play a role in obstructive sleep apnoea and metabolic dysfunction.
The psychobiology of nicotine dependence
Authors: Balfour D. J. K.
Published: January 2009

There is abundant evidence to show that nicotine is the principal addictive component of tobacco smoke. The results of laboratory studies have shown that nicotine has many of the behavioural and neurobiological properties of a drug of dependence.

This article focuses on the evidence that nicotine has the rewarding and reinforcing properties typical of an addictive drug and that these properties are mediated, in part, by its effects on mesolimbic dopamine neurones. However, in many experimental models of dependence, nicotine has relatively weak reinforcing properties that do not appear to explain adequately the powerful addiction to tobacco smoke experienced by many habitual smokers. Some of the reasons for this conundrum will be covered herein. This article focuses on the hypothesis that sensory stimuli and other pharmacologically active components in tobacco smoke play a pivotal role in the addiction to nicotine when it is inhaled in tobacco smoke.

The article will discuss the evidence that dependence upon tobacco smoke reflects a complex interaction between nicotine and the components of the smoke, which are mediated by complementary effects of nicotine on the dopamine projections to the shell and core subdivisions of the accumbens.

It will also discuss the extent to which the complexity of the dependence explains why nicotine replacement therapy does not provide a completely satisfying aid to smoking cessation and speculate on the properties treatments should exhibit if they are to provide a better treatment for tobacco dependence than those currently available.
Smoking and impact on health
Authors: Vineis P.
Published: January 2009

In 2005, the World Health Organization set a global goal to reduce the rate of death from chronic (noncommunicable) disease by an additional 2% every year. A major component in this strategy was a reduction in the use of tobacco products, as described in the World Health Organization Framework Convention on Tobacco Control. According to recent estimates, over 10 yrs (2006–2015) 13.8 million deaths could be averted by the implementation of such interventions, at a cost of less than US$0.40 person−1·yr−1in low-income and lower middle-income countries, and US$0.50–1.00 person−1·yr−1in upper middle-income countries. According to estimates, approximately one third of tobacco-related deaths will be due to respiratory causes, one third to cancer and one third to cardiovascular diseases. Most of the burden of tobacco in the future will be in low-income countries.
Pharmacological treatments for tobacco dependence
Authors: Fagerström K. O. , Jiménez-Ruiz C. A.
Published: January 2009

There are currently three licensed therapies for smoking cessation: nicotine replacement (NR), bupropion and varenicline.

NR can be indicated for: 1) aid in abrupt cessation; 2) gradual reduction in order to quit smoking; 3) temporary abstinence; and 4) smoking reduction maintenance. A meta-analysis has found that the relative risk of abstinence for any form of NR relative to control was 1.6. It has been found that starting NR treatment 1–3 weeks before smoking cessation and combining NR products, usually patch and gum, increases efficacy. Recently some new nicotine administration forms,i.e.lozenge, mouth spray and a pouch, have been developed. They seem to have the potential to relieve cravings faster than the current high-dose gum, and also be more preferred.

Varenicline is a selective partial agonist at the α4β2nicotinic acetylcholine receptors (nAChR). It decreases cravings and alleviates the symptoms of withdrawal. It can also reduce the rewarding and reinforcing effects of nicotine. Trials have shown varenicline to have increased efficacy relative to bupropion. Varenicline has also been compared with NR (21 mg transdermal patch) in one randomised study. Abstinence at the end of treatment at 12 weeks was significantly increased for varenicline (56%) compared with for nicotine patch (43%). Some post-marketing reports have expressed concern about psychiatric adverse effects, such as aggression, depression and suicides. The European Medicines Agency and the Food and Drug Administration of the USA are monitoring reported side-effects, but so far no confirmed casual relationship between these adverse effects and varenicline has been established.

Bupropion inhibits neuronal re-uptake of dopamine and norepinephrine and is an antagonist on the nAChR. Its efficacy, compared with placebo, has been proved in several meta-analyses. A recent study suggests that longer pre-cessation use of bupropion,e.g.for 4 weeks, can improve efficacy results.

Under development for the treatment of tobacco dependence are cannabinoid antagonists, immunotherapy against nicotine, monoaminooxidase inhibitors, dopamine receptor D3 receptor antagonists and partial agonists, glutamatergic and GABA-ergic compounds and novel selective nicotine cholinergic receptor agonists and antagonists.
Clinical and public health significance of treatments to aid smoking cessation
Authors: West R. , Stapleton J.
Published: January 2009

There is good epidemiological evidence to show that for every continued year of smoking over the age of 40 yrs, the average smoker loses 3 months of life expectancy.

Treatments to aid smoking cessation have the potential to save tens of thousands of lives annually if they: 1) lead users of those treatments to stop significantly earlier than they would otherwise have done; 2) do not undermine quitting in nonusers; and 3) are used by a significant proportion of smokers. There is strong evidence from high-quality randomised controlled trials to show that currently available treatments improve the chances of a cessation attempt succeeding permanently by between 2.5 and 10% points. For each success this brings forward quitting by an average of 25–30 yrs. Failure of a cessation attempt at 40 yrs of age costs an estimated 6–7 yrs of life expectancy.

There is no evidence that introducing and publicising treatments undermines quitting in nonusers. The major factor limiting the public health benefit of treatments to aid cessation is the numbers of smokers that use them. At present, the most effective treatment combination of behavioural support plus medication is used by a very small minority of smokers.

It is estimated that for every 100,000 smokers who use proven treatments to aid cessation, between 7,500 and 30,000 life-years will be saved in the future depending on the treatment. In England (UK), the use of smoking cessation treatment in 2008 is expected to save 270,000 life-years. A major priority for tobacco control should be finding ways of encouraging more smokers to use the most effective treatments.
Implications and priorities of tobacco control in Belgium and Europe: FIGURE 1.
Authors: Bartsch P.
Published: January 2009

The present article aims to define what tobacco control is both in Europe and around the world. The situation of tobacco control in Belgium will be compared to other European countries using the tobacco control scale (TCS). If countries demonstrating a high TCS score have lower tobacco smoking prevalence than countries with a low TCS, it is not known whether the decrease in smoking prevalence over several years is well correlated with the increase in TCS score in each country during the same period.

Moreover the article will raise the question of how far research will continue control into controlling the use of tobacco.

The remaining 20% of smokers in the best tobacco control scale countries who are still smoking are not similar to the 20% that are now ex-smokers. Indeed we are now facing the “hard core smokers”, who show great resistance to policy measures and be considered as ill individuals requiring specialised care rather than individuals with bad habits. The future tobacco control scale should place more importance on the quality of care and the implication of European countries providing improved access to this form of care and validated forms of treatment of this chronic, difficult to treat disease.
Crystallizing short-read assemblies around seeds
Authors: Hossain Mohammad Sajjad , Azimi Navid , Skiena Steven
Published: January 2009

Background

New short-read sequencing technologies produce enormous volumes of 25–30 base paired-end reads. The resulting reads have vastly different characteristics than produced by Sanger sequencing, and require different approaches than the previous generation of sequence assemblers. In this paper, we present a short-read de novo assembler particularly targeted at the new ABI SOLiD sequencing technology.

Results

This paper presents what we believe to be the first de novo sequence assembly results on real data from the emerging SOLiD platform, introduced by Applied Biosystems. Our assembler SHORTY augments short-paired reads using a trivially small number (5 – 10) of seeds of length 300 – 500 bp. These seeds enable us to produce significant assemblies using short-read coverage no more than 100×, which can be obtained in a single run of these high-capacity sequencers. SHORTY exploits two ideas which we believe to be of interest to the short-read assembly community: (1) using single seed reads to crystallize assemblies, and (2) estimating intercontig distances accurately from multiple spanning paired-end reads.

Conclusion

We demonstrate effective assemblies (N50 contig sizes ~40 kb) of three different bacterial species using simulated SOLiD data. Sequencing artifacts limit our performance on real data, however our results on this data are substantially better than those achieved by competing assemblers.
REMAS: a new regression model to identify alternative splicing events from exon array data
Authors: Zheng Hao , Hang Xingyi , Zhu Ji , Qian Minping , Qu Wubin , Zhang Chenggang , Deng Minghua
Published: January 2009

Background

Alternative splicing (AS) is an important regulatory mechanism for gene expression and protein diversity in eukaryotes. Previous studies have demonstrated that it can be causative for, or specific to splicing-related diseases. Understanding the regulation of AS will be helpful for diagnostic efforts and drug discoveries on those splicing-related diseases. As a novel exon-centric microarray platform, exon array enables a comprehensive analysis of AS by investigating the expression of known and predicted exons. Identifying of AS events from exon array has raised much attention, however, new and powerful algorithms for exon array data analysis are still absent till now.

Results

Here, we considered identifying of AS events in the framework of variable selection and developed a regression method for AS detection (REMAS). Firstly, features of alternatively spliced exons were scaled by reasonably defined variables. Secondly, we designed a hierarchical model which can represent gene structure and transcriptional influence to exons, and the lasso type penalties were introduced in calculation because of huge variable size. Thirdly, an iterative two-step algorithm was developed to select alternatively spliced genes and exons. To avoid negative effects introduced by small sample size, we ranked genes as parameters indicating their AS capabilities in an iterative manner. After that, both simulation and real data evaluation showed that REMAS could efficiently identify potential AS events, some of which had been validated by RT-PCR or supported by literature evidence.

Conclusion

As a new lasso regression algorithm based on hierarchical model, REMAS has been demonstrated as a reliable and effective method to identify AS events from exon array data.
Network-based support vector machine for classification of microarray samples
Authors: Zhu Yanni , Shen Xiaotong , Pan Wei
Published: January 2009

Background

The importance of network-based approach to identifying biological markers for diagnostic classification and prognostic assessment in the context of microarray data has been increasingly recognized. To our knowledge, there have been few, if any, statistical tools that explicitly incorporate the prior information of gene networks into classifier building. The main idea of this paper is to take full advantage of the biological observation that neighboring genes in a network tend to function together in biological processes and to embed this information into a formal statistical framework.

Results

We propose a network-based support vector machine for binary classification problems by constructing a penalty term from theF∞-norm being applied to pairwise gene neighbors with the hope to improve predictive performance and gene selection. Simulation studies in both low- and high-dimensional data settings as well as two real microarray applications indicate that the proposed method is able to identify more clinically relevant genes while maintaining a sparse model with either similar or higher prediction accuracy compared with the standard and theL1penalized support vector machines.

Conclusion

The proposed network-based support vector machine has the potential to be a practically useful classification tool for microarrays and other high-dimensional data.
Searching for bidirectional promoters in Arabidopsis thaliana
Authors: Wang Quan , Wan Lin , Li Dayong , Zhu Lihuang , Qian Minping , Deng Minghua
Published: January 2009

Background

A "bidirectional gene pair" is defined as two adjacent genes which are located on opposite strands of DNA with transcription start sites (TSSs) not more than 1000 base pairs apart and the intergenic region between two TSSs is commonly designated as a putative "bidirectional promoter". Individual examples of bidirectional gene pairs have been reported for years, as well as a few genome-wide analyses have been studied in mammalian and human genomes. However, no genome-wide analysis of bidirectional genes for plants has been done. Furthermore, the exact mechanism of this gene organization is still less understood.

Results

We conducted comprehensive analysis of bidirectional gene pairs through the whole Arabidopsis thaliana genome and identified 2471 bidirectional gene pairs. The analysis shows that bidirectional genes are often coexpressed and tend to be involved in the same biological function. Furthermore, bidirectional gene pairs associated with similar functions seem to have stronger expression correlation. We pay more attention to the regulatory analysis on the intergenic regions between bidirectional genes. Using a hierarchical stochastic language model (HSL) (which is developed by ourselves), we can identify intergenic regions enriched of regulatory elements which are essential for the initiation of transcription. Finally, we picked 27 functionally associated bidirectional gene pairs with their intergenic regions enriched of regulatory elements and hypothesized them to be regulated by bidirectional promoters, some of which have the same orthologs in ancient organisms. More than half of these bidirectional gene pairs are further supported by sharing similar functional categories as these of handful experimental verified bidirectional genes.

Conclusion

Bidirectional gene pairs are concluded also prevalent in plant genome. Promoter analyses of the intergenic regions between bidirectional genes could be a new way to study the bidirectional gene structure, which may provide a important clue for further analysis. Such a method could be applied to other genomes.
A structural interpretation of the effect of GC-content on efficiency of RNA interference
Authors: Chan Chi Yu , Carmack C Steven , Long Dang D , Maliyekkel Anil , Shao Yu , Roninson Igor B , Ding Ye
Published: January 2009

Background

RNA interference (RNAi) mediated by small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) has become a powerful technique for eukaryotic gene knockdown. siRNA GC-content negatively correlates with RNAi efficiency, and it is of interest to have a convincing mechanistic interpretation of this observation. We here examine this issue by considering the secondary structures for both the target messenger RNA (mRNA) and the siRNA guide strand.

Results

By analyzing a unique homogeneous data set of 101 shRNAs targeted to 100 endogenous human genes, we find that: 1) target site accessibility is more important than GC-content for efficient RNAi; 2) there is an appreciable negative correlation between GC-content and RNAi activity; 3) for the predicted structure of the siRNA guide strand, there is a lack of correlation between RNAi activity and either the stability or the number of free dangling nucleotides at an end of the structure; 4) there is a high correlation between target site accessibility and GC-content. For a set of representative structural RNAs, the GC content of 62.6% for paired bases is significantly higher than the GC content of 38.7% for unpaired bases. Thus, for a structured RNA, a region with higher GC content is likely to have more stable secondary structure. Furthermore, by partial correlation analysis, the correlation for GC-content is almost completely diminished, when the effect of target accessibility is controlled.

Conclusion

These findings provide a target-structure-based interpretation and mechanistic insight for the effect of GC-content on RNAi efficiency.
Computational prediction of novel non-coding RNAs in Arabidopsis thaliana
Authors: Song Dandan , Yang Yang , Yu Bin , Zheng Binglian , Deng Zhidong , Lu Bao-Liang , Chen Xuemei , Jiang Tao
Published: January 2009

Background

Non-coding RNA (ncRNA) genes do not encode proteins but produce functional RNA molecules that play crucial roles in many key biological processes. Recent genome-wide transcriptional profiling studies using tiling arrays in organisms such as human and Arabidopsis have revealed a great number of transcripts, a large portion of which have little or no capability to encode proteins. This unexpected finding suggests that the currently known repertoire of ncRNAs may only represent a small fraction of ncRNAs of the organisms. Thus, efficient and effective prediction of ncRNAs has become an important task in bioinformatics in recent years. Among the available computational methods, the comparative genomic approach seems to be the most powerful to detect ncRNAs. The recent completion of the sequencing of several major plant genomes has made the approach possible for plants.

Results

We have developed a pipeline to predict novel ncRNAs in the Arabidopsis (Arabidopsis thaliana) genome. It starts by comparing the expressed intergenic regions of Arabidopsis as provided in two whole-genome high-density oligo-probe arrays from the literature with the intergenic nucleotide sequences of all completely sequenced plant genomes including rice (Oryza sativa), poplar (Populus trichocarpa), grape (Vitis vinifera), and papaya (Carica papaya). By using multiple sequence alignment, a popular ncRNA prediction program (RNAz), wet-bench experimental validation, protein-coding potential analysis, and stringent screening against various ncRNA databases, the pipeline resulted in 16 families of novel ncRNAs (with a total of 21 ncRNAs).

Conclusion

In this paper, we undertake a genome-wide search for novel ncRNAs in the genome of Arabidopsis by a comparative genomics approach. The identified novel ncRNAs are evolutionarily conserved between Arabidopsis and other recently sequenced plants, and may conduct interesting novel biological functions.
Prediction of RNA secondary structure with pseudoknots using integer programming
Authors: Poolsap Unyanee , Kato Yuki , Akutsu Tatsuya
Published: January 2009

Background

RNA secondary structure prediction is one major task in bioinformatics, and various computational methods have been proposed so far. Pseudoknot is one of the typical substructures appearing in several RNAs, and plays an important role in some biological processes. Prediction of RNA secondary structure with pseudoknots is still challenging since the problem is NP-hard when arbitrary pseudoknots are taken into consideration.

Results

We introduce a new method of predicting RNA secondary structure with pseudoknots based on integer programming. In our formulation, we aim at minimizing the value of the objective function that reflects free energy of a folding structure of an input RNA sequence. We focus on a practical class of pseudoknots by setting constraints appropriately. Experimental results for a set of real RNA sequences show that our proposed method outperforms several existing methods in sensitivity. Furthermore, for a set of sequences of small length, our approach achieved good performance in both sensitivity and specificity.

Conclusion

Our integer programming-based approach for RNA structure prediction is flexible and extensible.
Sequence-structure relations of pseudoknot RNA
Authors: Huang Fenix WD , Li Linda YM , Reidys Christian M
Published: January 2009

Background

The analysis of sequence-structure relations of RNA is based on a specific notion and folding of RNA structure. The notion of coarse grained structure employed here is that of canonical RNA pseudoknot contact-structures with at most two mutually crossing bonds (3-noncrossing). These structures are folded by a novel, ab initio prediction algorithm, cross, capable of searching all 3-noncrossing RNA structures. The algorithm outputs the minimum free energy structure.

Results

After giving some background on RNA pseudoknot structures and providing an outline of the folding algorithm being employed, we present in this paper various, statistical results on the mapping from RNA sequences into 3-noncrossing RNA pseudoknot structures. We study properties, like the fraction of pseudoknot structures, the dominant pseudoknot-shapes, neutral walks, neutral neighbors and local connectivity. We then put our results into context of molecular evolution of RNA.

Conclusion

Our results imply that, in analogy to RNA secondary structures, 3-noncrossing pseudoknot RNA represents a molecular phenotype that is well suited for molecular and in particular neutral evolution. We can conclude that extended, percolating neutral networks of pseudoknot RNA exist.
SE: an algorithm for deriving sequence alignment from a pair of superimposed structures
Authors: Tai Chin-Hsien , Vincent James J , Kim Changhoon , Lee Byungkook
Published: January 2009

Background

Generating sequence alignments from superimposed structures is an important part of many structure comparison programs. The accuracy of the alignment affects structure recognition, classification and possibly function prediction. Many programs use a dynamic programming algorithm to generate the sequence alignment from superimposed structures. However, this procedure requires using a gap penalty and, depending on the value of the penalty used, can introduce spurious gaps and misalignments. Here we present a new algorithm, Seed Extension (SE), for generating the sequence alignment from a pair of superimposed structures. The SE algorithm first finds "seeds", which are the pairs of residues, one from each structure, that meet certain stringent criteria for being structurally equivalent. Three consecutive seeds form a seed segment, which is extended along the diagonal of the alignment matrix in both directions. Distance and the amino acid type similarity between the residues are used to resolve conflicts that arise during extension of more than one diagonal. The manually curated alignments in the Conserved Domain Database were used as the standard to assess the quality of the sequence alignments.

Results

SE gave an average accuracy of 95.9% over 582 pairs of superimposed proteins tested, while CHIMERA, LSQMAN, and DP extracted from SHEBA, which all use a dynamic programming algorithm, yielded 89.9%, 90.2% and 91.0%, respectively. For pairs of proteins with low sequence or structural similarity, SE produced alignments up to 18% more accurate on average than the next best scoring program. Improvement was most pronounced when the two superimposed structures contained equivalent helices or beta-strands that crossed at an angle. When the SE algorithm was implemented in SHEBA to replace the dynamic programming routine, the alignment accuracy improved by 10% on average for structure pairs with RMSD between 2 and 4 Å. SE also used considerably less CPU time than DP.

Conclusion

The Seed Extension algorithm is fast and, without using a gap penalty, produces more accurate sequence alignments from superimposed structures than three other programs tested that use dynamic programming algorithm.
ComPhy: prokaryotic composite distance phylogenies inferred from whole-genome gene sets
Authors: Lin Guan Ning , Cai Zhipeng , Lin Guohui , Chakraborty Sounak , Xu Dong
Published: January 2009

Background

With the increasing availability of whole genome sequences, it is becoming more and more important to use complete genome sequences for inferring species phylogenies. We developed a new tool ComPhy, 'Composite Distance Phylogeny', based on a composite distance matrix calculated from the comparison of complete gene sets between genome pairs to produce a prokaryotic phylogeny.

Results

The composite distance between two genomes is defined by three components: Gene Dispersion Distance (GDD), Genome Breakpoint Distance (GBD) and Gene Content Distance (GCD). GDD quantifies the dispersion of orthologous genes along the genomic coordinates from one genome to another; GBD measures the shared breakpoints between two genomes; GCD measures the level of shared orthologs between two genomes. The phylogenetic tree is constructed from the composite distance matrix using a neighbor joining method. We tested our method on 9 datasets from 398 completely sequenced prokaryotic genomes. We have achieved above 90% agreement in quartet topologies between the tree created by our method and the tree from the Bergey's taxonomy. In comparison to several other phylogenetic analysis methods, our method showed consistently better performance.

Conclusion

ComPhy is a fast and robust tool for genome-wide inference of evolutionary relationship among genomes. It can be downloaded from http://digbio.missouri.edu/ComPhy.
Mutual information estimation reveals global associations between stimuli and biological processes
Authors: Suzuki Taiji , Sugiyama Masashi , Kanamori Takafumi , Sese Jun
Published: January 2009

Background

Although microarray gene expression analysis has become popular, it remains difficult to interpret the biological changes caused by stimuli or variation of conditions. Clustering of genes and associating each group with biological functions are often used methods. However, such methods only detect partial changes within cell processes. Herein, we propose a method for discovering global changes within a cell by associating observed conditions of gene expression with gene functions.

Results

To elucidate the association, we introduce a novel feature selection method calledLeast-Squares Mutual Information (LSMI), which computes mutual information without density estimaion, and therefore LSMI can detect nonlinear associations within a cell. We demonstrate the effectiveness of LSMI through comparison with existing methods. The results of the application to yeast microarray datasets reveal that non-natural stimuli affect various biological processes, whereas others are no significant relation to specific cell processes. Furthermore, we discover that biological processes can be categorized into four types according to the responses of various stimuli: DNA/RNA metabolism, gene expression, protein metabolism, and protein localization.

Conclusion

We proposed a novel feature selection method called LSMI, and applied LSMI to mining the association between conditions of yeast and biological processes through microarray datasets. In fact, LSMI allows us to elucidate the global organization of cellular process control.
On optimal comparability editing with applications to molecular diagnostics
Authors: Böcker Sebastian , Briesemeister Sebastian , Klau Gunnar W
Published: January 2009

Background

The COMPARABILITY EDITING problem appears in the context of hierarchical disease classification based on noisy data. We are given a directed graph G representing hierarchical relationships between patient subgroups. The task is to identify the minimum number of edge insertions or deletions to transform G into a transitive graph, that is, if edges (u, v) and (v, w) are present then edge (u, w) must be present, too.

Results

We present two new approaches for the problem based on fixed-parameter algorithmics and integer linear programming. In contrast to previously used heuristics, our approaches compute provably optimal solutions.

Conclusion

Our computational results demonstrate that our exact algorithms are by far more efficient in practice than a previously used heuristic approach. In addition to the superior running time performance, our algorithms are capable of enumerating all optimal solutions, and naturally solve the weighted version of the problem.
Pleistocene glacial refugia across the Appalachian Mountains and coastal plain in the millipede genus Narceus: Evidence from population genetic, phylogeographic, and paleoclimatic data
Authors: Walker Matt J , Stockman Amy K , Marek Paul E , Bond Jason E
Published: January 2009

Background

Species that are widespread throughout historically glaciated and currently non-glaciated areas provide excellent opportunities to investigate the role of Pleistocene climatic change on the distribution of North American biodiversity. Many studies indicate that northern animal populations exhibit low levels of genetic diversity over geographically widespread areas whereas southern populations exhibit relatively high levels. Recently, paleoclimatic data have been combined with niche-based distribution modeling to locate possible refugia during the Last Glacial Maximum. Using phylogeographic, population, and paleoclimatic data, we show that the distribution and mitochondrial data for the millipede genus Narceus are consistent with classical examples of Pleistocene refugia and subsequent post-glacial population expansion seen in other organismal groups.

Results

The phylogeographic structure of Narceus reveals a complex evolutionary history with signatures of multiple refugia in southeastern North America followed by two major northern expansions. Evidence for refugial populations were found in the southern Appalachian Mountains and in the coastal plain. The northern expansions appear to have radiated from two separate refugia, one from the Gulf Coastal Plain area and the other from the mid-Atlantic coastal region. Distributional models of Narceus during the Last Glacial Maximum show a dramatic reduction from the current distribution, with suitable ecological zones concentrated along the Gulf and Atlantic coastal plain. We found a strong correlation between these zones of ecological suitability inferred from our paleo-model with levels of genetic diversity derived from phylogenetic and population estimates of genetic structuring.

Conclusion

The signature of climatic change, during and after the Pleistocene, on the distribution of the millipede genus Narceus is evident in the genetic data presented. Niche-based historical distribution modeling strengthens the conclusions drawn from the genetic data and proves useful in identifying probable refugia. Such interdisciplinary biogeographic studies provide a comprehensive approach to understanding these processes that generate and maintain biodiversity as well as the framework necessary to explore questions regarding evolutionary diversification of taxa.
Comparison of the MicroScan, VITEK 2, and Crystal GP with 16S rRNA sequencing and MicroSeq 500 v2.0 analysis for coagulase-negative Staphylococci
Authors: Kim Miyoung , Heo Se Ran , Choi Soon Hee , Kwon Hyelin , Park Jeong Su , Seong Moon-Woo , Lee Do-Hoon , Park Kyoung Un , Song Junghan , Kim Eui-Chong
Published: January 2009

Background

Three phenotypic identification systems (MicroScan, VITEK 2, and Crystal GP) were evaluated for their accuracy to identify coagulase-negative staphylococci (CNS). A total of 120 clinical isolates confirmed to be CNS via 16S rRNA sequencing and analysis with the MicroSeq 500 v2.0 database were assessed.

Results

The MicroScan, VITEK 2, and Crystal GP systems correctly identified 82.5%, 87.5%, and 67.5% of the isolates, respectively. Misidentification was the main problem in MicroScan (10.8%) and Crystal GP (23.3%) systems, whereas the main problem of VITEK 2 was low-level discrimination (7.5%).

Conclusion

None of the 3 phenotypic systems tested could accurately and reliably identify CNS at the species level. Further verifications such as biochemical testing or 16S rRNA sequencing together with analysis using a comparable database might be helpful in this regard.
Intradialytic versus home based exercise training in hemodialysis patients: a randomised controlled trial
Authors: Koh Kirsten P , Fassett Robert G , Sharman James E , Coombes Jeff S , Williams Andrew D
Published: January 2009

Background

Exercise training in hemodialysis patients improves fitness, physical function, quality of life and markers of cardiovascular disease such as arterial stiffness. The majority of trials investigating this area have used supervised exercise training during dialysis (intradialytic), which may not be feasible for some renal units. The aim of this trial is to compare the effects of supervised intradialytic with unsupervised home-based exercise training on physical function and arterial stiffness.

Methods and design

This is a randomised, controlled clinical trial. A total of 72 hemodialysis patients will be randomised to receive either six months of intradialytic exercise training, home-based exercise training or usual care. Intradialytic patients will undergo three training sessions per week on a cycle ergometer and home-based patients will be provided with a walking program to achieve the same weekly physical activity. Primary outcome measures are six-minute walk distance (6 MWD) and aortic pulse wave velocity (PWV). Secondary outcome measures include augmentation index, peripheral and central blood pressures, physical activity and self-reported health. Measures will be made at baseline, three and six months.

Discussion

The results of this study will help determine the efficacy of home-based exercise training in hemodialysis patients. This may assist in developing exercise guidelines specific for these patients.

Trial Registration

ACTRN12608000247370
Postnatal quality of life in women after normal vaginal delivery and caesarean section
Authors: Torkan Behnaz , Parsay Sousan , Lamyian Minoor , Kazemnejad Anoshirvan , Montazeri Ali
Published: January 2009

Background

Caesarean section might increase the incidence of surgical interventions and problems resulting from hospitalization and thus affecting quality of life in women after delivery. This study aimed to compare quality of life in women after normal delivery and caesarean section.

Methods

This was a prospective study. A sample of women with normal delivery and caesarean section from 5 health care centers in Isfahan, Iran were entered into the study. Quality of life was measured using the SF-36 at two points in time (time 1: 6 to 8 weeks after delivery; time 2: 12 to 14 weeks after delivery). Data were analyzed to compare quality of life in the two study groups.

Results

In all 100 women were interviewed (50 with normal delivery and 50 with caesarean section). Postnatal quality of life in both groups was improved from time1 to time 2. However, comparing the mean scores between the normal and caesarean delivery groups the results showed that in general the normal vaginal delivery group had a better quality of life for almost all subscales in both assessment times. The differences were significant for vitality (mean score 62.9 vs. 54.4 P = 0.03) and mental health (mean score 75.1 vs. 66.7, P = 0.03) at first assessment and for physical functioning (mean score 88.4 vs. 81.5, P = 0.03) at second evaluation. However, comparing the findings within each group the analysis showed that the normal vaginal delivery group improved more on physical health related quality of life while the caesarean section group improved more on mental health related quality of life.

Conclusion

Although the study did not show a clear cut benefit in favor of either methods of delivery that are normal vaginal delivery or caesarean section, the findings suggest that normal vaginal delivery might lead to a better quality of life especially resulting in a superior physical health. Indeed in the absence of medical indications normal vaginal delivery might be better to be considered as the first priority in term pregnancy.
Identification of a potent herbal molecule for the treatment of breast cancer
Authors: Koduru Srinivas , Sowmyalakshmi Srinivasan , Kumar Raj , Gomathinayagam Rohini , Rohr Jürgen , Damodaran Chendil
Published: January 2009

Background

Breast cancer (BCa)-related mortality still remains the second leading cause of cancer-related deaths worldwide. Patients with BCa have increasingly shown resistance and high toxicity to current chemotherapeutic drugs for which identification of novel targeted therapies are required.

Methods

To determine the effect of PDBD on BCa cells, estrogen-receptor positive (ER+)-MCF-7 and estrogen-receptor negative (ER-)-MDA 231 cells were treated with PDBD and the cell viability, apoptotic, cell cycle, Western blot and Promoter assays were performed.

Results

PDBD inhibits cell viability of ER+and ER-BCa cells by inducing apoptosis without causing significant toxicity in normal breast epithelial cells. While dissecting the mechanism of action of PDBD on BCa, we found that PDBD inhibits Akt signaling and its downstream targets such as NF-κB activation, IAP proteins and Bcl-2 expression. On the other hand, activation of JNK/p38 MAPK-mediated pro-apoptotic signaling was observed in both ER+and ER-BCa cells.

Conclusion

These findings suggest that PDBD may have wide therapeutic application in the treatment of BCa.
Using surveillance data to monitor entry into care of newly diagnosed HIV-infected persons: San Francisco, 2006–2007
Authors: Zetola Nicola M , Bernstein Kyle , Ahrens Katherine , Marcus Julia L , Philip Susan , Nieri Giuliano , Jones Diane , Hare C Bradley , Hsu Ling , Scheer Susan , Klausner Jeffrey D
Published: January 2009

Background

Linkage to care after HIV diagnosis is associated with both clinical and public health benefits. However, ensuring and monitoring linkage to care by public health departments has proved to be a difficult task. Here, we report the usefulness of routine monitoring of CD4 T cell counts and plasma HIV viral load as measures of entry into care after HIV diagnosis.

Methods

Since July 1, 2006, the San Francisco Department of Public Health (SFDPH) incorporated monitoring initial primary care visit into standard HIV public health investigation for newly diagnosed HIV-infected patients in select clinics. Entry into care was defined as having at least one visit to a primary HIV care provider after the initial diagnosis of HIV infection. Investigators collected reports from patients, medical providers, laboratories and reviewed medical records to determine the date of the initial health care visit after HIV diagnosis. We identified factors associated with increased likelihood of entering care after HIV diagnosis.

Results

One -hundred and sixty new HIV-infected cases were diagnosed between July 1, 2006 and June 30, 2007. Routine surveillance methods found that 101 of those cases entered HIV medical care and monitoring of CD4 T cell counts and plasma HIV viral load confirmed entry to care of 25 more cases, representing a 25% increase over routine data collection methods. We found that being interviewed by a public health investigator was associated with higher odds of entry into care after HIV diagnosis (OR 18.86 [1.83–194.80], p = .001) compared to cases not interviewed. Also, HIV diagnosis at the San Francisco county hospital versus diagnosis at the county municipal STD clinic was associated with higher odds of entry into care (OR 101.71 [5.29–1952.05], p < .001).

Conclusion

The time from HIV diagnosis to initial CD4 T cell count, CD4 T cell value and HIV viral load testing may be appropriate surveillance measures for evaluating entry into care, as well as performance outcomes for local public health departments' HIV testing programs. Case investigation performed by the public health department or case management by clinic staff was associated with increased and shorter time to entry into HIV medical care.
The effects of DNA formulation and administration route on cancer therapeutic efficacy with xenogenic EGFR DNA vaccine in a lung cancer animal model
Authors: Lai Ming-Derg , Yen Meng-Chi , Lin Chiu-Mei , Tu Cheng-Fen , Wang Chun-Chin , Lin Pei-Shan , Yang Huei-Jiun , Lin Chi-Chen
Published: January 2009

Background

Tyrosine kinase inhibitor gefitinib is effective against lung cancer cells carrying mutant epidermal growth factor receptor (EGFR); however, it is not effective against lung cancer carrying normal EGFR. The breaking of immune tolerance against self epidermal growth factor receptor with active immunization may be a useful approach for the treatment of EGFR-positive lung tumors. Xenogeneic EGFR gene was demonstrated to induce antigen-specific immune response against EGFR-expressing tumor with intramuscular administration.

Methods

In order to enhance the therapeutic effect of xenogeneic EGFR DNA vaccine, the efficacy of altering routes of administration and formulation of plasmid DNA was evaluated on the mouse lung tumor (LL2) naturally overexpressing endogenous EGFR in C57B6 mice. Three different combination forms were studied, including (1) intramuscular administration of non-coating DNA vaccine, (2) gene gun administration of DNA vaccine coated on gold particles, and (3) gene gun administration of non-coating DNA vaccine. LL2-tumor bearing C57B6 mice were immunized four times at weekly intervals with EGFR DNA vaccine.

Results

The results indicated that gene gun administration of non-coating xenogenic EGFR DNA vaccine generated the strongest cytotoxicty T lymphocyte activity and best antitumor effects. CD8(+) T cells were essential for anti-tumor immunityas indicated by depletion of lymphocytes in vivo.

Conclusion

Thus, our data demonstrate that administration of non-coating xenogenic EGFR DNA vaccine by gene gun may be the preferred method for treating EGFR-positive lung tumor in the future.