bluuebunny/crossref_metadata_2025 huggingface dataset:
Accessing the SEED Genome Databases via Web Services API: Tools for Programmers
Authors: Disz Terry , Akhter Sajia , Cuevas Daniel , Olson Robert , Overbeek Ross , Vonstein Veronika , Stevens Rick , Edwards Robert A
Published: June 2010

Background

The SEED integrates many publicly available genome sequences into a single resource. The database contains accurate and up-to-date annotations based on the subsystems concept that leverages clustering between genomes and other clues to accurately and efficiently annotate microbial genomes. The backend is used as the foundation for many genome annotation tools, such as the Rapid Annotation using Subsystems Technology (RAST) server for whole genome annotation, the metagenomics RAST server for random community genome annotations, and the annotation clearinghouse for exchanging annotations from different resources. In addition to a web user interface, the SEED also provides Web services based API for programmatic access to the data in the SEED, allowing the development of third-party tools and mash-ups.

Results

The currently exposed Web services encompass over forty different methods for accessing data related to microbial genome annotations. The Web services provide comprehensive access to the database back end, allowing any programmer access to the most consistent and accurate genome annotations available. The Web services are deployed using a platform independent service-oriented approach that allows the user to choose the most suitable programming platform for their application. Example code demonstrate that Web services can be used to access the SEED using common bioinformatics programming languages such as Perl, Python, and Java.

Conclusions

We present a novel approach to access the SEED database. Using Web services, a robust API for access to genomics data is provided, without requiring large volume downloads all at once. The API ensures timely access to the most current datasets available, including the new genomes as soon as they come online.
Comparison of translation loads for standard and alternative genetic codes
Authors: Sammet Stefanie Gabriele , Bastolla Ugo , Porto Markus
Published: June 2010

Background

The (almost) universality of the genetic code is one of the most intriguing properties of cellular life. Nevertheless, several variants of the standard genetic code have been observed, which differ in one or several of 64 codon assignments and occur mainly in mitochondrial genomes and in nuclear genomes of some bacterial and eukaryotic parasites. These variants are usually considered to be the result of non-adaptive evolution. It has been shown that the standard genetic code is preferential to randomly assembled codes for its ability to reduce the effects of errors in protein translation.

Results

Using a genotype-to-phenotype mapping based on a quantitative model of protein folding, we compare the standard genetic code to seven of its naturally occurring variants with respect to the fitness loss associated to mistranslation and mutation. These fitness losses are computed through computer simulations of protein evolution with mutations that are either neutral or lethal, and different mutation biases, which influence the balance between unfolding and misfolding stability. We show that the alternative codes may produce significantly different mutation and translation loads, particularly for genomes evolving with a rather large mutation bias. Most of the alternative genetic codes are found to be disadvantageous to the standard code, in agreement with the view that the change of genetic code is a mutationally driven event. Nevertheless, one of the studied alternative genetic codes is predicted to be preferable to the standard code for a broad range of mutation biases.

Conclusions

Our results show that, with one exception, the standard genetic code is generally better able to reduce the translation load than the naturally occurring variants studied here. Besides this exception, some of the other alternative genetic codes are predicted to be better adapted for extreme mutation biases. Hence, the fixation of alternative genetic codes might be a neutral or nearly-neutral event in the majority of the cases, but adaptation cannot be excluded for some of the studied cases.
Chromosome differentiation patterns during cichlid fish evolution
Authors: Poletto Andréia B , Ferreira Irani A , Cabral-de-Mello Diogo C , Nakajima Rafael T , Mazzuchelli Juliana , Ribeiro Heraldo B , Venere Paulo C , Nirchio Mauro , Kocher Thomas D , Martins Cesar
Published: June 2010

Background

Cichlid fishes have been the subject of increasing scientific interest because of their rapid adaptive radiation which has led to an extensive ecological diversity and their enormous importance to tropical and subtropical aquaculture. To increase our understanding of chromosome evolution among cichlid species, karyotypes of one Asian, 22 African, and 30 South American cichlid species were investigated, and chromosomal data of the family was reviewed.

Results

Although there is extensive variation in the karyotypes of cichlid fishes (from 2n = 32 to 2n = 60 chromosomes), the modal chromosome number for South American species was 2n = 48 and the modal number for the African ones was 2n = 44. The only Asian species analyzed, Etroplus maculatus, was observed to have 46 chromosomes. The presence of one or two macro B chromosomes was detected in two African species. The cytogenetic mapping of 18S ribosomal RNA (18S rRNA) gene revealed a variable number of clusters among species varying from two to six.

Conclusions

The karyotype diversification of cichlids seems to have occurred through several chromosomal rearrangements involving fissions, fusions and inversions. It was possible to identify karyotype markers for the subfamilies Pseudocrenilabrinae (African) and Cichlinae (American). The karyotype analyses did not clarify the phylogenetic relationship among the Cichlinae tribes. On the other hand, the two major groups of Pseudocrenilabrinae (tilapiine and haplochromine) were clearly discriminated based on the characteristics of their karyotypes. The cytogenetic mapping of 18S ribosomal RNA (18S rRNA) gene did not follow the chromosome diversification in the family. The dynamic evolution of the repeated units of rRNA genes generates patterns of chromosomal distribution that do not help follows the phylogenetic relationships among taxa. The presence of B chromosomes in cichlids is of particular interest because they may not be represented in the reference genome sequences currently being obtained.
A simple optimization can improve the performance of single feature polymorphism detection by Affymetrix expression arrays
Authors: Horiuchi Youko , Harushima Yoshiaki , Fujisawa Hironori , Mochizuki Takako , Kawakita Masanori , Sakaguchi Takayuki , Kurata Nori
Published: June 2010

Background

High-density oligonucleotide arrays are effective tools for genotyping numerous loci simultaneously. In small genome species (genome size: < ~300 Mb), whole-genome DNA hybridization to expression arrays has been used for various applications. In large genome species, transcript hybridization to expression arrays has been used for genotyping. Although rice is a fully sequenced model plant of medium genome size (~400 Mb), there are a few examples of the use of rice oligonucleotide array as a genotyping tool.

Results

We compared the single feature polymorphism (SFP) detection performance of whole-genome and transcript hybridizations using the Affymetrix GeneChip® Rice Genome Array, using the rice cultivars with full genome sequence, japonica cultivar Nipponbare and indica cultivar 93-11. Both genomes were surveyed for all probe target sequences. Only completely matched 25-mer single copy probes of the Nipponbare genome were extracted, and SFPs between them and 93-11 sequences were predicted. We investigated optimum conditions for SFP detection in both whole genome and transcript hybridization using differences between perfect match and mismatch probe intensities of non-polymorphic targets, assuming that these differences are representative of those between mismatch and perfect targets. Several statistical methods of SFP detection by whole-genome hybridization were compared under the optimized conditions. Causes of false positives and negatives in SFP detection in both types of hybridization were investigated.

Conclusions

The optimizations allowed a more than 20% increase in true SFP detection in whole-genome hybridization and a large improvement of SFP detection performance in transcript hybridization. Significance analysis of the microarray for log-transformed raw intensities of PM probes gave the best performance in whole genome hybridization, and 22,936 true SFPs were detected with 23.58% false positives by whole genome hybridization. For transcript hybridization, stable SFP detection was achieved for highly expressed genes, and about 3,500 SFPs were detected at a high sensitivity (> 50%) in both shoot and young panicle transcripts. High SFP detection performances of both genome and transcript hybridizations indicated that microarrays of a complex genome (e.g., of Oryza sativa) can be effectively utilized for whole genome genotyping to conduct mutant mapping and analysis of quantitative traits such as gene expression levels.
Whole genome analysis of a livestock-associated methicillin-resistant Staphylococcus aureus ST398 isolate from a case of human endocarditis
Authors: Schijffelen Maarten J , Boel CH Edwin , van Strijp Jos AG , Fluit Ad C
Published: June 2010

Background

Recently, a new livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) Sequence Type 398 (ST398) isolate has emerged worldwide. Although there have been reports of invasive disease in humans, MRSA ST398 colonization is much more common in livestock and demonstrates especially high prevalence rates in pigs and calves. The aim of this study was to compare the genome sequence of an ST398 MRSA isolate with other S. aureus genomes in order to identify genetic traits that may explain the success of this particular lineage. Therefore, we determined the whole genome sequence of S0385, an MRSA ST398 isolate from a human case of endocarditis.

Results

The entire genome sequence of S0385 demonstrated considerable accessory genome content differences relative to other S. aureus genomes. Several mobile genetic elements that confer antibiotic resistance were identified, including a novel composite of an type V (5C2&5) Staphylococcal Chromosome Cassette mec (SCCmec) with distinct joining (J) regions. The presence of multiple integrative conjugative elements combined with the absence of a type I restriction and modification system on one of the two νSa islands, could enhance horizontal gene transfer in this strain. The ST398 MRSA isolate carries a unique pathogenicity island which encodes homologues of two excreted virulence factors; staphylococcal complement inhibitor (SCIN) and von Willebrand factor-binding protein (vWbp). However, several virulence factors such as enterotoxins and phage encoded toxins, including Panton-Valentine leukocidin (PVL), were not identified in this isolate.

Conclusions

Until now MRSA ST398 isolates did not cause frequent invasive disease in humans, which may be due to the absence of several common virulence factors. However, the proposed enhanced ability of these isolates to acquire mobile elements may lead to the rapid acquisition of determinants which contribute to virulence in human infections.
A gene network switch enhances the oxidative capacity of ovine skeletal muscle during late fetal development
Authors: Byrne Keren , Vuocolo Tony , Gondro Cedric , White Jason D , Cockett Noelle E , Hadfield Tracy , Bidwell Christopher A , Waddell Jolena N , Tellam Ross L
Published: June 2010

Background

The developmental transition between the late fetus and a newborn animal is associated with profound changes in skeletal muscle function as it adapts to the new physiological demands of locomotion and postural support against gravity. The mechanisms underpinning this adaption process are unclear but are likely to be initiated by changes in hormone levels. We tested the hypothesis that this developmental transition is associated with large coordinated changes in the transcription of skeletal muscle genes.

Results

Using an ovine model, transcriptional profiling was performed on Longissimus dorsi skeletal muscle taken at three fetal developmental time points (80, 100 and 120 d of fetal development) and two postnatal time points, one approximately 3 days postpartum and a second at 3 months of age. The developmental time course was dominated by large changes in expression of 2,471 genes during the interval between late fetal development (120 d fetal development) and 1-3 days postpartum. Analysis of the functions of genes that were uniquely up-regulated in this interval showed strong enrichment for oxidative metabolism and the tricarboxylic acid cycle indicating enhanced mitochondrial activity. Histological examination of tissues from these developmental time points directly confirmed a marked increase in mitochondrial activity between the late fetal and early postnatal samples. The promoters of genes that were up-regulated during this fetal to neonatal transition were enriched for estrogen receptor 1 and estrogen related receptor alpha cis-regulatory motifs. The genes down-regulated during this interval highlighted de-emphasis of an array of functions including Wnt signaling, cell adhesion and differentiation. There were also changes in gene expression prior to this late fetal - postnatal transition and between the two postnatal time points. The former genes were enriched for functions involving the extracellular matrix and immune response while the latter principally involved functions associated with transcriptional regulation of metabolic processes.

Conclusions

It is concluded that during late skeletal muscle development there are substantial and coordinated changes in the transcription of a large number of genes many of which are probably triggered by increased estrogen levels. These changes probably underpin the adaption of muscle to new physiological demands in the postnatal environment.
Genomes of three tomato pathogens within the Ralstonia solanacearum species complex reveal significant evolutionary divergence
Authors: Remenant Benoît , Coupat-Goutaland Bénédicte , Guidot Alice , Cellier Gilles , Wicker Emmanuel , Allen Caitilyn , Fegan Mark , Pruvost Olivier , Elbaz Mounira , Calteau Alexandra , Salvignol Gregory , Mornico Damien , Mangenot Sophie , Barbe Valérie , Médigue Claudine , Prior Philippe
Published: June 2010

Background

The Ralstonia solanacearum species complex includes thousands of strains pathogenic to an unusually wide range of plant species. These globally dispersed and heterogeneous strains cause bacterial wilt diseases, which have major socio-economic impacts. Pathogenicity is an ancestral trait in R. solanacearum and strains with high genetic variation can be subdivided into four phylotypes, correlating to isolates from Asia (phylotype I), the Americas (phylotype IIA and IIB), Africa (phylotype III) and Indonesia (phylotype IV). Comparison of genome sequences strains representative of this phylogenetic diversity can help determine which traits allow this bacterium to be such a pathogen of so many different plant species and how the bacteria survive in many different habitats.

Results

The genomes of three tomato bacterial wilt pathogens, CFBP2957 (phy. IIA), CMR15 (phy. III) and PSI07 (phy. IV) were sequenced and manually annotated. These genomes were compared with those of three previously sequenced R. solanacearum strains: GMI1000 (tomato, phy. I), IPO1609 (potato, phy. IIB), and Molk2 (banana, phy. IIB). The major genomic features (size, G+C content, number of genes) were conserved across all of the six sequenced strains. Despite relatively high genetic distances (calculated from average nucleotide identity) and many genomic rearrangements, more than 60% of the genes of the megaplasmid and 70% of those on the chromosome are syntenic. The three new genomic sequences revealed the presence of several previously unknown traits, probably acquired by horizontal transfers, within the genomes of R. solanacearum, including a type IV secretion system, a rhi-type anti-mitotic toxin and two small plasmids. Genes involved in virulence appear to be evolving at a faster rate than the genome as a whole.

Conclusions

Comparative analysis of genome sequences and gene content confirmed the differentiation of R. solanacearum species complex strains into four phylotypes. Genetic distances between strains, in conjunction with CGH analysis of a larger set of strains, revealed differences great enough to consider reclassification of the R. solanacearum species complex into three species. The data are still too fragmentary to link genomic classification and phenotypes, but these new genome sequences identify a pan-genome more representative of the diversity in the R. solanancearum species complex.
Global characterization of interferon regulatory factor (IRF) genes in vertebrates: Glimpse of the diversification in evolution
Authors: Huang Bei , Qi Zhi T , Xu Zhen , Nie Pin
Published: June 2010

Background

Interferon regulatory factors (IRFs), which can be identified based on a unique helix-turn-helix DNA-binding domain (DBD) are a large family of transcription factors involved in host immune response, haemotopoietic differentiation and immunomodulation. Despite the identification of ten IRF family members in mammals, and some recent effort to identify these members in fish, relatively little is known in the composition of these members in other classes of vertebrates, and the evolution and probably the origin of the IRF family have not been investigated in vertebrates.

Results

Genome data mining has been performed to identify any possible IRF family members in human, mouse, dog, chicken, anole lizard, frog, and some teleost fish, mainly zebrafish and stickleback, and also in non-vertebrate deuterostomes including the hemichordate, cephalochordate, urochordate and echinoderm. In vertebrates, all ten IRF family members, i.e. IRF-1 to IRF-10 were identified, with two genes of IRF-4 and IRF-6 identified in fish and frog, respectively, except that in zebrafish exist three IRF-4 genes. Surprisingly, an additional member in the IRF family, IRF-11 was found in teleost fish. A range of two to ten IRF-like genes were detected in the non-vertebrate deuterostomes, and they had little similarity to those IRF family members in vertebrates as revealed in genomic structure and in phylogenetic analysis. However, the ten IRF family members, IRF-1 to IRF-10 showed certain degrees of conservation in terms of genomic structure and gene synteny. In particular, IRF-1, IRF-2, IRF-6, IRF-8 are quite conserved in their genomic structure in all vertebrates, and to a less degree, some IRF family members, such as IRF-5 and IRF-9 are comparable in the structure. Synteny analysis revealed that the gene loci for the ten IRF family members in vertebrates were also quite conservative, but in zebrafish conserved genes were distributed in a much longer distance in chromosomes. Furthermore, all ten different members are clustered in respectively different clades; but the IRF-11 was clustered with one in sea urchin.

Conclusions

In vertebrates, the ten well-characterized IRF family members shared a relatively high degree of similarity in genomic structure and syntenic gene arrangement, implying that they might have been evolved in a similar pattern and with similar selective pressure in different classes of vertebrates. Genome and/or gene duplication, and probably gene shuffling or gene loss might have occurred during the evolution of these IRF family members, but arrangement of chromosome or its segment might have taken place in zebrafish. However, the ten IRF family members in vertebrates and those IRF-like genes in non-vertebrate deuterostomes were quite different in those analyzed characters, as they might have undergone different patterns of evolution.
Pharmacokinetic-pharmacodynamic profiling of four antimicrobials against Gram-negative bacteria collected from Shenyang, China
Authors: Chu Yun Zhuo , Tian Su Fei , Chen Bai Yi , Nian Hua , Shang Hong , Sun Guo Quan
Published: June 2010

Background

To examine common antimicrobial regimens used in eradicating certain nosocomial Gram-negative pathogens and determine which ones are likely to be the most suitable as empirical choices in Shenyang, China.

Methods

A 5000-subject Monte Carlo simulation was conducted to determine the cumulative fraction of response (CFR) for meropenem, imipenem, cefepime, piperacillin/tazobactam and levofloxacin against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter baumannii and Pseudomonas aeruginosa collected in 2006 and 2007 from Shenyang.

Results

Meropenem and imipenem had the highest CFRs against the Enterobacteriaceae (97%-100%), followed by cefepime. No antibiotic simulated regimen achieved optimal CFR against P. aeruginosa and A. baumannii. Piperacillin/tazobactam dosed at 4.5 g q8h achieved the lowest CFR against all bacteria.

Conclusions

This study suggests that the carbapenems provide the greatest likelihood of clinical success for the Enterobacteriaceae, and combination therapy might be needed when choosing empirical therapy, especially when A. baumannii or P. aeruginosa are suspected.
The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature
Authors: Zhao Jianhua , Li Mingyao , Bradfield Jonathan P , Zhang Haitao , Mentch Frank D , Wang Kai , Sleiman Patrick M , Kim Cecilia E , Glessner Joseph T , Hou Cuiping , Keating Brendan J , Thomas Kelly A , Garris Maria L , Deliard Sandra , Frackelton Edward C , Otieno F George , Chiavacci Rosetta M , Berkowitz Robert I , Hakonarson Hakon , Grant Struan FA
Published: June 2010

Background

Human height is considered highly heritable and correlated with certain disorders, such as type 2 diabetes and cancer. Despite environmental influences, genetic factors are known to play an important role in stature determination. A number of genetic determinants of adult height have already been established through genome wide association studies.

Methods

To examine 51 single nucleotide polymorphisms (SNPs) corresponding to the 46 previously reported genomic loci for height in 8,184 European American children with height measurements. We leveraged genotyping data from our ongoing GWA study of height variation in children in order to query the 51 SNPs in this pediatric cohort.

Results

Sixteen of these SNPs yielded at least nominally significant association to height, representing fifteen different loci including EFEMP1-PNPT1, GPR126, C6orf173, SPAG17, Histone class 1, HLA class III and GDF5-UQCC. Other loci revealed no evidence for association, including HMGA1 and HMGA2. For the 16 associated variants, the genotype score explained 1.64% of the total variation for height z-score.

Conclusion

Among 46 loci that have been reported to associate with adult height to date, at least 15 also contribute to the determination of height in childhood.
Pim1 promotes human prostate cancer cell tumorigenicity and c-MYC transcriptional activity
Authors: Kim Jongchan , Roh Meejeon , Abdulkadir Sarki A
Published: June 2010

Background

The serine/threonine kinase PIM1 has been implicated as an oncogene in various human cancers including lymphomas, gastric, colorectal and prostate carcinomas. In mouse models, Pim1 is known to cooperate with c-Myc to promote tumorigenicity. However, there has been limited analysis of the tumorigenic potential of Pim1 overexpression in benign and malignant human prostate cancer cells in vivo.

Methods

We overexpressed Pim1 in three human prostate cell lines representing different disease stages including benign (RWPE1), androgen-dependent cancer (LNCaP) and androgen-independent cancer (DU145). We then analyzed in vitro and in vivo tumorigenicity as well as the effect of Pim1 overexpression on c-MYC transcriptional activity by reporter assays and gene expression profiling using an inducible MYC-ER system. To validate that Pim1 induces tumorigenicity and target gene expression by modulating c-MYC transcriptional activity, we inhibited c-MYC using a small molecule inhibitor (10058-F4) or RNA interference.

Results

Overexpression of Pim1 alone was not sufficient to convert the benign RWPE1 cell to malignancy although it enhanced their proliferation rates when grown as xenografts in vivo. However, Pim1 expression enhanced the in vitro and in vivo tumorigenic potentials of the human prostate cancer cell lines LNCaP and DU145. Reporter assays revealed increased c-MYC transcriptional activity in Pim1-expressing cells and mRNA expression profiling demonstrated that a large fraction of c-MYC target genes were also regulated by Pim1 expression. The c-MYC inhibitor 10058-F4 suppressed the tumorigenicity of Pim1-expressing prostate cancer cells. Interestingly, 10058-F4 treatment also led to a reduction of Pim1 protein but not mRNA. Knocking-down c-MYC using short hairpin RNA reversed the effects of Pim1 on Pim1/MYC target genes.

Conclusion

Our results suggest an in vivo role of Pim1 in promoting prostate tumorigenesis although it displayed distinct oncogenic activities depending on the disease stage of the cell line. Pim1 promotes tumorigenicity at least in part by enhancing c-MYC transcriptional activity. We also made the novel discovery that treatment of cells with the c-MYC inhibitor 10058-F4 leads to a reduction in Pim1 protein levels.
Identification of galectin-7 as a potential biomarker for esophageal squamous cell carcinoma by proteomic analysis
Authors: Zhu Xi , Ding Ming , Yu Mei-Lan , Feng Ming-Xiang , Tan Li-Jie , Zhao Fu-Kun
Published: June 2010

Background

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies. Early diagnosis is critical for guiding the therapeutic management of ESCC. It is imperative to find more effective biomarkers of ESCC.

Methods

To identify novel biomarkers for esophageal squamous cell carcinoma (ESCC), specimens from 10 patients with ESCC were subjected to a comparative proteomic analysis. The proteomic patterns of ESCC samples and normal esophageal epithelial tissues (NEETs) were compared using two-dimensional gel electrophoresis. And differentially expressed proteins were identified using MALDI-TOF-MS/MS. For further identification of protein in selected spot, western blotting and immunohistochemistry were employed.

Results

Twelve proteins were up-regulated and fifteen proteins were down-regulated in the ESCC samples compared with the NEET samples. Up-regulation of galectin-7 was further confirmed by western blotting and immunohistochemistry. Furthermore, immunohistochemical staining of galectin-7 was performed on a tissue microarray containing ESCC samples (n = 50) and NEET samples (n = 10). The expression levels of galectin-7 were markedly higher in the ESCC samples than in the NEET samples (P = 0.012). In addition, tissue microarray analysis also showed that the expression level of galectin-7 was related to the differentiation of ESCC.

Conclusions

The present proteomics analysis revealed that galectin-7 was highly expressed in ESCC tissues. The alteration in the expression of galectin-7 was confirmed using a tissue microarray. These findings suggest that galectin-7 could be used as a potential biomarker for ESCC.
Acupuncture for chronic low back pain: protocol for a multicenter, randomized, sham-controlled trial
Authors: Lee Jun-Hwan , Park Hi-Joon , Lee Hyangsook , Shin Im Hee , Song Mi-Yeon
Published: June 2010

Background

Use of acupuncture has widely increased in patients with chronic low back pain. However, the evidence supporting its efficacy remains unclear. In this article, we report the design and the protocol of a multi-center randomized sham-controlled trial to treat chronic low back pain. Our goal is to verify the effect of acupuncture on chronic low back pain.

Methods/Design

This study is a multi-center randomized sham-controlled trial with 2 parallel arms. Participants included in the study met the following criteria: 1) low back pain lasting for at least the last 3 months, 2) a documented ≥ 5 points on a 10 cm visual analog scale for bothersomeness of low back pain at the time of screening and 3) between 18 and 65 years of age. Participants were blinded to the real and sham acupuncture treatments. The real acupuncture treatment group received real acupuncture 2 times a week, during a total of 12 sessions over 6 weeks. The control group received sham acupuncture during the same period. In order to assess the primary and secondary outcome measures, the participants were asked to fill out a questionnaire at the baseline and 6, 8, 12 and 24 weeks after starting the treatments. The primary outcome was measured using the visual analog scale for bothersomeness of low back pain at 8 weeks after the initiation of treatments.

Discussion

The result of this trial (which will be available in 2010) will demonstrate the efficacy of using acupuncture to treat chronic low back pain.

Trial registration

This study is registered with the U.S. National Institutes of Health Clinical Trials registry: NCT00815529
A prospective cohort study to investigate cost-minimisation, of Traditional open, open fAst track recovery and laParoscopic fASt track multimodal management, for surgical patients with colon carcinomas (TAPAS study)
Authors: Reurings Jurrian C , Spanjersberg Willem R , Oostvogel Henk JM , Buskens Erik , Maring John , Kruijt Flip , Rosman Camiel , van Duivendijk Peter , Dejong Cees HC , van Laarhoven Cees JHM
Published: June 2010

Background

The present developments in colon surgery are characterized by two innovations: the introduction of the laparoscopic operation technique and fast recovery programs such as the Enhanced Recovery After Surgery (ERAS) recovery program. The Tapas-study was conceived to determine which of the three treatment programs: open conventional surgery, open 'ERAS' surgery or laparoscopic 'ERAS' surgery for patients with colon carcinomas is most cost minimizing?

Method/design

The Tapas-study is a three-arm multicenter prospective cohort study.

All patients with colon carcinoma, eligible for surgical treatment within the study period in four general teaching hospitals and one university hospital will be included. This design produces three cohorts: Conventional open surgery is the control exposure (cohort 1). Open surgery with ERAS recovery (cohort 2) and laparoscopic surgery with ERAS recovery (cohort 3) are the alternative exposures. Three separate time periods are used in order to prevent attrition bias.

Primary outcome parameters are the two main cost factors: direct medical costs (real cost price calculation) and the indirect non medical costs (friction method). Secondary outcome parameters are mortality, complications, surgical-oncological resection margins, hospital stay, readmission rates, time back to work/recovery, health status and quality of life.

Based on an estimated difference in direct medical costs (highest cost factor) of 38% between open and laparoscopic surgery (alfa = 0.01, beta = 0.05), a group size of 3×40 = 120 patients is calculated.

Discussion

The Tapas-study is three-arm multicenter cohort study that will provide a cost evaluation of three treatment programs for patients with colon carcinoma, which may serve as a guideline for choice of treatment and investment strategies in hospitals.

Trial registration

ISRCTN44649165.
Simultaneously performed off-pump coronary artery bypass grafting and colectomy: a case report
Authors: Dedeilias Panagiotis , Nenekidis Ioannis , Koletsis Efstratios , Baikoussis Nikolaos G , Hountis Panagiotis , Exarhos Dimitrios , Klimopoulos Serafim
Published: June 2010

This is written so as to report the case of a 71-year-old male with a diagnosis of sigmoid adenocarcinoma accompanied by severe coronary artery disease and unstable angina, which was subject to simultaneous surgical treatment. The patient initially underwent an off-pump coronary artery revascularization in order to avoid the complications of cardiopulmonary bypass, providing the opportunity of a colectomy at the same time with the use of safe surgical means. Our case suggests that performing an off-pump bypass procedure prior to cancer surgery can be an appropriate course of action in carefully selected cases.
A novel method for purifying bluetongue virus with high purity by co-immunoprecipitation with agarose protein A
Authors: Zhen Song , Changyuan Dong , Lulu Wang , Dong-E Chen , Guoming Bi , Ming Dai , Jun Liu
Published: June 2010

Background

Bluetongue virus (BTV) is an icosahedral non-enveloped virus within the genus Orbivirus of Reoviridae and exists as 24 distinct serotypes. BTV can infect all ruminant species and causes severe sickness in sheep. Recently, it was reported that BTV can infect some human cancer cells selectively. Because of the important oncolysis of this virus, we developed a novel purifying method for large-scale production. The purifying logic is simple, which is picking out all the components unwanted and the left is what we want. The process can be summarized in 4 steps: centrifugation, pulling down cell debrises and soluble proteins by co-immunoprecipitation with agarose Protein A, dialysis and filtration sterilization after concentration.

Results

The result of transmission electron microscope (TEM) observation showed that the sample of purified virus has a very clear background and the virions still kept intact. The result of 50% tissue culture infective dose (TCID50) assay showed that the bioactivity of purified virus is relatively high.

Conclusions

This method can purify BTV-10 with high quality and high biological activity on large-scale production. It also can be used for purifying other BTV serotypes.
Absence of Histamine-Induced Itch in the African Naked Mole-Rat and “Rescue” by Substance P
Authors: St John Smith Ewan , Blass Gregory RC , Lewin Gary R , Park Thomas J
Published: June 2010

Recent research has proposed a pathway in which sensory neurons expressing the capsaicin activated ion channel TRPV1 are required for histamine-induced itch and subsequent scratching behavior. We examined histamine-induced itch in the African naked mole-rat ( Heterocephalus glaber) and found that although naked mole-rats display innate scratching behavior, histamine was unable to evoke increased scratching as is observed in most mouse strains. Using calcium imaging, we examined the histamine sensitivity of naked mole-rat dorsal root ganglia (DRG) neurons and identified a population of small diameter neurons activated by histamine, the majority of which are also capsaicin-sensitive. This suggested that naked mole-rat sensory neurons are activated by histamine, but that spinal dorsal horn processing of sensory information is not the same as in other rodents. We have previously shown that naked mole-rats naturally lack substance P (SP) in cutaneous C-fibers, but that the neurokinin-1 receptor is expressed in the superficial spinal cord. This led us to investigate if SP deficiency plays a role in the lack of histamine-induced scratching in this species. After intrathecal administration of SP into the spinal cord we observed robust scratching behavior in response to histamine injection. Our data therefore support a model in which TRPV1-expressing sensory neurons are important for histamine-induced itch. In addition, we demonstrate a requirement for active, SP-induced post-synaptic drive to enable histamine sensitive afferents to drive itch-related behavior in the naked mole-rat. These results illustrate that it is altered dorsal horn connectivity of nociceptors that underlies the lack of itch and pain-related behavior in the naked mole-rat.
Therapeutic approach to Gradenigo's syndrome: a case report
Authors: Kantas Ilias , Papadopoulou Anna , Balatsouras Dimitrios G , Aspris Andreas , Marangos Nikolaos
Published: June 2010

Introduction

Traditional management of Gradenigo's syndrome requires aggressive and radical surgery without any attempt to preserve hearing. Recent reports, however, describe a successful outcome after conservative surgical intervention without labyrinthectomy. A similar outcome has also been reported in patients who were only prescribed with antibiotics and did not undergo myringotomy.

Case presentation

We report the case of a 24-year-old Caucasian Greek woman with Gradenigo's syndrome who was treated by draining her petrous apex via an infralabyrithine approach between her posterior semicircular canal and the jugular bulb. Her inner ear was not sacrificed during the procedure. She presented pre-operatively with ipsilateral conductive hearing loss, which recovered completely four weeks after the surgery.

Conclusions

Patients with Gradenigo's syndrome may be successfully treated with a combination of long-term permanent drainage and ventilation of the apical cells with corresponding hearing preservation. This can be achieved via a combination of transmastoid, infralabyrinthine and suprajugular approaches, if such would be allowed by the anatomy of the region or if there is enough space between the posterior semicircular canal and the jugular bulb.
Time to achieve remission determines time to be in remission
Authors: Schipper Lydia G , Fransen Jaap , den Broeder Alfons A , Van Riel Piet LCM
Published: June 2010

Introduction

Though remission is currently a treatment goal in patients with rheumatoid arthritis (RA), the number of patients who achieve and sustain remission in daily practice is still small. It is suggested that early remission will be associated with sustainability of remission. The aim was to study the association between time-to-remission and sustainability of remission in a cohort of early RA patients treated according to daily practice.

Methods

For this study, three-year follow-up data were used from the Nijmegen RA Inception Cohort of patients included between 1985 and 2005 (N = 753). Patients were included upon diagnosis (ACR criteria), were systematically evaluated at three-monthly visits and treated according to daily practice. Remission was defined according to the Disease Activity Score (DAS) <1.6 and the ACR remission criteria. Remission of at least 6 months duration was regarded as sustained remission. Predictors for time-to-remission were identified by Cox-regression analyses. The relation between time-to-remission and sustained remission was analyzed using longitudinal binary regression.

Results

N = 398 (52%) patients achieved remission with a median time-to-remission of 12 months. Male gender, younger age and low DAS at baseline were predictive to reach remission rapidly. There were n = 142 (36%) patients experiencing sustained remission, which was determined by a shorter time-to-remission only. The relationship between time-to-remission and sustained remission was described by a significant odds ratio (1.11) (1.10 to 1.12-95% CI) that was constant over the whole period 1985 to 2005. Results obtained with the ACR remission criteria were similar.

Conclusions

A shorter time-to-remission is related to sustainability of remission, supporting striving for early remission in patients with RA.
Primary Disseminated Multifocal Ewing Sarcoma: Results of the Euro-EWING 99 Trial
Authors: Ladenstein Ruth , Pötschger Ulrike , Le Deley Marie Cécile , Whelan Jeremy , Paulussen Michael , Oberlin Odile , van den Berg Henk , Dirksen Uta , Hjorth Lars , Michon Jean , Lewis Ian , Craft Alan , Jürgens Heribert
Published: June 2010

Purpose

To improve the poor prognosis of patients with primary disseminated multifocal Ewing sarcomas (PDMES) with a dose-intense treatment concept.

Patients and Methods

From 1999 to 2005, 281 patients with PDMES were enrolled onto the Euro-EWING 99 R3 study. Median age was 16.2 years (range, 0.4 to 49 years). Recommended treatment consisted of six cycles of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE), one cycle of vincristine, dactinomycin, and ifosfamide (VAI), local treatment (surgery and/or radiotherapy), and high-dose busulfan-melphalan followed by autologous stem-cell transplantation (HDT/SCT).

Results

After a median follow-up of 3.8 years, event-free survival (EFS) and overall survival (OS) at 3 years for all 281 patients were 27% ± 3% and 34% ± 4% respectively. Six VIDE cycles were completed by 250 patients (89%); 169 patients (60%) received HDT/SCT. The estimated 3-year EFS from the start of HDT/SCT was 45% for 46 children younger than 14 years. Cox regression analyses demonstrated increased risk at diagnosis for patients older than 14 years (hazard ratio [HR] = 1.6), a primary tumor volume more than 200 mL (HR = 1.8), more than one bone metastatic site (HR = 2.0), bone marrow metastases (HR = 1.6), and additional lung metastases (HR = 1.5). An up-front risk score based on these HR factors identified three groups with EFS rates of 50% for score ≤ 3 (82 patients), 25% for score more than 3 to less than 5 (102 patients), and 10% for score ≥ 5 (70 patients; P < .0001).

Conclusion

PDMES patients may survive with intensive multimodal therapy. Age, tumor volume, and extent of metastatic spread are relevant risk factors. A score based on these factors may facilitate risk-adapted treatment approaches.
Gene Expression Profile of BRCAness That Correlates With Responsiveness to Chemotherapy and With Outcome in Patients With Epithelial Ovarian Cancer
Authors: Konstantinopoulos Panagiotis A. , Spentzos Dimitrios , Karlan Beth Y. , Taniguchi Toshiyasu , Fountzilas Elena , Francoeur Nancy , Levine Douglas A. , Cannistra Stephen A.
Published: June 2010

Purpose

To define a gene expression profile of BRCAness that correlates with chemotherapy response and outcome in epithelial ovarian cancer (EOC).

Methods

A publicly available microarray data set including 61 patients with EOC with either sporadic disease or BRCA½ germline mutations was used for development of the BRCAness profile. Correlation with platinum responsiveness was assessed in platinum-sensitive and platinum-resistant tumor biopsy specimens from six patients with BRCA germline mutations. Association with poly-ADP ribose polymerase (PARP) inhibitor responsiveness and with radiation-induced RAD51 foci formation (a surrogate of homologous recombination) was assessed in Capan-1 cell line clones. The BRCAness profile was validated in 70 patients enriched for sporadic disease to assess its association with outcome.

Results

The BRCAness profile accurately predicted platinum responsiveness and mutation status in eight of 10 patient-derived tumor specimens and between PARP-inhibitor sensitivity and resistance in four of four Capan-1 clones. When applied to the 70 patients with sporadic disease, patients with the BRCA-like (BL) profile had improved disease-free survival (34 months v 15 months; log-rank P = .013) and overall survival (72 months v 41 months; log-rank P = .006) compared with patients with a non–BRCA-like (NBL) profile, respectively. The BRCAness profile maintained independent prognostic value in multivariate analysis, which controlled for other known clinical prognostic factors.

Conclusion

The BRCAness profile correlates with responsiveness to platinum and PARP inhibitors and identifies a subset of sporadic patients with improved outcome. Additional evaluation of this profile as a predictive tool in patients with sporadic EOC is warranted.
Usercentric Operational Decision Making in Distributed Information Retrieval
Authors: Hosanagar Kartik
Published: June 2010

Information specialists in enterprises regularly use distributed information retrieval (DIR) systems that query a large number of information retrieval (IR) systems, merge the retrieved results, and display them to users. There can be considerable heterogeneity in the quality of results returned by different IR servers. Further, because different servers handle collections of different sizes and have different processing and bandwidth capacities, there can be considerable heterogeneity in their response times. The broker in the DIR system has to decide which servers to query, how long to wait for responses, and which retrieved results to display based on the benefits and costs imposed on users. The benefit of querying more servers and waiting longer is the ability to retrieve more documents. The costs may be in the form of access fees charged by IR servers or user's cost associated with waiting for the servers to respond. We formulate the broker's decision problem as a stochastic mixed-integer program and present analytical solutions for the problem. Using data gathered from FedStats—a system that queries IR engines of several U.S. federal agencies—we demonstrate that the technique can significantly increase the utility from DIR systems. Finally, simulations suggest that the technique can be applied to solve the broker's decision problem under more complex decision environments.
Competitive Behavior-Based Price Discrimination for Software Upgrades
Authors: Mehra Amit , Bala Ram , Sankaranarayanan Ramesh
Published: June 2010

The introduction of product upgrades in a competitive environment is commonly observed in the software industry. When introducing a new product, a software vendor may employ behavior-based price discrimination (BBPD) by offering a discount over its market price to entice existing customers of the competitor. This type of pricing is referred to as competitive upgrade discount pricing and is possible because the vendor can use proof of purchase of a competitor's product as credible evidence to offer the discount. At the same time, the competitor may offer a discount to its own previous customers in order to induce them to buy its upgrade. We formulate a game-theoretic model involving an incumbent and entrant where both firms can offer discounts to existing customers of the incumbent. Although several equilibrium possibilities exist, we establish that an equilibrium with competitive upgrade discount pricing is observed only for a unique market structure and a corresponding unique set of prices. In this equilibrium, instead of leveraging its first mover advantage, the incumbent cedes market share to the entrant. Furthermore, the profits of both the incumbent and the entrant reduce with switching costs. This implies that the use of BBPD has product design implications because firms may influence the switching costs between their products by making appropriate compatibility decisions. In addition, lower switching costs result in reduced consumer surplus. Hence, a social planner may want to increase switching costs. The resulting policy implications are different from those prevalent in other industries such as mobile telecommunications where the regulators reduced switching costs by enforcing number portability.
Using Board Puzzles to Teach Operations Research
Authors: DePuy Gail W. , Taylor G. Don
Published: June 2010

Engineering design is a difficult task. Designers work at the boundaries between physical laws, societal or governmental regulations, the need for efficiency, and the desire to develop creative or aesthetic solutions. Teaching engineering design is therefore a difficult task. How is it possible to stimulate students to think of creative solutions while adhering to established principles and necessary rules? Certainly, it is important for students to have deep-seated roots in engineering fundamentals. These fundamentals include both a strong overall engineering core and coursework specific to the particular branch of engineering study undertaken by the student. For industrial engineers, the study of operations research is fundamental in preparing them for careers in engineering design. This paper addresses one way of encouraging creativity in teaching operations research in industrial engineering design curricula. Specifically, this paper provides examples of the use of games as pedagogical tools in teaching operations research. These games cannot be used as a substitute for teaching practical applications, but they are excellent supplementary tools that encourage students to tackle highly structured problems creatively while working on interesting and enjoyable tasks. Four examples are provided within the paper.