bluuebunny/crossref_metadata_2025_split huggingface dataset:
SIRAC: Supervised Identification of Regions of Aberration in aCGH datasets
Authors: Lai Carmen , Horlings Hugo M , van de Vijver Marc J , van Beers Eric H , Nederlof Petra M , Wessels Lodewyk FA , Reinders Marcel JT 
Published: October 2007

AbstractBackgroundArray comparative genome hybridization (aCGH) provides information about genomic aberrations. Alterations in the DNA copy number may cause the cell to malfunction, leading to cancer. Therefore, the identification of DNA amplifications or deletions across tumors may reveal key genes involved in cancer and improve our understanding of the underlying biological processes associated with the disease.ResultsWe propose a supervised algorithm for the analysis of aCGH data and the identification of regions of chromosomal alteration (SIRAC). We first determine the DNA-probes that are important to distinguish the classes of interest, and then evaluate in a systematic and robust scheme if these relevant DNA-probes are closely located, i.e. form a region of amplification/deletion. SIRAC does not need any preprocessing of the aCGH datasets, and requires only few, intuitive parameters.ConclusionWe illustrate the features of the algorithm with the use of a simple artificial dataset. The results on two breast cancer datasets show promising outcomes that are in agreement with previous findings, but SIRAC better pinpoints the dissimilarities between the classes of interest.
Investigation of factors affecting prediction of protein-protein interaction networks by phylogenetic profiling
Authors: Karimpour-Fard Anis , Hunter Lawrence , Gill Ryan T 
Published: October 2007

Abstract

Background
The use of computational methods for predicting protein interaction networks will continue to grow with the number of fully sequenced genomes available. The Co-Conservation method, also known as the Phylogenetic profiles method, is a well-established computational tool for predicting functional relationships between proteins.

Results
Here, we examined how various aspects of this method affect the accuracy and topology of protein interaction networks. We have shown that the choice of reference genome influences the number of predictions involving proteins of previously unknown function, the accuracy of predicted interactions, and the topology of predicted interaction networks. We show that while such results are relatively insensitive to the E-value threshold used in defining homologs, predicted interactions are influenced by the similarity metric that is employed. We show that differences in predicted protein interactions are biologically meaningful, where judicious selection of reference genomes, or use of a new scoring scheme that explicitly considers reference genome relatedness, produces known protein interactions as well as predicted protein interactions involving coordinated biological processes that are not accessible using currently available databases.

Conclusion
These studies should prove valuable for future studies seeking to further improve phylogenetic profiling methodologies as well for efforts to efficiently employ such methods to develop new biological insights.
Comparative transcriptomics in Yersinia pestis: a global view of environmental modulation of gene expression
Authors: Han Yanping , Qiu Jingfu , Guo Zhaobiao , Gao He , Song Yajun , Zhou Dongsheng , Yang Ruifu 
Published: October 2007

AbstractBackgroundEnvironmental modulation of gene expression inYersinia pestisis critical for its life style and pathogenesis. Using cDNA microarray technology, we have analyzed the global gene expression of this deadly pathogen when grown under different stress conditionsin vitro.ResultsTo provide us with a comprehensive view of environmental modulation of global gene expression inY. pestis, we have analyzed the gene expression profiles of 25 different stress conditions. Almost all known virulence genes ofY. pestiswere differentially regulated under multiple environmental perturbations. Clustering enabled us to functionally classify co-expressed genes, including some uncharacterized genes. Collections of operons were predicted from the microarray data, and some of these were confirmed by reverse-transcription polymerase chain reaction (RT-PCR). Several regulatory DNA motifs, probably recognized by the regulatory protein Fur, PurR, or Fnr, were predicted from the clustered genes, and a Fur binding site in the corresponding promoter regions was verified by electrophoretic mobility shift assay (EMSA).ConclusionThe comparative transcriptomics analysis we present here not only benefits our understanding of the molecular determinants of pathogenesis and cellular regulatory circuits inY. pestis, it also serves as a basis for integrating increasing volumes of microarray data using existing methods.
Maternal diabetes induces congenital heart defects in mice by altering the expression of genes involved in cardiovascular development
Authors: Kumar Srinivasan Dinesh , Dheen S Thameem , Tay Samuel Sam Wah 
Published: October 2007

Abstract

Background
Congenital heart defects are frequently observed in infants of diabetic mothers, but the molecular basis of the defects remains obscure. Thus, the present study was performed to gain some insights into the molecular pathogenesis of maternal diabetes-induced congenital heart defects in mice.

Methods and results
We analyzed the morphological changes, the expression pattern of some genes, the proliferation index and apoptosis in developing heart of embryos at E13.5 from streptozotocin-induced diabetic mice. Morphological analysis has shown the persistent truncus arteriosus combined with a ventricular septal defect in embryos of diabetic mice. Several other defects including defective endocardial cushion (EC) and aberrant myofibrillogenesis have also been found. Cardiac neural crest defects in experimental embryos were analyzed and validated by the protein expression of NCAM and PGP 9.5. In addition, the protein expression of Bmp4, Msx1 and Pax3 involved in the development of cardiac neural crest was found to be reduced in the defective hearts. The mRNA expression of Bmp4, Msx1 and Pax3 was significantly down-regulated (p < 0.001) in the hearts of experimental embryos. Further, the proliferation index was significantly decreased (p < 0.05), whereas the apoptotic cells were significantly increased (p < 0.001) in the EC and the ventricular myocardium of the experimental embryos.

Conclusion
It is suggested that the down-regulation of genes involved in development of cardiac neural crest could contribute to the pathogenesis of maternal diabetes-induced congenital heart defects.
A novel activating role of SRC and STAT3 on HGF transcription in human breast cancer cells
Authors: Sam Michelle R , Elliott Bruce E , Mueller Christopher R 
Published: October 2007

Abstract
We have previously determined that the HGF promoter can be transactivated by a combination of activated Src and wild-type Stat3 in the mouse breast cell lines HC11 and SP1. To determine if this pathway is of relevance for the human disease, a series of human breast and other human cells lines were examined, and the status of key proteins in these cells determined. All of the human breast cell lines exhibited strong transactivation by a combination of activated Src and Stat3. This activation was dependent on a Stat3 recognition element present at nt-95. The exception was the ErbB2 over-expressing cell line SK-BR-3 where Stat3 alone could transactivate HGF though Src augmented this effect. Increased phosphorylation of Stat3 tyrosine 705 was also observed in this line. Analysis of three ovarian cell lines revealed that Src/Stat3 expression was not able to activate the HGF promoter in two of these lines (SKOV3 and IOSE-80PC). Src/Stat3 expression did activate HGF transcription in OVCAR3 cells, but this effect was not mediated by the Stat3 site at nt-95. Stat3 phosphorylation at tyrosine 705 was observed in IOSE-80PC cells, but was insufficient to allow for activation of the HGF promoter. Human kidney (HEK293) and cervical carcinoma (HeLa) cells were also not Src/Stat3 permissive, despite high levels of Stat3 phospho-Y705. These results suggest that human breast cells are a uniquely permissive environment for HGF transactivation by Src/Stat3 which may allow for the inappropriate activation of HGF transcription during the early stages of breast transformation. This could lead to paracrine or autocrine activation of the Met receptor in breast carcinoma cells.
The outcomes of midline versus medio-lateral episiotomy
Authors: Sooklim Ratchadawan , Thinkhamrop Jadsada , Lumbiganon Pisake , Prasertcharoensuk Witoon , Pattamadilok Jeerichuda , Seekorn Kanok , Chongsomchai Chompilas , Pitak Prakai , Chansamak Sukanya 
Published: October 2007

Abstract

Background
Episiotomy is the surgical enlargement of the vaginal orifice by an incision of the perineum during the second stage of labor or just before delivery of the baby. During the 1970s, it was common to perform an episiotomy for almost all women having their first delivery, ostensibly for prevention of severe perineum tears and easier subsequent repair. However, there are no data available to indicate if an episiotomy should be midline or medio-lateral. We compared midline versus medio-lateral episiotomy for complication such as extended perineal tears, pain scores, wound infection rates and other complications.

Methods
We conducted a prospective cohort including 1,302 women, who gave birth vaginally between April 2005 and February 2006 at Srinagarind Hospital – a tertiary care center in Northeast Thailand. All women included had low risk pregnancies and delivered at term. The outcome measures included deep perineal tears (including perineal tears with anal sphincter and/or rectum tears), other complications, and women's satisfaction at 48 hours and 6-weeks postpartum.

Results
In women with midline episiotomy, deep perineal tears occurred in 14.8%, which is statistically significantly higher compared to 7% in women who underwent a medio-lateral episiotomy (p-value < 0.05). There was no difference between the groups for other outcomes (such as blood loss, vaginal hematoma, infection, pain, dyspareunia, and women's satisfaction with the method). The risk factors for deep perineal tears were: midline episiotomy, primiparity, maternal height < 145 cm, fetal birth weight > 3,500 g and forceps extraction.

Conclusion
Midline compared to medio-lateral episiotomy resulted in more deep perineal tears. It is more likely deep perineal tears would occur in cases with additional risk factors.
Regional radiotherapy versus an axillary lymph node dissection after lumpectomy: a safe alternative for an axillary lymph node dissection in a clinically uninvolved axilla in breast cancer. A case control study with 10 years follow up
Authors: Spruit Patty H , Siesling Sabine , Elferink Marloes AG , Vonk Ernest JA , Hoekstra Carel JM 
Published: October 2007

Abstract

Background
The standard treatment of the axilla in breast cancer used to be an axillary lymph node dissection. An axillary lymph node dissection is known to give substantial risks of morbidity. In recent years the sentinel node biopsy has become common practice. Future randomized study results will determine whether the expected decrease in morbidity can be proven.

Methods
Before the introduction of the sentinel node biopsy, we conducted a study in which 180 women of 50 years and older with T1/T2 cN0 breast cancer were treated with breast conserving therapy. Instead of an axillary lymph node dissection regional radiotherapy was given in combination with tamoxifen (RT-group). The study group was compared with 341 patients, with the same patient and tumour characteristics, treated with an axillary lymph node dissection (S-group).

Results
The treatment groups were comparable, except for age. The RT-group was significantly older than the S-group. The median follow up was 7.2 years. The regional relapse rates were low and equal in both treatment groups, 1.1% in RT-group versus 1.5% in S-group at 5 years. The overall survival was similar; the disease free survival was significant better in the RT-group.

Conclusion
Regional recurrence rates after regional radiotherapy are very low and equal to an axillary lymphnode dissection.
Surviving streptococcal toxic shock syndrome: a case report
Authors: Madhusudhan Thayur R , Sambamurthy Srivatsa , Williams Eileen , Smith Ian C 
Published: October 2007

Abstract
Streptococcal toxic shock syndrome and associated myositis caused by group A beta-hemolytic streptococcus pyogenes generally have a poor outcome despite aggressive operative treatment. Frequently the diagnosis is missed initially as the clinical features are non-specific. The progression to a toxic state is rapid and unless definitive treatment measures are initiated early, the end result can be catastrophic. We report a previously healthy patient who had features of toxic shock syndrome due to alpha haemolytic (viridans) streptococcus mitis which was treated successfully with antibiotics, aggressive intensive care support including the use of a 'sepsis care bundle', monitoring and continuous multidisciplinary review. Life and limb threatening emergencies due to streptococcus mitis in an immune-competent person are rare and to our knowledge, have not previously been described in the English scientific literature. Successful outcome is possible provided a high degree of suspicion is maintained and the patient is intensively monitored.
Collagen-induced arthritis in C57BL/6 mice is associated with a robust and sustained T-cell response to type II collagen
Authors: Inglis Julia J , Criado Gabriel , Medghalchi Mino , Andrews Melanie , Sandison Ann , Feldmann Marc , Williams Richard O 
Published: October 2007

AbstractMany genetically modified mouse strains are now available on a C57BL/6 (H-2b) background, a strain that is relatively resistant to collagen-induced arthritis. To facilitate the molecular understanding of autoimmune arthritis, we characterised the induction of arthritis in C57BL/6 mice and then validated the disease as a relevant pre-clinical model for rheumatoid arthritis.C57BL/6 mice were immunised with type II collagen using different protocols, and arthritis incidence, severity, and response to commonly used anti-arthritic drugs were assessed and compared with DBA/1 mice. We confirmed that C57BL/6 mice are susceptible to arthritis induced by immunisation with chicken type II collagen and develop strong and sustained T-cell responses to type II collagen. Arthritis was milder in C57BL/6 mice than DBA/1 mice and more closely resembled rheumatoid arthritis in its response to therapeutic intervention. Our findings show that C57BL/6 mice are susceptible to collagen-induced arthritis, providing a valuable model for assessing the role of specific genes involved in the induction and/or maintenance of arthritis and for evaluating the efficacy of novel drugs, particularly those targeted at T cells.
Intentional overdose with insulin: prognostic factors and toxicokinetic/toxicodynamic profiles
Authors: Mégarbane Bruno , Deye Nicolas , Bloch Vanessa , Sonneville Romain , Collet Corinne , Launay Jean-Marie , Baud Frédéric J 
Published: October 2007

Abstract
Introduction
Prognostic factors in intentional insulin self-poisoning and the significance of plasma insulin levels are unclear. We therefore conducted this study to investigate prognostic factors in insulin poisoning, in relation to the value of plasma insulin concentration.

Methods
We conducted a prospective study, and used logistic regression to explore prognostic factors and modelling to investigate toxicokinetic/toxicodynamic relationships.

Results
Twenty-five patients (14 female and 11 male; median [25th to 75th percentiles] age 46 [36 to 58] years) were included. On presentation, the Glasgow Coma Scale score was 9 (4 to 14) and the capillary glucose concentration was 1.4 (1.1 to 2.3) mmol/l. The plasma insulin concentration was 197 (161 to 1,566) mIU/l and the cumulative amount of glucose infused was 301 (184 to 1,056) g. Four patients developed sequelae resulting in two deaths. Delay to therapy in excess of 6 hours (odds ratio 60.0, 95% confidence interval 2.9 to 1,236.7) and ventilation for longer than 48 hours (odds ratio 28.5, 95% confidence interval 1.9 to 420.6) were identified as independent prognostic factors. Toxicokinetic/toxicodynamic relationships between glucose infusion rates and insulin concentrations fit the maximum measured glucose infusion rate (Emax) model (Emax 29.5 [17.5 to 41.1] g/hour, concentration associated with the half-maximum glucose infusion rate [EC50] 46 [35 to 161] mIU/l, and R2 range 0.70 to 0.98; n = 6).

Conclusion
Intentional insulin overdose is rare. Assessment of prognosis relies on clinical findings. The observed plasma insulin EC50 is 46 mIU/l.
On the association between chromosomal rearrangements and genic evolution in humans and chimpanzees
Authors: Marques-Bonet Tomàs , Sànchez-Ruiz Jesús , Armengol Lluís , Khaja Razi , Bertranpetit Jaume , Lopez-Bigas Núria , Rocchi Mariano , Gazave Elodie , Navarro Arcadi 
Published: October 2007

Abstract
Background
The role that chromosomal rearrangements might have played in the speciation processes that have separated the lineages of humans and chimpanzees has recently come into the spotlight. To date, however, results are contradictory. Here we revisit this issue by making use of the available human and chimpanzee genome sequence to study the relationship between chromosomal rearrangements and rates of DNA sequence evolution.

Results
Contrary to previous findings for this pair of species, we show that genes located in the rearranged chromosomes that differentiate the genomes of humans and chimpanzees, especially genes within rearrangements themselves, present lower divergence than genes elsewhere in the genome. Still, there are considerable differences between individual chromosomes. Chromosome 4, in particular, presents higher divergence in genes located within its rearrangement.

Conclusion
A first conclusion of our analysis is that divergence is lower for genes located in rearranged chromosomes than for those in colinear chromosomes. We also report that non-coding regions within rearranged regions tend to have lower divergence than non-coding regions outside them.
These results suggest an association between chromosomal rearrangements and lower non-coding divergence that has not been reported before, even if some chromosomes do not follow this trend and could be potentially associated with a speciation episode. In summary, without excluding it, our results suggest that chromosomal speciation has not been common along the human and chimpanzee lineage.
Phase III Double-Blind Trial of Arzoxifene Compared With Tamoxifen for Locally Advanced or Metastatic Breast Cancer
Authors: Deshmane VijayaLaxmi , Krishnamurthy S. , Melemed Allen S. , Peterson Patrick , Buzdar Aman U. 
Published: October 2007

Purpose To compare the efficacy of arzoxifene with tamoxifen for the treatment of locally advanced or metastatic breast cancer. Patients and Methods Women with estrogen- or progesterone-receptor–positive breast cancer who had not received prior systemic therapy, or who had relapsed more than 12 months after stopping adjuvant hormonal therapy, were randomly assigned to receive 20 mg arzoxifene or 20 mg tamoxifen daily. Each treatment arm was to have 240 patients enrolled. The primary end point was progression-free survival. Secondary end points included other measures of tumor response, overall survival, and safety. Results Enrollment was stopped when a planned interim analysis of the first 200 patients suggested arzoxifene to be significantly inferior to tamoxifen. The median progression-free survival for the 352 patients who had been randomly assigned when enrollment was stopped was 4.0 months (95% CI, 3.4 to 5.6 months) for the arzoxifene group and 7.5 months (95% CI, 5.9 to 8.8 months) for the tamoxifen group. On-study progression-free survival (P = .011) and time to treatment failure (P = .029) also favored tamoxifen. Overall tumor response rate and median response duration were comparable between the groups. Adverse events were similar between the treatments, except for nausea (more frequent with arzoxifene) and vaginal discharge (more frequent with tamoxifen). Conclusion Tamoxifen produced significantly longer progression-free survival and time to treatment failure compared with arzoxifene in the treatment of locally advanced and metastatic breast cancer. There were no significant differences between tumor response rate, clinical benefit rate, or median response duration.
Projecting Individualized Probabilities of Developing Bladder Cancer in White Individuals
Authors: Wu Xifeng , Lin Jie , Grossman H. Barton , Huang Maosheng , Gu Jian , Etzel Carol J. , Amos Christopher I. , Dinney Colin P. , Spitz Margaret R. 
Published: October 2007

Purpose There has been no risk assessment model for bladder cancer (BC). We developed the first model incorporating mutagen sensitivity and epidemiologic factors to predict BC risk. Patients and Methods We used epidemiologic and genetic data from a large case-control study to build the models and constructed receiver operating characteristic curves. The area under the curve (AUC) was used to evaluate model discriminatory ability. We also projected absolute risk of developing BC by taking into account competing causes of death. Results The study included 678 white BC patients and 678 controls. Significant risk factors in the epidemiologic model included pack-years smoked and exposures to diesel, aromatic amines, dry cleaning fluids, radioactive materials, and arsenic. This model yielded good discriminatory ability (AUC = 0.70; 95% CI, 0.67 to 0.73). When mutagen sensitivity data were incorporated, the AUC increased to 0.80 (95% CI, 0.72 to 0.82). The models showed excellent concordance in the internal validation. We also computed an easy to use ordinal risk score and provided examples for projecting absolute risk. Conclusion We have developed the first risk prediction model for BC. The enhanced model integrating the genetic factor exhibited excellent discriminatory ability. Our model only requires an individual to answer a few simple questions during a clinic visit to project individualized probability. This model may be used as a basis for developing a Web-based tool for BC risk assessment. Validation of our model in an external population is an essential next step towards practical use in the clinical setting.