bluuebunny/crossref_metadata_2025_split huggingface dataset:
Very Important Pool (VIP) genes – an application for microarray-based molecular signatures
Authors: Su Zhenqiang , Hong Huixiao , Fang Hong , Shi Leming , Perkins Roger , Tong Weida 
Published: August 2008

Abstract

Background
Advances in DNA microarray technology portend that molecular signatures from which microarray will eventually be used in clinical environments and personalized medicine. Derivation of biomarkers is a large step beyond hypothesis generation and imposes considerably more stringency for accuracy in identifying informative gene subsets to differentiate phenotypes. The inherent nature of microarray data, with fewer samples and replicates compared to the large number of genes, requires identifying informative genes prior to classifier construction. However, improving the ability to identify differentiating genes remains a challenge in bioinformatics.

Results
A new hybrid gene selection approach was investigated and tested with nine publicly available microarray datasets. The new method identifies a Very Important Pool (VIP) of genes from the broad patterns of gene expression data. The method uses a bagging sampling principle, where the re-sampled arrays are used to identify the most informative genes. Frequency of selection is used in a repetitive process to identify the VIP genes. The putative informative genes are selected using two methods, t-statistic and discriminatory analysis. In the t-statistic, the informative genes are identified based on p-values. In the discriminatory analysis, disjoint Principal Component Analyses (PCAs) are conducted for each class of samples, and genes with high discrimination power (DP) are identified. The VIP gene selection approach was compared with the p-value ranking approach. The genes identified by the VIP method but not by the p-value ranking approach are also related to the disease investigated. More importantly, these genes are part of the pathways derived from the common genes shared by both the VIP and p-ranking methods. Moreover, the binary classifiers built from these genes are statistically equivalent to those built from the top 50 p-value ranked genes in distinguishing different types of samples.

Conclusion
The VIP gene selection approach could identify additional subsets of informative genes that would not always be selected by the p-value ranking method. These genes are likely to be additional true positives since they are a part of pathways identified by the p-value ranking method and expected to be related to the relevant biology. Therefore, these additional genes derived from the VIP method potentially provide valuable biological insights.
Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer
Authors: FitzGerald Liesel M , Agalliu Ilir , Johnson Karynn , Miller Melinda A , Kwon Erika M , Hurtado-Coll Antonio , Fazli Ladan , Rajput Ashish B , Gleave Martin E , Cox Michael E , Ostrander Elaine A , Stanford Janet L , Huntsman David G 
Published: August 2008

AbstractBackgroundThe presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer.MethodsIn this study, fluorescentin situhybridization (FISH) assays were used to assess TMPRSS2-ERG fusion status in a group of 214 prostate cancer cases from two population-based studies. The FISH assays were designed to detect both fusion type (deletion vs. translocation) and the number of fusion copies (single vs. multiple). Genotyping of fourERGand oneTMPRSS2SNPs using germline DNA was also performed in a sample of the cases (n = 127).ResultsOf the 214 tumors scored for the TMPRSS2-ERG fusion, 64.5% were negative and 35.5% were positive for the fusion. Cases with the TMPRSS2-ERG fusion did not exhibit reduced prostate cancer survival (HR = 0.92, 95% CI = 0.22–3.93), nor was there a significant difference in cause-specific survival when stratifying by translocation or deletion (HR = 0.84, 95% CI = 0.23–3.12) or by the number of retained fusion copies (HR = 1.22, 95% CI = 0.45–3.34). However, evidence for reduced prostate cancer-specific survival was apparent in those cases whose tumor had multiple copies of the fusion. The variant T allele of theTMPRSS2SNP, rs12329760, was positively associated with TMPRSS2-ERG fusion by translocation (p = 0.05) and with multiple copies of the gene fusion (p = 0.03).ConclusionIf replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer.
EGFR and HER2 expression in primary cervical cancers and corresponding lymph node metastases: Implications for targeted radiotherapy
Authors: Shen Li , Shui Yongjie , Wang Xiaojia , Sheng Liming , Yang Zhengyan , Xue Danfeng , Wei Qichun 
Published: August 2008

Abstract

Background
Proteins overexpressed on the surface of tumor cells can be selectively targeted. Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are among the most often targeted proteins. The level and stability of expression in both primary tumors and corresponding metastases is crucial in the assessment of a receptor as target for imaging in nuclear medicine and for various forms of therapy. So far, the expression of EGFR and HER2 has only been determined in primary cervical cancers, and we have not found published data regarding the receptor status in corresponding metastatic lesions. The goal of this study was to evaluate whether any of these receptors are suitable as target for clinical diagnosis and therapy.

Methods
Expression of EGFR and HER2 was investigated immunohistochemically in both lymph node metastases and corresponding primary cervical cancers (n = 53). HER2 and EGFR expression was scored using HercepTest criteria (0, 1+, 2+ or 3+).

Results
EGFR overexpression (2+ or 3+) was found in 64% (35/53) of the primary cervical tumors and 60% (32/53) of the corresponding lymph node metastases. There was a good concordance between the primary tumors and the paired metastases regarding EGFR expression. Only four patients who had 2+ or 3+ in the primary tumors changed to 0 or 1+ in lymph node metastases, and another two cases changed the other way around. None of the primary tumors or the lymph node metastases expressed HER2 protein.

Conclusion
The EGFR expression seems to be common and stable during cervical cancer metastasis, which is encouraging for testing of EGFR targeted radiotherapy. HER2 appears to be of poor interest as a potential target in the treatment of cervical cancer.
Human eosinophil adhesion and degranulation stimulated with eotaxin and RANTES in vitro: Lack of interaction with nitric oxide
Authors: Lintomen Letícia , Franchi Gilberto , Nowill Alexandre , Condino-Neto Antonio , de Nucci Gilberto , Zanesco Angelina , Antunes Edson 
Published: August 2008

AbstractBackgroundAirway eosinophilia is considered a central event in the pathogenesis of asthma. The toxic components of eosinophils are thought to be important in inducing bronchial mucosal injury and dysfunction. Previous studies have suggested an interaction between nitric oxide (NO) and chemokines in modulating eosinophil functions, but this is still conflicting. In the present study, we have carried out functional assays (adhesion and degranulation) and flow cytometry analysis of adhesion molecules (VLA-4 and Mac-1 expression) to evaluate the interactions between NO and CC-chemokines (eotaxin and RANTES) in human eosinophils.MethodsEosinophils were purified using a percoll gradient followed by immunomagnetic cell separator. Cell adhesion and degranulation were evaluated by measuring eosinophil peroxidase (EPO) activity, whereas expression of Mac-1 and VLA-4 was detected using flow cytometry.ResultsAt 4 h incubation, both eotaxin (100 ng/ml) and RANTES (1000 ng/ml) increased by 133% and 131% eosinophil adhesion, respectively. L-NAME alone (but not D-NAME) also increased the eosinophil adhesion, but the co-incubation of L-NAME with eotaxin or RANTES did not further affect the increased adhesion seen with chemokines alone. In addition, L-NAME alone (but not D-NAME) caused a significant cell degranulation, but it did not affect the CC-chemokine-induced cell degranulation. Incubation of eosinophils with eotaxin or RANTES, in absence or presence of L-NAME, did not affect the expression of VLA-4 and Mac-1 on eosinophil surface. Eotaxin and RANTES (100 ng/ml each) also failed to elevate the cyclic GMP levels above baseline in human eosinophils.ConclusionEotaxin and RANTES increase the eosinophil adhesion to fibronectin-coated plates and promote cell degranulation by NO-independent mechanisms. The failure of CC-chemokines to affect VLA-4 and Mac-1 expression suggests that changes in integrin function (avidity or affinity) are rather involved in the enhanced adhesion.
Dissatisfaction with the laboratory services in conducting HIV related testing among public and private medical personnel in Tanzania
Authors: Mfinanga SG , Kahwa A , Kimaro G , Kilale A , Kivuyo S , Senkoro M , Ngowi B , Mtandu R , Mutayoba B , Ngadaya E , Mashoto K 
Published: August 2008

Abstract

Background
A comprehensive care and treatment program requires a well functioning laboratory services. We assessed satisfaction of medical personnel to the laboratory services to guide process of quality improvement of the services.

Methodology
A cross-sectional survey in 24 randomly selected health facilities in Mainland Tanzania was conducted to assess the satisfaction of the medical personnel with the laboratory services.

Results
Of 235 medical personnel interviewed, 196 were valid for analysis and about one quarter were dissatisfied with the laboratory services. Personnel dissatisfied with the services were 38.3% in timely test result, 24.5% in correct and accurate results and 22.4% in clear complete results. The personnel in public laboratories were more dissatisfied with timely test results (OR = 3.6, 95% CI 1.8, 7.3), correct results (OR = 4.1, 95% CI 1.6, 10.8) and clear complete results (OR = 5.0 95% CI 1.6, 15.2). Personnel dissatisfied with the services in 15 laboratories sending specimens to referral laboratories, varied from 13% in availability of equipment to 57% in timely results feedback from the referral laboratories. Personnel dissatisfied with the services in 14 referral laboratories, varied from 28.6% in properly identified specimen to 42.9% in clear, accurate test request and communication.

Conclusion
About one quarter of medical personnel in sending or receiving laboratories were dissatisfied with the services. Comparing the personnel in public and private, the personnel in public laboratories were 4 times more dissatisfied with the timely test and correct results; and 5 times more dissatisfied with clear and complete test results.
In vivo quantification of embryonic and placental growth during gestation in mice using micro-ultrasound
Authors: Mu Junwu , Slevin John C , Qu Dawei , McCormick Sarah , Adamson S Lee 
Published: August 2008

Abstract

Background
Non-invasive micro-ultrasound was evaluated as a method to quantify intrauterine growth phenotypes in mice. Improved methods are required to accelerate research using genetically-altered mice to investigate the interactive roles of genes and environments on embryonic and placental growth. We determined (1) feasible age ranges for measuring specific variables, (2) normative growth curves, (3) accuracy of ultrasound measurements in comparison with light microscopy, and (4) weight prediction equations using regression analysis for CD-1 mice and evaluated their accuracy when applied to other mouse strains.

Methods
We used 30–40 MHz ultrasound to quantify embryonic and placental morphometry in isoflurane-anesthetized pregnant CD-1 mice from embryonic day 7.5 (E7.5) to E18.5 (full-term), and for C57Bl/6J, B6CBAF1, and hIGFBP1 pregnant transgenic mice at E17.5.

Results
Gestational sac dimension provided the earliest measure of conceptus size. Sac dimension derived using regression analysis increased from 0.84 mm at E7.5 to 6.44 mm at E11.5 when it was discontinued. The earliest measurement of embryo size was crown-rump length (CRL) which increased from 1.88 mm at E8.5 to 16.22 mm at E16.5 after which it exceeded the field of view. From E10.5 to E18.5 (full term), progressive increases were observed in embryonic biparietal diameter (BPD) (0.79 mm to 7.55 mm at E18.5), abdominal circumference (AC) (4.91 mm to 26.56 mm), and eye lens diameter (0.20 mm to 0.93 mm). Ossified femur length was measureable from E15.5 (1.06 mm) and increased linearly to 2.23 mm at E18.5. In contrast, placental diameter (PD) and placental thickness (PT) increased from E10.5 to E14.5 then remained constant to term in accord with placental weight. Ultrasound and light microscopy measurements agreed with no significant bias and a discrepancy of less than 25%. Regression equations predicting gestational age from individual variables, and embryonic weight (BW) from CRL, BPD, and AC were obtained. The prediction equation BW = -0.757 + 0.0453 (CRL) + 0.0334 (AC) derived from CD-1 data predicted embryonic weights at E17.5 in three other strains of mice with a mean discrepancy of less than 16%.

Conclusion
Micro-ultrasound provides a feasible tool for in vivo morphometric quantification of embryonic and placental growth parameters in mice and for estimation of embryonic gestational age and/or body weight in utero.
Why did soft drink consumption decrease but screen time not? Mediating mechanisms in a school-based obesity prevention program
Authors: Chin A Paw Marijke JM , Singh Amika S , Brug Johannes , van Mechelen Willem 
Published: August 2008

Abstract

Objectives
This paper aims to identify the mediating mechanisms of a school-based obesity prevention program (DOiT).

Methods
The DOiT-program was implemented in Dutch prevocational secondary schools and evaluated using a controlled, cluster-randomised trial (September 2003 to May 2004). We examined mediators of effects regarding (1) consumption of sugar containing beverages (SCB); (2) consumption of high caloric snacks; (3) screen-viewing behaviour; and (4) active commuting to school. To improve these behaviours the DOiT-program tried to influence the following potentially mediating variables: attitude, subjective norm, perceived behavioural control, and habit-strength.

Results
Both in boys (n = 418) and girls (n = 436) the DOiT-intervention reduced SCB consumption (between group difference in boys = -303.5 ml/day, 95% CI: -502.4;-104.5, between group difference in girls = -222.3 ml/day, 95% CI: -371.3;-73.2). The intervention did not affect the other examined behaviours. In girls, no intervention effect on hypothetical mediators was found nor evidence of any mediating mechanisms. Boys in intervention schools improved their attitude towards decreasing SCB consumption, while this behaviour became less of a habit. Indeed, attitude and habit strength were significant mediators of the DOiT-intervention's effect (4.5 and 3.8%, respectively) on SCB consumption among boys.

Conclusion
Our findings imply that interventions aimed at EBRB-change should be gender-specific. Future studies aimed at reducing SCB consumption among boys should target attitude and habit strength as mediating mechanisms. Our study did not resolve the mediating mechanisms in girls.

Trial registration
International Standard Randomised Controlled Trial Number Register ISRCTN87127361
Modulation of Chloride Homeostasis by Inflammatory Mediators in Dorsal Root Ganglion Neurons
Authors: Funk Katharina , Woitecki Anne , Franjic-Würtz Christina , Gensch Thomas , Möhrlen Frank , Frings Stephan 
Published: August 2008

Background: Chloride currents in peripheral nociceptive neurons have been implicated in the generation of afferent nociceptive signals, as Cl− accumulation in sensory endings establishes the driving force for depolarizing, and even excitatory, Cl− currents. The intracellular Cl− concentration can, however, vary considerably between individual DRG neurons. This raises the question, whether the contribution of Cl− currents to signal generation differs between individual afferent neurons, and whether the specific Cl− levels in these neurons are subject to modulation. Based on the hypothesis that modulation of the peripheral Cl− homeostasis is involved in the generation of inflammatory hyperalgesia, we examined the effects of inflammatory mediators on intracellular Cl− concentrations and on the expression levels of Cl− transporters in rat DRG neurons. Results: We developed an in vitro assay for testing how inflammatory mediators influence Cl− concentration and the expression of Cl− transporters. Intact DRGs were treated with 100 ng/ml NGF, 1.8 μM ATP, 0.9 μM bradykinin, and 1.4 μM PGE2 for 1–3 hours. Two-photon fluorescence lifetime imaging with the Cl−-sensitive dye MQAE revealed an increase of the intracellular Cl− concentration within 2 hours of treatment. This effect coincided with enhanced phosphorylation of the Na+-K+−2Cl− cotransporter NKCC1, suggesting that an increased activity of that transporter caused the early rise of intracellular Cl− levels. Immunohistochemistry of NKCC1 and KCC2, the main neuronal Cl− importer and exporter, respectively, exposed an inverse regulation by the inflammatory mediators. While the NKCC1 immunosignal increased, that of KCC2 declined after 3 hours of treatment. In contrast, the mRNA levels of the two transporters did not change markedly during this time. These data demonstrate a fundamental transition in Cl− homeostasis toward a state of augmented Cl− accumulation, which is induced by a 1–3 hour treatment with inflammatory mediators. Conclusion: Our findings indicate that inflammatory mediators impact on Cl− homeostasis in DRG neurons. Inflammatory mediators raise intracellular Cl− levels and, hence, the driving force for depolarizing Cl− efflux. These findings corroborate current concepts for the role of Cl− regulation in the generation of inflammatory hyperalgesia and allodynia. As the intracellular Cl− concentration rises in DRG neurons, afferent signals can be boosted by excitatory Cl− currents in the presynaptic terminals. Moreover, excitatory Cl− currents in peripheral sensory endings may also contribute to the generation or modulation of afferent signals, especially in inflamed tissue.
Infraorbital cutaneous angiosarcoma: a diagnostic and therapeutic dilemma
Authors: Ettl Tobias , Kleinheinz Johannes , Mehrotra Ravi , Schwarz Stephan , Reichert Torsten E , Driemel Oliver 
Published: August 2008

Abstract

Background
A cutaneous angiosarcoma is a rare malignant tumour of vascular endothelial cells with aggressive clinical behaviour and poor prognosis. Diagnosis is often delayed due to its variable and often benign clinical appearance.

Case presentation
This case presents a 64-year-old man with a six-month-history of a recurrent diffuse and erythematous painless swelling below the left eye. Several resections with intraoperatively negative resection margins followed, but positive margins were repeatedly detected later on permanent sections. Histopathologic examination of the specimen diagnosed a cutaneous angiosarcoma. Neither, finally achieved negative margins on permanent sections, nor a following chemotherapy could prevent the recurrence of the disease after five months and the patient's dead 21 months after the first diagnosis.

Conclusion
The case elucidates the current diagnostic and therapeutic dilemma of this entity, which shows an unfavourable clinical course in spite of multimodal therapy.
Role of Caveolin 1, E-Cadherin, Enolase 2 and PKCalpha on resistance to methotrexate in human HT29 colon cancer cells
Authors: Selga Elisabet , Morales Cristina , Noé Véronique , Peinado Miguel A , Ciudad Carlos J 
Published: August 2008

AbstractBackgroundMethotrexate is one of the earliest cytotoxic drugs used in cancer therapy, and despite the isolation of multiple other folate antagonists, methotrexate maintains its significant role as a treatment for different types of cancer and other disorders. The usefulness of treatment with methotrexate is limited by the development of drug resistance, which may be acquired through different ways. To get insights into the mechanisms associated with drug resistance and sensitization we performed a functional analysis of genes deregulated in methotrexate resistant cells, either due to its co-amplification with thedhfrgene or as a result of a transcriptome screening using microarrays.MethodsGene expression levels were compared between triplicate samples from either HT29 sensitive cells and resistant to 10-5M MTX by hybridization to the GeneChip®HG U133 PLUS 2.0 from Affymetrix. After normalization, a list of 3-fold differentially expressed genes with a p-value < 0.05 including multiple testing correction (Benjamini and Hochberg false discovery rate) was generated. RT-Real-time PCR was used to validate the expression levels of selected genes and copy-number was determined by qPCR. Functional validations were performed either by siRNAs or by transfection of an expression plasmid.ResultsGenes adjacent to thedhfr locusand included in the 5q14 amplicon were overexpressed in HT29 MTX-resistant cells. Treatment with siRNAs against those genes caused a slight reduction in cell viability in both HT29 sensitive and resistant cells. On the other hand, microarray analysis of HT29 and HT29 MTX resistant cells unveiled overexpression of caveolin 1, enolase 2 and PKCα genes in resistant cells without concomitant copy number gain. siRNAs against these three genes effectively reduced cell viability and caused a decreased MTX resistance capacity. Moreover, overexpression of E-cadherin, which was found underexpressed in MTX-resistant cells, also sensitized the cells toward the chemotherapeutic agent. Combined treatments targeting siRNA inhibition of caveolin 1 and overexpression of E-cadherin markedly reduced cell viability in both sensitive and MTX-resistant HT29 cells.ConclusionWe provide functional evidences indicating that caveolin 1 and E-cadherin, deregulated in MTX resistant cells, may play a critical role in cell survival and may constitute potential targets for coadjuvant therapy.
Growing pains: contemporary knowledge and recommended practice
Authors: Evans Angela M 
Published: August 2008

AbstractBackgroundLeg pain in children, described as growing pains, is a frequent clinical presentation seen by an array of health care professionals. Described since 1823, growing pains continues to puzzle practitioners, yet diagnostic criteria and evidence based treatment is available.MethodsThe medical literature has been searched exhaustively to access all articles (English language) pertaining to leg pains in children which are ascribed to being ‘growing pains’.ResultsThe literature, whilst plentiful in quantity and spanning two centuries, is generally replete with reiterated opinion and anecdote and lacking in scientific rigour. The author searched 45 articles for relevance, determined according to title, abstract and full text, resulting in a yield of 22 original studies and 23 review articles. From the original studies, one small (non‐blinded) randomised controlled trial that focused on GP treatment with leg muscle stretching was found. Nine prevalence studies were found revealing disparate estimates. Ten cohort (some case‐controlled) studies, which investigated pain attribute differences in affected versus unaffected groups, were found. One series of single case experiment designs and one animal model study were found.ConclusionGrowing pains is prevalent in young children, presents frequently in the health care setting where it is poorly managed and is continuing to be researched. A common childhood complaint, growing pains needs to be acknowledged and better managed in the contemporary medical setting.