bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of cytoplasmic-to-nuclear ratio of survivin as an indicator of improved prognosis in breast cancer
Authors: Rexhepaj Elton , Jirstrom Karin , O'Connor Darran P , O'Brien Sallyann L , Landberg Goran , Duffy Michael J , Brennan Donal J , Gallagher William M 
Published: November 2010

Abstract

Background
Conflicting data exist regarding the prognostic and predictive impact of survivin (BIRC5) in breast cancer. We previously reported survivin cytoplasmic-to-nuclear ratio (CNR) as an independent prognostic indicator in breast cancer. Here, we validate survivin CNR in a separate and extended cohort. Furthermore, we present new data suggesting that a low CNR may predict outcome in tamoxifen-treated patients.

Methods
Survin expression was assessed using immunhistochemistry on a breast cancer tissue microarray (TMA) containing 512 tumours. Whole slide digital images were captured using an Aperio XT scanner. Automated image analysis was used to identify tumour from stroma and then to quantify tumour-specific nuclear and cytoplasmic survivin. A decision tree model selected using a 10-fold cross-validation approach was used to identify prognostic subgroups based on nuclear and cytoplasmic survivin expression.

Results
Following optimisation of the staining procedure, it was possible to evaluate survivin protein expression in 70.1% (n = 359) of the 512 tumours represented on the TMA. Decision tree analysis predicted that nuclear, as opposed to cytoplasmic, survivin was the most important determinant of overall survival (OS) and breast cancer-specific survival (BCSS). The decision tree model confirmed CNR of 5 as the optimum threshold for survival analysis. Univariate analysis demonstrated an association between a high CNR (>5) and a prolonged BCSS (HR 0.49, 95% CI 0.29-0.81, p = 0.006). Multivariate analysis revealed a high CNR (>5) was an independent predictor of BCSS (HR 0.47, 95% CI 0.27-0.82, p = 0.008). An increased CNR was associated with ER positive (p = 0.045), low grade (p = 0.007), Ki-67 (p = 0.001) and Her2 (p = 0.026) negative tumours. Finally, a high CNR was an independent predictor of OS in tamoxifen-treated ER-positive patients (HR 0.44, 95% CI 0.23-0.87, p = 0.018).

Conclusion
Using the same threshold as our previous study, we have validated survivin CNR as a marker of good prognosis in breast cancer in a large independent cohort. These findings provide robust evidence of the importance of survivin CNR as a breast cancer biomarker, and its potential to predict outcome in tamoxifen-treated patients.
Combination of Dll4/Notch and Ephrin-B2/EphB4 targeted therapy is highly effective in disrupting tumor angiogenesis
Authors: Djokovic Dusan , Trindade Alexandre , Gigante Joana , Badenes Marina , Silva Lilliana , Liu Ren , Li Xiuqing , Gong Ming , Krasnoperov Valery , Gill Parkash S , Duarte Antonio 
Published: November 2010

Abstract

Background
Dll4/Notch and Ephrin-B2/EphB4 pathways play critical roles in tumor vessel development and maturation. This study evaluates the efficacy of the inhibition of both signaling pathways, alone and in combination, in reducing the growth of an autochthonous mouse tumor and assesses potential adverse effects.

Methods
We used the transgenic RIP1-Tag2 tumor model to study the effects of 1) inhibition of Dll4/Notch by either Dll4 allelic deletion or use of a soluble extracellular Dll4 (sDll4), 2) inhibition of Ephrin-B2/EphB4 signaling by a soluble extracellular EphB4 fused to albumin (sEphB4-Alb), and 3) inhibition of both pathways by sEphB4-Alb combined with either Dll4 allelic deletion or sDll4. To investigate adverse effects, we used inducible endothelial-specific Dll4 knock-out mice, treated with sEphB4-Alb, and carried out histopathological analysis.

Results

Dll4 allele deletion or soluble Dll4 treatment resulted in increased tumor vessel density, reduced mural cell recruitment and vessel perfusion which resulted in reduced tumor size. The soluble EphB4 instead reduced vessel density and vessel perfusion, leading to reduction of tumor size. Greater efficacy was observed when sEphB4-Alb was combined with either Dll4 allele deletion or sDll4 in regards to tumor size, vessel perfusion and mural cell recruitment. Induced endothelial specific Dll4 loss-of-function caused hepatic vascular alterations, which were prevented by concomitant sEphB4-Alb treatment.

Conclusion
Combination targeting of Dll4/Notch and Ephrin-B2/EphB4 has potential for clinical investigation, providing cumulative efficacy and increased safety over Dll4/Notch inhibition alone.
Measuring change in health status of older adults at the population level: The transition probability model
Authors: Moineddin Rahim , Nie Jason X , Wang Li , Tracy C Shawn , Upshur Ross EG 
Published: November 2010

Abstract

Background
The current demographic transition will lead to increasing demands on health services. However, debate exists as to the role age plays relative to co-morbidity in terms of health services utilization. While age has been identified as a critical factor in health services utilization, health services utilization is not simply an outcome of ill health, nor is it an inevitable outcome of aging. Most data on health service utilization studies assess utilization at one point in time, and does not examine transitions in health service utilization. We sought to measure health services utilization and to investigate patterns in the transition of levels of utilization and outcomes associated with different levels of utilization.

Methods
We conducted a population-based retrospective cohort study of all Ontario residents aged 65+ eligible for public healthcare coverage from January 1998-December 2006. The main outcome measure was total number of utilization events. The total is computed by summing, on a per annum basis, the number of family physician visits, specialist visits, Emergency Department visits, drug claims, lab claims, X-rays, CT scans, MRI scans, and inpatient admissions. Three categories of utilization were created: low, moderate, and high.

Results
There is heterogeneity in health services utilization across the late lifespan. Utilization increased consistently in the 9-year study period. The probability of remaining at the high utilization category when the person was in the high category the previous year was more than 0.70 for both males and females and for all age groups. Overall healthcare utilization increases more rapidly among the high users compared to the low users. There was negligible probability for moving from high to low utilization category. Probability of death increased exponentially as age increased. Older adults in the low utilization category had the lowest probability of death. The number of male nonagenarians increased more rapidly than female nonagenarians.

Conclusion
There are measurable and identifiable differences in the patterns of health services utilization among older adults. This data will permit clinicians and policy makers to tailor interventions appropriate to the risk class of patients.
Health plan administrative records versus birth certificate records: quality of race and ethnicity information in children
Authors: Smith Ning , Iyer Rajan L , Langer-Gould Annette , Getahun Darios T , Strickland Daniel , Jacobsen Steven J , Chen Wansu , Derose Stephen F , Koebnick Corinna 
Published: November 2010

Abstract

Background
To understand racial and ethnic disparities in health care utilization and their potential underlying causes, valid information on race and ethnicity is necessary. However, the validity of pediatric race and ethnicity information in administrative records from large integrated health care systems using electronic medical records is largely unknown.

Methods
Information on race and ethnicity of 325,810 children born between 1998-2008 was extracted from health plan administrative records and compared to birth certificate records. Positive predictive values (PPV) were calculated for correct classification of race and ethnicity in administrative records compared to birth certificate records.

Results
Misclassification of ethnicity and race in administrative records occurred in 23.1% and 33.6% children, respectively; the majority due to missing ethnicity (48.3%) and race (40.9%) information. Misclassification was most common in children of minority groups. PPV for White, Black, Asian/Pacific Islander, American Indian/Alaskan Native, multiple and other was 89.3%, 86.6%, 73.8%, 18.2%, 51.8% and 1.2%, respectively. PPV for Hispanic ethnicity was 95.6%. Racial and ethnic information improved with increasing number of medical visits. Subgroup analyses comparing racial classification between non-Hispanics and Hispanics showed White, Black and Asian race was more accurate among non-Hispanics than Hispanics.

Conclusions
In children, race and ethnicity information from administrative records has significant limitations in accurately identifying small minority groups. These results suggest that the quality of racial information obtained from administrative records may benefit from additional supplementation by birth certificate data.
Dissection of an old protein reveals a novel application: domain D of Staphylococcus aureus Protein A (sSpAD) as a secretion - tag
Authors: Heel Thomas , Paal Michael , Schneider Rainer , Auer Bernhard 
Published: November 2010

AbstractBackgroundEscherichia colias a frequently utilized host organism for recombinant protein production offers different cellular locations with distinct qualities. The periplasmic space is often favored for the production of complex proteins due to enhanced disulfide bond formation, increased target product stability and simplified downstream processing. To direct proteins to the periplasmic space rather small proteinaceus tags that can be used for affinity purification would be advantageous.ResultsWe discovered that domain D of theStaphylococcus aureusprotein A was sufficient for the secretion of various target proteins into the periplasmic space ofE. coli. Our experiments indicated the Sec pathway as the mode of secretion, although N-terminal processing was not observed. Furthermore, the solubility of recombinant fusion proteins was improved for proteins prone to aggregation.The tag allowed a straightforward affinity purification of recombinant fusion protein via an IgG column, which was exemplified for the target protein human superoxide dismutase 1 (SOD).ConclusionsIn this work we present a new secretion tag that combines several advantages for the production of recombinant proteins inE. coli. Domain D ofS. aureusprotein A protects the protein of interest against N-terminal degradation, increases target protein solubility and enables a straight-forward purification of the recombinant protein using of IgG columns.
A multiplex assay for the simultaneous detection of antibodies against 15 Plasmodium falciparum and Anopheles gambiae saliva antigens
Authors: Ambrosino Elena , Dumoulin Chloé , Orlandi-Pradines Eve , Remoue Franck , Toure-Baldé Aissatou , Tall Adama , Sarr Jean Biram , Poinsignon Anne , Sokhna Cheikh , Puget Karine , Trape Jean-François , Pascual Aurélie , Druilhe Pierre , Fusai Thierry , Rogier Christophe 
Published: November 2010

AbstractBackgroundAssessment exposure and immunity to malaria is an important step in the fight against the disease. Increased malaria infection in non-immune travellers under anti-malarial chemoprophylaxis, as well as the implementation of malaria elimination programmes in endemic countries, raises new issues that pertain to these processes. Notably, monitoring malaria immunity has become more difficult in individuals showing low antibody (Ab) responses or taking medications against thePlasmodiumfalciparumblood stages. Commonly available techniques in malaria seroepidemiology have limited sensitivity, both against pre-erythrocytic, as against blood stages of the parasite. Thus, the aim of this study was to develop a sensitive tool to assess the exposure to malaria or to bites from the vectorAnopheles gambiae, despite anti-malarial prophylactic treatment.MethodsAb responses to 13 pre-erythrocyticP. falciparum-specific peptides derived from the proteins Lsa1, Lsa3, Glurp, Salsa, Trap, Starp, CSP and Pf11.1, and to 2 peptides specific for theAnopheles gambiaesaliva protein gSG6 were tested. In this study, 253 individuals from three Senegalese areas with different transmission intensities and 124 European travellers exposed to malaria during a short period of time were included.ResultsThe multiplex assay was optimized for most but not all of the antigens. It was rapid, reproducible and required a small volume of serum. Proportions of Ab-positive individuals, Ab levels and the mean number of antigens (Ags) recognized by each individual increased significantly with increases in the level of malaria exposure.ConclusionThe multiplex assay developed here provides a useful tool to evaluate immune responses to multiple Ags in large populations, even when only small amounts of serum are available, or Ab titres are low, as in case of travellers. Finally, the relationship of Ab responses with malaria endemicity levels provides a way to monitor exposure in differentially exposed autochthonous individuals from various endemicity areas, as well as in travellers who are not immune, thus indirectly assessing the parasite transmission and malaria risk in the new eradication era.
Genetic variability and natural selection at the ligand domain of the Duffy binding protein in brazilian Plasmodium vivax populations
Authors: Sousa Taís N , Tarazona-Santos Eduardo M , Wilson Daniel J , Madureira Ana P , Falcão Paula RK , Fontes Cor JF , Gil Luiz HS , Ferreira Marcelo U , Carvalho Luzia H , Brito Cristiana FA 
Published: November 2010

Abstract

Background

Plasmodium vivax malaria is a major public health challenge in Latin America, Asia and Oceania, with 130-435 million clinical cases per year worldwide. Invasion of host blood cells by P. vivax mainly depends on a type I membrane protein called Duffy binding protein (PvDBP). The erythrocyte-binding motif of PvDBP is a 170 amino-acid stretch located in its cysteine-rich region II (PvDBPII), which is the most variable segment of the protein.

Methods
To test whether diversifying natural selection has shaped the nucleotide diversity of PvDBPII in Brazilian populations, this region was sequenced in 122 isolates from six different geographic areas. A Bayesian method was applied to test for the action of natural selection under a population genetic model that incorporates recombination. The analysis was integrated with a structural model of PvDBPII, and T- and B-cell epitopes were localized on the 3-D structure.

Results
The results suggest that: (i) recombination plays an important role in determining the haplotype structure of PvDBPII, and (ii) PvDBPII appears to contain neutrally evolving codons as well as codons evolving under natural selection. Diversifying selection preferentially acts on sites identified as epitopes, particularly on amino acid residues 417, 419, and 424, which show strong linkage disequilibrium.

Conclusions
This study shows that some polymorphisms of PvDBPII are present near the erythrocyte-binding domain and might serve to elude antibodies that inhibit cell invasion. Therefore, these polymorphisms should be taken into account when designing vaccines aimed at eliciting antibodies to inhibit erythrocyte invasion.
Home visits by neighborhood Mentor Mothers provide timely recovery from childhood malnutrition in South Africa: results from a randomized controlled trial
Authors: le Roux Ingrid M , le Roux Karl , Comulada W Scott , Greco Erin M , Desmond Katherine A , Mbewu Nokwanele , Rotheram-Borus Mary Jane 
Published: November 2010

Abstract

Background
Child and infant malnourishment is a significant and growing problem in the developing world. Malnourished children are at high risk for negative health outcomes over their lifespans. Philani, a paraprofessional home visiting program, was developed to improve childhood nourishment. The objective of this study is to evaluate whether the Philani program can rehabilitate malnourished children in a timely manner.

Methods
Mentor Mothers were trained to conduct home visits. Mentor Mothers went from house to house in assigned neighborhoods, weighed children age 5 and younger, and recruited mother-child dyads where there was an underweight child. Participating dyads were assigned in a 2:1 random sequence to the Philani intervention condition (n = 536) or a control condition (n = 252). Mentor Mothers visited dyads in the intervention condition for one year, supporting mothers' problem-solving around nutrition. All children were weighed by Mentor Mothers at baseline and three, six, nine and twelve month follow-ups.

Results
By three months, children in the intervention condition were five times more likely to rehabilitate (reach a healthy weight for their ages) than children in the control condition. Throughout the course of the study, 43% (n = 233 of 536) of children in the intervention condition were rehabilitated while 31% (n = 78 of 252) of children in the control condition were rehabilitated.

Conclusions
Paraprofessional Mentor Mothers are an effective strategy for delivering home visiting programs by providing the knowledge and support necessary to change the behavior of families at risk.
Classification of root canal microorganisms using electronic-nose and discriminant analysis
Authors: Aksebzeci Bekir H , Asyalı Musa H , Kahraman Yasemin , Er Özgür , Kaya Esma , Özbilge Hatice , Kara Sadık 
Published: November 2010

Abstract

Background
Root canal treatment is a debridement process which disrupts and removes entire microorganisms from the root canal system. Identification of microorganisms may help clinicians decide on treatment alternatives such as using different irrigants, intracanal medicaments and antibiotics. However, the difficulty in cultivation and the complexity in isolation of predominant anaerobic microorganisms make clinicians resort to empirical medical treatments. For this reason, identification of microorganisms is not a routinely used procedure in root canal treatment. In this study, we aimed at classifying 7 different standard microorganism strains which are frequently seen in root canal infections, using odor data collected using an electronic nose instrument.

Method
Our microorganism odor data set consisted of 5 repeated samples from 7 different classes at 4 concentration levels. For each concentration, 35 samples were classified using 3 different discriminant analysis methods. In order to determine an optimal setting for using electronic-nose in such an application, we have tried 3 different approaches in evaluating sensor responses. Moreover, we have used 3 different sensor baseline values in normalizing sensor responses. Since the number of sensors is relatively large compared to sample size, we have also investigated the influence of two different dimension reduction methods on classification performance.

Results
We have found that quadratic type dicriminant analysis outperforms other varieties of this method. We have also observed that classification performance decreases as the concentration decreases. Among different baseline values used for pre-processing the sensor responses, the model where the minimum values of sensor readings in the sample were accepted as the baseline yields better classification performance. Corresponding to this optimal choice of baseline value, we have noted that among different sensor response model and feature reduction method combinations, the difference model with standard deviation based dimension reduction or normalized fractional difference model with principal component analysis based dimension reduction results in the best overall performance across different concentrations.

Conclusion
Our results reveal that the electronic nose technology is a promising and convenient alternative for classifying microorganisms that cause root canal infections. With our comprehensive approach, we have also determined optimal settings to obtain higher classification performance using this technology and discriminant analysis.
Luciferase expression and bioluminescence does not affect tumor cell growth in vitro or in vivo
Authors: Tiffen Jessamy C , Bailey Charles G , Ng Cynthia , Rasko John EJ , Holst Jeff 
Published: November 2010

Abstract
Live animal imaging is becoming an increasingly common technique for accurate and quantitative assessment of tumor burden over time. Bioluminescence imaging systems rely on a bioluminescent signal from tumor cells, typically generated from expression of the firefly luciferase gene. However, previous reports have suggested that either a high level of luciferase or the resultant light reaction produced upon addition of D-luciferin substrate can have a negative influence on tumor cell growth. To address this issue, we designed an expression vector that allows simultaneous fluorescence and luminescence imaging. Using fluorescence activated cell sorting (FACS), we generated clonal cell populations from a human breast cancer (MCF-7) and a mouse melanoma (B16-F10) cell line that stably expressed different levels of luciferase. We then compared the growth capabilities of these clones in vitro by MTT proliferation assay and in vivo by bioluminescence imaging of tumor growth in live mice. Surprisingly, we found that neither the amount of luciferase nor biophotonic activity was sufficient to inhibit tumor cell growth, in vitro or in vivo. These results suggest that luciferase toxicity is not a necessary consideration when designing bioluminescence experiments, and therefore our approach can be used to rapidly generate high levels of luciferase expression for sensitive imaging experiments.
Epigenetic control of the basal-like gene expression profile via Interleukin-6 in breast cancer cells
Authors: D'Anello Laura , Sansone Pasquale , Storci Gianluca , Mitrugno Valentina , D'Uva Gabriele , Chieco Pasquale , Bonafé Massimiliano 
Published: November 2010

Abstract

Background
Basal-like carcinoma are aggressive breast cancers that frequently carry p53 inactivating mutations, lack estrogen receptor-α (ERα) and express the cancer stem cell markers CD133 and CD44. These tumors also over-express Interleukin 6 (IL-6), a pro-inflammatory cytokine that stimulates the growth of breast cancer stem/progenitor cells.

Results
Here we show that p53 deficiency in breast cancer cells induces a loss of methylation at IL-6 proximal promoter region, which is maintained by an IL-6 autocrine loop. IL-6 also elicits the loss of methylation at the CD133 promoter region 1 and of CD44 proximal promoter, enhancing CD133 and CD44 gene transcription. In parallel, IL-6 induces the methylation of estrogen receptor (ERα) promoter and the loss of ERα mRNA expression. Finally, IL-6 induces the methylation of IL-6 distal promoter and of CD133 promoter region 2, which harbour putative repressor regions.

Conclusion
We conclude that IL-6, whose methylation-dependent autocrine loop is triggered by the inactivation of p53, induces an epigenetic reprogramming that drives breast carcinoma cells towards a basal-like/stem cell-like gene expression profile.