bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative study of classification algorithms for immunosignaturing data
Authors: Kukreja Muskan , Johnston Stephen Albert , Stafford Phillip 
Published: August 2012

Abstract

Background
High-throughput technologies such as DNA, RNA, protein, antibody and peptide microarrays are often used to examine differences across drug treatments, diseases, transgenic animals, and others. Typically one trains a classification system by gathering large amounts of probe-level data, selecting informative features, and classifies test samples using a small number of features. As new microarrays are invented, classification systems that worked well for other array types may not be ideal. Expression microarrays, arguably one of the most prevalent array types, have been used for years to help develop classification algorithms. Many biological assumptions are built into classifiers that were designed for these types of data. One of the more problematic is the assumption of independence, both at the probe level and again at the biological level. Probes for RNA transcripts are designed to bind single transcripts. At the biological level, many genes have dependencies across transcriptional pathways where co-regulation of transcriptional units may make many genes appear as being completely dependent. Thus, algorithms that perform well for gene expression data may not be suitable when other technologies with different binding characteristics exist. The immunosignaturing microarray is based on complex mixtures of antibodies binding to arrays of random sequence peptides. It relies on many-to-many binding of antibodies to the random sequence peptides. Each peptide can bind multiple antibodies and each antibody can bind multiple peptides. This technology has been shown to be highly reproducible and appears promising for diagnosing a variety of disease states. However, it is not clear what is the optimal classification algorithm for analyzing this new type of data.

Results
We characterized several classification algorithms to analyze immunosignaturing data. We selected several datasets that range from easy to difficult to classify, from simple monoclonal binding to complex binding patterns in asthma patients. We then classified the biological samples using 17 different classification algorithms. Using a wide variety of assessment criteria, we found ‘Naïve Bayes’ far more useful than other widely used methods due to its simplicity, robustness, speed and accuracy.

Conclusions
‘Naïve Bayes’ algorithm appears to accommodate the complex patterns hidden within multilayered immunosignaturing microarray data due to its fundamental mathematical properties.
Regulatory elements of Caenorhabditis elegans ribosomal protein genes
Authors: Sleumer Monica C , Wei Guifeng , Wang Yunfei , Chang Hao , Xu Tao , Chen Runsheng , Zhang Michael Q 
Published: August 2012

Abstract

Background
Ribosomal protein genes (RPGs) are essential, tightly regulated, and highly expressed during embryonic development and cell growth. Even though their protein sequences are strongly conserved, their mechanism of regulation is not conserved across yeast, Drosophila, and vertebrates. A recent investigation of genomic sequences conserved across both nematode species and associated with different gene groups indicated the existence of several elements in the upstream regions of C. elegans RPGs, providing a new insight regarding the regulation of these genes in C. elegans.

Results
In this study, we performed an in-depth examination of C. elegans RPG regulation and found nine highly conserved motifs in the upstream regions of C. elegans RPGs using the motif discovery algorithm DME. Four motifs were partially similar to transcription factor binding sites from C. elegans, Drosophila, yeast, and human. One pair of these motifs was found to co-occur in the upstream regions of 250 transcripts including 22 RPGs. The distance between the two motifs displayed a complex frequency pattern that was related to their relative orientation.
We tested the impact of three of these motifs on the expression of rpl-2 using a series of reporter gene constructs and showed that all three motifs are necessary to maintain the high natural expression level of this gene. One of the motifs was similar to the binding site of an orthologue of POP-1, and we showed that RNAi knockdown of pop-1 impacts the expression of rpl-2. We further determined the transcription start site of rpl-2 by 5’ RACE and found that the motifs lie 40–90 bases upstream of the start site. We also found evidence that a noncoding RNA, contained within the outron of rpl-2, is co-transcribed with rpl-2 and cleaved during trans-splicing.

Conclusions
Our results indicate that C. elegans RPGs are regulated by a complex novel series of regulatory elements that is evolutionarily distinct from those of all other species examined up until now.
CYP98A22, a phenolic ester 3’-hydroxylase specialized in the synthesis of chlorogenic acid, as a new tool for enhancing the furanocoumarin concentration in Ruta graveolens
Authors: Karamat Fazeelat , Olry Alexandre , Doerper Sébastien , Vialart Guilhem , Ullmann Pascaline , Werck-Reichhart Danièle , Bourgaud Frédéric , Hehn Alain 
Published: August 2012

Abstract

Background
Furanocoumarins are molecules with proven therapeutic properties and are produced in only a small number of medicinal plant species such as Ruta graveolens. In vivo, these molecules play a protective role against phytophageous insect attack. Furanocoumarins are members of the phenylpropanoids family, and their biosynthetic pathway is initiated from p-coumaroyl coA. The enzymes belonging to the CYP98A cytochrome P450 family have been widely described as being aromatic meta-hydroxylases of various substrates, such as p-coumaroyl ester derivatives, and are involved in the synthesis of coumarins such as scopoletin. In furanocoumarin-producing plants, these enzymes catalyze the step directly downstream of the junction with the furanocoumarin biosynthetic pathway and might indirectly impact their synthesis.

Results
In this work, we describe the cloning and functional characterization of the first CYP98A encoding gene isolated from R. graveolens. Using Nicotiana benthamiana as a heterologous expression system, we have demonstrated that this enzyme adds a 3-OH to p-coumaroyl ester derivatives but is more efficient to convert p-coumaroyl quinate into chlorogenic acid than to metabolize p-coumaroyl shikimate. Plants exposed to UV-B stress showed an enhanced expression level of the corresponding gene. The R. graveolens cyp98a22 open reading frame and the orthologous Arabidopsis thaliana cyp98a3 open reading frame were overexpressed in stable transgenic Ruta plants. Both plant series were analyzed for their production of scopoletin and furanocoumarin. A detailed analysis indicates that both genes enhance the production of furanocoumarins but that CYP98A22, unlike CYP98A3, doesn’t affect the synthesis of scopoletin.

Conclusions
The overexpression of CYP98A22 positively impacts the concentration of furanocoumarins in R. graveolens. This gene is therefore a valuable tool to engineer plants with improved therapeutical values that might also be more resistant to phytophageous insects.
Epidemiology of serogroup B invasive meningococcal disease in Ontario, Canada, 2000 to 2010
Authors: Dang Vica , Jamieson Frances B , Wilson Sarah , Rawte Prasad , Crowcroft Natasha S , Johnson Karen , Tsang Raymond S W , Deeks Shelley L 
Published: August 2012

Abstract

Background
Invasive meningococcal disease (IMD) caused by serogroup B is the last major serogroup in Canada to become vaccine-preventable. The anticipated availability of vaccines targeting this serogroup prompted an assessment of the epidemiology of serogroup B disease in Ontario, Canada.

Methods
We retrieved information on confirmed IMD cases reported to Ontario’s reportable disease database between January 1, 2000 and December 31, 2010 and probabilistically-linked these cases to Public Health Ontario Laboratory records. Rates were calculated with denominator data obtained from Statistics Canada. We calculated a crude number needed to vaccinate using the inverse of the infant (<1 year) age-specific incidence multiplied by expected vaccine efficacies between 70% and 80%, and assuming only direct protection (no herd effects).

Results
A total of 259 serogroup B IMD cases were identified in Ontario over the 11-year period. Serogroup B was the most common cause of IMD. Incidence ranged from 0.11 to 0.27/100,000/year, and fluctuated over time. Cases ranged in age from 13 days to 101 years; 21.4% occurred in infants, of which 72.7% were <6 months. Infants had the highest incidence (3.70/100,000). Case-fatality ratio was 10.7% overall. If we assume that all infant cases would be preventable by vaccination, we would need to vaccinate between 33,784 and 38,610 infants to prevent one case of disease.

Conclusions
Although rare, the proportion of IMD caused by serogroup B has increased and currently causes most IMD in Ontario, with infants having the highest risk of disease. Although serogroup B meningococcal vaccines are highly anticipated, our findings suggest that decisions regarding publicly funding serogroup B meningococcal vaccines will be difficult and may not be based on disease burden alone.
The fate of bone marrow-derived cells carrying a polycystic kidney disease mutation in the genetically normal kidney
Authors: Verghese Elizabeth , Johnson Chad , Bertram John F , Ricardo Sharon D , Deane James A 
Published: August 2012

Abstract

Background
Polycystic Kidney Disease (PKD) is a genetic condition in which dedifferentiated and highly proliferative epithelial cells form renal cysts and is frequently treated by renal transplantation. Studies have reported that bone marrow-derived cells give rise to renal epithelial cells, particularly following renal injury as often occurs during transplantation. This raises the possibility that bone marrow-derived cells from a PKD-afflicted recipient could populate a transplanted kidney and express a disease phenotype. However, for reasons that are not clear the reoccurrence of PKD has not been reported in a genetically normal renal graft. We used a mouse model to examine whether PKD mutant bone marrow-derived cells are capable of expressing a disease phenotype in the kidney.

Methods
Wild type female mice were transplanted with bone marrow from male mice homozygous for a PKD-causing mutation and subjected to renal injury. Y chromosome positive, bone marrow-derived cells in the kidney were assessed for epithelial markers.

Results
Mutant bone marrow-derived cells were present in the kidney. Some mutant cells were within the bounds of the tubule or duct, but none demonstrated convincing evidence of an epithelial phenotype.

Conclusions
Bone marrow-derived cells appear incapable of giving rise to genuine epithelial cells and this is the most likely reason cysts do not reoccur in kidneys transplanted into PKD patients.
Low BRMS1 expression promotes nasopharyngeal carcinoma metastasis in vitro and in vivo and is associated with poor patient survival
Authors: Cui Rui-Xue , Liu Na , He Qing-Mei , Li Wen-Fei , Huang Bi-Jun , Sun Ying , Tang Ling-Long , Chen Mo , Jiang Ning , Chen Lei , Yun Jing-Ping , Zeng Jing , Guo Ying , Wang Hui-Yun , Ma Jun 
Published: August 2012

Abstract

Background
Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene. This study aimed to investigate the impact of BRMS1 on metastasis in nasopharyngeal carcinoma (NPC) and to evaluate the prognostic significance of BRMS1 in NPC patients.

Methods
BRMS1 expression was examined in NPC cell lines using quantitative reverse transcription-polymerase chain reaction and Western blotting. NPC cells stably expressing BRMS1 were used to perform wound healing and invasion assays in vitro and a murine xenograft assay in vivo. Immunohistochemical staining was performed in 274 paraffin-embedded NPC specimens divided into a training set (n = 120) and a testing set (n = 154).

Results
BRMS1 expression was down-regulated in NPC cell lines. Overexpression of BRMS1 significantly reversed the metastatic phenotype of NPC cells in vitro and in vivo. Importantly, low BRMS1 expression was associated with poor distant metastasis-free survival (DMFS, P < 0.001) and poor overall survival (OS, P < 0.001) in the training set; these results were validated in the testing set and overall patient population. Cox regression analysis demonstrated that low BRMS1 expression was an independent prognostic factor for DMFS and OS in NPC.

Conclusions
Low expression of the metastasis suppressor BRMS1 may be an independent prognostic factor for poor prognosis in NPC patients.
The T-box transcription factor Brachyury regulates epithelial–mesenchymal transition in association with cancer stem-like cells in adenoid cystic carcinoma cells
Authors: Shimoda Miyuki , Sugiura Tsuyoshi , Imajyo Ikumi , Ishii Kotaro , Chigita Satomi , Seki Katsuhiro , Kobayashi Yousuke , Shirasuna Kanemitsu 
Published: August 2012

Abstract

Background
The high frequencies of recurrence and distant metastasis of adenoid cystic carcinoma (AdCC) emphasize the need to better understand the biological factors associated with these outcomes. To analyze the mechanisms of AdCC metastasis, we established the green fluorescence protein (GFP)-transfected subline ACCS-GFP from the AdCC parental cell line and the metastatic ACCS-M GFP line from an in vivo metastasis model.

Methods
Using these cell lines, we investigated the involvement of the epithelial–mesenchymal transition (EMT) and cancer stem cell (CSCs) in AdCC metastasis by real-time RT-PCR for EMT related genes and stem cell markers. Characteristics of CSCs were also analyzed by sphere-forming ability and tumorigenicity. Short hairpin RNA (shRNA) silencing of target gene was also performed.

Results
ACCS-M GFP demonstrated characteristics of EMT and additionally displayed sphere-forming ability and high expression of EMT-related genes (Snail, Twist1, Twist2, Slug, zinc finger E-box binding homeobox 1 and 2 [Zeb1 and Zeb2], glycogen synthase kinase 3 beta [Gsk3β and transforming growth factor beta 2 [Tgf-β2]), stem cell markers (Nodal, Lefty, Oct-4, Pax6, Rex1, and Nanog), and differentiation markers (sex determining region Y [Sox2], Brachyury, and alpha fetoprotein [Afp]). These observations suggest that ACCS-M GFP shows the characteristics of CSCs and CSCs may be involved in the EMT of AdCC. Surprisingly, shRNA silencing of the T-box transcription factor Brachyury (also a differentiation marker) resulted in downregulation of the EMT and stem cell markers. In addition, sphere-forming ability, EMT characteristics, and tumorigenicity were simultaneously lost. Brachyury expression in clinical samples of AdCC was extremely high and closely related to EMT. This finding suggests that regulation of EMT by Brachyury in clinical AdCC may parallel that observed in vitro in this study.

Conclusions
The use of a single cell line is a limitation of this study. However, parallel data from in vitro and clinical samples suggest the possibility that EMT is directly linked to CSCs and that Brachyury is a regulator of EMT and CSCs.
miRNA-21 is developmentally regulated in mouse brain and is co-expressed with SOX2 in glioma
Authors: Põlajeva Jelena , Swartling Fredrik J , Jiang Yiwen , Singh Umashankar , Pietras Kristian , Uhrbom Lene , Westermark Bengt , Roswall Pernilla 
Published: August 2012

Abstract

Background
MicroRNAs (miRNAs) and their role during tumor development have been studied in great detail during the last decade, albeit their expression pattern and regulation during normal development are however not so well established. Previous studies have shown that miRNAs are differentially expressed in solid human tumors. Platelet-derived growth factor (PDGF) signaling is known to be involved in normal development of the brain as well as in malignant primary brain tumors, gliomas, but the complete mechanism is still lacking. We decided to investigate the expression of the oncogenic miR-21 during normal mouse development and glioma, focusing on PDGF signaling as a potential regulator of miR-21.

Methods
We generated mouse glioma using the RCAS/tv-a system for driving PDGF-BB expression in a cell-specific manner. Expression of miR-21 in mouse cell cultures and mouse brain were assessed using Northern blot analysis and in situ hybridization. Immunohistochemistry and Western blot analysis were used to investigate SOX2 expression. LNA-modified siRNA was used for irreversible depletion of miR-21. For inhibition of PDGF signaling Gleevec (imatinib mesylate), Rapamycin and U0126, as well as siRNA were used. Statistical significance was calculated using double-sided unpaired Student´s t-test.

Results
We identified miR-21 to be highly expressed during embryonic and newborn brain development followed by a gradual decrease until undetectable at postnatal day 7 (P7), this pattern correlated with SOX2 expression. Furthermore, miR-21 and SOX2 showed up-regulation and overlapping expression pattern in RCAS/tv-a generated mouse brain tumor specimens. Upon irreversible depletion of miR-21 the expression of SOX2 was strongly diminished in both mouse primary glioma cultures and human glioma cell lines. Interestingly, in normal fibroblasts the expression of miR-21 was induced by PDGF-BB, and inhibition of PDGF signaling in mouse glioma primary cultures resulted in suppression of miR-21 suggesting that miR-21 is indeed regulated by PDGF signaling.

Conclusions
Our data show that miR-21 and SOX2 are tightly regulated already during embryogenesis and define a distinct population with putative tumor cell of origin characteristics. Furthermore, we believe that miR-21 is a mediator of PDGF-driven brain tumors, which suggests miR-21 as a promising target for treatment of glioma.
Potential risk of HIV transmission in barbering practice in Ethiopia: from public health and microbiological perspectives
Authors: Biadgelegn Fantahun , Belyhun Yeshambel , Anagaw Belay , Woldeyohannes Desalegn , Moges Feleke , Bekele Asegedech , Mulu Andargachew 
Published: August 2012

Abstract

Background
HIV and other blood borne infections can be transmitted through the use of improperly sterilized and disinfected sharp equipments.

Methods
A cross sectional study was conducted from January to June, 2010 to assess the potential risk of HIV transmission in barbering practice in Ethiopia from public health and microbiological perspectives. Barbers in barbershop were interviewed using pre-designed questionnaires and check lists were used to evaluate barbering practice. Microbiological data from tips of the sharpener before and after the barbering was collected and processed as per the standard procedure.

Results
One hundred and twenty three barbering sessions and barbers were observed in which 106 (86.2%) were males. Ninety six (78%) of the respondents knew that HIV could be transmitted by sharing non-sterile sharp instruments. Among the total participants 59 (48%) had the correct knowledge of what sterilization mean and 111 (94.1%) of them believed its importance in their work place. Barbers had a mean knowledge score of 6 ± 1.5 out of a score of 10 regarding sterilization and disinfection as well as in the transmission of HIV in their work place. Three (2.5%) barbers were disagreed that unsterilized blade can transmit skin diseases and 26 (21.3%) of them believed disinfection is enough to avoid microbes from sharp objects. Ninety two (76.7%) barbers were using sterilization in their establishment. According to Likert scaling almost all sterilization and disinfection procedures were riskily practiced and respondents had poor level of knowledge. No significant association was found to influence the decontamination and sterilization of barbering equipments except monthly income, pre and post colony count of microbes identified. The isolation of normal skin flora in the pre-and post- sterilization and disinfectant procedures and less average percent colony reduction showed that sterilization and disinfectant practices in barbershop were generally poor that proofed proper sterilization and/or disinfection techniques were unfavorable.

Conclusion
This study has revealed the presence of potential risk of HIV and other blood borne disease transmission among the barbers of the study areas. Thus continuous and intensified public health strategies on health education, training, supervision and monitoring are needed to facilitate the adoption of effective methods of sterilization and/or disinfection.
Italy SimSmoke: the effect of tobacco control policies on smoking prevalence and smoking attributable deaths in Italy
Authors: Levy David , Gallus Silvano , Blackman Kenneth , Carreras Giulia , La Vecchia Carlo , Gorini Giuseppe 
Published: August 2012

AbstractBackgroundWhile Italy has implemented some tobacco control policies over the last few decades, which resulted in a decreased smoking prevalence, there is still considerable scope to strengthen tobacco control policies consistent with the World Health Organization (WHO) policy guidelines. The present study aims to evaluate the effect of past and project the effect of future tobacco control policies on smoking prevalence and associated premature mortality in Italy.MethodsTo assess, individually and in combination, the effect of seven types of policies, we used theSimSmokesimulation model of tobacco control policy. The model uses population, smoking rates and tobacco control policy data for Italy.ResultsSignificant reductions of smoking prevalence and premature mortality can be achieved through tobacco price increases, high intensity media campaigns, comprehensive cessation treatment program, strong health warnings, stricter smoke-free air regulations and advertising bans, and youth access laws. With a comprehensive approach, the smoking prevalence can be decreased by as much as 12% soon after the policies are in place, increasing to a 30% reduction in the next twenty years and a 34% reduction by 30 years in 2040. Without effective tobacco control policies, a total of almost 300 thousand lives will be prematurely lost due to smoking by the year 2040.ConclusionBesides presenting the benefits of a comprehensive tobacco control strategy, the model helps identify information gaps in surveillance and evaluation schemes that will promote the effectiveness of future tobacco control policy in Italy.
A concise review of the efficacy of stereotactic radiosurgery in the management of melanoma and renal cell carcinoma brain metastases
Authors: Hanson Peter W , Elaimy Ameer L , Lamoreaux Wayne T , Demakas John J , Fairbanks Robert K , Mackay Alexander R , Taylor Blake , Cooke Barton S , Thumma Sudheer R , Lee Christopher M 
Published: August 2012

Abstract
Melanoma and renal cell carcinoma have a well-documented tendency to develop metastases to the brain. Treating these lesions has traditionally been problematic, because chemotherapy has difficulty crossing the blood brain barrier and whole brain radiation therapy (WBRT) is a relatively ineffective treatment against these radioresistant tumor histologies. In recent years, stereotactic radiosurgery (SRS) has emerged as an effective and minimally-invasive treatment modality for irradiating either single or multiple intracranial structures in one clinical treatment setting. For this reason, we conducted a review of modern literature analyzing the efficacy of SRS in the management of patients with melanoma and renal cell carcinoma brain metastases. In our analysis we found SRS to be a safe, effective and attractive treatment modality for managing radioresistant brain metastases and highlighted the need for randomized trials comparing WBRT alone vs. SRS alone vs. WBRT plus SRS in treating patients with radioresistant brain metastases.