bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequencing bias: comparison of different protocols of MicroRNA library construction
Authors: Tian Geng , Yin XuYang , Luo Hong , Xu XiaoHong , Bolund Lars , Zhang XiuQing 
Published: September 2010

Abstract

Background
MicroRNAs(miRNAs) are 18-25 nt small RNAs playing critical roles in many biological processes. The majority of known miRNAs were discovered by conventional cloning and a Sanger sequencing approach. The next-generation sequencing (NGS) technologies enable in-depth characterization of the global repertoire of miRNAs, and different protocols for miRNA library construction have been developed. However, the possible bias between the relative expression levels and sequences introduced by different protocols of library preparation have rarely been explored.

Results
We assessed three different miRNA library preparation protocols, SOLiD, Illumina versions 1 and 1.5, using cloning or SBS sequencing of total RNA samples extracted from skeletal muscles from Hu sheep and Dorper sheep, and then validated 9 miRNAs by qRT-PCR. Our results show that SBS sequencing data highly correlate with Illumina cloning data. The SOLiD data, when compared to Illumina's, indicate more dispersed distribution of length, higher frequency variation for nucleotides near the 3'- and 5'-ends, higher frequency occurrence for reads containing end secondary structure (ESS), and higher frequency for reads that do not map to known miRNAs. qRT-PCR results showed the best correlation with SOLiD cloning data. Fold difference of Hu sheep and Dorper sheep between qRT-PCR result and SBS sequencing data correlated well (r = 0.937), and fold difference of miR-1 and miR-206 among SOLiD cloning data, qRT-PCR and SBS sequencing data was similar.

Conclusions
The sequencing depth can influence the quantitative measurement of miRNA abundance, but the discrepancy caused by it was not statistically significant as high correlation was observed between Illumina cloning and SBS sequencing data. Bias of length distribution, sequence variation, and ESS was observed between data obtained with the different protocols. SOLiD cloning data differ from Illumina cloning data mainly because of distinct methods of adapter ligation. The good correlation between qRT-PCR result and SOLiD data might be due to the similarities of the hybridization-based methods. The fold difference analysis indicated that methods based on hybridization may be superior for quantitative measurement of miRNA abundance. Because of the genome sequence of the sheep is not available, our data may not explain how the entire miRNA bias in the natural miRNAs in sheep or other mammal miRNA expression, unbiased artificially synthesized miRNA will help on evaluating the methodology of miRNA library preparation.
Quantification of ETS exposure in hospitality workers who have never smoked
Authors: Kolb Stefanie , Brückner Ulrike , Nowak Dennis , Radon Katja 
Published: September 2010

AbstractBackgroundEnvironmental Tobacco Smoke (ETS) was classified as human carcinogen (K1) by the German Research Council in 1998. According to epidemiological studies, the relative risk especially for lung cancer might be twice as high in persons who have never smoked but who are in the highest exposure category, for example hospitality workers. In order to implement these results in the German regulations on occupational illnesses, a valid method is needed to retrospectively assess the cumulative ETS exposure in the hospitality environment.MethodsA literature-based review was carried out to locate a method that can be used for the German hospitality sector. Studies assessing ETS exposure using biological markers (for example urinary cotinine, DNA adducts) or questionnaires were excluded. Biological markers are not considered relevant as they assess exposure only over the last hours, weeks or months. Self-reported exposure based on questionnaires also does not seem adequate for medico-legal purposes. Therefore, retrospective exposure assessment should be based on mathematical models to approximate past exposure.ResultsFor this purpose a validated model developed by Repace and Lowrey was considered appropriate. It offers the possibility of retrospectively assessing exposure with existing parameters (such as environmental dimensions, average number of smokers, ventilation characteristics and duration of exposure). The relative risk of lung cancer can then be estimated based on the individual cumulative exposure of the worker.ConclusionIn conclusion, having adapted it to the German hospitality sector, an existing mathematical model appears to be capable of approximating the cumulative exposure. However, the level of uncertainty of these approximations has to be taken into account, especially for diseases with a long latency period such as lung cancer.
Reciprocal control of cell proliferation and migration
Authors: De Donatis Alina , Ranaldi Francesco , Cirri Paolo 
Published: September 2010

Abstract
In adult tissue the quiescent state of a single cell is maintained by the steady state conditions of its own microenvironment for what concern both cell-cell as well as cell-ECM interaction and soluble factors concentration. Physiological or pathological conditions can alter this quiescent state through an imbalance of both soluble and insoluble factors that can trigger a cellular phenotypic response. The kind of cellular response depends by many factors but one of the most important is the concentration of soluble cytokines sensed by the target cell. In addition, due to the intrinsic plasticity of many cellular types, every single cell is able, in response to the same stimulus, to rapidly switch phenotype supporting minimal changes of microenviromental cytokines concentration. Wound healing is a typical condition in which epithelial, endothelial as well as mesenchymal cells are firstly subjected to activation of their motility in order to repopulate the damaged region and then they show a strong proliferative response in order to successfully complete the wound repair process. This schema constitute the leitmotif of many other physiological or pathological conditions such as development vasculogenesis/angiogenesis as well as cancer outgrowth and metastasis.
Our review focuses on the molecular mechanisms that control the starting and, eventually, the switching of cellular phenotypic outcome in response to changes in the symmetry of the extracellular environment.
Eotaxin and FGF enhance signaling through an Extracellular signal-related kinase (ERK)-dependent pathway in the pathogenesis of Eosinophilic Esophagitis
Authors: Huang Jennifer J , Joh Jae Won , Fuentebella Judy , Patel Anup , Nguyen Tammie , Seki Scott , Hoyte Lisa , Reshamwala Neha , Nguyen Christine , Quiros Anthony , Bass Dorsey , Sibley Eric , Berquist William , Cox Kenneth , Kerner John , Nadeau Kari C 
Published: September 2010

AbstractBackgroundEosinophilic esophagitis (EoE) is characterized by the inflammation of the esophagus and the infiltration of eosinophils into the esophagus, leading to symptoms such as dysphagia and stricture formation. Systemic immune indicators like eotaxin and fibroblast growth factor were evaluated for possible synergistic pathological effects. Moreover, blood cells, local tissue, and plasma from EoE and control subjects were studied to determine if the localized disease was associated with a systemic effect that correlated with presence of EoE disease.MethodReal-time polymerase chain reaction from peripheral blood mononuclear cells (PBMC), immunohistochemistry from local esophageal biopsies, fluid assays on plasma, and fluorescence-activated cell sorting on peripheral blood cells from subjects were used to study the systemic immune indicators in newly diagnosed EoE (n = 35), treated EoE (n = 9), Gastroesophageal reflux disease (GERD) (n = 8), ulcerative colitis (n = 5), Crohn's disease (n = 5), and healthy controls (n = 8).ResultOf the transcripts tested for possible immune indicators, we found extracellular signal-regulated kinase (ERK), Bcl-2, bFGF (basic fibroblast growth factor), and eotaxin levels were highly upregulated in PBMC and associated with disease presence of EoE. Increased FGF detected by immunohistochemistry in esophageal tissues and in PBMC was correlated with low levels of pro-apoptotic factors (Fas, Caspase 8) in PBMC from EoE subjects. Plasma-derived bFGF was shown to be the most elevated and most specific in EoE subjects in comparison to healthy controls and disease control subjects.ConclusionWe describe for the first time a possible mechanism by which increased FGF is associated with inhibiting apoptosis in local esophageal tissues of EoE subjects as compared to controls. Eotaxin and FGF signaling pathways share activation through the ERK pathway; together, they could act to increase eosinophil activation and prolong the half-life of eosinophils in local tissues of the esophagus in EoE subjects.
Molluscicidal efficacies of different formulations of niclosamide: result of meta-analysis of Chinese literature
Authors: Yang Guo-Jing , Li Wei , Sun Le-Ping , Wu Feng , Yang Kun , Huang Yi-Xin , Zhou Xiao-Nong 
Published: September 2010

Abstract
The control efforts on Oncomelania hupensis, the intermediate snail host of Schistosoma japonicum, cannot be easily excluded from the integrated approach of schistosomiasis control in China. Application of chemical compounds, molluscicides, in snail habitats is a common method for snail control in addition to environmental modification. We conducted a systematic review and meta-analysis to assess the molluscicidal effects of the currently recommended 50% niclosamide ethanolamine salt wettable powder and a new 4% niclosamide ethanolamine salt powder developed by Chinese researchers. Literature was searched from three Chinese databases, i.e. Chinese Biomedical Database, VIP Database and Wanfang Database, on field mollusciciding trials of niclosamide in China (from January 1, 1990 to April 1, 2010). Molluscicidal effects on reduction of snail population of the 50% or 4% niclosamide formulations in field trial were evaluated 3 days, 7 days or 15 days post-application. Out of 90 publications, 20 papers were eventually selected for analysis. Publication bias and heterogeneity tests indicated that no publication bias existed but heterogeneity between studies was present. Meta-analysis in a random effect model showed that the snail mortality of 3, 7 and 15 days after spraying the 50% niclosamide ethanolamine salt wettable powder were 77% [95%CI: 0.68-0.86], 83% [95%CI: 0.77-0.89], and 88% [95%CI: 0.82-0.92], respectively. For the 4% niclosamide ethanolamine salt powder, the snail mortality after 3, 7 and 15 days were 81% [95%CI: 0.65-0.93], 90% [95%CI: 0.83-0.95] and 94% [95%CI: 0.91-0.97], respectively. Both are good enough to be used as molluscicides integrated with a schistosomiasis control programme. The 4% niclosamide ethanolamine salt powder can be applied in the field without water supply as the surrogate of the current widely used 50% niclosamide ethanolamine salt wettable powder. However, to consolidate the schistosomiasis control achievement gained, it is necessary to continuously perform mollusciciding more than twice annually in the field.
Elevated c-Src and c-Yes expression in malignant skin cancers
Authors: Lee Jang Hyun , Pyon Jae-Kyung , Kim Dong Wook , Lee Sang Han , Nam Hae Seon , Kim Chul Han , Kang Sang Gue , Lee Yoon Jin , Park Mi Youn , Jeong Dong Jun , Cho Moon Kyun 
Published: September 2010

Abstracts

Background
Src family kinases (SFKs) play an important role in cancer proliferation, survival, motility, invasiveness, metastasis, and angiogenesis. Among the SFKs, c-Src and c-Yes are particularly over-expressed or hyper-activated in many human epithelial cancers. However, only a few studies have attempted to define the expression and role of c-Src and c-Yes in cutaneous carcinomas.

Objectives
To investigate the expression of c-Src and c-Yes in cutaneous carcinomas to include malignant melanoma (MM), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC).

Methods
We examined 6 normal skin tissues and 18 malignant skin tumor tissues using western blotting for the expression of c-Src and c-Yes. In another set, 16 specimens of MM, 16 SCCs and 16 BCCs were analyzed for the expression of c-Src and c-Yes using immunohistochemical staining.

Results
Western blotting showed that c-Src was expressed in all malignant skin tumors, but not in normal skin, while c-Yes was expressed in MM and SCC, but not in BCC and normal skin. Immunohistochemical staining results of c-Src and c-Yes in MM, SCC, and BCC mirrored those of the western blot analysis.

Conclusions
c-Src, rather than c-Yes, plays a key role in the proliferation and progression of malignant skin cancers.
Expression and clinical significance of multidrug resistance proteins in brain tumors
Authors: Guo Zhenhua , Zhu Jin , Zhao Lihua , Luo Qing , Jin Xianqing 
Published: September 2010

Abstract

Background
To investigate the mechanisms of multidrug resistance of brain tumors, to identify the site of cellular expression of P-gp in human brains in situ and to morphologically determine whether an association may exist between P-gp and caveolin-1.

Methods
Immunohistochemistry was used to detect the expression and location of P-glycoprotein (P-gp), Multidrug resistance-associated protein (MDR), Lung resistance-related protein (LRP), Topoisomerase II (Topo II) and Glutathione-S-π (GST-π) in 30 patient tumor tissues and 5 normal brain tissues. The sections were subjected to double labeling for P-gp (TRITC labeled) and caveolin-1 (FITC labeled). The location and characteristics of expression of the two proteins in the blood brain barrier(BBB) was observed using a laser scanning microscope.

Results
High expression of P-gp was detected in vessel walls and the tissue surrounding the vessels. However, expression of P-gp was low in tumor cells. The expression of the other 4 multidrug resistance proteins was not observed in the vessel walls. Laser scanning microscopy showed P-gp and caveolin-1 co-expression: the two proteins co-localized either in the luminal endothelial compartment or at the border of the luminal/abluminal compartments.

Conclusion
Chemotherapeutics drugs are interrupted in the end-feet of neuroepithelial cells of the BBB by P-gp, which weakens the chemotherapeutic effect. P-gp marks the BBB, and the transporter is localized in the luminal endothelial compartment where it co-localizes with caveolin-1.
Prognostic and Predictive Gene Signature for Adjuvant Chemotherapy in Resected Non–Small-Cell Lung Cancer
Authors: Zhu Chang-Qi , Ding Keyue , Strumpf Dan , Weir Barbara A. , Meyerson Matthew , Pennell Nathan , Thomas Roman K. , Naoki Katsuhiko , Ladd-Acosta Christine , Liu Ni , Pintilie Melania , Der Sandy , Seymour Lesley , Jurisica Igor , Shepherd Frances A. , Tsao Ming-Sound 
Published: September 2010

Purpose The JBR.10 trial demonstrated benefit from adjuvant cisplatin/vinorelbine (ACT) in early-stage non–small-cell lung cancer (NSCLC). We hypothesized that expression profiling may identify stage-independent subgroups who might benefit from ACT. Patients and Methods Gene expression profiling was conducted on mRNA from 133 frozen JBR.10 tumor samples (62 observation [OBS], 71 ACT). The minimum gene set that was selected for the greatest separation of good and poor prognosis patient subgroups in OBS patients was identified. The prognostic value of this gene signature was tested in four independent published microarray data sets and by quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR). Results A 15-gene signature separated OBS patients into high-risk and low-risk subgroups with significantly different survival (hazard ratio [HR], 15.02; 95% CI, 5.12 to 44.04; P < .001; stage I HR, 13.31; P < .001; stage II HR, 13.47; P < .001). The prognostic effect was verified in the same 62 OBS patients where gene expression was assessed by qPCR. Furthermore, it was validated consistently in four separate microarray data sets (total 356 stage IB to II patients without adjuvant treatment) and additional JBR.10 OBS patients by qPCR (n = 19). The signature was also predictive of improved survival after ACT in JBR.10 high-risk patients (HR, 0.33; 95% CI, 0.17 to 0.63; P = .0005), but not in low-risk patients (HR, 3.67; 95% CI, 1.22 to 11.06; P = .0133; interaction P < .001). Significant interaction between risk groups and ACT was verified by qPCR. Conclusion This 15-gene expression signature is an independent prognostic marker in early-stage, completely resected NSCLC, and to our knowledge, is the first signature that has demonstrated the potential to select patients with stage IB to II NSCLC most likely to benefit from adjuvant chemotherapy with cisplatin/vinorelbine.
Survival Benefit With Proapoptotic Molecular and Pathologic Responses From Dual Targeting of Mammalian Target of Rapamycin and Epidermal Growth Factor Receptor in a Preclinical Model of Pancreatic Neuroendocrine Carcinogenesis
Authors: Chiu Christopher W. , Nozawa Hiroaki , Hanahan Douglas 
Published: September 2010

Purpose Pancreatic neuroendocrine tumors (PNETs), although rare, often metastasize, such that surgery, the only potentially curative therapy, is not possible. There is no effective systemic therapy for patients with advanced PNETs. Therefore, new strategies are needed. Toward that end, we investigated the potential benefit of dual therapeutic targeting of the epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) kinases, using a preclinical mouse model of PNET. Materials and Methods Rapamycin and erlotinib, inhibitors of mTOR and EGFR, respectively, were used to treat RIP-Tag2 transgenic mice bearing advanced multifocal PNET. Tumor growth and survival were monitored, and tumors were surveyed for potential biomarkers of response to the therapeutics. Results Rapamycin monotherapy was notably efficacious, prolonging survival concomitant with tumor stasis (stable disease). However, the tumors developed resistance, as evidenced by eventual relapse to progressive tumor growth. Erlotinib monotherapy slowed tumor growth and elicited a marginal survival benefit. In combination, there was an unprecedented survival benefit in the face of this aggressive multifocal cancer and, in contrast to either monotherapy, the development of adaptive resistance was not apparent. Additionally, the antiapoptotic protein survivin was implicated as a biomarker of sensitivity and beneficial responses to the dual targeted therapy. Conclusion Preclinical trials in a mouse model of endogenous PNET suggest that combined targeting of the mTOR and EGFR signaling pathways could have potential clinical benefit in treating PNET. These results have encouraged development of an ongoing phase II clinical trial aimed to evaluate the efficacy of this treatment regimen in human neuroendocrine tumors.
Do women consult more than men? A review of gender and consultation for back pain and headache
Authors: Hunt Kate , Adamson Joy , Hewitt Catherine , Nazareth Irwin 
Published: September 2010

Objectives: Because women consult their general practitioners more frequently on average than men, it is commonly assumed that they consult more for all symptoms and conditions. This assumption is reinforced by qualitative studies reporting a widespread reluctance to consult by men. However, few studies directly compare consultation in men and women experiencing similar symptoms or conditions. Methods: A systematic review of the evidence on gender and consultation for two common symptoms, back pain and headache. Extensive electronic searches identified 15 papers reporting the relationship between gender and help-seeking for back pain and 11 papers for headache. Two independent reviewers assessed articles for inclusion and extracted data from eligible studies. Results: Few studies compared consultation patterns for these symptoms among men and women known to have experienced the symptom. The quality of the studies was variable. Overall, evidence for greater consultation by women with back pain was weak and inconsistent. Among those with back pain, the odds ratios for women seeking help, compared with men, ranged from 0.6 (95% confidence intervals 0.3, 1.2, adjusted only for age) to 2.17 (95% confidence intervals 1.35, 3.57, unadjusted), although none of the reported odds ratio, below 1.00 was statistically significant. The evidence for women being more likely to consult for headache was a little stronger. Five studies showed a statistically elevated odds ratio, and none suggested that men with headache symptoms were more likely to consult than women with headache symptoms. Limitations to the studies are discussed. Conclusion: Given the strength of assumptions that women consult more readily for common symptoms, the evidence for greater consultation amongst women for two common symptoms, headache and back pain, was surprisingly weak and inconsistent, especially with respect to back pain.
RNA duplexes in transcriptional regulation
Authors: Swaminathan Sanjay , Hood Chantelle L. , Suzuki Kazuo , Kelleher Anthony D. 
Published: September 2010

AbstractTranscriptional regulation by small RNA molecules, including small interfering RNA and microRNA, has emerged as an important gene expression modulator. The regulatory pathways controlling gene expression, post-transcriptional gene silencing and transcriptional gene silencing (TGS) have been demonstrated in yeast, plants and more recently in human cells. In this review, we discuss the currents models of transcriptional regulation and the main components of the RNA-induced silencing complex and RNA-induced transcriptional silencing complex machinery, as well as confounding off-target effects and gene activation. We also discuss RNA-mediated TGS within the NF-κB motif of the human immunodeficiency virus type 1 5′ long tandem repeat promoter region and the associated epigenetic modifications. Finally, we outline the current RNA interference (RNAi) delivery methods and describe the current status of human trials investigating potential RNAi therapeutics for several human diseases.
Zur Problematik des Mitteleuropabegriffs in der Literaturwissenschaft: Einige methodologische Überlegungen
Authors: Ohme Andreas 
Published: September 2010

Zusammenfassung
In the course of the so-called cultural turn the construction of identities has become a central field of research in literary criticism. In describing an area with a supposed specific cultural tradition the concept of Central Europe in this context achieved a certain prominence within Slavonic Studies. This paper therefore discusses the consequences of this research interest for the self-concept of Slavonic Studies as an academic subject. Demonstrating that the concept of Central Europe cannot claim any plausible heuristic value for the exploration of literary works of art the conclusion is drawn that this concept, as with the preoccupation with the construction of cultural identities in general, does not make any contribution to subject-specific knowledge. Thus this research interest tends to undermine the legitimacy of literary criticism as an independent academic subject.
„Das Paradies des Herzens“ des Jan Amos Komenský
Authors: Ebeling Jana 
Published: September 2010

Zusammenfassung
This article is an interpretation of the second part of the famous “Labyrint svĕta a ráj srdce” of Jan Amos Komenský. This text was written in the early 17th century and is in most beautiful Czech telling the story of a pilgrim who finds God by returning from his way through the sinful world (this part of the journey is described in the “Labyrint svĕta”) to his inner self. There he meets Jesus Christ in the chamber of his heart, from where he is again sent out to explore what life in the service of God can be like, if he only decides to fully believe. Komenský hereby presents his own vision of the right way of life.