What Makes a Great Journal Great in the Sciences? Which Came First, the Chicken or the Egg?

The paper is concerned with analysing what makes a great journal great in the sciences, based on quantifiable Research Assessment Measures (RAM). Alternative RAM are discussed, with an emphasis on the Thomson Reuters ISI Web of Science database (hereafter ISI). Various ISI RAM that are calculated annually or updated daily are defined and analysed, including the classic 2-year impact factor (2YIF), 5-year impact factor (5YIF), Immediacy (or zero-year impact factor (0YIF)), Eigenfactor, Article Influence, C3PO (Citation Performance Per Paper Online), h-index, Zinfluence, PI-BETA (Papers Ignored - By Even The Authors), Impact Factor Inflation (IFI), and three new RAM, namely Historical Self-citation Threshold Approval Rating (H-STAR), 2 Year Self-citation Threshold Approval Rating (2Y-STAR), and Cited Article Influence (CAI). The RAM data are analysed for the 6 most highly cited journals in 20 highly-varied and well-known ISI categories in the sciences, where the journals are chosen on the basis of 2YIF. The application to these 20 ISI categories could be used as a template for other ISI categories in the sciences and social sciences, and as a benchmark for newer journals in a range of ISI disciplines. In addition to evaluating the 6 most highly cited journals in each of 20 ISI categories, the paper also highlights the similarities and differences in alternative RAM, finds that several RAM capture similar performance characteristics for the most highly cited scientific journals, determines that PI-BETA is not highly correlated with the other RAM, and hence conveys additional information regarding research performance. In order to provide a meta analysis summary of the RAM, which are predominantly ratios, harmonic mean rankings are presented of the 13 RAM for the 6 most highly cited journals in each of the 20 ISI categories. It is shown that emphasizing THE impact factor, specifically the 2-year impact factor, of a journal to the exclusion of other informative RAM can lead to a distorted evaluation of journal performance and influence on different disciplines, especially in view of inflated journal self citations

Synthesis and Biological Evaluation of Phenanthrenes as Cytotoxic Agents with Pharmacophore Modeling and ChemGPS-NP Prediction as Topo II Inhibitors

In a structure-activity relationship (SAR) study, 3-methoxy-1,4-phenanthrenequinones, calanquinone A (6a), denbinobin (6b), 5-OAc-calanquinone A (7a) and 5-OAc-denbinobin (7b), have significantly promising cytotoxicity against various human cancer cell lines (IC50 0.08–1.66 µg/mL). Moreover, we also established a superior pharmacophore model for cytotoxicity (r = 0.931) containing three hydrogen bond acceptors (HBA1, HBA2 and HBA3) and one hydrophobic feature (HYD) against MCF-7 breast cancer cell line. The pharmacophore model indicates that HBA3 is an essential feature for the oxygen atom of 5-OH in 6a–b and for the carbonyl group of 5-OCOCH3 in 7a–b, important for their cytotoxic properties. The SAR for moderately active 5a–b (5-OCH3), and highly active 6a–b and 7a–b, are also elaborated in a spatial aspect model. Further rational design and synthesis of new cytotoxic phenanthrene analogs can be implemented via this model. Additionally, employing a ChemGPS-NP based model for cytotoxicity mode of action (MOA) provides support for a preliminary classification of compounds 6a–b as topoisomerase II inhibitors

DeBi: Discovering Differentially Expressed Biclusters using a Frequent Itemset Approach

<p>Abstract</p> <p>Background</p> <p>The analysis of massive high throughput data via clustering algorithms is very important for elucidating gene functions in biological systems. However, traditional clustering methods have several drawbacks. Biclustering overcomes these limitations by grouping genes and samples simultaneously. It discovers subsets of genes that are co-expressed in certain samples. Recent studies showed that biclustering has a great potential in detecting marker genes that are associated with certain tissues or diseases. Several biclustering algorithms have been proposed. However, it is still a challenge to find biclusters that are significant based on biological validation measures. Besides that, there is a need for a biclustering algorithm that is capable of analyzing very large datasets in reasonable time.</p> <p>Results</p> <p>Here we present a fast biclustering algorithm called DeBi (Differentially Expressed BIclusters). The algorithm is based on a well known data mining approach called frequent itemset. It discovers maximum size homogeneous biclusters in which each gene is strongly associated with a subset of samples. We evaluate the performance of DeBi on a yeast dataset, on synthetic datasets and on human datasets.</p> <p>Conclusions</p> <p>We demonstrate that the DeBi algorithm provides functionally more coherent gene sets compared to standard clustering or biclustering algorithms using biological validation measures such as Gene Ontology term and Transcription Factor Binding Site enrichment. We show that DeBi is a computationally efficient and powerful tool in analyzing large datasets. The method is also applicable on multiple gene expression datasets coming from different labs or platforms.</p

Activation of Multiple Apoptotic Pathways in Human Nasopharyngeal Carcinoma Cells by the Prenylated Isoflavone, Osajin

Osajin is a prenylated isoflavone showing antitumor activity in different tumor cell lines. The underlying mechanism of osajin-induced cancer cell death is not clearly understood. In the present study, the mechanisms of osajin-induced cell death of human nasopharyngeal carcinoma (NPC) cells were explored. Osajin was found to significantly induce apoptosis of NPC cells in a dose- and time-dependent manner. Multiple molecular effects were observed during osajin treatment including a significant loss of mitochondrial transmembrane potential, release of cytochrome c into the cytosol, enhanced expression of Fas ligand (FasL), suppression of glucose-regulated protein 78 kDa (GRP78), and activation of caspases-9, -8, -4 and -3. In addition, up-regulation of proapoptotic Bax protein and down-regulation of antiapoptotic Bcl-2 protein were also observed. Taken together, osajin induces apoptosis in human NPC cells through multiple apoptotic pathways, including the extrinsic death receptor pathway, and intrinsic pathways relying on mitochondria and endoplasmic reticulum stress. Thus, osajin could be developed as a new effective and chemopreventive compound for human NPC

Long-Term Mortality of Patients with Septic Ocular or Central Nervous System Complications from Pyogenic Liver Abscess: A Population-Based Study

Background: Taiwan is endemic for pyogenic liver abscess (PLA). Septic ocular or central nervous system (CNS) complications derived from PLA can result in catastrophic disability. We investigated the epidemiology and long-term prognosis of PLA patients with septic ocular or CNS complications over an 8-year period. Methodology/Principal Findings: We extracted 21,307 patients with newly diagnosed PLA from a nationwide health registry in Taiwan between 2000 and 2007. The frequency of and risk factors for PLA with septic ocular or CNS complications were determined. The 2-year survival of these patients was compared between those with and without septic ocular or CNS complications. Septic ocular or CNS complications accounted for 2.1 % of all PLA patients. Age and the Charlson comorbidity index were significantly lower in PLA patients with ocular or CNS complications than those without. Diabetes and age,65 years were independent predictors of septic ocular or CNS complications. The 2-year mortality of patients with septic ocular or CNS complications was similar to those without complications (24.8 % vs. 27.5%, p = 0.502). However, among patients,65 years old and a Charlson index #1, the 2-year mortality was significantly higher in those with than without complications (18.6 % vs. 11.8%, p = 0.001). Conclusions/Significance: Physicians should recognize that catastrophic disability due to ocular or neurologica

Analysis of meniscal degeneration and meniscal gene expression

<p>Abstract</p> <p>Background</p> <p>Menisci play a vital role in load transmission, shock absorption and joint stability. There is increasing evidence suggesting that OA menisci may not merely be bystanders in the disease process of OA. This study sought: 1) to determine the prevalence of meniscal degeneration in OA patients, and 2) to examine gene expression in OA meniscal cells compared to normal meniscal cells.</p> <p>Methods</p> <p>Studies were approved by our human subjects Institutional Review Board. Menisci and articular cartilage were collected during joint replacement surgery for OA patients and lower limb amputation surgery for osteosarcoma patients (normal control specimens), and graded. Meniscal cells were prepared from these meniscal tissues and expanded in monolayer culture. Differential gene expression in OA meniscal cells and normal meniscal cells was examined using Affymetrix microarray and real time RT-PCR.</p> <p>Results</p> <p>The grades of meniscal degeneration correlated with the grades of articular cartilage degeneration (r = 0.672; P < 0.0001). Many of the genes classified in the biological processes of immune response, inflammatory response, biomineral formation and cell proliferation, including major histocompatibility complex, class II, DP alpha 1 (<it>HLA-DPA1</it>), integrin, beta 2 (<it>ITGB2</it>), ectonucleotide pyrophosphatase/phosphodiesterase 1 (<it>ENPP1</it>), ankylosis, progressive homolog (<it>ANKH</it>) and fibroblast growth factor 7 (<it>FGF7</it>), were expressed at significantly higher levels in OA meniscal cells compared to normal meniscal cells. Importantly, many of the genes that have been shown to be differentially expressed in other OA cell types/tissues, including ADAM metallopeptidase with thrombospondin type 1 motif 5 (<it>ADAMTS5</it>) and prostaglandin E synthase (<it>PTGES</it>), were found to be expressed at significantly higher levels in OA meniscal cells. This consistency suggests that many of the genes detected in our study are disease-specific.</p> <p>Conclusion</p> <p>Our findings suggest that OA is a whole joint disease. Meniscal cells may play an active role in the development of OA. Investigation of the gene expression profiles of OA meniscal cells may reveal new therapeutic targets for OA therapy and also may uncover novel disease markers for early diagnosis of OA.</p

Extracting the abstraction pyramid from complex networks

<p>Abstract</p> <p>Background</p> <p>At present, the organization of system modules is typically limited to either a multilevel hierarchy that describes the "vertical" relationships between modules at different levels (e.g., module A at level two is included in module B at level one), or a single-level graph that represents the "horizontal" relationships among modules (e.g., genetic interactions between module A and module B). Both types of organizations fail to provide a broader and deeper view of the complex systems that arise from an integration of vertical and horizontal relationships.</p> <p>Results</p> <p>We propose a complex network analysis tool, Pyramabs, which was developed to integrate vertical and horizontal relationships and extract information at various granularities to create a pyramid from a complex system of interacting objects. The pyramid depicts the nested structure implied in a complex system, and shows the vertical relationships between abstract networks at different levels. In addition, at each level the abstract network of modules, which are connected by weighted links, represents the modules' horizontal relationships. We first tested Pyramabs on hierarchical random networks to verify its ability to find the module organization pre-embedded in the networks. We later tested it on a protein-protein interaction (PPI) network and a metabolic network. According to Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), the vertical relationships identified from the PPI and metabolic pathways correctly characterized the <it>inclusion </it>(i.e., <it>part-of</it>) relationship, and the horizontal relationships provided a good indication of the functional closeness between modules. Our experiments with Pyramabs demonstrated its ability to perform knowledge mining in complex systems.</p> <p>Conclusions</p> <p>Networks are a flexible and convenient method of representing interactions in a complex system, and an increasing amount of information in real-world situations is described by complex networks. We considered the analysis of a complex network as an iterative process for extracting meaningful information at multiple granularities from a system of interacting objects. The quality of the interpretation of the networks depends on the completeness and expressiveness of the extracted knowledge representations. Pyramabs was designed to interpret a complex network through a disclosure of a pyramid of abstractions. The abstraction pyramid is a new knowledge representation that combines vertical and horizontal viewpoints at different degrees of abstraction. Interpretations in this form are more accurate and more meaningful than multilevel dendrograms or single-level graphs. Pyramabs can be accessed at <url>http://140.113.166.165/pyramabs.php/</url>.</p

Nonadhesive Culture System as a Model of Rapid Sphere Formation with Cancer Stem Cell Properties

BACKGROUND: Cancer stem cells (CSCs) play an important role in tumor initiation, progression, and metastasis and are responsible for high therapeutic failure rates. Identification and characterization of CSC are crucial for facilitating the monitoring, therapy, or prevention of cancer. Great efforts have been paid to develop a more effective methodology. Nevertheless, the ideal model for CSC research is still evolving. In this study, we created a nonadhesive culture system to enrich CSCs from human oral squamous cell carcinoma cell lines with sphere formation and to characterize their CSC properties further. METHODS: A nonadhesive culture system was designed to generate spheres from the SAS and OECM-1 cell lines. A subsequent investigation of their CSC properties, including stemness, self-renewal, and chemo- and radioresistance in vitro, as well as tumor initiation capacity in vivo, was also performed. RESULTS: Spheres were formed cost-effectively and time-efficiently within 5 to 7 days. Moreover, we proved that these spheres expressed putative stem cell markers and exhibited chemoradiotherapeutic resistance, in addition to tumor-initiating and self-renewal capabilities. CONCLUSIONS: Using this nonadhesive culture system, we successfully established a rapid and cost-effective model that exhibits the characteristics of CSCs and can be used in cancer research

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

The functional capacity and quality of life of women with advanced breast cancer

The rehabilitation needs of patients with metastatic breast cancer (MBC) are poorly studied. The primary aim of the study was to evaluate the functional capacity of women with MBC and quality of life (QoL). The present study is an open, non-randomized, prospective cross-sectional observation study. The functional capacity of 128 MBC patients with ongoing cancer treatments, were studied in Helsinki University Hospital (HUS): Peak expiratory flow (PEF), dynamic and static balance, 6 minute walking distance (6MWD), 10 meter walking, sit-to-stand test, repeated squat, grip strength, shoulder movement, pain, and QoL by Beck's depression scale (BDI), health assessment questionnaire (HAQ), RAND SF-36 and EORTC QLQ-30 items. The walking capacity was compromised in half and the strength of the lower extremities in one-third of the patients. PEF was below the normal reference in 55 %, static balance in 62 % and dynamic balance in 73 % (= 61 year olds). The grip power was lowered in 44/30 % of the patients (right/left) and the shoulder movement was restricted in 30 %. Some disability in physical functioning experienced 55 % (HAQ) and 37 % felt depressive (BDI). The QoL (RAND SF-36) was poor especially in the field of physical, role and social functioning and bodily pain (<0.001). Pain, depression, and a poor 6MWD results independently determined the physical component of QoL (p <0.001). The functional capacity of patients with MBC was significantly lowered. This, in association with distressing symptoms like pain and depression causes a vicious circle further leading to functional disabilities and impaired QoL.Peer reviewe