bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of combined data from heterogeneous study designs: an applied example from the patient navigation research program
Authors: Roetzheim Richard G , Freund Karen M , Corle Don K , Murray David M , Snyder Frederick R , Kronman Andrea C , Jean-Pierre Pascal , Raich Peter C , Holden Alan EC , Darnell Julie S , Warren-Mears Victoria , Patierno Steven ,   PNRP Design and Analysis Committee for the Patient Navigation Research Program Investigators
Published: January 2012

Background The Patient Navigation Research Program (PNRP) is a cooperative effort of nine research projects, with similar clinical criteria but with different study designs. To evaluate projects such as PNRP, it is desirable to perform a pooled analysis to increase power relative to the individual projects. There is no agreed-upon prospective methodology, however, for analyzing combined data arising from different study designs. Expert opinions were thus solicited from the members of the PNRP Design and Analysis Committee. Purpose To review possible methodologies for analyzing combined data arising from heterogeneous study designs. Methods The Design and Analysis Committee critically reviewed the pros and cons of five potential methods for analyzing combined PNRP project data. The conclusions were based on simple consensus. The five approaches reviewed included the following: (1) analyzing and reporting each project separately, (2) combining data from all projects and performing an individual-level analysis, (3) pooling data from projects having similar study designs, (4) analyzing pooled data using a prospective meta-analytic technique, and (5) analyzing pooled data utilizing a novel simulated group-randomized design. Results Methodologies varied in their ability to incorporate data from all PNRP projects, to appropriately account for differing study designs, and to accommodate differing project sample sizes. Limitations The conclusions reached were based on expert opinion and not derived from actual analyses performed. Conclusions The ability to analyze pooled data arising from differing study designs may provide pertinent information to inform programmatic, budgetary, and policy perspectives. Multisite community-based research may not lend itself well to the more stringent explanatory and pragmatic standards of a randomized controlled trial design. Given our growing interest in community-based population research, the challenges inherent in the analysis of heterogeneous study design are likely to become more salient. Discussion of the analytic issues faced by the PNRP and the methodological approaches we considered may be of value to other prospective community-based research programs.
HIF1α is required for survival maintenance of chronic myeloid leukemia stem cells
Authors: Zhang Haojian , Li Huawei , Xi Hualin S. , Li Shaoguang 
Published: January 2012

Abstract
Hypoxia-inducible factor-1α (HIF1α), a master transcriptional regulator of the cellular and systemic hypoxia response, is essential for the maintenance of self-renewal capacity of normal HSCs. It is still unknown whether HIF1α has a role in survival regulation of leukemia stem cells (LSCs) in chronic myeloid leukemia (CML). Using a mouse model of CML, here we report that HIF1α plays a crucial role in survival maintenance of LSCs. Deletion of HIF1α impairs the propagation of CML through impairing cell-cycle progression and inducing apoptosis of LSCs. Deletion of HIF1α results in elevated expression of p16Ink4a and p19Arf in LSCs, and knockdown of p16Ink4a and p19Arf rescues the defective colony-forming ability of HIF1α−/− LSCs. Compared with normal HSCs, LSCs appear to be more dependent on the HIF1α pathway. Together, these results demonstrate that HIF1α represents a critical pathway in LSCs and inhibition of the HIF1α pathway provides a therapeutic strategy for eradicating LSCs in CML.
Dysfunction of the TP53 tumor suppressor gene in lymphoid malignancies
Authors: Xu-Monette Zijun Y. , Medeiros L. Jeffrey , Li Yong , Orlowski Robert Z. , Andreeff Michael , Bueso-Ramos Carlos E. , Greiner Timothy C. , McDonnell Timothy J. , Young Ken H. 
Published: January 2012

AbstractMutations of the TP53 gene and dysregulation of the TP53 pathway are important in the pathogenesis of many human cancers, including lymphomas. Tumor suppression by p53 occurs via both transcription-dependent activities in the nucleus by which p53 regulates transcription of genes involved in cell cycle, DNA repair, apoptosis, signaling, transcription, and metabolism; and transcription-independent activities that induces apoptosis and autophagy in the cytoplasm. In lymphoid malignancies, the frequency of TP53 deletions and mutations is lower than in other types of cancer. Nonetheless, the status of TP53 is an independent prognostic factor in most lymphoma types. Dysfunction of TP53 with wild-type coding sequence can result from deregulated gene expression, stability, and activity of p53. To overcome TP53 pathway inactivation, therapeutic delivery of wild-type p53, activation of mutant p53, inhibition of MDM2-mediated degradation of p53, and activation of p53-dependent and -independent apoptotic pathways have been explored experimentally and in clinical trials. We review the mechanisms of TP53 dysfunction, recent advances implicated in lymphomagenesis, and therapeutic approaches to overcoming p53 inactivation.
SPARQL Assist language-neutral query composer
Authors: McCarthy Luke , Vandervalk Ben , Wilkinson Mark 
Published: January 2012

Abstract

Background
SPARQL query composition is difficult for the lay-person, and even the experienced bioinformatician in cases where the data model is unfamiliar. Moreover, established best-practices and internationalization concerns dictate that the identifiers for ontological terms should be opaque rather than human-readable, which further complicates the task of synthesizing queries manually.

Results
We present SPARQL Assist: a Web application that addresses these issues by providing context-sensitive type-ahead completion during SPARQL query construction. Ontological terms are suggested using their multi-lingual labels and descriptions, leveraging existing support for internationalization and language-neutrality. Moreover, the system utilizes the semantics embedded in ontologies, and within the query itself, to help prioritize the most likely suggestions.

Conclusions
To ensure success, the Semantic Web must be easily available to all users, regardless of locale, training, or preferred language. By enhancing support for internationalization, and moreover by simplifying the manual construction of SPARQL queries through the use of controlled-natural-language interfaces, we believe we have made some early steps towards simplifying access to Semantic Web resources.
miRdSNP: a database of disease-associated SNPs and microRNA target sites on 3'UTRs of human genes
Authors: Bruno Andrew E , Li Li , Kalabus James L , Pan Yuzhuo , Yu Aiming , Hu Zihua 
Published: January 2012

Abstract

Background
Single nucleotide polymorphisms (SNPs) can lead to the susceptibility and onset of diseases through their effects on gene expression at the posttranscriptional level. Recent findings indicate that SNPs could create, destroy, or modify the efficiency of miRNA binding to the 3'UTR of a gene, resulting in gene dysregulation. With the rapidly growing number of published disease-associated SNPs (dSNPs), there is a strong need for resources specifically recording dSNPs on the 3'UTRs and their nucleotide distance from miRNA target sites. We present here miRdSNP, a database incorporating three important areas of dSNPs, miRNA target sites, and diseases.

Description
miRdSNP provides a unique database of dSNPs on the 3'UTRs of human genes manually curated from PubMed. The current release includes 786 dSNP-disease associations for 630 unique dSNPs and 204 disease types. miRdSNP annotates genes with experimentally confirmed targeting by miRNAs and indexes miRNA target sites predicted by TargetScan and PicTar as well as potential miRNA target sites newly generated by dSNPs. A robust web interface and search tools are provided for studying the proximity of miRNA binding sites to dSNPs in relation to human diseases. Searches can be dynamically filtered by gene name, miRBase ID, target prediction algorithm, disease, and any nucleotide distance between dSNPs and miRNA target sites. Results can be viewed at the sequence level showing the annotated locations for miRNA target sites and dSNPs on the entire 3'UTR sequences. The integration of dSNPs with the UCSC Genome browser is also supported.

Conclusion
miRdSNP provides a comprehensive data source of dSNPs and robust tools for exploring their distance from miRNA target sites on the 3'UTRs of human genes. miRdSNP enables researchers to further explore the molecular mechanism of gene dysregulation for dSNPs at posttranscriptional level. miRdSNP is freely available on the web at http://mirdsnp.ccr.buffalo.edu.
Diagnostic value of fine-needle aspiration biopsy for breast mass: a systematic review and meta-analysis
Authors: Yu Ying-Hua , Wei Wei , Liu Jian-Lun 
Published: January 2012

Abstract

Background
Fine-needle aspiration biopsy (FNAB) of the breast is a minimally invasive yet maximally diagnostic method. However, the clinical use of FNAB has been questioned. The purpose of our study was to establish the overall value of FNAC in the diagnosis of breast lesions.

Methods
After a review and quality assessment of 46 studies, sensitivity, specificity and other measures of accuracy of FNAB for evaluating breast lesions were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize overall accuracy. The sensitivity and specificity for the studies data (included unsatisfactory samples) and underestimation rate of unsatisfactory samples were also calculated.

Results
The summary estimates for FNAB in diagnosis of breast carcinoma were as follows (unsatisfactory samples was temporarily exluded): sensitivity, 0.927 (95% confidence interval [CI], 0.921 to 0.933); specificity, 0.948 (95% CI, 0.943 to 0.952); positive likelihood ratio, 25.72 (95% CI, 17.35 to 28.13); negative likelihood ratio, 0.08 (95% CI, 0.06 to 0.11); diagnostic odds ratio, 429.73 (95% CI, 241.75 to 763.87); The pooled sensitivity and specificity for 11 studies, which reported unsatisfactory samples (unsatisfactory samples was considered to be positive in this classification) were 0.920 (95% CI, 0.906 to 0.933) and 0.768 (95% CI, 0.751 to 0.784) respectively. The pooled proportion of unsatisfactory samples that were subsequently upgraded to various grade cancers was 27.5% (95% CI, 0.221 to 0.296).

Conclusions
FNAB is an accurate biopsy for evaluating breast malignancy if rigorous criteria are used. With regard to unsatisfactory samples, futher invasive procedures are required in order to minimize the chance of a missed diagnosis of breast cancer.
Health literacy and public health: A systematic review and integration of definitions and models
Authors: Sørensen Kristine , Van den Broucke Stephan , Fullam James , Doyle Gerardine , Pelikan Jürgen , Slonska Zofia , Brand Helmut ,   (HLS-EU) Consortium Health Literacy Project European
Published: January 2012

Abstract

Background
Health literacy concerns the knowledge and competences of persons to meet the complex demands of health in modern society. Although its importance is increasingly recognised, there is no consensus about the definition of health literacy or about its conceptual dimensions, which limits the possibilities for measurement and comparison. The aim of the study is to review definitions and models on health literacy to develop an integrated definition and conceptual model capturing the most comprehensive evidence-based dimensions of health literacy.

Methods
A systematic literature review was performed to identify definitions and conceptual frameworks of health literacy. A content analysis of the definitions and conceptual frameworks was carried out to identify the central dimensions of health literacy and develop an integrated model.

Results
The review resulted in 17 definitions of health literacy and 12 conceptual models. Based on the content analysis, an integrative conceptual model was developed containing 12 dimensions referring to the knowledge, motivation and competencies of accessing, understanding, appraising and applying health-related information within the healthcare, disease prevention and health promotion setting, respectively.

Conclusions
Based upon this review, a model is proposed integrating medical and public health views of health literacy. The model can serve as a basis for developing health literacy enhancing interventions and provide a conceptual basis for the development and validation of measurement tools, capturing the different dimensions of health literacy within the healthcare, disease prevention and health promotion settings.
Omega-3 polyunsaturated fatty acids enrichment alters performance and immune response in infectious bursal disease challenged broilers
Authors: Maroufyan Elham , Kasim Azhar , Ebrahimi Mahdi , Loh Tech Chwen , Bejo Mohd Hair , Zerihun Hailemariam , Hosseni Fatemeh , Goh Yong Meng , Farjam Abdoreza Soleimani 
Published: January 2012

AbstractBackgroundInfectious bursal disease (IBD) results in economic loss due to mortality, reduction in production efficiency and increasing the usage of antibiotics. This study was carried out to investigate the modulatory roles of dietaryn-3polyunsaturated fatty acids (PUFA) enrichment in immune response and performance of IBD challenged broiler chickens.MethodsA total of 300 day old male broiler chicks were assigned to four dietaryn-3PUFA ascending levels as the treatment groups (T1: 0.5; T2: 8.0; T3: 11.5; T4: 16.5) using combinations of tuna oil and sunflower oil. All diets were isocaloric and isonitrogenous. On day 28, all birds were challenged with IBD virus. Antibody titer, cytokine production, bursa lesion pre and post-challenge and lymphoid organ weight were recorded.ResultsOn d 42 the highest body weight was observed in the T2 and T3 and the lowest in T4 chickens. Feed conversion ratio of the T2 broilers was significantly better than the other groups. Although productive parameters were not responded to the dietary n-3 PUFA in a dose-dependent manner, spleen weight, IBD and Newcastle disease antibody titers and IL-2 and IFN-γ concentrations were constantly elevated by n-3 PUFA enrichment.ConclusionsDietary n-3 PUFA enrichment may improve the immune response and IBD resistance, but the optimum performance does not coincide with the optimum immune response. It seems that dietary n-3 PUFA modulates the broiler chicken performance and immune response in a dose-dependent manner. Thus, a moderate level of dietary n-3 PUFA enrichment may help to put together the efficiency of performance and relative immune response enhancement in broiler chickens.
Induction of ebolavirus cross-species immunity using retrovirus-like particles bearing the Ebola virus glycoprotein lacking the mucin-like domain
Authors: Ou Wu , Delisle Josie , Jacques Jerome , Shih Joanna , Price Graeme , Kuhn Jens H , Wang Vivian , Verthelyi Daniela , Kaplan Gerardo , Wilson Carolyn A 
Published: January 2012

AbstractBackgroundThe genusEbolavirusincludes five distinct viruses. Four of these viruses cause hemorrhagic fever in humans. Currently there are no licensed vaccines for any of them; however, several vaccines are under development. Ebola virus envelope glycoprotein (GP1,2) is highly immunogenic, but antibodies frequently arise against its least conserved mucin-like domain (MLD). We hypothesized that immunization with MLD-deleted GP1,2(GPΔMLD) would induce cross-species immunity by making more conserved regions accessible to the immune system.MethodsTo test this hypothesis, mice were immunized with retrovirus-like particles (retroVLPs) bearing Ebola virus GPΔMLD, DNA plasmids (plasmo-retroVLP) that can produce such retroVLPsin vivo, or plasmo-retroVLP followed by retroVLPs.ResultsCross-species neutralizing antibody and GP1,2-specific cellular immune responses were successfully induced.ConclusionOur findings suggest that GPΔMLD presented through retroVLPs may provide a strategy for development of a vaccine against multiple ebolaviruses. Similar vaccination strategies may be adopted for other viruses whose envelope proteins contain highly variable regions that may mask more conserved domains from the immune system.
Translation and validation of the German version of the Bournemouth Questionnaire for Neck Pain
Authors: Soklic Marina , Peterson Cynthia , Humphreys B Kim 
Published: January 2012

Abstract

Background
Clinical outcome measures are important tools to monitor patient improvement during treatment as well as to document changes for research purposes. The short-form Bournemouth questionnaire for neck pain patients (BQN) was developed from the biopsychosocial model and measures pain, disability, cognitive and affective domains. It has been shown to be a valid and reliable outcome measure in English, French and Dutch and more sensitive to change compared to other questionnaires. The purpose of this study was to translate and validate a German version of the Bournemouth questionnaire for neck pain patients.

Methods
German translation and back translation into English of the BQN was done independently by four persons and overseen by an expert committee. Face validity of the German BQN was tested on 30 neck pain patients in a single chiropractic practice. Test-retest reliability was evaluated on 31 medical students and chiropractors before and after a lecture. The German BQN was then assessed on 102 first time neck pain patients at two chiropractic practices for internal consistency, external construct validity, external longitudinal construct validity and sensitivity to change compared to the German versions of the Neck Disability Index (NDI) and the Neck Pain and Disability Scale (NPAD).

Results
Face validity testing lead to minor changes to the German BQN. The Intraclass Correlation Coefficient for the test-retest reliability was 0.99. The internal consistency was strong for all 7 items of the BQN with Cronbach α's of .79 and .80 for the pre and post-treatment total scores. External construct validity and external longitudinal construct validity using Pearson's correlation coefficient showed statistically significant correlations for all 7 scales of the BQN with the other questionnaires. The German BQN showed greater responsiveness compared to the other questionnaires for all scales.

Conclusions
The German BQN is a valid and reliable outcome measure that has been successfully translated and culturally adapted. It is shorter, easier to use, and more responsive to change than the NDI and NPAD.
Predicting the physiological performance of ectotherms in fluctuating thermal environments
Authors: Niehaus Amanda C. , Angilletta Michael J. , Sears Michael W. , Franklin Craig E. , Wilson Robbie S. 
Published: January 2012

SUMMARYPhysiological ecologists have long sought to understand the plasticity of organisms in environments that vary widely among years, seasons and even hours. This is now even more important because human-induced climate change is predicted to affect both the mean and variability of the thermal environment. Although environmental change occurs ubiquitously, relatively few researchers have studied the effects of fluctuating environments on the performance of developing organisms. Even fewer have tried to validate a framework for predicting performance in fluctuating environments. Here, we determined whether reaction norms based on performance at constant temperatures (18, 22, 26, 30 and 34°C) could be used to predict embryonic and larval performance of anurans at fluctuating temperatures (18–28°C and 18–34°C). Based on existing theory, we generated hypotheses about the effects of stress and acclimation on the predictability of performance in variable environments. Our empirical models poorly predicted the performance of striped marsh frogs (Limnodynastes peronii) at fluctuating temperatures, suggesting that extrapolation from studies conducted under artificial thermal conditions would lead to erroneous conclusions. During the majority of ontogenetic stages, growth and development in variable environments proceeded more rapidly than expected, suggesting that acute exposures to extreme temperatures enable greater performance than do chronic exposures. Consistent with theory, we predicted performance more accurately for the less variable thermal environment. Our results underscore the need to measure physiological performance under naturalistic thermal conditions when testing hypotheses about thermal plasticity or when parameterizing models of life-history evolution.
Characterisation of chemosensory trigeminal receptors in the rainbow trout,Oncorhynchus mykiss: responses to chemical irritants and carbon dioxide
Authors: Mettam Jessica J. , McCrohan Catherine R. , Sneddon Lynne U. 
Published: January 2012

SUMMARYTrigeminally innervated, mechanically sensitive chemoreceptors (M) were previously identified in rainbow trout, Oncorhynchus mykiss, but it is not known whether these receptors are responsive only to noxious, chemical irritants or have a general chemosensory function. This study aimed to characterise the stimulus–response properties of these receptors in comparison with polymodal nociceptors (P). Both P and M gave similar response profiles to acetic acid concentrations. The electrophysiological properties were similar between the two different afferent types. To determine whether the receptors have a nociceptive function, a range of chemical stimulants was applied to these receptors, including non-noxious stimuli such as ammonium chloride, bile, sodium bicarbonate and alarm pheromone, and potentially noxious chemical irritants such as acetic acid, carbon dioxide, low pH, citric acid, citric acid phosphate buffer and sodium chloride. Only irritant stimuli evoked a response, confirming their nociceptive function. All receptor afferents tested responded to carbon dioxide (CO2) in the form of mineral water or soda water. The majority responded to 1% acetic acid, 2% citric acid, citric acid phosphate buffer (pH 3) and 5.0 mol l–1 NaCl. CO2 receptors have been characterised in the orobranchial cavity and gill arches in fish; however, this is the first time that external CO2 receptors have been identified on the head of a fish. Because the fish skin is in constant contact with the aqueous environment, contaminants with a low pH or hypercapnia may stimulate the nociceptive system in fish.
Establishing food site vectors in desert ants
Authors: Bolek Siegfried , Wittlinger Matthias , Wolf Harald 
Published: January 2012

SUMMARY
When returning to the site of a successful previous forage, where does one search for the goodies? Should one rely on experience from the previous homebound journey, or should one consider the outbound journey as well, or even exclusively? Desert ants are particularly well suited for pursuing this question because of their primary reliance on path integration in open and featureless desert habitats. Path integration has been studied particularly with regard to homing after lengthy foraging trips. The ants also use path integration to return to plentiful feeding sites, but what is memorised for revisiting the feeder remains controversial. Here, we demonstrate that desert ants consider, and indeed linearly average, both outbound and inbound travel for their return to a familiar feeder. This may be interpreted as a strategy to reduce navigation errors.