bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Promise of a Personalized Genomic Approach to Pancreatic Cancer and Why Targeted Therapies Have Missed the Mark
Authors: Fisher William E. 
Published: January 2011

AbstractPancreatic cancer (PC) carries the highest mortality rate of any cancer type. Although minor advances in chemotherapy have been made, the mortality rate has remained the same over the last several decades. Clinical trials examining therapies targeting the epidermal growth factor (EGFR), vascular endothelial growth factor (VEGF), specific mutated proteins such as K‐ras, immunotherapy employing tumor‐associated antigens, and biologic therapy such as TNFerade (GenVec, Inc., Gaithersburg, MD) have all failed to substantially improve survival. Pancreatic cancer is likely a heterogeneous disease; therefore, a personalized genomic approach offers the possibility to tailor treatment to the unique characteristics of individual patients and their tumors. Rapid advances in sequencing technology are decreasing the time and cost of obtaining this information to a clinically useful level. However, many challenges remain to be faced in applying this technology in the field of PC. Even if patients with PC could be identified early in the course of the disease, localizing the disease and treating it in a minimally invasive fashion will remain problematic. Ethical issues including patient discrimination and access to care will be particularly important in PC. As the field advances, validation, education of clinicians, and determining the true value and source of funding will be difficult. Although the era of personalized genomic medicine has arrived, it will certainly take many years to begin to realize its potential. It is to be hoped that this new approach will result in a significant improvement in the survival curve for patients with PC.
Roles and Mechanisms of MicroRNAs in Pancreatic Cancer
Authors: Zhang Lidong , Jamaluddin Md Saha , Weakley Sarah M. , Yao Qizhi , Chen Changyi 
Published: January 2011

AbstractPancreatic cancer (PC) is an aggressive malignancy with poor survival. The discovery of microRNAs (miRNAs) has provided a new opportunity to study the disease. Thus far, altered expression of miRNAs has been reported in a wide range of malignancies, including PC, and some miRNAs are associated with PC cell proliferation, invasion, chemoresistance, and patient survival. This review summarizes recent advances with respect to the roles and mechanisms of miRNAs in PC and discusses potential clinical applications.
Greater than the Sum of their Parts: The benefits of Youth Violence Prevention Centers
Authors: Azrael Deborah , Hemenway David 
Published: January 2011

AbstractAcademic Centers for Excellence on Youth Violence Prevention (ACE), which support a broad range of activities over and above RO1‐type research projects, can add significantly to a community's capacity to respond to youth violence. We use the example of the Harvard Youth Violence Prevention Center to describe the types of research‐practice collaborations these centers can promote, as well as the ways in which these collaborations can foster adoption of program planning, development, implementation and evaluation practices consistent with evidence‐based approaches to youth violence prevention. Throughout, we describe the ways in which the existence of a center led, under the ACE format, to research, policy and practice opportunities that would not have existed in the absence of a center.
The GAMY Project: young people’s attitudes to genetics in the South Wales valleys
Authors: Iredale Rachel , Madden Kim , Taverner Nicola , Yu Juping , McDonald Kevin 
Published: January 2011

Abstract
This paper explores young people’s attitudes to genetics. It describes a qualitative study involving a group of teenagers in a deprived South Wales valley town over a period of 18 months. The GAMY (Genetics and Merthyr Youth) Project involved a series of interactions with participants, including 2 interviews, 4 group days and 4 genetics tasks through which these young people learned about, and then reflected upon, issues relating to genetics and health. We have gathered data about the informed attitudes of teenagers to genetics based on deliberative learning and reflection over a long period of time, and as such this paper provides useful insights into the underlying values that are guiding young people’s views and the factors that are shaping their responses to new genetic technologies. Attitudes to genetics are complex and not easily generalisable. There were low levels of familiarity with, and knowledge of, genetics from the outset. Most young people did not have pre-existing attitudes towards genetics and had given little or no thought to the topic before the project began. However, levels of awareness and general genetic literacy increased as the project progressed. This study suggests that over time young people can develop an awareness of genetics that makes sense to them; they demonstrate that they can think creatively about genetics, and they are able to engage in considering genetic and other risk factors when thinking about health and disease.
A randomised double-blind placebo-controlled trial with Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis BB-12 for maintenance of remission in ulcerative colitis
Authors: Wildt Signe , Nordgaard Inge , Hansen Ulla , Brockmann Elke , Rumessen Jüri J. 
Published: January 2011

Abstract
Background and aims: To investigate the clinical effect of treatment with Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis BB-12 (Probio-Tec AB-25) to maintain remission in patients with ulcerative colitis.
Methods: Patients with left-sided ulcerative colitis in remission — including proctitis and at least one relapse within the last year were randomised (2:1) in a double-blind placebo-controlled study to Probio-Tec AB-25 or placebo for 52 weeks. The patients were evaluated clinically, endoscopically and histologically at entry and if relapsing. No other medication for ulcerative colitis than the study drug was allowed during the study. Primary endpoint was maintenance of clinical remission, secondary endpoints comparisons of days to relapse, and safety and tolerability of the study drug. The concentrations of the probiotic bacterial strains in stool were analysed in a subset of patients.
Results: Thirty-two patients were randomised. Twenty patients received Probio-Tec AB-25 and twelve patients received placebo. Five patients (25%) in the Probio-Tec AB-25 group and one patient (8%) in the placebo group maintained remission after 1 year of treatment (p = 0.37). The median time to relapse was 125.5 days (range 11–391 days) in the probiotic group and 104 days (range 28–369 days) in the placebo group respectively, (p = 0.683). Probio-Tec AB-25 was overall well tolerated.
Conclusions: In this small randomised placebo-controlled trial no significant clinical benefit of Probio-Tec AB-25 could be demonstrated in comparison with placebo for maintaining remission in patients with left-sided ulcerative colitis. A difference may be achieved in larger studies, but the clinical significance of this would be questionable. This study was registered in ClinicalTrial.gov (NCT00268164).
Preliminary findings from an Internet‐based dementia risk assessment
Authors: Brandt Jason , Rogerson Mark 
Published: January 2011

BackgroundThe identification of individuals who are at high risk of dementia may lead to earlier detection and diagnosis. In this study, we describe the development and preliminary validation of a very brief, Internet‐based risk assessment tool.MethodsThe Dementia Risk Assessment collected information on demographic, neurologic, and medical risk factors; perceived cognitive functioning; and emotional symptoms. Participants answered questions pertaining to themselves (“patient page”) or to a relative or friend (“proxy page”). Patients also completed a novel short‐delayed recognition memory test. Subjects received personalized feedback about their risk factors and were advised to seek clinical evaluation for concerning symptoms. By November 2009, 500 respondents completed the patient page.ResultsThe 352 respondents aged 50 years or older (M = 62 years) included a high percentage of women (72%) and college graduates (67%). Among the respondents, only 10% complained of having severe memory problems, whereas 38% reported having a first‐degree relative who experienced severe memory loss. The prevalence of major neurologic risk factors was low. Although the delay interval for the recognition memory test averaged around 2 minutes, there was sufficient variability in performance. Individuals with scores ≤10th percentile were significantly older and more likely to be men, have hypertension, and report having severe memory problems.ConclusionsHistory of major dementia risk factors can be ascertained through the Internet, and several of these factors are shown to be moderately predictive of performance on a brief test of episodic memory. These data provide preliminary validation of the Dementia Risk Assessment for identifying current cognitive impairment, and suggest its potential for assessing future dementia risk. Ongoing studies will further establish the validity of these findings against proxy reports of cognitive and functional decline, the results of more detailed cognitive assessments, and formal clinical diagnoses.
The economic costs of extreme weather events: a hydrometeorological CGE analysis for Malawi
Authors: PAUW KARL , THURLOW JAMES , BACHU MURTHY , VAN SEVENTER DIRK ERNST 
Published: January 2011

ABSTRACTExtreme weather events such as droughts and floods have potentially damaging implications for developing countries. Previous studies have estimated economic losses during hypothetical or single historical events, and have relied on historical production data rather than explicitly modeling climate. However, effective mitigation strategies require knowledge of the full distribution of weather events and their isolated effects on economic outcomes. We combine stochastic hydrometeorological crop-loss models with a regionalized computable general equilibrium model to estimate losses for the full distribution of possible weather events in Malawi. Results indicate that, based on repeated sampling from historical events, at least 1.7 per cent of Malawi's gross domestic product (GDP) is lost each year due to the combined effects of droughts and floods. Smaller-scale farmers in the southern region of the country are worst affected. However, poverty among urban and nonfarm households also increases due to national food shortages and higher domestic prices.
The role of fungi in mediating ecosystem responses to global change
Authors: Treseder Kathleen 
Published: January 2011

Abstract
Background/Question/Methods
In this synthesis of published studies, we address two global change scenarios (global warming and anthropogenic N deposition) in which fungi can form feedbacks on carbon cycling that are counterintuitive to prevailing predictions and models. In each case, a consideration of fungal ecology, physiology, or evolutionary constraints could lead to changes in the sign or magnitude of carbon storage within soils, compared to current predictions. In the case of global warming, the majority of global carbon models that address this issue are parameterized so that decomposition rates increase in response to warming, and that this increase is sustained in the long-term. Indeed, the majority of field studies have confirmed this response, at least within the first years after onset of warming. Nevertheless, longer-term studies have reported reductions in the warming effect over time. One mechanism for this decline is thermal adaptation of fungal communities, in which mass-specific respiration rates decrease following long-term exposure to warming, possibly owing to changes in efficiencies of enzymes. In addition, evolutionary trade-offs could reduce the ability of warming-adapted strains to use particular carbon substrates or to tolerate drier conditions that often coincide with warming. In respect to N deposition, recent coupled C-N models either (1) allow inorganic N availability to increase decomposition rates overall, or (2) do not include a direct effect of N availability on decomposition. However, meta-analyses indicate that microbes typically become less abundant following N enrichment, with corresponding reductions in respiration rates. In addition, turnover rates of recalcitrant material can decrease. These declines in microbial abundance and activity could result from sensitivity of microbial taxa (particularly white rot fungi) to toxins produced via “browning” of organic compounds by nitrogenous compounds. Moreover, mycorrhizal fungi decrease under N enrichment owing to reduction in investments by host plants. Any decomposition of soil organic matter by mycorrhizal fungi could likewise be reduced.

Results/Conclusions
Microbial ecologists can support the efforts of modelers by examining and quantifying relevant microbial mechanisms that provide feedbacks on global change, especially if these feedbacks are counter-intuitive. For large-scale models, global syntheses of empirical data would be especially valuable in determining the extent of these feedbacks.*The audio track for talks in this symposium may be obtained at the following web address:**https://sites.google.com/site/esa2010symposium13audiocontent/esa2010-symposium13-audio-content*
Patterns in soil ammonia-oxidizer response to global change
Authors: Docherty Kathryn , Bohannan Brendan , Niboyet Audrey , LeRoux Xavier 
Published: January 2011

Abstract
Background/Question/Methods
The Domains Archaea and Bacteria contain the vast majority of Earth’s biodiversity and biomass, and their members play critical, often exclusive, roles in many biogeochemical cycles and ecosystem services. Human-induced global change, particularly with respect to increased nitrogen deposition, has the potential to drastically alter how soil nitrifying communities perform their biogeochemical function. Additionally, multi-factor global change can alter how microbial communities interact with each other and with the associated plant communities. This study, performed in the context of the long-term Jasper Ridge Global Change Experiment (JRGCE) in a California grassland ecosystem, examines how ammonia-oxidizing Archaea and Bacteria (AOA and AOB, respectively) respond to multi-factor global change. Manipulations at the JRGCE include simultaneous increases in CO2, warming, precipitation and nitrogen deposition. Past studies have utilized DNA-fingerprinting methods to assess ammonia-oxidizer response to multi-factor global change. This study compares how seed bank (DNA-based) versus metabolically active (RNA-based) ammonia-oxidizing communities respond to global change manipulations over several seasons. We have employed ultra-deep 454-pyrosequencing techniques to examine these communities using the ammonia monooxygenase (amoA) functional gene marker. Effects of global change have been examined at several phylogenetic levels and linked this community information to gross rates of nitrification using 15N stable isotopic methods. Ammonia-oxidizer and plant communities have been compared using multivariate statistical methods.

Results/Conclusions
Our results show that both AOB and AOA communities are highly influenced by nitrogen deposition in both their abundance and community structure. These changes are linked to increased nitrification rate in the elevated nitrogen deposition plots. Our results further show that the relationship between the AOB and plant communities fundamentally changes under long-term nitrogen deposition manipulation. This positive feedback loop may enhance the rate of change in ammonia-oxidizer communities, which may further elevate nitrification rates. This study provides strong evidence that incorporating microbial community and abundance information into global change predictions is crucial for understanding how ecosystem-level nutrient cycling rates may change.*The audio track for talks in this symposium may be obtained at the following web address:**https://sites.google.com/site/esa2010symposium13audiocontent/esa2010-symposium13-audio-content*
Targeted Assembly of Short Sequence Reads
Authors: Warren Rene , Holt Robert 
Published: January 2011

AbstractAs next-generation sequence (NGS) production continues to increase, analysis is becoming a significant bottleneck. However, in situations where information is required only for specific sequence variants, it is not necessary to assemble or align whole genome data sets in their entirety. Rather, NGS data sets can be mined for the presence of sequence variants of interest by localized assembly, which is a faster, easier, and more accurate approach. We present TASR, a streamlined assembler that interrogates very large NGS data sets for the presence of specific variants, by only considering reads within the sequence space of input target sequences provided by the user. The NGS data set is searched for reads with an exact match to all possible short words within the target sequence, and these reads are then assembled strin-gently to generate a consensus of the target and flanking sequence. Typically, variants of a particular locus are provided as different target sequences, and the presence of the variant in the data set being interrogated is revealed by a successful assembly outcome. However, TASR can also be used to find unknown sequences that flank a given target. We demonstrate that TASR has utility in finding or confirming ge-nomic mutations, polymorphism, fusion and integration events. Targeted assembly is a powerful method for interrogating large data sets for the presence of sequence variants of interest. TASR is a fast, flexible and easy to use tool for targeted assembly.
Comparative theoretical investigation on the isomerization energies of long-chain perfluoroalkanes: A case study with perfluorooctanoic acid congeners
Authors: Rayne Sierra , Forest Kaya 
Published: January 2011

AbstractThe gas and solution phase relative thermodynamic stabilities of the 39 linear and branched perfluorooctanoic acid (PFOA) congeners in both their acid and anionic forms were calculated at various levels of density functional (B3LYP, wB97XD, and M062X functionals with the 6-311++G(d,p) basis set) and second order Moller-Plesset perturbation (MP2/6-311++G(d,p)//B3LYP/6-311++G(d,p)) theory using the SMD implicit solvation model. The B3LYP functional does not accurately model the expected trends in thermodynamic stability of PFOA isomers with linear versus branched perfluoroalkyl chains. Calculations obtained with the M062X and MP2 model chemistries suggest these theoretical methods may be more appropriate for relative thermodynamic stability studies on various perfluoroalkyl compounds.
PECAn: workflow management for data assimilation and forecasting
Authors: LeBauer David , Wang Dan , Feng Xiaohui , Dietze Michael 
Published: January 2011

Abstract
Background/Question/Methods
Ecosystem models use physiological traits and environmental data to model land-air carbon exchange. Such models can integrate heterogeneous ecological and environmental data, but rarely account for the contribution of each input to the overall uncertainty in model output. Quantifying uncertainty in each model input and propagating uncertainty through model ensembles directly estimates overall uncertainty in model output. Identification of data that would most effectively constrain uncertainty can also be directly inferred by processing output. Real-time data assimilation and forecasting benefits from a method that is transparent, scalable, and adaptable. A tool that manages these steps while tracking the provenance of data inputs, model parameters, output, and post-processing would facilitate evaluation, reproducibility, and adaptation of the workflow.

Results/Conclusions
We present such a workflow management tool, the Predictive Ecophysiological Carbon flux Analyzer (PECAn). PECAn is an open source utility that encapsulates 1) acquisition of meteorological inputs, 2) synthesis of physiological trait data as the posterior distribution of a Bayesian meta-analysis, 3) sampling trait meta-analysis posterior distributions to parameterize ensembles of an ecophysiological model, Ecosystem Demography, version 2 (ED2), 4) probabilistic forecasts,5) postprocessing to constrain forecasts and model parameters with field, meterological, eddy flux, and spectral data, and 6) provenance tracking. This system provides a detailed analysis of the past and present ecosystem functioning that seamlessly transitions into forecasts. We demonstrate an application of PECAn to an intensively monitored and data-rich plot of a perennial biofuel crop, switchgrass (Panicum virgatum). This particular context will be used to highlight PECAn's general utility to support model-data integration, ecological research, and decision support.
In Situ Production of Prebiotic AXOS by Hyperthermophilic Xylanase B from Thermotoga maritima in High‐Quality Bread
Authors: Dornez Emmie , Verjans Priscilla , Broekaert Willem F. , Cappuyns Astrid M. , Van Impe Jan F. , Arnaut Filip , Delcour Jan A. , Courtin Christophe M. 
Published: January 2011

ABSTRACTIn situ enrichment of bread with arabinoxylan‐oligosaccharides (AXOS) through enzymic degradation of wheat flour arabinoxylan (AX) by the hyperthermophilic xylanase B from Thermotoga maritima (rXTMB) was studied. The xylanolytic activity of rXTMB during breadmaking was essentially restricted to the baking phase. This prevented problems with dough processability and bread quality that generally are associated with thorough hydrolysis of the flour AX during dough mixing and fermentation. rXTMB action did not affect loaf volume. Bread with a dry matter AXOS content of 1.5% was obtained. Further increase in bread AXOS levels was achieved by combining rXTMB with xylanases from Pseudoalteromonas haloplanktis or Bacillus subtilis. Remarkably, such a combination synergistically increased the specific bread loaf volume. Assuming an average daily consumption of 180 g of fresh bread, the bread AXOS levels suffice to provide a substantial part of the AXOS intake leading to desired physiological effects in humans.
Cytological changes induced by embolization in meningiomas
Authors: Jiménez‐Heffernan J. A. , Corbacho C. , Cañizal J. M. , Pérez‐Campos A. , Vicandi B. , López‐Ibor L. , Viguer J. M. 
Published: January 2011

J. A. Jiménez‐Heffernan, C. Corbacho, J. M. Cañizal, A. Pérez‐Campos, B. Vicandi, L. López‐Ibor and J. M. Viguer  Cytological changes induced by embolization in meningiomasObjective:  To describe cytological changes in meningiomas induced by embolization, which may be carried out a few days before surgery in order to soften the tumour and minimize intraoperative bleeding. Although histological changes have been described, we have found no description of such changes in the cytological literature.Methods:  We reviewed 22 cases of meningiomas with prior embolization in which cytological material was obtained during intraoperative consultation. In 13 of them recognizable cytological changes induced by embolization were present. On histology, these 13 tumours were grade I and showed intravascular embolic material.Results:  Cellular dissociation was prominent, with frequent single cells and small groups. Ischaemic cellular changes were a common finding and consisted of cell shrinkage, nuclear pyknosis and karyorrhexis. Confluent areas of necrosis were seen in one case. Additionally, numerous macrophages were present, many containing cellular debris, and neutrophils, giving a characteristic appearance of acute cellular ischaemia. Embolic material was seen cytologically in four cases as well‐defined spherules surrounded by empty halos. Features of viable meningioma were recognized in all cases.Conclusion:  Embolization of meningiomas induces cytological changes that mirror those seen on histology, but cellular dissociation with changes of ischaemia may result in a worrisome image. When faced with such changes the pathologist should consider the possibility of embolization, avoiding misdiagnosis of higher grade meningioma or metastatic carcinoma.