bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic rather than genetic factors may explain phenotypic divergence between coastal populations of diploid and tetraploid Limonium spp. (Plumbaginaceae) in Portugal
Authors: Róis Ana Sofia , Rodríguez López Carlos M , Cortinhas Ana , Erben Matthias , Espírito-Santo Dalila , Wilkinson Michael J , Caperta Ana D 
Published: December 2013

AbstractBackgroundThe genusLimoniumMiller comprises annual and perennial halophytes that can produce sexual and/or asexual seeds (apomixis). Genetic and epigenetic (DNA methylation) variation patterns were investigated in populations of three phenotypically similar putative sexual diploid species (L. nydeggeri, L. ovalifolium,L. lanceolatum), one sexual tetraploid species (L. vulgare) and two apomict tetraploid species thought to be related (L. dodartii, L. multiflorum). The extent of morphological differentiation between these species was assessed using ten diagnostic morphometric characters.ResultsA discriminant analysis using the morphometric variables reliably assigns individuals into their respective species groups. We found that only modest genetic and epigenetic differentiation was revealed between species by Methylation Sensitive Amplification Polymorphism (MSAP). However, whilst there was little separation possible between ploidy levels on the basis of genetic profiles, there was clear and pronounced interploidy discrimination on the basis of epigenetic profiles. Here we investigate the relative contribution of genetic and epigenetic factors in explaining the complex phenotypic variability seen in problematic taxonomic groups such asLimoniumthat operate both apomixis and sexual modes of reproduction.ConclusionsOur results suggest that epigenetic variation might be one of the drivers of the phenotypic divergence between diploid and tetraploidtaxaand discuss that intergenome silencing offers a plausible mechanistic explanation for the observed phenotypic divergence between these microspecies. These results also suggest that epigenetic profiling offer an additional tool to infer ploidy level in stored specimens and that stable epigenetic change may play an important role in apomict evolution and species recognition.
Role of serotonin in fatty acid-induced non-alcoholic fatty liver disease in mice
Authors: Ritze Yvonne , Böhle Maureen , Haub Synia , Hubert Astrid , Enck Paul , Zipfel Stephan , Bischoff Stephan C 
Published: December 2013

Abstract

Background
Saturated fatty acids are thought to be of relevance for the development of non-alcoholic fatty liver disease and obesity. However, the underlying mechanisms are poorly understood. In previous studies we found that food-derived carbohydrates such as fructose alter the intestinal serotonergic system while inducing fatty liver disease in mice. Here, we examined the effect of fatty acid quantity (11% versus 15%) and quality (saturated, monounsaturated, or polyunsaturated fatty acids) on hepatic fat accumulation, intestinal barrier and the intestinal serotonergic system.

Methods
C57BL/6 mice had free access to diets enriched with one of the three fatty acids or standard diet, for 8 weeks. In an additional experiment mice were fed diets enriched with saturated, monounsaturated fatty acids or standard diet supplemented with tryptophan (0.4 g/(kg.d), 8 weeks) or not. Hepatic fat accumulation, small intestinal barrier impairment and components of the serotonergic system were measured with RT-PCR, western blot or immunoassays. For statistical analysis t-test and one-way ANOVA with Tukey’s post hoc test and Bartlett’s test for equal variances was used.

Results
Hepatic triglycerides, liver weight and liver to body weight ratio were significantly changed depending on the fat quality but not fat quantity. In contrast, fat quantity but not quality decreased the expression of the tight junction proteins occludin and claudin-1 in the small intestine. These changes seemed to result in enhanced portal vein endotoxin concentrations and fatty liver disease after feeding diet enriched with saturated and monounsaturated fatty acids but not polyunsaturated fatty acids. Neither fatty acid quantity nor quality significantly influenced the intestinal serotonergic system. Similarly, tryptophan supplementation had no impact on small intestinal barrier or fatty liver disease.

Conclusion
In conclusion, diets rich in saturated or monounsaturated fatty acids promote the development of fatty liver disease in mice, likely by a dysfunction of the small intestinal mucosal barrier.
Sex differences in circumstances and consequences of outdoor and indoor falls in older adults in the MOBILIZE Boston cohort study
Authors: Duckham Rachel L , Procter-Gray Elizabeth , Hannan Marian T , Leveille Suzanne G , Lipsitz Lewis A , Li Wenjun 
Published: December 2013

AbstractBackgroundDespite extensive research on risk factors associated with falling in older adults, and current fall prevention interventions focusing on modifiable risk factors, there is a lack of detailed accounts of sex differences in risk factors, circumstances and consequences of falls in the literature. We examined the circumstances, consequences and resulting injuries of indoor and outdoor falls according to sex in a population study of older adults.MethodsMen and women 65 years and older (N = 743) were followed for fall events from the Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly (MOBILIZE) Boston prospective cohort study. Baseline measurements were collected by comprehensive clinical assessments, home visits and questionnaires. During the follow-up (median = 2.9 years), participants recorded daily fall occurrences on a monthly calendar, and fall circumstances were determined by a telephone interview. Falls were categorized by activity and place of falling. Circumstance-specific annualized fall rates were calculated and compared between men and women using negative binomial regression models.ResultsWomen had lower rates of outdoor falls overall (Crude Rate Ratio (RR): 0.72, 95% Confidence Interval (CI): 0.56-0.92), in locations of recreation (RR: 0.34, 95% CI: 0.17-0.70), during vigorous activity (RR: 0.38, 95% CI: 0.18-0.81) and on snowy or icy surfaces (RR: 0.55, 95% CI: 0.36-0.86) compared to men. Women and men did not differ significantly in their rates of falls outdoors on sidewalks, streets, and curbs, and during walking. Compared to men, women had greater fall rates in the kitchen (RR: 1.88, 95% CI: 1.04-3.40) and while performing household activities (RR: 3.68, 95% CI: 1.50-8.98). The injurious outdoor fall rates were equivalent in both sexes. Women’s overall rate of injurious indoor falls was nearly twice that of men’s (RR: 1.98, 95% CI: 1.44-2.72), especially in the kitchen (RR: 6.83, 95% CI: 2.05-22.79), their own home (RR: 1.84, 95% CI: 1.30-2.59) and another residential home (RR: 4.65, 95% CI: 1.05-20.66) or other buildings (RR: 2.29, 95% CI: 1.18-4.44).ConclusionsSignificant sex differences exist in the circumstances and injury potential when older adults fall indoors and outdoors, highlighting a need for focused prevention strategies for men and women.
S-1 combined with docetaxel following doxorubicin plus cyclophosphamide as neoadjuvant therapy in breast cancer: phase II trial
Authors: Moon Yong Wha , Lee Soohyeon , Park Byeong-Woo , Kim Eun-Kyung , Kim Seung Il , Koo Ja Seung , Park Seho , Kim Min Jung , Chung Hyun Cheol , Kim Joo-Hang , Sohn Joohyuk 
Published: December 2013

Abstract

Background
This study evaluated the efficacy and safety of S-1 combined with docetaxel (SD) following doxorubicin plus cyclophosphamide (AC) as neoadjuvant therapy in patients with HER2-negative, stage II-III breast cancer.

Methods
Patients received AC every 3 weeks for four cycles followed by S-1 (30 mg/m2 orally b.i.d. on days 1–14) and docetaxel (75 mg/m2 i.v. on day 1) every 3 weeks for four cycles. The primary endpoint was the pathological complete response (pCR) rate in breast and axillary lymph nodes.

Results
The study included 49 patients with a median age of 43 years. The median breast tumor size was 4.0 cm by palpation. All patients were positive for involvement of axillary lymph node and five patients also had supraclavicular lymph node metastasis, which was confirmed by histological examination. In total, 85.4% of patients (41/49) completed eight cycles of therapy and 95.9% of patients (47/49) received curative surgery. The pCR rate was 22.5% (n = 11). The clinical response rate was 67.4%. During SD chemotherapy, the most frequent grade 3–4 toxicity was neutropenia (8.5% by cycle). There was a single treatment-related mortality from severe neutropenia. Grade 3 S-1 specific toxicities such as epigastric pain (12.2% by person), stomatitis (4.1% by person), and diarrhea (2.0% by person) were also observed. In particular, gastrointestinal discomfort led to dose reduction of S-1 in 45.8% of patients.

Conclusions
Given all axillary lymph node positive diseases, neoadjuvant S-1 combined with docetaxel following AC showed a favorable anti-tumor activity but gastrointestinal discomfort should be carefully considered for future studies.

Trial registration

NCT00994968
Robust c-prototypes algorithms for color image segmentation
Authors: Mújica-Vargas Dante , Gallegos-Funes Francisco J , Rosales-Silva Alberto J , de Jesús Rubio José 
Published: December 2013

Abstract
In this paper, we present a modified clustering algorithm to segment color images. The proposed technique is based on the robust c-prototypes algorithm with some modifications in its objective function and updating equations. The JK chromatic subspace of the IJK color space is used to segment color images. The algorithm performance is tested on real images with natural artifacts that make the segmentation process difficult. Additionally, a remote sensing image is segmented to demonstrate that the proposed algorithm can be used in real applications. Simulation results indicate that the proposed method is more effective than others proposed in the literature in terms of objective and subjective criteria.
Diagram-based Analysis of Causal Systems (DACS): elucidating inter-relationships between determinants of acute lower respiratory infections among children in sub-Saharan Africa
Authors: Rehfuess Eva A , Best Nicky , Briggs David J , Joffe Mike 
Published: December 2013

Abstract
Background
Effective interventions require evidence on how individual causal pathways jointly determine disease. Based on the concept of systems epidemiology, this paper develops Diagram-based Analysis of Causal Systems (DACS) as an approach to analyze complex systems, and applies it by examining the contributions of proximal and distal determinants of childhood acute lower respiratory infections (ALRI) in sub-Saharan Africa.

Results
Diagram-based Analysis of Causal Systems combines the use of causal diagrams with multiple routinely available data sources, using a variety of statistical techniques. In a step-by-step process, the causal diagram evolves from conceptual based on a priori knowledge and assumptions, through operational informed by data availability which then undergoes empirical testing, to integrated which synthesizes information from multiple datasets. In our application, we apply different regression techniques to Demographic and Health Survey (DHS) datasets for Benin, Ethiopia, Kenya and Namibia and a pooled World Health Survey (WHS) dataset for sixteen African countries. Explicit strategies are employed to make decisions transparent about the inclusion/omission of arrows, the sign and strength of the relationships and homogeneity/heterogeneity across settings.
Findings about the current state of evidence on the complex web of socio-economic, environmental, behavioral and healthcare factors influencing childhood ALRI, based on DHS and WHS data, are summarized in an integrated causal diagram. Notably, solid fuel use is structured by socio-economic factors and increases the risk of childhood ALRI mortality.

Conclusions
Diagram-based Analysis of Causal Systems is a means of organizing the current state of knowledge about a specific area of research, and a framework for integrating statistical analyses across a whole system. This partly a priori approach is explicit about causal assumptions guiding the analysis and about researcher judgment, and wrong assumptions can be reversed following empirical testing. This approach is well-suited to dealing with complex systems, in particular where data are scarce.
Accessibility evaluation system for site layout planning – a tractor trailer example
Authors: Lin Jacob Je-Chian , Yang Chi-En , Hung Wei-Han , Kang Shih-Chung 
Published: December 2013

Abstract

Background
Accessibility is a critical issue in site planning. A good accessibility plan can avoid possible conflicts involving equipment and allows for smooth transportation during the entire project. It can also ensure that sufficient space is available so that all onsite equipment, such as trucks, cranes and excavators can be safely operated. In current practice, the evaluation of accessibility is done manually, relying heavily on the experience of the construction planners. However, the evaluation needs to deal with temporal and spatial information simultaneously, which make the manual evaluations very challenging.

Methods
This research develops a sandbox environment for construction planners. As tractor-trailers are usually critical in accessibility evaluations, the simulation specifically focuses on these two-section vehicles. Four major steps were involved: Step 1: deriving a generic tractor-trailer mathematical model allowing real-time, physics-based computer simulation; Step 2: digitalizing a 2D site plan to the 3D virtual environment; Step 3: developing evaluation methods for accessibility, considering both safety and operability; Step 4: visualizing the evaluation results. We implemented these four steps using Microsoft XNA (a game platform) and Nvidia PhysX (a game engine). An example case is presented which uses the sandbox environment to evaluate the accessibility of a construction site.

Results
From the case study, we found that realistic visualizations and simulations provide solid references for construction planners. They are able to identify potential accessibility problems and unsafe situations in the sandbox environment and avoid them early on in the design and planning stages.

Conclusion
This paper proposed an innovative approach for evaluating accessibility during pre-construction site layout planning. It can present an intuitive and easily understood visualization result which clearly indicated the unsafe parts of the site layout plan.
Serum level of adiponectin is a surrogate independent biomarker of radiographic disease progression in early rheumatoid arthritis: results from the ESPOIR cohort
Authors: Meyer Magali , Sellam Jérémie , Fellahi Soraya , Kotti Salma , Bastard Jean-Philippe , Meyer Olivier , Lioté Frédéric , Simon Tabassome , Capeau Jacqueline , Berenbaum Francis 
Published: December 2013

Abstract
Introduction
Adipokines such as adiponectin, leptin, and visfatin/nicotinamide phosphoribosyltransferase (NAMPT) have recently emerged as pro-inflammatory mediators involved in the pathophysiology of rheumatoid arthritis (RA). We aimed to determine whether serum adipokine levels independently predicted early radiographic disease progression in early RA.

Methods
In total, 791 patients were included from the prospective Etude et Suivi des POlyarthrites Indifférenciées Récentes (ESPOIR) cohort who met the American College of Rheumatology-European League Against Rheumatism criteria for RA (n = 632) or had undifferentiated arthritis (UA) (n = 159). Enzyme-linked immunosorbent assay (ELISA) was used to assess baseline serum levels of adiponectin, leptin, and visfatin/NAMPT. In the RA group, we tested the association of serum adipokine levels and (a) baseline radiographic damage and (b) radiographic disease progression, defined as a change >0 or ≥5 in total Sharp-van der Heijde Score (∆SHS) between inclusion and 1 year (∆SHS ≥1 or rapid radiographic progression: ∆SHS ≥5), adjusting for confounders (age, sex, body-mass index, insulin resistance, C-reactive protein level, Disease Activity Score in 28 joints, Health Assessment Questionnaire score, autoantibody status, steroid use, and radiographic evidence of RA damage at inclusion).

Results
Adiponectin level was independently associated with baseline total SHS (adjusted β = 0.12; P = 0.006). It was also associated with ∆SHS ≥1 (adjusted odds ratio (aOR) = 1.84 (1.25 to 2.72)) involving erosive as well as narrowing disease progression (aOR = 1.73 (1.17 to 2.55) and 1.93 (1.04 to 3.57), respectively). Serum adiponectin level predicted ∆SHS ≥5 (aOR = 2.0 (1.14 to 3.52)). Serum leptin level was independently associated only with ∆SHS >0 (aOR = 1.59 (1.05 to 2.42)). Conversely, serum visfatin/NAMPT level and radiographic disease progression were unrelated. Considering the receiver-operated characteristic curves, the best adiponectin cut-offs were 4.14 μg/ml for ∆SHS ≥1 and 6.04 μg/ml for ∆SHS ≥5, with a good specificity (58% and 75% for ∆SHS ≥1 and ∆SHS ≥5, respectively) and high negative predictive values (75% and 92% for ∆SHS ≥1 or ∆SHS ≥5, respectively).

Conclusion
Serum adiponectin level is a simple useful biomarker associated with early radiographic disease progression in early RA, independent of RA-confounding factors and metabolic status.
A zebrafish model of chordoma initiated by notochord-driven expression of HRASV12
Authors: Burger Alexa , Vasilyev Aleksandr , Tomar Ritu , Selig Martin K. , Nielsen G. Petur , Peterson Randall T. , Drummond Iain A. , Haber Daniel A. 
Published: December 2013

Summary
Chordoma is a malignant tumor thought to arise from remnants of the embryonic notochord with its origin in the bones of the axial skeleton. Surgical resection is the standard treatment usually in combination with radiation therapy, but neither chemotherapeutic nor targeted therapeutic approaches have demonstrated success. No animal model and only few chordoma cell lines are available for preclinical drug testing, and while no drugable genetic drivers have been identified, activation of EGFR and downstream AKT/PI3K pathways have been described. Here, we report a zebrafish model of chordoma, based on stable transgene-driven expression of HRASV12 in notochord cells during development. Extensive intra-notochordal tumor formation is evident within days of transgene expression, ultimately leading to larval death. The zebrafish tumors share characteristics of human chordoma as demonstrated by immunohistochemistry and electron microscopy. The mTORC1 inhibitor rapamycin, which has some demonstrated activity in a chordoma cell line, delays the onset of tumor formation in our zebrafish model, and improves survival of tumor-bearing fish. Consequently, the HRASV12-driven zebrafish model of chordoma may enable high-throughput screening of potential therapeutic agents for the treatment of this refractory cancer.
TorsinA rescues ER-associated stress and locomotive defects in C. elegans models of ALS
Authors: Thompson Michelle L. , Chen Pan , Yan Xiaohui , Kim Hanna , Borom Akeem R. , Roberts Nathan B. , Caldwell Kim A. , Caldwell Guy A. 
Published: December 2013

Summary
Molecular mechanisms underlying neurodegenerative diseases converge at the interface of pathways impacting cellular stress, protein homeostasis, and aging. Targeting the intrinsic capacities of neuroprotective proteins to restore neuronal function and/or attenuate degeneration represents a potential means toward therapeutic intervention. The product of the human DYT1 gene, torsinA, is a member of the functionally diverse AAA+ family of proteins and exhibits robust molecular chaperone-like activity, both in vitro and in vivo. While mutations in DYT1 are associated with a rare form of heritable generalized dystonia, the native function of torsinA appears cytoprotective in maintaining the cellular threshold to endoplasmic reticulum (ER) stress. Here we explore the potential for torsinA to serve as a buffer to attenuate the cellular consequences of misfolded protein stress as it pertains to the neurodegenerative disease, amyotrophic lateral sclerosis (ALS). The selective vulnerability of motor neurons to degeneration in ALS mice models harboring mutations in the superoxide dismutase, SOD1, has been found to correlate with regional-specific ER stress in brains. Using Caenorhabditis elegans as a system to model ER stress, we generated transgenic nematodes overexpressing either wildtype or mutant human SOD1 to evaluate their relative impact on ER stress induction in vivo. These studies revealed a mutant SOD1-specific increase in ER stress that was further exacerbated by changes in temperature, all of which was robustly attenuated by co-expression of torsinA. Moreover, through complementary behavioral analysis, torsinA was able to restore normal neuronal function in mutant G85R SOD1 animals. Furthermore, torsinA targeted mutant SOD1 for degradation via the proteasome, representing a mechanistic insight into the activity torsinA has on aggregate prone proteins. These results expand our understanding of proteostatic mechanisms influencing neuronal dysfunction in ALS, while simultaneously highlighting the potential for torsinA as a novel target for therapeutic development.
A comparative analysis of marine mammal tracheas
Authors: Moore Colby , Moore Michael , Trumble Stephen , Niemeyer Misty , Lentell Betty , McLellan William , Costidis Alexander , Fahlman Andreas 
Published: December 2013

SummaryIn 1940, Scholander suggested that stiffened upper airways remained open and received air from highly compressible alveoli during marine mammal diving. There are little data available on the structural and functional adaptations of the marine mammal respiratory system. The aim of this research was to investigate the anatomical (gross) and structural (compliance) characteristics of excised marine mammal tracheas. Here we defined different types of tracheal structures, categorizing pinniped tracheas by varying degrees of continuity of cartilage (categories 1-4) and cetacean tracheas by varying compliance values (categories 5A and 5B). Some tracheas fell into more than one category, along their length, for example, the harbor seal (Phoca vitulina) demonstrated complete rings cranially, and as the trachea progressed caudally tracheal rings changed morphology. Dolphins and porpoises had less stiff, more compliant spiraling rings while beaked whales had very stiff, less compliant spiraling rings. The pressure-volume (P-V) relationships of isolated tracheas from different species were measured to assess structural differences between species. These findings lend evidence for pressure-induced collapse and re-inflation of lungs, perhaps influencing variability in dive depth or ventilation rates of the species investigated.