bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTLA4-Ig (abatacept) therapy modulates T cell effector functions in autoantibody-positive rheumatoid arthritis patients
Authors: Pieper Jennifer , Herrath Jessica , Raghavan Sukanya , Muhammad Khalid , Vollenhoven Ronald van , Malmström Vivianne 
Published: August 2013

AbstractBackgroundRheumatoid arthritis is a chronic inflammatory disease with a strong MHC class II component and where many patients develop characteristic autoantibodies towards the noncoding amino acid citrulline. Such anti-citrullinated protein antibodies (ACPA) have recently been put forward as an independent predictive factor for treatment response by co-stimulation blockade by CTLA4-Ig (abatacept). We have performed a mechanism of action study to dissect T cell functionality in RA patients with long-standing disease undergoing abatacept treatment and the influence of ACPA status.ResultsPeripheral blood samples were collected from RA patients as they started CTLA4-Ig treatment and 3 and 6 months later. A general decrease of regulatory T cell subsets was observed in the cohort. Additionally within the ACPA-positive group significant down-regulation of all key T cell effector subsets including Th1, Th2, and Th17 was observed by analyzing cytokines by intracellular flow cytometry and in cell culture supernatants.RA synovial fluid samples were cultured in vitro in the presence or absence of CTLA4-Ig (abatacept). T cell cytokine production was diminished, but without increasing the functional capacity of CD4+CD25hi regulatory T cells as previously demonstrated in the context of TNF-blockade and anti-IL6R therapy.ConclusionsOur immunological study of T cell functionality in RA patients, both ACPA-positive and ACPA-negative, starting biological therapy with the co-stimulation blockade abatacept (CTLA4-Ig) supports the recently published registry study implicating ACPA seropositivity as an independent predictive factor to treatment response as we observed the most striking effect on T cell subset modulation in ACPA-positive patients. These data further support the notion of RA as a disease with several sub-entities, where the ACPA-positive fraction represents a classical HLA-associated autoimmune disorder while ACPA-negative patients may have other driving forces apart from classical adaptive immune responses.
BAP1 deficiency causes loss of melanocytic cell identity in uveal melanoma
Authors: Matatall Katie A , Agapova Olga A , Onken Michael D , Worley Lori A , Bowcock Anne M , Harbour J William 
Published: August 2013

Abstract

Background
Uveal melanoma is a highly aggressive cancer with a strong propensity for metastasis, yet little is known about the biological mechanisms underlying this metastatic potential. We recently showed that most metastasizing uveal melanomas, which exhibit a class 2 gene expression profile, contain inactivating mutations in the tumor suppressor BAP1. The aim of this study was to investigate the role of BAP1 in uveal melanoma progression.

Methods
Uveal melanoma cells were studied following RNAi-mediated depletion of BAP1 using proliferation, BrdU incorporation, flow cytometry, migration, invasion, differentiation and clonogenic assays, as well as in vivo tumorigenicity experiments in NOD-SCID-Gamma mice.

Results
Depletion of BAP1 in uveal melanoma cells resulted in a loss of differentiation and gain of stem-like properties, including expression of stem cell markers, increased capacity for self-replication, and enhanced ability to grow in stem cell conditions. BAP1 depletion did not result in increased proliferation, migration, invasion or tumorigenicity.

Conclusions
BAP1 appears to function in the uveal melanocyte lineage primarily as a regulator of differentiation, with cells deficient for BAP1 exhibiting stem-like qualities. It will be important to elucidate how this effect of BAP1 loss promotes metastasis and how to reverse this effect therapeutically.
Use of statins in lower extremity artery disease: a review
Authors: Gargiulo Giuseppe , Giugliano Giuseppe , Brevetti Linda , Sannino Anna , Schiattarella Gabriele Giacomo , Serino Federica , Carbone Andreina , Scudiero Fernando , Ferrone Marco , Corrado Roberto , Izzo Raffaele , Chiariotti Lorenzo , Perrino Cinzia , Amato Bruno , Trimarco Bruno , Esposito Giovanni 
Published: August 2013

Abstract

Background
Lower extremity artery disease (LE-PAD) is one of the most common manifestations of atherosclerosis, particularly in elderly patients, and it is related to a high cardiovascular risk.

Description
It is well established that statin therapy is characterized by crucial benefits on cardiovascular system by limiting atherosclerotic progression and reducing cardiovascular events and mortality. A growing body of evidence support efficacy of statins in LE-PAD due to the ability of both reducing cardiovascular risk and improving walking distance and, hence, quality of life. Consequently, statin therapy should be considered in all LE-PAD patients and new LDL-cholesterol targets should be reached.

Conclusions
Our opinion is that statin therapy remains still underutilized or with inadequate dosage, so therapy of LE-PAD patients should be improved to obtain all the demonstrated benefits of statins.
Rectosigmoid stump washout as an alternative to permanent mucous fistula in patients undergoing subtotal colectomy for ulcerative colitis in emergency settings
Authors: Pellino Gianluca , Sciaudone Guido , Candilio Giuseppe , Canonico Silvestro , Selvaggi Francesco 
Published: August 2013

AbstractBackgroundRestorative proctocolectomy with ileopouch-anal anastomosis (IPAA) is the treatment of choice for intractable or complicated ulcerative colitis(UC). Elderly patients often present with acute colitis requiring emergent subtotal colectomy(SC). Frail patients are at risk of developing septic complications related to the closed rectosigmoidal stump, often requiring formation of a second stoma to be reversed at the time of completion proctectomy. This carries nuisance to such exhausted patients. We propose a simple and inexpensive trick to avoid the need for creating a mucous fistula.MethodsIPAA was performed as a 3-stage procedure in emergency settings. The rectosigmoidal stump was closed and placed subcutaneously; skin was closed over it. After SC, if patients showed signs of stump-related pelvic sepsis, a lavage of the rectal stump with povidone iodine solution and with saline was carried out as a rescue treatment aiming to avoid the need of opening the rectal stump to drain sepsis.ResultsThirty-five patients underwent SC for UC between 1987 and 2012. The skin was closed over the closed stump in the 20. Seven patients out of these 20 experienced early stump-related septic complication. In five cases, we were able to avoid opening of the rectal stump, and a second stoma was unnecessary. After opening the closed stump in the remaining ones, a prompt improving of symptoms was observed.ConclusionsRectal washout was well tolerated and avoided a second stoma in five out of seven patients, with better quality of life and body perception after IPAA surgery. This is relevant when dealing with geriatric patients, needing to completely recover before undergoing completion proctectomy.
BOSS: context-enhanced search for biomedical objects
Authors: Choi Jaehoon , Kim Donghyeon , Kim Seongsoon , Lee Sunwon , Lee Kyubum , Kang Jaewoo 
Published: August 2013

Abstract

Background
There exist many academic search solutions and most of them can be put on either ends of spectrum: general-purpose search and domain-specific "deep" search systems. The general-purpose search systems, such as PubMed, offer flexible query interface, but churn out a list of matching documents that users have to go through the results in order to find the answers to their queries. On the other hand, the "deep" search systems, such as PPI Finder and iHOP, return the precompiled results in a structured way. Their results, however, are often found only within some predefined contexts. In order to alleviate these problems, we introduce a new search engine, BOSS, Biomedical Object Search System.

Methods
Unlike the conventional search systems, BOSS indexes segments, rather than documents. A segment refers to a Maximal Coherent Semantic Unit (MCSU) such as phrase, clause or sentence that is semantically coherent in the given context (e.g., biomedical objects or their relations). For a user query, BOSS finds all matching segments, identifies the objects appearing in those segments, and aggregates the segments for each object. Finally, it returns the ranked list of the objects along with their matching segments.

Results
The working prototype of BOSS is available at http://boss.korea.ac.kr. The current version of BOSS has indexed abstracts of more than 20 million articles published during last 16 years from 1996 to 2011 across all science disciplines.

Conclusion
BOSS fills the gap between either ends of the spectrum by allowing users to pose context-free queries and by returning a structured set of results. Furthermore, BOSS exhibits the characteristic of good scalability, just as with conventional document search engines, because it is designed to use a standard document-indexing model with minimal modifications. Considering the features, BOSS notches up the technological level of traditional solutions for search on biomedical information.
Color differences among feral pigeons (Columba livia) are not attributable to sequence variation in the coding region of the melanocortin-1 receptor gene (MC1R)
Authors: Derelle Romain , Kondrashov Fyodor A , Arkhipov Vladimir Y , Corbel Hélène , Frantz Adrien , Gasparini Julien , Jacquin Lisa , Jacob Gwenaël , Thibault Sophie , Baudry Emmanuelle 
Published: August 2013

AbstractBackgroundGenetic variation at the melanocortin-1 receptor (MC1R) gene is correlated with melanin color variation in many birds. Feral pigeons (Columba livia) show two major melanin-based colorations: a red coloration due to pheomelanic pigment and a black coloration due to eumelanic pigment. Furthermore, within each color type, feral pigeons display continuous variation in the amount of melanin pigment present in the feathers, with individuals varying from pure white to a full dark melanic color. Coloration is highly heritable and it has been suggested that it is under natural or sexual selection, or both. Our objective was to investigate whether MC1R allelic variants are associated with plumage color in feral pigeons.FindingsWe sequenced 888 bp of the coding sequence of MC1R among pigeons varying both in the type, eumelanin or pheomelanin, and the amount of melanin in their feathers. We detected 10 non-synonymous substitutions and 2 synonymous substitution but none of them were associated with a plumage type. It remains possible that non-synonymous substitutions that influence coloration are present in the short MC1R fragment that we did not sequence but this seems unlikely because we analyzed the entire functionally important region of the gene.ConclusionsOur results show that color differences among feral pigeons are probably not attributable to amino acid variation at the MC1R locus. Therefore, variation in regulatory regions of MC1R or variation in other genes may be responsible for the color polymorphism of feral pigeons.
Polycyclic Aromatic Hydrocarbons in drinking water of Tehran, Iran
Authors: Karyab Hamid , Yunesian Masud , Nasseri Simin , Mahvi Amir Hosein , Ahmadkhaniha Reza , Rastkari Noushin , Nabizadeh Ramin 
Published: August 2013

Abstract
Distribution and seasonal variation of sixteen priority polycyclic aromatic hydrocarbons (PAHs) were investigated in the drinking water of Tehran, the capital of Iran. Detected single and total PAHs concentrations were in the range of 2.01-38.96 and 32.45-733.10 ng/L, respectively, which were quite high compared to the values recorded in other areas of the world. The average occurrence of PAHs with high molecular weights was 79.55%; for example, chrysene occurred in 60.6% of the samples, with a maximum concentration of 438.96 ng/L. In addition, mean carcinogen to non-carcinogen PAHs ratio was 63.84. Although the concentration of benzo[a]pyrene, as an indicator of water pollution to PAHs, was lower than the guideline value proposed by World Health Organization (WHO) as well as that of Iranian National Drinking Water Standards for all of the samples, the obtained results indicated that carcinogen PAHs present in the drinking water of Tehran can cause threats to human health.
Intra-ER sorting of the peroxisomal membrane protein Pex3 relies on its luminal domain
Authors: Fakieh Mohammad H. , Drake Peter J. M. , Lacey Joanne , Munck Joanne M. , Motley Alison M. , Hettema Ewald H. 
Published: August 2013

Summary
Pex3 is an evolutionarily conserved type III peroxisomal membrane protein required for peroxisome formation. It is inserted into the ER membrane and sorted via an ER subdomain (the peroxisomal ER, or pER) to peroxisomes. By constructing chimeras between Pex3 and the type III ER membrane protein Sec66, we have been able to separate the signals that mediate insertion of Pex3 into the ER from those that mediate sorting within the ER to the pER subdomain. The N-terminal 17-amino acid segment of Pex3 contains two signals that are each sufficient for sorting to the pER: a chimeric protein containing the N-terminal domain of Pex3 fused to the transmembrane and cytoplasmic segments of Sec66 sorts to the pER in wild type cells, and does not colocalise with peroxisomes. Subsequent transport to existing peroxisomes requires the Pex3 transmembrane segment. When expressed in Drosophila S2R+ cells, ScPex3 targeting to peroxisomes is dependent on the intra-ER sorting signals in the N-terminal segment. The N-terminal segments of both human and Drosophila Pex3 contain intra-ER sorting information and can replace that of ScPex3. Our analysis has uncovered the signals within Pex3 required for the various steps of its transport to peroxisomes. Our generation of versions of Pex3 that are blocked at each stage along its transport pathway provides a tool to dissect the mechanism, as well as the molecular machinery required at each step of the pathway.
Sex-specific trade-offs and compensatory mechanisms: bite force and sprint speed pose conflicting demands on the design of geckos (Hemidactylus frenatus)
Authors: Cameron Skye F. , Wynn Melissa L. , Wilson Robbie S. 
Published: August 2013

SummaryOne of the more intuitive viability costs that can result from the possession of exaggerated sexually selected traits is increased predation pressure due to reduced locomotor capacity. Despite mixed empirical support for such locomotor costs, recent studies suggest such costs may be masked by compensatory traits that effectively offset any detrimental effects. In this study, we provide a comprehensive assessment of the locomotor costs associated with improved male-male competitive ability by simultaneously testing for locomotor trade-offs and potential compensatory mechanisms in territorial male and non-territorial female geckos. Fighting capacity and escape performance of male Asian house geckos (Hemidactylus frenatus) are likely to pose conflicting demands on the optimum phenotype for each task. Highly territorial and aggressive males may require greater investment in head size/strength but such an enhancement may affect overall escape performance. Among male geckos, we found that greater biting capacity due to larger head size was associated with reduced sprint performance; this trade-off was further exacerbated when sprinting on an incline. Females, however, showed no evidence of this trade-off on either flat or inclined surfaces. The sex specificity of this trade-off suggests that the sexes differ in their optimal strategies for dealing with the conflicting requirements of bite force and sprint speed. Unlike males, female H. frenatus had a positive association between hind-limb lengths and head size, suggesting that they have utilised a compensatory mechanism to alleviate for the possible locomotor costs of larger head sizes. It appears that there is greater selection on traits that improve fighting ability (bite force) for males but it is viability traits (sprint speed) that appear to be of greater importance for females. Our results emphasise that only by examining both functional trade-offs and potential compensatory mechanisms is it possible to discover the varied mechanisms affecting the morphological design of a species.
Experimental infection dynamics: using immunosuppression andin vivoparasite tracking to understand host resistance in an amphibian-trematode system
Authors: LaFonte Bryan E. , Johnson Pieter T. J. 
Published: August 2013

SummaryWhile naturally occurring hosts often exhibit pronounced differences in infection and pathology, the relative importance of factors associated with host life history and immunity in explaining such patterns often remains speculative. Research in eco-immunology highlights the trade-offs between host physiology and immunity, for which natural variations in disease susceptibility offer a valuable platform to test predictions within this framework. Here, we combined use of a novel, in vivo assay for tracking parasite fate and an experimental manipulation of host immune function (via chronic corticosterone exposure) to assess the role of host immunity in regulating susceptibility of amphibian hosts to three larval trematodes: Ribeiroia ondatrae, Echinostoma trivolvis, and Alaria sp. 2. Results from the in vivo parasite tracking assay revealed marked differences in initial parasite penetration and subsequent host clearance. Relative to infections in a highly susceptible species (Pseudacris regilla), the virulent trematode R. ondatrae was ~25% less successful at penetrating larvae of three hylid frog species and was cleared &gt;45× faster, such that all parasites were rapidly cleared from hylid hosts over 72 hours following a Weibull distribution. Immune suppression of Hyla versicolor sharply reduced this resistance and increased infection of all three trematodes by 67 to 190%, with particularly strong increases for Ribeiroia. Diminished resistance correlated with a 62% decrease in circulating eosinophils. Correspondingly, ten days after corticosterone exposures ended, infections declined dramatically while eosinophil levels returned to normal. In light of ongoing declines and deformities in amphibian populations, these findings have application potential for mitigating disease-driven effects.
A toxic diet: transfer of contaminants to offspring through a parental care mechanism
Authors: Maunder Richard J. , Buckley Jonathan , Val Adalberto L. , Sloman Katherine A. 
Published: August 2013

Summary
The transfer of maternal contaminants to offspring during oogenesis and gestation is documented in many animals and in mammals contaminants may pass from mother to offspring during lactation. Although other non-mammalian vertebrates provide parental care in the form of nutritive secretions for offspring to feed from, the potential for toxicant transfer during non-mammalian parental care is rarely considered. The discus fish, Symphysodon sp., employs an unusual parental care strategy where fry feed on parental epidermal mucus for several weeks after hatch. This strategy has the potential to act as a method of contaminant transfer. In discus adults, both waterborne and dietary toxicants are sequestered and secreted into their epidermal mucus, the food on which fry depend. To determine whether parents could channel these contaminants directly to offspring, we exposed parents to aqueous cadmium and recorded the subsequent feeding behaviour and cadmium content of fry. Fry continued to feed normally from contaminated mucus and accumulated significant tissue concentrations of cadmium. In conclusion, this parental care mechanism of the discus fish can expose offspring to harmful contaminants during the sensitive early stages of life and highlights that parent to offspring contaminant transfer after birth may be more widespread than previously thought.
A comparative study of metal oxide nanoparticles embryotoxicity using the embryonic stem cell test
Authors: Vecchione Lucia , Massimiani Micol , Camaioni Antonella , Sifrani Luna , Magrini Andrea , Pietroiusti Antonio , Campagnolo Luisa 
Published: August 2013

AbstractMany in vitro studies demonstrated that metal oxide nanoparticles like zinc oxide and titanium dioxide are versatile platforms for industrial and biomedical applications. In this paper, investigation of the embryotoxic potential of these nanoparticles using the Embryonic stem Cells Test (EST) was evaluated. The EST is a validated in vitro toxicity test used to predict embryotoxicity of soluble chemical compounds, which only recently has been applied to nanoparticles, demonstrating its suitability also in nanotoxicology. Through such test, we were able to classify zinc oxide nanoparticles as not embryotoxic, while titanium dioxide nanoparticles appeared to be weakly embryotoxic.
The Use Context of Digital Archival Collections: Mapping with Historical Research Topics and the Content of Digital Archival Collections
Authors: Sinn Donghee 
Published: August 2013

AbstractDigital archives have been used extensively in historical research. While many user studies regarding digital collections have focused on their users and information behaviors, there is not much research on how digital archives have contributed to historical scholarship and why historians use them. Understanding which digital collections are useful for topical coverage in historical studies will provide important information in the development and assessment of digital preservation projects. This study examines the topical coverage of historical articles that cite digital archival collections, and also the content of digital archival collections that appear in these articles. By mapping the contents of the articles and digital archival collections, this study aims to understand historians’ use context for their historical research and to relate the association of digital projects to the scholarship of history
General actions of hyperstructures and some applications
Authors: Chvalina Jan , Hošková-Mayerová Šárka , Nezhad A. D. 
Published: August 2013

Abstract The aim of this paper is to investigate useful generalizations of the classical concept of a quasi-automaton without outputs or a discrete dynamical system, which are also called actions of semigroups or groups on given phase sets. The paper contains also certain applications of presented concepts and examples from various areas of mathematics.
Model for implementing a reengineering solution of the production process in a printing house
Authors: Epure Dănuţ-Tiberius , Micu Adrian , Susanu Irina , Micu Angela-Eliza 
Published: August 2013

Abstract The main objective of the present paper is to highlight the importance and impact of the concept of reengineering, both by identifying certain opportunities to improve the performance of Romanian printing companies and some strategies of total redesign of the production process based on highlighting some of their effective combinations as well as the integration of some proper mathematical models. First of all, this study will focus on achieving results that are based on identifying some specific problems that companies have faced at a certain point and on concrete problem solving solutions. Second, there should be emphasized that reengineering works in almost any situation related to a big or small company or the production area or NGOs. Specific objectives: designing and testing a mathematical model that can be adapted to the specific activities of the printing organization, providing the best solution of variable allocation to increase performance.
Commutativity of near-rings with (σ;τ)-derivations
Authors: Kamal Ahmed A. M. , Al-Shaalan Khalid H. 
Published: August 2013

Abstract
In this paper we study some conditions under which a near-ring R admitting a (multiplicative) (σ; τ )-derivation d must be a commutative ring with constrained-suitable conditions on d, σ and τ. Consequently, we obtain some results which generalize some recent theorems in the literature.