bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tectonic and magmatic evolution of the mantle lithosphere during the rifting stages of a fossil slow–ultraslow spreading basin: insights from the Erro–Tobbio peridotite (Voltri Massif, NW Italy)
Authors: Padovano Matteo , Piccardo Giovanni B. , Vissers Reinoud L. M. 
Published: December 2014

Abstract
We investigate the structural, petrological and compositional features recorded by strongly deformed and melt-percolated Erro–Tobbio peridotites (Voltri Massif, Ligurian Alps, NW Italy), in order to demonstrate that the processes of shear-zone formation and melt percolation are intimately linked by a positive feedback. We focus on spinel and plagioclase peridotites, and extensional shear zones that underwent infiltration by upwelling asthenospheric melts. Shear and porosity bands, which developed during extension prior to melt infiltration, represent important structural and rheological pathways to facilitate and enhance melt infiltration into the extending lithosphere and the ascent of such melts to shallower levels.
Our results lend strong support to numerical models addressing the physical processes underlying extensional systems. These show that, in the case of slow–ultraslow continental extension and the subsequent formation of slow–ultraslow spreading oceans, porosity and shear-localization bands may develop in a previously unstructured lithosphere, prior to melt infiltration. Our studies on the Erro–Tobbio peridotites allow a model for the inception of continental extension and rifting to drifting of slow–ultraslow spreading oceans to be proposed. We suggest that integrated studies of on-land peridotites, coupled with geophysical–structural results from modern oceans, may provide clues to the geodynamic processes governing continental extension and passive rifting.
Evaluation of a Tumor Microenvironment–Based Prognostic Score in Primary Operable Colorectal Cancer
Authors: Park James H. , McMillan Donald C. , Powell Arfon G. , Richards Colin H. , Horgan Paul G. , Edwards Joanne , Roxburgh Campbell S.D. 
Published: December 2014

Abstract
Purpose: The tumor microenvironment is recognized as an important determinant of progression and outcome in colorectal cancer. The aim of the present study was to evaluate a novel tumor microenvironment–based prognostic score, based on histopathologic assessment of the tumor inflammatory cell infiltrate and tumor stroma, in patients with primary operable colorectal cancer.
Experimental Design: Using routine pathologic sections, the tumor inflammatory cell infiltrate and stroma were assessed using Klintrup–Mäkinen (KM) grade and tumor stroma percentage (TSP), respectively, in 307 patients who had undergone elective resection for stage I–III colorectal cancer. The clinical utility of a cumulative score based on these characteristics was examined.
Results: On univariate analysis, both weak KM grade and high TSP were associated with reduced survival (HR, 2.42; P = 0.001 and HR, 2.05; P = 0.001, respectively). A cumulative score based on these characteristics, the Glasgow Microenvironment Score (GMS), was associated with survival (HR, 1.93; 95% confidence interval, 1.36–2.73; P &lt; 0.001), independent of TNM stage and venous invasion (both P &lt; 0.05). GMS stratified patients in to three prognostic groups: strong KM (GMS = 0), weak KM/low TSP (GMS = 1), and weak KM/high TSP (GMS = 2), with 5-year survival of 89%, 75%, and 51%, respectively (P &lt; 0.001). Furthermore, GMS in combination with node involvement, venous invasion, and mismatch repair status further stratified 5-year survival (92% to 37%, 93% to 27%, and 100% to 37%, respectively).
Conclusions: The present study further confirms the clinical utility of assessment of the tumor microenvironment in colorectal cancer and introduces a simple, routinely available prognostic score for the risk stratification of patients with primary operable colorectal cancer. Clin Cancer Res; 21(4); 882–8. ©2014 AACR.
PI3′-Kinase Inhibition Forestalls the Onset of MEK1/2 Inhibitor Resistance in BRAF-Mutated Melanoma
Authors: Deuker Marian M. , Marsh Durban Victoria , Phillips Wayne A. , McMahon Martin 
Published: December 2014

Abstract
Phosphatidylinositide 3′ (PI3′)-lipid signaling cooperates with oncogenic BRAFV600E to promote melanomagenesis. Sustained PI3′-lipid production commonly occurs via silencing of the PI3′-lipid phosphatase PTEN or, less commonly, through mutational activation of PIK3CA, encoding the 110-kDa catalytic subunit of PI3′-kinase-α (PI3Kα). To define the PI3K catalytic isoform dependency of BRAF-mutated melanoma, we used pharmacologic, isoform-selective PI3K inhibitors in conjunction with melanoma-derived cell lines and genetically engineered mouse (GEM) models. Although BRAFV600E/PIK3CAH1047R melanomas were sensitive to the antiproliferative effects of selective PI3Kα blockade, inhibition of BRAFV600E/PTENNull melanoma proliferation required combined blockade of PI3Kα, PI3Kδ, and PI3Kγ, and was insensitive to PI3Kβ blockade. In GEM models, isoform-selective PI3K inhibition elicited cytostatic effects, but significantly potentiated melanoma regression in response to BRAFV600E pathway–targeted inhibition. Interestingly, PI3K inhibition forestalled the onset of MEK inhibitor resistance in two independent GEM models of BRAFV600E-driven melanoma. These results suggest that combination therapy with PI3K inhibitors may be a useful strategy to extend the duration of clinical response of patients with BRAF-mutated melanoma to BRAFV600E pathway–targeted therapies.
Significance: Although BRAFV600E pathway–targeted therapies elicit melanoma regression, the onset of drug resistance limits the durability of response. Here, we show that combined treatment with PI3K inhibitors significantly forestalled the onset of MEK1/2 inhibitor–resistant disease in BRAF-mutated GEM melanoma models. These results provide a conceptual framework for the combined deployment of BRAFV600E plus PI3K pathway–targeted inhibitors in the treatment of a subset of patients with BRAF-mutated melanoma. Cancer Discov; 5(2); 143–53. ©2014 AACR.
This article is highlighted in the In This Issue feature, p. 97
CXCR5-Mediated Shaping of the Lymphoid Follicle in Chronic Lymphocytic Leukemia
Authors: López-Guerra Mònica , Xargay-Torrent Sílvia , Colomer Dolors 
Published: December 2014

AbstractSummary: Heinig and colleagues, using the Eμ-Tcl1 mouse model of chronic lymphocytic leukemia (CLL), shed light on the trafficking routes of CLL cells into the protective microenvironmental niches in secondary lymphoid organs. The authors propose a crucial role of the resident follicular dendritic cells for leukemia pathogenesis that is essentially orchestrated by the chemokine receptor CXCR5. Cancer Discov; 4(12); 1374–6. ©2014 AACR.See related article by Heinig and colleagues, p. 1448
Adverse Epigenetic Signatures by Histone Methyltransferase Set7 Contribute to Vascular Dysfunction in Patients With Type 2 Diabetes Mellitus
Authors: Paneni Francesco , Costantino Sarah , Battista Rodolfo , Castello Lorenzo , Capretti Giuliana , Chiandotto Sergio , Scavone Giuseppe , Villano Angelo , Pitocco Dario , Lanza Gaetano , Volpe Massimo , Lüscher Thomas F. , Cosentino Francesco 
Published: December 2014

Background—
Cellular studies showed that histone methyltransferase Set7 mediates high glucose–induced inflammation via epigenetic regulation of the transcription factor NF-kB. However, the link between Set7 and vascular dysfunction in patients with diabetes mellitus remains unknown. This study was designed to investigate whether Set7 contributes to vascular dysfunction in patients with type 2 diabetes mellitus (T2DM).

Methods and Results—

Set7-driven epigenetic changes on NF-kB p65 promoter and expression of NF-kB-dependent genes, cyclooxygenase 2 and inducible endothelial nitric oxide synthase, were assessed in peripheral blood mononuclear cells isolated from 68 subjects (44 patients with T2DM and 24 age-matched controls). Brachial artery flow–mediated dilation, 24-hour urinary levels of 8-isoprostaglandin F
2α
, and plasma adhesion molecules, intercellular cell adhesion molecule-1 and monocyte chemoattractant protein-1, were also determined. Experiments in human aortic endothelial cells exposed to high glucose were performed to elucidate the mechanisms of Set7-driven inflammation and oxidative stress. Set7 expression increased in peripheral blood mononuclear cells from patients with T2DM when compared with controls. Patients with T2DM showed Set7-dependent monomethylation of lysine 4 of histone 3 on NF-kB p65 promoter. This epigenetic signature was associated with upregulation of NF-kB, subsequent transcription of oxidant/inflammatory genes, and increased plasma levels of intercellular cell adhesion molecule-1 and monocyte chemoattractant protein-1. Interestingly, we found that Set7 expression significantly correlated with oxidative marker 8-isoprostaglandin F
2α
(
r
=0.38;
P
=0.01) and flow-mediated dilation (
r
=−0.34;
P
=0.04). In human aortic endothelial cells, silencing of Set7 prevented monomethylation of lysine 4 of histone 3 and abolished NF-kB-dependent oxidant and inflammatory signaling.

Conclusions—
Set7-induced epigenetic changes contribute to vascular dysfunction in patients with T2DM. Targeting this chromatin-modifying enzyme may represent a novel therapeutic approach to prevent atherosclerotic vascular disease in this setting.
Sull’uso di rescindere in materia di testamenta inofficiosa nelle fonti romane
Authors: Tuzov Daniil 
Published: December 2014

On the use of rescindere in the Roman sources concerning testamenta inofficiosa. – The judgement which ascertained that a testament was inofficiosum, had in Roman law a constitutive effect, in that it annulled the testament. It will be shown that the use of rescindere in this respect is classical and can be used to prove the thesis in question. A critical analysis shall be made of the doctrine according to which the same term is used with respect to testamentum inofficiosum, to indicate the declaration of nullity (inexistence). The following sources will be analyzed: Val. Max. 7,7 init.; 7,7,2; 7,7,6; 7,8 init.; 7,8,1; 7,8,5; CTh. 2,19,2 (Const.); CTh. 15,14,9 (Arcad., Honor.); FV. 270 (Herm., tit. de donat.); C. 3,28,24 (Diocl., Maxim.); C. 3,28,30pr. (Iust.); C. 3,28,32 (Iust.); C. 3,28,34 (Iust.); C. 3,29,4 (Diocl., Maxim.); C. 3,36,16 (Diocl., Maxim.); C. 6,20,17 (Leo); D. 5,2,8,5 (Ulp. 14 ad ed.); D. 5,2,8,16 (Ulp. 14 ad ed.); D. 5,2,17pr. (Paul. 2 quest.); D. 5,2,19 (Paul. 2 quaest.); D. 5,2,25,1 (Ulp. 2 disp.).
Revision of the genus Acanthaspis Amyot &amp; Serville (Hemiptera: Heteroptera: Reduviidae: Reduviinae) from China, with new records of species to adjacent countries
Authors: CAO LIANGMING , RÉDEI DÁVID , LI HU , CAI WANZHI 
Published: December 2014

The assassin bugs of the genus Acanthaspis Amyot & Serville (Reduviinae) from China are revised. Fourteen species are recognized, described or redescribed and illustrated. Three species, A. fulviconnexa, A. melanota, and A. octoguttata, are described as new to science. Acanthaspis subinermis Hsiao 1976 is synonymized with A. laoensis Distant 1919. A key for the identification of Chinese species of Acanthaspis is provided. The biology of A. cincticrus Stål is briefly noted. The following species are newly recorded from adjacent countries: A. collaris Hsiao from Laos and Thailand, A. geniculata Hsiao from Vietnam, A. picta Hsiao from Laos, Myanmar and Thailand, A. quinquespinosa (Fabricius) from Nepal, A. ruficeps Hsiao from Laos, Thailand and Vietnam, and A. laoensis Distant from Thailand.
A crucial role for the homeodomain transcription factor Hhex in lymphopoiesis
Authors: Jackson Jacob T. , Nasa Chayanica , Shi Wei , Huntington Nicholas D. , Bogue Clifford W. , Alexander Warren S. , McCormack Matthew P. 
Published: December 2014

Key PointsHhex regulates development of diverse lymphoid lineages. Hhex regulates cycling of lymphoid precursors.
Construction and evaluation of controlled-release delivery system of Abamectin using porous silica nanoparticles as carriers
Authors: Wang Yan , Cui Haixin , Sun Changjiao , Zhao Xiang , Cui Bo 
Published: December 2014

Abstract
Photolysis and poor solubility in water of Abamectin are key issues to be addressed, which causes low bioavailability and residual pollution. In this study, a novel hydrophilic delivery system through loading Abamectin with porous silica nanoparticles (Abam-PSNs) was developed in order to improve the chemical stability, dispersity, and the controlled release of Abamectin. These results suggest that Abam-PSNs can significantly improve the performance of controllable release, photostability, and water solubility of Abamectin by changing the porous structure of silica nanoparticles, which is favorable to improve the bioavailability and reduce the residues of pesticides.
Incentives in cooperative networks: a contract-theoretic perspective
Authors: Liu Yinshan , Zhong Xiaofeng , Yan Yang , Wang Jing , Saad Walid 
Published: December 2014

Abstract
Multiuser cooperative communication significantly improves the performance of wireless communication networks. One key challenge of multiuser cooperative communication is how to design a cooperative mechanism to incentivize potential relay nodes to help a source node in its data transmission. In this paper, to address this problem, a contract-based principal-agent framework is proposed in the context of a cognitive-radio-based wireless relaying networks in which the sources’ wireless characteristics constitute hidden information which is not known by the relay. The problem is modeled as a monopolist’s problem, in which a mobile relay node acts as the principal who designs incentive-compatible (IC) and individually rational (IR) contract items, consisting of a set of rate-price pairs. Subsequently, contract items can be broadcast by the relay to nearby mobile users that want to send data. Once these sources optimally select an item and notify the relay that they are willing to accept it, the relay then chooses one source based on the highest revenue for which to provide service. The cooperative gain, relay’s revenue, and expected data rate are characterized for the optimal contract under complete information and incomplete information. Theoretical analysis and numerical results show that this pricing mechanism can lead to a win-win situation in which source nodes get good communication service and relay nodes maximize their own profit that can, in turn, be used to purchase the relay service of other nodes when needed in the future. Moreover, the proposed mechanism is shown to also exhibit other important features such as low complexity and low signaling overhead.
The impact of hydroxyethyl starches in cardiac surgery: a meta-analysis
Authors: Jacob Matthias , Fellahi Jean-Luc , Chappell Daniel , Kurz Andrea 
Published: December 2014

Abstract
Introduction
Recent studies in septic patients showed that adverse effects of hydroxyethyl starches (HESs) possibly outweigh their benefits in severely impaired physiological haemostasis. It remains unclear whether this also applies to patient populations that are less vulnerable. In this meta-analysis, we evaluated the impact of various HES generations on safety and efficacy endpoints in patients undergoing cardiac surgery.

Methods
We searched the PubMed, Embase and Cochrane Central Register of Controlled Trials databases for randomised controlled trials (RCTs) in the English or German language comparing the use of HES to any other colloid or crystalloid during open heart surgery.

Results
Blood loss and transfusion requirements were higher for older starches with mean molecular weights more than 200 kDa compared to other volume substitutes. In contrast, this effect was not observed with latest-generation tetrastarches (130/0.4), which performed even better when compared to albumin (blood loss of tetrastarch versus albumin: standardised mean difference (SMD), −0.34; 95% CI, −0.63, −0.05; P = 0.02; versus gelatin: SMD, −0.06; 95% CI, −0.20, 0.08; P = 0.39; versus crystalloids: SMD, −0.05; 95% CI, −0.20, 0.10; P = 0.54). Similar results were found for transfusion needs. Lengths of stay in the intensive care unit or hospital were significantly shorter with tetrastarches compared to gelatin (intensive care unit: SMD, −0.10; 95% CI, −0.15, −0.05; P = 0.0002) and crystalloids (hospital: SMD, −0.52; 95% CI, −0.90, −0.14; P = 0.007).

Conclusions
In this meta-analysis of RCTs, we could not identify safety issues with tetrastarches compared with other colloid or crystalloid solutions in terms of blood loss, transfusion requirements or hospital length of stay in patients undergoing cardiac surgery. The safety data on coagulation with older starches raise some issues that need to be addressed in future trials.
Early high protein intake is associated with low mortality and energy overfeeding with high mortality in non-septic mechanically ventilated critically ill patients
Authors: Weijs Peter JM , Looijaard Wilhelmus GPM , Beishuizen Albertus , Girbes Armand RJ , Oudemans-van Straaten Heleen M 
Published: December 2014

Abstract
Introduction
Early protein and energy feeding in critically ill patients is heavily debated and early protein feeding hardly studied.

Methods
A prospective database with mixed medical-surgical critically ill patients with prolonged mechanical ventilation (>72 hours) and measured energy expenditure was used in this study. Logistic regression analysis was used to analyse the relation between admission day-4 protein intake group (with cutoffs 0.8, 1.0, and 1.2 g/kg), energy overfeeding (ratio energy intake/measured energy expenditure > 1.1), and admission diagnosis of sepsis with hospital mortality after adjustment for APACHE II (Acute Physiology and Chronic Health Evaluation II) score.

Results
A total of 843 patients were included. Of these, 117 had sepsis. Of the 736 non-septic patients 307 were overfed. Mean day-4 protein intake was 1.0 g/kg pre-admission weight per day and hospital mortality was 36%. In the total cohort, day-4 protein intake group (odds ratio (OR) 0.85; 95% confidence interval (CI) 0.73 to 0.99; P = 0.047), energy overfeeding (OR 1.62; 95%CI 1.07 to 2.44; P = 0.022), and sepsis (OR 1.77; 95%CI 1.18 to 2.65; P = 0.005) were independent risk factors for mortality besides APACHE II score. In patients with sepsis or energy overfeeding, day-4 protein intake was not associated with mortality. For non-septic, non-overfed patients (n = 419), mortality decreased with higher protein intake group: 37% for <0.8 g/kg, 35% for 0.8 to 1.0 g/kg, 27% for 1.0 to 1.2 g/kg, and 19% for ≥1.2 g/kg (P = 0.033). For these, a protein intake level of ≥1.2 g/kg was significantly associated with lower mortality (OR 0.42, 95%CI 0.21 to 0.83, P = 0.013).

Conclusions
In non-septic critically ill patients, early high protein intake was associated with lower mortality and early energy overfeeding with higher mortality. In septic patients early high protein intake had no beneficial effect on mortality.
Sex differences in the genome-wide DNA methylation pattern and impact on gene expression, microRNA levels and insulin secretion in human pancreatic islets
Authors: Hall Elin , Volkov Petr , Dayeh Tasnim , Esguerra Jonathan Lou S , Salö Sofia , Eliasson Lena , Rönn Tina , Bacos Karl , Ling Charlotte 
Published: December 2014

Abstract
Background
Epigenetic factors regulate tissue-specific expression and X-chromosome inactivation. Previous studies have identified epigenetic differences between sexes in some human tissues. However, it is unclear whether epigenetic modifications contribute to sex-specific differences in insulin secretion and metabolism. Here, we investigate the impact of sex on the genome-wide DNA methylation pattern in human pancreatic islets from 53 males and 34 females, and relate the methylome to changes in expression and insulin secretion.

Results
Glucose-stimulated insulin secretion is higher in female versus male islets. Genome-wide DNA methylation data in human islets clusters based on sex. While the chromosome-wide DNA methylation level on the X-chromosome is higher in female versus male islets, the autosomes do not display a global methylation difference between sexes. Methylation of 8,140 individual X-chromosome sites and 470 autosomal sites shows sex-specific differences in human islets. These include sites in/near AR, DUSP9, HNF4A, BCL11A and CDKN2B. 61 X-chromosome genes and 18 autosomal genes display sex-specific differences in both DNA methylation and expression. These include NKAP, SPESP1 and APLN, which exhibited lower expression in females. Functional analyses demonstrate that methylation of NKAP and SPESP1 promoters in vitro suppresses their transcriptional activity. Silencing of Nkap or Apln in clonal beta-cells results in increased insulin secretion. Differential methylation between sexes is associated with altered levels of microRNAs miR-660 and miR-532 and related target genes.

Conclusions
Chromosome-wide and gene-specific sex differences in DNA methylation associate with altered expression and insulin secretion in human islets. Our data demonstrate that epigenetics contribute to sex-specific metabolic phenotypes.
Complex host genetics influence the microbiome in inflammatory bowel disease
Authors: Knights Dan , Silverberg Mark S , Weersma Rinse K , Gevers Dirk , Dijkstra Gerard , Huang Hailiang , Tyler Andrea D , van Sommeren Suzanne , Imhann Floris , Stempak Joanne M , Huang Hu , Vangay Pajau , Al-Ghalith Gabriel A , Russell Caitlin , Sauk Jenny , Knight Jo , Daly Mark J , Huttenhower Curtis , Xavier Ramnik J 
Published: December 2014

Abstract
Background
Human genetics and host-associated microbial communities have been associated independently with a wide range of chronic diseases. One of the strongest associations in each case is inflammatory bowel disease (IBD), but disease risk cannot be explained fully by either factor individually. Recent findings point to interactions between host genetics and microbial exposures as important contributors to disease risk in IBD. These include evidence of the partial heritability of the gut microbiota and the conferral of gut mucosal inflammation by microbiome transplant even when the dysbiosis was initially genetically derived. Although there have been several tests for association of individual genetic loci with bacterial taxa, there has been no direct comparison of complex genome-microbiome associations in large cohorts of patients with an immunity-related disease.

Methods
We obtained 16S ribosomal RNA (rRNA) gene sequences from intestinal biopsies as well as host genotype via Immunochip in three independent cohorts totaling 474 individuals. We tested for correlation between relative abundance of bacterial taxa and number of minor alleles at known IBD risk loci, including fine mapping of multiple risk alleles in the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene exon. We identified host polymorphisms whose associations with bacterial taxa were conserved across two or more cohorts, and we tested related genes for enrichment of host functional pathways.

Results
We identified and confirmed in two cohorts a significant association between NOD2 risk allele count and increased relative abundance of Enterobacteriaceae, with directionality of the effect conserved in the third cohort. Forty-eight additional IBD-related SNPs have directionality of their associations with bacterial taxa significantly conserved across two or three cohorts, implicating genes enriched for regulation of innate immune response, the JAK-STAT cascade, and other immunity-related pathways.

Conclusions
These results suggest complex interactions between genetically altered host functional pathways and the structure of the microbiome. Our findings demonstrate the ability to uncover novel associations from paired genome-microbiome data, and they suggest a complex link between host genetics and microbial dysbiosis in subjects with IBD across independent cohorts.