bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of ligand‐independent constitutive activation of the Met oncogenic receptor by the engineered chemically‐modified antibody DN30
Authors: Vigna Elisa , Chiriaco Cristina , Cignetto Simona , Fontani Lara , Basilico Cristina , Petronzelli Fiorella , Comoglio Paolo M. 
Published: June 2015

An awesome number of experimental and clinical evidences indicate that constitutive activation of the Met oncogenic receptor plays a critical role in the progression of cancer toward metastasis and/or resistance to targeted therapies. While mutations are rare, the common mechanism of Met activation is overexpression, either by gene amplification (‘addiction’) or transcriptional activation (‘expedience’). In the first instance ligand‐independent kinase activation plays a major role in sustaining the transformed phenotype. Anti‐Met antibodies directed against the receptor binding site behave essentially as ligand (Hepatocyte Growth Factor, HGF) antagonists and are ineffective to counteract ligand‐independent activation. The monovalent chimeric MvDN30 antibody fragment, PEGylated to extend its half‐life, binds the fourth IPT domain and induces ‘shedding’ of the Met extracellular domain, dramatically reducing both the number of receptors on the surface and their phosphorylation. Downstream signaling is thus inhibited, both in the absence or in the presence of the ligand. In vitro, MvDN30 is a strong inhibitor not only of ligand‐dependent invasive growth, sustained by both paracrine and autocrine HGF, but notably, also of ligand‐independent growth of ‘Met‐addicted’ cells. In immunocompromised mice, lacking expression of Hepatocyte Growth Factor cross‐reacting with the human receptor – thus providing, by definition, a model of ‘ligand‐independent’ Met activation – PEGylated MvDN30 impairs growth of Met ‘addicted’ human gastric carcinoma cells. In a Met‐amplified patient‐derived colo‐rectal tumor (xenopatient) MvDN30‐PEG overcomes the resistance to EGFR targeted therapy (Cetuximab). The PEGylated MvDN30 is thus a strong candidate for targeting tumors sustained by ligand‐independent Met oncogenic activation.
Lithologic and facies characteristics of the Lower Cambrian Usolka Formation and its age analogs in the Cis-Yenisei sedimentary basin, West Siberia
Authors: Saraev S.V. 
Published: June 2015

Abstract
Based on the correlation between Lower Cambrian sections of deep wells on the left bank of the Yenisei River and outcrops in the westernmost Yenisei Ridge, the sedimentologic characteristics of the Usolka Formation and coeval deposits are compared. Three paleogeographic regions (subbasins) are distinguished in the Cis-Yenisei basin in Usolka time. The leading role in the sediment genesis was played by the region of barrier reefs stretching northwestward and northward as a ~ 70 km wide band to their joint with the reefs of the Igarka–Noril’sk facies region in the north. The salt basin east of the barrier reef ridge was a bay of the East Siberian salt basin, separated from the latter by the Yenisei paleoislands (at the place of the Yenisei Ridge). Sedimentation in that basin was controlled by evaporite processes, the supply of terrigenous material from the islands and carbonate debris from the opposite side (barrier reef), and the predominance of storm processes. The subbasin west of the barrier reefs evolved under different scenario. Since the Early Cambrian, a trough has been forming here, which was initially characterized by a regime of starvation and the first appearance of carbonaceous rocks (Lower Churbiga Subformation), regarded as Domanic oil source rocks, in the general Cambrian section. On the estimation of the prospects for the distribution of reservoirs whose origin depends on the facies regularities, the leading role is played by the barrier reef region. Importantly, the Lower Cambrian section of the Cis-Yenisei basin contains two large adjacent paleogeomorphologic structures and the corresponding facies zones of a starved prereef depression with the Domanic oil source rocks of the Lower Churbiga Subformation at the early stage of evolution and a potentially productive barrier reef system with a steep slope toward the basin. The favorable combination of these factors suggests that the Cis-Yenisei basin has a high petroleum potential.
Whole Genome Sequencing in Real-Time Investigation and Management of a Pseudomonas aeruginosa Outbreak on a Neonatal Intensive Care Unit
Authors: Davis Rebecca J. , Jensen Slade O. , Van Hal Sebastiaan , Espedido Björn , Gordon Adrienne , Farhat Rima , Chan Raymond 
Published: June 2015

OBJECTIVETo use whole genome sequencing to describe the likely origin of an outbreak of Pseudomonas aeruginosa in a neonatal unit.DESIGNOutbreak investigation.SETTINGThe neonatal intensive care unit service of a major obstetric tertiary referral center.PATIENTSInfants admitted to the neonatal unit who developed P. aeruginosa colonization or infection.METHODSWe undertook whole genome sequencing of P. aeruginosa strains isolated from colonized infants and from the neonatal unit environment.RESULTSEighteen infants were colonized with P. aeruginosa. Isolates from 12 infants and 7 environmental samples were sequenced. All but one of the clinical isolates clustered in ST253 and no differences were detected between unmapped reads. The environmental isolates revealed a variety of sequence types, indicating a large diverse bioburden within the unit, which was subsequently confirmed via enterobacterial repetitive intergenic consensus–polymerase chain reaction typing of post-outbreak isolates. One environmental isolate, obtained from a sink in the unit, clustered within ST253 and differed from the outbreak strain by 9 single-nucleotide polymorphisms only. This information allowed us to focus infection control activities on this sink.CONCLUSIONSWhole genome sequencing can provide detailed information in a clinically relevant time frame to aid management of outbreaks in critical patient management areas. The superior discriminatory power of this method makes it a powerful tool in infection control.Infect. Control Hosp. Epidemiol. 2015;36(9):1058–1064
The dynamic relationship between cash transfers and child health: can the child support grant in South Africa make a difference to child nutrition?
Authors: Zembe-Mkabile Wanga , Ramokolo Vundli , Sanders David , Jackson Debra , Doherty Tanya 
Published: June 2015

AbstractObjectiveCash transfer programmes targeting children are considered an effective strategy for addressing child poverty and for improving child health outcomes in developing countries. In South Africa, the Child Support Grant (CSG) is the largest cash transfer programme targeting children from poor households. The present paper investigates the association of the duration of CSG receipt with child growth at 2 years in three diverse areas of South Africa.DesignThe study analysed data on CSG receipt and anthropometric measurements from children. Predictors of stunting were assessed using a backward regression model.SettingPaarl (peri-urban), Rietvlei (rural) and Umlazi (urban township), South Africa, 2008.SubjectsChildren (n746), median age 22 months.ResultsHigh rates of stunting were observed in Umlazi (28 %), Rietvlei (20 %) and Paarl (17 %). Duration of CSG receipt had no effect on stunting. HIV exposure (adjusted OR=2·30; 95 % CI 1·31, 4·03) and low birth weight (adjusted=OR 2·01, 95 % CI 1·02, 3·96) were associated with stunting, and maternal education had a protective effect on stunting.ConclusionsOur findings suggest that, despite the presence of the CSG, high rates of stunting among poor children continue unabated in South Africa. We argue that the effect of the CSG on nutritional status may have been eroded by food price inflation and limited progress in the provision of other important interventions and social services.
Effect of Different Stocking Densities on Growth and Production Performances of Chevron Snakehead Channa striata in Fiberglass Tanks
Authors: Amin S M N , Muntaziana M P A , Kamarudin M S , Rahim A A , Rahman M Aminur 
Published: June 2015

Abstract
Grow-out culture trials of the highly valued Chevron Snakehead Channa sriata were carried out under different stocking densities in fiberglass tanks. Fingerlings stocked at 20 individuals/m2 were designated as treatment 1 (T1), 30 individuals/m2 as treatment 2 (T2), and 40 individuals/m2 as treatment 3 (T3). The initial mean ± SE body weights (1.93 ± 0.01, 1.57 ± 0.16, and 1.90 ± 0.02 g, respectively) and initial mean ± SE body lengths (6.22 ± 0.05, 5.86 ± 0.20, and 6.26 ± 0.01 cm, respectively) of snakeheads at stocking were similar in all the treatments. After stocking, fish in all the experimental tanks were fed commercial pellets containing 44% crude protein and 6% crude fat. The feed was given at a rate of 6% of the estimated body weight of fish twice daily (0900 and 1700 hours). Physicochemical water quality conditions such as temperature, dissolved oxygen, pH, and total ammonia nitrogen were maintained within the suitable range for fish culture. Final weight, final length, and weight gain of snakeheads were significantly higher in T1 than in T2 and T3. The specific growth rate (SGR) was significantly (P &lt; 0.05) higher in T1 and T2 than in T3. The best feed conversion ratio (FCR) was obtained by fish in T2, followed by those in T1 and T3. Survival was slightly higher in T1 and T2 than in T3, but no significant differences were recognized among the treatments. Despite this, the significantly highest gross and net productions of snakehead were obtained at the highest density (T3) and the lowest at the lowest density (T1). Therefore, in terms of production, a stocking density of 40 individuals/m2 may be recommended for the large-scale culture of Chevron Snakehead in captivity.
Quantitative frame analysis and the annotation of GC-rich (and other) prokaryotic genomes. An application to Anaeromyxobacter dehalogenans
Authors: Oden Steve , Brocchieri Luciano 
Published: June 2015

Abstract
Motivation: Graphical representations of contrasts in GC usage among codon frame positions (frame analysis) provide evidence of genes missing from the annotations of prokaryotic genomes of high GC content but the qualitative approach of visual frame analysis prevents its applicability on a genomic scale.
Results: We developed two quantitative methods for the identification and statistical characterization in sequence regions of three-base periodicity (hits) associated with open reading frame structures. The methods were implemented in the N-Profile Analysis Computational Tool (NPACT), which highlights in graphical representations inconsistencies between newly identified ORFs and pre-existing annotations of coding-regions. We applied the NPACT procedures to two recently annotated strains of the deltaproteobacterium Anaeromyxobacter dehalogenans, identifying in both genomes numerous conserved ORFs not included in the published annotation of coding regions.
Availability and implementation: NPACT is available as a web-based service and for download at http://genome.ufl.edu/npact.
Contact: lucianob@ufl.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Sparse multi-view matrix factorization: a multivariate approach to multiple tissue comparisons
Authors: Wang Zi , Yuan Wei , Montana Giovanni 
Published: June 2015

Abstract
Motivation: Within any given tissue, gene expression levels can vary extensively among individuals. Such heterogeneity can be caused by genetic and epigenetic variability and may contribute to disease. The abundance of experimental data now enables the identification of features of gene expression profiles that are shared across tissues and those that are tissue-specific. While most current research is concerned with characterizing differential expression by comparing mean expression profiles across tissues, it is believed that a significant difference in a gene expression’s variance across tissues may also be associated with molecular mechanisms that are important for tissue development and function.
Results: We propose a sparse multi-view matrix factorization (sMVMF) algorithm to jointly analyse gene expression measurements in multiple tissues, where each tissue provides a different ‘view’ of the underlying organism. The proposed methodology can be interpreted as an extension of principal component analysis in that it provides the means to decompose the total sample variance in each tissue into the sum of two components: one capturing the variance that is shared across tissues and one isolating the tissue-specific variances. sMVMF has been used to jointly model mRNA expression profiles in three tissues obtained from a large and well-phenotyped twins cohort, TwinsUK. Using sMVMF, we are able to prioritize genes based on whether their variation patterns are specific to each tissue. Furthermore, using DNA methylation profiles available, we provide supporting evidence that adipose-specific gene expression patterns may be driven by epigenetic effects.
Availability and implementation: Python code is available at http://wwwf.imperial.ac.uk/~gmontana/.
Contact: giovanni.montana@kcl.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
Electronic health record usability: analysis of the user-centered design processes of eleven electronic health record vendors
Authors: Ratwani Raj M , Fairbanks Rollin J , Hettinger A Zachary , Benda Natalie C 
Published: June 2015

Abstract
The usability of electronic health records (EHRs) continues to be a point of dissatisfaction for providers, despite certification requirements from the Office of the National Coordinator that require EHR vendors to employ a user-centered design (UCD) process. To better understand factors that contribute to poor usability, a research team visited 11 different EHR vendors in order to analyze their UCD processes and discover the specific challenges that vendors faced as they sought to integrate UCD with their EHR development. Our analysis demonstrates a diverse range of vendors’ UCD practices that fall into 3 categories: well-developed UCD, basic UCD, and misconceptions of UCD. Specific challenges to practicing UCD include conducting contextually rich studies of clinical workflow, recruiting participants for usability studies, and having support from leadership within the vendor organization. The results of the study provide novel insights for how to improve usability practices of EHR vendors.
Sphingosine 1-phosphate Receptor 2 Signaling Suppresses Macrophage Phagocytosis and Impairs Host Defense against Sepsis
Authors: Hou JinChao , Chen QiXing , Zhang Kai , Cheng BaoLi , Xie GuoHao , Wu XiaoLiang , Luo Cheng , Chen LiMin , Liu Hong , Zhao Bing , Dai KeZhi , Fang XiangMing 
Published: June 2015

AbstractAbstract
Deficiency in sphingosine 1-phosphate receptor 2 (S1PR2) enhanced bacterial clearance and improved survival in the mouse model of sepsis. These beneficial effects are attributed to an increase in the phagocytic activity of S1PR2-deficient macrophages. Interventions targeting S1PR2 signaling may thus offer a promising therapeutic approach for the prevention and/or treatment of sepsis.
Supplemental Digital Content is available in the text.

Background:
Sepsis is characterized by an inappropriate systemic inflammatory response and bacteremia that promote multiorgan failure and mortality. Sphingosine 1-phosphate receptor 2 (S1PR2) modulates endotoxin-induced inflammation in endothelium. However, as a highly expressed S1P receptor in macrophages, its role in regulating macrophage response to bacterial infection remains unclear.

Methods:
Cecal ligation and puncture or intratracheal instillation of Escherichia coli was induced in wild-type or S1pr2-deficient mice. The antibacterial ability of cell-specific S1PR2 was tested in bone marrow reconstitution mice or mice with macrophage-specific deletion. Signaling molecules responsible for S1PR2-mediated phagocytosis were also measured in the bone marrow–derived macrophages. In addition, S1PR2 expression levels and its correlation with severity of sepsis were determined in critically ill patients (n = 25).

Results:
Both genetic deletion and pharmaceutical inhibition of S1PR2 significantly limited bacterial burden, reduced lung damage, and improved survival (genetic deletion, 0% in S1pr2
+/+
vs. 78.6% in S1pr2
−/−, P < 0.001; pharmaceutical inhibition, 9.1% in vehicle vs. 22.2% in S1PR2 antagonist, P < 0.05). This protection was attributed to the enhanced phagocytic function of S1PR2-deficient macrophages (mean fluorescent intensity, 2035.2 ± 202.1 vs. 407.8 ± 71.6, P < 0.001). Absence of S1PR2 in macrophage inhibits RhoA-dependent cell contraction and promotes IQGAP1-Rac1-dependent lamellipodial protrusion, whose signaling pathways depend on extracellular stimulators. In septic patients, increased S1PR2 levels in peripheral blood mononuclear cells were positively correlated with the severity of sepsis (r = 0.845, P < 0.001).

Conclusions:
This study implies that S1PR2, as a critical receptor in macrophage, impairs phagocytosis and antimicrobial defense in the pathogenesis of sepsis. Interventions targeting S1PR2 signaling may serve as promising therapeutic approaches for sepsis.
Lung Inhomogeneities and Time Course of Ventilator-induced Mechanical Injuries
Authors: Cressoni Massimo , Chiurazzi Chiara , Gotti Miriam , Amini Martina , Brioni Matteo , Algieri Ilaria , Cammaroto Antonio , Rovati Cristina , Massari Dario , di Castiglione Caterina Bacile , Nikolla Klodiana , Montaruli Claudia , Lazzerini Marco , Dondossola Daniele , Colombo Angelo , Gatti Stefano , Valerio Vincenza , Gagliano Nicoletta , Carlesso Eleonora , Gattinoni Luciano 
Published: June 2015

AbstractAbstract
Ventilator-induced lung injury detected as an increased density on computed tomography scan, first occurred at inhomogeneous interfaces, including at the visceral pleura and the subpleural alveolar walls in anesthetized piglets ventilated with a tidal volume/end-expiratory lung volume more than 2.5. New lung densities were found within 8 h of the ventilation, and their number increased exponentially up to 15 h. Lung elastance and gas exchange deteriorated significantly after 18 h, and full lung edema developed after 20 h.
Supplemental Digital Content is available in the text.

Background:
During mechanical ventilation, stress and strain may be locally multiplied in an inhomogeneous lung. The authors investigated whether, in healthy lungs, during high pressure/volume ventilation, injury begins at the interface of naturally inhomogeneous structures as visceral pleura, bronchi, vessels, and alveoli. The authors wished also to characterize the nature of the lesions (collapse vs. consolidation).

Methods:
Twelve piglets were ventilated with strain greater than 2.5 (tidal volume/end-expiratory lung volume) until whole lung edema developed. At least every 3 h, the authors acquired end-expiratory/end-inspiratory computed tomography scans to identify the site and the number of new lesions. Lung inhomogeneities and recruitability were quantified.

Results:
The first new densities developed after 8.4 ± 6.3 h (mean ± SD), and their number increased exponentially up to 15 ± 12 h. Afterward, they merged into full lung edema. A median of 61% (interquartile range, 57 to 76) of the lesions appeared in subpleural regions, 19% (interquartile range, 11 to 23) were peribronchial, and 19% (interquartile range, 6 to 25) were parenchymal (P < 0.0001). All the new densities were fully recruitable. Lung elastance and gas exchange deteriorated significantly after 18 ± 11 h, whereas lung edema developed after 20 ± 11 h.

Conclusions:
Most of the computed tomography scan new densities developed in nonhomogeneous lung regions. The damage in this model was primarily located in the interstitial space, causing alveolar collapse and consequent high recruitability.
Does electronic health record use improve hospital financial performance? Evidence from panel data
Authors: Collum Taleah H. , Menachemi Nir , Sen Bisakha 
Published: June 2015

Purpose:
The aim of this study was to examine the impact of electronic health record (EHR) adoption on hospital financial performance.

Methodology/Approach:
We constructed a longitudinal panel using data from the three secondary sources: (a) the 2007–2010 American Hospital Association (AHA) Annual Survey, (b) the 2007–2010 AHA Annual Survey Information Technology Supplement, and (c) the 2007–2011 Medicare Cost Reports from Centers for Medicare and Medicaid Services. Because potential financial benefits attributable to EHR adoption may take some time to accrue, we ran regressions with lags of 1 and 2 years that included hospital and year fixed effects to examine the relationship between the level of EHR adoption and three hospital financial performance measures.

Findings:
A change in the level of EHR adoption was not associated with changes in operating margin or return on assets within hospitals. However, total margin was significantly improved, after 2 years, in hospitals that moved from no EHR to having a comprehensive EHR in all areas of their hospital (β = 0.030, p < .034). On the other hand, hospitals that increased their level of EHR adoption but did not achieve hospital-wide comprehensive adoption did not experience changes in any financial performance measures examined.

Practice Implications:
The improvements in total margin, as opposed to operating margin, are likely due to hospital incentive payments under the Health Information Technology for Economic and Clinical Health Act that are reflected in nonpatient revenues and therefore show up in total margin calculations. Thus, after 2 years of EHR adoption, hospital financial performance is observed to improve based only on meaningful use incentive payments. More research will be needed to determine whether EHR adoption impacts financial performance on a longer time horizon.
Exploring the link between clinical managers involvement in budgeting and performance
Authors: Macinati Manuela S. , Rizzo Marco G. 
Published: June 2015

Background:
The public health care sector has had an increase in initiatives, mostly inspired by New Public Management principles, aimed at assigning financial accountability to clinical managers. However, clinical managers might experience a scarce alignment between professional values and organizational requirements, which is a potentially important phenomena that may result in negative consequences on clinical managers' job performance.

Purposes:
Building on Psychological Ownership Theory and adopting a psychology-based management accounting research approach, we focus on the managerial (nonmedical) role the clinical manager fulfills and explore the budgetary participation–performance link via the indirect effects of job-based psychological ownership, role clarity, and clinical managers' affective commitment toward managerial roles.

Methodology/Approach:
The data were collected by a survey conducted in an Italian hospital. The research hypotheses were tested employing a path model.

Findings:
Our study revealed new insights that shed some light on underexplored processes through which mental states mediate the participation–performance link. Among these latter, the findings demonstrate that (a) budgetary participation has a direct effect on job-based psychological ownership; (b) role clarity mediates participation- and job-based psychological ownership link; (c) role clarity and job-based psychological ownership partially mediate the participation–commitment link; and (d) job-based psychological ownership, role clarity, and commitment fully mediate the participation–performance link.

Practice Implications:
From a managerial viewpoint, an understanding of how clinical managers' feelings of ownership toward managerial roles could be enhanced is imperative in health care because ownership accounts for important attitudinal and organizational consequences. Results suggest that health care organizations that invest in budgetary participation will directly and indirectly affect clinical managers' psychological ownership, and this, along with role clarity, motivates clinical managers' managerial work attitudes and performance.