bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a Novel Putative Xer-Dependent Integrative Mobile Element Carrying the
bla
NMC-A
Carbapenemase Gene, Inserted into the Chromosome of Members of the Enterobacter cloacae Complex
Authors: Antonelli Alberto , D'Andrea Marco Maria , Di Pilato Vincenzo , Viaggi Bruno , Torricelli Francesca , Rossolini Gian Maria 
Published: July 2015

ABSTRACT

An
Enterobacter ludwigii
strain was isolated during routine screening of a Japanese patient for carriage of carbapenem-resistant
Enterobacteriaceae
. PCR analysis revealed the
bla
NMC-A
carbapenemase gene. Whole-genome sequencing revealed that
bla
NMC-A
was inserted in the chromosome and associated with a novel 29.1-kb putative Xer-dependent integrative mobile element, named EludIMEX-1. Bioinformatic analysis identified similar elements in the genomes of an
Enterobacter asburiae
strain and of other
Enterobacter cloacae
complex strains, confirming the mobile nature of this element.
Detection of a New
cfr
-Like Gene,
cfr
(B), in Enterococcus faecium Isolates Recovered from Human Specimens in the United States as Part of the SENTRY Antimicrobial Surveillance Program
Authors: Deshpande Lalitagauri M. , Ashcraft Deborah S. , Kahn Heather P. , Pankey George , Jones Ronald N. , Farrell David J. , Mendes Rodrigo E. 
Published: July 2015

ABSTRACT

Two linezolid-resistant
Enterococcus faecium
isolates (MICs, 8 μg/ml) from unique patients of a medical center in New Orleans were included in this study. Isolates were initially investigated for the presence of mutations in the V domain of 23S rRNA genes and L3, L4, and L22 ribosomal proteins, as well as
cfr
. Isolates were subjected to pulsed-field gel electrophoresis (just one band difference), and one representative strain was submitted to whole-genome sequencing. Gene location was also determined by hybridization, and
cfr
genes were cloned and expressed in a
Staphylococcus aureus
background. The two isolates had one out of six 23S rRNA alleles mutated (G2576T), had wild-type L3, L4, and L22 sequences, and were positive for a
cfr
-like gene. The sequence of the protein encoded by the
cfr
-like gene was most similar (99.7%) to that found in
Peptoclostridium difficile
, which shared only 74.9% amino acid identity with the proteins encoded by genes previously identified in staphylococci and non-
faecium
enterococci and was, therefore, denominated Cfr(B). When expressed in
S. aureus
, the protein conferred a resistance profile similar to that of Cfr. Two copies of
cfr
(B) were chromosomally located and embedded in a Tn
6218
similar to the
cfr
-carrying transposon described in
P. difficile.
This study reports the first detection of
cfr
genes in
E. faecium
clinical isolates in the United States and characterization of a new
cfr
variant,
cfr
(B).
cfr
(B) has been observed in mobile genetic elements in
E. faecium
and
P. difficile
, suggesting potential for dissemination. However, further analysis is necessary to access the resistance levels conferred by
cfr
(B) when expressed in enterococci.
Draft Genome Sequence of Ochrobactrum anthropi Strain W13P3, a Halotolerant Polycyclic Aromatic Hydrocarbon-Degrading Bacterium
Authors: Wang Xinxin , Jin Decai , Zhou Lisha , Zhang Zhuo 
Published: July 2015

ABSTRACT

Ochrobactrum anthropi
W13P3 was isolated from saline soil contaminated by polycyclic aromatic hydrocarbons (PAHs) and could degrade PAHs with 5% NaCl. We report the 5.3-Mb draft genome sequence of this strain, which is helpful for understanding the diversity of
Ochrobactrum
spp. and the mechanism of PAH degradation in saline environments.
Chemotaxis Control of Transient Cell Aggregation
Authors: Alexandre Gladys 
Published: July 2015

ABSTRACT
Chemotaxis affords motile cells the ability to rapidly respond to environmental challenges by navigating cells to niches favoring growth. Such a property results from the activities of dedicated signal transduction systems on the motility apparatus, such as flagella, type IV pili, and gliding machineries. Once cells have reached a niche with favorable conditions, they often stop moving and aggregate into complex communities termed biofilms. An intermediate and reversible stage that precedes commitment to permanent adhesion often includes transient cell-cell contacts between motile cells. Chemotaxis signaling has been implicated in modulating the transient aggregation of motile cells. Evidence further indicates that chemotaxis-dependent transient cell aggregation events are behavioral responses to changes in metabolic cues that temporarily prohibit permanent attachment by maintaining motility and chemotaxis. This minireview discusses a few examples illustrating the role of chemotaxis signaling in the initiation of cell-cell contacts in bacteria moving via flagella, pili, or gliding.
Bacillus anthracis SlaQ Promotes S-Layer Protein Assembly
Authors: Nguyen-Mau Sao-Mai , Oh So-Young , Schneewind Daphne I. , Missiakas Dominique , Schneewind Olaf 
Published: July 2015

ABSTRACT

Bacillus anthracis
vegetative forms assemble an S-layer comprised of two S-layer proteins, Sap and EA1. A hallmark of S-layer proteins are their C-terminal crystallization domains, which assemble into a crystalline lattice once these polypeptides are deposited on the bacterial surface via association between their N-terminal S-layer homology domains and the secondary cell wall polysaccharide. Here we show that
slaQ
, encoding a small cytoplasmic protein conserved among pathogenic bacilli elaborating S-layers, is required for the efficient secretion and assembly of Sap and EA1. S-layer protein precursors cosediment with SlaQ, and SlaQ appears to facilitate Sap assembly. Purified SlaQ polymerizes and when mixed with purified Sap promotes the
in vitro
formation of tubular S-layer structures. A model is discussed whereby SlaQ, in conjunction with S-layer secretion factors SecA2 and SlaP, promotes localized secretion and S-layer assembly in
B. anthracis
.

IMPORTANCE
S-layer proteins are endowed with the propensity for self-assembly into crystalline arrays. Factors promoting S-layer protein assembly have heretofore not been reported. We identified
Bacillus anthracis
SlaQ, a small cytoplasmic protein that facilitates S-layer protein assembly
in vivo
and
in vitro
.
Female genital mutilation in children presenting to a London safeguarding clinic: a case series
Authors: Hodes Deborah , Armitage Alice , Robinson Kerry , Creighton Sarah M 
Published: July 2015

ObjectiveTo describe the presentation and management of children referred with suspected female genital mutilation (FGM) to a UK safeguarding clinic.Design and settingCase series of all children under 18 years of age referred with suspected FGM between June 2006 and May 2014.Main outcome measuresThese include indication for referral, demographic data, circumstances of FGM, medical symptoms, type of FGM, investigations and short-term outcome.ResultsOf the 47 girls referred, 27 (57%) had confirmed FGM. According to the WHO classification of genital findings, FGM type 1 was found in 2 girls, type 2 in 8 girls and type 4 in 11 girls. No type 3 FGM was seen. The circumstances of FGM were known in 17 cases, of which 12 (71%) were performed by a health professional or in a medical setting (medicalisation). Ten cases were potentially illegal, yet despite police involvement there have been no prosecutions.ConclusionsThis study is an important snapshot of FGM within the UK paediatric population. The most frequent genital finding was type 4 FGM with no tissue damage or minimal scarring. FGM was performed at a young age, with 15% reported under the age of 1 year. The study also demonstrated significant medicalisation of FGM, which matches recent trends in international data. Type 4 FGM performed in infancy is easily missed on examination and so vigilance in assessing children with suspected FGM is essential.
Euthanasia requests, procedures and outcomes for 100 Belgian patients suffering from psychiatric disorders: a retrospective, descriptive study
Authors: Thienpont Lieve , Verhofstadt Monica , Van Loon Tony , Distelmans Wim , Audenaert Kurt , De Deyn Peter P 
Published: July 2015

ObjectivesTo identify patterns in euthanasia requests and practices relating to psychiatric patients; to generate recommendations for future research.DesignRetrospective analysis of data obtained through medical file review.SettingOutpatient psychiatric clinical setting in the Dutch-speaking region of Belgium, between October 2007 and December 2011; follow-up at the end of December 2012.Participants100 consecutive psychiatric patients requesting euthanasia based on psychological suffering associated with psychiatric disorders (77 women, 23 men; mean age 47 years; age range 21–80 years).Main outcome measuresPatient sociodemographic characteristics; diagnoses; decisions on euthanasia requests; circumstances of euthanasia procedures; patient outcomes at follow-up.ResultsMost patients had been referred for psychiatric counselling by their physician (n=55) or by LEIF (Life End Information Forum) (n=36). 90 patients had >1 disorder; the most frequent diagnoses were depression (n=58) and personality disorder (n=50). 38 patients required further testing and/or treatment, including 13 specifically tested for autism spectrum disorder (ASD); 12 received an ASD diagnosis (all Asperger syndrome). In total, 48 of the euthanasia requests were accepted and 35 were carried out. Of the 13 remaining patients whose requests were accepted, 8 postponed or cancelled the procedure, because simply having this option gave them enough peace of mind to continue living. In December 2012, 43 patients had died, including 35 by euthanasia; others died by suicide (6), palliative sedation (1) and anorexia nervosa (1).ConclusionsDepression and personality disorders are the most common diagnoses in psychiatric patients requesting euthanasia, with Asperger syndrome representing a neglected disease burden. Further research is needed, especially prospective quantitative and qualitative studies, to obtain a better understanding of patients with psychiatric disorders who request euthanasia due to unbearable psychological suffering.
Floor and ceiling effects in the OHS:an analysis of the NHS PROMs data set
Authors: Lim Christopher R , Harris Kristina , Dawson Jill , Beard David J , Fitzpatrick Ray , Price Andrew J 
Published: July 2015

ObjectivesThe objective was to examine whether the Oxford Hip Score (OHS) demonstrated a floor or a ceiling effect when used to measure the outcome of hip replacement surgery in a large national cohort.SettingSecondary database analysis of a national audit conducted in England and Wales on patient undergoing hip and knee arthroplasty in a secondary care setting.Participants93 253 primary arthroplasty patients completed preoperative OHS questionnaires and 69 361 completed 6-month postoperative OHS questionnaires. The population had a mean age of 67.78 (range 14–100, SD 11.3) and 59% were female.Primary Secondary Outcome MeasuresPrimary outcome measure was the Oxford Hip Score (OHS). Secondary outcome measures were the OHS-FCS and OHS-PCS. Floor and ceiling effects were considered present if >15% of patients achieved the worst score/floor effect (0/48) or best/ceiling effect (48/48) score.ResultsPreoperatively, 0% of patients achieved the best score (48) and 0.1% achieved the worst score (0). Postoperatively, 0.1% patients achieved the worst score, but the percentage achieving the best score increased to 11.6%. Subgroup analyses demonstrated that patients between 50 and 59 years of age had the highest postoperative best score, at 15.3%. The highest postoperative OHS worst score percentage was in a group of patients who had a preoperative OHS above 41/48 at 28%. Furthermore, 22.6% of patients achieved the best postoperative OHS-PCS and 19.9% best postoperative OHS-FCS.ConclusionsBased on NHS PROMS data the overall OHS does not exhibit a ceiling or floor effect and should continue to be used as a valid measure of patient-reported outcomes for patients undergoing total hip arthroplasty. However, subscale analysis does indicate some limitations in the OHS-PCS and OHS-FCS.Trial registration numberNDORMS. Introducing standardised and evidence-based thresholds for hip and knee replacement surgery. The Arthroplasty Candidacy Help Engine (ACHE tool). HTA Project 11/63/01.
Low rate of and rapid attention to inappropriate ICD shocks with remote device and rhythm monitoring: a qualitative study
Authors: Sandgren Emma , Rorsman Cecilia , Engdahl Johan , Edvardsson Nils 
Published: July 2015

ObjectivesInappropriate shocks are unpleasant and painful. We hypothesise that remote monitoring and careful attention to known and incident atrial fibrillation (AF) can reduce inappropriate shocks to a very low level in clinical praxis.MethodsAltogether 259 patients with implantable cardioverter defibrillator implanted for secondary (S, n=113) and primary (P, n=146) prevention were followed via remote monitoring. At implant, 42S (37%) and 54P (37%) patients had known AF.ResultsInappropriate shocks, all but five due to AF, occurred in 7S (6.2%) and 11P (7.5%), and there were only inappropriate shocks in 5/7S and in 8/11P. They occurred in four of 42S (9.5%) with and in three of 71S (4.2%) without known AF, and in seven of 54P (13%) with and in four of 92P (4.3%) without known AF. The median time from shock to action was 5 and 1 day, respectively. Actions were medication with amiodarone, β blockers, β blockers+amiodarone or β blockers+digoxin (n=5), β blockers+insertion of an atrial lead (n=1), replacement of a fractured lead (n=2), reprogramming in combination with β blockers, digoxin or amiodarone (n=4), reprogramming (n=2) and none (n=4). After action, four further inappropriate shocks occurred during more than 2 years of follow-up, all due to AF.ConclusionsInappropriate shocks occurred at a low rate and most often because of AF known at implant. Remote monitoring enabled rapid action, after which few inappropriate shocks occurred over more than 2 years. Attention to known and incident AF was the most important action to reduce inappropriate shocks.
Exploration of upside in a stranded discovery: Lochranza, a Donan Field satellite
Authors: Ings R. J. , Konings S. P. M. , Kumar R. , Wood E. L. , Melvin A. , Stanbrook D. A. , Agnew C. 
Published: July 2015

Abstract
The Lochranza Field was developed using seismic amplitude analysis, evolving conceptual geological models and the implementation of horizontal well technology, built on the knowledge gained from the adjacent Donan Field redevelopment. Subtle depositional and structural complexities were, however, encountered in the Lochranza development wells. These had the potential to impact on the successful targeting of reservoir sands.
Thinning sands and erratic lateral sand pinch-outs at the margins of the deep-water Balmoral Fan complex, small-scale sand injection and subtle structural complexity across the Lochranza Field were identified in the first phase of development. These introduced greater interpretation uncertainty and made further development challenging. This highlighted the importance of considering alternative geological scenarios, whilst these insights aided the identification of infill well opportunities.
These uncertainties were partially mitigated by the planned development well trajectory, the data acquisition programme and the ability to geosteer based upon the geology encountered. It proved important to be mindful of different geological scenarios whilst geosteering, guided by the real-time dataset, keeping the 3D geological model peripheral to decision-making to limit the impact of anchoring bias.
Identification of infill targets used a pragmatic approach based upon empirical data that showed that well recovery efficiency could be characterized by net pay length, stand-off from the oil–water contact (OWC) and connected hydrocarbon volume. Infill opportunities were defined probabilistically and subsequently supported by 3D reservoir simulation. This assessment was helped significantly by additional appraisal being undertaken as part of development well drilling.
Air meshes for robust collision handling
Authors: Müller Matthias , Chentanez Nuttapong , Kim Tae-Yong , Macklin Miles 
Published: July 2015

We propose a new method for both collision detection and collision response geared towards handling complex deformable objects in close contact. Our method does not miss collision events between time steps and solves the challenging problem of untangling automatically and robustly. It is conceptually simple and straight forward to parallelize due to the regularity of the algorithm.
The main idea is to tessellate the air between objects once before the simulation and by considering one unilateral constraint per element that prevents its inversion during the simulation. If large relative rotations and translations are present in the simulation, an additional dynamic mesh optimization step is needed to prevent mesh locking. This step is fast in 2D and allows the simulation of arbitrary scenes. Because mesh optimization is expensive in 3D, however, the method is best suited for the subclass of 3D scenarios in which relative motions are limited. This subclass contains two important problems, namely the simulation of multi-layered clothing and tissue on animated characters.
A stream function solver for liquid simulations
Authors: Ando Ryoichi , Thuerey Nils , Wojtan Chris 
Published: July 2015

This paper presents a liquid simulation technique that enforces the incompressibility condition using a stream function solve instead of a pressure projection. Previous methods have used stream function techniques for the simulation of detailed single-phase flows, but a formulation for liquid simulation has proved elusive in part due to the free surface boundary conditions. In this paper, we introduce a stream function approach to liquid simulations with novel boundary conditions for free surfaces, solid obstacles, and solid-fluid coupling.
Although our approach increases the dimension of the linear system necessary to enforce incompressibility, it provides interesting and surprising benefits. First, the resulting flow is guaranteed to be divergence-free regardless of the accuracy of the solve. Second, our free-surface boundary conditions guarantee divergence-free motion even in the un-simulated air phase, which enables two-phase flow simulation by only computing a single phase. We implemented this method using a variant of FLIP simulation which only samples particles within a narrow band of the liquid surface, and we illustrate the effectiveness of our method for detailed two-phase flow simulations with complex boundaries, detailed bubble interactions, and two-way solid-fluid coupling.
Reversal of Warburg Effect and Reactivation of Oxidative Phosphorylation by Differential Inhibition of EGFR Signaling Pathways in Non–Small Cell Lung Cancer
Authors: De Rosa Viviana , Iommelli Francesca , Monti Marcello , Fonti Rosa , Votta Giuseppina , Stoppelli Maria Patrizia , Del Vecchio Silvana 
Published: July 2015

Abstract
Purpose: One of the hallmarks of cancer cells is the excessive conversion of glucose to lactate under normoxic conditions, also known as the Warburg effect. Here, we tested whether the targeted inhibition of EGFR may revert this effect and reactivate mitochondrial oxidative phosphorylation in non–small cell lung cancer (NSCLC).
Experimental Design: Sensitive (HCC827) and resistant (H1975 and H1993) NSCLC cells were treated with a panel of EGFR or MET inhibitors, and then tested for changes of EGFR signaling, glycolytic cascade, and mitochondrial function. Silencing of key glycolytic enzymes was then performed with targeted siRNAs. Furthermore, tumor-bearing nude mice treated with EGFR inhibitors were evaluated with 18F-FDG PET/CT and tumors were analyzed for glycolytic and mitochondrial proteins.
Results: Effective inhibition of EGFR signaling in NSCLC cells induced a dramatic reduction of hexokinase II (HKII) and phospho-pyruvate kinase M2 (p-PKM2, Tyr105) levels as well as an upregulation of mitochondrial complexes subunits (OXPHOS). Accordingly, a decreased lactate secretion and increased intracellular ATP levels were also observed in response to EGFR inhibitors. Downregulation of HKII and PKM2 by targeted siRNA transfection did not cause upregulation of OXPHOS but enhanced the effects of EGFR TKIs. Conversely, selective inhibition of AKT and ERK1/2 caused OXPHOS upregulation and glycolysis inhibition, respectively. Similar findings were obtained in tumors from animals treated with appropriate EGFR inhibitors.
Conclusions: Our findings indicate that EGFR inhibitors may reactivate oxidative phosphorylation of cancer cells and provide a mechanistic clue for the rational combination of agents targeting EGFR-dependent proliferation and glucose metabolism in cancer therapy. Clin Cancer Res; 21(22); 5110–20. ©2015 AACR.
Mechanistic Dissection of PARP1 Trapping and the Impact on In Vivo Tolerability and Efficacy of PARP Inhibitors
Authors: Hopkins Todd A. , Shi Yan , Rodriguez Luis E. , Solomon Larry R. , Donawho Cherrie K. , DiGiammarino Enrico L. , Panchal Sanjay C. , Wilsbacher Julie L. , Gao Wenqing , Olson Amanda M. , Stolarik DeAnne F. , Osterling Donald J. , Johnson Eric F. , Maag David 
Published: July 2015

Abstract
Poly(ADP-ribose) polymerases (PARP1, -2, and -3) play important roles in DNA damage repair. As such, a number of PARP inhibitors are undergoing clinical development as anticancer therapies, particularly in tumors with DNA repair deficits and in combination with DNA-damaging agents. Preclinical evidence indicates that PARP inhibitors potentiate the cytotoxicity of DNA alkylating agents. It has been proposed that a major mechanism underlying this activity is the allosteric trapping of PARP1 at DNA single-strand breaks during base excision repair; however, direct evidence of allostery has not been reported. Here the data reveal that veliparib, olaparib, niraparib, and talazoparib (BMN-673) potentiate the cytotoxicity of alkylating agents. Consistent with this, all four drugs possess PARP1 trapping activity. Using biochemical and cellular approaches, we directly probe the trapping mechanism for an allosteric component. These studies indicate that trapping is due to catalytic inhibition and not allostery. The potency of PARP inhibitors with respect to trapping and catalytic inhibition is linearly correlated in biochemical systems but is nonlinear in cells. High-content imaging of γH2Ax levels suggests that this is attributable to differential potentiation of DNA damage in cells. Trapping potency is inversely correlated with tolerability when PARP inhibitors are combined with temozolomide in mouse xenograft studies. As a result, PARP inhibitors with dramatically different trapping potencies elicit comparable in vivo efficacy at maximum tolerated doses. Finally, the impact of trapping on tolerability and efficacy is likely to be context specific.
Implications: Understanding the context-specific relationships of trapping and catalytic inhibition with both tolerability and efficacy will aid in determining the suitability of a PARP inhibitor for inclusion in a particular clinical regimen. Mol Cancer Res; 13(11); 1465–77. ©2015 AACR.