bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Ferrous Iron Exporter Mediates Iron Resistance in Shewanella oneidensis MR-1
Authors: Bennett Brittany D. , Brutinel Evan D. , Gralnick Jeffrey A. 
Published: September 2015

ABSTRACT

Shewanella oneidensis
strain MR-1 is a dissimilatory metal-reducing bacterium frequently found in aquatic sediments. In the absence of oxygen,
S. oneidensis
can respire extracellular, insoluble oxidized metals, such as iron (hydr)oxides, making it intimately involved in environmental metal and nutrient cycling. The reduction of ferric iron (Fe
3+
) results in the production of ferrous iron (Fe
2+
) ions, which remain soluble under certain conditions and are toxic to cells at higher concentrations. We have identified an inner membrane protein in
S. oneidensis
, encoded by the gene SO_4475 and here called FeoE, which is important for survival during anaerobic iron respiration. FeoE, a member of the cation diffusion facilitator (CDF) protein family, functions to export excess Fe
2+
from the MR-1 cytoplasm. Mutants lacking
feoE
exhibit an increased sensitivity to Fe
2+
. The export function of FeoE is specific for Fe
2+
, as an
feoE
mutant is equally sensitive to other metal ions known to be substrates of other CDF proteins (Cd
2+
, Co
2+
, Cu
2+
, Mn
2+
, Ni
2+
, or Zn
2+
). The substrate specificity of FeoE differs from that of FieF, the
Escherichia coli
homolog of FeoE, which has been reported to be a Cd
2+
/Zn
2+
or Fe
2+
/Zn
2+
exporter. A complemented
feoE
mutant has an increased growth rate in the presence of excess Fe
2+
compared to that of the Δ
feoE
mutant complemented with
fieF
. It is possible that FeoE has evolved to become an efficient and specific Fe
2+
exporter in response to the high levels of iron often present in the types of environmental niches in which
Shewanella
species can be found.
A Novel Type Pathway-Specific Regulator and Dynamic Genome Environments of a Solanapyrone Biosynthesis Gene Cluster in the Fungus Ascochyta rabiei
Authors: Kim Wonyong , Park Jeong-Jin , Gang David R. , Peever Tobin L. , Chen Weidong 
Published: September 2015

ABSTRACT

Secondary metabolite genes are often clustered together and situated in particular genomic regions, like the subtelomere, that can facilitate niche adaptation in fungi. Solanapyrones are toxic secondary metabolites produced by fungi occupying different ecological niches. Full-genome sequencing of the ascomycete
Ascochyta rabiei
revealed a solanapyrone biosynthesis gene cluster embedded in an AT-rich region proximal to a telomere end and surrounded by
Tc1/Mariner
-type transposable elements. The highly AT-rich environment of the solanapyrone cluster is likely the product of repeat-induced point mutations. Several secondary metabolism-related genes were found in the flanking regions of the solanapyrone cluster. Although the solanapyrone cluster appears to be resistant to repeat-induced point mutations, a
P450
monooxygenase gene adjacent to the cluster has been degraded by such mutations. Among the six solanapyrone cluster genes (
sol1
to
sol6
),
sol4
encodes a novel type of Zn(II)2Cys6 zinc cluster transcription factor. Deletion of
sol4
resulted in the complete loss of solanapyrone production but did not compromise growth, sporulation, or virulence. Gene expression studies with the
sol4
deletion and
sol4
-overexpressing mutants delimited the boundaries of the solanapyrone gene cluster and revealed that
sol4
is likely a specific regulator of solanapyrone biosynthesis and appears to be necessary and sufficient for induction of the solanapyrone cluster genes. Despite the dynamic surrounding genomic regions, the solanapyrone gene cluster has maintained its integrity, suggesting important roles of solanapyrones in fungal biology.
Function and Regulation of Cph2 in Candida albicans
Authors: Lane Shelley , Di Lena Pietro , Tormanen Kati , Baldi Pierre , Liu Haoping 
Published: September 2015

ABSTRACT

Candida albicans
is associated with humans as both a harmless commensal organism and a pathogen. Cph2 is a transcription factor whose DNA binding domain is similar to that of mammalian sterol response element binding proteins (SREBPs). SREBPs are master regulators of cellular cholesterol levels and are highly conserved from fungi to mammals. However, ergosterol biosynthesis is regulated by the zinc finger transcription factor Upc2 in
C. albicans
and several other yeasts. Cph2 is not necessary for ergosterol biosynthesis but is important for colonization in the murine gastrointestinal (GI) tract. Here we demonstrate that Cph2 is a membrane-associated transcription factor that is processed to release the N-terminal DNA binding domain like SREBPs, but its cleavage is not regulated by cellular levels of ergosterol or oxygen. Chromatin immunoprecipitation sequencing (ChIP-seq) shows that Cph2 binds to the promoters of
HMS1
and other components of the regulatory circuit for GI tract colonization. In addition, 50% of Cph2 targets are also bound by Hms1 and other factors of the regulatory circuit. Several common targets function at the head of the glycolysis pathway. Thus, Cph2 is an integral part of the regulatory circuit for GI colonization that regulates glycolytic flux. Transcriptome sequencing (RNA-seq) shows a significant overlap in genes differentially regulated by Cph2 and hypoxia, and Cph2 is important for optimal expression of some hypoxia-responsive genes in glycolysis and the citric acid cycle. We suggest that Cph2 and Upc2 regulate hypoxia-responsive expression in different pathways, consistent with a synthetic lethal defect of the
cph2 upc2
double mutant in hypoxia.
Origin and Dissemination of Antimicrobial Resistance among Uropathogenic
Escherichia coli
Authors: Nolan Lisa K. , Li Ganwu , Logue Catherine M. 
Published: September 2015

ABSTRACT

Antimicrobial agents of various types have important bearing on the outcomes of microbial infections. These agents may be bacteriostatic or –cidal, exert their impact via various means, originate from a living organism or a laboratory, and appropriately be used in or on living tissue or not. Though the primary focus of this chapter is on resistance to the antimicrobial agents used to treat uropathogenic
Escherichia coli
(UPEC)-caused urinary tract infections (UTIs), some attention will be given to UPEC’s resistance to silver-containing antiseptics, which may be incorporated into catheters to prevent foreign body-associated UTIs.
Socioeconomic variation in height: analysis of National Child Measurement Programme data for England
Authors: Hancock Caroline , Bettiol Silvana , Smith Lesley 
Published: September 2015

ObjectiveShort stature is associated with increased risk of ill health and mortality and can negatively impact on an individual's economic opportunity and psychological well-being. The aim of this study was to investigate the association between height and area-level deprivation by ethnic group in children in England.DesignCross-sectional analysis of data gathered from the National Child Measurement Programme 2008/2009 to 2012/2013.Participants/methodsChildren (n=1 213 230) aged 4–5 and 10–11 years attending state-maintained primary schools in England. Mean height SD score (SDS) (based on the British 1990 growth reference) was calculated for children by Income Deprivation Affecting Children Index as a measure of area-level deprivation. Analyses were performed by sex and age group for white British, Asian and black ethnicities.ResultsFor white British children mean height decreased 0.2 SDS between the least and the most deprived quintile. For Asian children the relationship was weaker and varied between 0.08 and 0.18 SDS. For white British boys the magnitude of association was similar across age groups; for Asian boys the magnitude was higher in the age group of 10–11 years and in white British girls aged 10–11 years the association decreased. Height SDS was similar across all levels of deprivation for black children.ConclusionsSocial inequalities were shown in the height of children from white British and Asian ethnic groups. Further evaluation of height in black children is warranted. Action is needed to reduce inequalities in height by addressing the modifiable negative environmental factors that prevent healthy growth and development of children.
Admission to hospital for bronchiolitis in England: trends over five decades, geographical variation and association with perinatal characteristics and subsequent asthma
Authors: Green Christopher A , Yeates David , Goldacre Allie , Sande Charles , Parslow Roger C , McShane Philip , Pollard Andrew J , Goldacre Michael J 
Published: September 2015

BackgroundAdmission of infants to hospital with bronchiolitis consumes considerable healthcare resources each winter. We report an analysis of hospital admissions in England over five decades.MethodsData were analysed from the Hospital In-Patient Enquiry (HIPE, 1968–1985), Hospital Episode Statistics (HES, 1989–2011), Oxford Record Linkage Study (ORLS, 1963–2011) and Paediatric Intensive Care Audit Network (PICANet, 2003–2012). Cases were identified using International Classification of Diseases (ICD) codes in discharge records. Bronchiolitis was given a separate code in ICD9 (used in England from 1979). Geographical variation was analysed using Local Authority area boundaries. Maternal and perinatal risk factors associated with bronchiolitis and subsequent admissions for asthma were analysed using record-linkage.ResultsAll-England HIPE and HES data recorded 468 138 episodes of admission for bronchiolitis in infants aged <1 year between 1979 and 2011. In 2011 the estimated annual hospital admission rate was 46.1 (95% CI 45.6 to 46.6) per 1000 infants aged <1 year. Between 2004 and 2011 the rates rose by an average of 1.8% per year in the all-England HES data, whereas admission rates to paediatric intensive care changed little (1.3 to 1.6 per 1000 infants aged <1 year). A fivefold geographical variation in hospital admission rates was observed. Young maternal age, low social class, low birth weight and maternal smoking were among factors associated with an increased risk of hospital admission with bronchiolitis.ConclusionsHospital admissions for infants with bronchiolitis have increased substantially in recent years. However, cases requiring intensive care have changed little since 2004.
Comparison of drug coverage in Canada before and after the establishment of the pan-Canadian Pharmaceutical Alliance
Authors: Milliken Debbie , Venkatesh Jaya , Yu Rebecca , Su Zhuo , Thompson Melissa , Eurich Dean 
Published: September 2015

ObjectivesThis study was conducted to determine whether establishment of the pan-Canadian Pharmaceutical Alliance (pCPA) was associated with significant changes in drug listing decisions across Canada.Analysis and resultsThis study included drug indications that received a Common Drug Review or pan-Canadian Oncology Drug Review listing recommendation within 3 years before (‘pre-PCPA era’ group; n=79) and 3 years after (‘PCPA era’ group; n=91) the pCPA was established in August 2010. At the time of this study (30 April 2014), nine pCPA-participating jurisdictions had listed 35–59% of drug indications in the pre-pCPA era group and a nearly identical range, 36–59%, in the pCPA era group. Within the pCPA-era group, 31 drug indications (34%) had completed pCPA negotiations (‘pCPA negotiation’ subgroup); the jurisdictions had listed 39–77% of these drug indications. Comparison of the pCPA era group to the pre-pCPA era group indicated that the proportion listed did not change significantly in any jurisdiction, and time-to-listing increased significantly in New Brunswick and decreased significantly in Alberta, Manitoba, and Ontario. When the pCPA negotiation subgroup was compared to the pre-pCPA era group, the proportion listed increased significantly in British Columbia, Saskatchewan, Manitoba and Newfoundland and Labrador, and time-to-listing increased significantly in New Brunswick and Nova Scotia and decreased significantly in Manitoba and Ontario. A sensitivity analysis suggested more favourable results regarding the pCPA's impact.ConclusionsWhile the pCPA might have had a varied effect on time-to-listing, this study's primary analysis did not observe a significant impact on the overall proportion of new drug indications listed across jurisdictions. This may be due to the fact that, at the time of this study, only a limited number of drug indications had completed pCPA negotiations. This study provides a framework for future evaluations of the pCPA's impact as it continues to evolve.
Designing and recruiting to UK autism spectrum disorder research databases: do they include representative children with valid ASD diagnoses?
Authors: Warnell F , George B , McConachie H , Johnson M , Hardy R , Parr J R 
Published: September 2015

Objectives(1) Describe how the Autism Spectrum Database-UK (ASD-UK) was established; (2) investigate the representativeness of the first 1000 children and families who participated, compared to those who chose not to; (3) investigate the reliability of the parent-reported Autism Spectrum Disorder (ASD) diagnoses, and present evidence about the validity of diagnoses, that is, whether children recruited actually have an ASD; (4) present evidence about the representativeness of the ASD-UK children and families, by comparing their characteristics with the first 1000 children and families from the regional Database of children with ASD living in the North East (Daslne), and children and families identified from epidemiological studies.SettingRecruitment through a network of 50 UK child health teams and self-referral.PatientsParents/carers with a child with ASD, aged 2–16 years, completed questionnaires about ASD and some gave professionals’ reports about their children.Results1000 families registered with ASD-UK in 30 months. Children of families who participated, and of the 208 who chose not to, were found to be very similar on: gender ratio, year of birth, ASD diagnosis and social deprivation score. The reliability of parent-reported ASD diagnoses of children was very high when compared with clinical reports (over 96%); no database child without ASD was identified. A comparison of gender, ASD diagnosis, age at diagnosis, school placement, learning disability, and deprivation score of children and families from ASD-UK with 1084 children and families from Daslne, and families from population studies, showed that ASD-UK families are representative of families of children with ASD overall.ConclusionsASD-UK includes families providing parent-reported data about their child and family, who appear to be broadly representative of UK children with ASD. Families continue to join the databases and more than 3000 families can now be contacted by researchers about UK autism research.
Improving the recording of surgical drain output
Authors: Lyons Nicholas , Heron Paul , Bethune Rob 
Published: September 2015

AbstractMonitoring the output from surgical drains is an important part of post-operative care and is often undertaken poorly. Failure to have accurate documentation of daily outputs may delay the removal of drains and increase the risk of complications. Following discussions with medical and nursing staff we listed eight key criteria that should be routinely monitored for surgical drains. A baseline measurement demonstrated only 20% compliance with these criteria. As such we decided to design a chart, after discussing with the multidisciplinary team, with adequate space to document drain output clearly. Post-intervention data collection showed a reasonable uptake of the chart (70%) with overall criteria compliance increasing to 55%.We made further interventions designed to raise awareness of the chart, which increased chart uptake to 79% and compliance to 63%, leading to the adoption of the chart by the department. Twelve months after introducing the chart we conducted a final data collection which demonstrated the chart was now being used in 100% of patients and that overall criteria compliance had increased to 78%. While some of the key criteria are still not documented for all patients, we have demonstrated that the introduction of a simple and well-designed drain chart can significantly improve the documentation of drain output, thereby improving patient safety and discharge efficiency.
Patient characteristics associated with longer emergency department stay: a rapid review
Authors: Kreindler Sara A , Cui Yang , Metge Colleen J , Raynard Melissa 
Published: September 2015

BackgroundProlonged emergency department (ED) stays make a disproportionate contribution to ED overcrowding, but the factors associated with longer stays have not been systematically reviewed.ObjectiveTo identify the patient characteristics associated with ED length of stay (LOS) and ascertain whether a predictive model existed.MethodsThis rapid systematic review included published, English-language studies that assessed at least one patient-level predictor of ED LOS (defined as a continuous or dichotomous variable) in an adult or mixed adult/paediatric population within an Organization for Economic Cooperation and Development country. Findings were synthesised narratively.ResultsWe identified 35 relevant studies; most included multiple predictors, but none developed a predictive model. The factors most commonly associated with long ED LOS were need for admission (10 of 10 studies) and older age (which may be a proxy for age-related differences in health condition and severity; 9 of 10), receipt of diagnostic tests or consults (8 of 8) and ambulance arrival (4 of 5). Acuity often showed a bell-shaped relationship with LOS (ie, patients with moderate acuity stayed longest).LimitationsMethodological choices made in the interests of rapidity limited the review's comprehensiveness and depth.ConclusionsDespite a sizeable body of literature, the available information is insufficiently precise to inform clinical or service-planning decisions; there is a need for a predictive model, including specific patient complaints. Deeper understanding of the determinants of ED LOS could help to identify patients and/or populations who require special intervention or resources to prevent a protracted stay.
Outcomes following repair of anomalous coronary artery from the pulmonary artery in infants: results from a procedure-based national database
Authors: Fudulu Daniel Paul , Dorobantu Dan Mihai , Sharabiani Mansour Taghavi Azar , Angelini Gianni Davide , Caputo Massimo , Parry Andrew John , Stoica Serban Constantin 
Published: September 2015

BackgroundAnomalous coronary artery from the pulmonary artery (ACAPA) is a very rare congenital anomaly that often occurs during infancy. Patients can present in a critical condition.MethodsWe analysed procedure-related data from a national audit database for the period 2000–2013.ResultsA total of 120 patients <1 year had repair of isolated ACAPA using a coronary transfer or the tunnel (Takeuchi) operation. Seven patients (6.8%) required a mitral valve procedure at index and eight patients (7.8%) had a mitral valve repair/replacement during follow-up, including mitral reoperations. Follow-up data (>30 days) were available in 102 patients and the mean follow-up time was 4.7 years. The 30-day overall mortality was 1.9%, higher for neonates (16.7% vs 1%, p=0.1) and after postoperative extracorporeal membrane oxygenation (ECMO) (20% vs 1%, p=0.09). At 10 years the survival estimate is 95.1%, freedom from coronary and mitral reintervention being 95.9% and 91.2%, respectively. Use of postoperative ECMO was a risk factor for long-term mortality (p<0.001). Risk factors for coronary reintervention were age under 30 days (p=0.06) and the need for postoperative ECMO (p=0.02). Age under 30 days (p=0.002) was a risk factor for mitral reintervention.ConclusionsTo our knowledge this is the largest series to date. These preliminary national results show that early outcomes are good and medium-term attrition acceptable. Poor outcomes are correlated with early presentation, also with the need for postoperative circulatory support.
Synthesis and structure stability of Ba2CuO3+δ under high pressure
Authors: Li W. M. , Liu Q. Q. , Liu Y. , Feng S. M. , Wang X. C. , Jin C. Q. , Li X. D. , Liu J. 
Published: September 2015

The [Formula: see text] sample with the nominal composition was synthesized. Powder X-ray diffraction (XRD) experiments confirm that it crystallizes in an orthorhombic structure with space group Immm. The synchrotron powder XRD results suggest that the crystal structure of [Formula: see text] keeps stable under pressure up to 34 GPa at room temperature with nearly isotropic compressibility. The equation of state for [Formula: see text] was obtained. The results offer opportunities to further synthesize and research [Formula: see text] superconductor with tetragonal [Formula: see text] structure.
Geometric conemanifold structures on 𝕋p/q, the result of p/q surgery in the left-handed trefoil knot 𝕋
Authors: Lozano María Teresa , Montesinos-Amilibia José María 
Published: September 2015

As an example of the transitions between some of the eight geometries of Thurston, investigated in [M. T. Lozano and J. M. Montesinos-Amilibia, On the degeneration of some 3-manifold geometries via unit groups of quaternion algebras RACSAM 109 (2015) 669–715], we study the geometries supported by the conemanifolds obtained by surgery on the trefoil knot with singular set the core of the surgery. The geometric structures are explicitly constructed. The most interesting phenomenon is the transition from SL(2, ℝ)-geometry to S3-geometry through Nil-geometry. A plot of the different geometries is given, in the spirit of the analogous plot of Thurston for the geometries supported by surgeries on the figure-eight knot.
Analysis of KRAS/NRAS Mutations in a Phase III Study of Panitumumab with FOLFIRI Compared with FOLFIRI Alone as Second-line Treatment for Metastatic Colorectal Cancer
Authors: Peeters Marc , Oliner Kelly S. , Price Timothy J. , Cervantes Andrés , Sobrero Alberto F. , Ducreux Michel , Hotko Yevhen , André Thierry , Chan Emily , Lordick Florian , Punt Cornelis J.A. , Strickland Andrew H. , Wilson Gregory , Ciuleanu Tudor E. , Roman Laslo , Van Cutsem Eric , He Pei , Yu Hua , Koukakis Reija , Terwey Jan-Henrik , Jung Andre S. , Sidhu Roger , Patterson Scott D. 
Published: September 2015

Abstract
Purpose: We evaluated the influence of RAS mutation status on the treatment effect of panitumumab in a prospective–retrospective analysis of a randomized, multicenter phase III study of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) versus FOLFIRI alone as second-line therapy in patients with metastatic colorectal cancer (mCRC; ClinicalTrials.gov, NCT0039183).
Experimental Design: Outcomes were from the study's primary analysis. RAS mutations beyond KRAS exon 2 (KRAS exons 3, 4; NRAS exons 2, 3, 4; BRAF exon 15) were detected by bidirectional Sanger sequencing in wild-type KRAS exon 2 tumor specimens. Progression-free survival (PFS) and overall survival (OS) were coprimary endpoints.
Results: The RAS ascertainment rate was 85%; 18% of wild-type KRAS exon 2 tumors harbored other RAS mutations. For PFS and OS, the hazard ratio (HR) for panitumumab plus FOLFIRI versus FOLFIRI alone more strongly favored panitumumab in the wild-type RAS population than in the wild-type KRAS exon 2 population [PFS HR, 0.70 (95% confidence interval [CI], 0.54–0.91); P = 0.007 vs. 0.73 (95% CI, 0.59–0.90); P = 0.004; OS HR, 0.81 (95% CI, 0.63–1.03); P = 0.08 vs. 0.85 (95% CI, 0.70–1.04); P = 0.12]. Patients with RAS mutations were unlikely to benefit from panitumumab. Among RAS wild-type patients, the objective response rate was 41% in the panitumumab–FOLFIRI group versus 10% in the FOLFIRI group.
Conclusions: Patients with RAS mutations were unlikely to benefit from panitumumab–FOLFIRI and the benefit–risk of panitumumab–FOLFIRI was improved in the wild-type RAS population compared with the wild-type KRAS exon 2 population. These findings support RAS testing for patients with mCRC. Clin Cancer Res; 21(24); 5469–79. ©2015 AACR.
See related commentary by Salazar and Ciardiello, p. 5415