bluuebunny/crossref_metadata_2025_split huggingface dataset:
The LacI-Type Transcriptional Regulator AraR Acts as an
l
-Arabinose-Responsive Repressor of
l
-Arabinose Utilization Genes in Corynebacterium glutamicum ATCC 31831
Authors: Kuge Takayuki , Teramoto Haruhiko , Yukawa Hideaki , Inui Masayuki 
Published: April 2014

ABSTRACT

The
Corynebacterium glutamicum
ATCC 31831
araBDA
operon consists of three
l
-arabinose catabolic genes, upstream of which the
galM
,
araR
, and
araE
genes are located in opposite orientation.
araR
encodes a LacI-type transcriptional regulator that negatively regulates the
l
-arabinose-inducible expression of
araBDA
and
araE
(encoding an
l
-arabinose transporter), through a mechanism that has yet to be identified. Here we show that the AraR protein binds
in vitro
to three sites: one upstream of
araBDA
and two upstream of
araE
. We verify that a 16-bp consensus palindromic sequence is essential for binding of AraR, using a series of mutations introduced upstream of
araB
in electrophoretic mobility shift assays. Moreover, the DNA-binding activity of AraR is reduced by
l
-arabinose. We employ quantitative reverse transcription-PCR (qRT-PCR) analyses using various mutant strains deficient in
l
-arabinose utilization genes to demonstrate that the prominent upregulation of
araBDA
and
araE
within 5 min of
l
-arabinose supplementation is dependent on the uptake but independent of the catabolism of
l
-arabinose. Similar expression patterns, together with the upregulation by
araR
disruption without
l
-arabinose, are evident with the apparent
galM-araR
operon, although attendant changes in expression levels are much smaller than those realized with the expression of
araBDA
and
araE
. The AraR-binding site upstream of
araB
overlaps the −10 region of the divergent
galM
promoter. These observations indicate that AraR acts as a transcriptional repressor of
araBDA
,
araE
, and
galM-araR
and that
l
-arabinose acts as an intracellular negative effector of the AraR-dependent regulation.
A Proposed Genus Boundary for the Prokaryotes Based on Genomic Insights
Authors: Qin Qi-Long , Xie Bin-Bin , Zhang Xi-Ying , Chen Xiu-Lan , Zhou Bai-Cheng , Zhou Jizhong , Oren Aharon , Zhang Yu-Zhong 
Published: April 2014

ABSTRACT
Genomic information has already been applied to prokaryotic species definition and classification. However, the contribution of the genome sequence to prokaryotic genus delimitation has been less studied. To gain insights into genus definition for the prokaryotes, we attempted to reveal the genus-level genomic differences in the current prokaryotic classification system and to delineate the boundary of a genus on the basis of genomic information. The average nucleotide sequence identity between two genomes can be used for prokaryotic species delineation, but it is not suitable for genus demarcation. We used the percentage of conserved proteins (POCP) between two strains to estimate their evolutionary and phenotypic distance. A comprehensive genomic survey indicated that the POCP can serve as a robust genomic index for establishing the genus boundary for prokaryotic groups. Basically, two species belonging to the same genus would share at least half of their proteins. In a specific lineage, the genus and family/order ranks showed slight or no overlap in terms of POCP values. A prokaryotic genus can be defined as a group of species with all pairwise POCP values higher than 50%. Integration of whole-genome data into the current taxonomy system can provide comprehensive information for prokaryotic genus definition and delimitation.
Improving the accessibility of trust guidelines for junior doctors at North Bristol NHS Trust
Authors: Tarrant Madelaine , Honeyman Calum , Aquilina Alex , Young Katie 
Published: April 2014

AbstractMedicine is becoming increasingly protocol driven. This provides a standardised format for doctors to deliver best practice, especially in the acute setting.40 junior doctors were asked to locate three Trust guidelines: venous thromboembolism (VTE) prophylaxis; antibiotic prescribing; and management of upper gastrointestinal bleed (UGIB). For each doctor the time taken and number of mouse clicks to access each guideline was recorded. Following successful redesign of the Trust intranet we completed a re-audit.Initial results showed 48% of doctors were unable to locate the UGIB or the VTE guidelines within 5 min. For those who were able to locate the guidelines it took an average of 111 sec and 17 mouse clicks. 100% of doctors were able to locate the antibiotic guidelines in 12 sec and with two clicks. These are accessible via a single port of access.Following our redesign of the Trust intranet 100% of doctors located all three guidelines in an average time of 7.2 sec and in 2.1 clicks. Improvement in access to VTE prophylaxis and UGIB was statistically significant (p=0.001).Redesigning our Trust intranet homepage has significantly improved the accessibility of acute surgical and medical guidelines.
Obesity management in a Paediatric Emergency Department
Authors: Knight Martin , Booth Charlotte 
Published: April 2014

AbstractIncreasing numbers of children are either overweight or obese, which has a significant negative impact on their current quality of life and their future health. The results of England's National Child Measurement Programme 2012-13 revealed that approximately one fifth of 4- to 5-year-olds and one third of children aged 10 to 11 years were overweight or obese. Emergency departments (EDs) see large numbers of children every year and therefore represent a potential opportunity to address the obesity issue.A pathway was devised to guide referral of overweight or obese children attending the ED to an existing local healthy living programme. Training sessions on the referral process were provided to ED staff. Audits of ED attendance records were undertaken before and after the implementation of the pathway, and the local programme uptake rate for the first 25 referrals was assessed.Of the first 25 children referred, two (8%) had participated in a programme, six (24%) were on a waiting list, and four (16%) were referred on to services in their local area, giving an overall engagement rate of 48%.Further work needs to be undertaken to increase referrals; however, addressing childhood obesity by accessing existing local services from the ED remains a valuable endeavour.
Prehospital use of furosemide for the treatment of heart failure
Authors: Pan Andy , Stiell Ian G , Dionne Richard , Maloney Justin 
Published: April 2014

IntroductionThe diagnosis and management of acute decompensated heart failure (HF) in the prehospital setting can be challenging. The objectives of this study are to evaluate the appropriateness of furosemide use by Emergency Medical Services (EMS) and its association with adverse outcomes.MethodsThis study was a multi-centre health records review of EMS patients who received prehospital furosemide or had an emergency department (ED) diagnosis of HF. We included acutely ill patients ≥50 years of age with shortness of breath transported by land EMS. Univariate and logistic regression analyses were performed to determine associations between furosemide use and serious adverse outcomes (acute renal failure, intubation, vasopressors or death).ResultsThe study population consisted of 330 patients (N=58, furosemide given by EMS but no HF diagnosed in ED; N=110, furosemide given, HF diagnosed; N=162, no furosemide given, HF diagnosed). The median dose of intravenous furosemide was 80 mg (range 20–80 mg). Serious adverse outcomes occurred in 61 patients (19.0%, 23.6% and 14.8% of the three groups, respectively; p=0.18). The adjusted ORs for adverse events with furosemide use was 0.62 (95% CI 0.33 to 1.43) in patients with a diagnosis of HF and 1.14 (95% CI 0.58 to 2.23) in those without.ConclusionsMore than a third of patients who received prehospital furosemide did not have an HF diagnosis, suggesting that the prehospital diagnosis of HF can be challenging. Serious adverse outcomes were identified in all patient groups and we found no statistically significant associations between furosemide use and adverse events.
Enquiry time as part of turnaround time: when do our clinicians really consult our results?
Authors: Rodríguez-Borja Enrique , Villalba-Martínez C , Carratalá-Calvo A 
Published: April 2014

BackgroundTraditionally, laboratories’ turnaround times (TAT) have been calculated by only considering analytical or intralaboratory steps. The measure of the postanalytical impact in TAT has barely been studied and, more specifically, the running time from when finalised results are available to when clinicians make their first enquiry with an electronic medical record.MethodsDuring May–June of 2013, two ‘Times’ were collected from our laboratory information system for all the priority requests coming from our day hospitals: ‘Validation time’ (TV), as the request report time with full verified results and ‘Enquiry time’ (TQ), as the time when the first consult was made via electronic medical record. We classified requests in groups depending on time results, and TQ-TV (percentiles) were calculated for each group.Results654 (69%) requests were consulted by clinicians before 15 : 00 on the same day with available results. 191 (20%) were consulted after 15 : 00 and had complete results as well (p50 (TQ–TV): 5 days) while 61 (7%) were never consulted (up to 31/12/2013). 39 (4%) requests were finally consulted before 15 : 00 h with no available results, but the average time difference between validation and enquiry was 31 min.ConclusionsThe results obtained lead us to reconsider the TAT established with our day hospitals in order to know if priority has to be reviewed or if there are failures in follow-up results. ‘Enquiry time’ appears to be a powerful tool in detecting these issues and shows that TATs are no longer just a ‘laboratory problem’.
Evidence for exsolution of Au-ore fluids from granites crystallized in the mid-crust, Archaean Louis Lake Batholith, Wyoming
Authors: Vaughn E. S. , Ridley J. R. 
Published: April 2014

Abstract

The Louis Lake Batholith is contemporaneous with and sits adjacent to Archaean lode gold deposits and minor copper stockwork vein systems of the South Pass Greenstone Belt, Wyoming Province, and may thus have contributed fluid into these hydrothermal systems. The batholith is granodiorite to granite, lacks extreme fractionation, and contains evidence for early formation and later replacement of an immiscible early sulphide phase. Mafic enclaves contain anomalous concentrations of gold and copper, suggesting that metals were introduced from in-mixed mafic magma. Apatite SO
3
and Cl values imply relatively early exsolution of sulphur- and chlorine-bearing fluids during fractionation. Exsolution of possibly immiscible high- and low-salinity fluids is implied from fluid inclusion petrography, even though crystallization pressures were greater than 3 kbar. Low salinity inclusions share affinities with those of orogenic gold systems, but contain notably higher Pb and Zn concentrations. High salinity inclusions have similar elemental compositions to brines of intrusion-centred ore systems.

It is proposed that sulphide melt separated early during magma fractionation, scavenging Au and Cu, but became later destabilized, possibly because of increased
f
O
2
, releasing scavenged metals. Metals were transported from the pluton in sulphur- and chlorine-bearing hydrothermal fluids of low and high salinity, with Au being preferentially transported in the low-salinity fluid.

Supplementary material:

Whole Rock Geochemical data are available at
http://www.geolsoc.org.uk/SUP18751
.
More gap than record? Qualitative and quantitative assessment of stratigraphic gaps in a field based study, with examples from the Lower Silurian Pentamerus Beds of Shropshire, England and the Lower Ordovician Ribband Gp of County Wexford, Ireland
Authors: Crossley Joseph D. , Clark Hazel E. 
Published: April 2014

Abstract
To assess the extent to which it is possible to identify, characterize and quantify gaps in the stratigraphic record, two contrasting sections, the Silurian Pentamerus Beds of Shropshire, England, and the Ordovician Ribband Gp of County Wexford, Ireland, have been examined in the field. In the Pentamerus Beds the life assemblages contained in silty mudstones suggest slow to little/no deposition during fair weather periods. Interbedded lenticular calcirudites characteristically feature death assemblages of thick-shelled brachiopods and are interpreted as storm deposits, implying erosional breaks in accumulation. In contrast, the Ribband Gp's regular ribbon banding of fine sandstones, siltstones and mudstones/silty mudstones suggests a more distal shelf environment. Fodinichnial trace fossils are witness to periods of more or less continuous sedimentation. The succession may have formed during seasonal alternations of stormy (thin cross-laminated sandstone beds) and fair weather periods (laminated mudstones); though longer-term climatic variations cannot be ruled out. There is minimal evidence for hiatuses in the accumulation.
Phosphatidylinositol 4-Phosphate in the Golgi Apparatus Regulates Cell–Cell Adhesion and Invasive Cell Migration in Human Breast Cancer
Authors: Tokuda Emi , Itoh Toshiki , Hasegawa Junya , Ijuin Takeshi , Takeuchi Yukiko , Irino Yasuhiro , Fukumoto Miki , Takenawa Tadaomi 
Published: April 2014

Abstract
Downregulation of cell–cell adhesion and upregulation of cell migration play critical roles in the conversion of benign tumors to aggressive invasive cancers. In this study, we show that changes in cell–cell adhesion and cancer cell migration/invasion capacity depend on the level of phosphatidylinositol 4-phosphate [PI(4)P] in the Golgi apparatus in breast cancer cells. Attenuating SAC1, a PI(4)P phosphatase localized in the Golgi apparatus, resulted in decreased cell–cell adhesion and increased cell migration in weakly invasive cells. In contrast, silencing phosphatidylinositol 4-kinase IIIβ, which generates PI(4)P in the Golgi apparatus, increased cell–cell adhesion and decreased invasion in highly invasive cells. Furthermore, a PI(4)P effector, Golgi phosphoprotein 3, was found to be involved in the generation of these phenotypes in a manner that depends on its PI(4)P-binding ability. Our results provide a new model for breast cancer cell progression in which progression is controlled by PI(4)P levels in the Golgi apparatus. Cancer Res; 74(11); 3054–66. ©2014 AACR.
Strengths, Weaknesses, and Opportunities of Diagnostic Breathomics in Pleural Mesothelioma—A Hypothesis
Authors: Lamote Kevin , Nackaerts Kristiaan , van Meerbeeck Jan P. 
Published: April 2014

Abstract
Past and present asbestos use will reflect in increasing numbers of mesothelioma cases in the next decades, diagnosed at a late stage and with a dismal prognosis. This stresses the need for early detection tools, which could improve patients' survival. Recently, breath analysis as a noninvasive and fast diagnostic tool has found its way into biomedical research. High-throughput breathomics uses spectrometric, chromatographic, and sensor techniques to diagnose asbestos-related pulmonary diseases based upon volatile organic compounds (VOC) in breath. This article reviews the state-of-the-art available breath analyzing techniques and provides the insight in the current use of VOCs as early diagnostic or prognostic biomarkers of mesothelioma to stimulate further research in this field. Cancer Epidemiol Biomarkers Prev; 23(6); 898–908. ©2014 AACR.
Cancer Screening and Genetics: A Tale of Two Paradigms
Authors: Hamilton Jada G. , Edwards Heather M. , Khoury Muin J. , Taplin Stephen H. 
Published: April 2014

Abstract
The long-standing medical tradition to “first do no harm” is reflected in population-wide evidence-based recommendations for cancer screening tests that focus primarily on reducing morbidity and mortality. The conventional cancer screening process is predicated on finding early-stage disease that can be treated effectively; yet emerging genetic and genomic testing technologies have moved the target earlier in the disease development process to identify a probabilistic predisposition to disease. Genetic risk information can have varying implications for the health and well-being of patients and their relatives, and has raised important questions about the evaluation and value of risk information. This article explores the paradigms that are being applied to the evaluation of conventional cancer screening tests and emerging genetic and genomic tests of cancer susceptibility, and how these perspectives are shifting and evolving in response to advances in our ability to detect cancer risks. We consider several challenges germane to the evaluation of both categories of tests, including defining benefits and harms in terms of personal and clinical utility, addressing healthcare consumers' information preferences, and managing scientific uncertainty. We encourage research and dialogue aimed at developing a better understanding of the value of all risk information, nongenetic and genetic, to people's lives. Cancer Epidemiol Biomarkers Prev; 23(6); 909–16. ©2014 AACR.
UPARANT: A Urokinase Receptor–Derived Peptide Inhibitor of VEGF-Driven Angiogenesis with Enhanced Stability and In Vitro and In Vivo Potency
Authors: Carriero Maria Vincenza , Bifulco Katia , Minopoli Michele , Lista Liliana , Maglio Ornella , Mele Luigi , Di Carluccio Gioconda , De Rosa Mario , Pavone Vincenzo 
Published: April 2014

Abstract
This work is based on previous evidence showing that chemotactic sequence of the urokinase receptor (uPAR88-92) drives angiogenesis in vitro and in vivo in a protease-independent manner, and that the peptide Ac-Arg-Glu-Arg-Phe-NH2 (RERF) prevents both uPAR88–92- and VEGF-induced angiogenesis. New N-acetylated and C-amidated peptide analogues containing α-methyl α-amino acids were designed and synthesized to optimize the biochemical properties for therapeutic applications. Among these, Ac-L-Arg-Aib-L-Arg-D-Cα(Me)Phe-NH2, named UPARANT, adopts in solution a turned conformation similar to that found for RERF, is stable to sterilization in 3 mg/mL sealed vials in autoclave for 20 minutes at 120°C, is stable in blood, and displays a long-time resistance to enzymatic proteolysis. UPARANT competes with N-formyl-Met-Leu-Phe (fMLF) for binding to the formyl-peptide receptor, inhibits VEGF-directed endothelial cell migration, and prevents cytoskeletal organization and αvβ3 activation in endothelial cells exposed to VEGF. In vitro, UPARANT inhibits VEGF-dependent tube formation of endothelial cells at a 100× lower concentration than RERF. In vivo, UPARANT reduces to the basal level VEGF-dependent capillary sprouts originating from the host vessels that invaded Matrigel sponges implanted in mice, and completely prevents neovascularization induced by subcorneal implantation of pellets containing VEGF in rabbits. Both excellent stability and potency position UPARANT as a promising new therapeutic agent for the control of diseases fueled by excessive angiogenesis, such as cancer and inflammation. Mol Cancer Ther; 13(5); 1092–104. ©2014 AACR.
Development of an Active Site Peptide Analog of α-Fetoprotein That Prevents Breast Cancer
Authors: Jacobson Herbert I. , Andersen Thomas T. , Bennett James A. 
Published: April 2014

Abstract
Epidemiologic studies associate elevated maternal serum levels of α-fetoprotein (AFP) with reduced breast cancer risk for parous women. Laboratory studies demonstrate direct anti-breast cancer activity of AFP. Here, we review the development of a small cyclic peptide that is an active site analog of AFP, referred to as AFPep, which is composed exclusively of amino acids, is orally active, has no discernable toxicity, and is effective for the treatment and prevention of breast cancer in animal models. Cancer Prev Res; 7(6); 565–73. ©2014 AACR.
Transplantation-Free Survival and Interventions at 3 Years in the Single Ventricle Reconstruction Trial
Authors: Newburger Jane W. , Sleeper Lynn A. , Frommelt Peter C. , Pearson Gail D. , Mahle William T. , Chen Shan , Dunbar-Masterson Carolyn , Mital Seema , Williams Ismee A. , Ghanayem Nancy S. , Goldberg Caren S. , Jacobs Jeffrey P. , Krawczeski Catherine D. , Lewis Alan B. , Pasquali Sara K. , Pizarro Christian , Gruber Peter J. , Atz Andrew M. , Khaikin Svetlana , Gaynor J. William , Ohye Richard G. 
Published: April 2014

Background—
In the Single Ventricle Reconstruction (SVR) trial, 1-year transplantation-free survival was better for the Norwood procedure with right ventricle–to–pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt (MBTS). At 3 years, we compared transplantation-free survival, echocardiographic right ventricular ejection fraction, and unplanned interventions in the treatment groups.

Methods and Results—

Vital status and medical history were ascertained from annual medical records, death indexes, and phone interviews. The cohort included 549 patients randomized and treated in the SVR trial. Transplantation-free survival for the RVPAS versus MBTS groups did not differ at 3 years (67% versus 61%;
P
=0.15) or with all available follow-up of 4.8±1.1 years (log-rank
P
=0.14). Pre-Fontan right ventricular ejection fraction was lower in the RVPAS group than in the MBTS group (41.7
±
5.1% versus 44.7
±
6.0%;
P
=0.007), and right ventricular ejection fraction deteriorated in RVPAS (
P
=0.004) but not MBTS (
P
=0.40) subjects (pre-Fontan minus 14-month mean, −3.25±8.24% versus 0.99±8.80%;
P
=0.009). The RVPAS versus MBTS treatment effect had nonproportional hazards (
P
=0.004); the hazard ratio favored the RVPAS before 5 months (hazard ratio=0.63; 95% confidence interval, 0.45–0.88) but the MBTS beyond 1 year (hazard ratio=2.22; 95% confidence interval, 1.07–4.62). By 3 years, RVPAS subjects had a higher incidence of catheter interventions (
P
<0.001) with an increasing HR over time (
P
=0.005): <5 months, 1.14 (95% confidence interval, 0.81–1.60); from 5 months to 1 year, 1.94 (95% confidence interval, 1.02–3.69); and >1 year, 2.48 (95% confidence interval, 1.28–4.80).

Conclusions—
By 3 years, the Norwood procedure with RVPAS compared with MBTS was no longer associated with superior transplantation-free survival. Moreover, RVPAS subjects had slightly worse right ventricular ejection fraction and underwent more catheter interventions with increasing hazard ratio over time.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00115934.
Intraoperatively Diagnosed Cerebellopontine Angle Facial Nerve Schwannoma
Authors: Bacciu Andrea , Medina Marimar , Ben Ammar Mehdi , D’Orazio Flavia , Di Lella Filippo , Russo Alessandra , Magnan Jacques , Sanna Mario 
Published: April 2014

Objective: This study aimed to report our experience in the management of patients with intraoperatively diagnosed intracranial facial nerve schwannomas (FNSs) and propose a decision-making strategy. Methods: Twenty-three patients with FNS of the internal auditory canal and/or cerebellopontine angle operated on between 1992 and 2012 were identified. Results: Preoperatively, all cases have been radiographically diagnosed as vestibular schwannomas. Operative procedures consisted of total tumor resection with grafting in 43.4% of patients, near-total resection leaving behind the tumor capsule overlying the facial nerve in 21.7%, total tumor resection with preservation of anatomic continuity of the facial nerve in 13%, and subtotal resection in 4.3%. Four patients (17.4%) underwent bony decompression with no tumor removal. Conclusion: Management of FNS diagnosed at surgery represents a significant clinical challenge. We considered total tumor resection with grafting when patients presented with preoperative facial nerve palsy (≥ grade III). Both subtotal and near-total tumor removal can be performed in patients with preoperative good facial function and/or large tumors with brainstem compression. Patients with small tumors who were selected for hearing preservation surgery can be considered for bony decompression. Fascicle preservation surgery may be an option when a clear cleavage plane between the tumor and the facial nerve is found.