bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations within the
mepA
Operator Affect Binding of the MepR Regulatory Protein and Its Induction by MepA Substrates in Staphylococcus aureus
Authors: Schindler Bryan D. , Seo Susan M. , Birukou Ivan , Brennan Richard G. , Kaatz Glenn W. 
Published: January 2015

ABSTRACT

The expression of
mepA
, encoding the
Staphylococcus aureus
MepA multidrug efflux protein, is repressed by the MarR homologue MepR. Repression occurs through binding of two MepR dimers to an operator with two homologous and closely approximated pseudopalindromic binding sites (site 1 [S1] and site 2 [S2]). MepR binding is impeded in the presence of pentamidine, a MepA substrate. The effects of various
mepA
operator mutations on MepR binding were determined using electrophoretic mobility shift assays and isothermal titration calorimetry, and an
in vivo
confirmation of the effects observed was established for a fully palindromic operator mutant. Altering the S1-S2 spacing by 1 to 4 bp severely impaired S2 binding, likely due to a physical collision between adjacent MepR dimers. Extension of the spacing to 9 bp eliminated the S1 binding-mediated DNA allostery required for efficient S2 binding, consistent with positive cooperative binding of MepR dimers. Binding of a single dimer to S1 was maintained when S2 was disrupted, whereas disruption of S1 eliminated any significant binding to S2, also consistent with positive cooperativity. Palindromization of binding sites, especially S2, enhanced MepR affinity for the
mepA
operator and reduced MepA substrate-mediated MepR induction. As a result, the on-off equilibrium between MepR and its binding sites was shifted toward the on state, resulting in less free MepR being available for interaction with inducing ligand. The selective pressure(s) under which
mepA
expression is advantageous likely contributed to the accumulation of mutations in the
mepA
operator, resulting in the current sequence from which MepR is readily induced by MepA substrates.
A predictive model of hospitalization cost after cerebral aneurysm clipping
Authors: Bekelis Kimon , Missios Symeon , MacKenzie Todd A , Labropoulos Nicos , Roberts David W 
Published: January 2015

BackgroundCost containment is the cornerstone of the Affordable Care Act. Although studies have compared the cost of cerebral aneurysm clipping (CAC) and coiling, they have not focused on identification of drivers of cost after CAC, or prediction of its magnitude. The objective of the present study was to develop and validate a predictive model of hospitalization cost after CAC.MethodsWe performed a retrospective study involving CAC patients who were registered in the Nationwide Inpatient Sample (NIS) database from 2005 to 2010. The two cohorts of ruptured and unruptured aneurysms underwent 1:1 randomization to create derivation and validation subsamples. Regression techniques were used for the creation of a parsimonious predictive model.ResultsOf the 7798 patients undergoing CAC, 4505 (58%) presented with unruptured and 3293 (42%) with ruptured aneurysms. Median hospitalization cost was US$24 398 (IQR $17 079 to $38 249) and $73 694 (IQR $46 270 to $115 128) for the two cohorts, respectively. Common drivers of cost identified in the multivariate analyses included the following: length of stay, number of admission diagnoses and procedures, hospital size and region, and patient income. The models were validated in independent cohorts and demonstrated final R2values very similar to the initial models. The predicted and observed values in the validation cohort demonstrated good correlation.ConclusionsThis national study identified significant drivers of hospitalization cost after CAC. The presented model can be utilized as an adjunct in the cost containment debate and the creation of data driven policies.
Scar Dechanneling
Authors: Berruezo Antonio , Fernández-Armenta Juan , Andreu David , Penela Diego , Herczku Csaba , Evertz Reinder , Cipolletta Laura , Acosta Juan , Borràs Roger , Arbelo Elena , Tolosana Jose María , Brugada Josep , Mont Lluis 
Published: January 2015

Background—
Ventricular tachycardia (VT) substrate ablation usually requires extensive ablation. Scar dechanneling technique may limit the extent of ablation needed.

Methods and Results—

The study included 101 consecutive patients with left ventricular scar–related VT (75 ischemic patients; left ventricular ejection fraction, 36±13%). Procedural end point was the elimination of all identified conducting channels (CCs) by ablation at the CC entrance followed by abolition of residual inducible VTs. By itself, scar dechanneling rendered noninducibility in 54.5% of patients; ablation of residual inducible VT increased noninducibility to 78.2%. Patients needing only scar dechanneling had a shorter procedure (213±64 versus 244±71 minutes;
P
=0.027), fewer radiofrequency applications (19±11% versus 27±18%;
P
=0.01), and external cardioversion/defibrillation shocks (20% versus 65.2%;
P
<0.001). At 2 years, patients needing scar dechanneling alone had better event-free survival (80% versus 62%) and lower mortality (5% versus 11%). Incomplete CC-electrogram elimination was the only independent predictor (hazard ratio, 2.54 [1.06–6.10]) for the primary end point. Higher end point-free survival rates were observed in patients noninducible after scar dechanneling (log-rank
P
=0.013) and those with complete CC-electrogram elimination (log-rank
P
=0.013). The complications rate was 6.9%, with no deaths.

Conclusions—
Scar dechanneling alone results in low recurrence and mortality rates in more than half of patients despite the limited ablation extent required. Residual inducible VT ablation improves acute results, but patients who require it have worse outcomes. Recurrences are mainly related to incomplete CC-electrogram elimination.
Percutaneous Treatment of Adult Isthmic Aortic Coarctation
Authors: Kische Stephan , D’Ancona Giuseppe , Stoeckicht Yannik , Ortak Jasmin , Elsässer Albrecht , Ince Hüseyin 
Published: January 2015

Background—
To present perioperative and long-term results of percutaneous treatment of adult isthmic coarctation of the aorta by means of a self-expandable closed-web uncovered nitinol stent (Sinus-XL, Optimed, Esslingen, Germany).

Methods and Results—

Preoperative, perioperative, and long-term clinical and computed tomographic angiography data were collected and analyzed prospectively. A total of 52 consecutive patients were treated with the Sinus-XL stent. Mean age was 36.6 (21–67) years, peak invasive trans–coarctation of the aorta gradient was 54.7±9.9 mm Hg, and upper body hypertension unresponsive to medical treatment was present in all patients. Mean stent diameter and length were 24.2 mm (22–28 mm) and 70.4 mm (40–80 mm), respectively. Eight patients (15.4%) required coarctation of the aorta predilatation. All patients underwent poststent dilatation with a noncompliant balloon. Postoperative peak gradient (3.3±2.5 mm Hg) was reduced significantly (
P
<0.001) and minimal aortic diameter was increased significantly (4.6±1.9 versus 18.6±2.5 mm;
P
<0.001). All patients were discharged home (mean hospitalization, 3.5 days). At follow-up (47.6 months; 12–84), 1 (1.9%) noncardiovascular mortality was reported. Aortic computed tomography confirmed the absence of stent collapse and secondary migration and documented stability in aortic diameter (18.3±2.7 mm). Thirty patients (57.7%) were completely weaned-off antihypertensive medications and their use dropped from 2.6 to 0.9 drugs/patient (
P
<0.001). Ankle-brachial pressure index increased from 0.75 to 0.98 (
P
<0.001).

Conclusions—
Adult coarctation of the aorta treatment by means of a self-expandable uncovered stent is safe and durable. The peculiar stent design maintains adequate localized radial strength over time with minimal trauma on the adjacent aortic wall and negligible device-related complications. Blood pressure control optimization is immediate and persistent even at long-term follow-up.
Streptococcal M1 protein triggers chemokine formation, neutrophil infiltration, and lung injury in an NFAT-dependent manner
Authors: Zhang Songen , Zhang Su , Garcia-Vaz Eliana , Herwald Heiko , Gomez Maria F , Thorlacius Henrik 
Published: January 2015

Abstract
Streptococcus pyogenes of the M1 serotype can cause STSS, which is associated with significant morbidity and mortality. The purpose of the present study was to examine the role of NFAT signaling in M1 protein-induced lung injury. NFAT-luc mice were treated with the NFAT inhibitor A-285222 before administration of the M1 protein. Neutrophil infiltration, edema, and CXC chemokines were quantified in the lung, 4 h after challenge with the M1 protein. Flow cytometry was used to determine Mac-1 expression. Challenge with the M1 protein increased NFAT-dependent transcriptional activity in the lung, spleen, and liver in NFAT-luc mice. Administration of the NFAT inhibitor A-285222 abolished M1 protein-evoked NFAT activation in the lung, spleen, and liver. M1 protein challenge induced neutrophil recruitment, edema, and CXC chemokine production in the lung, as well as up-regulation of Mac-1 on circulating neutrophils. Inhibition of NFAT activity attenuated M1 protein-induced neutrophil infiltration by 77% and edema formation by 50% in the lung. Moreover, administration of A-285222 reduced M1 protein-evoked pulmonary formation of CXC chemokine &gt;80%. In addition, NFAT inhibition decreased M1 protein-triggered Mac-1 up-regulation on neutrophils. These findings indicate that NFAT signaling controls pulmonary infiltration of neutrophils in response to streptococcal M1 protein via formation of CXC chemokines and neutrophil expression of Mac-1. Thus, the targeting of NFAT activity might be a useful way to ameliorate lung injury in streptococcal infections.
Randomized Phase III Trial Comparing Weekly Docetaxel Plus Cisplatin Versus Docetaxel Monotherapy Every 3 Weeks in Elderly Patients With Advanced Non–Small-Cell Lung Cancer: The Intergroup Trial JCOG0803/WJOG4307L
Authors: Abe Tetsuya , Takeda Koji , Ohe Yuichiro , Kudoh Shinzoh , Ichinose Yukito , Okamoto Hiroaki , Yamamoto Nobuyuki , Yoshioka Hiroshige , Minato Koichi , Sawa Toshiyuki , Iwamoto Yasuo , Saka Hideo , Mizusawa Junki , Shibata Taro , Nakamura Shinichiro , Ando Masahiko , Yokoyama Akira , Nakagawa Kazuhiko , Saijo Nagahiro , Tamura Tomohide 
Published: January 2015

Purpose This phase III trial aimed to confirm the superiority of weekly docetaxel and cisplatin over docetaxel monotherapy in elderly patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Chemotherapy-naïve patients with stage III, stage IV, or recurrent NSCLC age ≥ 70 years with a performance status of 0 or 1 who were considered unsuitable for bolus cisplatin administration were randomly assigned to receive docetaxel 60 mg/m2 on day 1, every 3 weeks, or docetaxel 20 mg/m2 plus cisplatin 25 mg/m2 on days 1, 8, and 15, every 4 weeks. The primary end point was overall survival (OS). Results In the first interim analysis, OS of the doublet arm was inferior to that of the monotherapy arm (hazard ratio [HR], 1.56; 95% CI, 0.98 to 2.49), and the predictive probability that the doublet arm would be statistically superior to the monotherapy arm on final analysis was 0.996%, which led to early study termination. In total, 276 patients with a median age of 76 years (range, 70 to 87 years) were enrolled. At the updated analysis, the median survival time was 14.8 months for the monotherapy arm and 13.3 months for the doublet arm (HR, 1.18; 95% CI, 0.83 to 1.69). The rates of grade ≥ 3 neutropenia and febrile neutropenia were higher in the monotherapy arm, and those of anorexia and hyponatremia were higher in the doublet arm. Conclusion This study failed to demonstrate any survival advantage of weekly docetaxel plus cisplatin over docetaxel monotherapy as first-line chemotherapy for advanced NSCLC in elderly patients.
Actions of the Small Molecule Ligands SW106 and AH-3960 on the Type-1 Parathyroid Hormone Receptor
Authors: Carter Percy H. , Dean Thomas , Bhayana Brijesh , Khatri Ashok , Rajur Raj , Gardella Thomas J. 
Published: January 2015

AbstractThe parathyroid hormone receptor-1 (PTHR1) plays critical roles in regulating blood calcium levels and bone metabolism and is thus of interest for small-molecule ligand development. Of the few small-molecule ligands reported for the PTHR1, most are of low affinity, and none has a well-defined mechanism of action. Here, we show that SW106 and AH-3960, compounds previously identified to act as an antagonist and agonist, respectively, on the PTHR1, each bind to PTHR1-delNT, a PTHR1 construct that lacks the large amino-terminal extracellular domain used for binding endogenous PTH peptide ligands, with the same micromolar affinity with which it binds to the intact PTHR1. SW106 antagonized PTHR1-mediated cAMP signaling induced by the peptide analog, M-PTH(1–11), as well as by the native PTH(1–9) sequence, as tethered to the extracellular end of transmembrane domain (TMD) helix-1 of the receptor. SW106, however, did not function as an inverse agonist on either PTHR1-H223R or PTHR1-T410P, which have activating mutations at the cytoplasmic ends of TMD helices 2 and 6, respectively. The overall data indicate that SW106 and AH-3960 each bind to the PTHR1 TMD region and likely to within an extracellularly exposed area that is occupied by the N-terminal residues of PTH peptides. Additionally, they suggest that the inhibitory effects of SW106 are limited to the extracellular portions of the TMD region that mediate interactions with agonist ligands but do not extend to receptor-activation determinants situated more deeply in the helical bundle. The study helps to elucidate potential mechanisms of small-molecule binding at the PTHR1.
Game—The Dressing Change Game
Authors: Tucker Anita L , Lefton Cindy 
Published: January 2015

Many employees face operational failures—missing or insufficient supplies, equipment, information, and personnel—that interfere with their workflow and can negatively impact organizational performance. However, employees often devise methods to work around these obstacles that may come with negative side effects. The Dressing Change Game is a 40-minute in-class exercise that enables students to directly experience workarounds as a natural response to operational failures and allows them to see the trade-off between short-term and longer-term organizational performance that occurs as a result of workarounds. The overarching learning objective is for students to gain an appreciation that optimizing individual- or unit-level performance likely undermines organizational-level performance. Teaching Note: Interested Instructors please see the Instructor Materials page for access to the restricted materials. To maintain the integrity and usefulness of cases published in ITE, unapproved distribution of the case teaching notes and other restricted materials to any other party is prohibited.
The effectiveness of auditory stimulation in children with autism spectrum disorders: A case–control study
Authors: Gee Bryan , Thompson Kelly , Pierce Aaron , Toupin Megan , Holst Jennifer 
Published: January 2015

Background/Aim: The Listening Program (TLP) is a sound-based intervention that claims to treat the behavioural challenges of children diagnosed on the autism spectrum with sensory processing difficulties. There is a paucity of peer-reviewed evidence supporting its use. The purpose of this study was to determine whether TLP reduces sensory over-responsitivity (SOR) to auditory stimuli. Methods: Data were collected over a 28-week period using an ABAB multiple events case–control design of testing and treatment intervals to capture the responses of three participants to TLP. Results: Graphs from repeated measures data were drawn to analyse the direction and level of trend lines. There was a high variability of responses, with participants responding positively and others negatively at different stages of the study. Conclusions: The results lend some support to the use of TLP with children on the autism spectrum who are experiencing auditory SOR.
Cognitive-Behavioral Counseling for Exclusive Breastfeeding in Rural Pediatrics: A Cluster RCT
Authors: Sikander Siham , Maselko Joanna , Zafar Shamsa , Haq Zaeem , Ahmad Ikhlaq , Ahmad Mansoor , Hafeez Assad , Rahman Atif 
Published: January 2015

OBJECTIVE:
To test the effectiveness of cognitive-behavioral counseling on the rate and duration of exclusive breastfeeding (EBF) during the first 6 months of an infant’s life compared with routine counseling.

METHODS:
A single blind cluster-randomized controlled trial was undertaken in 40 Union Councils of a rural district in the northwest province of Pakistan between May 2009 and April 2010. By simple unmatched randomization, 20 Union Councils were each allocated to intervention and control arms. Two hundred twenty-four third trimester pregnant women in the intervention and 228 third trimester pregnant women in the control arm were enrolled and followed-up biweekly until 6 months postpartum. Analyses were by intention to treat. Mothers in the intervention group received 7 sessions of cognitive-behavioral counseling from antenatal to 6 months postpartum, whereas the control group received an equal number of routine sessions. Proportion of mothers exclusively breastfeeding at 6 months postpartum and duration of EBF through these 6 months was assessed.

RESULTS:
At 6 months postpartum, 59.6% of mothers in the intervention arm and 28.6% in the control arm were exclusively breastfeeding. This translates into a 60% reduced risk of stopping exclusively breastfeeding during the first 6 months (adjusted hazard ratio, 0.40 [95% confidence interval: 0.27–0.60], P &lt; .001). Mothers in the intervention group were half as likely to use prelacteal feeds with their infants (adjusted relative risk, 0.51 [95% confidence interval: 0.34–0.78]).

CONCLUSIONS:
Compared with routine counseling, cognitive-behavioral counseling significantly prolonged the duration of EBF, doubling the rates of EBF at 6 months postpartum.
Waterflood Using a Muskeg Water Source - Milligan Creek Unit, B.C.
Authors: Cracknell W.C. 
Published: January 2015

Abstract
The Milligan Creek field, in northeastern British Columbia, is a small but high-capacity sand reservoir of Triassic age. Waterflooding was initiated early in the life of the reservoir to provide pressure maintenance and increase oil recovery from the pool. Due to the lack of a subsurface supply in the area, muskeg water from a nearby creek was utilized. This cold water, with its high content of iron and organic material, has proved to be a major water treatment problem. After considerable experimentation, a process using flocculation, filtration through a sand-anthracite filter and deaeration was found to yield water satisfactory for injection, although a seasonal variation in water quality remains a problem.
Four years of waterflooding have yielded satisfactory results, with a decrease in voidage, an increase in reservoir pressure and the attainment of a high level of production for a pool of this size. Performance has been accurately predicted by means of a potentiometric model, which has proved to be a useful tool in guiding the progress of pool operation. Recovery to date of 15 per cent of the original oil in place is approaching what was expected under primary solution gas drive, and this should more than double under waterflood.
Interpretation of Dipmeter Data in the Devonian Carbonates and Evaporites of the Rainbow and Zama Areas
Authors: Cox John W. 
Published: January 2015

Abstract
Knowledge of structural dip in the carbonates and evaporites overlying Keg River reefs is a valuable aid in describing reef geometry. Access to this information can be achieved through the interpretation of the continuous dipmeter log.
The route to structural dip and direction is not always straightforward, as local bedding patterns may be quite different from the over-all structural dip. With selectivity in the computing system and an understanding of the environment from which data are extracted, reliable resolution of structural dip is made possible.
Correlations between wells drilled on close spacing indicate excellent continuity on many of the very thin beds and bedding planes used for dipmeter computation. The structural dip computed from this device compares favorably with the dip calculated from correlations between wells.
The use of the dipmeter tool has enabled operators to evaluate adjoining acreage and to whipstock up-dip into production from a dry hole.
Automatic 1D integrated geophysical modelling of lithospheric discontinuities: a case study from Carpathian-Pannonian Basin region
Authors: Grinč Michal , Zeyen Hermann , Bielik Miroslav 
Published: January 2015

Abstract
Using a very fast 1D method of integrated geophysical modelling, we calculated models of the Moho discontinuity and the lithosphere-asthenosphere boundary in the Carpathian-Pannonian Basin region and its surrounding tectonic units. This method is capable to constrain complicated lithospheric structures by using joint interpretation of different geophysical data sets (geoid and topography) at the same time. The Moho depth map shows significant crustal thickness variations. The thickest crust is found underneath the Carpathian arc and its immediate Foredeep. High values are found in the Eastern Carpathians and Vrancea area (44 km). The thickest crust modelled in the Southern Carpathians is 42 km. The Dinarides crust is characterized by thicknesses more than 40 km. In the East European Platform, crust has a thickness of about 34 km. In the Apuseni Mountains, the depth of the Moho is about 36 km. The Pannonian Basin and the Moesian Platform have thinner crust than the surrounding areas. Here the crustal thicknesses are less than 30 km on average. The thinnest crust can be found in the SE part of the Pannonian Basin near the contact with the Southern Carpathians where it is only 26 km. The thickest lithosphere is placed in the East European Platform, Eastern Carpathians and Southern Carpathians. The East European Platform lithosphere thickness is on average more than 120 km. A strip of thicker lithosphere follows the Eastern Carpathians and its Foredeep, where the values reach in average 160 km. A lithosphere thickness minimum can be observed at the southern border of the Southern Carpathians and in the SE part of the Pannonian Basin. Here, it is only 60 km. The extremely low values of lithospheric thickness in this area were not shown before. The Moesian Platform is characterized by an E-W trend of lithospheric thickness decrease. In the East, the thickness is about 110 km and in the west it is only 80 km. The Pannonian Basin lithospheric thickness ranges from 80 to 100 km.
A new intermediate-depth ice-core drilling system
Authors: Sheldon Simon G. , Popp Trevor J. , Hansen Steffen B. , Hedegaard Thomas M. , Mortensen Carsten 
Published: January 2015

AbstractSeveral recent projects associated with the IPICS (International Partnerships in Ice Core Sciences) 2k array have demanded the recovery of ice core to depths in excess of several hundred metres (e.g. Flade Isblink, Greenland (2006), Aurora Basin, Antarctica (2008/09), NEEM, Greenland (2011), Aurora Basin North (2013/14) and Renland ice cap, Greenland (2015)). These projects require that the overall system weight is low, that the ability to set up and operate are within the limitations of a small-camp environment and that the overall logistical and transportation costs are kept to a minimum. Using these criteria, a new drilling system capable of drilling >400m depth was seen as a useful future development. Here we report on a new intermediate-depth drilling system designed to recover high-quality 98 mm diameter ice cores from close to surface down to depths of 1000 m by two or more operators in a small deep-field camp environment. The total weight of the system on the snow surface is ∼490 kg, of which the intermediate-depth winch is the single heaviest component at 305 kg with 1000 m of cable.