bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential for Waterborne and Invertebrate Transmission of West Nile Virus in the Great Salt Lake, Utah
Authors: Lund Melissa , Shearn-Bochsler Valerie , Dusek Robert J. , Shivers Jan , Hofmeister Erik 
Published: May 2017

ABSTRACT

In November and December of 2013, a large mortality event involving 15,000 to 20,000 eared grebes (
Podiceps nigricollis
) occurred at the Great Salt Lake (GSL), UT. The onset of the outbreak in grebes was followed by a mortality event in >86 bald eagles (
Haliaeetus leucocephalus
). During the die-off, West Nile virus (WNV) was detected by reverse transcription-PCR (RT-PCR) or viral culture in the carcasses of grebes and eagles submitted to the National Wildlife Health Center. However, no activity of mosquitoes, the primary vectors of WNV, was detected by the State of Utah's WNV monitoring program. The transmission of WNV has rarely been reported during the winter in North America in the absence of known mosquito activity; however, the size of this die-off, the habitat in which it occurred, and the species involved are unique. We experimentally investigated whether WNV could survive in water with a high salt content, as found at the GSL, and whether brine shrimp, the primary food of migrating eared grebes on the GSL, could have played a role in the transmission of WNV to feeding birds. We found that WNV can survive up to 72 h at 4°C in water containing 30 to 150 ppt NaCl, and brine shrimp incubated with WNV in 30 ppt NaCl may adsorb WNV to their cuticle and, through feeding, infect epithelial cells of their gut. Both mechanisms may have potentiated the WNV die-off in migrating eared grebes on the GSL.

IMPORTANCE
Following a major West Nile virus die-off of eared grebes and bald eagles at the Great Salt Lake (GSL), UT, in November to December 2013, this study assessed the survival of West Nile virus (WNV) in water as saline as that of the GSL and whether brine shrimp, the major food for migrating grebes, could have played a role as a vector for the virus. While mosquitoes are the major vector of WNV, under certain circumstances, transmission may occur through contaminated water and invertebrates as food.
RoxB Is a Novel Type of Rubber Oxygenase That Combines Properties of Rubber Oxygenase RoxA and Latex Clearing Protein (Lcp)
Authors: Birke Jakob , Röther Wolf , Jendrossek Dieter 
Published: May 2017

ABSTRACT

Only two types of rubber oxygenases, rubber oxygenase (RoxA) and latex clearing protein (Lcp), have been described so far. RoxA proteins (RoxAs) are
c
-type cytochromes of ≈70 kDa produced by Gram-negative rubber-degrading bacteria, and they cleave polyisoprene into 12-oxo-4,8-dimethyltrideca-4,8-diene-1-al (ODTD), a C
15
oligo-isoprenoid, as the major end product. Lcps are common among Gram-positive rubber degraders and do not share amino acid sequence similarities with RoxAs. Furthermore, Lcps have much smaller molecular masses (≈40 kDa), are
b
-type cytochromes, and cleave polyisoprene to a mixture of C
20
, C
25
, C
30
, and higher oligo-isoprenoids as end products. In this article, we purified a new type of rubber oxygenase, RoxB

Xsp

(RoxB of
Xanthomonas
sp. strain 35Y). RoxB

Xsp

is distantly related to RoxAs and resembles RoxAs with respect to molecular mass (70.3 kDa for mature protein) and cofactor content (2
c
-type hemes). However, RoxB

Xsp

differs from all currently known RoxAs in having a distinctive product spectrum of C
20
, C
25
, C
30
, and higher oligo-isoprenoids that has been observed only for Lcps so far. Purified RoxB

Xsp

revealed the highest specific activity of 4.5 U/mg (at 23°C) of all currently known rubber oxygenases and exerts a synergistic effect on the efficiency of polyisoprene cleavage by RoxA

Xsp

. RoxB homologs were identified in several other Gram-negative rubber-degrading species, pointing to a prominent function of RoxB for the biodegradation of rubber in Gram-negative bacteria.

IMPORTANCE
The enzymatic cleavage of rubber (polyisoprene) is of high environmental importance given that enormous amounts of rubber waste materials are permanently released (e.g., by abrasion of tires). Research from the last decade has discovered rubber oxygenase A, RoxA, and latex clearing protein (Lcp) as being responsible for the primary enzymatic attack on the hydrophobic and water-insoluble biopolymer poly(
cis
-1,4-isoprene) in Gram-negative and Gram-positive rubber-degrading bacteria, respectively. Here, we provide evidence that a third type of rubber oxygenase is present in Gram-negative rubber-degrading species. Due to its characteristics, we suggest the designation RoxB for the new type of rubber oxygenase. Bioinformatic analysis of genome sequences indicates the presence of
roxB
homologs in other Gram-negative rubber degraders.
Quadriceps strengthening with and without blood flow restriction in the treatment of patellofemoral pain: a double-blind randomised trial
Authors: Giles Lachlan , Webster Kate E , McClelland Jodie , Cook Jill L 
Published: May 2017

BackgroundQuadriceps strengthening exercises are part of the treatment of patellofemoral pain (PFP), but the heavy resistance exercises may aggravate knee pain. Blood flow restriction (BFR) training may provide a low-load quadriceps strengthening method to treat PFP.MethodsSeventy-nine participants were randomly allocated to a standardised quadriceps strengthening (standard) or low-load BFR. Both groups performed 8 weeks of leg press and leg extension, the standard group at 70% of 1 repetition maximum (1RM) and the BFR group at 30% of 1RM. Interventions were compared using repeated-measures analysis of variance for Kujala Patellofemoral Score, Visual Analogue Scale for ‘worst pain’ and ‘pain with daily activity’, isometric knee extensor torque (Newton metre) and quadriceps muscle thickness (cm). Subgroup analyses were performed on those participants with painful resisted knee extension at 60°.ResultsSixty-nine participants (87%) completed the study (standard, n=34; BFR, n=35). The BFR group had a 93% greater reduction in pain with activities of daily living (p=0.02) than the standard group. Participants with painful resisted knee extension (n=39) had greater increases in knee extensor torque with BFR than standard (p<0.01). No between-group differences were found for change in Kujala Patellofemoral Score (p=0.31), worst pain (p=0.24), knee extensor torque (p=0.07) or quadriceps thickness (p=0.2). No difference was found between interventions at 6 months.ConclusionCompared with standard quadriceps strengthening, low load with BFR produced greater reduction in pain with daily living at 8 weeks in people with PFP. Improvements were similar between groups in worst pain and Kujala score. The subgroup with painful resisted knee extension had larger improvements in quadriceps strength from BFR.Trial registration number12614001164684.
Exercise therapy for functional capacity in chronic diseases: an overview of meta-analyses of randomised controlled trials
Authors: Pasanen Tero , Tolvanen Samppa , Heinonen Ari , Kujala Urho M 
Published: May 2017

ObjectiveTo summarise all meta-analyses of randomised controlled trials that have evaluated the effects of exercise therapy on functional capacity in patients with chronic diseases.DesignUmbrella review of meta-analyses of randomised controlled trials.Data sourcesWe systematically searched the CENTRAL, CINAHL, DARE, Medline, OTSeeker, PEDro, SPORTDiscus, ProQuest Nursing & Allied Health Database, Web of Science, Scopus, OpenGrey and BMC Proceedings from database inception to 1 September 2016.Eligibility criteria for selecting studiesWe included meta-analyses that compared the effects of exercise therapy with no treatment or usual care in adults with non-communicable chronic diseases and included outcomes related to functional capacity. We excluded meta-analyses with less than 100 patients.ResultsEighty-five meta-analyses with 22 different chronic diseases were included. The exercise interventions resulted in statistically significant (p<0.05) improvements for 126 of 146 (86%) functional capacity outcomes, compared with the control group. The standardised mean differences were small in 64 (44%), moderate in 54 (37%) and large in 28 (19%) of the 146 functional capacity outcomes. The results were similar for aerobic exercise, resistance training, and aerobic and resistance training combined. There were no significant differences in serious adverse effects between the intervention and control groups in any of the meta-analyses.ConclusionExercise therapy appears to be a safe way to improve functional capacity and reduce disability in individuals with chronic disease.
Proper Electronic Order Linkage of Electrocardiograms at a Large Children's Hospital Improves Reporting and Revenue
Authors: Spar David S , Mays Wayne A , Cooper David S , Sullivan Lucille , Hicks Terra , B Anderson Jeffrey 
Published: May 2017

Electrocardiograms (ECGs) are performed to determine an individual's cardiac rhythm. Approximately 25,000 ECGs are performed yearly throughout our hospital system. Historically only 68% of all ECGs were performed with the proper order linked to the electronic ECG reading system (MUSE). Failure to link the orders to the electronic reading system leads to problems in patient safety, reporting and hospital revenue.Our aim was to increase the percentage of linked ECG orders in MUSE compared to total ECGs performed from 68% to 95%.We created a detailed process map of ECG order linking to the MUSE electronic system. FMEA and Pareto chart creation were used to determine etiology of process failures. Multiple interventions (LOR1 to LOR3) were implemented utilizing the PDSA technique. Process control charts were used to evaluate change.FMEA and Pareto chart determined most common failures were related to: 1) ECG order not electronically acquired properly, 2) duplicate ECGs and 3) ECG order was not electronically placed. We performed multiple interventions including: 1) ECG performance education, 2) created reminders on the ECG machines, 3) specialized electronic linking system for physician readers and 4) bar-code scanners for all ECG machines. These changes improved ECG order linking to MUSE from 68% to 95% over 6-months. In direct comparison between fiscal year (FY) FY2014 to FY2015, the number of ECGs performed increased 2% while billing increased by 23%.Utilization of quality improvement methodology allowed us to identify failures for ECG order linking. We established multiple successful interventions amongst different hospital locations and improved our compliance, billing and reporting of ECGs.
Sound: a non-invasive measure of cough intensity
Authors: Lee Kai K , Matos Sergio , Ward Katie , Rafferty Gerrard F , Moxham John , Evans David H , Birring Surinder S 
Published: May 2017

IntroductionCough intensity is an important determinant of cough severity reported by patients. Cough sound analysis has been widely validated for the measurement of cough frequency but few studies have validated its use in the assessment of cough strength. We investigated the relationship between cough sound and physiological measures of cough strength.Methods32 patients with chronic cough and controls underwent contemporaneous measurements of voluntary cough sound, flow and oesophageal pressure. Sound power, peak energy, rise-time, duration, peak-frequency, bandwidth and centroid-frequency were assessed and compared with physiological measures. The relationship between sound and subjective cough strength Visual Analogue Score (VAS), the repeatability of cough sounds and the effect of microphone position were also assessed.ResultsSound power and energy correlated strongly with cough flow (median Spearman’s r=0.87–0.88) and oesophageal pressure (median Spearman’s r=0.89). Sound power and energy correlated strongly with cough strength VAS (median Spearman’s r=0.84–0.86) and were highly repeatable (intraclass correlation coefficient=0.93–0.94) but both were affected by change in microphone position.ConclusionsCough sound power and energy correlate strongly with physiological measures and subjective perception of cough strength. Power and energy are highly repeatable measures but the microphone position should be standardised. Our findings support the use of cough sound as an index of cough strength.
Feasibility of the Manchester Acute Coronary Syndromes (MACS) decision rule to safely reduce unnecessary hospital admissions: a pilot randomised controlled trial
Authors: Body Richard , Boachie Charles , McConnachie Alex , Carley Simon , Van Den Berg Patricia , Lecky Fiona E 
Published: May 2017

BackgroundObservational studies suggest that the Manchester Acute Coronary Syndromes (MACS) decision rule can effectively ‘rule out’ and ‘rule in’ acute coronary syndromes (ACS) following a single blood test. In a pilot randomised controlled trial, we aimed to determine whether a large trial is feasible.MethodsPatients presenting to two EDs with suspected cardiac chest pain were randomised to receive care guided by the MACS decision rule (intervention group) or standard care (controls). The primary efficacy outcome was a successful discharge from the ED, defined as a decision to discharge within 4 hours of arrival providing that the patient did not have a missed acute myocardial infarction (AMI) or develop a major adverse cardiac event (MACE: death, AMI or coronary revascularisation) within 30 days. Feasibility outcomes included recruitment and attrition rates.ResultsIn total, 138 patients were included between October 2013 and October 2014, of whom 131 (95%) were randomised (66 to intervention and 65 controls). Nine (7%) patients had prevalent AMI and six (5%) had incident MACE within 30 days. All 131 patients completed 30-day follow-up and were included in the final analysis with no missing data for the primary analyses. Compared with standard care, a significantly greater proportion of patients whose care was guided by the MACS rule were successfully discharged within 4 hours (26% vs 8%, adjusted OR 5.45, 95% CI 1.73 to 17.11, p=0.004). No patients in either group who were discharged within 4 hours had a diagnosis of AMI or incident MACE within 30 days (0.0%, 95% CI 0% to 20.0% in the intervention group).ConclusionsIn this pilot trial, use of the MACS rule led to a significant increase in safe discharges from the ED but a larger, fully powered trial remains necessary. Our findings seem to support the feasibility of that trial.Trial registration numberISRCTN 86818215.Research Ethics Committee reference13/NW/0081.UKCRN registration ID14334.
Closing the theory to practice gap for newly qualified doctors: evaluation of a peer-delivered practical skills training course for newly qualified doctors in preparation for clinical practice
Authors: Beane A , Padeniya A , De Silva A P , Stephens T , De Alwis S , Mahipala P G , Sigera P C , Munasinghe S , Weeratunga P , Ranasinghe D , Deshani E M , Weerasinghe T , Thilakasiri K , Jayasinghe K A S , Dondorp A M , Haniffa R 
Published: May 2017

ABSTRACTPurposeThe Good Intern Programme (GIP) in Sri Lanka has been implemented to bridge the ’theory to practice gap’ of doctors preparing for their internship. This paper evaluates the impact of a 2-day peer-delivered Acute Care Skills Training (ACST) course as part of the GIP.Study designThe ACST course was developed by an interprofessional faculty, including newly graduated doctors awaiting internship (pre-intern), focusing on the recognition and management of common medical and surgical emergencies. Course delivery was entirely by pre-intern doctors to their peers. Knowledge was evaluated by a pre- and post-course multiple choice test. Participants’ confidence (post-course) and 12 acute care skills (pre- and post-course) were assessed using Likert scale-based questions. A subset of participants provided feedback on the peer learning experience.ResultsSeventeen courses were delivered by a faculty consisting of eight peer trainers over 4 months, training 320 participants. The mean (SD) multiple choice questionnaire score was 71.03 (13.19) pre-course compared with 77.98 (7.7) post-course (p&lt;0.05). Increased overall confidence in managing ward emergencies was reported by 97.2% (n=283) of respondents. Participants rated their post-course skills to be significantly higher (p&lt;0.05) than pre-course in all 12 assessed skills. Extended feedback on the peer learning experience was overwhelmingly positive and 96.5% would recommend the course to a colleague.ConclusionsA peer-delivered ACST course was extremely well received and can improve newly qualified medical graduates’ knowledge, skills and confidence in managing medical and surgical emergencies. This peer-based model may have utility beyond pre-interns and beyond Sri Lanka.
A brief introduction to the use of X-ray computed tomography (CT) for analysis of natural deformation structures in reservoir rocks
Authors: Wennberg Ole Petter , Rennan Lars 
Published: May 2017

Abstract
X-ray computed tomography (CT) is frequently used for non-destructive imaging and analysis of internal features in rock samples. In this paper we review the method for analysis of subseismic deformation structures in reservoir rocks, and provide some examples of different types of structures. Both medical CT and high-resolution µCT have great potential for identification of small-scale deformation structures in reservoir rocks and samples from outcrop analogues. The CT imaging techniques provide 3D data that are used in combination with 2D information from core or outcrop, thin-section and scanning electron microscopy (SEM). CT and µCT are used for quantitative and qualitative analysis of individual fractures and fracture networks, and for imaging and analysis of internal heterogeneities of fault rocks and deformation bands. The benefit of CT is that 3D properties (e.g. structure size, connectivity and variation in aperture) are actually characterized in 3D, contrary to traditional 2D methods using core surface, thin-section and outcrop. Limitations and uncertainties arise from artefacts during acquisition and processing, scale of observation and resolution, and manual steps involved in the segmentation of the CT volume. Increased availability of medical CT and µCT scanners and improved resolution should in the future lead to improved description and modelling of small-scale reservoir structures.
β-Catenin Inhibitor BC2059 Is Efficacious as Monotherapy or in Combination with Proteasome Inhibitor Bortezomib in Multiple Myeloma
Authors: Savvidou Ioanna , Khong Tiffany , Cuddihy Andrew , McLean Catriona , Horrigan Stephen , Spencer Andrew 
Published: May 2017

Abstract
Currently available treatment options are unlikely to be curative for the majority of multiple myeloma patients, emphasizing a continuing role for the introduction of investigational agents that can overcome drug resistance. The canonical Wnt/β-catenin signaling pathway, essential for self-renewal, growth, and survival, has been found to be dysregulated in multiple myeloma, particularly in advanced stages of disease. This provides the rationale for evaluating the novel β-catenin inhibitor BC2059 as monotherapy and in combination with proteasome inhibitors in vitro and in vivo. Here, we show nuclear localization of β-catenin in human myeloma cell lines (HMCL), consistent with activation of the canonical Wnt pathway. BC2059 attenuates β-catenin levels, in both the cytoplasm and the nucleus, reducing the transcriptional activity of the TCF4/LEF complex and the expression of its target gene axin 2. Treatment of HMCL with BC2059 inhibits proliferation and induces apoptosis in a dose-dependent manner. This is also observed in HMCL–stromal cell cocultures, mitigating the protective effect afforded by the stroma. Similarly, BC2059 induces apoptosis in primary multiple myeloma samples in vitro, causing minimal apoptosis on healthy peripheral blood mononuclear cells. Furthermore, it synergizes with the proteasome inhibitor bortezomib both in HMCL and primary multiple myeloma samples. Finally, in xenograft models of human myelomatosis, BC2059 delays tumor growth and prolongs survival with minor on-target side effects. Collectively, these results demonstrate the efficacy of targeting the Wnt/β-catenin pathway with BC2059 both in vitro and in vivo, at clinically achievable doses. These findings support further clinical evaluation of BC2059 for the treatment of multiple myeloma. Mol Cancer Ther; 16(9); 1765–78. ©2017 AACR.
Identification of the Serine Biosynthesis Pathway as a Critical Component of BRAF Inhibitor Resistance of Melanoma, Pancreatic, and Non–Small Cell Lung Cancer Cells
Authors: Ross Kayleigh C. , Andrews Andrew J. , Marion Christopher D. , Yen Timothy J. , Bhattacharjee Vikram 
Published: May 2017

Abstract
Metastatic melanoma cells commonly acquire resistance to BRAF V600E inhibitors (BRAFi). In this study, we identified serine biosynthesis as a critical mechanism of resistance. Proteomic assays revealed differential protein expression of serine biosynthetic enzymes PHGDH, PSPH, and PSAT1 following vemurafenib (BRAFi) treatment in sensitive versus acquired resistant melanoma cells. Ablation of PHGDH via siRNA sensitized acquired resistant cells to vemurafenib. Inhibiting the folate cycle, directly downstream of serine synthesis, with methotrexate also displayed similar sensitization. Using the DNA-damaging drug gemcitabine, we show that gemcitabine pretreatment sensitized resistant melanoma cells to BRAFis vemurafenib and dabrafenib. We extended our findings to BRAF WT tumor cell lines that are intrinsically resistant to vemurafenib and dabrafenib. Pretreatment of pancreatic cancer and non–small cell lung cancer cell lines with sublethal doses of 50 and 5 nmol/L of gemcitabine, respectively, enhanced killing by both vemurafenib and dabrafenib. The novel aspects of this study are the direct identification of serine biosynthesis as a critical mechanism of BRAF V600E inhibitor resistance and the first successful example of using gemcitabine + BRAFis in combination to kill previously drug-resistant cancer cells, creating the translational potential of pretreatment with gemcitabine prior to BRAFi treatment of tumor cells to reverse resistance within the mutational profile and the WT. Mol Cancer Ther; 16(8); 1596–609. ©2017 AACR.
NKG2D Ligand–Targeted Bispecific T-Cell Engagers Lead to Robust Antitumor Activity against Diverse Human Tumors
Authors: Godbersen Claire , Coupet Tiffany A. , Huehls Amelia M. , Zhang Tong , Battles Michael B. , Fisher Jan L. , Ernstoff Marc S. , Sentman Charles L. 
Published: May 2017

AbstractTwo new bispecific T-cell engaging (BiTE) molecules with specificity for NKG2D ligands were developed and functionally characterized. One, huNKG2D-OKT3, was derived from the extracellular portion of the human NKG2D receptor fused to a CD3ϵ binding single-chain variable fragment (scFv), known as OKT3. NKG2D has multiple ligands, including MICA, which are expressed by a variety of malignant cells. A second molecule, B2-OKT3, was created in the tandem scFv BiTE format that targets MICA on tumor cells and CD3ϵ on human T cells. Both BiTEs specifically activated T cells to kill human tumor cell lines. Cytotoxicity by B2-OKT3, but not huNKG2D-OKT3, is blocked by soluble rMICA. The huNKG2D-OKT3 induced greater T-cell cytokine production in comparison with B2-OKT3. No T-cell pretreatment was required for IFNγ production upon coculture of B2-OKT3 or huNKG2D-OKT3 with T cells and target cells. The effector memory T-cell compartment was the primary source of IFNγ, and culture of T cells and these BiTEs with plate-bound rMICA showed ligand density–dependent production of IFNγ from both CD4+ and CD8+ T cells. There was 2-fold more IFNγ produced per CD8+ T cell and 5-fold greater percentage of CD8+ T cells producing IFNγ compared with CD4+ T cells. In addition, both BiTEs elicited significant antitumor responses against human metastatic melanoma tumor samples using autologous or healthy donor T cells. These data demonstrate the robust antitumor activity of these NKG2D ligand–binding bispecific proteins and support their further development for clinical use. Mol Cancer Ther; 16(7); 1335–46. ©2017 AACR.