bluuebunny/crossref_metadata_2025_split huggingface dataset:
The PAS Domain-Containing Protein HeuR Regulates Heme Uptake in Campylobacter jejuni
Authors: Johnson Jeremiah G. , Gaddy Jennifer A. , DiRita Victor J. 
Published: November 2016

ABSTRACT

Campylobacter jejuni
is a leading cause of bacterially derived gastroenteritis. A previous mutant screen demonstrated that the heme uptake system (Chu) is required for full colonization of the chicken gastrointestinal tract. Subsequent work identified a PAS domain-containing regulator, termed HeuR, as being required for chicken colonization. Here we confirm that both the heme uptake system and HeuR are required for full chicken gastrointestinal tract colonization, with the
heuR
mutant being particularly affected during competition with wild-type
C. jejuni
. Transcriptomic analysis identified the
chu
genes—and those encoding other iron uptake systems—as regulatory targets of HeuR. Purified HeuR bound the
chuZA
promoter region in electrophoretic mobility shift assays. Consistent with a role for HeuR in
chu
expression,
heuR
mutants were unable to efficiently use heme as a source of iron under iron-limiting conditions, and mutants exhibited decreased levels of cell-associated iron by mass spectrometry. Finally, we demonstrate that an
heuR
mutant of
C. jejuni
is resistant to hydrogen peroxide and that this resistance correlates to elevated levels of catalase activity. These results indicate that HeuR directly and positively regulates iron acquisition from heme and negatively impacts catalase activity by an as yet unidentified mechanism in
C. jejuni
.

IMPORTANCE
Annually,
Campylobacter jejuni
causes millions of gastrointestinal infections in the United States, due primarily to its ability to reside within the gastrointestinal tracts of poultry, where it can be released during processing and contaminate meat. In the developing world, humans are often infected by consuming contaminated water or by direct contact with livestock. Following consumption of contaminated food or water, humans develop disease that is characterized by mild to severe diarrhea. There is a need to understand both colonization of chickens, to make food safer, and colonization of humans, to better understand disease. Here we demonstrate that to efficiently colonize a host,
C. jejuni
requires iron from heme, which is regulated by the protein HeuR. Understanding how HeuR functions, we can develop ways to inhibit its function and reduce iron acquisition during colonization, potentially reducing
C. jejuni
in the avian host, which would make food safer, or limiting human colonization.
The Cytoplasmic Tail Domain of Epstein-Barr Virus gH Regulates Membrane Fusion Activity through Altering gH Binding to gp42 and Epithelial Cell Attachment
Authors: Chen Jia , Jardetzky Theodore S. , Longnecker Richard 
Published: November 2016

ABSTRACT
Epstein-Barr virus (EBV) is associated with infectious mononucleosis and a variety of cancers as well as lymphoproliferative disorders in immunocompromised patients. EBV mediates viral entry into epithelial and B cells using fusion machinery composed of four glycoproteins: gB, the gH/gL complex, and gp42. gB and gH/gL are required for both epithelial and B cell fusion. The specific role of gH/gL in fusion has been the most elusive among the required herpesvirus entry glycoproteins. Previous mutational studies have focused on the ectodomain of EBV gH and not on the gH cytoplasmic tail domain (CTD). In this study, we chose to examine the function of the gH CTD by making serial gH truncation mutants as well as amino acid substitution mutants to determine the importance of the gH CTD in epithelial and B cell fusion. Truncation of 8 amino acids (aa 698 to 706) of the gH CTD resulted in diminished fusion activity using a virus-free syncytium formation assay and fusion assay. The importance of the amino acid composition of the gH CTD was also investigated by amino acid substitutions that altered the hydrophobicity or hydrophilicity of the CTD. These mutations also resulted in diminished fusion activity. Interestingly, some of the gH CTD truncation mutants and hydrophilic tail substitution mutants lost the ability to bind to gp42 and epithelial cells. In summary, our studies indicate that the gH CTD is an important functional domain.

IMPORTANCE
Infection with Epstein-Barr virus (EBV) causes diseases ranging from the fairly benign infectious mononucleosis to life-threatening cancer. Entry into target cells is the first step for viral infection and is important for EBV to cause disease. Understanding the EBV entry mechanism is useful for the development of infection inhibitors and developing EBV vaccine approaches. Epithelial and B cells are the main target cells for EBV infection. The essential glycoproteins for EBV entry include gB, gH/gL, and gp42. We characterized the function of the EBV gH C-terminal cytoplasmic tail domain (CTD) in fusion using a panel of gH CTD truncation or substitution mutants. We found that the gH CTD regulates fusion by altering gp42 and epithelial cell attachment. Our studies may lead to a better understanding of EBV fusion and entry, which may result in novel therapies that target the EBV entry step.
Nursing skill mix in European hospitals: cross-sectional study of the association with mortality, patient ratings, and quality of care
Authors: Aiken Linda H , Sloane Douglas , Griffiths Peter , Rafferty Anne Marie , Bruyneel Luk , McHugh Matthew , Maier Claudia B , Moreno-Casbas Teresa , Ball Jane E , Ausserhofer Dietmar , Sermeus Walter 
Published: November 2016

ObjectivesTo determine the association of hospital nursing skill mix with patient mortality, patient ratings of their care and indicators of quality of care.DesignCross-sectional patient discharge data, hospital characteristics and nurse and patient survey data were merged and analysed using generalised estimating equations (GEE) and logistic regression models.SettingAdult acute care hospitals in Belgium, England, Finland, Ireland, Spain and Switzerland.ParticipantsSurvey data were collected from 13 077 nurses in 243 hospitals, and 18 828 patients in 182 of the same hospitals in the six countries. Discharge data were obtained for 275 519 surgical patients in 188 of these hospitals.Main outcome measuresPatient mortality, patient ratings of care, care quality, patient safety, adverse events and nurse burnout and job dissatisfaction.ResultsRicher nurse skill mix (eg, every 10-point increase in the percentage of professional nurses among all nursing personnel) was associated with lower odds of mortality (OR=0.89), lower odds of low hospital ratings from patients (OR=0.90) and lower odds of reports of poor quality (OR=0.89), poor safety grades (OR=0.85) and other poor outcomes (0.80<OR<0.93), after adjusting for patient and hospital factors. Each 10 percentage point reduction in the proportion of professional nurses is associated with an 11% increase in the odds of death. In our hospital sample, there were an average of six caregivers for every 25 patients, four of whom were professional nurses. Substituting one nurse assistant for a professional nurse for every 25 patients is associated with a 21% increase in the odds of dying.ConclusionsA bedside care workforce with a greater proportion of professional nurses is associated with better outcomes for patients and nurses. Reducing nursing skill mix by adding nursing associates and other categories of assistive nursing personnel without professional nurse qualifications may contribute to preventable deaths, erode quality and safety of hospital care and contribute to hospital nurse shortages.
Film tension of liquid nano-film from molecular modeling
Authors: Peng Tiefeng , Yang Siyuan , Xiang Fan , Liang Yunpei , Li Qibin , Gao Xuechao , Liu Sanjun 
Published: November 2016

Due to its geometry simplicity, the forces of thin liquid film are widely investigated and equivalently employed to explore the phys–chemical properties and mechanical stability of many other surfaces or colloid ensembles. The surface tension of bulk liquid ([Formula: see text]) and film tension ([Formula: see text]) are the most important parameters. Considering the insufficiency of detailed interpretation of film tension under micro-scale circumstances, a method for film tension was proposed based on numerical modeling. Assuming surface tension at different slab thicknesses being identical to the surface tension of film, the surface tension and disjoining pressure were subsequently used to evaluate the film tension based on the derivation of film thermodynamics, and a decreasing tendency was discovered for low temperature regions. The influence of saline concentration on nano-films was also investigated, and the comparison of film tensions suggested that higher concentration yielded larger film tension, with stronger decreasing intensity as a function of film thickness. Meanwhile, at thick film range (15–20 nm), film tension of higher concentration film continued to decrease as thickness increase, however it arrived to constant value for that of lower concentration. Finally, it was found that the film tension was almost independent on the film curvature, but varied with the thickness. The approach is applicable to symmetric emulsion films containing surfactants and bi-layer lipid films.
Synthesis of Mesoporous Silica Monoliths — A Novel Approach Towards Fabrication of Solid-State Optical Sensors for Environmental Applications
Authors: Prabhakaran D. , Subashini C. , Akhila Maheswari M. 
Published: November 2016

Mesoporous silica monoliths are an attractive area of research owing to their high specific surface area, uniform channels and mesoporous size (2–30[Formula: see text]nm). This paper deals with the direct templating synthesis of a mesoporous worm-like silica monolithic material using F127 — a triblock copolymer, by micro-emulsion technique using trimethyl benzene (TMB), as the solvent. The synthesized silica monolith is characterized using SEM-EDAX, XRD, BET, NMR and FT-IR. The monolith shows an ordered worm-like mesoporous structure with tuneable through pores, an excellent host for the anchoring of chromo-ionophores for the naked-eye metal ion-sensing. The mesoporous monoliths were loaded with 4-dodecyl-6-(2-pyridylazo)-phenol (DPAP) ligand through direct immobilization, thereby acting as solid-state naked-eye colorimetric ion-sensors for the sensing toxic Pb[Formula: see text] ions at parts-per-billion (ppb) level in various industrial and environmental systems. The influence of various experimental parameters such as solution pH, limiting ligand loading concentration, amount of monolith material, matrix tolerance level, limit of detection and quantification has been studied and optimized.
Increases in human motoneuron excitability after cervical spinal cord injury depend on the level of injury
Authors: Thomas Christine K. , Häger Charlotte K. , Klein Cliff S. 
Published: November 2016

After human spinal cord injury (SCI), motoneuron recruitment and firing rate during voluntary and involuntary contractions may be altered by changes in motoneuron excitability. Our aim was to compare F waves in single thenar motor units paralyzed by cervical SCI to those in uninjured controls because at the single-unit level F waves primarily reflect the intrinsic properties of the motoneuron and its initial segment. With intraneural motor axon stimulation, F waves were evident in all 4 participants with C4-level SCI, absent in 8 with C5 or C6 injury, and present in 6 of 12 Uninjured participants ( P < 0.001). The percentage of units that generated F waves differed across groups (C4: 30%, C5 or C6: 0%, Uninjured: 16%; P < 0.001). Mean (±SD) proximal axon conduction velocity was slower after C4 SCI [64 ± 4 m/s ( n = 6 units), Uninjured: 73 ± 8 m/s ( n = 7 units); P = 0.037]. Mean distal axon conduction velocity differed by group [C4: 40 ± 8 m/s ( n = 20 units), C5 or C6: 49 ± 9 m/s ( n = 28), Uninjured: 60 ± 7 m/s ( n = 45); P < 0.001]. Motor unit properties (EMG amplitude, twitch force) only differed after SCI ( P ≤ 0.004), not by injury level. Motor units with F waves had distal conduction velocities, M-wave amplitudes, and twitch forces that spanned the respective group range, indicating that units with heterogeneous properties produced F waves. Recording unitary F waves has shown that thenar motoneurons closer to the SCI (C5 or C6) have reduced excitability whereas those further away (C4) have increased excitability, which may exacerbate muscle spasms. This difference in motoneuron excitability may be related to the extent of membrane depolarization following SCI. NEW & NOTEWORTHY Unitary F waves were common in paralyzed thenar muscles of people who had a chronic spinal cord injury (SCI) at the C4 level compared with uninjured people, but F waves did not occur in people that had SCI at the C5 or C6 level. These results highlight that intrinsic motoneuron excitability depends, in part, on how close the motoneurons are to the site of the spinal injury, which could alter the generation and strength of voluntary and involuntary muscle contractions.
Novel p21-Activated Kinase 4 (PAK4) Allosteric Modulators Overcome Drug Resistance and Stemness in Pancreatic Ductal Adenocarcinoma
Authors: Aboukameel Amro , Muqbil Irfana , Senapedis William , Baloglu Erkan , Landesman Yosef , Shacham Sharon , Kauffman Michael , Philip Philip A. , Mohammad Ramzi M. , Azmi Asfar S. 
Published: November 2016

Abstract
The p21-activated kinase 4 (PAK4) is a key downstream effector of the Rho family GTPases and is found to be overexpressed in pancreatic ductal adenocarcinoma (PDAC) cells but not in normal human pancreatic ductal epithelia (HPDE). Gene copy number amplification studies in PDAC patient cohorts confirmed PAK4 amplification making it an attractive therapeutic target in PDAC. We investigated the antitumor activity of novel PAK4 allosteric modulators (PAM) on a panel of PDAC cell lines and chemotherapy-resistant flow-sorted PDAC cancer stem cells (CSC). The toxicity and efficacy of PAMs were evaluated in multiple subcutaneous mouse models of PDAC. PAMs (KPT-7523, KPT-7189, KPT-8752, KPT-9307, and KPT-9274) show antiproliferative activity in vitro against different PDAC cell lines while sparing normal HPDE. Cell growth inhibition was concurrent with apoptosis induction and suppression of colony formation in PDAC. PAMs inhibited proliferation and antiapoptotic signals downstream of PAK4. Co-immunoprecipitation experiments showed disruption of PAK4 complexes containing vimentin. PAMs disrupted CSC spheroid formation through suppression of PAK4. Moreover, PAMs synergize with gemcitabine and oxaliplatin in vitro. KPT-9274, currently in a phase I clinical trial (clinicaltrials.gov; NCT02702492), possesses desirable pharmacokinetic properties and is well tolerated in mice with the absence of any signs of toxicity when 200 mg/kg daily is administered either intravenously or orally. KPT-9274 as a single agent showed remarkable antitumor activity in subcutaneous xenograft models of PDAC cell lines and CSCs. These proof-of-concept studies demonstrated the antiproliferative effects of novel PAMs in PDAC and warrant further clinical investigations. Mol Cancer Ther; 16(1); 76–87. ©2016 AACR.
Power of an Adaptive Trial Design for Endovascular Stroke Studies
Authors: Lansberg Maarten G. , Bhat Ninad S. , Yeatts Sharon D. , Palesch Yuko Y. , Broderick Joseph P. , Albers Gregory W. , Lai Tze L. , Lavori Philip W. 
Published: November 2016

Background and Purpose—
Adaptive trial designs that allow enrichment of the study population through subgroup selection can increase the chance of a positive trial when there is a differential treatment effect among patient subgroups. The goal of this study is to illustrate the potential benefit of adaptive subgroup selection in endovascular stroke studies.

Methods—
We simulated the performance of a trial design with adaptive subgroup selection and compared it with that of a traditional design. Outcome data were based on 90-day modified Rankin Scale scores, observed in IMS III (Interventional Management of Stroke III), among patients with a vessel occlusion on baseline computed tomographic angiography (n=382). Patients were categorized based on 2 methods: (1) according to location of the arterial occlusive lesion and onset-to-randomization time and (2) according to onset-to-randomization time alone. The power to demonstrate a treatment benefit was based on 10 000 trial simulations for each design.

Results—
The treatment effect was relatively homogeneous across categories when patients were categorized based on arterial occlusive lesion and time. Consequently, the adaptive design had similar power (47%) compared with the fixed trial design (45%). There was a differential treatment effect when patients were categorized based on time alone, resulting in greater power with the adaptive design (82%) than with the fixed design (57%).

Conclusions—
These simulations, based on real-world patient data, indicate that adaptive subgroup selection has merit in endovascular stroke trials as it substantially increases power when the treatment effect differs among subgroups in a predicted pattern.
Atmospheric Data Visualization in Mixed Reality
Authors: Cherukuru Nihanth W. , Calhoun Ronald , Scheitlin Tim , Rehme Matt , Kumar Raghu Raj Prasanna 
Published: November 2016

Abstract
Mixed reality taps into intuitive human perception by merging computer-generated views of digital objects (or flow fields) with natural views. Digital objects can be positioned in 3D space and can mimic real objects in the sense that walking around the object produces smoothly changing views toward the other side. Only recently have advances in gaming graphics advanced to the point that views of moving 3D digital objects can be calculated in real time and displayed together with digital video streams. Auxiliary information can be positioned and timed to give the viewer a deeper understanding of a scene; for example, a pilot landing an aircraft might “see” zones of shear or decaying vortices from previous heavy aircraft. A rotating digital globe might be displayed on a table top to demonstrate the evolution of El Niño. In this article, the authors explore a novel mixed reality data visualization application for atmospheric science data, present the methodology using game development platforms, and demonstrate a few applications to help users quickly and intuitively understand evolving atmospheric phenomena.
Comparison and Validation of Acoustic Response Models for Wind Noise Reduction Pipe Arrays
Authors: Marty Julien , Denis Stéphane , Gabrielson Thomas , Garcés Milton , Brown David 
Published: November 2016

AbstractThe detection capability of the infrasound component of the International Monitoring System (IMS) is tightly linked to the performance of its wind noise reduction systems. The wind noise reduction solution implemented at all IMS infrasound measurement systems consists of a spatial distribution of air inlets connected to the infrasound sensor through a network of pipes. This system, usually referred to as “pipe array,” has proven its efficiency in operational conditions. The objective of this paper is to present the results of the comparison and validation of three distinct acoustic response models for pipe arrays. The characteristics of the models and the results obtained for a defined set of pipe array configurations are described. A field experiment using a newly developed infrasound generator, dedicated to the validation of these models, is then presented. The comparison between the modeled and empirical acoustic responses shows that two of the three models can be confidently used to estimate pipe array acoustic responses. This study paves the way to the deconvolution of IMS infrasound data from pipe array responses and to the optimization of pipe array design to IMS applications.
Middle Ear Obliteration with Blind‐Sac Closure of the External Auditory Canal for Spontaneous CSF Otorrhea
Authors: Stevens Shawn M. , Crane Ryan , Pensak Myles L. , Samy Ravi N. 
Published: November 2016

Outcome ObjectivesTo (1) identify unique features of patients who underwent middle ear/mastoid obliteration with blind‐sac closure of the external auditory canal for spontaneous cerebrospinal fluid (CSF) otorrhea and (2) explore outcomes.Study DesignCase series with chart review.SettingTertiary care center.Subjects and MethodsAdults treated for spontaneous cerebrospinal fluid otorrhea from 2007 through 2015 were reviewed and stratified into 2 groups based on the surgery performed: (1) 11 patients underwent middle ear/mastoid obliteration with blind‐sac closure of the external auditory canal and (2) 26 patients underwent other procedures. Demographics, body mass index, revised cardiac risk index, Duke Activity Status Index scores, and anticoagulation use were documented. Audiologic data were gathered from pre‐ and postoperative visits. The primary outcome measure was leak recurrence. Complications were tabulated.ResultsPoor preoperative hearing was a relative indication for obliteration. Obliteration patients had higher body mass index (43.2 vs 34.9 kg/m2; P <. 05), incidence of super‐morbid obesity (45% vs 7.6%; P =. 015), anticoagulation usage (36% vs 0%; P =. 004), cardiac risk scores (1.2 vs 0.1 dB; P <. 0004), and Duke Activity Status Index scores. There was 1 leak recurrence (9%). Major and minor complication rates were 9% and 36%, respectively. Mean follow‐up was 30.8 ± 8.6 months.ConclusionMiddle ear and mastoid obliteration with blind‐sac closure of the external auditory canal is effective for treating spontaneous CSF otorrhea. The small cohort reviewed did not experience any major perioperative morbidity. The technique may be best suited for patients with poor hearing, the infirm, and those in whom craniotomy is contraindicated.
Sustaining people with dementia or mild cognitive impairment in employment: A systematic review of qualitative evidence
Authors: McCulloch Shona , Robertson David , Kirkpatrick Pamela 
Published: November 2016

Introduction The World Health Organization estimates that 10% of the 35.6 million people worldwide with dementia are aged under 65 years. In an ageing workforce this has implications for employers, employees, and statutory and third sector services. Limited research has been conducted into this emerging global issue. Method This systematic review, employing the methodology of the Joanna Briggs Institute, aimed to identify and synthesise the best available qualitative evidence regarding the needs, experiences and perspectives of people with early onset dementia or mild cognitive impairment who were either in employment or wished to gain employment. Results Of 69 studies identified, eight met the inclusion criteria. From these, four themes emerged: disease progression and recognition; the emotional impact of change; the employer’s management of the worker; and changes to the worker role. Conclusion There are health benefits to the individual with dementia or mild cognitive impairment of continuing to engage in meaningful occupation. Retirement policy changes have resulted in an ageing workforce with concurrent risk factors for dementia. A lack of understanding of reasonable adjustments and sheltered employment opportunities was evident from the literature. This review highlights the potential for occupational therapists to engage this client group in vocational rehabilitation.