bluuebunny/crossref_metadata_2025_split huggingface dataset:
SuhB Associates with Nus Factors To Facilitate 30S Ribosome Biogenesis in Escherichia coli
Authors: Singh Navjot , Bubunenko Mikhail , Smith Carol , Abbott David M. , Stringer Anne M. , Shi Ronald , Court Donald L. , Wade Joseph T. 
Published: March 2016

ABSTRACT

A complex of highly conserved proteins consisting of NusB, NusE, NusA, and NusG is required for robust expression of rRNA in
Escherichia coli
. This complex is proposed to prevent Rho-dependent transcription termination by a process known as “antitermination.” The mechanism of this antitermination in rRNA is poorly understood but requires association of NusB and NusE with a specific RNA sequence in rRNA known as BoxA. Here, we identify a novel member of the rRNA antitermination machinery: the inositol monophosphatase SuhB. We show that SuhB associates with elongating RNA polymerase (RNAP) at rRNA in a NusB-dependent manner. Although we show that SuhB is required for BoxA-mediated antitermination in a reporter system, our data indicate that the major function of the NusB/E/A/G/SuhB complex is not to prevent Rho-dependent termination of rRNA but rather to promote correct rRNA maturation. This occurs through formation of a SuhB-mediated loop between NusB/E/BoxA and RNAP/NusA/G. Thus, we have reassigned the function of these proteins at rRNA and identified another key player in this complex.

IMPORTANCE
As RNA polymerase transcribes the rRNA operons in
E. coli
, it complexes with a set of proteins called Nus that confer enhanced rates of transcription elongation, correct folding of rRNA, and rRNA assembly with ribosomal proteins to generate a fully functional ribosome. Four Nus proteins were previously known, NusA, NusB, NusE, and NusG; here, we discover and describe a fifth, SuhB, that is an essential component of this complex. We demonstrate that the main function of this SuhB-containing complex is not to prevent premature transcription termination within the rRNA operon, as had been long claimed, but to enable rRNA maturation and a functional ribosome fully competent for translation.
Feasibility of surgical randomised controlled trials with a placebo arm: a systematic review
Authors: Wartolowska Karolina , Collins Gary S , Hopewell Sally , Judge Andrew , Dean Benjamin J F , Rombach Ines , Beard David J , Carr Andrew J 
Published: March 2016

ObjectivesTo find evidence, either corroborating or refuting, for many persisting beliefs regarding the feasibility of carrying out surgical randomised controlled trials with a placebo arm, with emphasis on the challenges related to recruitment, funding, anaesthesia or blinding.DesignSystematic review.Data sources and study selectionThe analysis involved studies published between 1959 and 2014 that were identified during an earlier systematic review of benefits and harms of placebo-controlled surgical trials published in 2014.Results63 trials were included in the review. The main problem reported in many trials was a very slow recruitment rate, mainly due to the difficulty in finding eligible patients. Existing placebo trials were funded equally often from commercial and non-commercial sources. General anaesthesia or sedation was used in 41% of studies. Among the reviewed trials, 81% were double-blinded, and 19% were single-blinded. Across the reviewed trials, 96% (range 50–100%) of randomised patients completed the study. The withdrawal rate during the study was similar in the surgical and in the placebo groups.ConclusionsThis review demonstrated that placebo-controlled surgical trials are feasible, at least for procedures with a lower level of invasiveness, but also that recruitment is difficult. Many of the presumed challenges to undertaking such trials, for example, funding, anaesthesia or blinding of patients and assessors, were not reported as obstacles to completion in any of the reviewed trials.
Mining social media data for opinion polarities about electronic cigarettes
Authors: Dai Hongying , Hao Jianqiang 
Published: March 2016

BackgroundThere is an ongoing debate about harm and benefit of e-cigarettes, usage of which has rapidly increased in recent years. By separating non-commercial (organic) tweets from commercial tweets, we seek to evaluate the general public's attitudes towards e-cigarettes.MethodsWe collected tweets containing the words ‘e-cig’, ‘e-cigarette’, ‘e-liquid’, ‘vape’, ‘vaping’, ‘vapor’ and ‘vaporizer’ from 23 July to 14 October 2015 (n=757 167). A multilabel Naïve Bayes model was constructed to classify tweets into 5 polarities (against, support, neutral, commercial, irrelevant). We further analysed the prevalence of e-cigarette tweets, geographic variations in these tweets and the impact of socioeconomic factors on the public attitudes towards e-cigarettes.ResultsOpinions from organic tweets about e-cigarettes were mixed (against 17.7%, support 10.8% and neutral 19.4%). The organic—against tweets delivered strong educational information about the risks of e-cigarette use and advocated for the general public, especially youth, to stop vaping. However, the organic—against tweets were outnumbered by commercial tweets and organic—support tweets by a ratio of over 1 to 3. Higher prevalence of organic tweets was associated with states with higher education rates (r=0.60, p<0.0001), higher percentage of black and African-American population (r=0.34, p=0.01), and higher median household income (r=0.33, p=0.02). The support rates for e-cigarettes were associated with states with fewer persons under 18 years old (r=−0.33, p=0.02) and a higher percentage of female population (r=0.3, p=0.02).ConclusionsThe organic—against tweets raised public awareness of potential health risks and could aid in preventing non-smokers, adolescents and young adults from using e-cigarettes. Opinion polarities about e-cigarettes from social networks could be highly influential to the general public, especially youth. Further educational campaigns should include measuring their effectiveness.
The EGF Receptor Promotes the Malignant Potential of Glioma by Regulating Amino Acid Transport System xc(—)
Authors: Tsuchihashi Kenji , Okazaki Shogo , Ohmura Mitsuyo , Ishikawa Miyuki , Sampetrean Oltea , Onishi Nobuyuki , Wakimoto Hiroaki , Yoshikawa Momoko , Seishima Ryo , Iwasaki Yoshimi , Morikawa Takayuki , Abe Shinya , Takao Ayumi , Shimizu Misato , Masuko Takashi , Nagane Motoo , Furnari Frank B. , Akiyama Tetsu , Suematsu Makoto , Baba Eishi , Akashi Koichi , Saya Hideyuki , Nagano Osamu 
Published: March 2016

Abstract
Extracellular free amino acids contribute to the interaction between a tumor and its microenvironment through effects on cellular metabolism and malignant behavior. System xc(–) is composed of xCT and CD98hc subunits and functions as a plasma membrane antiporter for the uptake of extracellular cystine in exchange for intracellular glutamate. Here, we show that the EGFR interacts with xCT and thereby promotes its cell surface expression and function in human glioma cells. EGFR-expressing glioma cells manifested both enhanced antioxidant capacity as a result of increased cystine uptake, as well as increased glutamate, which promotes matrix invasion. Imaging mass spectrometry also revealed that brain tumors formed in mice by human glioma cells stably overexpressing EGFR contained higher levels of reduced glutathione compared with those formed by parental cells. Targeted inhibition of xCT suppressed the EGFR-dependent enhancement of antioxidant capacity in glioma cells, as well as tumor growth and invasiveness. Our findings establish a new functional role for EGFR in promoting the malignant potential of glioma cells through interaction with xCT at the cell surface. Cancer Res; 76(10); 2954–63. ©2016 AACR.
Molecular Pathways: Immunosuppressive Roles of IRE1α-XBP1 Signaling in Dendritic Cells of the Tumor Microenvironment
Authors: Cubillos-Ruiz Juan R. , Bettigole Sarah E. , Glimcher Laurie H. 
Published: March 2016

Abstract
The endoplasmic reticulum (ER) is a massive cytoplasmic membrane network that functions primarily to ensure proper folding and posttranslational modification of newly synthesized secreted and transmembrane proteins. Abnormal accumulation of unfolded proteins in this organelle causes a state of "ER stress," which is a hallmark feature of various diseases, including cancer, neurodegeneration, and metabolic dysfunction. Cancer cells exploit the IRE1α-XBP1 arm of the ER stress response to efficiently adjust their protein-folding capacity and ensure survival under hostile tumor microenvironmental conditions. However, we recently found that dendritic cells (DC) residing in the ovarian cancer microenvironment also experience sustained ER stress and demonstrate persistent activation of the IRE1α-XBP1 pathway. This previously unrecognized process disrupts metabolic homeostasis and antigen-presenting capacity in DCs, thereby crippling their natural ability to support the protective functions of infiltrating antitumor T cells. In this review, we briefly discuss some of the mechanisms that fuel ER stress in tumor-associated DCs, the biologic processes altered by aberrant IRE1α-XBP1 signaling in these innate immune cells, and the unique immunotherapeutic potential of targeting this pathway in cancer hosts. Clin Cancer Res; 22(9); 2121–6. ©2016 AACR.
Blocking Indolamine-2,3-Dioxygenase Rebound Immune Suppression Boosts Antitumor Effects of Radio-Immunotherapy in Murine Models and Spontaneous Canine Malignancies
Authors: Monjazeb Arta M. , Kent Michael S. , Grossenbacher Steven K. , Mall Christine , Zamora Anthony E. , Mirsoian Annie , Chen Mingyi , Kol Amir , Shiao Stephen L. , Reddy Abhinav , Perks Julian R. , T.N. Culp William , Sparger Ellen E. , Canter Robert J. , Sckisel Gail D. , Murphy William J. 
Published: March 2016

Abstract
Purpose: Previous studies demonstrate that intratumoral CpG immunotherapy in combination with radiotherapy acts as an in-situ vaccine inducing antitumor immune responses capable of eradicating systemic disease. Unfortunately, most patients fail to respond. We hypothesized that immunotherapy can paradoxically upregulate immunosuppressive pathways, a phenomenon we term “rebound immune suppression,” limiting clinical responses. We further hypothesized that the immunosuppressive enzyme indolamine-2,3-dioxygenase (IDO) is a mechanism of rebound immune suppression and that IDO blockade would improve immunotherapy efficacy.
Experimental Design: We examined the efficacy and immunologic effects of a novel triple therapy consisting of local radiotherapy, intratumoral CpG, and systemic IDO blockade in murine models and a pilot canine clinical trial.
Results: In murine models, we observed marked increase in intratumoral IDO expression after treatment with radiotherapy, CpG, or other immunotherapies. The addition of IDO blockade to radiotherapy + CpG decreased IDO activity, reduced tumor growth, and reduced immunosuppressive factors, such as regulatory T cells in the tumor microenvironment. This triple combination induced systemic antitumor effects, decreasing metastases, and improving survival in a CD8+ T-cell–dependent manner. We evaluated this novel triple therapy in a canine clinical trial, because spontaneous canine malignancies closely reflect human cancer. Mirroring our mouse studies, the therapy was well tolerated, reduced intratumoral immunosuppression, and induced robust systemic antitumor effects.
Conclusions: These results suggest that IDO maintains immune suppression in the tumor after therapy, and IDO blockade promotes a local antitumor immune response with systemic consequences. The efficacy and limited toxicity of this strategy are attractive for clinical translation. Clin Cancer Res; 22(17); 4328–40. ©2016 AACR.
Early Fiber Number Ratio Is a Surrogate of Corticospinal Tract Integrity and Predicts Motor Recovery After Stroke
Authors: Bigourdan Antoine , Munsch Fanny , Coupé Pierrick , Guttmann Charles R.G. , Sagnier Sharmila , Renou Pauline , Debruxelles Sabrina , Poli Mathilde , Dousset Vincent , Sibon Igor , Tourdias Thomas 
Published: March 2016

Background and Purpose—
The contribution of imaging metrics to predict poststroke motor recovery needs to be clarified. We tested the added value of early diffusion tensor imaging (DTI) of the corticospinal tract toward predicting long-term motor recovery.

Methods—
One hundred seventeen patients were prospectively assessed at 24 to 72 hours and 1 year after ischemic stroke with diffusion tensor imaging and motor scores (Fugl-Meyer). The initial fiber number ratio (iFNr) and final fiber number ratio were computed as the number of streamlines along the affected corticospinal tract normalized to the unaffected side and were compared with each other. The prediction of motor recovery (ΔFugl-Meyer) was first modeled using initial Fugl-Meyer and iFNr. Multivariate ordinal logistic regression models were also used to study the association of iFNr, initial Fugl-Meyer, age, and stroke volume with Fugl-Meyer at 1 year.

Results—

The iFNr correlated with the final fiber number ratio at 1 year (
r
=0.70;
P
<0.0001). The initial Fugl-Meyer strongly predicted motor recovery (≈73% of initial impairment) for all patients except those with initial severe stroke (Fugl-Meyer<50). For these severe patients (n=26), initial Fugl-Meyer was not correlated with motor recovery (
R
2
=0.13; p=ns), whereas iFNr showed strong correlation (
R
2
=0.56;
P
<0.0001). In multivariate analysis, the iFNr was an independent predictor of motor outcome (β=2.601; 95% confidence interval=0.304–5.110;
P
=0.031), improving prediction compared with using only initial Fugl-Meyer, age, and stroke volume (
P
=0.026).

Conclusions—
Early measurement of FNr at 24 to 72 hours poststroke is a surrogate marker of corticospinal tract integrity and provides independent prediction of motor outcome at 1 year especially for patients with severe initial impairment.
Paracetamol, Ibuprofen, and Recurrent Major Cardiovascular and Major Bleeding Events in 19 120 Patients With Recent Ischemic Stroke
Authors: Gonzalez-Valcarcel Jaime , Sissani Leila , Labreuche Julien , Bousser Marie-Germaine , Chamorro Angel , Fisher Marc , Ford Ian , Fox Kim M. , Hennerici Michael G. , Mattle Heinrich P. , Rothwell Peter M. , Steg Philippe Gabriel , Vicaut Eric , Amarenco Pierre ,   for the PERFORM Investigators
Published: March 2016

Background and Purpose—
The presumed safety of paracetamol in high–cardiovascular risk patients has been questioned. We determined whether paracetamol or ibuprofen use is associated with major cardiovascular events (MACE) or major bleeding in 19 120 patients with recent ischemic stroke or transient ischemic attack of mainly atherothrombotic origin included in the Prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) trial.

Methods—
We performed 2 nested case–control analysis (2153 cases with MACE during trial follow-up and 4306 controls matched on Essen stroke risk score; 809 cases with major bleeding matched with 1616 controls) and a separate time-varying analysis.

Results—
12.3% were prescribed paracetamol and 2.5% ibuprofen. Median duration of treatment was 14 (interquartile range 5–145) days for paracetamol and 9 (5–30) days for ibuprofen. Paracetamol, but not ibuprofen, was associated with increased risk of MACE (odds ratio 1.21, 95% confidence interval [CI] 1.04–1.42) or a major bleeding (odds ratio 1.60, 95% CI 1.26–2.03), with no impact of daily dose and duration of paracetamol treatment. Time-varying analysis found an increased risk of MACE with both paracetamol (hazard ratio 1.22, 95% CI 1.05–1.43) and ibuprofen (hazard ratio 1.47, 95% CI 1.06–2.03) and of major bleeding with paracetamol (hazard ratio 1.95, 95% CI 1.45–2.62).

Conclusions—
There was a weak and inconsistent signal for association between paracetamol or ibuprofen and MACE or major bleeding, which may be related to either a genuine but modest effect of these drugs or to residual confounding.

Clinical Trial Registration—

http://www.isrctn.com
. Unique identifier: ISRCTN66157730.
Directional escape strategy by the striped plateau lizard (Sceloporus virgatus): turning to direct escape away from predators at variable escape angles
Authors: Cooper William E. 
Published: March 2016

A prey’s orientation to a predator’s approach path affects risk of fleeing straight ahead. By turning to flee closer to straight away from the predator before fleeing, prey can reduce risk. Laboratory studies suggest that escape angles should lead away from predators and be unpredictable. I studied orientation, turn, and escape angles and in a study of striped plateau lizards,Sceloporus virgatus. Lizards fled away from a predator, but often not straight away. Escape angles were variable and bimodally distributed: one mode was straight away for distancing prey from predator and one was near 90°, which maintains ability to monitor the predator or requires turning by the predator. Turn angles increased as orientation shifted toward the predator. Escape angle was closer to straight away when turn angle was larger, but turning did not fully compensate for degree of orientation toward the predator. Directional escape strategies of diverse prey are compared.
SUBCLASSIFICATION OF ADJECTIVES IN THE PEKING DIALECT
Authors: Mingyang Hu 
Published: March 2016

Dans le parler de Pékin, les adjectifs ne constituent pas un ensemble homogène. Ils peuvent être subdivisés selon des critères morphologiques et syntaxiques.
Les adjectifs peuvent être redoublés. Le schéma de redoublement est AA ou AAr pour les adjectifs dissyllabiques. Cependant, tous les adjectifs ne sont pas susceptibles de redoublement. Lesquels le sont et lesquels ne le sont pas ?
Certains adjectifs peuvent avoir des suffixes modaux (au sens de "modulation"). Quels suffixes de ce type y a t-il dans le dialecte de Pékin ? Quels sont les adjectifs avec lesquels ils sont compatibles ?
D'autre part, il est admis que les adjectifs peuvent être employés aussi bien en fonction attributive qu'en fonction prédicative, alors qu'en réalité tous les adjectifs n'ont pas cette double aptitude : certains ne s'emploient qu'en fonction predicative et d'autres seulement en fonction attributive.
Enfin, certains adjectifs peuvent être employés adverbialement, d'autres pas.
L'auteur, qui a examiné, selon les critères énumérés cidessus, un ensemble de quatre cents adjectifs usuels du parler de Pékin, présente les résultats complets de son enquête : liste des formes, statistiques et conclusions.
Austerity and old-age mortality in England: a longitudinal cross-local area analysis, 2007–2013
Authors: Loopstra Rachel , McKee Martin , Katikireddi Srinivasa Vittal , Taylor-Robinson David , Barr Ben , Stuckler David 
Published: March 2016

Objective There has been significant concern that austerity measures have negatively impacted health in the UK. We examined whether budgetary reductions in Pension Credit and social care have been associated with recent rises in mortality rates among pensioners aged 85 years and over. Design Cross-local authority longitudinal study. Setting Three hundred and twenty-four lower tier local authorities in England. Main outcome measure Annual percentage changes in mortality rates among pensioners aged 85 years or over. Results Between 2007 and 2013, each 1% decline in Pension Credit spending (support for low income pensioners) per beneficiary was associated with an increase in 0.68% in old-age mortality (95% CI: 0.41 to 0.95). Each reduction in the number of beneficiaries per 1000 pensioners was associated with an increase in 0.20% (95% CI: 0.15 to 0.24). Each 1% decline in social care spending was associated with a significant rise in old-age mortality (0.08%, 95% CI: 0.0006–0.12) but not after adjusting for Pension Credit spending. Similar patterns were seen in both men and women. Weaker associations observed for those aged 75 to 84 years, and none among those 65 to 74 years. Categories of service expenditure not expected to affect old-age mortality, such as transportation, showed no association. Conclusions Rising mortality rates among pensioners aged 85 years and over were linked to reductions in spending on income support for poor pensioners and social care. Findings suggest austerity measures in England have affected vulnerable old-age adults.
Impact of Sensory and Motor Defects on Oral Function in an Animal Model
Authors: Doyle Edward J. , Gratton Michael Anne , Varvares Mark A. 
Published: March 2016

ObjectiveTo evaluate the combined functional impact on swallowing of tongue sensory and motor loss using a rat model.Study DesignRats underwent selective neurectomies with transection of the motor (hypoglossal) nerve or motor and sensory (lingual) nerves. Postoperative functional parameters were followed for 2 weeks.SettingTranslational research.Subjects and MethodsThirty‐six adolescent male Wistar rats were divided into 4 groups: anesthetic (n = 6), sham surgery (n = 8), hypoglossal transection (n = 10), and hypoglossal and lingual transection (n = 12). Each morning on postoperative days 1 to 14, the water and food intake were quantified and the animal weighed. Two‐way analyses of variance (SigmaPlot; SYSTAT, San Jose, California) were performed with factors of “group” and “postoperative day” (POD) to analyze whether a significant difference existed between water intake, pellet consumption, and weight change.ResultsThe hypoglossal and lingual group consumed significantly less water during PODs 1 to 2 and significantly less food during PODs 1 to 3 than any other group. This established a significant difference in body weight between the hypoglossal and lingual group and all other groups for the duration of the study. Measured parameters in the hypoglossal group better approximated those of the control anesthetic and sham groups.ConclusionsThe addition of a sensory loss to a motor deficit involving the oral tongue results in a measurably significant difference in weight gain, a marker of function, compared with rats with only a motor deficit. Additional studies are needed to determine if there would be similar findings in a model of sensate vs asensate oral tongue reconstruction.
Use of Pericranial Flap Coverage in Cochlear Implantation of the Radical Cavity
Authors: Nieman Carrie L. , Weinreich Heather M. , Sharon Jeffrey D. , Chien Wade W. , Francis Howard W. 
Published: March 2016

Cochlear implant (CI) surgery in the setting of an open mastoid cavity is evolving. Two strategies are commonly pursued: a staged approach, clearing the disease, closing the meatus or the external auditory canal (EAC), and reevaluating in 3 to 6 months prior to implantation, or a single‐stage procedure with mastoid obliteration without EAC closure. Meatal closure is often employed in the setting of an open mastoid cavity to reduce the risk of electrode extrusion and infection. An open cavity offers the advantages of being a single‐stage procedure, permitting direct surveillance for recurrent cholesteatoma, and reducing the need for repeat computed tomography scans. We describe an approach to the coverage of a CI within a dry, open mastoid cavity using an anteriorly‐based postauricular pericranial flap.