bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for the trismus trial—therabite versus wooden spatula in the amelioration of trismus in patients with head and neck cancer: randomised pilot study
Authors: Lee Rana , Molassiotis Alex , Rogers Simon N , Edwards Rhiannon Tudor , Ryder David , Slevin Nick 
Published: December 2018

IntroductionPatients can develop trismus from their head and neck cancer or as a result of treatment. Trismus affects the jaw muscles and makes mouth opening difficult. To potentially combat trismus, patients could undertake proactive jaw stretching exercises prior to, during and after radiotherapy, although currently these are not the standard of care.Methods and analysisThis is a randomised, open-label, controlled, two-centre feasibility study, to assess the objective and subjective effectiveness and cost-effectiveness of therabite use compared with wooden spatula in ameliorating trismus in patients treated for stage 3 and 4 oral and oropharyngeal cancer, managed either by primary surgery followed by (chemo)radiotherapy or primary (chemo)radiotherapy. The principal objective assessment is measurement of maximum jaw opening. Assessments in all cases will be performed preradiotherapy and again at 3 and 6 months postintervention.Secondary aims of the study will be (1) to assess whether therabite or the wooden spatula intervention improves patients’ quality of life, (2) reduce the level of post-treatment clinical management/healthcare use and (3) a nested qualitative study will explore the experience of the patient taking part in the intervention; data will be transcribed verbatim and analysis will be based on content analysis methods using the interview questions as the framework for examination.Ethics and disseminationNorth West Greater Manchester granted ethical approval (REC Reference 11/NW/0744). Good Clinical Practice and the Declaration of Helsinki have been adhered to. The results will be presented internationally and submitted to a peer-reviewed journal. Head and neck cancer charities and information websites will also be approached.Trial registration numberNCT01733797.
The most mentioned neurointervention articles in online media: a bibliometric analysis of the top 101 articles with the highest altmetric attention scores
Authors: Kim Hye Jeong , Yoon Dae Young , Kim Eun Soo , Yun Eun Joo , Jeon Hong Jun , Lee Jong Young , Cho Byung-Moon 
Published: December 2018

Background and purposeAlternative metrics (altmetrics), based on mentions in online media, is a new tool that can help to identify the most influential articles to diverse public audiences. This article aimed to determine the 100 most mentioned articles in the field of neurointervention and to analyze their characteristics.Materials and methodsWe selected the 808 journals that were considered journals potentially publishing articles on neurointervention. We also selected articles using keywords. Using the Altmetric.com search tool, we identified the 101 most mentioned neurointervention articles based on the highest altmetric attention scores (AASs) within selected journals and articles. Each article was evaluated for several characteristics including AAS, number of citations, journal title, journal category, impact factor of the journal, year of publication, authorship, country, type of document, and topic.ResultsThe AASs for the top 101 articles ranged from 1586 to 39.Strokepublished the largest number of articles (19.8%) followed by theNew England Journal of Medicine(17.8%). The majority of articles were published in multidisciplinary journals (38.6%), were published in 2017–2018 (43.6%), originated from the USA (54.5%), were original articles (66.3%), and dealt with intra-arterial thrombolysis or thrombectomy for acute ischemic stroke (58.4%). Tudor G Jovin was the most prolific author, authoring 18 of the most mentioned neurointervention articlesConclusionsThis study presents a detailed list of the 101 most mentioned neurointervention articles in online media, thus providing useful information on the dissemination of neurointervention research to the general public.
A closer study of the framed standard model yielding testable new physics plus a hidden sector with dark matter candidates
Authors: Bordes José , Chan Hong-Mo , Tsou Sheung Tsun 
Published: December 2018

This closer study of the FSM (I) retains the earlier results of Ref. 1 in offering explanation for the existence of three fermion generations, as well as the hierarchical mass and mixing patterns of leptons and quarks; (II) predicts a vector boson [Formula: see text] with mass of order TeV which mixes with [Formula: see text] and [Formula: see text] of the standard model. The subsequent deviations from the standard mixing scheme are calculable in terms of the [Formula: see text] mass. While these deviations for (i) [Formula: see text], (ii) [Formula: see text], and (iii) [Formula: see text] are all within present experimental errors so long as [Formula: see text] TeV, they should soon be detectable if the [Formula: see text] mass is not too much bigger; (III) suggests that in parallel to the standard sector familiar to us, there is another where the roles of flavour and colour are interchanged. Though quite as copiously populated and as vibrant in self-interactions as our own, it communicates but little with the standard sector except via mixing through a couple of known portals, one of which is the [Formula: see text] complex noted in (II), and the other is a scalar complex which includes the standard model Higgs. As a result, the new sector appears hidden to us as we appear hidden to them, and so its lowest members with masses of order 10 MeV, being electrically neutral and seemingly stable, but abundant, may make eligible candidates as constituents of dark matter. A more detailed summary of these results together with some remarks on the model’s special theoretical features can be found in the last section of this paper.
First-principles calculations of optoelectronic properties of CaO: Eu+2 (SrO: Eu+2) for energy applications
Authors: Azam Sikander , Abbas Zeesham , Gul Banat , Khan M. Shoaib , Irfan Muhammad , Sohail M. , Khan Saleem Ayaz , Naseer Faiza , Irfan Ali , Khan Gulzar , Rai D. P. , Khenata R. 
Published: December 2018

We have performed the first-principles density functional theory (DFT) and DFT[Formula: see text]U calculations on the electronic and optical properties of CaO: Eu[Formula: see text] (SrO: Eu[Formula: see text]) phosphors compounds. Herein, we have focused on the polarization of the electronic structures, i.e., the energy bandgap and the density of states. All electrons were treated within the most common exchange and correlation functional called generalized gradient approximation plus optimized effective Hubbard parameter U as GGA[Formula: see text]U. GGA[Formula: see text]U is a very effective tool for describing the electronic band energy upto considerable accuracy. Hence, we have opted for the arbitrary values of U as 3.0, 4.0, 5.0 and 7.0 eV to treat the strongly correlated electrons for obtaining the matching result with the experimental one. However, GGA[Formula: see text]U is highly expensive in terms of computation due to interaction of d or f electrons. The result shows that the appearance of Eu-4f states at the valance band maximum of the spin-up causes a substantial impact on the electronic properties of the studied compounds. The value of energy bandgap is smaller in case of spin up as compared to spin down case. In case of majority spin, the energy gap of 2.224 (2.14) eV belongs to the Eu-4f orbitals and governs the CBM. The partial densities of states (PDOS) structure displays a strong hybridization that may be pointed to the formation of covalent bonds. The calculated and the measured values are in good agreement with each other. In the study of optical properties of the compound, the optical spectral structure shows a lossless region and uniaxial anisotropy. The value of uniaxial anisotropy is positive at static limit and its value is negative above this value.
Self-sensing characteristics of vibration isolation bearing based on modified magneto-rheological elastomer
Authors: Li Rui , Zhou Mengjiao , Wang Minglian , Liu Lin , Yang Ping’an 
Published: December 2018

A new self-sensing bearing based on magneto-rheological elastomers (MREs) was proposed in this paper. For the application in vibration isolation system, the effects of force input and semi-active controlled electric current (force and magnetic fields) on the self-sensing characteristics of bearing were simultaneously investigated. The modified anisotropic MRE with multi-walled carbon nanotubes (MWNTs) was studied to improve its electrical properties, and the MWNTs can reduce the initial resistivity from 325.06 to [Formula: see text]. To understand the sensing behaviors of bearing, the experimental system was built. The results confirmed that the self-sensing characteristic presents an obvious monotonous declining trend with the vibration force increases, and the mechanical properties of MRB can be regulated in real-time when they are subjected to varying currents (0–1 A). This finding is significant because it suggests that the bearings based on the modified MREs are potentially capable of being used for vibration absorbers and sensors simultaneously. Based on these results, it is expected to simplify the system structure and improve the response performance of vibration isolation.
Natural and anthropogenic influences on the Nhecolândia wetlands, SE Pantanal, Brazil
Authors: de Oliveira Emiliano Castro , Pla-Pueyo Sila , Hackney Christopher R. 
Published: December 2018

Abstract
The Nhecolândia region covers the southern wetlands of the Pantanal basin in Brazil. Characterized by myriad shallow freshwater and alkaline–saline lakes, the distinct natural features of the Nhecolândia wetland make it highly sensitive to climate change and the effects of human activities. This paper summarizes the natural and social aspects that have affected this delicate wetland and potential future impacts. We analysed the response of the wetland to historical changes in climate and human activity and used this understanding to forecast the response of the wetland to future changes. The data presented here show that this region is particularly sensitive to alterations in the flood regime, droughts and deforestation, which are intrinsically related to both global and local changes in climate and the intensification of cattle-ranching activities, which include deforestation and the introduction of cultivated pastures.
TET2-Dependent Hydroxymethylome Plasticity Reduces Melanoma Initiation and Progression
Authors: Bonvin Elise , Radaelli Enrico , Bizet Martin , Luciani Flavie , Calonne Emilie , Putmans Pascale , Nittner David , Singh Nitesh Kumar , Santagostino Sara Francesca , Petit Valérie , Larue Lionel , Marine Jean Christophe , Fuks François 
Published: December 2018

Abstract

Although numerous epigenetic aberrancies accumulate in melanoma, their contribution to initiation and progression remain unclear. The epigenetic mark 5-hydroxymethylcytosine (5hmC), generated through TET-mediated DNA modification, is now referred to as the sixth base of DNA and has recently been reported as a potential biomarker for multiple types of cancer. Loss of 5hmC is an epigenetic hallmark of melanoma, but whether a decrease in 5hmc levels contributes directly to pathogenesis or whether it merely results from disease progression–associated epigenetic remodeling remains to be established. Here, we show that NRAS-driven melanomagenesis in mice is accompanied by an overall decrease in 5hmC and specific 5hmC gains in selected gene bodies. Strikingly, genetic ablation of Tet2 in mice cooperated with oncogenic NRASQ61K to promote melanoma initiation while suppressing specific gains in 5hmC. We conclude that TET2 acts as a barrier to melanoma initiation and progression, partly by promoting 5hmC gains in specific gene bodies.

Significance:
This work emphasizes the importance of epigenome plasticity in cancer development and highlights the involvement of druggable epigenetic factors in cancer.
The COX2 Effector Microsomal PGE2 Synthase 1 is a Regulator of Immunosuppression in Cutaneous Melanoma
Authors: Kim Sun-Hee , Roszik Jason , Cho Sung-Nam , Ogata Dai , Milton Denái R. , Peng Weiyi , Menter David G. , Ekmekcioglu Suhendan , Grimm Elizabeth A. 
Published: December 2018

AbstractPurpose:Microsomal prostaglandin E2 synthase 1 (mPGES1) was evaluated as an important downstream effector of the COX2 pathway responsible for tumor-mediated immunosuppression in melanoma.Experimental Design:The analysis of a stage III melanoma tissue microarray (n = 91) was performed to assess the association between mPGES1, COX2, CD8, and patient survival. Pharmacologic inhibitors and syngeneic mouse models using PTGES-knockout (KO) mouse melanoma cell lines were used to evaluate the mPGES1-mediated immunosuppressive function.Results:We observed correlations in expression and colocalization of COX2 and mPGES1, which are associated with increased expression of immunosuppressive markers in human melanoma. In a syngeneic melanoma mouse model, PTGES KO increased melanoma expression of PD-L1, increased infiltration of CD8a+ T cells, and CD8a+ dendritic cells into tumors and suppressed tumor growth. Durable tumor regression was observed in mice bearing PTGES KO tumors that were given anti–PD-1 therapy. Analysis of a stage III melanoma tissue microarray revealed significant associations between high mPGES1 expression and low CD8+ infiltration, which correlated with a shorter patient survival.Conclusions:Our results are the first to illustrate a potential role for mPGES1 inhibition in melanoma immune evasion and selective targeting in supporting the durability of response to PD-1 checkpoint immunotherapy. More research effort in this drug development space is needed to validate the use of mPGES1 inhibitors as safe treatment options.
Tumor Microenvironment Remodeling by Intratumoral Oncolytic Vaccinia Virus Enhances the Efficacy of Immune-Checkpoint Blockade
Authors: Chon Hong Jae , Lee Won Suk , Yang Hannah , Kong So Jung , Lee Na Keum , Moon Eun Sang , Choi Jiwon , Han Eun Chun , Kim Joo Hoon , Ahn Joong Bae , Kim Joo Hang , Kim Chan 
Published: December 2018

Abstract

Purpose:
Cancer immunotherapy is a potent treatment modality, but its clinical benefit depends on the tumor's immune profile. Here, we used mJX-594 (JX), a targeted and GM-CSF–armed oncolytic vaccinia virus, as a strategy to remodel the tumor microenvironment (TME) and subsequently increase sensitivity to αPD-1 and/or αCTLA-4 immunotherapy.

Experimental Design:
The remodeling of the TME was determined using histologic, flow-cytometric, and NanoString immune profiling analyses. JX was intratumorally injected into implanted Renca kidney tumors or MMTV-PyMT transgenic mouse breast cancers with or without αPD-1 and/or αCTLA-4. Various combination regimens were used to evaluate immunotherapeutic anticancer responses.

Results:
Intratumoral injection of JX remodeled the TME through dynamic changes in the immune system, as shown by increased tumor-infiltrating T cells and upregulation of immune-related gene signatures. This remodeling induced conversion of a noninflamed tumor into an inflamed tumor. JX virotherapy led to enhanced abscopal effects in distant tumors, with increased intratumoral infiltration of CD8+ T cells. A depletion study revealed that GM-CSF is an indispensable regulator of anticancer efficacy of JX. Dual-combination therapy with intratumoral JX and systemic αPD-1 or αCTLA-4 further enhanced the anticancer immune response, regardless of various treatment schedules. Of note, triple combination immunotherapy with JX, αPD-1, and αCTLA-4 elicited the most potent anticancer immunity and induced complete tumor regression and long-term overall survival.

Conclusions:
Our results show that intratumoral JX treatment induces dramatic remodeling of the TME and more potently suppresses cancer progression with immune-checkpoint blockades by overcoming resistance to immunotherapy.
Identification and Characterization of Synthetic Viability with ERCC1 Deficiency in Response to Interstrand Crosslinks in Lung Cancer
Authors: Heyza Joshua R. , Lei Wen , Watza Donovan , Zhang Hao , Chen Wei , Back Jessica B. , Schwartz Ann G. , Bepler Gerold , Patrick Steve M. 
Published: December 2018

Abstract

Purpose:
ERCC1/XPF is a DNA endonuclease with variable expression in primary tumor specimens, and has been investigated as a predictive biomarker for efficacy of platinum-based chemotherapy. The failure of clinical trials utilizing ERCC1 expression to predict response to platinum-based chemotherapy suggests additional mechanisms underlying the basic biology of ERCC1 in the response to interstrand crosslinks (ICLs) remain unknown. We aimed to characterize a panel of ERCC1 knockout (Δ) cell lines, where we identified a synthetic viable phenotype in response to ICLs with ERCC1 deficiency.

Experimental Design:
We utilized the CRISPR-Cas9 system to create a panel of ERCC1Δ lung cancer cell lines which we characterized.

Results:
We observe that loss of ERCC1 hypersensitizes cells to cisplatin when wild-type (WT) p53 is retained, whereas there is only modest sensitivity in cell lines that are p53mutant/null. In addition, when p53 is disrupted by CRISPR-Cas9 (p53*) in ERCC1Δ/p53WT cells, there is reduced apoptosis and increased viability after platinum treatment. These results were recapitulated in 2 patient data sets utilizing p53 mutation analysis and ERCC1 expression to assess overall survival. We also show that kinetics of ICL-repair (ICL-R) differ between ERCC1Δ/p53WT and ERCC1Δ/p53* cells. Finally, we provide evidence that cisplatin tolerance in the context of ERCC1 deficiency relies on DNA-PKcs and BRCA1 function.

Conclusions:
Our findings implicate p53 as a potential confounding variable in clinical assessments of ERCC1 as a platinum biomarker via promoting an environment in which error-prone mechanisms of ICL-R may be able to partially compensate for loss of ERCC1.
See related commentary by Friboulet et al., p. 2369
Hyperglycemia, Classified with Multiple Biomarkers Simultaneously in Men without Diabetes, and Risk of Fatal Prostate Cancer
Authors: Marrone Michael T. , Selvin Elizabeth , Barber John R. , Platz Elizabeth A. , Joshu Corinne E. 
Published: December 2018

Abstract
The association between hyperglycemia and prostate cancer risk is inconsistent, and its association with prostate cancer mortality is understudied. Thus, we investigated the association between hyperglycemia and prostate cancer risk and mortality using multiple biomarkers simultaneously to classify hyper- and normoglycemia. We conducted a prospective analysis of 5,162 cancer-free men attending visit 2 (1990–1992) of the Atherosclerosis Risk in Communities (ARIC) study followed for total (N = 671) and lethal (N = 69) prostate cancer incidence and prostate cancer mortality (N = 64) through 2012. Men without diagnosed diabetes were classified as normo- or hyperglycemic using joint categories of fasting glucose, glycated hemoglobin, and glycated albumin (or fructosamine) defined by clinical or research cutpoints. We evaluated the multivariable-adjusted association of hyperglycemia with prostate cancer incidence and mortality using Cox proportional hazards regression; men with diagnosed diabetes were included as a separate exposure category. Among 4,753 men without diagnosed diabetes, 61.5% were classified as having hyperglycemia (high on ≥1 biomarker). HbA1c and glycated albumin together classified 61.9% of 1,736 men with normal fasting glucose as normoglycemic. Compared with men who were normal on all three biomarkers, men who were high on ≥1 biomarker had an increased risk of lethal [HR, 2.50; 95% confidence interval (CI), 1.12–5.58] and fatal (HR, 3.20; 95% CI, 1.26–8.48) disease, but not total prostate cancer incidence (HR, 0.98; 95% CI, 0.81–1.20); associations were similar including fructosamine instead of glycated albumin. Our findings indicate hyperglycemia is associated with an increased risk of lethal and fatal prostate cancer, but not total prostate cancer incidence.
Case-only Methods Identified Genetic Loci Predicting a Subgroup of Men with Reduced Risk of High-grade Prostate Cancer by Finasteride
Authors: Dai James Y. , LeBlanc Michael , Goodman Phyllis J. , Lucia M. Scott , Thompson Ian M. , Tangen Catherine M. 
Published: December 2018

Abstract
In the Prostate Cancer Prevention Trial (PCPT), genotypes that may modify the effect of finasteride on the risk of prostate cancer have not been identified. Germline genetic data from 1,157 prostate cancer cases in PCPT were analyzed by case-only methods. Genotypes included 357 SNPs from 83 candidate genes in androgen metabolism, inflammation, circadian rhythm, and other pathways. Univariate case-only analysis was conducted to evaluate whether individual SNPs modified the finasteride effect on the risk of high-grade and low-grade prostate cancer. Case-only classification trees and random forests, which are powerful machine learning methods with resampling-based controls for model complexity, were employed to identify a predictive signature for genotype-specific treatment effects. Accounting for multiple testing, a single SNP in SRD5A1 gene (rs472402) significantly modified the finasteride effect on high-grade prostate cancer (Gleason score &gt; 6) in PCPT (family-wise error rate &lt; 0.05). Men carrying GG genotype at this locus had a 55% reduction of the risk in developing high-grade cancer when assigned to finasteride (RR = 0.45; 95% confidence interval, 0.27–0.75). Additional effect-modifying SNPs with moderate statistical significance were identified by case-only trees and random forests. A prediction model built by the case-only random forest method with 28 selected SNPs classified 37% of PCPT men to have reduced risk of high-grade prostate cancer when taking finasteride, while the others have increased risk. In conclusion, case-only methods identified SNPs that modified the effect of finasteride on the risk of high-grade prostate cancer and predicted a subgroup of men who had reduced cancer risk by finasteride.
Two new species of Novantinoe (Disteniini, Disteniidae), two new species of Eurysthea (Elaphidiini, Cerambycinae, Cerambycidae), and new geographical records
Authors: Botero Juan Pablo , Heffern Daniel , Santos-Silva Antonio 
Published: December 2018

Two new species of Novantinoe from Mexico, N. oaxaquena and N. fabiolae; and two new species of Eurysthea, E. nogueirai, from Mexico, and E. nakagomei from Colombia are described. Furthermore, geographical distributions of three species are expanded.