bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted sequencing and intracranial outcomes of patients with lung adenocarcinoma brain metastases treated with radiotherapy
Authors: Press Robert H. , Zhang Chao , Cassidy Richard J. , Ferris Matthew J. , Zhong Jim , Steuer Conor E. , Pillai Rathi N. , Owonikoko Taofeek K. , Kahn Shannon , Ramalingam Suresh S. , Patel Pretesh R. , Curran Walter J. , Shu Hui‐Kuo G. , Sica Gabriel L. , Higgins Kristin A. 
Published: August 2018

BACKGROUNDTreatment for advanced lung adenocarcinoma (AC) has become increasingly personalized based on molecular results. However, for patients with AC brain metastases (BMs), intracranial outcomes based on molecular subtype and the frequency of molecular aberrations are less well defined. This study sought to report targeted next‐generation sequencing results and investigate molecularly based outcomes for patients with AC‐BMs treated with radiotherapy.METHODSThe records of 132 patients with AC‐BMs treated at Emory University from September 2008 to August 2016 with successful next‐generation sequencing were reviewed. Rates of local disease recurrence, distant brain failure (DBF), and salvage whole‐brain radiotherapy (WBRT) were estimated using cumulative incidence with competing risk analysis. Univariate and multivariate analyses were performed.RESULTSThe most common aberrations included tumor protein 53 (TP53) (60%), KRAS (29%), epidermal growth factor receptor (EGFR) (20.5%), phosphatase and tensin homolog (PTEN) loss (15.5%), and MET amplification (13%). The majority of patients (62%) were treated with stereotactic radiosurgery alone. In these patients, KRAS mutation, anaplastic lymphoma kinase (ALK) rearrangement, and having ≥ 6 BMs were associated with an increased risk of salvage WBRT (P < .05). KRAS mutation remained significant for an increased risk of salvage WBRT when compared with EGFR/ALK/KRAS‐negative patients (hazard ratio, 5.17; P < .05), despite a similar risk of DBF. PTEN loss was associated with increased risk of DBF (P < .05), whereas EGFR and ALK aberrations were associated with a decreased risk of local disease recurrence (P < .05).CONCLUSIONSThe results of the current study quantified the frequency of genetic aberrations in patients with AC‐BMs and demonstrated their association with intracranial outcomes. In particular, a cohort of patients with KRAS mutations and ≥6 BMs were identified to be at high risk of requiring salvage WBRT after undergoing upfront stereotactic radiosurgery.
Monte Carlo on Manifolds: Sampling Densities and Integrating Functions
Authors: Zappa Emilio , Holmes‐Cerfon Miranda , Goodman Jonathan 
Published: August 2018

AbstractWe describe and analyze some Monte Carlo methods for manifolds in euclidean space defined by equality and inequality constraints. First, we give an MCMC sampler for probability distributions defined by unnormalized densities on such manifolds. The sampler uses a specific orthogonal projection to the surface that requires only information about the tangent space to the manifold, obtainable from first derivatives of the constraint functions, hence avoiding the need for curvature information or second derivatives. Second, we use the sampler to develop a multistage algorithm to compute integrals over such manifolds. We provide single‐run error estimates that avoid the need for multiple independent runs. Computational experiments on various test problems show that the algorithms and error estimates work in practice. The method is applied to compute the entropies of different sticky hard sphere systems. These predict the temperature or interaction energy at which loops of hard sticky spheres become preferable to chains. © 2018 Wiley Periodicals, Inc.
Development of a methodology to combine fMRI and EMG to measure emotional responses in patients with anorexia nervosa
Authors: Hildebrandt Tom , Schulz Kurt , Fleysher Lazar , Griffen Trevor , Heywood Ashley , Sysko Robyn 
Published: August 2018

AbstractObjectiveIndividuals with eating disorders are theorized to have basic impairments in affective appraisal and social–emotional processing that contribute to pathogenesis of the disease. We aimed to determine if facial electromyography could be used to discriminate between happy and disgust emotions during simultaneous acquisition of an fMRI BOLD sequence in efforts to establish a novel tool for investigating emotion‐driven hypotheses about eating pathology. In line with standards for rigor and reproducibility, we provide detailed protocols and code to support each step of this project.MethodSixteen adolescents with low‐weight eating disorders viewed emotional faces (Happy or Disgust) and were asked to mimic their facial expression during simultaneous BOLD and EMG (Corrugator supercilli, Lavator lavii, Zygomaticus major) acquisition. Trials were repeated with the scanner off and again with scanner on (i.e., fatigue).ResultsThe Levator and Zygomaticus activation patterns discriminated disgust and happy faces successfully. The pattern held between scanner on and off conditions, but muscle activation attenuated in the Fatigue condition, especially for the Zygomaticus.DiscussionSimultaneous fMRI–EMG is a new tool capable of discriminating specific emotions based on muscle activation patterns and can be leveraged to answer emotion‐driven hypotheses about clinical populations characterized by difficulty labeling or processing emotions.
Liraglutide and weight loss among patients with advanced heart failure and a reduced ejection fraction: insights from the FIGHT trial
Authors: Sharma Abhinav , Ambrosy Andrew P. , DeVore Adam D. , Margulies Kenneth B. , McNulty Steven E. , Mentz Robert J. , Hernandez Adrian F. , Michael Felker Gary , Cooper Lauren B. , Lala Anuradha , Vader Justin , Groake John D. , Borlaug Barry A. , Velazquez Eric J. 
Published: August 2018

AbstractAimsObesity is present in up to 45% of patients with heart failure (HF). Liraglutide, a glucagon‐like peptide‐1 (GLP‐1) receptor antagonist, facilitates weight loss in obese patients. The efficacy of liraglutide as a weight loss agent among patients with HF and reduced ejection fraction (HFrEF) and a recent acute HF hospitalization remains unknown.Methods and resultsThe Functional Impact of GLP‐1 for Heart Failure Treatment study randomized 300 patients with HFrEF (ejection fraction ≤ 40%), both with and without diabetes and a recent HF hospitalization to liraglutide or placebo. The primary outcome for this post hoc analysis was the change in weight from baseline to last study visit. We conducted an ‘on‐treatment’ analysis of patients with at least one follow‐up visit on study drug (123 on liraglutide and 124 on placebo). The median age was 61 years, 21% were female, and 69% of patients had New York Heart Association functional Class III or IV symptoms. The median ejection fraction was 25% (25th, 75th percentile 19–32%). Liraglutide use was associated with a significant weight reduction [liraglutide −1.00 lbs vs. placebo 2.00 lbs; treatment difference −4.10 lbs; 95% confidence interval (CI) −7.94, −0.25; P = 0.0367; percentage treatment difference −2.07%, 95% CI −3.86, −0.28; P = 0.0237]. Similar results were seen after multivariable adjustments. Liraglutide also significantly reduced triglyceride levels (liraglutide 7.5 mg/dL vs. placebo 12.0 mg/dL; treatment difference −33.1 mg/dL; 95% CI −60.7, −5.6; P = 0.019).ConclusionsLiraglutide is an efficacious weight loss agent in patients with HFrEF. These findings will require further exploration in a well‐powered cardiovascular outcomes trial.
Grassland renovation has important consequences for C and N cycling and losses
Authors: Kayser Manfred , Müller Jürgen , Isselstein Johannes 
Published: August 2018

AbstractSward degradation is a serious threat to the functioning of agricultural grassland and the provision of ecosystem services. Renovation measures are frequently applied to restore degraded swards. The success is highly variable, and substantial trade‐offs can be related to the process of renovation. This paper starts with a general classification of renovation measures and then investigates the processes that are directly related to renovation and lead to a change in botanical composition and affect soil functions and C and N fluxes. These processes are strongly interrelated and dependent on site, climate, and management condition as well as on the timescale. The more an existing and degraded sward is deliberately disturbed prior to a renovation measure, for example, by ploughing, the stronger will be the change in sward composition, and the stronger will be the potential yield and quality advantage. However, the risk of a release of soil organic C and N emissions to the environment will also increase. These emissions will usually decrease in time, but so will the positive effects on sward composition. This demonstrates that the renovation of swards is normally the second best solution and a proper and well‐adapted grassland utilization and management should be adopted to avoid degradation in the first place.
Stability of wheat grain yields over three field seasons in the UK
Authors: Pennacchi João Paulo , Carmo‐Silva Elizabete , Andralojc P. John , Lawson Tracy , Allen Alexandra M. , Raines Christine A. , Parry Martin A. J. 
Published: August 2018

AbstractEnsuring food security in a changing climate is a major contemporary challenge and requires development of climate‐resilient crops that perform well under variable environments. The hypothesis that yield stability in suboptimal conditions is linked to yield penalties in optimal conditions was investigated in field‐grown wheat in the UK. The phenotypic responses, rate of wheat crop development, and final grain yield to varying sowing date, rainfall, air temperature, and radiation patterns were studied for a panel of 61 elite commercial wheat cultivars grown in the UK in 2012, 2013, and 2014. Contrasting climatic patterns, particularly rainfall accumulation and distribution over the season, influenced the relative performance of the cultivars affecting the duration of grain development stage and impacting on productivity. Indices for crop productivity, yield stability, and performance under suboptimal conditions revealed four cultivars with a combination of stable and high relative grain yields over the three seasons: Gladiator, Humber, Mercato, and Zebedee. Genetic similarity between cultivars partially explained yield performance in the contrasting seasons. The year of release of the cultivars correlated with grain yield but not with yield stability, supporting the contention that breeding for yield potential does not select for climate resilience and yield stability of crops. Further analysis of the outstanding cultivars may unravel target traits for breeding efforts aimed at increasing wheat yield potential and stability in the changing climate.
The evidential statistical paradigm in genetics
Authors: Strug Lisa J. 
Published: August 2018

AbstractConcerns over reproducibility in research has reinvigorated the discourse onP‐values as measures of statistical evidence. In a position statement by the American Statistical Association board of directors, they warn ofP‐value misuse and refer to the availability of alternatives. Despite the common practice of comparingP‐values across different hypothesis tests in genetics, it is well‐appreciated thatP‐values must be interpreted alongside the sample size and experimental design used for their computation. Here, we discuss the evidential statistical paradigm (EP), an alternative to Bayesian and Frequentist paradigms, that has been implemented in human genetics studies. Using applications in Cystic Fibrosis genetic association analyses, and describing recent theoretical developments, we review how to measure statistical evidence using the EP in the presence of covariates, model misspecification, and for composite hypotheses. Novel graphical displays are presented, and software for their computation is highlighted. The implications of multiple hypothesis testing for the EP are delineated in the analyses, demonstrating a view more consistent with scientific reasoning; the EP provides a theoretical justification for replication that is a requirement in genetic association studies. As genetic studies grow in size and complexity, a fresh look at measures of statistical evidence that are sensible amid the analysis of big data are required.
Singing in the brain: Neural representation of music and voice as revealed by fMRI
Authors: Whitehead Jocelyne C. , Armony Jorge L. 
Published: August 2018

AbstractThe ubiquity of music across cultures as a means of emotional expression, and its proposed evolutionary relation to speech, motivated researchers to attempt a characterization of its neural representation. Several neuroimaging studies have reported that specific regions in the anterior temporal lobe respond more strongly to music than to other auditory stimuli, including spoken voice. Nonetheless, because most studies have employed instrumental music, which has important acoustic distinctions from human voice, questions still exist as to the specificity of the observed “music‐preferred” areas. Here, we sought to address this issue by testing 24 healthy young adults with fast, high‐resolution fMRI, to record neural responses to a large and varied set of musical stimuli, which, critically, includeda capellasinging, as well as purely instrumental excerpts. Our results confirmed that music; vocal or instrumental, preferentially engaged regions in the superior STG, particularly in the anterior planum polare, bilaterally. In contrast, human voice, either spoken or sung, activated more strongly a large area along the superior temporal sulcus. Findings were consistent between univariate and multivariate analyses, as well as with the use of a “silent” sparse acquisition sequence that minimizes any potential influence of scanner noise on the resulting activations. Activity in music‐preferred regions could not be accounted for by any basic acoustic parameter tested, suggesting these areas integrate, likely in a nonlinear fashion, a combination of acoustic attributes that, together, result in the perceived musicality of the stimuli, consistent with proposed hierarchical processing of complex auditory information within the temporal lobes.
Neural representation of word categories is distinct in the temporal lobe: An activation likelihood analysis
Authors: Faroqi‐Shah Yasmeen , Sebastian Rajani , Woude Ashlyn Vander 
Published: August 2018

AbstractThe distinction between nouns and verbs is a language universal. Yet, functional neuroimaging studies comparing noun and verb processing have yielded inconsistent findings, ranging from a complete frontal(verb)–temporal(noun) dichotomy to a complete overlap in activation patterns. The current study addressed the debate about neural distinctions between nouns and verbs by conducting an activation likelihood estimation (ALE) meta‐analysis of probabilistic cytoarchitectonic maps. Two levels of analysis were conducted: simple effects (Verbs vs. Baseline, Nouns vs. Baseline), and direct comparisons (Verbs vs. Nouns, Nouns vs. Verbs). Nouns were uniquely associated with a left medial temporal cluster (BA37). Activation foci for verbs included extensive inferior frontal (BA44–47) and mid‐temporal (BA22, 21) regions in the left hemisphere. These findings confirm that the two grammatical classes have distinct neural architecture in supra‐modal brain regions. Further, nouns and verbs overlapped in a small left lateral inferior temporal activation cluster (BA37), which is a region for modality‐independent, grammatical class‐independent lexical representations. These findings are most consistent with the view that as one acquires language, linguistic representations for a lexical category shift from the modality specific cortices which represent prototypical members of that category (e.g., motion for verbs) to abstract amodal representations in close proximity to modality specific cortices.
Noninvasive, tube‐based, continuous vagal nerve monitoring using the laryngeal adductor reflex: Feasibility study of 134 nerves at risk
Authors: Sinclair Catherine F. , Téllez Maria J. , Ulkatan Sedat 
Published: August 2018

AbstractBackgroundContinuous vagal intraoperative neuromonitoring (IONM) currently requires placement of a vagal nerve electrode. Herein, we present data from 100 patients (134 nerves‐at‐risk) monitored continuously during neck endocrine surgeries using a noninvasive, new methodology that solely utilizes endotracheal tube electrodes to simultaneously stimulate laryngeal mucosa and record a laryngeal adductor reflex continuous IONM (LAR‐C‐IONM) response.MethodsThe laryngeal adductor reflex (LAR) was elicited by electrical laryngeal mucosal stimulation on the side contralateral to the operative field using endotracheal tube electrodes. All patients completed preoperative and postoperative laryngeal and voice examinations.ResultsOne hundred patients (134 nerves‐at‐risk) were included. Significantly more nerves‐at‐risk with an LAR opening to closing amplitude decrement >60% or with absolute closing amplitude <100 μV had postoperative vocal fold paralysis (P < .001). The LAR‐C‐IONM was highly sensitive to recurrent laryngeal nerve (RLN) stretch or compression.ConclusionThe LAR‐C‐IONM is a promising new way to perform continuous vagal monitoring that requires no equipment other than an electromyography (EMG) endotracheal tube and is undergoing further, large‐scale evaluation.
Epithelial‐mesenchymal transition and microRNAs: Challenges and future perspectives in oral cancer
Authors: Domingues Cátia Sofia da Costa , Serambeque Beatriz Prazeres , Laranjo Cândido Mafalda Sofia , Marto Carlos Miguel Machado , Veiga Francisco José de Baptista , Sarmento Antunes Cruz Ribeiro Ana Bela , Figueiras Ana Rita Ramalho , Botelho Maria Filomena Roque , Dourado Marília de Assunção Rodrigues Ferreira 
Published: August 2018

AbstractBackgroundHead and neck cancer is the sixth most common cancer worldwide, with oral squamous cell carcinoma (OSCC) being the most representative type. OSCC is a public health problem with high morbidity and poor survival rate. Epithelial‐mesenchymal transition is emerging as a hallmark in OSCC.MethodsIn this study, we described the role of microRNAs in epithelial‐mesenchymal transition regulation in OSCC based on a PubMed search using articles published in English between January 1, 2010, and January 31, 2018.ResultsMicroRNA's regulatory networks seem to be a hallmark of epithelial‐mesenchymal transition in OSCC pathophysiology becoming a growing challenge to design new studies and strategies from biology to clinical applications.ConclusionTherefore, we propose that targeting therapies to epithelial‐mesenchymal transition‐type cells, namely, coordinating microRNAs and/or hydrophobic drugs, such as conventional therapy, could be a promising strategy to improve the outcomes of patients with OSCC.
Hydrogen‐Bonded Siloxane Liquid Crystals for Hybrid Nanomaterials
Authors: Nickmans Koen , Jansma Sjoerd O. , Hey Daniela , Velpula Gangamallaiah , Teyssandier Joan , De Feyter Steven , Schenning Albert P. H. J. 
Published: August 2018

The self‐assembly of molecular inorganic/organic hybrid building blocks into ordered hierarchical nanomaterials with a tunable morphology is an enormous challenge. Here, we describe the synthesis and characterization of a novel liquid crystalline hydrogen‐bonding hepta(dimethylsiloxane) azobenzene carboxylic acid dimer. This inorganic/organic hybrid dimer forms sub‐5 nm lamellar features in the bulk and at the liquid solid interface. When mixed with a complementary hydrogen‐bonding disk‐shaped small molecule, a columnar hexagonal phase is formed. When adding a block copolymer containing hydrogen bond‐accepting moieties, a hierarchical nanostructured material is obtained with a hexagonal columnar arrangement perpendicular to lamellae super structure. Our supramolecular approach shows that hierarchical hybrid nanomaterials can be fabricated with controlled properties which is appealing for applications such as nanoporous materials, organic electronics, and nanolithography.
Reducing stress and burnout in the public‐sector work environment: A mindfulness meditation pilot study
Authors: Vella Elizabeth , McIver Shane 
Published: August 2018

AbstractIssue addressedIdentifying ways to manage the psychological and emotional costs of workplace stress is essential. Mindfulness meditation is reported to support mental well‐being; however, findings are limited in Australian business settings. Accordingly, this study explored the efficacy of a mindfulness meditation program tailored for an Australian public‐sector workplace.MethodsA mixed‐methods, single‐group, pre‐/post‐test design was used to evaluate a proof‐of‐concept mindfulness intervention. Quantitative measures included the Perceived Stress Scale and Maslach Burnout Inventory. Survey data were collected to analyse participant experiences. Participants (n = 65) were recruited from a government organisation. The 8‐week program ran weekly for 45 minutes and had a 65% retention rate. Resources were provided to support home practice.ResultsStatistically significant decreases were obtained for perceived stress (d = 0.8) and emotional exhaustion (d = 0.4). Themes from qualitative findings suggested participants experienced an increased recognition of stress triggers, increased ability to detach from stressors, increased calmness and increased ability to prioritise work.ConclusionsQualitative results extend comparable quantitative research by detailing how an appropriately tailored 8‐week meditation‐based program has the potential to decrease perceived stress in highly stressful work environments.So what?Triangulated data suggest that an appropriately adapted mindfulness meditation program can be an effective, efficient and low‐cost inclusion within an organisation's health promotion repertoire to help increase mental health among staff.
Regulation of antigen 85C activity by reversible S‐glutathionylation
Authors: Mandato Alysia , Chai Yuh‐Cherng 
Published: August 2018

AbstractMycobacterium tuberculosis is the causative agent of many strains of tuberculosis, as it is composed of an impenetrable, complex cell wall. The proteins active in the synthesis of the cell wall are mycolyl transferase antigens 85A, 85B, and 85C, encoded by genes fbpA, fbpB, and fbpC. Antigen 85C contains one cysteine residue. S‐Glutathionylation is the formation of a mixed disulfide between a protein cysteine residue and glutathione (GSH), an abundant antioxidant molecule. It is a post‐translational modification of cysteine residues which can occur under oxidative stress or physiological conditions. It is a known mechanism to regulate enzyme activity, signaling pathways, and the progression of diseases. By S‐glutathionylation, the lone cysteine residue in antigen 85C is modified by biotinylated GSH ethyl ester to form a mixed disulfide. This modification results in a decrease in enzyme activity by 90%, representing a decrease in ability of the protein to synthesize the bacterial cell wall. Both the modification and the enzymatic activity of the protein are concentration dependent and can be reversed upon addition of a thiol reducing agent. The results provide a potential strategy for inhibiting the synthesis of the cell wall of M. tuberculosis by promoting oxidation of the lone cysteine residue. To our knowledge, this is a novel finding to demonstrate the modification of antigen 85C and the regulation of its activity by a physiological molecule. © 2018 IUBMB Life, 70(11):1111–1114, 2018