bluuebunny/crossref_metadata_2025_split huggingface dataset:
FA03.02: IS SURGERY STILL NECESSARY IN RESECTABLE OESOPHAGEAL CANCER? META-ANALYSES OF DEFINITIVE CHEMORADIOTHERAPY VERSUS TRIMODALITY THERAPY
Authors: Voeten Daan , Den Bakker Chantal , Van Der Peet Donald 
Published: September 2018

Abstract

Background
Standard therapy for resectable oesophageal carcinoma is trimodality therapy (TMT) consisting of neoadjuvant chemoradiotherapy and oesophagectomy. Evidence of survival advantage of TMT over organ preserving definitive chemoradiotherapy (dCRT) is inconclusive. The aim of this study is to compare survival between TMT and dCRT.

Methods
A systematic review and meta-analyses were conducted. Randomised controlled trials and observational studies on primary resectable, curatively treated, oesophageal carcinoma patients above 18 years were included. Three online databases were searched for studies comparing TMT with dCRT. Primary outcomes were two-, three- and five-year overall survival rates. Risk of bias was assessed using the Cochrane risk of bias tools for RCTs and cohort studies.

Results
Thirty-two studies described in 35 articles were included in this systematic review, thirty-three were included in the meta-analyses. Two-, three- and five-year overall survival was significantly lower in dCRT compared to TMT, with relative risks (RR) of 0.69 (95%CI, 0.57–0.83), 0.76 (95%CI, 0.63–0.92), and 0.57 (95%CI, 0.47–0.71) respectively. However, when only analysing studies with equal patient groups at baseline no differences for two-, three- and five-year overall survival were found with RRs of 0.83 (95%CI, 0.62–1.10), 0.81 (95%CI 0.57–1.14), 0.63 (95%CI, 0.36–1.12). The forest plot for three-year overall survival is presented in figure 1. Figure 1. 3 year overall survival rates

Conclusion
Despite limitations of the available evidence these meta-analyses suggest there is no survival advantage for TMT over dCRT, assuming comparable groups at baseline. Selection of surgical candidates in oesophageal carcinoma should be part of personalised and tailored care.

Disclosure
All authors have declared no conflicts of interest.
FA03.06: THE COST BENEFIT OF A WATCH AND WAIT POLICY FOR COMPLETE CLINICAL RESPONDERS FOLLOWING NEO-ADJUVANT THERAPY IN ESOPHAGEAL CANCER
Authors: Abdelatif Asila , Walsh Thomas , Coomara Arielle 
Published: September 2018

Abstract

Background
Survival for esophageal cancer remains poor despite neo-adjuvant chemo-radiotherapy (nCRT) and surgical resection. The median survival for nCRT plus surgery in the CROSS trial was 48 months with a pathological complete response (pCR) rate of 29%. All pCR patients will have been clinical complete responders (cCR) and while surveillance and salvage surgery (S + SS) for cCR in rectal cancer is well investigated, it is unclear whether the outcomes are similar in esophageal cancer. As morbidity and mortality following esophagectomy is high, avoidance of surgery for predicted pCR would represent a clear advantage. Our unit offers a supported choice for cCR patients to opt for surgery or for surveillance. There is currently no literature on the cost benefit of a watch and wait policy for esophageal cancer patients with a complete clinical response.

Methods
We identified all cCR patients from a prospectively collected database of esophageal cancer patients offered curative treatment with nCRT from 1999 to 2017. We costed the S + SS group for whom accurate costing data was available and we matched these, according to time of follow up, to a control group of cCR who underwent surgery. Cost (from the National DRG cost manual) was calculated based on cost of surgery, ICU stay, admission length, and follow up radiological and endoscopic procedures. The data was analysed using a two-tailed, equal variance t-test.

Results
Of 237 patients who received nCRT, 86 had a cCR. Of these, 15 patients in the S + SS fulfilled the selection criteria with a mean follow up of 10.2 compared with 10.4 months in the control group (P = 0.925). The mean number of days in hospital was 19.2 vs. 43.2 days consecutively during the follow up period. The mean estimated cost to the HSE was €91,480 for S + SS compared with €301,280 for the controlled surgery group (P = 0.01).

Conclusion
This study identified a significant cost benefit for surveillance over surgery. Further studies are required to accurately identify those who cannot benefit from surgery and to assess quality of life years gained and cost per year of life are needed.

Disclosure
All authors have declared no conflicts of interest.
Unusual Presentation of Severe Endobronchial Obstruction Caused by Cryptococcus gattii in a Child
Authors: Huynh Julie , Saddi Vishal , Cooper Peter , Cheng Alan T , Meyer Weiland , Chen Sharon , Isaacs David 
Published: September 2018

AbstractDisease caused by Cryptococcus gattii typically manifests as meningoencephalitis or pulmonary nodules. Endobronchial lesions are rare, and most cases are caused by Cryptococcus neoformans. We describe here a case of endobronchial disease in a child caused by C gattii. The disease spectrum in this patient was notable for the discovery of anti–granulocyte macrophage colony-stimulating factor autoantibodies.
Multiple modulation synthesis with high spatial resolution for noninvasive deep neurostimulation
Authors: Xiao Qiaoqin , Lai Xiaozheng , Chen Hao 
Published: September 2018

ABSTRACTNoninvasive neurostimulation plays a pivotal role in direct control of neural circuit and modulating neuronal function. However, it is difficult to balance both spatial focality and depth of penetration in stimulating deep neurons. Here, we designed time-division, frequency & polarity modulation synthesis (TMFPMS) for stimulating deep neurons noninvasively with low-frequency envelope. We demonstrated its spatial resolution: mm-level via computational simulation including finite element analysis and Hodgkin-Huxley action potential model. Taken together, the results of this study indicate that TMFPMS neurostimulation with high spatial resolution is steerable and may replace traditional implanted electrode.
Can pharmacological enhancement of the placebo effect be a novel therapy for working memory impairments?
Authors: Zhao Weihua , Becker Benjamin , Yao Shuxia , Ma Xiaole , Kou Juan , Kendrick Keith M 
Published: September 2018

AbstractWorking memory is considered as a core aspect of cognitive function and its impairment in a wide range of mental disorders has resulted in it being considered as an important transdiagnostic feature. To date pharmacological and behavioural strategies for augmenting working memory have achieved only moderate success. Here we have taken a different approach by combining expectancy effects with intranasal oxytocin as an adjunct given previous evidence that it may enhance placebo effects. In a randomised controlled clinical trial we demonstrate that while working memory performance is not influenced by expectancy per se when it is given in conjunction with oxytocin performance in terms of accuracy can be significantly enhanced following positive expectancy induction (placebo effect) and impaired following negative expectancy induction (nocebo effect). Thus combining expectancy effects with intranasal oxytocin may represent a radical new approach for improving working memory function in mental disorders.
Oxytocin amplifies sex differences in human mate choice
Authors: Xu Lei , Becker Benjamin , Luo Ruixue , Zheng Xiaoxiao , Zhao Weihua , Zhang Qiong , Kendrick Keith M. 
Published: September 2018

AbstractInfidelity is the major cause of breakups and individuals with a history of infidelity are more likely to repeat it, but may also present a greater opportunity for short-term sexual relationships. Here in a pre-registered, double-blind study involving 160 subjects we report that while both sexes valued faithful individuals most for long-term relationships, both single men and those in a relationship were more interested in having short-term relationships with previously unfaithful individuals than women. Oxytocin administration resulted in men rating the faces of unfaithful women as more attractive but in women rating those of unfaithful men as less attractive and also finding them less memorable. Oxytocin also increased men’s interest in having short-term relationships with previously unfaithful women whereas it increased women’s interest in having long-term relationships with faithful men. Thus, oxytocin release during courtship may first act to amplify sex-dependent priorities in attraction and mate choice before subsequently promoting romantic bonds.
Evaluating the evidence for biotypes of depression: attempted replication of Drysdale et.al. 2017
Authors: Dinga Richard , Schmaal Lianne , Penninx Brenda , Tol Marie Jose van , Veltman Dick J. , Velzen Laura van , Wee Nic van der , Marquand Andre 
Published: September 2018

AbstractBackgroundPsychiatric disorders are highly heterogeneous, defined based on symptoms with little connection to potential underlying biological mechanisms. A possible approach to dissect biological heterogeneity is to look for biologically meaningful subtypes. A recent study Drysdale et al. (2017) showed promising results along this line by simultaneously using resting state fMRI and clinical data and identified four distinct subtypes of depression with different clinical profiles and abnormal resting state fMRI connectivity. These subtypes were predictive of treatment response to transcranial magnetic stimulation therapy.ObjectiveHere, we attempted to replicate the procedure followed in the Drysdale et al. study and their findings in an independent dataset of a clinically more heterogeneous sample of 187 participants with depression and anxiety. We aimed to answer the following questions: 1) Using the same procedure, can we find a statistically significant and reliable relationship between brain connectivity and clinical symptoms? 2) Is the observed relationship similar to the one found in the original study? 3) Can we identify distinct and reliable subtypes? 4) Do they have similar clinical profiles as the subtypes identified in the original study?MethodsWe followed the original procedure as closely as possible, including a canonical correlation analysis to find a low dimensional representation of clinically relevant resting state fMRI features, followed by hierarchical clustering to identify subtypes. We extended the original procedure using additional statistical tests, to test the statistical significance of the relationship between resting state fMRI and clinical data, and the existence of distinct subtypes. Furthermore, we examined the stability of the whole procedure using resampling.Results and ConclusionWe were not able to replicate the findings of the original study. Relationships between brain connectivity and clinical symptoms were not statistically significant and we also did not find clearly distinct subtypes of depression. We argue, that based on our rigorous approach and in-depth review of the original results, that the evidence for the existence of the distinct resting state connectivity based subtypes of depression is weak and should be interpreted with caution.
Telomere length, individual quality and fitness in female European starlings (Sturnus vulgaris) during breeding
Authors: Criscuolo F. , Fowler M.F. , Fuhrer V.A. , Zahn S. , Williams T.D. 
Published: September 2018

AbstractTelomeres, short guanine-rich repeats that cap linear chromosomes, are involved in cell senescence and organismal ageing. Our present understanding of telomere function oscillates between a marker of individual quality, which should be positively correlated with reproduction, to a marker of costs of reproduction (e.g. due to DNA damage). To test these ‘quality’ and ‘cost’ hypotheses, we tested the output of very simple predictions in a free-living population of European starlings Sturnus vulgaris where reproductive success of adult females was followed over 2 breeding seasons (with 2 broods per breeding). If telomere length indicate individual quality, low quality females (LQ, no fledgling) should have lower telomere lengths than high quality females (which produced fledglings in 1st and 2nd broods). Additionally, physiological determinants of adult individual quality (established in a previous study) and provisioning rate should be positively associated with adult telomere lengths. Finally, telomere length should predict future reproductive success. Adult telomere length was lower in LQ females but only during the chick-rearing period. Females producing larger clutches at fledging in the 1st brood of the 1st year also had longer telomeres. Provisioning rate was positively related to telomere length, as were plasma markers of oxidative damage, non-esterified fatty acids and triglycerides. Despite these associations, we found weak support for telomeres as indicators of individual quality. Telomere length failed in predicting future reproduction success and there was a lack of consistency in within-individual telomere length over the breeding season. In starlings, we suggest that telomere length may indicate current breeding capacities and energy status of female adults, rather than future fecundity/survival.
Transite: A computational motif-based analysis platform that identifies RNA-binding proteins modulating changes in gene expression
Authors: Krismer Konstantin , Varmeh Shohreh , Bird Molly A. , Gattinger Anna , Kong Yi Wen , Handly Erika D. , Bernwinkler Thomas , Anderson Daniel A. , Heinzel Andreas , Joughin Brian A. , Cannell Ian G. , Yaffe Michael B. 
Published: September 2018

AbstractRNA-binding proteins (RBPs) play critical roles in regulating gene expression by modulating splicing, RNA stability, and protein translation. In response to various stimuli, alterations in RBP function contribute to global changes in gene expression, but identifying which specific RBPs are responsible for the observed changes in gene expression patterns remains an unmet need. Here, we presentTransitea multi-pronged computational approach that systematically infers RBPs influencing gene expression changes through alterations in RNA stability and degradation. As a proof of principle, we applied Transite to public RNA expression data from human patients with non-small cell lung cancer whose tumors were sampled at diagnosis, or after recurrence following treatment with platinum-based chemotherapy. Transite implicated known RBP regulators of the DNA damage response and identified hnRNPC as a new modulator of chemotherapeutic resistance, which we subsequently validated experimentally. Transite serves as a generalizable framework for the identification of RBPs responsible for gene expression changes that drive cell-state transitions and adds additional value to the vast wealth of publicly-available gene expression data.
DNA copy number imbalances in primary cutaneous lymphomas (PCL)
Authors: Gug Georgiana , Huang Qingyao , Chiticariu Elena , Solovan Caius , Baudis Michael 
Published: September 2018

AbstractCutaneous lymphomas (CL) represent a clinically defined group of extranodal non-Hodgkin lymphomas harboring heterogeneous and incompletely delineated molecular aberrations. Over the past decades, molecular studies have identified several chromosomal aberrations, but the interpretation of individual genomic studies can be challenging.We conducted a meta-analysis to delineate genomic alterations for different types of PCL. Searches of PubMed and ISI Web of Knowledge for the years 1996 to 2016 identified 32 publications reporting the investigation of PCL for genome-wide copy number alterations, by means of comparative genomic hybridization techniques and whole genome and exome sequencing. For 449 samples from 22 publications, copy number variation data was accessible for sample based meta-analysis. Summary profiles for genomic imbalances, generated from case-specific data, identified complex genomic imbalances, which could discriminate between different subtypes of CL and promise a more accurate classification. The collected data presented in this study are publicly available through the “Progenetix” online repository.
Tree reconciliation combined with subsampling improves large scale inference of orthologous group hierarchies
Authors: Heller Davide , Szklarczyk Damian , Mering Christian von 
Published: September 2018

AbstractBackgroundAn orthologous group (OG) comprises a set of orthologous and paralogous genes that share a last common ancestor (LCA). OGs are defined with respect to a chosen taxonomic level, which delimits the position of the LCA in time to a specified speciation event. A hierarchy of OGs expands on this notion, connecting more general OGs, distant in time, to more recent, fine-grained OGs, thereby spanning multiple levels of the tree of life. Large scale inference of OG hierarchies with independently computed taxonomic levels can suffer from inconsistencies between successive levels, such as the position in time of a duplication event. This can be due to confounding genetic signal or algorithmic limitations. Importantly, inconsistencies limit the potential use of OGs for functional annotation and third-party applications.ResultsHere we present a new methodology to ensure hierarchical consistency of OGs across taxonomic levels. To resolve an inconsistency, we subsample the protein space of the OG members and perform gene tree-species tree reconciliation for each sampling. Differently from previous approaches, by subsampling the protein space, we avoid the notoriously diffcult task of accurately building and reconciling very large phylogenies. We implement the method into a high-throughput pipeline and apply it to the eggNOG database. We use independent protein domain definitions to validate its performance.ConclusionThe presented consistency pipeline shows that, contrary to previous limitations, tree reconciliation can be a useful instrument for the construction of OG hierarchies. The key lies in the combination of sampling smaller trees and aggregating their reconciliations for robustness. Results show comparable or greater performance to previous pipelines. The code is available on Github at: https://github.com/meringlab/og_consistency_pipeline
Accelerating the Calculation of Protein-Ligand Binding Free Energy and Residence Times using Dynamically Optimized Collective Variables
Authors: Brotzakis Z. Faidon , Limongelli Vittorio , Parrinello Michele 
Published: September 2018

AbstractElucidation of the ligand/protein binding interaction is of paramount relevance in pharmacology to increase the success rate of drug design. To this end a number of computational methods have been proposed, however all of them suffer from limitations since the ligand binding/unbinding transitions to the molecular target involve many slow degrees of freedom that hamper a full characterization of the binding process. Being able to express this transition in simple and general slow degrees of freedom, would give a distinctive advantage, since it would require minimal knowledge of the system under study, while in turn it would elucidate its physics and accelerate the convergence speed of enhanced sampling methods relying on collective variables. In this study we pursuit this goal by combining for the first time Variation Approach to Conformational dynamics with Funnel-Metadynamics. In so doing, we predict for the benzamidine/trypsin system the ligand binding mode, and we accurately compute the absolute protein-ligand binding free energy and unbinding rate at unprecedented low computational cost. Finally, our simulation protocol reveals the energetics and structural details of the ligand binding mechanism and shows that water and binding pocket solvation/desolvation are the dominant slow degrees of freedom.
Deuteros: software for rapid analysis and visualization of data from differential hydrogen deuterium exchange-mass spectrometry
Authors: Lau Andy M. C. , Ahdash Zainab , Martens Chloe , Politis Argyris 
Published: September 2018

AbstractSummaryHydrogen deuterium exchange-mass spectrometry (HDX-MS) has emerged as a powerful technique for interrogating the conformational dynamics of proteins and their complexes. Currently, analysis of HDX-MS data remains a laborious procedure, mainly due to the lack of streamlined software to process the large datasets. We present Deuteros which is a standalone software designed to be coupled with Waters DynamX HDX data analysis software, allowing the rapid analysis and visualization of data from differential HDX-MS.AvailabilityDeuteros is open-source and can be downloaded from https://github.com/andymlau/Deuteros, under the Apache 2.0 license.Implementationwritten in MATLAB and supported on both Windows and MacOS. Requires the MATLAB runtime library.Contactargyris.politis@kcl.ac.uk
Genomic prediction of cognitive traits in childhood and adolescence
Authors: Allegrini A.G. , Selzam S. , Rimfeld K. , von Stumm S. , Pingault J.B. , Plomin R. 
Published: September 2018

AbstractRecent advances in genomics are producing powerful DNA predictors of complex traits, especially cognitive abilities. Here, we leveraged summary statistics from the most recent genome-wide association studies of intelligence and educational attainment to build prediction models of general cognitive ability and educational achievement. To this end, we compared the performances of multi-trait genomic and polygenic scoring methods. In a representative UK sample of 7,026 children at age 12 and 16, we show that we can now predict up to 11 percent of the variance in intelligence and 16 percent in educational achievement. We also show that predictive power increases from age 12 to age 16 and that genomic predictions do not differ for girls and boys. Multivariate genomic methods were effective in boosting predictive power and, even though prediction accuracy varied across polygenic scores approaches, results were similar using different multivariate and polygenic score methods. Polygenic scores for educational attainment and intelligence are the most powerful predictors in the behavioural sciences and exceed predictions that can be made from parental phenotypes such as educational attainment and occupational status.
The Resistome: updating a standardized resource for analyzing resistance phenotypes
Authors: Winkler J.D. 
Published: September 2018

AbstractAdvances in genome engineering have enabled routine engineering and interrogation of microbial resistance on a scale previously impossible, but developing an integrated understanding of resistance from these data remains challenging. As part of our continued efforts to address this challenge, we present a significant update of our previously released Resistome database of standardized genotype-resistance phenotype relationships, along with a new web interface to enable facile searches of genomic, transcriptomic, and phenotypic data within the database. Revisiting our previous analysis of resistance, we again find distinct mutational biases associated with random selection versus genome-scale libraries, along with pervasive pleiotropy among resistant mutants. Attempts to predict mutant phenotypes using machine learning identified the lack of comprehensive phenotype screening and small size of the Resistome corpus as challenges for effective model training. Overall, the Resistome represents a unique platform for understanding the interconnections between both current and future resistant mutants, and is available for use at https://resistome-web-interface.herokuapp.com.