bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fat Grafting in Hollow Upper Eyelids and Volumetric Upper Blepharoplasty
Authors: Ramil Mariano E. 
Published: July 2017

Background:
Periorbital volume loss creates a shadow frame, and traditional excisional blepharoplasties may aggravate the situation. Divergence in filling treatments establishes a demand for simple and reproducible techniques to achieve consistent results. Here, the author’s hollow upper eyelid evaluation and treatment approach are presented.

Methods:
A retrospective photographic analysis was conducted of 32 women who underwent fat grafting for hollow upper eyelids between 2012 and 2016. Preoperative and postoperative evaluations of upper eyelid ratios at the medial and lateral corneal limbus, together with lateral contour modifications, were used to determine the efficacy of the technique to restore youthful proportions and contours.

Results:
Preoperative analysis showed 20 eyelids with an inner shadow, or A-pattern; and 44 eyelids with the complete extension of the hollow, or C-pattern. Three patients presented mild blepharoptosis, and eight patients had undergone a previous upper blepharoplasty. Mean grafting volume was 0.4 cc in the deep plane and 2.8 cc in the superficial plane. Fat grafting exclusively was performed in six patients, improving all ratios and correcting the A-pattern deformity. Volumetric upper blepharoplasty combining fat grafting in two levels and orbicularis oculi muscle imbrication was performed in 26 patients, correcting every inverted ratio (p < 0.001). On the lateral view, all cases with a concave pattern changed to a convex one, regardless of the approach used.

Conclusion:
Synergy between fat grafting and orbicularis imbrication proved adequate to restore the lateral convex contour and return youthful proportions to the hollow upper eyelids.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours
Authors: Izquierdo Elisa , Yuan Lina , George Sally , Hubank Michael , Jones Chris , Proszek Paula , Shipley Janet , Gatz Susanne A , Stinson Caedyn , Moore Andrew S. , Clifford Steven C. , Hicks Debbie , Lindsey Janet , Hill Rebecca , Jacques Thomas S. , Chalker Jane , Thway Khin , O’Connor Simon , Marshall Lynley , Moreno Lucas , Pearson Andrew , Chesler Louis , Walker Brian A. , De Castro David Gonzalez 
Published: July 2017

AbstractThe implementation of personalised medicine in childhood cancers has been limited by a lack of clinically validated multi-target sequencing approaches specific for paediatric solid tumours. In order to support innovative clinical trials in high-risk patients with unmet need, we have developed a clinically relevant targeted sequencing panel spanning 311 kb and comprising 78 genes involved in childhood cancers. A total of 132 samples were used for the validation of the panel, including Horizon Discovery cell blends (n=4), cell lines (n=15), formalin-fixed paraffin embedded (FFPE, n=83) and fresh frozen tissue (FF, n=30) patient samples. Cell blends containing known single nucleotide variants (SNVs, n=528) and small insertion-deletions (indels n=108) were used to define panel sensitivities of ≥98% for SNVs and ≥83% for indels [95% CI] and panel specificity of ≥98% [95% CI] for SNVs. FFPE samples performed comparably to FF samples (n=15 paired). Of 95 well-characterised genetic abnormalities in 33 clinical specimens and 13 cell lines (including SNVs, indels, amplifications, rearrangements and chromosome losses), 94 (98.9%) were detected by our approach. We have validated a robust and practical methodology to guide clinical management of children with solid tumours based on their molecular profiles. Our work demonstrates the value of targeted gene sequencing in the development of precision medicine strategies in paediatric oncology.
Is coding a relevant metaphor for the brain?
Authors: Brette Romain 
Published: July 2017

Short abstractI argue that the popular neural coding metaphor is often misleading. First, the “neural code” often spans both the experimental apparatus and the brain. Second, a neural code is information only by reference to something with a known meaning, which is not the kind of information relevant for a perceptual system. Third, the causal structure of neural codes (linear, atemporal) is incongruent with the causal structure of the brain (circular, dynamic). I conclude that a causal description of the brain cannot be based on neural codes, because spikes are more like actions than hieroglyphs.Long abstract“Neural coding” is a popular metaphor in neuroscience, where objective properties of the world are communicated to the brain in the form of spikes. Here I argue that this metaphor is often inappropriate and misleading. First, when neurons are said to encode experimental parameters, the neural code depends on experimental details that are not carried by the coding variable. Thus, the representational power of neural codes is much more limited than generally implied. Second, neural codes carry information only by reference to things with known meaning. In contrast, perceptual systems must build information from relations between sensory signals and actions, forming a structured internal model. Neural codes are inadequate for this purpose because they are unstructured. Third, coding variables are observables tied to the temporality of experiments, while spikes are timed actions that mediate coupling in a distributed dynamical system. The coding metaphor tries to fit the dynamic, circular and distributed causal structure of the brain into a linear chain of transformations between observables, but the two causal structures are incongruent. I conclude that the neural coding metaphor cannot provide a basis for theories of brain function, because it is incompatible with both the causal structure of the brain and the informational requirements of cognition.
Conjunction of Factors Triggering Waves of Seasonal Influenza
Authors: Chattopadhyay Ishanu , Kıcıman Emre , Elliott Joshua W. , Shaman Jeffrey L. , Rzhetsky Andrey 
Published: July 2017

AbstractUnderstanding the subtle confluence of factors triggering pan-continental, seasonal epidemics of influenza-like illness is an extremely important problem, with the potential to save tens of thousands of lives and billions of dollars every year in the US alone. Beginning with several large, longitudinal datasets on putative factors and clinical data on the disease and health status of over 150 million human subjects observed over a decade, we investigated the source and the mechanistic triggers of epidemics. Our analysis included insurance claims for a significant cross-section of the US population in the past decade, human movement patterns inferred from billions of tweets, whole-US weekly weather data covering the same time span as the medical records, data on vaccination coverage over the same period, and sequence variations of key viral proteins. We also explicitly accounted for the spatio-temporal auto-correlations of infectious waves, and a host of socioeconomic and demographic factors. We carried out multiple orthogonal statistical analyses on these diverse, large geo-temporal datasets to bolster and corroborate our findings. We conclude that the initiation of a pan-continental influenza wave emerges from the simultaneous realization of a complex set of conditions, the strongest predictor groups are as follows, ranked by importance: (1) the host population’s socio- and ethno-demographic properties; (2) weather variables pertaining to relevant area specific humidity, temperature, and solar radiation; (3) the virus’ antigenic drift over time; (4) the host population’s land-based travel habits, and; (5) the spatio-temporal dynamics’ immediate history, as reflected in the influenza wave autocorrelation. The models we infer are demonstrably predictive (area under the Receiver Operating Characteristic curve ≈ 80%) when tested with out-of-sample data, opening the door to the potential formulation of new population-level intervention and mitigation policies.
DiGeST: Distributed Computing for Scalable Gene and Variant Ranking with Hadoop/Spark
Authors: Borgne Yann-Aël Le , Helaers Raphaël , Lenaerts Tom , Abramowicz Marc , Smits Guillaume , Bontempi Gianluca 
Published: July 2017

AbstractBackgroundThe advent of next-generation sequencing technologies has opened new avenues for clinical genomics research. In particular, as sequencing costs continue to decrease, an ever-growing number of clinical genomics institutes now rely on DNA sequencing studies at varying scales - genome, exome, mendeliome - for uncovering disease-associated variants or genes, in both rare and non-rare diseases.A common methodology for identifying such variants or genes is to rely on genetic association studies (GAS), that test whether allele or genotype frequencies differ between two groups of individuals, usually diseased subjects and healthy controls. Current bioinformatics tools for performing GAS are designed to run on standalone machines, and do not scale well with the increasing size of study designs and the search for multi-locus genetic associations. More efficient distributed and scalable data analysis solutions are needed to address this challenge.ResultsWe developed a Big Data solution stack for distributing computations in genetic association studies, that address both single and multi-locus associations. The proposed stack, called DiGeST (Distributed Gene/variant Scoring Tool) is divided in two main components: a Hadoop/Spark high-performance computing back-end for efficient data storage and distributed computing, and a Web front-end providing users with a rich set of options to filter, compare and explore exome data from different sample populations. Using exome data from the 1000 Genomes Project, we show that our distributed implementation smoothly scales with computing resources. We make the resulting software stack Open-Source, and provide virtualisation scripts to run the complete environment both on standalone machine or Hadoop-based cluster.ConclusionsHadoop/Spark provides a powerful and well-suited distributed computing framework for genetic association studies. Our work illustrates the flexibility, ease of use and scalability of the framework, and more generally advocates for its wider adoption in bioinformatics pipelines.
A new full-length virus genome sequencing method reveals that antiviral RNAi changes geminivirus populations in field-grown cassava
Authors: Mehta Devang , Hirsch-Hoffmann Matthias , Were Mariam , Patrignani Andrea , Were Hassan , Gruissem Wilhelm , Vanderschuren Hervé 
Published: July 2017

ABSTRACTDeep-sequencing of virus isolates using short-read sequencing technologies is problematic since viruses are often present in complexes sharing a high-degree of sequence identity. The full-length genomes of such highly-similar viruses cannot be assembled accurately from short sequencing reads. We present a new method, CIDER-Seq (Circular DNA Enrichment Sequencing) which successfully generates accurate full-length virus genomes from individual sequencing reads with no sequence assembly required. CIDER-Seq operates by combining a PCR-free, circular DNA enrichment protocol with Single Molecule Real Time sequencing and a new sequence deconcatenation algorithm. We apply our technique to produce more than 1,200 full-length, highly accurate geminivirus genomes from RNAi-transgenic and control plants in a field trial in Kenya. Using CIDER-Seq we can demonstrate for the first time that the expression of antiviral doublestranded RNA (dsRNA) in transgenic plants causes a consistent shift in virus populations towards species sharing low homology to the transgene derived dsRNA. Our results show that CIDER-seq is a powerful, cost-effective tool for accurately sequencing circular DNA viruses, with future applications in deep-sequencing other forms of circular DNA such as transposons and plasmids.
Using epidemiological principles to explain fungicide resistance management strategies: why do mixtures outperform alternations?
Authors: Elderfield James A.D. , Lopez-Ruiz Francisco J. , van den Bosch Frank , Cunniffe Nik J. 
Published: July 2017

ABSTRACTWhether fungicide resistance management is optimised by spraying chemicals with different modes of action as a mixture (i.e. simultaneously) or in alternation (i.e. sequentially) has been studied by experimenters and modellers for decades, largely inconclusively.We use previously-parameterised and validated mathematical models of wheat septoria leaf blotch and grapevine powdery mildew to test which strategy provides better resistance management, using the total yield before fungicide-resistance causes disease control to become economically-ineffective (“lifetime yield”) to measure effectiveness.Lifetime yield is optimised by spraying as much low-risk fungicide as is permitted, combined with slightly more high-risk fungicide than needed for acceptable initial disease control, applying these fungicides as a mixture. This is invariant to model parameterisation and structure, as well as the pathosystem in question. However if comparison focuses on other metrics, for example lifetime yield at full label dose, either mixtures or alternation can be optimal.Our work shows how epidemiological principles can explain the evolution of fungicide resistance, and highlights a theoretical framework to address the question of whether mixtures or alternation provide better resistance management. Our work also demonstrates that precisely how spray strategies are compared must be given extremely careful consideration.
Catecholaminergic Manipulation Alters Dynamic Network Topology Across Behavioral States
Authors: Shine James M. , van den Brink Ruud L. , Hernaus Dennis , Nieuwenhuis Sander , Poldrack Russell A. 
Published: July 2017

AbstractThe human brain is able to flexibly adapt its information processing capacity to meet a variety of cognitive challenges. Recent evidence suggests that this flexibility is reflected in the dynamic reorganization of the functional connectome. The ascending catecholaminergic arousal systems of the brain are a plausible candidate mechanism for driving alterations in network architecture, enabling efficient deployment of cognitive resources when the environment demands them. We tested this hypothesis by analyzing both task-free and task-based fMRI data following the administration of atomoxetine, a noradrenaline reuptake inhibitor, compared to placebo, in two separate human fMRI studies. Our results demonstrate that the manipulation of central catecholamine levels leads to a reorganization of the functional connectome in a manner that is sensitive to ongoing cognitive demands.
Functional corticostriatal connection topographies predict goal directed behaviour in humans
Authors: Marquand Andre F. , Haak Koen V. , Beckmann Christian F. 
Published: July 2017

SummaryAnatomical tracing studies in non-human primates have suggested that corticostriatal connectivity is topographically organized: nearby locations in striatum are connected with nearby locations in cortex. The topographic organization of corticostriatal connectivity is thought to underpin many goal-directed behaviours, but these topographies have not been completely characterised in humans and their relationship to uniquely human behaviours remains to be fully determined. Instead, the dominant approach employs parcellations that cannot model the continuous nature of the topography, nor accommodate overlapping cortical projections in the striatum. Here, we employ a different approach to studying human corticostriatal circuitry: we estimate smoothly-varying and spatially overlapping ‘connection topographies’ from resting state fMRI. These correspond exceptionally well with and extend the topographies predicted from primate tracing studies. We show that striatal topography is preserved in regions not previously known to have topographic connections with the striatum and that many goal-directed behaviours can be mapped precisely onto individual variations in the spatial layout of striatal connectivity.
VPS18 recruits VPS41 to the human HOPS complex via a RING-RING interaction
Authors: Hunter Morag R. , Scourfield Edward J. , Emmott Edward , Graham Stephen C. 
Published: July 2017

ABSTRACTEukaryotic cells use conserved multisubunit membrane tethering complexes, including CORVET and HOPS, to control the fusion of endomembranes. These complexes have been extensively studied in yeast, but to date there have been far fewer studies of metazoan CORVET and HOPS. Both of these complexes comprise six subunits: a common four-subunit core and two unique subunits. Once assembled, these complexes function to recognise specific endosomal membrane markers and facilitate SNARE-mediated membrane fusion. CORVET promotes the homotypic fusion of early endosomes, while HOPS promotes the fusion of lysosomes to late endosomes and autophagosomes. Many of the subunits of both CORVET and HOPS contain putative C-terminal zinc-finger domains. Here, the contribution of these domains to the assembly of the human CORVET and HOPS complexes has been examined. Using biochemical techniques, we demonstrate that the zinc-containing RING domains of human VPS18 and VPS41 interact directly to form a stable heterodimer. In cells, these RING domains are able to integrate into endogenous HOPS, showing that the VPS18 RING domain is required to recruit VPS41 to the core complex subunits. Importantly, this mechanism is not conserved throughout eukaryotes, as yeast Vps41 does not contain a C-terminal zinc-finger motif. The subunit analogous to VPS41 in human CORVET is VPS8, in which the RING domain has an additional C-terminal segment that is predicted to be disordered. Both the RING and disordered C-terminal domains are required for integration of VPS8 into endogenous CORVET complexes, suggesting that HOPS and CORVET recruit VPS41 and VPS8 via distinct molecular interactions.
In crystalloactivity tests with latent apple tyrosinase and two mutants reveal the importance of the mutated sites for polyphenol oxidase activity
Authors: Kampatsikas Ioannis , Bijelic Aleksandar , Pretzler Matthias , Rompel Annette 
Published: July 2017

Tyrosinases are type 3 copper enzymes that belong to the polyphenol oxidase (PPO) family and are able to catalyze both theortho-hydroxylation of monophenols and their subsequent oxidation too-quinones, which are precursors for the biosynthesis of colouring substances such as melanin. The first plant pro-tyrosinase fromMalus domestica(MdPPO1) was recombinantly expressed in its latent form (56.4 kDa) and mutated at four positions around the catalytic pocket which are believed to influence the activity of the enzyme. Mutating the amino acids, which are known as activity controllers, yielded the mutantsMdPPO1-Ala239Thr andMdPPO1-Leu243Arg, whereas mutation of the so-called water-keeper and gatekeeper residues resulted in the mutantsMdPPO1-Glu234Ala andMdPPO1-Phe259Ala, respectively. The wild-type enzyme and two of the mutants,MdPPO1-Ala239Thr andMdPPO1-Phe259Ala, were successfully crystallized, leading to single crystals that diffracted to 1.35, 1.55 and 1.70 Å resolution, respectively. All crystals belonged to space groupP212121, exhibiting similar unit-cell parameters:a= 50.70,b= 80.15,c = 115.96 Å for the wild type,a= 50.58,b= 79.90,c= 115.76 Å forMdPPO1-Ala239Thr anda = 50.53,b= 79.76,c= 116.07 Å forMdPPO1-Phe259Ala.In crystalloactivity tests with the crystals of the wild type and the two mutants were performed by adding the monophenolic substrate tyramine and the diphenolic substrate dopamine to crystal-containing drops. The effects of the mutation on the activity of the enzyme were observed by colour changes of the crystals owing to the conversion of the substrates to dark chromophore products.
Audit quality following the Public Company Accounting Oversight Board’s operation
Authors: Chiu She-Chih , Chien Chin-Chen , Lin Hsuan-Chu 
Published: July 2017

Purpose
The purpose of this paper is to investigate the extent to which the transition from self-regulation to heteronomy has changed the gap in audit quality between Big Four and non-Big Four auditors.

Design/methodology/approach
This study analyzes publicly held companies in the USA between 1999 and 2012 using univariate analysis, multivariate analysis and quantile regression analysis. Audit quality is measured with discretionary accruals.

Findings
This study shows an insignificant difference in audit quality between the clients of Big Four and non-Big Four auditors after Public Company Accounting Oversight Board (hereafter, PCAOB) began its operations. In the analysis of the effects of PCAOB inspections on the audit quality of audit firms that are inspected annually and triennially, the findings show that the inspections have more positive effects when carried out annually. This suggests that the frequency of inspection is positively associated with audit quality. Overall, these results provide evidence that recent improvements in audit quality have been caused by changes in regulatory standards.

Originality/value
The paper provides three major original contributions. First, the authors add to the literature on audit quality by further demonstrating a reduced gap in audit quality between Big Four and non-Big Four audit firms due to heteronomy. Secondly, this study contributes to the debate as to whether independent inspections on audit firms are beneficial or not and suggests that the PCAOB inspections help increase audit quality. Finally, the results of this work contribute to the growing literature examining discretionary accruals.
Tax avoidance, value creation and CSR – a European perspective
Authors: Kiesewetter Dirk , Manthey Johannes 
Published: July 2017

Purpose
This paper aims to answer how corporate governance and corporate social responsibility (“CSR”) affect the relationship between value creation and tax avoidance. This study further analyses the impact of the institutional environment, i.e. whether a country is rather a liberal or a coordinated market economy, on the relationship between CSR and tax avoidance.

Design/methodology/approach
The empirical analysis comprises a panel data set of 7,924 observations for the years from 2005 to 2014 for European companies. The relationship between value creation and tax avoidance is tested by grouping the sample in high and low CSR performers. Similarly, the impact of the type of market economy is analysed for the firms.

Findings
The research design does not find evidence that tax avoidance is creating value. The empirical findings reveal that there is a positive relationship between value creation and the effective tax rate for firms with low social and environmental characteristics. Further, this analysis could show that stronger corporate governance is associated with a lower effective tax rate in both coordinated and liberal market economies. The analysis identifies social strengths being associated with a higher effective tax rate for coordinated market economies.

Practical implications
It is proposed to encourage CSR disclosure. The creation of incentives for social strengths could increase tax revenue. Firms should reconsider whether the engagement in tax avoidance is worth it and pursue social responsibility to achieve higher value creation for their stakeholders.

Originality/value
The paper challenges the intuitive expectation that tax avoidance creates value. It is suggested that the governance and CSR culture, as well as the tax legislation in Europe, is different to the USA. Conclusively, tax avoidance is not generating value for the European sample.