bluuebunny/crossref_metadata_2025_split huggingface dataset:
Donor Diabetes and Prolonged Cold Ischemia Time Synergistically Increase the Risk of Graft Failure After Liver Transplantation
Authors: Brüggenwirth Isabel M.A. , Dolgin Natasha H. , Porte Robert J. , Bozorgzadeh Adel , Martins Paulo N.A. 
Published: June 2017

Background
Both prolonged cold ischemia time (CIT) and donor history of diabetes mellitus (DM) are associated with reduced graft survival after liver transplantation. However, it is unknown whether the adverse effect of prolonged CIT on posttransplant graft survival is more pronounced after transplant with DM versus non-DM donor grafts.

Methods
The study sample included 58 226 liver transplant recipients (2002-2015) from the Scientific Registry of Transplant Recipients. Multivariable Cox survival regression with interaction analysis was used to quantify the extent to which history of donor DM (n = 6478) potentiates the adverse effect of prolonged (≥8 hours) CIT (n = 18 287) on graft survival.

Results
Donor DM and CIT 8 hours or longer were each associated with increased risk of graft failure (GF) (adjusted hazard ratio [aHR], 1.19; 95% confidence interval [CI], 1.06-1.35 and aHR, 1.42; 95% CI, 1.32-1.53, respectively) compared with transplanted grafts without either risk factor. However, the combination of DM and CIT 8 hours or longer was associated with a higher risk of GF than either factor alone (aHR, 1.79; 95% CI, 1.55-2.06) and had a synergy index of 1.30. The interaction was significant on a multiplicative scale in the later postoperative period, days 31 to 365 (P = 0.047).

Conclusions
These results suggest that liver grafts from DM donors are more susceptible to the adverse effects of prolonged CIT than livers from non-DM donors. We need to be cognizant that they are more susceptible to ischemic injury, and this may be considered during the allocation process.
Rapid Detection of Sepsis using CESDA: theCaenorabditis elegansSepsis Detection Assay
Authors: Tee Ling Fei , Tan Toh Leong , Neoh Hui-min , Jamal Rahman 
Published: June 2017

AbstractSepsis is a life-threatening condition which could be alleviated by rapid diagnosis and appropriate antibiotic administration. However, currently available laboratory tests for sepsis diagnosis lacks sensitivity and specificity; they also have long turn-around times. In this proof-of-concept study, the nematodeCaenorhabditis eleganswas used as a biological sensor to detect urine of sepsis patients in an assay designated as theC. elegansSepsis Detection Assay (CESDA). From January to June 2016, 45 patients who were admitted to the Emergency Department of a university hospital due to suspected sepsis were included into the study. Urine samples were obtained from these patients and healthy controls and spotted onto CESDA assay plates. Subsequently,C. eleganswere aliquoted onto the centre of the plates and allowed to migrate freely. Number of worms found in either spots or quadrants of the plates containing control or suspected sepsis samples were scored in 10 minute intervals in a 60-minute duration. The CESDA index was then calculated for each sample, where an index near +1 represented attraction of the worms towards the sample, while an index near -1 signified repulsion. Confirmatory diagnosis for suspected sepsis samples was determined using a combination of clinical criteria assessment and standard laboratory protocols. All patients who were positive for sepsis were found to have a CESDA index of > 0.1 (positive predictive value, PPV ≥87%). In addition, the worms were able to differentiate urine of sepsis patients from control as early as 20 minutes (p=0.012). Interestingly, the assay was also able to identify infection within 40 minutes of the test (AUROC = 0.80, p= 0.016). The rapidity of CESDA in sepsis and infection identification as well as the usability of urine samples which are non-invasive towards the patient in this method makes it an interesting protocol to be further explored for sepsis diagnosis.
Reverse-Correlation Analysis of the Mechanosensation Circuit and Behavior inC. elegansReveals Temporal and Spatial Encoding
Authors: Porto Daniel A. , Giblin John , Zhao Yiran , Lu Hang 
Published: June 2017

AbstractAnimals must integrate the activity of multiple mechanoreceptors to navigate complex environments. InCaenorhabditis elegans, the general roles of the mechanosensory neurons have been defined, but most studies involve end-point or single-time-point measurements, and thus lack dynamical information. Here, we formulate a set of unbiased quantitative characterizations of the mechanosensory system by using reverse correlation analysis on behavior. We use a custom tracking, selective illumination, and optogenetics platform to compare two mechanosensory systems: the gentle-touch (TRNs) and harsh-touch (PVD) circuits. This method yields characteristic linear filters that allow for prediction of behavioral responses. The resulting filters are consistent with previous findings, and further provide new insights on the dynamics and spatial encoding of the systems. Our results suggest that the tiled network of the gentle-touch neurons has better resolution for spatial encoding than the harsh-touch neurons. Additionally, linear-nonlinear models can predict behavioral responses based only on sensory neuron activity. Our results capture the overall dynamics of behavior induced by the activation of sensory neurons, providing simple transformations that quantitatively characterize these systems. Furthermore, this platform can be extended to capture the behavioral dynamics induced by any neuron or other excitable cells in the animal.
Mutations in theDrosophilasplicing regulatorPrp31as a model for Retinitis pigmentosa 11
Authors: Lehmann Malte , Hebbar Sarita , Brandl Holger , Leng Weihua , Lakshmanaperumal Naharajan , Winkler Sylke , Knust Elisabeth 
Published: June 2017

AbstractRetinitis pigmentosa is a clinically heterogeneous disease affecting 1.6 million people worldwide. A growing number of identified disease-causing genes are associated with the spliceosome, but the molecular consequences that link defects in splicing factor genes to the aetiology of the disease remain to be elucidated. In this paper, we present aDrosophilamodel for Retinitis pigmentosa 11, a human disease caused by mutations in the splicing factor PRPF31. Here, we induced mutations in theDrosophilaorthologuePrp31. Mutant flies are viable and show a normal eye phenotype when kept under regular light conditions. However, when exposed to constant light, photoreceptors of mutant flies degenerate, thus resembling the human disease phenotype. Degeneration could be shown to be associated with increased oxidative stress. This increase was in agreement with severe dysregulation of genes involved in oxidation/reduction processes, as revealed by high throughput transcriptome sequencing. In fact, light induced photoreceptor cell degeneration could be attenuated by experimentally reducing oxidative stress. A comparable decrease in retinal degeneration was achieved by raising mutant larvae on a vitamin A-depleted medium, thereby reducing rhodopsin levels. Finally, transcriptome data further uncovered an overall retention of introns in mRNAs. Among those, mRNAs of genes involved in synapse assembly, growth and stability were most prominent. These results point to a multifactorial genesis of light induced degeneration in retinae ofPrp31mutant flies, including transcriptional and splicing dysregulation, oxidative stress and defects in vitamin A metabolism.
pulse2percept: A Python-based simulation framework for bionic vision
Authors: Beyeler Michael , Boynton Geoffrey M. , Fine Ione , Rokem Ariel 
Published: June 2017

AbstractBy 2020 roughly 200 million people worldwide will suffer from photoreceptor diseases such as retinitis pigmentosa and age-related macular degeneration, and a variety of retinal sight restoration technologies are being developed to target these diseases. One technology, analogous to cochlear implants, uses a grid of electrodes to stimulate remaining retinal cells. Two brands of retinal prostheses are currently approved for implantation in patients with late stage photoreceptor disease. Clinical experience with these implants has made it apparent that the vision restored by these devices differs substantially from normal sight. To better understand the outcomes of this technology, we developedpulse2percept, an open-source Python implementation of a computational model that predicts the perceptual experience of retinal prosthesis patients across a wide range of implant configurations. A modular and extensible user interface exposes the different building blocks of the software, making it easy for users to simulate novel implants, stimuli, and retinal models. We hope that this library will contribute substantially to the field of medicine by providing a tool to accelerate the development of visual prostheses.
Indoril: An I-PV Add-On for Visualization of Point Mutations on 3D Cartesian Coordinates
Authors: Tanyalcin Ibrahim , Ferte Julien , Khan Taushif , Assaf Carla Al 
Published: June 2017

ABSTRACTSummaryOne of the main goals of proteomics is to understand how point mutations impact on the protein structure. Visualization and clustering of point mutations on user-defined 3 dimensional space can allow researchers to have new insights and hypothesis about the mutation’s mechanism of action.Availability and ImplementationWe have developed an interactive I-PV add-on called INDORIL to visualize point mutations. Indoril can be downloaded fromhttp://www.i-pv.org.Contactibrahim.tanyalcin@i-pv.org║support@i-pv.orgSupplementary InformationPlease refer to the supplementary section andhttp://www.i-pv.org.
Near-Atomic Resolution Structure Determination in Over-Focus with Volta Phase Plate by Cs-corrected Cryo-EM
Authors: Fan Xiao , Zhao Lingyun , Liu Chuan , Zhang Jin-Can , Fan Kelong , Yan Xiyun , Peng Hai-Lin , Lei Jianlin , Wang Hong-Wei 
Published: June 2017

SummaryVolta phase plate (VPP) is a recently developed transmission electron microscope (TEM) apparatus that can significantly enhance the image contrast of biological samples in cryo-electron microscopy (cryo-EM) therefore impose the possibility to solve structures of relatively small macromolecules at high resolution. In this work, we performed theoretical analysis and found that using phase plate on objective lens spherical aberration (Cs)-corrected TEM may gain some interesting optical properties, including the over-focus imaging of macromolecules. We subsequently evaluated the imaging strategy of frozen-hydrated apo-ferritin with VPP on a Cs-corrected TEM and obtained the structure of apo-ferritin at near atomic resolution from both under- and over-focused dataset, illustrating the feasibility and new potential of combining VPP with Cs-corrected TEM for high resolution cryo-EM.HighlightsThe successful combination of volta phase plate and Cs-corrector in single particle cryo-EM.Near-atomic structure determined from over-focused images by cryo-EM. VPP-Cs-corrector coupled EM provides interesting optical properties.In BriefWe took the unique advantage of the optical system by combining the volta phase plate and Cs-corrector in a modern TEM to collect high resolution micrographs of frozen-hydrated apo-ferritin in over-focus imaging conditions and determined the structure of apo-ferritin at 3.0 Angstrom resolution.
Quantifying the impact of rare and ultra-rare coding variation across the phenotypic spectrum
Authors: Ganna Andrea , Satterstrom Kyle F. , Zekavat Seyedeh M , Das Indraniel , Kurki Mitja I. , Churchhouse Claire , Alfoldi Jessica , Martin Alicia R. , Havulinna Aki S. , Byrnes Andrea , Thompson Wesley K. , Nielsen Philip R. , Karczewski Konrad J. , Saarentaus Elmo , Rivas Manuel A. , Gupta Namrata , Pietiläinen Olli , Emdin Connor A , Lescai Francesco , Bybjerg-Grauholm Jonas , Flannick Jason ,   on behalf of GoT2D/T2D-GENES consortium, Mercader Josep , Udler Miriam ,   on behalf of SIGMA consortium, Helmsley IBD Exome Sequencing Project, FinMetSeq Consortium, iPSYCH-Broad Consortium, Laakso Markku , Salomaa Veikko , Hultman Christina , Ripatti Samuli , Hämäläinen Eija , Moilanen Jukka S , Körkkö Jarmo , Kuismin Outi , Nordentoft Merete , Hougaard David M. , Mors Ole , Werge Thomas , Mortensen Preben Bo , MacArthur Daniel , Daly Mark J. , Sullivan Patrick F. , Locke Adam E. , Palotie Aarno , Børglum Anders D. , Kathiresan Sekar , Neale Benjamin M. 
Published: June 2017

AbstractThere is a limited understanding about the impact of rare protein truncating variants across multiple phenotypes. We explore the impact of this class of variants on 13 quantitative traits and 10 diseases using whole-exome sequencing data from 100,296 individuals. Protein truncating variants in genes intolerant to this class of mutations increased risk of autism, schizophrenia, bipolar disorder, intellectual disability, ADHD. In individuals without these disorders, there was an association with shorter height, lower education, increased hospitalization and reduced age. Gene sets implicated from GWAS did not show a significant protein truncating variants-burden beyond what captured by established Mendelian genes. In conclusion, we provide the most thorough investigation to date of the impact of rare deleterious coding variants on complex traits, suggesting widespread pleiotropic risk.Main abbreviationsPTV= Protein Truncating VariantsPI= Protein Truncating IntolerantPI-PTV= Protein Truncating Variant in genes that are Intolerant to Protein Truncating Variants
OneD: increasing reproducibility of Hi-C Samples with abnormal karyotypes
Authors: Vidal Enrique , Dily François le , Quilez Javier , Stadhouders Ralph , Cuartero Yasmina , Graf Thomas , Martí-Renom Marc A. , Beato Miguel , Filion Guillaume J. 
Published: June 2017

AbstractThe three-dimensional conformation of genomes is an essential component of their biological activity. The advent of the Hi-C technology enabled an unprecedented progress in our understanding of genome structures. However, Hi-C is subject to systematic biases that can compromise downstream analyses. Several strategies have been proposed to remove those biases, but the issue of abnormal karyotypes received little attention. Many experiments are performed in cancer cell lines, which typically harbor large-scale copy number variations that create visible defects on the raw Hi-C maps. The consequences of these widespread artifacts on the normalized maps are mostly unexplored. We observed that current normalization methods are not robust to the presence of large-scale copy number variations, potentially obscuring biological differences and enhancing batch effects. To address this issue, we developed an alternative approach designed to take into account chromosomal abnormalities. The method, calledOneD, increases reproducibility among replicates of Hi-C samples with abnormal karyotype, outperforming previous methods significantly. On normal karyotypes,OneDfared equally well as state-of-the-art methods, making it a safe choice for Hi-C normalization.OneDis fast and scales well in terms of computing resources for resolutions up to 1 kbp.OneDis implemented as an R package available athttp://www.github.com/qenvio/dryhic.
Reciprocal Control of Motility and Biofilm Formation by the PdhS2 Two-Component Sensor Kinase ofAgrobacterium tumefaciens
Authors: Heindl Jason E. , Crosby Daniel , Brar Sukhdev , Singletary Tiyan , Merenich Daniel , Eagan Justin L. , Buechlein Aaron M. , Bruger Eric L. , Waters Christopher M. , Fuqua Clay 
Published: June 2017

ABSTRACTA core regulatory pathway that directs developmental transitions and cellular asymmetries inAgrobacterium tumefaciensinvolves two overlapping, integrated phosphorelays. One of these phosphorelays putatively includes four histidine sensor kinase homologues, DivJ, PleC, PdhS1, and PdhS2, and two response regulators, DivK and PleD. In several different alphaproteobacteria, this pathway influences a conserved downstream phosphorelay that ultimately controls the phosphorylation state of the CtrA master response regulator. The PdhS2 sensor kinase reciprocally regulates biofilm formation and swimming motility. In the current study the mechanisms by which theA. tumefacienssensor kinase PdhS2 directs this regulation are delineated. PdhS2 lacking a key residue for phosphatase activity is markedly deficient in proper control of attachment and motility phenotypes, whereas a kinase-deficient PdhS2 mutant is only modestly affected. A genetic interaction between DivK and PdhS2 is revealed, unmasking one of several connections between PdhS2-dependent phenotypes and transcriptional control by CtrA. Epistasis experiments suggest that PdhS2 can function independently of the CckA sensor kinase, the cognate sensor kinase for CtrA which is inhibited by DivK. PdhS2 dynamically localizes to the daughter cell pole in dividing cells. Global expression analysis of thepdhS2mutant reveals a restricted regulon, functioning through CtrA to separately control motility and regulate levels of the intracellular signal cyclic diguanylate monophosphate (cdGMP), thereby affecting production of adhesive polysaccharides and attachment. We hypothesize that inA. tumefaciensthe CtrA regulatory circuit has expanded to include additional inputs through addition of PdhS-type sensor kinases, likely fine-tuning the response of this organism to the soil microenvironment.IMPORTANCEBacterial developmental processes, such as morphological transformations and behavioral transitions, are tightly regulated. In many alphaproteobacteria cell division and development are coordinated by a specific suite of conserved histidine kinases and their partnered regulatory proteins. Here we describe how the histidine kinase PdhS2 ofAgrobacterium tumefaciensregulates complex phenotypes including biofilm formation and motility. PdhS2 genetically interacts with a single-domain response regulator, DivK, and the intracellular signal cyclic diguanylate monophosphate. PdhS2 dynamically localizes to the new pole of recently divided cells, contributing to the regulatory processes that dictate whether these cells remain motile or initiate biofilm formation. These findings expand our understanding of the complex network that integrates cell division and developmental control inA. tumefaciensand related alphaproteobacteria.
Accurate Phasing of Pedigree Genotypes Using Whole Genome Sequence Data
Authors: Blackburn A.N. , Kos M.Z. , Blackburn N.B. , Peralta J.M. , Stevens P. , Lehman D.M. , Blondell L. , Blangero J. , Göring H.H.H. 
Published: June 2017

AbstractPhasing, the process of predicting haplotypes from genotype data, is an important undertaking in genetics and an ongoing area of research. Phasing methods, and associated software, designed specifically for pedigrees are urgently needed. Here we present a new method for phasing genotypes from whole genome sequencing data in pedigrees: PULSAR (PhasingUsingLineageSpecificAlleles /Rare variants). The method is built upon the idea that alleles that are specific to a single founding chromosome within a pedigree, which we refer to as lineage-specific alleles, are highly informative for identifying haplotypes that are identical-by-decent between individuals within a pedigree. Through extensive simulation we assess the performance of PULSAR in a variety of pedigree sizes and structures, and we explore the effects of genotyping errors and presence of non-sequenced individuals on its performance. If the genotyping error rate is sufficiently low PULSAR can phase > 99.9% of heterozygous genotypes with a switch error rate below 1 x 10-4in pedigrees where all individuals are sequenced. We demonstrate that the method is highly accurate and consistently outperforms the long-range phasing approach used for comparison in our benchmarking. The method also holds promise for fixing genotype errors or imputing missing genotypes. The software implementation of this method is freely available.
An overview of construction procurement methods in Australia
Authors: Rahmani Farshid , Maqsood Tayyab , Khalfan Malik 
Published: June 2017

Purpose
The purpose of this paper is to review the use of various construction procurement systems in the past and present, specifically within the Australian construction industry and to overview the historical development of procurement both globally and in the Australian context through the existing literature.

Design/methodology/approach
The paper is an in-depth literature review of various construction procurement systems used in the past and present, both in general and within the context of Australian construction industry.

Findings
The findings suggest that even though relationship-based procurement (RBP) systems offer significant benefits to all project participants, they are unproved by many decision makers because of lack of robust theoretical concept and inability in demonstrating value for money (VfM) for public projects, which would be one of the factors causing move away from RBP in the future.

Originality/value
This review is one of its kind. There is no such review done before within the context of Australian construction industry in such a detail. This review is a part of a recently completed PhD study.
Openness and innovation performance
Authors: Lazzarotti Valentina , Bengtsson Lars , Manzini Raffaella , Pellegrini Luisa , Rippa Pierluigi 
Published: June 2017

PurposeFocusing on some relevant constructs defined by the open innovation (OI) literature (i.e. determinants of openness; openness choices operationalized in terms of collaboration depth with scientific and business partners; organizational and social context; innovation performance in terms of novelty and efficiency), this paper investigates the relationships among such constructs. More specifically, the purpose of this paper is to empirically analyse two types of relationships: between some contextual factors and firms’ openness choices; and among openness choices, a set of organizational-managerial and social factors, and OI performance outcomes.Design/methodology/approachThe authors carried out a theory testing survey, involving four European countries (Finland, Italy, Sweden and the UK). The authors applied descriptive statistics and a series of regressions.FindingsThe authors analysed the impact exerted by external and internal variables on the collaboration depth with scientific and business partners: technological trends are relevant to move firms towards external collaborations, with both types of partners; efficiency goals pursued in collaborations are related to the collaboration depth with both types of partners, while an aggressive innovation strategy is positively related only to scientific-partner depth. Besides, collaboration depths with both partners are positively related to the both sides of innovation performance (i.e. novelty and efficiency), but the organizational-managerial and social contexts emerge as relevant mediator variables. Organizational-managerial and external relational social capital exert a beneficial role on the both types of innovation performance, while internal relational social capital benefits only novelty.Research limitations/implicationsThe work shows important limitations such as the low level of the explanatory values in the regression models. Therefore, the results must be considered as preliminary explorative insights that may be useful to encourage further studies.Practical implicationsThis work serves to raise managers’ awareness on the opportunity of developing organizational-managerial mechanisms, as well as on the importance of social capital to profit from collaborations.Originality/valueAlthough during the last decade many researchers have claimed that we are in the era of OI, empirical works, which provide both a more comprehensive and detailed understanding of the phenomenon, are still few. Moreover, the specific action of the context (managerial, organizational and social) as possible mediator of the performance outcomes of openness is empirically under-studied. The authors’ work attempts to fulfil these gaps.