bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fractionation of impulsive and compulsive trans-diagnostic phenotypes and their longitudinal associations
Authors: Chamberlain Samuel R. , Tiego Jeggan , Fontenelle Leonardo F. , Hook Roxanne , Parkes Linden , Segrave Rebecca , Hauser Tobias U. , Dolan Ray J. , Goodyer Ian M. , Bullmore Ed , Grant Jon E. , Yücel Murat 
Published: March 2019

AbstractObjectiveYoung adulthood is a crucial neurodevelopmental period during which impulsive and compulsive problem behaviours commonly emerge. While traditionally considered diametrically opposed, impulsive and compulsive symptoms tend to co-occur. The objectives of this study were: (i) to identify the optimal trans-diagnostic structural framework for measuring impulsive and compulsive problem behaviours; and (ii) to use this optimal framework to identify common/distinct antecedents of these latent phenotypes.Methods654 young adults were recruited as part of the Neuroscience in Psychiatry Network (NSPN), a population-based cohort in the United Kingdom. The optimal trans-diagnostic structural model capturing 33 types of impulsive and compulsive problem behaviours was identified. Baseline predictors of subsequent impulsive and compulsive trans-diagnostic phenotypes were characterised, along with cross-sectional associations, using Partial Least Squares (PLS).ResultsCurrent problem behaviours were optimally explained by a bi-factor model, which yielded dissociable measures of impulsivity and compulsivity, as well as a general disinhibition factor. Impulsive problem behaviours were significantly explained by prior antisocial and impulsive personality traits, male gender, general distress, perceived dysfunctional parenting, and teasing/arguments within friendships. Compulsive problem behaviours were significantly explained by prior compulsive traits, and female gender.ConclusionsThis study demonstrates that trans-diagnostic phenotypes of 33 impulsive and compulsive problem behaviours are identifiable in young adults, utilizing a bi-factor model based on responses to a single questionnaire. Furthermore, these phenotypes have different antecedents. The findings yield a new framework for fractionating impulsivity and compulsivity; and suggest different early intervention targets to avert emergence of problem behaviours. This framework may be useful for future biological and clinical dissection of impulsivity and compulsivity.
KLK4 inhibition by cyclic and acyclic peptides: structural and dynamical insights into standard-mechanism protease inhibitors
Authors: Riley Blake T. , Ilyichova Olga , de Veer Simon J. , Swedberg Joakim E. , Wilson Emily , Hoke David E. , Harris Jonathan M. , Buckle Ashley M. 
Published: March 2019

AbstractSunflower Trypsin Inhibitor (SFTI-1) is a 14-amino acid serine protease inhibitor. The dual anti-parallel β-sheet arrangement of SFTI-1 is stabilized by a N-terminal-C-terminal backbone cyclization and a further disulfide bridge to form a final bicyclic structure. This constrained structure is further rigidified by an extensive network of internal hydrogen bonds. Thus, the structure of SFTI-1 in solution resembles the protease-bound structure, reducing the entropic penalty upon protease binding. When cleaved at the scissile bond, it is thought that the rigidifying features of SFTI-1 maintain its structure, allowing the scissile bond to be reformed. The lack of structural plasticity for SFTI-1 is proposed to favour initial protease binding and continued occupancy in the protease active site, resulting in an equilibrium between cleaved and uncleaved inhibitor in the presence of protease. We have determined, at 1.15 Å resolution, the x-ray crystal structures of complexes between human kallikrein-related peptidase 4 (KLK4) and SFTI-FCQR(Asn14), and between KLK4 and an acyclic form of the same inhibitor, SFTI-FCQR(Asn14)[1,14], with the latter displaying a cleaved scissile bond. Structural analysis and MD simulations together reveal the roles of altered contact sequence, intramolecular hydrogen bonding network and backbone cyclization, in altering the state of SFTI’s scissile bond ligation at the protease active site. Taken together, the data presented reveal insights into the role of dynamics in the standard-mechanism inhibition, and suggest that modifications on the noncontact strand may be a useful, underexplored approach for generating further potent or selective SFTI-based inhibitors against members of the serine protease family.
A Clustering Approach for Detecting Implausible Observation Values in Electronic Health Records Data
Authors: Estiri Hossein , Murphy Shawn N. 
Published: March 2019

AbstractBackgroundIdentifying implausible clinical observations (e.g., laboratory test and vital sign values) in Electronic Health Record (EHR) data using rule-based procedures is challenging. Anomaly/outlier detection methods can be applied as an alternative algorithmic approach to flagging such implausible values in EHRs.ObjectiveThe primary objectives of this research were to develop and test an unsupervised clustering-based anomaly/outlier detection approach for detecting implausible observations in EHR data as an alternative algorithmic solution to the existing procedures.MethodsOur approach is built upon two underlying hypotheses that, (i) when there are large number of observations, implausible records should be sparse, and therefore (ii) if these data are clustered properly, clusters with sparse populations should represent implausible observations. To test these hypotheses, we applied an unsupervised clustering algorithm to EHR observation data on 50 laboratory tests. We tested different specifications of the clustering approach and computed confusion matrix indices against a set of silver-standard plausibility thresholds. We compared the results from the proposed approach with conventional anomaly detection (CAD) approach’s, including standard deviation and Mahalanobis distance.ResultsWe found that the clustering approach produced results with exceptional specificity and high sensitivity. Compared with the conventional anomaly detection approaches, our proposed clustering approach resulted in significantly smaller number of false positive cases.ConclusionOur contributions include (i) a clustering approach for identifying implausible EHR observations, (ii) evidence that implausible observations are sparse in EHR laboratory test results, (iii) a parallel implementation of the clustering approach on i2b2 star schema, and (3) a set of silver-standard plausibility thresholds for 50 laboratory tests that can be used in other studies for validation. The proposed algorithmic solution can augment human decisions to improve data quality. Therefore, a workflow is needed to complement the algorithm’s job and initiate necessary actions that need to be taken in order to improve the quality of data.
Native protein delivery into rice callus using ionic complexes of protein and cell-penetrating peptides
Authors: Guo Boyang , Itami Jun , Oikawa Kazusato , Motoda Yoko , Kigawa Takanori , Numata Keiji 
Published: March 2019

AbstractDirect protein delivery into intact plants remains a challenge for the agricultural and plant science fields. Cell-penetrating peptide (CPP)-mediated protein delivery requires the binding of CPPs to a protein to carry the protein into the cell through the cell wall and lipid bilayer. Thus, we prepared ionic complexes of a CPP-containing carrier peptide and a cargo protein, namely, Citrine yellow fluorescent protein, and subsequently studied their physicochemical properties. Two types of carrier peptides, BP100(KH)9 and BP100CH7, were investigated for delivery efficiency into rice callus. Both BP100(KH)9 and BP100CH7 successfully introduced Citrine protein into rice callus cells under pressure and vacuum treatment. Moreover, delivery efficiency varied at different growth stages of rice callus; 5-day rice callus was a more efficient recipient for Citrine than 21-day callus.
Epistasis detectably alters correlations between genomic sites in a narrow parameter window
Authors: Pedruzzi Gabriele , Rouzine Igor M. 
Published: March 2019

AbstractDifferent genomic sites evolve inter-dependently due to the combined action of epistasis, non-additive contributions of different loci to genome fitness, and physical linkage of different loci due to their common heritage. Both epistasis and linkage, partially compensated by recombination, cause correlations between allele frequencies at the loci (linkage disequilibrium, LD). The interaction and competition between epistasis and linkage are not fully understood, nor is their relative sensitivity to recombination. Modeling an adapting population in the presence of random mutation, natural selection, pairwise epistasis, and random genetic drift, we compare the contributions of epistasis and linkage. For this end, we use a panel of haplotype-based measures of LD and their various combinations calculated for epistatic and non-epistatic pairs separately. We compute the optimal percentages of detected and false positive pairs in a one-time sample of a population of moderate size. We demonstrate that true interacting pairs can be told apart in a sufficiently short genome within a narrow window of time and parameters. Outside of this parameter region, unless the population is extremely large, shared ancestry of individual sequences generates pervasive stochastic LD for non-interacting pairs masking true epistatic associations. In the presence of sufficiently strong recombination, linkage effects decrease faster than those of epistasis, and the detection of epistasis improves. We demonstrate that the epistasis component of locus association can be isolated, at a single time point, by averaging haplotype frequencies over multiple independent populations. These results demonstrate the existence of fundamental restrictions on the protocols for detecting true interactions in DNA sequence sets.
Quality of Life, Salivary Cortisol and Atopic Diseases in Young Children
Authors: Rolfsjord Leif Bjarte , Skjerven Håvard Ove , Bakkeheim Egil , Løvold Berents Teresa , Carlsen Kai-Håkon , Lødrup Carlsen Karin C 
Published: March 2019

ABSTRACTBackgroundChildren with atopic disease may have reduced health-related quality of life (QoL) and morning cortisol. The link between QoL, cortisol and atopic disease is unclear.We aimed to determine if QoL was associated with morning salivary cortisol at two years of age, and if asthma, atopic dermatitis and/or allergic sensitisation influenced this association. Secondarily, we aimed to determine if QoL at one year of age was associated with salivary cortisol one year later.Methods and findingsFrom the Bronchiolitis All SE-Norway study, enrolling infants during hospitalisation for acute bronchiolitis in infancy (bronchiolitis group) and population based control infants (controls), we included all 358 subjects with available Infant Toddler Quality of Life Questionnaire™ (ITQOL) consisting of 13 domains, and morning salivary cortisol measurements at two years of age. Additionally, QoL nine months after enrolment was available for 289 of these children at one year of age. Recurrent bronchial obstruction was used as an asthma proxy. Atopic dermatitis was defined by Hanifin and Rajka criteria and allergic sensitisation by a positive skin prick test. Associations between QoL and cortisol were analysed by multivariate analyses, stratified by bronchiolitis and control groups due to interaction. At two years of age, QoL was significantly associated with 8/13 QoL domains in the bronchiolitis group, but only with General health in the controls. The associations in the bronchiolitis group showed 0.06-0.19 percentage points changes per nmol/L cortisol for each of the eight domains (p-values 0.0001-0.034). The associations for all domains remained significant, but were diminished by independently including recurrent bronchial obstruction and atopic dermatitis, but remained unchanged by allergic sensitisation.In the bronchiolitis group only, 8/13 age and gender adjusted QoL domains in one-year old children were significantly associated with cortisol levels at two years (p= 0.0005-0.04).Conclusions:At two years, most QoL domains were associated with salivary cortisol in children who had been hospitalised for acute bronchiolitis in infancy, but for one domain only in controls. The associations were weakened, but remained significant by taking into account asthma and atopic dermatitis. The QoL in one-year old children was associated with salivary cortisol 10 months later.
An ancient lineage of highly divergent parvoviruses infects both vertebrate and invertebrate hosts
Authors: Pénzes Judit J , de Souza William Marciel , Agbandje-McKenna Mavis , Gifford Robert J. 
Published: March 2019

ABSTRACTChapparvoviruses are a highly divergent group of parvoviruses (familyParvoviridae) first identified in 2013. Interest in these poorly characterized viruses has been raised by recent studies indicating that they are the cause of chronic kidney disease that arises spontaneously in laboratory mice. In this study, we investigate the biological and evolutionary characteristics of chapparvoviruses via comparative analysis of genome sequence data. Our analysis, which incorporates sequences derived from endogenous viral elements (EVEs) as well as exogenous viruses, reveals that chapparvoviruses are an ancient lineage within the familyParvoviridae, clustering separately from members of both currently established parvoviral subfamilies. Consistent with this, they exhibit a number of characteristic genomic and structural features, i.e. a large number of putative auxiliary protein-encoding genes, capsid protein genes non-homologous to any hitherto parvoviralcap, as well as a putative capsid structure lacking the canonical fifth strand of the ABIDG sheet comprising the luminal side of the jelly roll. Our findings demonstrate that the chapparvovirus lineage infects an exceptionally broad range of host species, including both vertebrates and invertebrates. Furthermore, we observe that chapparvoviruses found in fish are more closely related to those from invertebrates than they are to those that infect amniote vertebrates. This suggests that transmission between distantly related host species may have occurred in the past. Our study provides the first integrated overview of the chapparvovirus group, and revises current views of parvovirus evolutionAUTHOR SUMMARYChapparvoviruses are a recently identified group of viruses about which relatively little is known. However, recent studies have shown that these viruses cause disease in laboratory mice and are prevalent in the fecal virome of pigs and poultry, raising interest in their potential impact as pathogens, and utility as experimental tools. We examined the genomes of chapparvoviruses and endogenous viral elements (‘fossilized’ virus sequences derived from ancestral viruses) using a variety of bioinformatics-based approaches. We show that the chapparvoviruses have an ancient origin and are evolutionarily distinct from all other related viruses. Accordingly, their genomes and virions exhibit a range of distinct characteristic features. We examine the distribution of these features in the light of chapparvovirus evolutionary history (which we can also infer from genomic data), revealing new insights into chapparvovirus biology.
Mapping Histone Modifications in Low Cell Number and Single Cells Using Antibody-guided Chromatin Tagmentation (ACT-seq)
Authors: Carter Benjamin , Ku Wai Lim , Tang Qingsong , Kang Jee Youn , Zhao Keji 
Published: March 2019

ABSTRACTModern next-generation sequencing-based methods have empowered researchers to assay the epigenetic states of individual cells. Existing techniques for profiling epigenetic marks in single cells often require the use and optimization of time-intensive procedures such as drop fluidics, chromatin fragmentation, and end repair. Here we describe ACT-seq, a novel and streamlined method for mapping genome-wide distributions of histone tail modifications, histone variants, and chromatin-binding proteins in a small number of or single cells. ACT-seq utilizes a fusion of Tn5 transposase to Protein A that is targeted to chromatin by a specific antibody, allowing chromatin fragmentation and sequence tag insertion specifically at genomic sites presenting the relevant antigen. The Tn5 transposase enables the use of an index multiplexing strategy (iACT-seq), which enables construction of thousands of single-cell libraries in one day by a single researcher without the need for drop-based fluidics or visual sorting. We conclude that ACT-seq present an attractive alternative to existing techniques for mapping epigenetic marks in single cells.
Quantitative high-throughput tests of ubiquitous RNA secondary structure prediction algorithms via RNA/protein binding
Authors: Becker Winston R. , Jarmoskaite Inga , Kappel Kalli , Vaidyanathan Pavanapuresan P. , Denny Sarah K. , Das Rhiju , Greenleaf William J. , Herschlag Daniel 
Published: March 2019

AbstractNearest-neighbor (NN) rules provide a simple and powerful quantitative framework for RNA structure prediction that is strongly supported for canonical Watson-Crick duplexes from a plethora of thermodynamic measurements. Predictions of RNA secondary structure based on nearest-neighbor (NN) rules are routinely used to understand biological function and to engineer and control new functions in biotechnology. However, NN applications to RNA structural features such as internal and terminal loops rely on approximations and assumptions, with sparse experimental coverage of the vast number of possible sequence and structural features. To test to what extent NN rules accurately predict thermodynamic stabilities across RNAs with non-WC features, we tested their predictions using a quantitative high-throughput assay platform, RNA-MaP. Using a thermodynamic assay with coupled protein binding, we carried out equilibrium measurements for over 1000 RNAs with a range of predicted secondary structure stabilities. Our results revealed substantial scatter and systematic deviations between NN predictions and observed stabilities. Solution salt effects and incorrect or omitted loop parameters contribute to these observed deviations. Our results demonstrate the need to independently and quantitatively test NN computational algorithms to identify their capabilities and limitations. RNA-MaP and related approaches can be used to test computational predictions and can be adapted to obtain experimental data to improve RNA secondary structure and other prediction algorithms.Significance statementRNA secondary structure prediction algorithms are routinely used to understand, predict and design functional RNA structures in biology and biotechnology. Given the vast number of RNA sequence and structural features, these predictions rely on a series of approximations, and independent tests are needed to quantitatively evaluate the accuracy of predicted RNA structural stabilities. Here we measure the stabilities of over 1000 RNA constructs by using a coupled protein binding assay. Our results reveal substantial deviations from the RNA stabilities predicted by popular algorithms, and identify factors contributing to the observed deviations. We demonstrate the importance of quantitative, experimental tests of computational RNA structure predictions and present an approach that can be used to routinely test and improve the prediction accuracy.
Mindfulness in organizations (Part 2): a practitioners’ guide to applying mindfulness-based approaches in leadership development, workplace wellbeing and coaching
Authors: Passmore Jonathan 
Published: March 2019

PurposeThe purpose of this paper is to explore the application of mindfulness in organizational development and provide a useful guide for practitioners in their work as managers, consultants and coaches.Design/methodology/approachThe paper offers practical applications of mindfulness in organizations, specifically its use in leadership development, organizational wellbeing and coaching.FindingsThe paper notes a variety of ways in which mindfulness can be applied. While it recognizes that the research into the application of mindfulness at work is under developed, it suggests that through applied organizational research our understanding of its value to employees and organizations can be enhanced.Practical implicationsThe paper provides insights drawn from practice that can be applied by HR practitioners or consultants addressing modern organizational challenges from workplace stress to developing leaders with greater situational awareness and empathy.Originality/valueThe paper is distinctive in providing a strong practitioners focus and from broadening the inquiry from the individual toward considering organizational benefits that may be obtained from workplace mindfulness programs.
Sunk time fallacy with recoverable monetary costs
Authors: Pandey Shivendra Kumar , Sharma Dheeraj 
Published: March 2019

PurposeThe purpose of this paper is to examine the sunk-time fallacy in the context of simultaneous variations of time and money when financial expenditures are recoverable. The study compares a recoverable monetary scenario with conditions where money is either not spent or spent, but purchase and payment are decoupled.Design/methodology/approachA sample of 184 participants was utilised in three experiments. A randomised design was used, and experimental manipulations were achieved using the vignette method.FindingsThe results indicate that consumers are susceptible to sunk-time fallacy. Specifically, results suggest that there is no significant difference in sunk cost fallacy when a consumer spends only time vs when a consumer spends money and time both but money can be recovered. The sunk-time fallacy did not occur in credit card purchases. The sunk-time fallacy did not happen in temporal investments of less than a week but appeared in the temporal investments of two weeks.Research limitations/implicationsThe study indicates that sunk-time fallacy occurs after a minimum threshold of time is spent on a particular activity.Practical implicationsOnline retailers may vary the delivery period of ordered merchandise to reduce product returns. Online retailers may not deliver the merchandise too early to take advantage of the sunk-time fallacy. Bestseller products should be quickly delivered as there are lesser chances of product return. On the other hand, new products or products with mixed consumer reviews should be provided preferably with a time lag beyond a week. Managers should incentivise payments through debit card/net banking and cash-on-delivery to reduce returns by using sunk-time fallacy.Originality/valueThe study is perhaps the first one to study the sunk-time fallacy in a simultaneous variation of time and money where monetary costs can be recovered fully.