bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T Cell Decline and Per-Parasite Pathogenicity
Authors: Bertels Frederic , Marzel Alex , Leventhal Gabriel , Mitov Venelin , Fellay Jacques , Günthard Huldrych F , Böni Jürg , Yerly Sabine , Klimkait Thomas , Aubert Vincent , Battegay Manuel , Rauch Andri , Cavassini Matthias , Calmy Alexandra , Bernasconi Enos , Schmid Patrick , Scherrer Alexandra U , Müller Viktor , Bonhoeffer Sebastian , Kouyos Roger , Regoes Roland R ,   the Swiss HIV Cohort Study
Published: May 2017

AbstractPathogen strains may differ in virulence because they attain different loads in their hosts, or because they induce different disease-causing mechanisms independent of their load. In evolutionary ecology, the latter is referred to as “per-parasite pathogenicity”. Using viral load and CD4+ T cell measures from 2014 HIV-1 subtype B infected individuals enrolled in the Swiss HIV Cohort Study, we investigated if virulence — measured as the rate of decline of CD4+ T cells — and per-parasite pathogenicity are heritable from donor to recipient. We estimated heritability by donor-recipient regressions applied to 196 previously identified transmission pairs, and by phylogenetic mixed models applied to a phylogenetic tree inferred from HIVpolsequences. Regressing the CD4+ T cell declines and per-parasite pathogenicities of the transmission pairs did not yield heritability estimates significantly different from zero. With the phylogenetic mixed model, however, our best estimate for the heritability of the CD4+ T cell decline is 17% (5%–30%), and that of the per-parasite pathogenicity is 17% (4%–29%). Further, we confirm that the set-point viral load is heritable, and estimate a heritability of 29% (12%–46%). Interestingly, the pattern of evolution of all these traits differs significantly from neutrality, and is most consistent with stabilizing selection for the set-point viral load, and with directional selection for the CD4+ T cell decline and the per-parasite pathogenicity. Our analysis shows that the viral genetype affects virulence mainly by modulating the per-parasite pathogenicity, while the indirect effect via the set-point viral load is minor.
Transparency in Authors’ Contributions and Responsibilities to Promote Integrity in Scientific Publication
Authors: McNutt Marcia , Bradford Monica , Drazen Jeffrey , Hanson Brooks , Howard Bob , Jamieson Kathleen Hall , Kiermer Véronique , Magoulias Michael , Marcus Emilie , Pope Barbara Kline , Schekman Randy , Swaminathan Sowmya , Stang Peter , Verma Inder 
Published: May 2017

AbstractIn keeping with the growing movement in scientific publishing toward transparency in data and methods, we argue that the names of authors accompanying journal articles should provide insight into who is responsible for which contributions, a process should exist to confirm that the list is complete, clearly articulated standards should establish whether and when the contributions of an individual justify authorship credit, and those involved in the generation of scientific knowledge should follow these best practices.To accomplish these goals, we recommend that journals adopt common and transparent standards for authorship, outline responsibilities for corresponding authors, adopt the CRediT (Contributor Roles Taxonomy)1methodology for attributing contributions, include this information in article metadata, and encourage authors to use the digital persistent identifier ORCID.2Furthermore, we suggest that research institutions have regular open conversations on authorship criteria and ethics and that funding agencies adopt ORCID and accept CRediT. Scientific societies should further authorship transparency by promoting these recommendations through their meetings and publications programs.
Consequences of NMDA receptor deficiency can be rescued in the adult brain
Authors: Mielnik Catharine A. , Binko Mary A. , Funk Adam J. , Johansson Emily M. , Intson Katheron , Sivananthan Nirun , Chen Yuxiao , Islam Rehnuma , Milenkovic Marija , Horsfall Wendy , Ross Ruth A. , Tripathy Shreejoy , Groc Laurent , Salahpour Ali , McCullumsmith Robert E. , Lambe Evelyn K. , Ramsey Amy J. 
Published: May 2017

AbstractN-methyl-D-aspartate receptors (NMDARs) are required to shape activity-dependent connections in the developing and adult brain. Impaired NMDAR signaling through genetic or environmental insults causes a constellation of neurodevelopmental disorders that manifest as intellectual disability, epilepsy, autism, or schizophrenia. It is not clear whether the developmental impacts of NMDAR dysfunction can be overcome by interventions in adulthood. This question is paramount for neurodevelopmental disorders arising from mutations that occur in theGRINgenes, which encode NMDAR subunits, and the broader set of mutations that disrupt NMDAR function. We developed a mouse model where a congenital loss-of-function allele ofGrin1is restored to wildtype by gene editing with Cre recombinase. Rescue of NMDARs in adult mice yields surprisingly robust improvements in cognitive behaviors, including those that are refractory to treatment with current medications. These results suggest that neurodevelopmental disorders arising from NMDAR deficiency can be effectively treated in adults.
Oscillatory default mode network coupling in concussion
Authors: Dunkley B.T , Urban K. , Da Costa L. , Wong S. , Pang E.W. , Taylor M.J. 
Published: May 2017

AbstractBackgroundConcussion is a common form of mild traumatic brain injury (mTBI). Despite the descriptor ‘mild’, a single injury can leave long-lasting and sustained alterations to brain function, including changes to localised activity and large-scale interregional communication. Cognitive complaints are thought to arise from such functional deficits. We investigated the impact of injury on neurophysiological and functionally-specialised resting networks, known as intrinsic connectivity networks (ICNs), using MEG.MethodsWe assessed neurophysiological connectivity in 40 males, 20 with concussion, 20 without, using MEG. Regions-of-interest that comprise nodes of ICNs were defined, and their time courses derived using a beamformer approach. Pairwise fluctuations and covariations in band-limited amplitude envelopes were computed reflecting measures of functional connectivity. Intra-network connectivity was compared between groups using permutation testing, and correlated with symptoms.ResultsWe observedincreasedresting spectral connectivity in the default mode and motor networks in our concussion group when compared with controls, across alpha through gamma ranges. Moreover, these differences were not explained by power spectrum density (absolute changes in the spectral profiles within the ICNs). Furthermore, this increased coupling was significantly associated with symptoms in the DMN and MOT networks – but once accounting for comorbid symptoms (including, depression, anxiety, and ADHD) only the DMN continued to be associated with symptoms.ConclusionThe DMN network plays a critical role in shifting between cognitive tasks. These data suggest even a single concussion can perturb the intrinsic coupling of functionally-specialised networks in the brain and may explain persistent and wide-ranging symptomatology.
A robust dissociation among the language, multiple demand, and default mode networks: evidence from inter-region correlations in effect size
Authors: Mineroff Zachary , Blank Idan , Mahowald Kyle , Fedorenko Evelina 
Published: May 2017

AbstractComplex cognitive processes, including language, rely on multiple mental operations that are carried out by several large-scale functional networks in the frontal, temporal, and parietal association cortices of the human brain. The central division of cognitive labor is between two fronto-parietal bilateral networks: (a) the multiple demand (MD) network, which supports executive processes, such as working memory and cognitive control, and is engaged by diverse task domains, including language, especially when comprehension gets difficult; and (b) the default mode network (DMN), which supports introspective processes, such as mind wandering, and is active when we are not engaged in processing external stimuli. These two networks are strongly dissociated in both their functional profiles and their patterns of activity fluctuations during naturalistic cognition. Here, we focus on the functional relationship between these two networks and a third network: (c) the fronto-temporal left-lateralized “core” language network, which is selectively recruited by linguistic processing. Is the language network distinct and dissociated from both the MD network and the DMN, or is it synchronized and integrated with one or both of them? Recent work has provided evidence for a dissociation between the language network and the MD network. However, the relationship between the language network and the DMN is less clear, with some evidence for coordinated activity patterns and similar response profiles, perhaps due to the role of both in semantic processing. Here we use a novel fMRI approach to examine the relationship among the three networks: we measure the strength of activations in different language, MD, and DMN regions to functional contrasts typically used to identify each network, and then test which regions co-vary in their contrast effect sizes across 60 individuals. We find that effect sizes correlate strongly within each network (e.g., one language region and another language region, or one DMN region and another DMN region), but show little or no correlation for region pairs across networks (e.g., a language region and a DMN region). Thus, we replicate the language/MD network dissociation discovered previously with other methods, and also show that the language network is robustly dissociated from the DMN, overall suggesting that these three networks support distinct computations and contribute to high-level cognition in different ways. Inter-individual differences in effect sizes therefore do not simply reflect general differences in vascularization or attention, but exhibit sensitivity to the functional architecture of the brain. The strength of activation in each network can thus be probed separately in studies that attempt to link neural variability to behavioral or genetic variability.
High-NA open-top selective-plane illumination microscopy for biological imaging
Authors: McGorty Ryan , Xie Dan , Huang Bo 
Published: May 2017

Abstract:Selective-plane illumination microscopy (SPIM) provides unparalleled advantages for volumetric imaging of living organisms over extended times. However, the spatial configuration of a SPIM system often limits its compatibility with many widely used biological sample holders such as multi-well chambers and plates. To solve this problem, we developed a high numerical aperture (NA) open-top configuration that places both the excitation and detection objectives on the opposite of the sample coverglass. We carried out a theoretical calculation to analyze the structure of the system-induced aberrations. We then experimentally compensated the system aberrations using adaptive optics combined with static optical components, demonstrating near-diffraction-limited performance in imaging fluorescently labeled cells.© 2017 Optical Society of AmericaOCIS codes:(080.080) Geometric Optics; (110.0110) Imaging systems; (110.0180) Microscopy.
Assigning function to natural allelic variation via dynamic modeling of gene network induction
Authors: Richard Magali , Chuffart Florent , Duplus-Bottin Hélène , Pouyet Fanny , Spichty Martin , Fulcrand Etienne , Entrevan Marianne , Barthelaix Audrey , Springer Michael , Jost Daniel , Yvert Gaёl 
Published: May 2017

ABSTRACTMore and more natural DNA variants are being linked to physiological traits. Yet, understanding what differences they make on molecular regulations remains challenging. Important properties of gene regulatory networks can be captured by computational models. If model parameters can be ‘personalized’ according to the genotype, their variation may then reveal how DNA variants operate in the network. Here, we combined experiments and computations to visualize natural alleles of the yeastGAL3gene in a space of model parameters describing the galactose response network. Alleles altering the activation of Gal3p by galactose were discriminated from those affecting its activity (production/degradation or efficiency of the activated protein). The approach allowed us to correctly predict that a non-synonymous SNP would change the binding affinity of Gal3p with the Gal80p transcriptional repressor. Our results illustrate how personalizing gene regulatory models can be used for the mechanistic interpretation of genetic variants.
Cancer Genome Interpreter annotates the biological and clinical relevance of tumor alterations
Authors: Tamborero David , Rubio-Perez Carlota , Deu-Pons Jordi , Schroeder Michael P , Vivancos Ana , Rovira Ana , Tusquets Ignasi , Albanell Joan , Rodon Jordi , Tabernero Josep , Torres Carmen de , Dienstmann Rodrigo , Gonzalez-Perez Abel , Lopez-Bigas Nuria 
Published: May 2017

AbstractWhile tumor genome sequencing has become widely available in clinical and research settings, the interpretation of tumor somatic variants remains an important bottleneck. Most of the alterations observed in tumors, including those in well-known cancer genes, are of uncertain significance. Moreover, the information on tumor genomic alterations shaping the response to existing therapies is fragmented across the literature and several specialized resources. Here we present the Cancer Genome Interpreter (http://www.cancergenomeinterpreter.org), an open access tool that we have implemented to annotate genomic alterations and interpret their possible role in tumorigenesis and in the response to anti-cancer therapies.
Experimental and statistical re-evaluation provides no evidence forDrosophilacourtship song rhythms
Authors: Stern David L. , Clemens Jan , Coen Philip , Calhoun Adam J. , Hogenesch John B. , Arthur Ben , Murthy Mala 
Published: May 2017

AbstractFrom 1980 to 1992, a series of influential papers reported on the discovery, genetics, and evolution of a periodic cycling of the interval betweenDrosophilamale courtship song pulses. The molecular mechanisms underlying this periodicity were never described. To reinitiate investigation of this phenomenon, we performed automated segmentation of songs, but failed to detect the proposed periodicity [Arthur BJ et al. (2013)BMC Biol11:11; Stern DL (2014)BMC Biol12:38]. Kyriacou CP et al. [(2017)PNAS114:1970-1975] report that we failed to detect song rhythms because i) our flies did not sing enough and ii) our segmenter did not identify many of the song pulses. Kyriacou et al. manually annotated a subset of our recordings and reported that two strains displayed rhythms with genotype-specific periodicity, in agreement with their original reports. We cannot replicate this finding and show that the manually-annotated data, the original automatically segmented data, and a new data set provide no evidence for either the existence of song rhythms or song periodicity differences between genotypes. Furthermore, we have re-examined our methods and analysis and find that our automated segmentation method was not biased to prevent detection of putative song periodicity. We conclude that there is currently no evidence for the existence ofDrosophilacourtship song rhythms.Significance statementPrevious studies have reported that male vinegar flies sing courtship songs with a periodic rhythm of approximately 55 seconds. Several years ago, we showed that we could not replicate this observation. Recently, the original authors have claimed that we failed to find rhythms because 1) our flies did not sing enough and 2) our software for detecting song did not detect all song events. They claimed that they could detect rhythms in song annotated by hand. We report here that we cannot replicate their observation of rhythms in the hand-annotated data or in any dataset and that our original methods were not biased against detecting rhythms. We conclude that song rhythms cannot be detected.
Framework for quality assessment of whole genome, cancer sequences
Authors: Whalley Justin P. , Buchhalter Ivo , Rheinbay Esther , Raine Keiran M. , Kleinheinz Kortine , Stobbe Miranda D. , Werner Johannes , Beltran Sergi , Gut Marta , Huebschmann Daniel , Hutter Barbara , Livitz Dimitri , Perry Marc , Rosenberg Mara , Saksena Gordon , Trotta Jean-Rémi , Eils Roland , Korbel Jan , Gerhard Daniela S. , Campbell Peter , Getz Gad , Schlesner Matthias , Gut Ivo G. 
Published: May 2017

AbstractWorking with cancer whole genomes sequenced over a period of many years in different sequencing centres requires a validated framework to compare the quality of these sequences. The Pan-Cancer Analysis of Whole Genomes (PCAWG) of the International Cancer Genome Consortium (ICGC), a project a cohort of over 2800 donors provided us with the challenge of assessing the quality of the genome sequences. A non-redundant set of five quality control (QC) measurements were assembled and used to establish a star rating system. These QC measures reflect known differences in sequencing protocol and provide a guide to downstream analyses of these whole genome sequences. The resulting QC measures also allowed for exclusion samples of poor quality, providing researchers within PCAWG, and when the data is released for other researchers, a good idea of the sequencing quality. For a researcher wishing to apply the QC measures for their data we provide a Docker Container of the software used to calculate them. We believe that this is an effective framework of quality measures for whole genome, cancer sequences, which will be a useful addition to analytical pipelines, as it has to the PCAWG project.
Attitudinal factors, financial literacy, and stock market participation
Authors: Sivaramakrishnan Sreeram , Srivastava Mala , Rastogi Anupam 
Published: May 2017

Purpose
The purpose of this paper is to study the influence of factors such as financial literacy on a consumer’s investment decisions, particularly in the stock market. Based on two empirical studies, the theory of planned behaviour (TPB) was used to understand stock market participation (SMP) in India while developing a model to represent the relationships between the various factors. Consumer financial literacy was conceptualised to be a part of perceived behavioural control and included in the TPB.

Design/methodology/approach
A mixed methods research was followed where qualitative research preceded a quantitative survey-based study. In-depth interviews were conducted with investors and experts, results of which, when combined with the literature review, revealed seven variables including financial literacy which were pooled into three distinct groups based on the TPB. Responses obtained from 506 retail investors from four cities in India were analysed. Structural equation modelling was used to test the models and arrive at a final empirical model.

Findings
Results of the study indicated that investment intention predicts actual investments in the stock market (which represented behaviour). Financial literacy – both subjective and objective – were also found to be significant influencers on intention while only objective financial literacy seemed to affect behaviour. Three variables – perception of regulator, risk avoidance, and hassle factor – were combined to form a second-order construct which was named “Attitude to Investment Behaviour”. This had a negative impact on intention to invest in the equity markets. Financial well-being seemed to have a negative impact on intention while having a positive relationship with behaviour.

Practical implications
The results present significant investor behaviour and policy implications for financial services marketing. Some interventions, especially in the area of consumer financial literacy, are more likely than others to help consumers bridge the gap between non-participation and participation in the stock market.

Originality/value
The study makes a contribution to investor behaviour theory in the form of a comprehensive model to explain SMP in an emerging market. This can be further tested across geographies.
Impact of board structure on firm performance: evidence from an emerging economy
Authors: Yasser Qaiser Rafique , Mamun Abdullah Al , Rodrigs Marcus 
Published: May 2017

PurposeThe aim of this paper is to examine the association between board demographics and firm financial performance of Karachi Stock Exchange companies and describe the attributes of these firms and their boards. The connection between board structure and firm performance has attracted much attention, especially in emerging economies, yet yielded many inconsistent empirical results.Design/methodology/approachThis study examines the relationship between board structure and the performance of Pakistani public listed companies by using a sample of Karachi Stock Exchange 100 (KSE-100) indexed companies. This study exploits the corporate performance by accounting-based measures (return on assets), market-based measures (Tobin’s Q), and economic profit (economic value added).FindingsThe outcome of the study shows the positive relationship between the board size, minority representation in board, and family director’s in-board and firm performance. The authors also find that, instead of adding value, independent directors in Pakistan are negatively associated with firm value.Research limitations/implicationsThe study is based on KSE-100 indexed companies from 2009 to 2013; however, a large sample and multiple years’ data are required.Practical implicationsThe paper provides empirical evidence that board independence is not necessary for public-listed companies in Pakistan and would be of interest to regulatory bodies, business practitioners, and academic researchers.Originality/valueThe paper contributes to the literature on corporate governance and firm performance by introducing a framework for identifying and analyzing moderating variables that affect the relationship between board structure and firm performance.
Modeling the Scaling Up of Early Crime Prevention
Authors: Sullivan Christopher J. , Welsh Brandon C. , Ilchi Omeed S. 
Published: May 2017

Research SummaryAlthough the amount of research evidence on the effectiveness of developmental crime prevention has grown considerably in recent decades, the translation of this scientific knowledge into policy and practice has lagged behind. In this article, we consider the challenges as well as the opportunities associated with scaling up evidence‐based programs and we offer an approach for considering the potential effects of deviations in implementation protocols during replications. We use results from the series of studies on the Nurse‐Family Partnership (NFP) to develop a computer simulation model. Based on a large number of simulations, we systematically adjusted key inputs (e.g., target population and fidelity) to mimic a range of possible implementation conditions and to observe the impacts on the estimated intervention effects. As the process progresses from the baseline condition, which reflects the initial implementation conditions specified in the NFP model, to alternative experimental scenarios reflecting problematic deviations in implementation, the number of arrests accumulated by treatment participants begins to increase. This indicates that these implementation challenges have a negative impact on program effects and that we can go some way toward predicting what might occur in implementation as they emerge and interact.Policy ImplicationsThe challenges facing program dissemination and their impact on program results have not been enumerated all that precisely in the literature, which has resulted in the assignment of arbitrary penalties when evaluating the prospects for taking programs to scale. Establishing efficacious interventions is only one part of the process of moving research to practice, and further consideration of the scaling‐up process is integral to translational criminology. Informed computer simulation may be one tool to help guide this program implementation process.