bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peer review and competition in the Art Exhibition Game
Authors: Balietti Stefano , Goldstone Robert L. , Helbing Dirk 
Published: July 2016

Significance
Competition is an essential mechanism in increasing the effort and performance of human groups in real life. However, competition has side effects: it can be detrimental to creativity and reduce cooperation. We conducted an experiment called the Art Exhibition Game to investigate the effect of competitive incentives in environments where the quality of creative products and the amount of innovation allowed are decided through peer review. Our approach is general and can provide insights in domains such as clinical evaluations, scientific admissibility, and science funding. Our results show that competition leads to more innovation but also to more unfair reviews and to a lower level of agreement between reviewers. Moreover, competition does not improve the average quality of published works.
Single-cell analysis delineates a trajectory toward the human early otic lineage
Authors: Ealy Megan , Ellwanger Daniel C. , Kosaric Nina , Stapper Andres P. , Heller Stefan 
Published: July 2016

Significance
Understanding early human development relies on studies of in vitro-generated tissues from human embryonic or induced pluripotent stem cells that recapitulate in vivo cell types. End-point analyses of specific cell types can be hindered by inappropriate cell-culture conditions that may drive cells to undesired fates. We address these issues by reconstructing the trajectory of gene expression dynamics of 90 marker genes during early human otic development at the single-cell level. To determine the efficacy of our guidance protocol we compare these cells to native cells from the developing mouse otocyst. We find that otic induction follows the predicted dynamics of gene expression and resembles otic cells from native mouse tissue up to 12 days of culture.
The integration of quantitative genetics, paleontology, and neontology reveals genetic underpinnings of primate dental evolution
Authors: Hlusko Leslea J. , Schmitt Christopher A. , Monson Tesla A. , Brasil Marianne F. , Mahaney Michael C. 
Published: July 2016

Significance
Experimental research on mice has yielded tremendous biological insight. However, the ∼140 million y of evolution that separate mice from humans pose a hurdle to direct application of this knowledge to humans. We report here that considerable progress for identifying genetically patterned skeletal phenotypes beyond the mouse model is possible through transdisciplinary approaches that include the anatomical sciences. Indeed, anatomy and paleontology offer unique opportunities through which to develop and test hypotheses about the underlying genetic mechanisms of the skeleton for taxa that are not well suited to experimental manipulation, such as ourselves.
Reversal of dendritic phenotypes in 16p11.2 microduplication mouse model neurons by pharmacological targeting of a network hub
Authors: Blizinsky Katherine D. , Diaz-Castro Blanca , Forrest Marc P. , Schürmann Britta , Bach Anthony P. , Martin-de-Saavedra Maria Dolores , Wang Lei , Csernansky John G. , Duan Jubao , Penzes Peter 
Published: July 2016

Significance
The architecture of neuronal dendritic trees is crucial for brain connectivity, whereas dendritic abnormalities are associated with psychiatric disorders. Rare copy number variations (CNVs) are a category of mutations often associated with schizophrenia, autism, and other mental disorders. However, the genetic complexity of CNV disorders poses a serious challenge for the identification of experimentally approachable mechanisms. Here we used network analysis to identify the most topologically important hub in protein–protein interaction networks within such a CNV, and in broader gene networks of psychiatric CNVs. We then show that pharmacological targeting of this node reverses dendritic alterations in a neuronal model of this CNV, outlining a strategy for the analysis and reversal of cellular phenotypes in CNV-related psychiatric disorders.
AKAP220 manages apical actin networks that coordinate aquaporin-2 location and renal water reabsorption
Authors: Whiting Jennifer L. , Ogier Leah , Forbush Katherine A. , Bucko Paula , Gopalan Janani , Seternes Ole-Morten , Langeberg Lorene K. , Scott John D. 
Published: July 2016

Significance
Systemic control of water homeostasis is a vital physiological process. Vasopressin-regulated reabsorption of water through aquaporin-2 (AQP2) water pores in the kidney preserves fluid balance and results in more concentrated urine. We have discovered that the scaffolding protein A-Kinase Anchoring Protein 220 (AKAP220) controls vasopressin-independent aspects of AQP2 trafficking at apical membranes of cells of the kidney-collecting ducts. We postulate that this proceeds via a molecular mechanism that evokes RhoA-mediated modulation of “actin barrier” dynamics. Loss of AKAP220 leads to accumulation of AQP2 at the apical plasma membrane and reduces urine-diluting capacity during overhydration. This phenotype may be clinically relevant, as accumulation of AQP2 at the apical membrane is the desired therapeutic outcome when treating patients with certain renal disorders, including nephrogenic diabetes insipidus.
Testimonial injustice and prescriptive credibility deficits
Authors: Munroe Wade 
Published: July 2016

AbstractIn light of recent social psychological literature, I expand Miranda Fricker’s important notion of testimonial injustice. A fair portion of Fricker’s account rests on an older paradigm of stereotype and prejudice. Given recent empirical work, I argue for what I dub prescriptive credibility deficits in which a backlash effect leads to the assignment of a diminished level of credibility to persons who act in counter-stereotypic manners, thereby flouting prescriptive stereotypes. The notion of a prescriptive credibility deficit is not merely an interesting conceptual addendum that can be appended to Fricker’s theory without need for further emendation. I develop the wider implications of prescriptive credibility deficits and argue that they pose a challenge to Fricker’s conception of (1) the function of credibility assignments in conversational exchange and (2) how a virtuous listener should respond to the potential threat of a prejudicial stereotype affecting her credibility assignments.
Macrophage Migration Inhibitory Factor as a Novel Biomarker of Portopulmonary Hypertension
Authors: DuBrock Hilary M. , Rodriguez‐Lopez Josanna M. , LeVarge Barbara L. , Curry Michael P. , VanderLaan Paul A. , Zsengeller Zsuzsanna K. , Pernicone Elizabeth , Preston Ioana R. , Yu Paul B. , Nikolic Ivana , Xu Dihua , Thadhani Ravi I. , Channick Richard N. , Karumanchi S. Ananth 
Published: July 2016

Portopulmonary hypertension (POPH) is a poorly understood complication of liver disease associated with significant morbidity and mortality. We sought to identify novel biomarkers of POPH disease presence and severity. We performed a prospective, multicenter, case‐control study involving patients with liver disease undergoing right heart catheterization. POPH cases were defined as a mean pulmonary arterial pressure (mPAP) ≥25 mmHg and pulmonary vascular resistance (PVR) >240 dynes·s·cm−5. Plasma samples were collected from the systemic and pulmonary circulation, and antibody microarray was used to identify biomarkers. Characterization and validation of a candidate cytokine, macrophage migration inhibitory factor (MIF), was performed using enzyme‐linked immunosorbent assay. Continuous variables were compared using a Mann‐Whitney U test and correlated with disease severity using Spearman correlation. MIF levels were elevated in both the systemic and pulmonary circulation in patients with POPH compared with controls (median MIF level [interquartile range] in systemic circulation: 46.68 ng/mL [32.31–76.04] vs. 31.19 ng/mL [26.92–42.17], P = 0.009; in pulmonary circulation: 49.59 ng/mL [35.90–108.80] vs. 37.78 [21.78–45.53], P = 0.002). In patients with POPH, MIF levels were positively correlated with PVR (r = 0.58, P = 0.006) and inversely correlated with cardiac output (r = −0.57, P = 0.007). MIF >60 ng/mL or tricuspid regurgitation gradient >50 mmHg had a 92% sensitivity and specificity for the diagnosis of POPH, with a positive predictive value of 86% and a negative predictive value of 96%. MIF is a promising novel biomarker of POPH disease presence and severity in patients with liver disease and portal hypertension.
Trade-off among different anti-herbivore defence strategies along an altitudinal gradient
Authors: Dostálek Tomáš , Rokaya Maan Bahadur , Maršík Petr , Rezek Jan , Skuhrovec Jiří , Pavela Roman , Münzbergová Zuzana 
Published: July 2016

AbstractThe type and intensity of plant–herbivore interactions are likely to be altered under climate change as a consequence of differential dispersal rates of plants and their herbivores. Here, we studied variation in herbivore damage on Salvia nubicola in the field and compared its growth and defence strategies against herbivores in controlled conditions using seeds from populations along a broad altitudinal gradient. Our work is one of the first studies to simultaneously measure complex intraspecific variation in plant growth, direct and indirect defences as well as plant tolerance (ability to regrow) as a consequence of herbivore attack simulated by clipping. In the field, we found that plants experienced higher herbivore pressure in lower altitudes. In the greenhouse, plants grown from seeds collected in lower-altitude populations grew better and produced a higher content of phenolic compounds (direct defence) and volatile organic compounds (indirect defence) in response to simulated herbivory. However, there were no differences in tolerance and effect of S. nubicola extracts on the model generalist herbivore Spodoptera littoralis (direct defence) along the altitudinal gradient. Although we found that S. nubicola developed a range of defence strategies, the strategies do not seem to be used simultaneously in all populations even though most of them are correlated with altitudinal gradient. Our finding is in agreement with the current knowledge that co-expression of multiple defences might be costly for a plant, since investment in defensive traits is assumed to reduce the resource availability for growth and reproduction. Our study thus shows the importance of simultaneous study of different defence strategies since understanding these trade-offs could be necessary for detecting the mechanisms by which plants are able to cope with future climate change.
A subpopulation model to analyze heterogeneous cell differentiation dynamics
Authors: Chan Yat Hin , Intosalmi Jukka , Rautio Sini , Lähdesmäki Harri 
Published: July 2016

Abstract
Motivation: Cell differentiation is steered by extracellular signals that activate a cell type specific transcriptional program. Molecular mechanisms that drive the differentiation can be analyzed by combining mathematical modeling with population average data. For standard mathematical models, the population average data is informative only if the measurements come from a homogeneous cell culture. In practice, however, the differentiation efficiencies are always imperfect. Consequently, cell cultures are inherently mixtures of several cell types, which have different molecular mechanisms and exhibit quantitatively different dynamics. There is an urgent need for data-driven mathematical modeling approaches that can detect possible heterogeneity and, further, recover the molecular mechanisms from heterogeneous data.
Results: We develop a novel method that models a heterogeneous population using homogeneous subpopulations that evolve in parallel. Different subpopulations can represent different cell types and each subpopulation can have cell type specific molecular mechanisms. We present statistical methodology that can be used to quantify the effect of heterogeneity and to infer the subpopulation specific molecular interactions. After a proof of principle study with simulated data, we apply our methodology to analyze the differentiation of human Th17 cells using time-course RNA sequencing data. We construct putative molecular networks driving the T cell activation and Th17 differentiation and allow the cell populations to be split into two subpopulations in the case of heterogeneous samples. Our analysis shows that the heterogeneity indeed has a statistically significant effect on observed dynamics and, furthermore, our statistical methodology can infer both the subpopulation specific molecular mechanisms and the effect of heterogeneity.
Availability and Implementation: An implementation of the method is available at http://research.ics.aalto.fi/csb/software/subpop/ .
Contact: jukka.intosalmi@aalto.fi or harri.lahdesmaki@aalto.fi
Supplementary information: Supplementary data are available at Bioinformatics online.
BioNetGen 2.2: advances in rule-based modeling
Authors: Harris Leonard A. , Hogg Justin S. , Tapia José-Juan , Sekar John A. P. , Gupta Sanjana , Korsunsky Ilya , Arora Arshi , Barua Dipak , Sheehan Robert P. , Faeder James R. 
Published: July 2016

Abstract
Summary : BioNetGen is an open-source software package for rule-based modeling of complex biochemical systems. Version 2.2 of the software introduces numerous new features for both model specification and simulation. Here, we report on these additions, discussing how they facilitate the construction, simulation and analysis of larger and more complex models than previously possible.
Availability and Implementation : Stable BioNetGen releases (Linux, Mac OS/X and Windows), with documentation, are available at http://bionetgen.org . Source code is available at http://github.com/RuleWorld/bionetgen .
Contact: bionetgen.help@gmail.com
Supplementary information: Supplementary data are available at Bioinformatics online.
MIMEAnTo: profiling functional RNA in mutational interference mapping experiments
Authors: Smith Maureen R. , Smyth Redmond P. , Marquet Roland , von Kleist Max 
Published: July 2016

Abstract
Summary: The mutational interference mapping experiment (MIME) is a powerful method that, coupled to a bioinformatics analysis pipeline, allows the identification of domains and structures in RNA that are important for its function. In MIME, target RNAs are randomly mutated, selected by function, physically separated and sequenced using next-generation sequencing (NGS). Quantitative effects of each mutation at each position in the RNA can be recovered with statistical certainty using the herein developed user-friendly, cross-platform software MIMEAnTo ( MIME An alysis To ol).
Availability and implementation: MIMEAnTo is implemented in C ++ using the boost library as well as Qt for the graphical user interface and is distributed under GPL ( http://www.gnu.org/licences/gpl ). The libraries are statically linked in a stand alone executable and are not required on the system. The plots are generated with gnuplot. Gnuplot-iostream ( https://github.com/dstahlke/gnuplot-iostream ) serves as gnuplot interface. Standalone executables including examples and source code can be downloaded from https://github.com/maureensmith/MIMEAnTo .
Contacts: msmith@zedat.fu-berlin.de or vkleist@zedat.fu-berlin.de
Supplementary information: Supplementary data are available at Bioinformatics online.
Phenotype, proliferation and apoptosis of B lymphocytes in hemodialysis patients treated with recombinant human erythropoietin
Authors: Jasiulewicz Aleksandra , Lisowska Katarzyna A. , Dębska-Ślizień Alicja , Witkowski Jacek M. 
Published: July 2016

AbstractOne of the major causes of disorders of the immune response in patients undergoing hemodialysis (HD) is weaker activity of their helper T lymphocytes (T h cells), mainly reduced proliferative capacity associated with decreased expression of key surface antigens. Since cooperation between T h and B lymphocytes is essential for B cell function, changes in T h cell phenotype and ability to proliferate or produce cytokines could directly translate into an impaired humoral response. Therefore, we investigated the T cell-dependent activity of B cells in HD patients focusing mainly on their proliferative kinetics, susceptibility to apoptosis and the ability to produce antibodies. Since our previous studies have shown the beneficial effects of recombinant human erythropoietin (rhEPO) on T lymphocytes, we also investigated the in vivo and in vitro influence of rhEPO on B cells. Our results show that B lymphocytes of HD patients, especially of those who are not treated with rhEPO, have reduced proliferative capacity in vitro , reflected in low number of cell divisions, decreased percentage of proliferating cells and an increased susceptibility to apoptosis. They are also characterized by impaired ability to produce immunoglobulins. We have found no significant changes in the expression of key antigens of B lymphocytes with the exception of IL-10R. Furthermore, we demonstrated a time- and health status-dependent impact of rhEPO on patient’s B cells. Our results show possible mechanisms responsible for the deficiency of humoral responses in HD patients which, at least partially, can be modulated through the supplementation with rhEPO.
Online cancer communities as informatics intervention for social support: conceptualization, characterization, and impact
Authors: Zhang Shaodian , Bantum Erin O’Carroll , Owen Jason , Bakken Suzanne , Elhadad Noémie 
Published: July 2016

Objectives: The Internet and social media are revolutionizing how social support is exchanged and perceived, making online health communities (OHCs) one of the most exciting research areas in health informatics. This paper aims to provide a framework for organizing research of OHCs and help identify questions to explore for future informatics research. Based on the framework, we conceptualize OHCs from a social support standpoint and identify variables of interest in characterizing community members. For the sake of this tutorial, we focus our review on online cancer communities.Target audience: The primary target audience is informaticists interested in understanding ways to characterize OHCs, their members, and the impact of participation, and in creating tools to facilitate outcome research of OHCs. OHC designers and moderators are also among the target audience for this tutorial.Scope: The tutorial provides an informatics point of view of online cancer communities, with social support as their leading element. We conceptualize OHCs according to 3 major variables: type of support, source of support, and setting in which the support is exchanged. We summarize current research and synthesize the findings for 2 primary research questions on online cancer communities: (1) the impact of using online social support on an individual's health, and (2) the characteristics of the community, its members, and their interactions. We discuss ways in which future research in informatics in social support and OHCs can ultimately benefit patients.
Online patient websites for electronic health record access among vulnerable populations: portals to nowhere?
Authors: Tieu Lina , Schillinger Dean , Sarkar Urmimala , Hoskote Mekhala , Hahn Kenneth J , Ratanawongsa Neda , Ralston James D , Lyles Courtney R 
Published: July 2016

Objective: With the rapid rise in the adoption of patient portals, many patients are gaining access to their personal health information online for the first time. The objective of this study was to examine specific usability barriers to patient portal engagement among a diverse group of patients and caregivers.
Materials and Methods: We conducted interviews using performance testing and think-aloud methods with 23 patients and 2 caregivers as they first attempted to use features of a newly launched patient portal.
Results: In navigating the portal, participants experienced basic computer barriers (eg, difficulty using a mouse), routine computer barriers (eg, mistyping, navigation issues), reading/writing barriers, and medical content barriers. Compared to participants with adequate health literacy, participants with limited health literacy required 2 additional minutes to complete each task and were more likely to experience each type of navigational barrier. They also experienced more inaccuracies in interpreting a test result and finding a treatment plan within an after-visit summary.
Discussion: When using a patient portal for the first time, participants with limited health literacy completed fewer tasks unassisted, had a higher prevalence of encountering barriers, took longer to complete tasks, and had more problems accurately interpreting medical information.
Conclusion: Our findings suggest a strong need for tailored and accessible training and support to assist all vulnerable patients and/or caregivers with portal registration and use. Measuring the health literacy of a patient population might serve as a strong proxy for identifying patients who need the most support in using health technologies.
Feasibility of Posterior Cervical Foraminotomy in Cervical Foraminal Stenosis
Authors: Gu Bon Sub , Park Jin Hoon , Seong Han Yu , Jung Sang Ku , Roh Sung Woo 
Published: July 2016

Study Design.
A retrospective cohort study.

Objective.
The aim of this study was to compare the feasibility of posterior cervical laminoforaminotomy (PCF) for V- or parallel-shaped foraminal stenosis (FS).

Summary of Background Data.
During PCF, the need for extensive facet resection would depend on the extent of any pathology. When resection is extensive, the possibilities of instability and incomplete decompression should be considered.

Methods.
From March 2004 to March 2015, we enrolled 36 patients following single-level PCF procedures for FS. We classified patients by foraminal shape on preoperative computed tomography (CT) scan into V-shaped and parallel-shaped groups. We then compared arm and neck pain using a numeric rating scale (NRS) and clinical outcomes using Odom criteria. Radiological evaluation included dynamic X-rays for instability and CT scans for facet resection.

Result.
We enrolled 16 and 20 patients in the V-shape and parallel-shape groups, respectively. By Odom criteria, no patient was graded fair or poor in the V group, but five patients were graded as fair and one patient as poor in the parallel group. Continued postoperative arm pain at 1 year, which was related to incomplete decompression, was significantly higher in parallel group. Only one patient complained of postoperative neck pain with an NRS >5, and another five patients sustained radiculopathy with an NRS >5. Among five patients who complained sustained radiculopathy, one patient required revision surgery for incomplete decompression. The amount of facet removal was not different significantly between groups, and no patient had postoperative instability.

Conclusion.
Although PCF seems to be a good surgical option for V-shaped FS, we experienced worse outcomes for patients with parallel-shaped FS. We recommend that ACDF or more aggressive posterior foraminotomy be performed with fusion when presented with parallel neuroforaminal compression.

Level of Evidence: 4