bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bayesian Model Selection Maps for group studies using M/EEG data
Authors: Harris Clare D. , Rowe Elise G. , Randeniya Roshini , Garrido Marta I. 
Published: July 2018

AbstractPredictive coding postulates that we make (top-down) predictions about the world and that we continuously compare incoming (bottom-up) sensory information with these predictions, in order to update our models and perception so as to better reflect reality. That is, our so-called ‘Bayesian brains’ continuously create and update generative models of the world, inferring (hidden) causes from (sensory) consequences. Neuroimaging datasets enable the detailed investigation of such modelling and updating processes, and these datasets can themselves be analysed with Bayesian approaches. These offer methodological advantages over classical statistics. Specifically, any number of models can be compared, the models need not be nested, and the ‘null model’ can be accepted (rather than only failing to be rejected as in frequentist inference). This methodological paper explains how to construct posterior probability maps (PPMs) for Bayesian Model Selection (BMS) at the group level using electroencephalography (EEG) or magnetoencephalography (MEG) data. The method has only recently been used for EEG data, after originally being developed and applied in the context of functional magnetic resonance imaging (fMRI) analysis. Here, we describe how this method can be adapted for EEG using the Statistical Parametric Mapping (SPM) software package for MATLAB. The method enables the comparison of an arbitrary number of hypotheses (or explanations for observed responses), at each and every voxel in the brain (source level) and/or in the scalp-time volume (scalp level), both within participants and at the group level. The method is illustrated here using mismatch negativity (MMN) data from a group of participants performing an audio-spatial oddball attention task. All data and code are provided in keeping with the Open Science movement. In so doing, we hope to enable others in the field of M/EEG to implement our methods so as to address their own questions of interest.
White matter connectivity disruptions in the pre-clinical continuum of psychosis: A connectome study
Authors: Oestreich Lena K. L. , Randeniya Roshini , Garrido Marta I. 
Published: July 2018

AbstractBackgroundWidespread white matter disruptions in schizophrenia have been commonly reported, but it remains unanswered whether these abnormalities are associated with schizophrenia specifically or whether they range along a psychotic continuum into the healthy population. Investigating the extent of white matter connectivity disruptions specific to psychotic-like experiences in healthy individuals is insofar important as it is a necessary first step towards the development of prodromal psychosis biomarkers.MethodsHigh resolution, multi-shell diffusion-weighted magnetic resonance images were acquired from 89 healthy individuals. Whole-brain white matter fiber tracking was performed to quantify the strength of white matter connections. Network-based statistics were applied to white matter connections in a regression model in order to test for a linear relationship between streamline count and psychotic-like experiences.ResultsA significant subnetwork was identified whereby streamline count declined with increasing quantity of psychotic-like experiences. This network of significant connectivity reductions affected all cortical lobes, subcortical structures and the cerebellum.ConclusionA widespread network of linearly declining connectivity strength with increasing number of psychotic-like experiences was identified in healthy individuals. This finding is in line with white matter connectivity reductions reported from early to chronic stages of schizophrenia. We suggest that these white matter changes might be a potential biomarker for the identification of individuals at high risk for transitioning to psychosis.
Psychosocial stress and central adiposity: A Brazilian study with users of the public health system
Authors: Freitas Flávia Vitorino , Barbosa Wagner Miranda , Azevedo Silva Laíz Aparecida , de Oliveira Garozi Marianna Junger , de Assis Pinheiro Júlia , Borçoi Aline Ribeiro , Conti Catarine Lima , Arpini Juliana Krüger , de Paula Heberth , de Oliveira Mayara Mota , Archanjo Anderson Barros , Silva de Freitas Érika Aparecida , de Oliveira Daniela Rodrigues , Borloti Elizeu Batista , Louro Iuri Drumond , Alvares-da-Silva Adriana Madeira 
Published: July 2018

AbstractObjectiveTo assess the association between indicators of psychosocial stress and central adiposity in adult users of the Unified Health System (SUS) from Southeast of Brazil.MethodsThis cross-sectional study was conducted with 384 adults (20 to 59 years old) from the city of Alegre, Southeastern Brazil. The simple random sample represented the population using the public health system of the municipality. The prevalence of obesity was based on the Body Mass Index, and central adiposity (dependent variable) was measured by waist circumference in centimeters. The independent variables were the following indicators of psychosocial stress: food and nutrition insecurity (yes/no), serum cortisol (μg/dL), symptoms suggestive of depression using the Beck Depression Inventory-II ≥ 17 (yes/no), and altered blood pressure ≥ 130/85 mmHg (yes/no). Univariate linear regression was performed between central adiposity and each stress indicator, and later the models were adjusted for socioeconomic, health, and lifestyle variables. All analyses were stratified by rural and urban location.ResultsThe prevalence of weight excess was 68.3%, and 71.5% of individuals presented an increased risk for metabolic complications related to central adiposity. Mean waist circumference scores for the rural and urban population were 89.3 ± 12.7 cm and 92.9 ± 14.7 cm, respectively (p = 0.012). Indicators of stress that were associated with central adiposity were: cortisol in the rural population and altered blood pressure in the urban population. This occurred both in the raw analysis and in the models adjusted for confounding factors.ConclusionThe associations between stress and adiposity were different between rural (cortisol - inverse association) and urban (altered blood pressure) lifestyles, confirming the influence of local and psychosocial subsistence on the modulation of stress and on how individuals react or restrain stressors. Stress reduction strategies can be useful in public health programs designed to prevent or treat obesity.
Retention of adults from fishing communities in an HIV vaccine preparedness study in Masaka, Uganda
Authors: Bahemuka Ubaldo , Abaasa Andrew , Ruzagira Eugene , Lindan Christina , Price Matt A , Kamali Anatoli , Fast Pat 
Published: July 2018

AbstractIntroductionPeople living in fishing communities around Lake Victoria may be suitable for enrolment in HIV prevention trials because of high HIV incidence. We assessed the ability to recruit and retain individuals from fishing communities into an HIV vaccine preparedness cohort study in Masaka, Uganda.MethodsHIV high risk, sero-negative adults (18-49 years) were identified from four fishing villages bordering Lake Victoria through door-to-door HIV counselling and testing (HCT). Interested persons were referred for: screening, enrolment, and quarterly follow-up visits at a study clinic located approximately 40 kilometres away. Repeat HCT, HIV risk assessment, and evaluation and treatment for sexually transmitted infections were provided. Rates of and factors associated with study dropout were assessed using Poisson regression models.ResultsA total of 940 participants were screened between January 2012 and February 2015, of whom 654 were considered for the analysis. Over a two-year follow-up period, 197 (30.1%) participants dropped out of the study over 778.9 person-years, a dropout rate of 25.3 / 100 person-years. Dropout was associated with being female (aRR =1.56, 95% confidence interval [CI] 1.12-2.18), age, being 18-24 years (aRR=1.64; 95% CI 1.03-2.60), 25-34 years (aRR=1.63; 95% CI 1.04-2.55); having no education (aRR=2.02; 95% CI: 1.23-3.31); living in the community for less than one year (aRR=2.22; 95% CI: 1.46-3.38) or 1-5 years (aRR=1.68; 95% CI: 1.16-2.45) and occupation.ConclusionsIt is possible to recruit and retain individuals from fishing communities, however, intensified participant tracing may be necessary in a vaccine trial to keep in follow up female, young, less educated, those in mobile occupations and new residents.
Drosophila ZDHHC8 palmitoylates scribble and Ras64B and controls growth and viability
Authors: Strassburger Katrin , Kang Evangeline , Teleman Aurelio A. 
Published: July 2018

SummaryPalmitoylation is an important posttranslational modification regulating diverse cellular functions. Consequently, aberrant palmitoylation can lead to diseases such as neuronal disorders or cancer. In humans there are roughly one hundred times more palmitoylated proteins than enzymes catalyzing palmitoylation (palmitoyltransferases). Therefore, it is an important challenge to establish the links between palmitoyltransferases and their targets. From publicly available data, we find that expression of human ZDHHC8 correlates significantly with cancer survival. To elucidate the organismal function of ZDHHC8, we study the Drosophila ortholog of hZDHHC8, CG34449/dZDHHC8. Knockdown of dZDHHC8 causes tissue overgrowth while dZDHHC8 mutants are larval lethal. We provide a list of 159 palmitoylated proteins in Drosophila and present data suggesting that scribble and Ras64B are targets of dZDHHC8.
Modulation of ADARs mRNA expression in congenital heart defect patients
Authors: Altaf Faiza , Vesely Cornelia , Sheikh Abdul Malik , Munir Rubab , Shah Syed Tahir Abbass , Tariq Aamira 
Published: July 2018

AbstractAdenosine (A) to inosine (I) RNA editing, is a hydrolytic deamination reaction catalyzed by adenosine deaminase (ADAR) acting on RNA enzymes. RNA editing is a molecular process that involves the post-transcriptional modification of RNA transcripts. Interestingly, few studies have been carried out to determine the role of RNA editing in vascular disease. The current study found that in blood samples positive for congenital heart disease (CHD) ADAR1 and ADAR2 expression change at RNA level was opposite to each other. That is, an increase of ADAR1 mRNA was noticed in human CHD cases, whereas ADAR2 mRNA was vastly down-regulated. The increase in ADAR1 may be explained by the stress induced by CHD. The dramatic decrease in ADAR2 in CHD cases was unexpected and prompted further investigation into its effects on the heart. Therefore we performed expression analysis on a microarray data encompassing ischemic and non-Ischemic cardiomyopathy patient myocardial tissues. A strong down-regulation of ADAR2 was observed in both ischemic and especially non-ischemic cases. However, ADAR1 showed a mild increase in the case of non-ischemic myocardial tissues. To further explore the role of ADAR2 with respect to heart physiology. We selected a protein coding gene filamin B (FLNB). FLNB is known to play an important role in heart development. Although there were no observable changes in its expression, the editing levels of FLNB dropped dramatically in ADAR2-/- mice. We also performed miRNA profiling from ADAR2 -/- mice heart tissue revealed a decrease in expression of miRNAs. It is established that aberrant expression of these miRNAs is often associated with cardiac defects. This study proposes that sufficient amounts of ADAR2 might play a vital role in preventing cardiovascular defects.
Survey of bacteria associated with western corn rootworm life stages reveals no difference between insects reared in different soils
Authors: Ludwick Dalton C. , Ericsson Aaron C. , Meihls Lisa N. , Gregory Michelle L.J. , Finke Deborah L. , Coudron Thomas A. , Hibbard Bruce E. , Shelby Kent S. 
Published: July 2018

AbstractWestern corn rootworm (Diabrotica virgifera virgifera LeConte) is a serious pest of maize (Zea mays L.) in North America and parts of Europe. With most of its life cycle spent in the soil feeding on maize root tissues, this insect is likely to encounter and interact with a wide range of soil and rhizosphere microbes. Our knowledge of the role of microbes in pest management and plant health remains incomplete. An important component of an effective pest management strategy is to know which microorganisms are present that could play a role in life history or management. For this study, insects were reared in soils from different locations. Insects were sampled at each life stage to determine the possible core bacteriome. Additionally, soil was sampled at each life stage and resulting bacteria were identified to determine the contribution of soil to the rootworm bacteriome, if any. We analyzed the V4 hypervariable region of bacterial 16S rRNA genes with Illumina MiSeq to survey the different species of bacteria associated with the insects and the soils. The bacterial community associated with insects was significantly different from that in the soil. Some differences appear to exist between insects from non-diapausing and diapausing colonies while no significant differences in community composition existed between the insects reared on different soils. Despite differences in the bacteria present in immature stages and in male and female adults, there is a possible core bacteriome of approximately 16 operational taxonomic units (i.e., present across all life stages). This research may give insights into how resistance to Bt develops, improved nutrition in artificial rearing systems, and new management strategies.
A three year follow-up study of gadolinium enhanced and non-enhanced regions in multiple sclerosis lesions using a multi-compartment T2 relaxometry model
Authors: Chatterjee Sudhanya , Commowick Olivier , Afacan Onur , Combes Benoit , Warfield Simon K. , Barillot Christian 
Published: July 2018

AbstractDemyelination, axonal damage and inflammation are critical indicators of the onset and progress of neurodegenerative diseases such as multiple sclerosis (MS) in patients. Due to physical limitations of imaging such as acquisition time and imaging resolution, a voxel in a MR image is heterogeneous in terms of tissue microstructure such as myelin, axons, intra and extra cellular fluids and free water. We present a multi-compartment tissue model which estimates the water fraction (WF) of tissues with short, medium and high T2 relaxation times in a T2 relaxometry MRI voxel. The proposed method is validated on test-retest data of healthy controls. This model was then used to study longitudinal trends of the tissue microstructures for two sub-regions of the lesions: gadolinium enhanced (E+) and non-enhanced (L–) regions of MS lesions in 10 MS patients over a period of three years. The water fraction values in E+ and L– regions were found to be significantly different (p < 0.05) over the period of first three months. The results of this study also showed that the estimates of the proposed T2 relaxometry model on brain tissue microstructures have potential to distinguish between regions undergoing active blood brain barrier breakdown from the other regions of the lesion.
Integrative data analysis predicts YY1 as a Cis-regulator in the 3D Cell Culture Models of MCF10A at the Stiffness Level of High Mammographic Density
Authors: Cheng Qingsu , Khoshdeli Mina , Zang Chongzhi , Parvin Bahram 
Published: July 2018

AbstractPrevious studies have shown that in 3D cell culture models of human mammary cells (HMEC) (i) colony organizations are heterogeneous, and (ii) ERBB2 is overexpressed in MCF10A when the stiffness of the microenvironment is increased to that of high mammographic density (MD). The goal of the current study is to identify transcription factors that regulate processes associated with the increased stiffness of the microenvironment. Two HMEC premalignant lines of MCF7 and 184A1 are cultured in 3D, colonies are imaged using confocal microscopy, and colony organizations and heterogeneity are quantified as a function of the stiffness of the microenvironment. In parallel and surrogate assays, colony organizations are profiled by transcriptomics. Transcriptome data are enriched by correlative analysis with the computed morphometric indices, from 3D culture, and a subset of transcriptome data is selected. This subset is then processed with Model-based Analysis of Regulation of Gene Expression (MARGE) and publicly available ChIP-seq data to predict regulatory transcription factors. The integrative analysis indicated that YY1 regulates ERBB2 in the 3D cell culture of MCF10A when the stiffness of the microenvironment is increased to that of high MD. Subsequent experimental validation confirmed that YY1 is only expressed at the high stiffness value of the microenvironment concomitant with the overexpression of ERBB2 in MCF10A. Furthermore, using ERBB2 positive SKBR3 cell line, co-expression of YY1 and ERBB2 is absent, which indicates that YY1 regulates tumorigenicity through multiple pathways.Author’s summaryMCF10A is a premalignant immortalized human mammary cell that has been isolated from a patient with fibrocystic and lost several barriers toward transformation. In an earlier study, we showed that ERBB2 is upregulated in 3D cultures of MCF10A when the stiffness of the microenvironment is increased to that of high mammographic density. Here, we leverage publicly available ChIP-seq data to predict and validate the cis-regulator of ERBB2. Our integrated experimental and computation protocol provides a pathway for elucidating regulators that can potentially be targeted for intervention.
BCG overexpressing an endogenous STING agonist provides enhanced protection against pulmonary tuberculosis
Authors: Dey Ruchi Jain , Dey Bappaditya , Singh Alok Kumar , Praharaj Monali , Bishai William 
Published: July 2018

ABSTRACTStimulator of interferon genes (STING) has emerged as a key signaling receptor that induces proinflammatory cytokines, and small molecule STING agonists are being developed as anticancer and antiviral agents. Here we report a strategy of delivering a STING agonist from within live BCG. We generated a recombinant BCG (BCG-disA-OE) that overexpresses the endogenous mycobacterial diadenylate cyclase gene and releases high levels of the STING agonist c-di-AMP. In macrophages BCG-disA-OE elicited statistically significantly stronger TNF-α, IL-6, IL-1β, IRF3, and IFN-β levels than BCG-WT. In a 24-week guinea pig vaccination-Mtb challenge model, BCG-disA-OE reduced lung weights, pathology scores, and Mtb CFU counts in lungs by 28% (p<0.05), 34%, and 2.0 log10 CFU units (p < 0.5) compared with BCG-WT, respectively. Overproduction of the STING agonist c-di-AMP significantly enhanced the protective efficacy of BCG against pulmonary and extrapulmonary tuberculosis. Our findings support the development of BCG-vectored STING agonists as a TB vaccine strategy.
A novel truncating variant of GLI2 associated with Culler-Jones syndrome impairs Hedgehog signalling
Authors: Valenza Fabiola , Cittaro Davide , Stupka Elia , Biancolini Donatella , Patricelli Maria Grazia , Bonanomi Dario , Lazarević Dejan 
Published: July 2018

AbstractBackgroundGLI2 encodes for a transcription factor that controls the expression of several genes in the Hedgehog pathway. Mutations in GLI2 have been described as causative of a spectrum of clinical phenotypes, notably holoprosencephaly, hypopituitarism and postaxial polydactyl. Methods: In order to identify causative genetic variant, we performed exome sequencing of a trio from an Italian family with multiple affected individuals presenting clinical phenotypes in the Culler-Jones syndrome spectrum. We performed a series of assays, both in vitro and in ovo (Chicken model) to test the functional properties of GLI2 mutation.ResultsHere we report a novel deletion c.3493delC (p.P1167LfsX52) in the C-terminal activation domain of GLI2, and cell-based functional assays confirmed the pathogenicity of the identified variant and revealed a dominant-negative effect of mutant GLI2 on Hedgehog signalling.ConclusionOur results highlight the variable clinical manifestation of GLI2 mutations and emphasize the value of functional characterisation of novel gene variants to assist genetic counselling and diagnosis.
A Reproducible Neurobiology of Depressive Rumination
Authors: Pisner D.A. , Shumake J. , Beevers C.G. , Schnyer D.M. 
Published: July 2018

AbstractDepressive Rumination (DR), which involves a repetitive focus on one’s distress, has been linked to alterations in functional connectivity of the ‘triple-network’, consisting of Default-Mode, Salience, and Executive Control networks. A structural basis for these functional alterations that can dually explain DR’s persistence as a stable trait remains unexplored, however. Using diffusion and functional Magnetic Resonance Imaging, we investigated multimodal relationships between DR severity, white-matter microstructure, and resting-state functional connectivity in depressed adults, and then directly replicated our results in a phenotypically-matched, independent sample (total N = 78). Among the fully-replicated findings, DR severity was associated with: (a) global microstructure of the right Superior Longitudinal Fasciculus and local microstructure of distributed primary-fiber and crossing-fiber white-matter; (b) an imbalance of functional connectivity segregation and integration of the triple-network; and (c) ‘multi-layer’ associations linking these microstructural and functional connectivity biomarkers to one another. Taken together, the results provide reproducible evidence for a multi-layer, microstructural-functional network model of rumination in the depressed brain.
Patenting or not? The dilemma of academic spin-off founders
Authors: Ferri Salvatore , Fiorentino Raffaele , Parmentola Adele , Sapio Alessandro 
Published: July 2018

PurposeThe purpose of this paper is to analyze the impact of patenting on the performance of academic spin-off firms (ASOs) in the post-creation stage. Specifically, our study analyses how the combination of knowledge transfer mechanisms by ASOs and patents can foster ASOs’ early growth performance.Design/methodology/approachThe authors explored the relations between patenting processes and spin-off performance through econometric methods applied to a broad sample of Italian ASOs. The research adopts a deductive approach, and the hypotheses are tested using panel data models by considering the sales growth rate as the dependent variable regressed over measures of patenting activity and quality and assuming that firm-specific unobservable drivers of growth are captured by random effects.FindingsThe empirical analysis shows that the incorporation of knowledge transferred by the parent university and academic founders through patents affects the performance of ASOs. Specifically, the authors find that the number of patents is a positive driver of ASOs’ performance, whilst patent age does not have a significant impact on growth. Moreover, spin-offs with a larger endowment of patents obtained before foundation, surprisingly, grow less on average.Practical implicationsThe findings have implications for ASO founders by suggesting that patenting processes reap benefits. However, in the trade-off of external knowledge access vs internal knowledge protection, it may be better to begin patenting after the foundation of ASOs.Originality/valueThe authors enrich the on-going debate about the connections between knowledge transfer and organizational performance. This paper combines the concepts of patents and ASOs by providing evidence on the role of patenting processes as a transfer mechanism of explicit knowledge in ASOs. Furthermore, the authors contribute to the literature on costs and benefits of patents by hinting at unexpected findings.