bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term cardiovascular re-programming by short-term perinatal exposure to nicotine‘s main metabolite cotinine
Authors: Bastianini Stefano , Martire Viviana Lo , Silvani Alessandro , Zoccoli Giovanna , Berteotti Chiara , Lagercrantz Hugo , Arner Anders , Cohen Gary 
Published: September 2017

AbstractBackgroundCotinine - a nicotine by-product and biomarker of passive perinatal tobacco smoke exposure - is historically considered to lack significant health effects. We challenged this notion and sought “proof-of-concept” evidence of the adverse developmental potential of exposure to this substance at real-life levels.MethodsPregnant C57 mice drank nicotine or cotinine-laced water for 6wks from conception (NPRE= 2% saccharin+100μg nicotine/ml; CPRE= 2% saccharin + 10μg cotinine/ml) or for 3wks after birth (CPOST= 2% saccharin + 30μg cotinine/ml). Controls drank 2% saccharin (CTRL). At 17±1weeks male pups (CTRL n=6; CPOSTn=6; CPREn=8; NPREn=9) were instrumented for EEG and blood pressure (BP) telemetry. We evaluated (i) cardiovascular control during sleep (at rest / during stress); (ii) arterial reactivity ex vivo; (iii) expression of genes involved in arterial constriction/dilation.ResultsBlood cotinine levels (ELISA) recapitulated passive smoker mothers-infants. Pups exposed only to cotinine exhibited (i) mild bradycardia - hypotension at rest (p<0.001); (ii) attenuated (CPRE, p<0.0001) or reverse (CPOST; p<0.0001) BP reactivity to asphyxia; (iii) pronounced adrenergic hypo-contractility (p<0.0003), low Protein Kinase C (p<0.001) and elevated adrenergic receptor mRNA (p<0.05) (all drug-treated arteries). NPREpups also exhibited endothelium-mediated dysfunction.ConclusionsCotinine has subtle, enduring developmental consequences. Some cardiovascular effects of nicotine can plausibly arise via conversion to cotinine. Low-level exposure to this metabolite may pose unrecognized perinatal risks. Adults must avoid inadvertently exposing a fetus or infant to cotinine as well as nicotine.
Genetic validation of bipolar disorder identified by automated phenotyping using electronic health records
Authors: Chen Chia-Yen , Lee Phil H. , Castro Victor M. , Minnier Jessica , Charney Alexander W. , Stahl Eli A. , Ruderfer Douglas M. , Murphy Shawn N. , Gainer Vivian , Cai Tianxi , Jones Ian , Pato Carlos , Pato Michele , Landén Mikael , Sklar Pamela , Perlis Roy H. , Smoller Jordan W. 
Published: September 2017

AbstractBipolar disorder (BD) is a heritable mood disorder characterized by episodes of mania and depression. Although genomewide association studies (GWAS) have successfully identified genetic loci contributing to BD risk, sample size has become a rate-limiting obstacle to genetic discovery. Electronic health records (EHRs) represent a vast but relatively untapped resource for high-throughput phenotyping. As part of the International Cohort Collection for Bipolar Disorder (ICCBD), we previously validated automated EHR-based phenotyping algorithms for BD against in-person diagnostic interviews (Castro et al. 2015). Here, we establish the genetic validity of these phenotypes by determining their genetic correlation with traditionally-ascertained samples. Case and control algorithms were derived from structured and narrative text in the Partners Healthcare system comprising more than 4.6 million patients over 20 years. Genomewide genotype data for 3,330 BD cases and 3,952 controls of European ancestry were used to estimate SNP-based heritability (h2g) and genetic correlation(rg) between EHR-based phenotype definitions and traditionally-ascertained BD cases in GWAS by the ICCBD and Psychiatric Genomics Consortium (PGC) using LD score regression. We evaluated BD cases identified using 4 EHR-based algorithms: an NLP-based algorithm (95-NLP) and 3 rule-based algorithms using codified EHR with decreasing levels of stringency - “coded-strict”, “coded-broad”, and “coded-broad based on a single clinical encounter” (coded-broad-SV). The analytic sample comprised 862 95-NLP, 1,968 coded-strict, 2,581 coded-broad, 408 coded-broad-SV BD cases, and 3,952 controls. The estimated h2gwere 0.24 (p=0.015), 0.09 (p=0.064), 0.13 (p=0.003), 0.00 (p=0.591) for 95-NLP, coded-strict, coded-broad and coded-broad-SV BD, respectively. The h2gfor all EHR-based cases combined except coded-broad-SV (excluded due to 0 h2g) was 0.12 (p=0.004). These h2gwere lower or similar to the h2gobserved by the ICCBD+PGCBD (0.23, p=3.17E-80, total N=33,181). However, the rgbetween ICCBD+PGCBD and the EHR-based cases were high for 95-NLP (0.66, p=3.69x10-5), coded-strict (1.00, p=2.40x10-4), and coded-broad (0.74, p=8.11x10-7). The rgbetween EHR-based BDs ranged from 0.90 to 0.98. These results provide the first genetic validation of automated EHR-based phenotyping for BD and suggest that this approach identifies cases that are highly genetically correlated with those ascertained through conventional methods. High throughput phenotyping using the large data resources available in EHRs represents a viable method for accelerating psychiatric genetic research.
A common pattern of DNase-I footprinting throughout the human mtDNA unveils clues for a chromatin-like organization
Authors: Blumberg Amit , Danko Charles G. , Kundaje Anshul , Mishmar Dan 
Published: September 2017

AbstractHuman mitochondrial DNA (mtDNA) is believed to lack chromatin and histones. Instead, it is coated solely by the transcription factor TFAM, which binds the mtDNA without sequence specificity and packs it into a bacterial-like nucleoid in a dose-dependent fashion. We asked whether mtDNA packaging is more regulated than once thought. As a first step to address this question, we analyzed mtDNA DNase-I-seq experiments in 324 different human cell types and found, for the first time, a pattern of 29 Genomic footprinting (DGF) sites throughout the mtDNA shared by ∼90% of the tested samples. Low SNP density at the DGF sites, and their conservation in mouse DNase-seq experiments, reflect strong selective constraints. Co-localization of the DGFs with known mtDNA regulatory elements and with recently-discovered transcription pausing sites, suggest a role for such DGFs in mtDNA transcription. Altered mtDNA DGF pattern in IL-3 treated CD+34 cells offer first clue to their physiological importance. Taken together, human mtDNA has a conserved and regulated protein-DNA organization, which is likely involved in regulation of mtDNA gene expression.
Structure and function of the intermembrane space domain of mammalian FoF1ATP synthase
Authors: Fischer Niels , Beilsten-Edmands Victoria , Chorev Dror S. , Hauer Florian , Jiko Chimari , Shimada Satoru , Shinzawa-Itoh Kyoko , Robinson Carol V. , Stark Holger , Gerle Christoph 
Published: September 2017

AbstractMitochondrial FoF1ATP synthase is a membrane bound molecular machine central to cellular energy conversion and cristae architecture. Recently, a novel domain has been visualized in the intermembrane space region of mammalian ATP synthase. The complete three-dimensional (3D) structure, composition and function of this domain - which we term intermembrane space domain (IMD) - are unknown. Here, we present two distinct 3D structures of monomeric bovine FoF1ATP synthase by single particle cryo-electron microscopy (cryo-EM) that differ by the presence and absence of the IMD. Comparison of both structures reveals the IMD to be a bipartite and weakly associated domain of FoF1ATP synthase. The tubular sub-domain of the IMD appears to contact the rotor-ring region, its globular sub-domain is anchored in the membrane-bending kink of the ATP synthase. However, absence of the IMD does not impact the kink in the transmembrane region ruling out a functional role in membrane bending. By combining our structural analysis with chemical cross-linking and reported biochemical, genetic and structural data we identify 6.8PL and DAPIT as the subunits forming the intermembrane space domain. We compare the present structure of the mammalian IMD in the bovine FoF1ATP synthase monomer with structures of dimeric FoF1ATP synthase from yeast and ciliate showing that the IMD is a common, but structurally divergent feature of several mitochondrial ATP synthases. On the basis of our analysis we discuss potential functions of the novel domain in rotary catalysis, oligomerization and mitochondrial permeability transition.
miRNAgFree: prediction and profiling of novel microRNAs without genome assembly
Authors: Aparicio EL , Rueda A , Fromm B. , Gómez-Martín C , Lebrón R , Oliver JL , Marchal JA , Kotsyfakis M , Hackenberg M 
Published: September 2017

AbstractThe prediction of novel miRNA genes generally requires the availability of genome sequences in order to assess important properties such as the characteristic hairpin-shaped secondary structure. However, although the sequencing costs have decreased over the last years, still many important species lack an assembled genome of certain quality. We implemented an algorithm which for the first time exploits characteristic biogenesis features like the 5’ homogeneity that can be assessed without genome sequences. We used a phylogenetically broad spectrum of well annotated animal genomes for benchmarking. We found that between 90-100% of the most expressed miRNA candidates (top quartile) corresponded to known miRNA sequences.
Multi-platform discovery of haplotype-resolved structural variation in human genomes
Authors: Chaisson Mark J.P. , Sanders Ashley D. , Zhao Xuefang , Malhotra Ankit , Porubsky David , Rausch Tobias , Gardner Eugene J. , Rodriguez Oscar , Guo Li , Collins Ryan L. , Fan Xian , Wen Jia , Handsaker Robert E. , Fairley Susan , Kronenberg Zev N. , Kong Xiangmeng , Hormozdiari Fereydoun , Lee Dillon , Wenger Aaron M. , Hastie Alex , Antaki Danny , Audano Peter , Brand Harrison , Cantsilieris Stuart , Cao Han , Cerveira Eliza , Chen Chong , Chen Xintong , Chin Chen-Shan , Chong Zechen , Chuang Nelson T. , Lambert Christine C. , Church Deanna M. , Clarke Laura , Farrell Andrew , Flores Joey , Galeev Timur , Gorkin David , Gujral Madhusudan , Guryev Victor , Heaton William Haynes , Korlach Jonas , Kumar Sushant , Kwon Jee Young , Lee Jong Eun , Lee Joyce , Lee Wan-Ping , Lee Sau Peng , Li Shantao , Marks Patrick , Viaud-Martinez Karine , Meiers Sascha , Munson Katherine M. , Navarro Fabio , Nelson Bradley J. , Nodzak Conor , Noor Amina , Kyriazopoulou-Panagiotopoulou Sofia , Pang Andy , Qiu Yunjiang , Rosanio Gabriel , Ryan Mallory , Stütz Adrian , Spierings Diana C.J. , Ward Alistair , Welch AnneMarie E. , Xiao Ming , Xu Wei , Zhang Chengsheng , Zhu Qihui , Zheng-Bradley Xiangqun , Lowy Ernesto , Yakneen Sergei , McCarroll Steven , Jun Goo , Ding Li , Koh Chong Lek , Ren Bing , Flicek Paul , Chen Ken , Gerstein Mark B. , Kwok Pui-Yan , Lansdorp Peter M. , Marth Gabor , Sebat Jonathan , Shi Xinghua , Bashir Ali , Ye Kai , Devine Scott E. , Talkowski Michael , Mills Ryan E. , Marschall Tobias , Korbel Jan O. , Eichler Evan E. , Lee Charles 
Published: September 2017

ABSTRACTThe incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long-read, short-read, and strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehensively analyze three human parent–child trios to define the full spectrum of human genetic variation in a haplotype-resolved manner. We identify 818,054 indel variants (<50 bp) and 27,622 SVs (≥50 bp) per human genome. We also discover 156 inversions per genome—most of which previously escaped detection. Fifty-eight of the inversions we discovered intersect with the critical regions of recurrent microdeletion and microduplication syndromes. Taken together, our SV callsets represent a sevenfold increase in SV detection compared to most standard high-throughput sequencing studies, including those from the 1000 Genomes Project. The method and the dataset serve as a gold standard for the scientific community and we make specific recommendations for maximizing structural variation sensitivity for future large-scale genome sequencing studies.
Predicting drug safety and communicating risk: benefits of a Bayesian approach
Authors: Lazic Stanley E , Edmunds Nicholas , Pollard Christopher E. 
Published: September 2017

AbstractDrug toxicity is a major source of attrition in drug discovery and development. Pharmaceutical companies routinely use preclinical data to predict clinical outcomes and continue to invest in new assays to improve predictions. However, there are many open questions about how to make the best use of available data, combine diverse data, quantify risk, and communicate risk and uncertainty to enable good decisions. The costs of suboptimal decisions are clear: resources are wasted and patients may be put at risk. We argue that Bayesian methods provide answers to all of these problems and use hERG-mediated QT prolongation as a case study. Benefits of Bayesian machine learning models include intuitive probabilistic statements of risk that incorporate all sources of uncertainty, the option to include diverse data and external information, and visualisations that have a clear link between the output from a statistical model and what this means for risk. Furthermore, Bayesian methods are easy to use with modern software, making their adoption for safety screening straightforward. We include R and Python code to encourage the adoption of these methods.
Residents’ perceptions of the impact of tourism in Abu Dhabi, United Arab Emirates
Authors: Hammad Nada , Ahmad Syed Zamberi , Papastathopoulos Avraam 
Published: September 2017

PurposeThis paper aims to investigate residents’ perceptions of tourism’s impact on their support for tourism development in Abu Dhabi, United Arab Emirates (UAE).Design/methodology/approachData were collected using self-administered questionnaires from Abu Dhabi residents (n= 407), who represented 30 nationalities residing in the emirate. Based on social exchange theory, structural equation modeling was used to test hypotheses.FindingsResults suggest that Abu Dhabi residents perceive the impacts of tourism positively and are more sensitive to the environmental and economic influences of tourism than the social and cultural influences.Research limitations/implicationsThis study was limited to Abu Dhabi residents; findings cannot be generalized to other emirates in the UAE, or other countries.Originality/valueThis study adds value to extant tourism literature by investigating residents’ perceptions of the influence of tourism in one of the richest cities worldwide, which aspires to be one of the fastest growing tourism destinations in the Middle East.
Vacation happiness bias
Authors: Chang Seohee 
Published: September 2017

Purpose
The purpose of this paper is to theoretically formulate the plausibility of affective recalling through the analysis of different psychological theories and assumptions and develops the theory of vacation happiness bias on the emergence of some variations on affective recalling and forecasting intertwined with dispositional affect, affect regulation and types of situational affect.

Design/methodology/approach
This study uses a non-empirical method to find gaps in the literature and the existing theories and build a new theoretical model, vacation happiness bias.

Findings
The theory of vacation happiness bias accounts for how the modified focalism model that is expanded to affective recalling beyond affective forecasting works, and thus the modified model is better accounted particularly for the vacation field. In addition, the theory of vacation happiness bias explains how different types of affect and affect regulation are intertwined with one another within the modified focalism frame, thereby yielding some variation. Recalled vacation experiences are more positive than vacation experiences as of the present as a result of affect that is controlled through affect regulation merged with social desirability bias.

Originality/value
Research in tourism and psychology fields has not yet deemed affective recalling, even though affective recalling would likely be more salient in the vacation context that is different from the context of daily life.
Earnings management in interconnected networks: a perspective
Authors: Ozili Peterson K. 
Published: September 2017

Purpose
The purpose of this paper is to examine how firms manage earnings when firms are in interconnected networks, that is, when firms are interconnected to each other in a way that the survival of one firm is crucial to the survival of other firms connected to it.

Design/methodology/approach
The paper employs network typology to provide some insight on the earnings management behaviour of firms in regulated and unregulated networks or systems.

Findings
The author shows that firms in the inner core of interconnected networks are more likely to rely on income-smoothing behaviour as a preferred form of earnings management because it stabilises the firm’s link with other firms in the network. In regulated networks, the author proposes a negative relationship between a firm’s network centrality and the number of earnings management strategies the manager can adopt. Also, the author proposes a positive relationship between a firm’s network centrality and the propensity to smooth earnings or income when firms are concerned about their reputation or regulatory scrutiny.

Originality/value
This paper is a brief note on earnings management, and is the first study to provide a perspective on how earnings management can be explained using a network typology.
Don't be so emotional! How tone of voice and service type affect the relationship between message valence and consumer responses to WOM in social media
Authors: De Keyzer Freya , Dens Nathalie , De Pelsmacker Patrick 
Published: September 2017

Purpose
The purpose of this paper is to shed light on the boundary conditions of the effect of the valence of word-of-mouth on social networking sites (sWOM) on consumer responses (attitude toward the service provider, purchase intention and positive word-of-mouth intention). Specifically, the authors examine two moderators: the tone of voice (factual vs emotional) of the sWOM and service type (utilitarian vs hedonic) of the service that the sWOM is about.

Design/methodology/approach
A 2 (message valence: positive vs negative) × 2 (tone of voice: factual vs emotional) × 2 (service type: utilitarian vs hedonic) full-factorial between-subjects online experiment with 400 respondents was conducted and the data were analyzed using Hayes’ PROCESS macro.

Findings
The results show that message valence exerts a greater impact on consumer responses with factual sWOM messages compared to emotional ones. Furthermore, the impact of message valence is stronger for hedonic services compared to utilitarian services. In contrast to the authors’ expectations, there is no significant impact of matching the tone of voice to the service type.

Practical implications
First, for sWOM senders, factual messages are found to be more influential: backing an sWOM up with arguments and specific details increases the chance of it affecting consumers’ responses. As a result, marketers, especially of predominantly hedonic services, should encourage their followers and customers to spread positive factual sWOM about their service.

Originality/value
The study tests two previously unstudied moderating variables that affect the relationship between message valence and consumer responses to sWOM messages. Moreover, this study provides interesting insights for marketers and bloggers or reviewers.
miR‐181d‐5p promotes neurite outgrowth in PC12 Cells via PI3K/Akt pathway
Authors: Shen Li‐Ming , Song Zhi‐Wen , Hua Yin , Chao Xu , Liu Jin‐Bo 
Published: September 2017

SummaryIntroductionmiRNAs dysregulate in spinal cord injury (SCI) and have been demonstrated to play a crucial role in neurite outgrowth. However, the underlying mechanism remains elusive. In this study, we constructed a mouse model of SCI, extracted RNA from injured spinal cord tissue for the use of microarray assay. miR‐181d‐5p which is one of the most significantly expressed miRNAs in miRNA‐mRNA network, abundantly expressed in center system and highly conserved across different spices, was chosen for our further study.AimsTo demonstrate whether miR‐181d‐5p can promote neurite outgrowth in PC12 cells via PI3K/Akt signaling pathway, we performed function analysis of miR‐181d‐5p with LV‐miR‐181d‐5p and LV‐sh‐GFP to infect PC12 cells.ResultsThrough microarray assay analysis, we totally found 262 significantly expressed miRNAs and 2973 target genes in SCI and observed that their expression dynamically changed postinjury. Here, we provided enough evidences that the overexpression of miR181d‐5p significantly decreased the expression of PTEN, upregulated p‐Akt expression, increased neurite outgrowth‐related proteins (GAP‐43 and NF‐200) and synaptic vesicle‐related proteins (Synapsin and PSD95), and then promoted neurite outgrowth in PC12 cells. Furthermore, we confirmed that miR‐181d‐5p could directly target to the 3′‐UTR of PTEN mRNA through dual‐luciferase report assay.ConclusionsOur study supports that aberrant expression of miRNAs is involved in the pathogenesis of SCI, miR‐181d‐5p plays an important role in neurite growth in PC12 cells via PI3K/Akt signaling pathway and may be a candidate target for the treatment of SCI in the future.
Differences in right ventricular morphology, not function, indicate the nature of increased afterload in pulmonary hypertensive subjects with normal left ventricular function
Authors: Raza Farhan , Dillane Catherine , Mirza Arslan , Brailovsky Yevgeniy , Weaver Sheila , Keane Martin G. , Forfia Paul 
Published: September 2017

BackgroundThe aim of study was to assess whether a specific morphology of the right ventricle (RV) by 2D echo predicts the hemodynamic nature of pulmonary hypertension (PH).MethodsWe reviewed clinical, 2D echo, and hemodynamic data of 100 patients with PH: divided into three groups: PH from pulmonary vascular disease (PHPVD; n = 34) with pulmonary vascular resistance (PVR) > 3 mm Hg/L/min (Wood unit [WU]) and pulmonary artery wedge pressure (PAWP) ≤ 15 mm Hg, pulmonary venous hypertension (PVH; n = 33) with PVR < 3 WU and PAWP > 15 mm Hg and PHMIXED (n = 33) with PVR > 3 WU and PAWP > 15 mm Hg. We analyzed several two‐dimensional parameters of right heart morphology and function, including the degree of tapering of the RV diameter from base (just above tricuspid annulus) to apex (level of moderator band) in the apical four‐chamber view. P = <.05.ResultsBaseline characteristics were similar in all three groups: age 62 ± 14.4 years, 69% females, 57% Caucasians. Hemodynamics and 2D echo data of PHPVD vs PVH vs PHMIXED were as follows: PVR 13 ± 6 vs 2 ± 1 vs 7 ± 2 WU, mean pulmonary artery pressure 53 ± 14 vs 34 ± 8 vs 49 ± 8 mm Hg and cardiac index 2.0 ± 0.5 vs 2.8 ± 0.7 vs 2.2 ± 0.7 L/m2, RV base/apex ratio during systole (sRVb/a) 1.3 ± 0.2 vs 2.6 ± 0.5 vs 1.5 ± 0.3. Thus, sRVb/a was twofold higher in the PVH vs PHPVD cohort. On ROC analysis, the AUC for sRVb/a for predicting PVR > 3 WU was 0.873, with optimal cutoff of 1.5.ConclusionSystolic RV base/apex ratio is a simple 2D index of RV shape that powerfully predicts a PVR > 3 WU and provides powerful discriminating ability between PVH and PHPVD.
Custom extracellular matrix cylinder mitral valve in a pediatric patient
Authors: Cua Clifford L. , Johnston Pace , Harmon Jill , Shelton Kathryn , McConnell Patrick I. 
Published: September 2017

Mitral valve construction using extracellular matrix (ECM) is a relatively new procedure. In this case, a 15‐month‐old boy with a history of severe mitral valve regurgitation secondary to endocarditis underwent mitral valve surgery. Mitral valve repair was not possible, and thus, a 17 mm extracellular matrix cylinder valve (ECM‐CV) was constructed for valve replacement. The ECM‐CV is clearly imaged using echocardiography, especially three‐dimensional imaging, that helped define valve function. As the use of ECM for valve construction increases, echocardiography will play an essential role in evaluating the function and mechanics of these novel valves.