bluuebunny/crossref_metadata_2025_split huggingface dataset:
A change-point model for identifying 3′UTR switching by next-generation RNA sequencing
Authors: Wang Wei , Wei Zhi , Li Hongzhe 
Published: April 2014

AbstractMotivation: Next-generation RNA sequencing offers an opportunity to investigate transcriptome in an unprecedented scale. Recent studies have revealed widespread alternative polyadenylation (polyA) in eukaryotes, leading to various mRNA isoforms differing in their 3′ untranslated regions (3′UTR), through which, the stability, localization and translation of mRNA can be regulated. However, very few, if any, methods and tools are available for directly analyzing this special alternative RNA processing event. Conventional methods rely on annotation of polyA sites; yet, such knowledge remains incomplete, and identification of polyA sites is still challenging. The goal of this article is to develop methods for detecting 3′UTR switching without any prior knowledge of polyA annotations.Results: We propose a change-point model based on a likelihood ratio test for detecting 3′UTR switching. We develop a directional testing procedure for identifying dramatic shortening or lengthening events in 3′UTR, while controlling mixed directional false discovery rate at a nominal level. To our knowledge, this is the first approach to analyze 3′UTR switching directly without relying on any polyA annotations. Simulation studies and applications to two real datasets reveal that our proposed method is powerful, accurate and feasible for the analysis of next-generation RNA sequencing data.Conclusions: The proposed method will fill a void among alternative RNA processing analysis tools for transcriptome studies. It can help to obtain additional insights from RNA sequencing data by understanding gene regulation mechanisms through the analysis of 3′UTR switching.Availability and implementation: The software is implemented in Java and can be freely downloaded from http://utr.sourceforge.net/ .Contact: zhiwei@njit.edu or hongzhe@mail.med.upenn.eduSupplementary information: Supplementary data are available at Bioinformatics online.
Computational identification of natural peptides based on analysis of molecular evolution
Authors: Toporik Amir , Borukhov Itamar , Apatoff Avihay , Gerber Doron , Kliger Yossef 
Published: April 2014

Abstract
Motivation: Many secretory peptides are synthesized as inactive precursors that must undergo post-translational processing to become biologically active peptides. Attempts to predict natural peptides are limited by the low performance of proteolytic site predictors and by the high combinatorial complexity of pairing such sites. To overcome these limitations, we analyzed the site-wise evolutionary mutation rates of peptide hormone precursors, calculated using the Rate4Site algorithm.
Results: Our analysis revealed that within their precursors, peptide residues are significantly more conserved than the pro-peptide residues. This disparity enables the prediction of peptides with a precision of ∼60% at a recall of 40% [receiver-operating characteristic curve (ROC) AUC 0.79]. Subsequently, combining the Rate4Site score with additional features and training a Random Forest classifier enable the prediction of natural peptides hidden within secreted human proteins at a precision of ∼90% at a recall of 50% (ROC AUC 0.96). The high performance of our method allows it to be applied to full secretomes and to predict naturally occurring active peptides. Our prediction on Homo sapiens revealed several putative peptides in the human secretome that are currently unannotated. Furthermore, the unique expression of some of these peptides implies a potential hormone function, including peptides that are highly expressed in endocrine glands.
Availability and implementation: A pseudocode is available in the Supplementary information.
Contact: doron.gerber@biu.ac.il or kliger@cgen.com
Supplementary information : Supplementary data are available at Bioinformatics online.
Random survival forests for competing risks
Authors: Ishwaran Hemant , Gerds Thomas A. , Kogalur Udaya B. , Moore Richard D. , Gange Stephen J. , Lau Bryan M. 
Published: April 2014

Abstract
We introduce a new approach to competing risks using random forests. Our method is fully non-parametric and can be used for selecting event-specific variables and for estimating the cumulative incidence function. We show that the method is highly effective for both prediction and variable selection in high-dimensional problems and in settings such as HIV/AIDS that involve many competing risks.
Bimodality of wind-fed accretion in high-mass X-ray binaries
Authors: Karino Shigeyuki 
Published: April 2014

Abstract
We here consider the influence of X-ray photoionization from an accreting neutron star in a high-mass X-ray binary. Our aim is to unveil a new principle governing the X-ray luminosity of X-ray binaries, through a simple analysis of fluid equations simulating line-driven wind flow under the influence of X-ray irradiation. In this study, we solved the equation of motion of the accretion flow while taking into account the line-driven acceleration and X-ray photoionization. Under the influence of X-ray irradiation, we have found that the flow equations have two types of solutions. The first is characterized by a slow wind velocity, which causes a large accretion rate. The second solution is a fast wind flow, which results in a small accretion rate. We find that only the solution with a fast wind and faint X-ray luminosity is a steady solution. On the other hand, a slow wind solution with a large X-ray luminosity is not a realizable solution. In bright X-ray binary systems, the X-ray luminosity would increase until strong X-rays reduce the line-driven acceleration, and cause a stagnation of the wind. This implies an important consequence; that is, the X-ray luminosity of the wind-fed, X-ray emitting binary is settled by the limit of wind stagnation. At the same time, the fast-wind solution with a small X-ray luminosity can also represent a steady state. Bright X-ray sources, such as Vela X-1, would have limiting luminosities of wind stagnation, while faint systems, such as quiescent supergiant fast X-ray transients, could follow the faint solution.
Boom-Bust Turnovers of Megabase-Sized Centromeric DNA inSolanumSpecies: Rapid Evolution of DNA Sequences Associated with Centromeres
Authors: Zhang Haiqin , Koblížková Andrea , Wang Kai , Gong Zhiyun , Oliveira Ludmila , Torres Giovana A. , Wu Yufeng , Zhang Wenli , Novák Petr , Buell C. Robin , Macas Jiří , Jiang Jiming 
Published: April 2014

AbstractCentromeres are composed of long arrays of satellite repeats in most multicellular eukaryotes investigated to date. The satellite repeat–based centromeres are believed to have evolved from “neocentromeres” that originally contained only single- or low-copy sequences. However, the emergence and evolution of the satellite repeats in centromeres has been elusive. Potato (Solanum tuberosum) provides a model system for studying centromere evolution because each of its 12 centromeres contains distinct DNA sequences, allowing comparative analysis of homoeologous centromeres from related species. We conducted genome-wide analysis of the centromeric sequences in Solanum verrucosum, a wild species closely related to potato. Unambiguous homoeologous centromeric sequences were detected in only a single centromere (Cen9) between the two species. Four centromeres (Cen2, Cen4, Cen7, and Cen10) in S. verrucosum contained distinct satellite repeats that were amplified from retrotransposon-related sequences. Strikingly, the same four centromeres in potato contain either different satellite repeats (Cen2 and Cen7) or exclusively single- and low-copy sequences (Cen4 and Cen10). Our sequence comparison of five homoeologous centromeres in two Solanum species reveals rapid divergence of centromeric sequences among closely related species. We propose that centromeric satellite repeats undergo boom-bust cycles before a favorable repeat is fixed in the population.
Job strain and the risk of severe asthma exacerbations: a meta‐analysis of individual‐participant data from 100 000 European men and women
Authors: Heikkilä K. , Madsen I. E. H. , Nyberg S. T. , Fransson E. I. , Westerlund H. , Westerholm P. J. M. , Virtanen M. , Vahtera J. , Väänänen A. , Theorell T. , Suominen S. B. , Shipley M. J. , Salo P. , Rugulies R. , Pentti J. , Pejtersen J. H. , Oksanen T. , Nordin M. , Nielsen M. L. , Kouvonen A. , Koskinen A. , Koskenvuo M. , Knutsson A. , Ferrie J. E. , Dragano N. , Burr H. , Borritz M. , Bjorner J. B. , Alfredsson L. , Batty G. D. , Singh‐Manoux A. , Kivimäki M. ,   the IPD‐Work Consortium
Published: April 2014

AbstractBackgroundMany patients and healthcare professionals believe that work‐related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations in working‐age European men and women.MethodsWe analysed individual‐level data, collected between 1985 and 2010, from 102 175 working‐age men and women in 11 prospective European studies. Job strain (a combination of high demands and low control at work) was self‐reported at baseline. Incident severe asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study‐specific findings combined using random‐effects meta‐analyses.ResultsDuring a median follow‐up of 10 years, 1 109 individuals experienced a severe asthma exacerbation (430 with asthma as the primary diagnostic code). In the age‐ and sex‐adjusted analyses, job strain was associated with an increased risk of severe asthma exacerbations defined using the primary diagnostic code (hazard ratio, HR: 1.27, 95% confidence interval, CI: 1.00, 1.61). This association attenuated towards the null after adjustment for potential confounders (HR: 1.22, 95% CI: 0.96, 1.55). No association was observed in the analyses with asthma defined using any diagnostic code (HR: 1.01, 95% CI: 0.86, 1.19).ConclusionsOur findings suggest that job strain is probably not an important risk factor for severe asthma exacerbations leading to hospitalization or death.
Intrauterine growth restriction – a population‐based study of the association with academic performance and psychiatric health
Authors: Kierulf Strømme Kirsten , Strømme Petter , Bjertness Espen , Lien Lars 
Published: April 2014

AbstractAimTo investigate whether intrauterine growth restriction (IUGR), resulting in small for gestational age (SGA) infants, is associated with increased susceptibility to psychiatric problems and academic impairment in late teens.MethodsA cohort of all 10th‐grade students in Oslo, Norway, followed up between 2001 and 2004 (n = 2131), was linked with foetal growth data. IUGR was considered equal to SGA at the lowest 2.5th, 5th, and 10th percentiles and appropriate for gestational age (AGA) as the highest 90th percentile. Mental health was evaluated using the Hopkins Symptoms Check List and the Strength and Difficulties Questionnaire, and academic achievements and ambitions were self‐reported by the students.ResultsPsychiatric problems were equally prevalent in all groups. However, the SGA girls performed inferiorly compared to their AGA peers in the school subjects English [3.6 vs 3.9 (p = 0.03)], mathematics [4.0 vs 4.3 (p = 0.01)] and social science [4.2 vs 4.4 (p = 0.05)], but not for Norwegian. This association was not observed in boys. There was an association between academic impairment and prematurity, occurring more frequently among immigrants (p < 0.001).ConclusionSGA had a small negative impact on academic achievements in adolescent girls, but not boys. There was no association between SGA and psychiatric problems in either gender.
Association of obesity and treated hypertension and diabetes with cognitive ability in bipolar disorder and schizophrenia
Authors: Depp Colin A , Strassnig Martin , Mausbach Brent T , Bowie Christopher R , Wolyniec Paula , Thornquist Mary H , Luke James R , McGrath John A , Pulver Ann E , Patterson Thomas L , Harvey Philip D 
Published: April 2014

ObjectivesPeople with bipolar disorder or schizophrenia are at greater risk for obesity and other cardio‐metabolic risk factors, and several prior studies have linked these risk factors to poorer cognitive ability. In a large ethnically homogenous outpatient sample, we examined associations among variables related to obesity, treated hypertension and/or diabetes and cognitive abilities in these two patient populations.MethodsIn a study cohort of outpatients with either bipolar disorder (n = 341) or schizophrenia (n = 417), we investigated the association of self‐reported body mass index and current use of medications for hypertension or diabetes with performance on a comprehensive neurocognitive battery. We examined sociodemographic and clinical factors as potential covariates.ResultsPatients with bipolar disorder were less likely to be overweight or obese than patients with schizophrenia, and also less likely to be prescribed medication for hypertension or diabetes. However, obesity and treated hypertension were associated with worse global cognitive ability in bipolar disorder (as well as with poorer performance on individual tests of processing speed, reasoning/problem‐solving, and sustained attention), with no such relationships observed in schizophrenia. Obesity was not associated with symptom severity in either group.ConclusionsAlthough less prevalent in bipolar disorder compared to schizophrenia, obesity was associated with substantially worse cognitive performance in bipolar disorder. This association was independent of symptom severity and not present in schizophrenia. Better understanding of the mechanisms and management of obesity may aid in efforts to preserve cognitive health in bipolar disorder.
Increased temporo‐insular engagement in unmedicated bipolar II disorder: an exploratory resting state study using independent component analysis
Authors: Yip Sarah W , Mackay Clare E , Goodwin Guy M 
Published: April 2014

ObjectivesDespite numerous structural and functional magnetic resonance imaging studies, the neurobiology of bipolar disorder (BD) is still incompletely understood. Resting‐state functional magnetic resonance imaging (rsFMRI) allows for the study of intrinsic functional connections between brain areas, which may reflect the pathophysiology of BD. Most previous rsFMRI studies conducted in BD have included a majority of medicated patients, making simple interpretation with respect to pathophysiology difficult.MethodsParticipants were 15 antipsychotic agent‐ and mood‐stabilizer‐naïve young adults with bipolar II disorder (BD‐II), and 20 healthy controls group‐matched for gender, age, and cognitive ability. Independent component analysis (ICA) was used to identify eight commonly studied resting‐state networks (RSNs). Between‐group comparisons were conducted using dual regression and corrected for family‐wise error (FWE) across space and the number of components (pFWE < 0.05).ResultsIn comparison to controls, participants with BD‐II had increased coherence across several brain regions, including the bilateral insula and putamen, across a temporo‐insular network. No between‐group differences in engagement of the default mode network were found.ConclusionsThis was the first ICA‐based rsFMRI study conducted among unmedicated individuals with BD. Given the young age (mean = 23 years) and antipsychotic agent‐ and mood‐stabilizer‐naïve status of our participants with BD‐II, temporo‐insular functional connectivity is a candidate vulnerability marker for BD. Further work is needed to relate resting‐state differences to detailed understanding of pathophysiology.
The Additional Value of Three‐Dimensional Transesophageal Echocardiography in Complex Aortic Prosthetic Heart Valve Endocarditis
Authors: Tanis Wilco , Teske Arco J. , van Herwerden Lex A. , Chamuleau Steven , Meijboom Folkert , Budde Ricardo P.J. , Cramer Maarten‐Jan 
Published: April 2014

BackgroundTwo‐dimensional transthoracic and transesophageal echocardiography (2DTTE and 2DTEE) may fail to detect signs of prosthetic heart valve (PHV) endocarditis due to acoustic shadowing. Three‐dimensional (3D) TEE may have additional value; however, data are scarce. This study was performed to investigate the additional value of 3DTEE for the detection of aortic PHV endocarditis and the extent of the disease process.MethodsRetrospective analysis of complex aortic PHV endocarditis cases that underwent 2DTTE, 2DTEE, and 3DTEE before surgery. Echocardiograms were individually assessed by 2 cardiologists blinded for the outcome. Surgical and pathological inspection served as the reference standard for vegetations and peri‐annular extensions (abscesses/mycotic aneurysms). To determine if the proximal coronary arteries were involved in the inflammatory process as well, computed tomography angiography findings were added to reference standard.ResultsFifteen aortic PHV endocarditis cases were identified. According to the reference standard, all 15 cases had peri‐annular extensions, 13 of which had a close relationship with the proximal right and/or left coronary artery. In 6 of 15 patients, a vegetation was present. Combined 2DTTE/TEE missed 1/6 vegetations and 1/15 peri‐annular extensions. After addition of 3DTEE, all vegetations (6/6) and peri‐annular extensions (15/15) were detected, without adding false positives. Compared to 2DTEE, in 3/15 cases, 3DTEE resulted in better delineation of the anatomical relationship of the proximal coronary arteries to the peri‐annular extensions. As a result, 3DTEE had an additional value in 5/15 cases.ConclusionIn complex aortic, PHV endocarditis 3DTEE may have additional value compared to 2D echocardiography.
Prey C:P ratio and phosphorus recycling by a planktivorous fish: advantages of fish selection towards pelagic cladocerans
Authors: Reissig Mariana , Queimaliños Claudia , Modenutti Beatriz , Balseiro Esteban 
Published: April 2014

AbstractPrey selection by the small planktivore Galaxias maculatus and phosphorus gain depending on diet has been examined related to predator–prey daily distribution. Prey elemental composition (C:P ratio) was analysed as a factor of selectivity. Field experiments were carried out to evaluate the effect of prey on phosphorus recycling. Results revealed that the pelagic cladoceran Ceriodaphnia dubia was a highly selected prey by all fish sizes at dawn and dusk, despite its low abundances in comparison with other zooplankters, while the littoral were ingested only during day. The high selectivity for C. dubia showed that G. maculatus moved to pelagic zone during night to consume this prey but returned to littoral areas during day due to the increase in predation risk. Analysis of elemental composition revealed that P content of C. dubia was significantly higher than other planktonic or littoral prey (Bosmina longirostris, Boeckella gracilipes and chironomids). Phosphorus recycling experiments showed that G. maculatus would transport and supply P in available forms for primary producers. Fish size was observed to influence P recycling as YOY had significant higher mass‐specific P release in the morning and mid‐day when they preyed mainly upon C. dubia. Low prey C:P ratio appears as a factor that would add benefits to the classical visual fish selection towards cladocerans, as this preference would imply a net phosphorus gain for fish.
Identification of the major HHV‐6 antigen recognized by cerebrospinal fluid IgG in multiple sclerosis
Authors: Alenda R. , Álvarez‐Lafuente R. , Costa‐Frossard L. , Arroyo R. , Mirete S. , Álvarez‐Cermeño J. C. , Villar L. M. 
Published: April 2014

Background and purposeDifferent data show an association between human herpesvirus 6 (HHV‐6) and multiple sclerosis (MS). Intrathecal anti‐HHV‐6 immunoglobulin G (IgG) was detected in MS patients, but the antigen recognized by cerebrospinal fluid (CSF) IgG has not been characterized yet. Our objective was to identify the HHV‐6 antigens recognized by IgG present in the CSF of patients with MS.MethodsCerebrospinal fluid IgG of 15 MS patients and eight patients with other neurological diseases was purified on protein G Sepharose columns. Purified IgG from every patient was linked to a CNBr‐activated Sepharose 4B column. Fifty micrograms of viral extract was applied to each column. Bound proteins were eluted and analysed by SDS‐PAGE and silver staining. The viral protein was characterized by mass spectrometry.ResultsA protein of 150 kD was eluted from CSF IgG columns of three of eight patients with primary progressive MS and one of seven with relapsing−remitting MS. After digestion and mass spectrometry analysis 10 peptides were found with 100% homology with the major capsid protein of the HHV‐6A.DiscussionThese findings confirm the presence of anti‐HHV‐6 IgG in CSF of MS patients, particularly in progressive forms, and identify major capsid protein as the major antigen recognized by CSF IgG from MS patients.
Predictors of hippocampal atrophy in critically ill patients
Authors: Lindlau A. , Widmann C. N. , Putensen C. , Jessen F. , Semmler A. , Heneka M. T. 
Published: April 2014

Background and purposeHippocampal atrophy is presumably one morphological sign of critical illness encephalopathy; however, predictors have not yet been determined.MethodsThe data for this report derived from patients treated at the intensive care units (ICUs) of the University Hospital in Bonn in the years 2004–2006. These patients underwent structural magnetic resonance imaging 6–24 months after discharge. Volumes (intracranial, whole brain, white matter, grey matter, cerebral spinal fluid, bilateral hippocampus) were compared with healthy controls. Pro‐inflammatory parameters and ICU scoring systems were explored in conjunction with brain volumes. Cut‐scores were defined to differentiate patients with high from those with low inflammatory response.ResultsHippocampal and white matter volume were reduced in critically ill patients compared with healthy controls. Procalcitonin showed a very strong correlation (r = −0.903, P = 0.01) and interleukin‐6 a moderate correlation (r = −0.538, P = 0.031) with hippocampal volume, but not with other brain volumes. C‐reactive protein was linked to grey matter volume. There was no correlation with systemic inflammatory response syndrome criteria (body temperature, heart rate, respiratory rate, white blood cell count) or for hippocampal or whole brain volume. Furthermore, parameters representing severity of disease (APACHE II score, SOFA score, duration of stay and duration of mechanical ventilation) were not associated with hippocampal or other brain volumes.ConclusionsThis analysis suggests that high levels of procalcitonin and interleukin‐6 in the blood serum of critically ill patients are associated with a high likelihood of hippocampal atrophy irrespective of the severity of disease measured by ICU scoring systems and other inflammatory parameters.