bluuebunny/crossref_metadata_2025_split huggingface dataset:
RECAP reveals the true statistical significance of ChIP-seq peak calls
Authors: Chitpin Justin G , Awdeh Aseel , Perkins Theodore J 
Published: February 2019

AbstractMotivationChromatin Immunopreciptation (ChIP)-seq is used extensively to identify sites of transcription factor binding or regions of epigenetic modifications to the genome. A key step in ChIP-seq analysis is peak calling, where genomic regions enriched for ChIP versus control reads are identified. Many programs have been designed to solve this task, but nearly all fall into the statistical trap of using the data twice—once to determine candidate enriched regions, and again to assess enrichment by classical statistical hypothesis testing. This double use of the data invalidates the statistical significance assigned to enriched regions, thus the true significance or reliability of peak calls remains unknown.ResultsUsing simulated and real ChIP-seq data, we show that three well-known peak callers, MACS, SICER and diffReps, output biased P-values and false discovery rate estimates that can be many orders of magnitude too optimistic. We propose a wrapper algorithm, RECAP, that uses resampling of ChIP-seq and control data to estimate a monotone transform correcting for biases built into peak calling algorithms. When applied to null hypothesis data, where there is no enrichment between ChIP-seq and control, P-values recalibrated by RECAP are approximately uniformly distributed. On data where there is genuine enrichment, RECAP P-values give a better estimate of the true statistical significance of candidate peaks and better false discovery rate estimates, which correlate better with empirical reproducibility. RECAP is a powerful new tool for assessing the true statistical significance of ChIP-seq peak calls.Availability and implementationThe RECAP software is available through www.perkinslab.ca or on github at https://github.com/theodorejperkins/RECAP.Supplementary informationSupplementary data are available at Bioinformatics online.
VHost-Classifier: virus-host classification using natural language processing
Authors: Kitson Ezra , Suttle Curtis A 
Published: February 2019

Abstract

Motivation
When analyzing viral metagenomic sequences, it is often desired to filter the results of a BLAST analysis by the host species of the virus. VHost-Classifier automates this procedure using a natural language processing algorithm written in Python 3, which takes a list of taxonomic identifiers (taxids) returned from a BLAST query using viral sequences as input. The taxid output is binned by the evolutionary lineage of their host, based on string matching the words in their English names. If VHost-Classifier cannot identify a host, it attempts to bin the sequences by the environment from which the sample originated. VHost-Classifier predicts the evolutionary lineage of the host from the virus name and does not rely on referencing taxids against a database; therefore, it is not constrained by the size of a database and can host classify newly characterized viruses.

Results
Benchmarked on a test dataset of 1000 randomly selected viral taxids on the NCBI taxonomy database, VHost-Classifier assigned, with 100% accuracy, a host to the rank of Class for &gt;93% of viruses, and to the rank of Family for &gt;37% of viruses.

Availability and implementation
For more information about VHost-Classifier as well as implementation instructions, visit https://github.com/Kzra/VHost-Classifier.

Supplementary information
Supplementary data are available at Bioinformatics online.
Enhancing the prediction of disease–gene associations with multimodal deep learning
Authors: Luo Ping , Li Yuanyuan , Tian Li-Ping , Wu Fang-Xiang 
Published: February 2019

Abstract

Motivation
Computationally predicting disease genes helps scientists optimize the in-depth experimental validation and accelerates the identification of real disease-associated genes. Modern high-throughput technologies have generated a vast amount of omics data, and integrating them is expected to improve the accuracy of computational prediction. As an integrative model, multimodal deep belief net (DBN) can capture cross-modality features from heterogeneous datasets to model a complex system. Studies have shown its power in image classification and tumor subtype prediction. However, multimodal DBN has not been used in predicting disease–gene associations.

Results
In this study, we propose a method to predict disease–gene associations by multimodal DBN (dgMDL). Specifically, latent representations of protein-protein interaction networks and gene ontology terms are first learned by two DBNs independently. Then, a joint DBN is used to learn cross-modality representations from the two sub-models by taking the concatenation of their obtained latent representations as the multimodal input. Finally, disease–gene associations are predicted with the learned cross-modality representations. The proposed method is compared with two state-of-the-art algorithms in terms of 5-fold cross-validation on a set of curated disease–gene associations. dgMDL achieves an AUC of 0.969 which is superior to the competing algorithms. Further analysis of the top-10 unknown disease–gene pairs also demonstrates the ability of dgMDL in predicting new disease–gene associations.

Availability and implementation
Prediction results and a reference implementation of dgMDL in Python is available on https://github.com/luoping1004/dgMDL.

Supplementary information
Supplementary data are available at Bioinformatics online.
Unraveling UCA1 lncRNA prognostic utility in urothelial bladder cancer
Authors: Avgeris Margaritis , Tsilimantou Anastasia , Levis Panagiotis K , Rampias Theodoros , Papadimitriou Maria-Alexandra , Panoutsopoulou Konstantina , Stravodimos Konstantinos , Scorilas Andreas 
Published: February 2019

AbstractIn the era of precision oncology, bladder cancer (BlCa) is characterized by generic patient management and lack of personalized prognosis and surveillance. Herein, we have studied the clinical significance of urothelial cancer associated 1 (UCA1) lncRNA in improving patients’ risk stratification and prognosis. A screening cohort of 176 BlCa patients was used for UCA1 quantification. The Hedegaard et al. (n = 476) and The Cancer Genome Atlas (TCGA) provisional (n = 413) were analyzed as validation cohorts for non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), respectively. Patients’ survival outcome was assessed using recurrence and progression for NMIBC or death for MIBC as clinical endpoint events. Bootstrap analysis was performed for internal validation of Cox regression analysis, whereas the clinical benefit of disease prognosis was assessed by decision curve analysis. UCA1 was significantly overexpressed in bladder tumors compared with normal urothelium, which was confirmed only in the case of NMIBC. Interestingly, reduced expression of UCA1 was correlated with muscle-invasive disease as well as with tumors of higher stage and grade. UCA1 loss was strongly associated with higher risk of short-term relapse [hazard ratio (HR) = 1.974; P = 0.032] and progression to invasive stages (HR = 3.476; P = 0.023) in NMIBC. In this regard, Hedegaard et al. and TCGA validation cohorts confirmed the unfavorable prognostic nature of UCA1 loss in BlCa. Finally, prognosis prediction models integrating UCA1 underexpression and established clinical disease markers contributed to improved stratification specificity and superior clinical benefit for NMIBC prognosis. Underexpression of UCA1 correlates with worse disease outcome in NMIBC and contributes to superior prediction of disease early relapse and progression as well as improved patient stratification specificity.
FMRP Modulates Activity-Dependent Spine Plasticity by Binding Cofilin1 mRNA and Regulating Localization and Local Translation
Authors: Feuge Jonas , Scharkowski Franziska , Michaelsen-Preusse Kristin , Korte Martin 
Published: February 2019

AbstractMultiple variants of intellectual disability, e.g., the Fragile X Syndrome are associated with alterations in dendritic spine morphology, thereby pointing to dysregulated actin dynamics during development and processes of synaptic plasticity. Surprisingly, although the necessity of spine actin remodeling was demonstrated repeatedly, the importance and precise role of actin regulators is often undervalued. Here, we provide evidence that structural and functional plasticity are severely impaired after NMDAR-dependent LTP in the hippocampus of Fmr1 KO mice. We can link these defects to an aberrant activity-dependent regulation of Cofilin 1 (cof1) as activity-dependent modulations of local cof1 mRNA availability, local cof1 translation as well as total cof1 expression are impaired in the absence of FMRP. Finally, we can rescue activity-dependent structural plasticity in KO neurons by mimicking the regulation of cof1 observed in WT cells, thereby illustrating the potential of actin modulators to provide novel treatment strategies for the Fragile X Syndrome.
Derivation and Validation of a Clinical Decision Guideline for Influenza Testing in 4 US Emergency Departments
Authors: Dugas Andrea F , Hsieh Yu-Hsiang , LoVecchio Frank , Moran Gregory J , Steele Mark T , Talan David A , Rothman Richard E ,   Emergency Department National Influenza Network Investigators, Stubbs Amy , Kemble Laurie , Beckham Danielle , Neal Niccole , Mulrow Mary , Krishnadasan Anusha , Pathmarajah Kavitha , Pathmarajah Kavitha , Torrez Raquel , Gonzalez Eva , Martin Gabina , Urzagaste Noemi Quinteros , Furoy Jacklyn , Hernandez Mayra , Collison Claire , Duval Anna , Beard Raphaelle , Avornu Ama , Medina Rebecca , McBryde Breana 
Published: February 2019

Abstract

Background
An accurate diagnosis of influenza is essential for appropriate antiviral treatment, in accordance with Centers for Disease Control and Prevention (CDC) guidelines. However, no clear guidance exists on which patients should be tested. We sought to develop a clinical decision guideline (CDG) to inform influenza testing decisions for those adult emergency department (ED) patients deemed appropriate for antiviral treatment by CDC guidelines.

Methods
A prospective cohort study was performed at 4 US EDs. From November 2013 to April 2014, we enrolled adult ED patients with fever or respiratory symptoms who met criteria for antiviral treatment, per 2013 CDC guidelines. All patients were tested for influenza using polymerase chain reaction. Data were randomly split into derivation (80%) and validation (20%) data sets. A discrete set of independent variables was selected by logistic regression, using the derivation set to create a scoring system, with a target sensitivity of at least 90%. The derived CDG was then validated.

Results
Of 1941 enrolled participants, 183 (9.4%) had influenza. The derived CDG included new or increased cough (2 points), headache (1 point), subjective fever (1 point), and triage temperature &gt;100.4°C (1 point), with a score of ≥3 indicating influenza testing was warranted. The CDG had a sensitivity and specificity of 94.1% and 36.6%, respectively, in the derivation set and of 91.5% and 34.6%, respectively, in the validation set.

Conclusions
A CDG with high sensitivity was derived and validated. Incorporation into practice could standardize testing for high-risk patients in adult EDs during influenza seasons, potentially improving diagnoses and treatment.

Clinical Trial Registration
NCT01947049.
Psychosocial Barriers to Viral Suppression in a Community-based Sample of Human Immunodeficiency Virus–infected Men Who Have Sex With Men and People Who Inject Drugs in India
Authors: Prabhu Sandeep , McFall Allison M , Mehta Shruti H , Srikrishnan Aylur K , Kumar Muniratnam Suresh , Anand Santhanam , Shanmugam Saravanan , Celentano David D , Lucas Gregory M , Solomon Sunil S 
Published: February 2019

AbstractBackgroundLittle is known about the impact of psychosocial factors and substance use on viral suppression among human immunodeficiency virus (HIV)–infected key populations in resource-limited settings. Accordingly, we examined the association and interactions between depression, alcohol use, and recreational drug use on viral suppression among men who have sex with men (MSM) and people who inject drugs (PWID) in India.MethodsMSM and PWID were recruited across India using respondent-driven sampling (RDS). Correlates of viral suppression were determined using Poisson regression models incorporating RDS-II weights. Two-way multiplicative interactions were assessed with separate models of all combinations of the 3 variables of interest using interaction terms; 3-way interactions were evaluated by stratifying 2-way interactions by the third variable.ResultsAmong 1454 treatment-eligible HIV-infected MSM and 1939 PWID, older age (adjusted prevalence ratio [aPR], 1.14 for MSM; 1.41 for PWID) and higher HIV treatment literacy (aPR, 1.58 for MSM; 3.04 for PWID) were positively associated with viral suppression. Among MSM, there was evidence of a synergistic negative association between severe depression and recreational drug use (aPR, 0.37 [95% confidence interval {CI}, .16–.84]), alcohol dependence and recreational drug use (aPR, 0.45 [95% CI, .20–.99]), and severe depression, alcohol dependence, and recreational drug use (aPR, 0.23 [95% CI, .09–.57]). Among PWID, daily injection (aPR, 0.51 [95% CI, .31–.82]) was the primary barrier to suppression.ConclusionsIncorporating psychosocial and harm-reduction services into differentiated care models targeting MSM and PWID in low-resource settings is critical to achieving the 90-90-90 HIV/AIDS targets.
Assessment of left ventricular outflow tract and aortic root: comparison of 2D and 3D transthoracic echocardiography with multidetector computed tomography
Authors: Visby Lasse , Kristensen Charlotte Burup , Pedersen Frederik Holm Grund , Sigvardsen Per Ejlstrup , Kofoed Klaus Fuglsang , Hassager Christian , Møgelvang Rasmus 
Published: February 2019

Abstract

Aims
Accurate echocardiographic assessment of left ventricular outflow tract (LVOT) and the aortic root is necessary for risk stratification and choice of appropriate treatment in patients with pathologies of the aortic valve and aortic root. Conventional 2D transthoracic echocardiographic (TTE) assessment is based on the assumption of a circular shaped LVOT and aortic root, although previous studies have indicated a more ellipsoid shape. 3D TTE and multidetector computed tomography (MDCT) applies planimetry and are not dependent on geometrical assumptions. The aim was to test accuracy, feasibility, and reproducibility of 3D TTE compared to 2D TTE assessment of LVOT and aortic root areas, with MDCT as reference.

Methods and results
We examined 51 patients with 2D/3D TTE and MDCT at the same day. All patients were re-examined with 2D/3D TTE on a different day to evaluate 2D and 3D re-test variability. Areas of LVOT, aortic annulus, and sinus were assessed using 2D, 3D TTE, and MDCT. Both 2D/3D TTE underestimated the areas compared to MDCT; however, 3D TTE areas were significantly closer to MDCT-areas. 2D vs. 3D mean MDCT-differences: LVOT 1.61 vs. 1.15 cm2, P = 0.019; aortic annulus 1.96 vs. 1.06 cm2, P < 0.001; aortic sinus 1.66 vs. 1.08 cm2, P = 0.015. Feasibility was 3D 76–79% and 2D 88–90%. LVOT and aortic annulus areas by 3D TTE had lowest variabilities; intraobserver coefficient of variation (CV) 9%, re-test variation CV 18–20%.

Conclusion
Estimation of LVOT and aortic root areas using 3D TTE is feasible, more precise and more accurate than 2D TTE.
Is low serum albumin associated with postoperative bronchopleural fistula in patients undergoing pulmonary resections?
Authors: Zhang Wenbiao , Li Shuangjiang , Chen Longqi , Zhou Qinghua 
Published: February 2019

Abstract
A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether low serum albumin (sAlb) was associated with postoperative bronchopleural fistula (BPF) in patients undergoing pulmonary resections. Altogether 660 papers were found using the reported search, of which 5 retrospective cohort studies represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Four of the 5 cohort studies showed that the preoperative sAlb level in patients who experience a BPF was significantly lower than that in patients who did not experience a BPF. One of the 5 studies also reported that the incidence of BPF in patients with a lower sAlb (13.6%) was found to be significantly higher than that in patients with a higher sAlb (7.0%). The level of hypoalbuminaemia is not defined, but it may be <3.5 g/dl. This cut-off value of sAlb is assumed from the currently available retrospective data. No prospective study has been reported to address this issue. In summary, low preoperative sAlb can serve as a significant risk factor for postoperative BPF in patients undergoing pulmonary resections.
Are cities good for health? A study of the impacts of planned urbanization in China
Authors: Hou Bo , Nazroo James , Banks James , Marshall Alan 
Published: February 2019

Abstract

Background
Urbanization in developing countries is usually accompanied by migration to cities, making it a challenge to unpack the independent relationships between migration, urbanization and health, particularly in the presence of health-selective migration. Since 1978, unprecedented planned urbanization has taken place in China and further increases to the urban population are expected. This paper explored the impacts of urbanization in China through a comparative study of in situ urbanized population.

Methods
Using the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative dataset for people aged 45 years or older, we compared self-assessed general health, depressive symptoms and waist circumference among three groups: (i) in situ urbanized-rural residents; (ii) rural residents; and (iii) urban residents. Using a model informed by the literature on the social determinants of health in later life, we investigated the patterning and drivers of differences in health outcomes between these three groups, in order to explore the impact of urbanization independent of the impact of migration.

Results
There are consistent advantages in health and less depression among urbanized-rural residents compared with the rural group; and this group has even better health outcomes than the urban group after adjusting for early life differences. However, this relationship is reversed for waist circumference. Socioeconomic circumstances and factors related to a planned urbanization partly explain these effects.

Conclusions
Urbanization in China has, on average, had an independent and positive effect on health and well-being. Planned urbanization could benefit people’s health in developing countries. It is likely that improved infrastructure is a key driver.
Analysis of hard-thresholding for distributed compressed sensing with one-bit measurements
Authors: Maly Johannes , Palzer Lars 
Published: February 2019

Abstract
A simple hard-thresholding operation is shown to be able to uniformly recover $L$ signals $\textbf{x}_1,...,\textbf{x}_L \in{\mathbb{R}}^n$ that share a common support of size $s$ from $m = \mathscr{O}(s)$ one-bit measurements per signal if $L \geqslant \ln (en/s)$. This result improves the single signal recovery bounds with $m = \mathscr{O}(s\ln (en/s))$ measurements in the sense that asymptotically fewer measurements per non-zero entry are needed. Numerical evidence supports the theoretical considerations.
Twist Automorphisms on Quantum Unipotent Cells and Dual Canonical Bases
Authors: Kimura Yoshiyuki , Oya Hironori 
Published: February 2019

Abstract
In this paper, we construct twist automorphisms on quantum unipotent cells, which are quantum analogues of the Berenstein–Fomin–Zelevinsky twist automorphisms on unipotent cells. We show that those quantum twist automorphisms preserve the dual canonical bases of quantum unipotent cells. Moreover, we prove that quantum twist automorphisms are described by the syzygy functors for representations of preprojective algebras in the symmetric case. This is the quantum analogue of Geiß–Leclerc–Schröer’s description, and Geiß–Leclerc–Schröer’s results are essential in our proof. As a consequence, we show that quantum twist automorphisms are compatible with quantum cluster monomials. The 6-periodicity of specific quantum twist automorphisms is also verified.
Towards the Finite Slope Part for GLn
Authors: Breuil Christophe , Herzig Florian 
Published: February 2019

Abstract
Let $L$ be a finite extension of ${\mathbb{Q}}_p$ and $n\geq 2$. We associate to a crystabelline $n$-dimensional representation of ${\operatorname{Gal}}(\overline L/L)$ satisfying mild genericity assumptions a finite length locally ${\mathbb{Q}}_p$-analytic representation of ${\operatorname{GL}}_n(L)$. In the crystalline case and in a global context, using the recent results on the locally analytic socle from [6], we prove that this representation indeed occurs in spaces of $p$-adic automorphic forms. We then use this latter result in the ordinary case to show that certain “ordinary” $p$-adic Banach space representations constructed in our previous work appear in spaces of $p$-adic automorphic forms. This gives strong new evidence to our previous conjecture in the $p$-adic case.
Tied Labour, Savings and Rural Labour Market Wages: Evidence from a Framed Field Experiment
Authors: Nanyiti Aisha , Pamuk Haki , Bulte Erwin 
Published: February 2019

Abstract
How does the introduction of tied labour or a saving product affect labour market decisions and wages in rural agricultural labour markets? We develop a theoretical model of labour tying that incorporates diminishing marginal returns to consumption and inequality (behindness) aversion in the context of a rural agricultural labour market with seasonally fluctuating demand for labour, and test model predictions using a framed field experiment (modified ultimatum game) in rural Uganda. Our main findings are that (1) wages fluctuate with productivity, (2) access to tied contracts decreases wages for casual labour and (3) access to a saving technology does not improve wages for tied labour. Consistent with model predictions and earlier theory, we empirically find that income for workers goes down (and income for landlords goes up) if an institutional innovation enables consumption smoothing by workers (tied contracts or a saving technology).
A Novel Liquid Chromatography Tandem Mass Spectrometry Technique using Multi-Period-Multi-Experiment of MRM-EPI-MRM3 with Library Matching for Simultaneous Determination of Amphetamine Type Stimulants Related Drugs in Whole Blood, Urine and Dried Blood Stain (DBS)—Application to Forensic Toxicology Cases in Malaysia
Authors: Zubaidi Fathiah A , Choo Yeun-Mun , Tan Guan-Huat , Hamid Hamimah Abd , Choy Yap Ken 
Published: February 2019

Abstract
A novel mass spectrometry detection technique based on a multi-period and multi- experiment (MRM-EPI-MRM3) with library matching in a single run for fast and rapid screening and identification of amphetamine type stimulants (ATS) related drugs in whole blood, urine and dried blood stain was developed and validated. The ATS-related drugs analyzed in this study include ephedrine, pseudoephedrine, amphetamine, methamphetamine, MDMA (3,4-Methylenedioxymethamphetamine), MDA (3,4-Methylenedioxyamphetamine), MDEA (3,4-Methylenedioxy-N-ethylamphetamine) and phentermine. The relative standard deviation for inter and intraday was less than 15% while recoveries ranged from 80% to 120% for all three matrices, i.e., whole blood, urine and dried blood stain. All compounds gave library matching percentage of more than 85% based on the purity. This method was proven to be simple and robust, and provide high confident results complemented with library matching confirmation.