bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overlap graph-based generation of haplotigs for diploids and polyploids
Authors: Baaijens Jasmijn A , Schönhuth Alexander 
Published: April 2019

Abstract

Motivation
Haplotype-aware genome assembly plays an important role in genetics, medicine and various other disciplines, yet generation of haplotype-resolved de novo assemblies remains a major challenge. Beyond distinguishing between errors and true sequential variants, one needs to assign the true variants to the different genome copies. Recent work has pointed out that the enormous quantities of traditional NGS read data have been greatly underexploited in terms of haplotig computation so far, which reflects that methodology for reference independent haplotig computation has not yet reached maturity.

Results
We present POLYploid genome fitTEr (POLYTE) as a new approach to de novo generation of haplotigs for diploid and polyploid genomes of known ploidy. Our method follows an iterative scheme where in each iteration reads or contigs are joined, based on their interplay in terms of an underlying haplotype-aware overlap graph. Along the iterations, contigs grow while preserving their haplotype identity. Benchmarking experiments on both real and simulated data demonstrate that POLYTE establishes new standards in terms of error-free reconstruction of haplotype-specific sequence. As a consequence, POLYTE outperforms state-of-the-art approaches in various relevant aspects, where advantages become particularly distinct in polyploid settings.

Availability and implementation
POLYTE is freely available as part of the HaploConduct package at https://github.com/HaploConduct/HaploConduct, implemented in Python and C++.

Supplementary information
Supplementary data are available at Bioinformatics online.
Fast detection of maximal exact matches via fixed sampling of queryK-mers and Bloom filtering of indexK-mers
Authors: Liu Yuansheng , Zhang Leo Yu , Li Jinyan 
Published: April 2019

AbstractMotivationDetection of maximal exact matches (MEMs) between two long sequences is a fundamental problem in pairwise reference-query genome comparisons. To efficiently compare larger and larger genomes, reducing the number of indexed k-mers as well as the number of query k-mers has been adopted as a mainstream approach which saves the computational resources by avoiding a significant number of unnecessary matches.ResultsUnder this framework, we proposed a new method to detect all MEMs from a pair of genomes. The method first performs a fixed sampling of k-mers on the query sequence, and adds these selected k-mers to a Bloom filter. Then all the k-mers of the reference sequence are tested by the Bloom filter. If a k-mer passes the test, it is inserted into a hash table for indexing. Compared with the existing methods, much less number of query k-mers are generated and much less k-mers are inserted into the index to avoid unnecessary matches, leading to an efficient matching process and memory usage savings. Experiments on large genomes demonstrate that our method is at least 1.8 times faster than the best of the existing algorithms. This performance is mainly attributed to the key novelty of our method that the fixed k-mer sampling must be conducted on the query sequence and the index k-mers are filtered from the reference sequence via a Bloom filter.Availability and implementationhttps://github.com/yuansliu/bfMEMSupplementary informationSupplementary data are available at Bioinformatics online.
DeepSignal: detecting DNA methylation state from Nanopore sequencing reads using deep-learning
Authors: Ni Peng , Huang Neng , Zhang Zhi , Wang De-Peng , Liang Fan , Miao Yu , Xiao Chuan-Le , Luo Feng , Wang Jianxin 
Published: April 2019

Abstract

Motivation
The Oxford Nanopore sequencing enables to directly detect methylation states of bases in DNA from reads without extra laboratory techniques. Novel computational methods are required to improve the accuracy and robustness of DNA methylation state prediction using Nanopore reads.

Results
In this study, we develop DeepSignal, a deep learning method to detect DNA methylation states from Nanopore sequencing reads. Testing on Nanopore reads of Homo sapiens (H. sapiens), Escherichia coli (E. coli) and pUC19 shows that DeepSignal can achieve higher performance at both read level and genome level on detecting 6 mA and 5mC methylation states comparing to previous hidden Markov model (HMM) based methods. DeepSignal achieves similar performance cross different DNA methylation bases, different DNA methylation motifs and both singleton and mixed DNA CpG. Moreover, DeepSignal requires much lower coverage than those required by HMM and statistics based methods. DeepSignal can achieve 90% above accuracy for detecting 5mC and 6 mA using only 2× coverage of reads. Furthermore, for DNA CpG methylation state prediction, DeepSignal achieves 90% correlation with bisulfite sequencing using just 20× coverage of reads, which is much better than HMM based methods. Especially, DeepSignal can predict methylation states of 5% more DNA CpGs that previously cannot be predicted by bisulfite sequencing. DeepSignal can be a robust and accurate method for detecting methylation states of DNA bases.

Availability and implementation
DeepSignal is publicly available at https://github.com/bioinfomaticsCSU/deepsignal.

Supplementary information
Supplementary data are available at bioinformatics online.
Phylogeny of Thripophagini ovenbirds (Aves: Synallaxinae: Furnariidae)
Authors: Quintero Esther , Perktaş Utku 
Published: April 2019

AbstractIn this study, we address the evolutionary relationships and discuss the biogeographical history of a complex and diverse group of ovenbirds, the Thripophagini. We reconstruct the phylogeny and estimate the time of divergence of this group, using sequences from two complete mitochondrial genes (cytochrome b and NADH subunit 2) from a total of 115 fresh tissue samples. The results provide a better understanding of the phylogenetic relationships of the taxa within this group, some of which require a thorough taxonomic revision. We discuss the biogeographical history of the group, and find parallels with other previously studied Andean birds which may indicate that tectonic and climatic events might, at least in part, be linked to its diversification through the uplift of the Andes, the creation of new montane habitats and barriers, the evolution of Amazonian drainages and landscapes, and the climatic oscillations of the Pleistocene.
The National Council for Civil Liberties and the British State during the First World War, 1916–1919
Authors: Keil André 
Published: April 2019

Abstract
The First World War saw an unprecedented expansion of the executive powers of the British government that radically changed the relationship between individual citizens and the state. This article offers a new perspective on these developments by analysing the activities of the National Council for Civil Liberties (NCCL) between 1916 and 1918. It explores the emergence of civil liberties activism in Britain during the war and its impact on British political culture. The NCCL became an efficiently organised pressure group, campaigning against press censorship, political policing and the suppression of anti-war dissent. This article argues that the innovative campaigning and propaganda methods used by the NCCL mark a moment of innovation that can be described as a revolution in activism. It represents a shift from the grass-roots political associations of the nineteenth century towards more professional forms of political activism that foreshadowed the rise of modern pressure groups and NGOs. The article also explains the emergence of a new discourse about the relationship between civil liberties, democracy and socialism in Britain during the First World War. The NCCL became an important locus for the networks of protest and dissent that emerged in Britain in response to the expansion of the wartime state. The article thus presents a new perspective on the beginnings of civil liberties activism in Britain and the impact of the First World War on its political culture.
Associations Between Self-Reported Sensory Impairment and Risk of Cognitive Decline and Impairment in the Health and Retirement Study Cohort
Authors: Maharani Asri , Dawes Piers , Nazroo James , Tampubolon Gindo , Pendleton Neil ,   Sense-Cog WP1 Group, Bertelsen Geir , Cosh Suzanne , Cougnard-Grégoire Audrey , Dawes Piers , Delcourt Cécile , Constantinidou Fofi , Goedegebure Andre , Helmer Catherine , Ikram M Arfan , Klaver Caroline C W , Leroi Iracema , Maharani Asri , Meester-Smor Magda , Nael Virginie , Oosterloo Neelke , Pendleton Neil , Schirmer Henrik , Tampubolon Gindo , Tiemeier Henning , von Hanno Therese 
Published: April 2019

Abstract

Objectives
We aimed to determine whether self-assessed single (hearing or visual) and dual sensory (hearing and visual) impairments are associated with cognitive decline and incident possible cognitive impairment, no dementia (CIND) and probable dementia.

Method
Data were drawn from the 1996–2014 surveys of the Health and Retirement Study (HRS), involving 19,618 respondents who had no probable dementia and who were aged 50 years or older at the baseline. We used linear mixed models to test the association between self-assessed sensory impairment and cognitive decline followed by a Cox proportional hazard model to estimate the relative risk of incident possible CIND and probable dementia associated with the presence of sensory impairment.

Results
Respondents with self-assessed single and dual sensory impairment performed worse in cognitive tests than those without sensory impairment. The fully adjusted incidence of developing possible CIND was 17% higher for respondents with hearing impairment than those without hearing impairment. Respondents with visual impairment had 35% and 25% higher risk for developing possible CIND and probable dementia, respectively, than those without visual impairment. Respondents with dual sensory impairment at baseline were 38% and 26% more likely to develop possible CIND and probable dementia, respectively, than those with no sensory impairment.

Discussion
Self-assessed sensory impairment is independently associated with cognitive decline and incident possible CIND and probable dementia. Further studies are needed to identify the mechanism underlying this association and to determine whether treatment of sensory impairment could ameliorate cognitive decline and delay the onset of dementia among older adults.
Dysregulation of NRAP degradation by KLHL41 contributes to pathophysiology in nemaline myopathy
Authors: Jirka Caroline , Pak Jasmine H , Grosgogeat Claire A , Marchetii Michael Mario , Gupta Vandana A 
Published: April 2019

Abstract
Nemaline myopathy (NM) is the most common form of congenital myopathy that results in hypotonia and muscle weakness. This disease is clinically and genetically heterogeneous, but three recently discovered genes in NM encode for members of the Kelch family of proteins. Kelch proteins act as substrate-specific adaptors for Cullin 3 (CUL3) E3 ubiquitin ligase to regulate protein turnover through the ubiquitin-proteasome machinery. Defects in thin filament formation and/or stability are key molecular processes that underlie the disease pathology in NM; however, the role of Kelch proteins in these processes in normal and diseases conditions remains elusive. Here, we describe a role of NM causing Kelch protein, KLHL41, in premyofibil-myofibil transition during skeletal muscle development through a regulation of the thin filament chaperone, nebulin-related anchoring protein (NRAP). KLHL41 binds to the thin filament chaperone NRAP and promotes ubiquitination and subsequent degradation of NRAP, a process that is critical for the formation of mature myofibrils. KLHL41 deficiency results in abnormal accumulation of NRAP in muscle cells. NRAP overexpression in transgenic zebrafish resulted in a severe myopathic phenotype and absence of mature myofibrils demonstrating a role in disease pathology. Reducing Nrap levels in KLHL41 deficient zebrafish rescues the structural and function defects associated with disease pathology. We conclude that defects in KLHL41-mediated ubiquitination of sarcomeric proteins contribute to structural and functional deficits in skeletal muscle. These findings further our understanding of how the sarcomere assembly is regulated by disease-causing factors in vivo, which will be imperative for developing mechanism-based specific therapeutic interventions.
Late-stage obstruction due to preventative wrapping of left ventricular assist device outflow graft
Authors: Hsu Steven , Freed Kristin E , Choi Chun W , Kilic Ahmet 
Published: April 2019

Abstract
Preventative polytetrafluoroethylene coverings are often used to protect the left ventricular assist device outflow graft during sternal re-entry. We herein describe 5 cases of late-onset, significant left ventricular assist device outflow graft obstruction due to external outflow graft compression. We present clinical presentations, therapies and outcomes.
Adding tricuspid repair to standard open heart surgery does not increase risk but improves right ventricular function
Authors: Pingpoh Clarence , Nuss Sarah , Kueri Sami , Kreibich Maximillian , Czerny Martin , Beyersdorf Friedhelm , Siepe Matthias 
Published: April 2019

Abstract

OBJECTIVES
To evaluate outcome of concomitant tricuspid annuloplasty in mild or moderate regurgitation on perioperative outcome and on right ventricular function in patients undergoing major cardiac surgery.

METHODS
Among 14 500 patients who underwent cardiac surgery at our institution between January 2000 and April 2016, 1023 patients had a documented history of tricuspid regurgitation (TR). Of those patients, 324 patients were diagnosed with mild or moderate secondary TR with a dilated annulus (≥40 mm or >21 mm/m2) and composed the study population. The decision to perform concomitant annuloplasty was subjected to the individual decision of the treating surgeon. Our analysis focused on a comparison between patients with concomitant TR-repair (group 1, n = 184) and patients without concomitant TR-repair (group 2, n = 140) after propensity score matching.

RESULTS
Following a preliminary data preprocessing, we observed a mean age of 73.8 years, mean logistic EuroSCORE of 10.5%. Perioperative mortality was 4.4% in group 1 and 5.7% in group 2. There was no significant difference in mid-term mortality. TR after surgery was significantly higher in group 2. After propensity score matching regression analysis, patients who had a repaired tricuspid valve (group 1) had better right ventricle (RV) function than those without TR-repair (group 2) (P > 0.05 at 95% confidence interval following Kolmogorov–Smirnov Goodness of fit Test).

CONCLUSIONS
Adding tricuspid valve repair in patients with mild or moderate secondary TR with a dilated annulus (≥40 mm or >21 mm/m2) to standard open heart surgery does not increase perioperative risk but improves right ventricular function. Therefore, standard tricuspid repair in this subgroup might be considered on a routine basis.
Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and risk of total and cause-specific mortality: results from the Golestan Cohort Study
Authors: Mokhtari Zeinab , Sharafkhah Maryam , Poustchi Hossein , Sepanlou Sadaf G , Khoshnia Masoud , Gharavi Abdolsamad , Sohrabpour Amir Ali , Sotoudeh Masoud , Dawsey Sanford M , Boffetta Paolo , Abnet Christian C , Kamangar Farin , Etemadi Arash , Pourshams Akram , FazeltabarMalekshah Akbar , Islami Farhad , Brennan Paul , Malekzadeh Reza , Hekmatdoost Azita 
Published: April 2019

AbstractObjectiveTo evaluate the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and overall and cause-specific mortality in the Golestan Cohort Study (GCS).MethodsA total of 50 045 participants aged 40 years or older were recruited from Golestan Province, Iran, from 2004 to 2008 and followed for a mean of 10.64 years. The DASH diet score was calculated for each individual based on food groups. The primary outcome measure was death from any cause.ResultsDuring 517 326 person-years of follow-up, 6763 deaths were reported. After adjustment for potential confounders, DASH diet score was inversely associated with risk of death from all causes and cancers [hazard ratio (HR): 0.86; 95% confidence interval (CI): 0.75, 0.98; and HR: 0.65; 95% CI: 0.47, 0.90, respectively]. A higher DASH diet score was associated with lower risk of gastrointestinal cancer mortality in men (HR: 0.55; 95% CI: 0.30, 0.99). A greater adherence to DASH diet was also associated with lower other-cancer mortality in women (HR: 0.50; 95% CI: 0.24, 0.99). No association between DASH diet score and cardiovascular disease mortality was observed, except that those dying of cardiovascular disease were younger than 50 years of age and smokers.ConclusionsOur findings suggest that maintaining a diet similar to the DASH diet is independently associated with reducing the risk of total death, cancers, and especially gastrointestinal cancers in men.
Software application profile: the Rapid Inquiry Facility 4.0: an open access tool for environmental public health tracking
Authors: Piel Frédéric B , Parkes Brandon , Hambly Peter , Roca-Barceló Aina , McCallion Martin , Leonardi Giovanni , Strosnider Heather , Yip Fuyuen , Elliott Paul , Hansell Anna L 
Published: April 2019

AbstractThe Rapid Inquiry Facility 4.0 (RIF) is a new user-friendly and open-access tool, developed by the UK Small Area Health Statistics Unit (SAHSU), to facilitate environment public health tracking (EPHT) or surveillance (EPHS). The RIF is designed to help public health professionals and academics to rapidly perform exploratory investigations of health and environmental data at the small-area level (e.g. postcode or detailed census areas) in order to identify unusual signals, such as disease clusters and potential environmental hazards, whether localized (e.g. industrial site) or widespread (e.g. air and noise pollution). The RIF allows the use of advanced disease mapping methods, including Bayesian small-area smoothing and complex risk analysis functionalities, while accounting for confounders. The RIF could be particularly useful to monitor spatio-temporal trends in mortality and morbidity associated with cardiovascular diseases, cancers, diabetes and chronic lung diseases, or to conduct local or national studies on air pollution, flooding, low-magnetic fields or nuclear power plants.
Keeping the Engine Running: The Relevance and Predictive Value of Preclinical Models for CAR-T Cell Development
Authors: Migliorini Denis , Mason Nicola J , Posey Avery D 
Published: April 2019

Abstract
The cellular immunotherapy field has achieved important milestones in the last 30 years towards the treatment of a variety of cancers due to improvements in ex-vivo T cell manufacturing processes, the invention of synthetic T cell receptors, and advances in cellular engineering. Here, we discuss major preclinical models that have been useful for the validation of chimeric antigen receptor (CAR)-T cell therapies and also promising new models that will fuel future investigations towards success. However, multiple unanswered questions in the CAR-T cell field remain to be addressed that will require innovative preclinical models. Key challenges facing the field include premature immune rejection of universal CAR-T cells and the immune suppressive tumor microenvironment. Immune competent models that accurately recapitulate tumor heterogeneity, the hostile tumor microenvironment, and barriers to CAR-T cell homing, toxicity, and persistence are needed for further advancement of the field.
A New Affine Invariant Geometric Functional for Polytopes and Its Associated Affine Isoperimetric Inequalities
Authors: Hu Jiaqi , Xiong Ge 
Published: April 2019

Abstract
A new affine invariant geometric functional for convex polytopes is introduced. Some new sharp affine isoperimetric inequalities are established for this new functional, which are extensions of Lutwak–Yang–Zhang’s results on their celebrated cone-volume functional.
Discrimination in the Age of Algorithms
Authors: Kleinberg Jon , Ludwig Jens , Mullainathan Sendhil , Sunstein Cass R 
Published: April 2019

Abstract
The law forbids discrimination. But the ambiguity of human decision-making often makes it hard for the legal system to know whether anyone has discriminated. To understand how algorithms affect discrimination, we must understand how they affect the detection of discrimination. With the appropriate requirements in place, algorithms create the potential for new forms of transparency and hence opportunities to detect discrimination that are otherwise unavailable. The specificity of algorithms also makes transparent tradeoffs among competing values. This implies algorithms are not only a threat to be regulated; with the right safeguards, they can be a potential positive force for equity.
Loss of mismatch repair signaling impairs the WNT–bone morphogenetic protein crosstalk and the colonic homeostasis
Authors: Nørgaard Katrine , Müller Carolin , Christensen Nadja , Chiloeches María L , Madsen Cesilie L , Nielsen Sabine S , Thingholm Tine E , Belcheva Antoaneta 
Published: April 2019

AbstractThe fine balance between proliferation, differentiation, and apoptosis in the colonic epithelium is tightly controlled by the interplay between WNT, Notch, and bone morphogenetic protein (BMP) signaling. How these complex networks coordinate the colonic homeostasis, especially if cancer predisposing mutations such as mutations in the DNA mismatch repair (MMR) are present, is unclear. Inactivation of the MMR system has long been linked to colorectal cancer; however, little is known about its role in the regulation of the colonic homeostasis. It has been shown that loss of MMR promotes the proliferation of colon epithelial cells that renders them highly susceptible to transformation. The mechanism through which MMR mediates this effect, yet, remains to be determined. Using an MMR-deficient mouse model, we show that increased methylation of Dickkopf1 impacts its expression, and consequently, the ability to negatively regulate WNT signaling. As a result, excessive levels of active β-catenin promote strong crypt progenitor-like phenotype and abnormal proliferation. Under these settings, the development and function of the goblet cells are affected. MMR-deficient mice have fewer goblet cells with enlarged mucin-loaded vesicles. We further show that MMR inactivation impacts the WNT–BMP signaling crosstalk.