bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reclassification of Hypertensive Outpatients According to New US Guidelines on High Blood Pressure
Authors: Tocci Giuliano , Presta Vivianne , Figliuzzi Ilaria , Miceli Francesca , Citoni Barbara , Coluccia Roberta , Paini Anna , Salvetti Massimo , Ferrucci Andrea , Muiesan Maria Lorenza , Volpe Massimo 
Published: September 2018

Abstract

BACKGROUND
US guidelines on high blood pressure (BP) have recently proposed a new BP stratification.

OBJECTIVE
To evaluate the redistribution of adult outpatients according to 2003 and 2017 US hypertension guidelines.

METHODS
We extracted data referred to individuals aged between 40 and 70 years with valid BP assessment from a national, cross-sectional database. The following systolic/diastolic BP strata were considered: (i) 2003 guidelines: 0 = normal (&lt;120/180 mm Hg), 1 = prehypertension (≥120 and ≤139/≥80 and ≤89 mm Hg), 2 = stage 1 (≥140 and ≤159/≥90 and ≤99 mm Hg), 3 = stage 2 (≥160/≥100 mm Hg) and (ii) 2017 American College of Cardiology/American Heart Association guidelines: 0 = normal (&lt;120/80 mm Hg), 1 = elevated (≥120 and ≤129/&lt;80 mm Hg); 2 = stage 1 (≥130 and ≤139/≥80 and ≤89 mm Hg), 3 = stage 2 (≥140/≥90 mm Hg). Cardiovascular (CV) risk profile characterization was based on Framingham, 10-year risk of a first atherosclerotic cardiovascular disease and European score equations.

RESULTS
From an overall population sample of 10,012 individuals, we selected 8,911 (89.0%) with valid clinic BP data (44.4% female, age = 60.7 ± 6.6 years, body mass index = 28.2 ± 4.9 kg/m2, clinic BP = 136.8 ± 14.5/82.1 ± 8.3 mm Hg), among whom 339 (3.8%) were in the normal BP range. According to 2003 guidelines, 3,919 (44.0%) patients had prehypertension, 3,698 (41.5%) had stage-1 and 955 (10.7%) had stage-2 hypertension. According to 2017 guidelines, 635 (3.8%) patients had elevated BP, 3,284 (36.9%) had stage-1 and 4,653 (52.2%) had stage-2 hypertension. New BP classification moved 37% individuals from “pre-hypertension” to “stage 1” and 41% from “stage 1” to “stage 2” hypertension, respectively.

CONCLUSIONS
Redistribution of hypertensive patients according to 2017 US hypertension guidelines compared with previous ones may help to better identify uncontrolled hypertensive patients with high CV risk profile.
Inference and visualization of DNA damage patterns using a grade of membership model
Authors: Al-Asadi Hussein , Dey Kushal K , Novembre John , Stephens Matthew 
Published: September 2018

Abstract

Motivation
Quality control plays a major role in the analysis of ancient DNA (aDNA). One key step in this quality control is assessment of DNA damage: aDNA contains unique signatures of DNA damage that distinguish it from modern DNA, and so analyses of damage patterns can help confirm that DNA sequences obtained are from endogenous aDNA rather than from modern contamination. Predominant signatures of DNA damage include a high frequency of cytosine to thymine substitutions (C-to-T) at the ends of fragments, and elevated rates of purines (A & G) before the 5′ strand-breaks. Existing QC procedures help assess damage by simply plotting for each sample, the C-to-T mismatch rate along the read and the composition of bases before the 5′ strand-breaks. Here we present a more flexible and comprehensive model-based approach to infer and visualize damage patterns in aDNA, implemented in an R package aRchaic. This approach is based on a ‘grade of membership’ model (also known as ‘admixture’ or ‘topic’ model) in which each sample has an estimated grade of membership in each of K damage profiles that are estimated from the data.

Results
We illustrate aRchaic on data from several aDNA studies and modern individuals from 1000 Genomes Project Consortium (2012). Here, aRchaic clearly distinguishes modern from ancient samples irrespective of DNA extraction, lab and sequencing protocols. Additionally, through an in-silico contamination experiment, we show that the aRchaic grades of membership reflect relative levels of exogenous modern contamination. Together, the outputs of aRchaic provide a concise visual summary of DNA damage patterns, as well as other processes generating mismatches in the data.

Availability and implementation
aRchaic is available for download from https://www.github.com/kkdey/aRchaic.

Supplementary information
Supplementary data are available at Bioinformatics online.
Ambiguous splice sites distinguish circRNA and linear splicing in the human genome
Authors: Dehghannasiri Roozbeh , Szabo Linda , Salzman Julia 
Published: September 2018

Abstract

Motivation
Identification of splice sites is critical to gene annotation and to determine which sequences control circRNA biogenesis. Full-length RNA transcripts could in principle complete annotations of introns and exons in genomes without external ontologies, i.e., ab initio. However, whether it is possible to reconstruct genomic positions where splicing occurs from full-length transcripts, even if sampled in the absence of noise, depends on the genome sequence composition. If it is not, there exist provable limits on the use of RNA-Seq to define splice locations (linear or circular) in the genome.

Results
We provide a formal definition of splice site ambiguity due to the genomic sequence by introducing equivalent junction, which is the set of local genomic positions resulting in the same RNA sequence when joined through RNA splicing. We show that equivalent junctions are prevalent in diverse eukaryotic genomes and occur in 88.64% and 78.64% of annotated human splice sites in linear and circRNA junctions, respectively. The observed fractions of equivalent junctions and the frequency of many individual motifs are statistically significant when compared against the null distribution computed via simulation or closed-form. The frequency of equivalent junctions establishes a fundamental limit on the possibility of ab initio reconstruction of RNA transcripts without appealing to the ontology of “GT-AG” boundaries defining introns. Said differently, completely ab initio is impossible in the vast majority of splice sites in annotated circRNAs and linear transcripts.

Availability and implementation
Two python scripts generating an equivalent junction sequence per junction are available at: https://github.com/salzmanlab/Equivalent-Junctions.

Supplementary information
Supplementary data are available at Bioinformatics online.
German senior citizens’ capabilities for physical activity: a qualitative study
Authors: Sauter Alexandra , Curbach Janina , Rueter Jana , Lindacher Verena , Loss Julika 
Published: September 2018

Abstract
Sen’s capability approach (CA) has found its way into health promotion over the last few years. The approach takes both individual factors as well as social and environmental conditions into account and therefore appears to have great potential to explore opportunities for (‘capabilities’) and barriers to active lifestyles. Thus, our objective in this study was to investigate which capabilities senior citizens perceive to have available to them in order to be physically active. In Southern Germany, we conducted 26 semi-standardized interviews with senior citizens aged 66–97, as well as 9 interviews with key persons who have close contact to senior citizens in their work life. We identified 11 capabilities which the interviewees considered as important in leading an active lifestyle. They could be grouped into four domains: (1) individual resources, (2) social interactions and norms, (3) living conditions and (4) organizational environment. Results highlight the need for health-promoting interventions that widen the range of capabilities on social and environmental levels in a way that individuals can freely choose to be as physically active as they like. The results make clear that interventions should not only target and involve older adults themselves, but also their families, nursing home staff or community representatives, because these groups are important in shaping older adults’ capabilities for an active lifestyle.
Internal dynamics of the Large Magellanic Cloud from Gaia DR2
Authors: Vasiliev Eugene 
Published: September 2018

Abstract
We use the proper motions (PM) of half a million red giant stars in the Large Magellanic Cloud measured by Gaia to construct a 2D kinematic map of mean PM and its dispersion across the galaxy, out to 7 kpc from its centre. We then explore a range of dynamical models and measure the rotation curve, mean azimuthal velocity, velocity dispersion profiles, and the orientation of the galaxy. We find that the circular velocity reaches ∼90 km s−1 at 5 kpc, and that the velocity dispersion ranges from ∼30–40 km s−1 in the galaxy centre to ∼15–20 km s−1 at 7 kpc.
The Predictive Validity of Physical Performance Measures in Determining Markers of Preclinical Disability in Community-Dwelling Middle-Aged and Older Adults: A Systematic Review
Authors: Cavanaugh Ellen J , Richardson Jenna , McCallum Christine A , Wilhelm Mark 
Published: September 2018

Abstract

Background
Identification of preclinical disability in middle-aged and older adults might allow early identification of and treatment for functional mobility deficits.

Purpose
This study aimed to determine which physical performance measures (PPMs) were effective in identifying preclinical disability in individuals at risk for future disability.

Data Sources
CINHAL, PubMed, Scopus, and Web of Science databases were searched until September 2017 using key words.

Study Selection
Two individuals screened peer-reviewed prospective longitudinal studies that assessed healthy individuals &gt; 45 years old using PPMs at baseline. Eight studies met inclusion criteria.

Data Extraction
Two individuals extracted data on participant demographics, PPMs, predictive validity effect size, and disability outcomes. Risk of bias was assessed using the Quality Assessment Tool for Cohort Studies II (Q-Coh II).

Data Synthesis
Four constructs were used to guide data synthesis: functional mobility, activities of daily living disability, fall(s), and hospitalization. Multiple sit-to-stands from a chair, standing balance, and gait speed were found to have some merit in identifying preclinical disability across all 4 disability constructs. All studies were scored as good-quality studies using the Q-Coh II.

Limitations
The heterogeneity in follow-up times and reporting of risk prediction statistics made it difficult to compare results across studies, PPMs, and constructs. The 4 constructs used as markers of preclinical disability potentially do not fully capture the progression of disability.

Conclusions
Physical therapists should consider using PPMs on healthy adult populations to gather baseline data during annual health screens for use in identifying preclinical disability.
Galleria mellonellaas an infection model for the multi-host pathogenStreptococcus agalactiaereflects hypervirulence of ST283
Authors: Six Anne , Kranjangwong Sakranmanee , Crumlish Margaret , Zadoks Ruth , Walker Daniel 
Published: September 2018

AbstractStreptococcus agalactiae, or group B streptococcus (GBS), infects diverse hosts including humans, economically important livestock and fishes. In the context of human health, GBS is a major cause of neonatal infections and an emerging cause of invasive disease in adults. Here we show that GBS is able to establish a systemic infection inG. mellonellalarvae that is associated with extensive bacterial replication and dose dependent larval survival. This infection model is suitable for use with GBS isolates from both homeothermic and poikilothermic hosts and a hypervirulent sequence type (ST) associated with invasive human disease, ST283, shows increased virulence in this model, indicating it may be useful in studying GBS virulence determinants. In addition, we demonstrate that larval survival can be afforded by antibiotic treatment and so the model may also be useful in the development of novel anti-GBS strategies. The use ofG. mellonellain GBS research has the potential to provide a low cost infection model that could reduce the number of vertebrates used in the study of GBS infection.
Sex differences in post-stroke aphasia rates are caused by age. A meta-analysis and database query
Authors: Wallentin Mikkel 
Published: September 2018

AbstractBackgroundStudies have suggested that aphasia rates are different in men and women following stroke. One hypothesis says that men have more lateralized language function than women. Given unilateral stroke, this would lead to a prediction of men having higher aphasia rates than women. Another line of observations suggest that women are more severely affected by stroke, which could lead to a higher aphasia rate among women. An additional potential confounding variable could be age, given that women are typically older at the time of stroke.Methods & ProceduresThis study consists of two parts. First, a meta-analysis of the available reports of aphasia rates in the two sexes was conducted. A comprehensive literature search yielded 25 studies with sufficient information about both aphasia and gender. These studies included a total of 48,362 stroke patients for which aphasia rates were calculated. Second, data were extracted from an American health database (with 1,967,038 stroke patients), in order to include age and stroke severity into a regression analysis of sex differences in aphasia rates.Outcomes & ResultsBoth analyses revealed significantly larger aphasia rates in women than in men (1.1-1.14 ratio). This speaks against the idea that men should be more lateralized in their language function. When age and stroke severity were included as covariates, sex failed to explain any aphasia rate sex difference above and beyond that which is explained by age differences at time of stroke.
Structural instability of IкB kinase β promotes autophagic degradation through enhancement of Keap1 binding
Authors: Kanamoto Mayu , Tsuchiya Yoshihiro , Nakao Yuki , Suzuki Takafumi , Motohashi Hozumi , Yamamoto Masayuki , Kamata Hideaki 
Published: September 2018

AbstractIKKβ, an essential kinase of NF-кB signaling, is composed of an N-terminal kinase domain (KD) and a C-terminal scaffolding domain, containing a ubiquitin-like domain (ULD). The Hsp90 chaperon has special responsibility for folding of protein kinases including IKKβ. Here, we found that Hsp90 inhibition induced IKKβ degradation, which is partially mediated by Keap1. Geldanamycin (GA), a Hsp90 inhibitor, enhances association of IKKβ with Keap1 through the binding site in KD, and translocates IKKβ to detergent-insoluble fractions leading its autophagic degradation. An electrophile tBHQ suppressed Keap1-mediated proteasomal Nrf2 degradation but not autophagic IKKβ degradation. Substitution mutation of Leu353 to Ala in the ULD destabilizes IKKβ, enhances its association with Keap1, translocates it to detergent-insoluble fractions, and causes its autophagic degradation. These results suggest that Keap1 is involved in the degradation of structural destabilized IKKβ and negative regulation of NF-кB under proteotoxic stress.
A Flexible Model of Working Memory
Authors: Bouchacourt Flora , Buschman Timothy J. 
Published: September 2018

AbstractWorking memory is fundamental to cognition, allowing one to hold information ‘in mind’ and use it to guide behavior. A defining characteristic of working memory is its flexibility: we can hold anything in mind. However, typical models of working memory rely on finely tuned, content-specific, attractors to persistently maintain neural activity and therefore do not allow for the flexibility observed in behavior. Here we present a flexible model of working memory that maintains representations through random recurrent connections between two layers of neurons: a structured ‘sensory’ layer and a randomly connected, unstructured, layer. As the interactions are untuned with respect to the content being stored, the network is able to maintain any arbitrary input. However, this flexibility comes at a cost: the random connections overlap, leading to interference between representations and limiting the memory capacity of the network. Additionally, our model captures several other key behavioral and neurophysiological characteristics of working memory.
USP21 and OTUD3 Antagonize Regulatory Ribosomal Ubiquitylation and Ribosome-Associated Quality Control
Authors: Garshott Danielle M. , Sundaramoorthy Elayanambi , Leonard Marilyn , Bennett Eric J. 
Published: September 2018

SUMMARYDefects within mRNAs or nascent chains that halt ribosomal progression can trigger ribosome-associated quality control (RQC) pathways that facilitate mRNA and nascent polypeptide destruction as well as ribosome recycling. Failure to remove defective mRNAs or nascent chains can lead to the accumulation of cytotoxic protein aggregates and proteotoxic stress. We previously established that the E3 ligase ZNF598 catalyzes regulatory ribosomal ubiquitylation of specific 40S ribosomal proteins required for downstream RQC events. Utilizing an optical RQC reporter we identify OTUD3 and USP21 as deubiquitylating enzymes that antagonize ZNF598-mediated 40S ubiquitylation and facilitate ribosomal deubiquitylation following RQC activation. Overexpression of either USP21 or OTUD3 enhances readthrough of stall-inducing sequences as compared to knock-in cells lacking individual RRub sites suggesting that combinatorial ubiquitylation of RPS10 (eS10) and RPS20 (uS10) is required for optimal resolution of RQC events and that deubiquitylating enzymes can limit RQC activation.
How good are pathogenicity predictors in detecting benign variants?
Authors: Niroula Abhishek , Vihinen Mauno 
Published: September 2018

ABSTRACTComputational tools are widely used for interpreting variants detected in sequencing projects. The choice of computational tools is critical for reliable variant impact interpretation for precision medicine and should be based on systematic performance assessment. The performance of the methods varies widely in different performance assessments, for example due to the sizes of test datasets. To address this issue, we obtained 63,160 common amino acid substitutions (allele frequency ≥1% and <25%) from the Exome Aggregation Consortium (ExAC) database, which contains variants from 60,706 genomes or exomes. We evaluated the specificity, the capability to detect benign variants, for 10 variant interpretation tools. In addition to overall specificity of the tools, we tested their performance for variants in six geographical populations. PON-P2 had the best performance (95.5%) followed by FATHMM (86.4%) and VEST (83.5%). While these tools had excellent performance, the poorest method predicted more than one third of the benign variants to be disease-causing. The results allow choosing reliable methods for benign variant interpretation, for both research and clinical purposes, as well as provide a benchmark for method developers.AUTHOR SUMMARYIn precision/personalized medicine of many conditions it is essential to investigate individual’s genome. Interpretation of the observed variation (mutation) sets is feasible only with computational approaches. We assessed the performance of variant pathogenicity/tolerance prediction programs on benign variants. Variants were obtained from high-quality ExAC database and selected to have minor allele frequency between 1 and 25%. We obtained 63,160 such cases and investigated 10 widely used predictors. Specificities of the methods showed large differences, from 0.64 to 0.96%, thus users of these methods have to be careful when choosing the one(s) they will use. We investigated further the performances on different populations, allele frequencies, separately for males and females, chromosome wise and for population unique and non-unique variants. The ranking of the tools remained the same in all these scenarios, i.e. the best methods were the best irrespective on how the data is filtered and grouped. This is to our knowledge the first evaluation of method performance on benign variants.
Photon-separation to enhance the spatial resolution in pulsed STED microscopy
Authors: Tortarolo Giorgio , Sun Yuansheng , Teng Kai-Wen , Ishitsuka Yuji , Lanzanó Luca , Selvin Paul R. , Barbieri Beniamino , Diaspro Alberto , Vicidomini Giuseppe 
Published: September 2018

AbstractStimulated emission depletion microscopy (STED) is one of the pivotal super-resolution techniques. It overcomes the spatial resolution limit imposed by the diffraction by using an additional laser beam, the STED beam, whose intensity is directly related to the achievable resolution. Despite achieving nanometer resolution, much effort in recent years has been devoted to reduce the STED beam intensity because it may lead to photo-damaging effects. Exploring the temporal dynamics of the detected fluorescence photons and accessing the encoded spatial information has proven to be a powerful strategy, and has contributed to the separation by lifetime tuning (SPLIT) technique. The SPLIT technique uses the phasor analysis to efficiently distinguish photons emitted from the center and the periphery of the excitation spot. It thus improves the resolution without increasing the STED beam intensity. This method was proposed for architectures based on STED beam running in continuous wave (CW-STED microscopy). Here, we extend it to architectures based on pulsed STED beam (pSTED microscopy). We show, through simulated and experimental data, that the SPLIT-pSTED method reduces the detection volume of the pSTED microscope without significantly reducing the signal-to-noise ratio of the final image, thus effectively improving the resolution without increasing the STED beam intensity.
Estimating HLA disease associations using similarity trees
Authors: Dorp Christiaan H. van , Keşmir Can 
Published: September 2018

AbstractThe human leukocyte antigen (HLA) is associated with many (infectious) disease outcomes. These associations are perhaps best documented for HIV-1. For example, the HLA-B*58:01 allele is associated with control of the virus, while HLA-B*18:01 is considered detrimental. In HLA disease association studies, it is often ignored that certain HLA molecules are functionally very similar to others. For instance, HLA-B*18:03 differs “only” at 3 positions in its peptide binding site from HLA-B*18:01, and not surprisingly, HLA-B*18:03 is also associated with fast progression to AIDS. Here, we present a Bayesian method that takes functional HLA similarities into account to find HLA associations with quantitative traits such as HIV-1 viral load. The method is based on the so-called phylogenetic mixed model (a model for the evolution of a quantitative trait on the branches of a phylogeny), and can easily be modified to study a wide range of research questions, like the role of the heterozygote advantage, or KIR ligands on disease outcomes. We show that in the case of HIV-1, our model is significantly better at predicting set-point virus load than a model that ignores HLA similarities altogether. Furthermore, our method provides a comprehensible visualization of HLA associations. The software is available online at www.github.com/chvandorp/MHCshrubs