bluuebunny/crossref_metadata_2025_split huggingface dataset:
The EVcouplings Python framework for coevolutionary sequence analysis
Authors: Hopf Thomas A , Green Anna G , Schubert Benjamin , Mersmann Sophia , Schärfe Charlotta P I , Ingraham John B , Toth-Petroczy Agnes , Brock Kelly , Riesselman Adam J , Palmedo Perry , Kang Chan , Sheridan Robert , Draizen Eli J , Dallago Christian , Sander Chris , Marks Debora S 
Published: October 2018

Abstract

Summary
Coevolutionary sequence analysis has become a commonly used technique for de novo prediction of the structure and function of proteins, RNA, and protein complexes. We present the EVcouplings framework, a fully integrated open-source application and Python package for coevolutionary analysis. The framework enables generation of sequence alignments, calculation and evaluation of evolutionary couplings (ECs), and de novo prediction of structure and mutation effects. The combination of an easy to use, flexible command line interface and an underlying modular Python package makes the full power of coevolutionary analyses available to entry-level and advanced users.

Availability and implementation
https://github.com/debbiemarkslab/evcouplings
Long noncoding RNA Hoxaas3 contributes to hypoxia-induced pulmonary artery smooth muscle cell proliferation
Authors: Zhang Hongyue , Liu Ying , Yan Lixin , Wang Siqi , Zhang Min , Ma Cui , Zheng Xiaodong , Chen He , Zhu Daling 
Published: October 2018

AbstractAimsLong noncoding RNAs (lncRNAs) are involved in the regulation of vascular smooth muscle cells and cardiovascular pathology. However, the contribution of lncRNAs to pulmonary hypertension (PH) remains largely unknown. The over-proliferation of pulmonary artery smooth muscle cells (PASMCs) causes pulmonary arterial smooth muscle hypertrophy and stenosis of the pulmonary vascular lumen, resulting in PH. Here, we investigated the biological role of a novel lncRNA, Hoxa cluster antisense RNA 3 (Hoxaas3), in the regulation of cell proliferation in PH.Methods and resultsHoxaas3 was up-regulated in the lung vasculature of hypoxic mice and in PASMCs under hypoxic conditions. Histone H3 Lysine 9 acetylation of Hoxaas3 promoted gene expression. Moreover, high expression of Hoxaas3 was associated with cell proliferation and modulated cell cycle distribution by up-regulating Homeobox a3 at the mRNA and protein levels.ConclusionThis study defined the role and mechanism of action of Hoxaas3 in the regulation of cell proliferation in PH, which should facilitate the development of new therapeutic strategies for the treatment of this disease.
Is Living Alone “Aging Alone”? Solitary Living, Network Types, and Well-Being
Authors: Djundeva Maja , Dykstra Pearl A , Fokkema Tineke 
Published: October 2018

AbstractObjectivesWhen identifying older adults who may be at risk of being without necessary supports, policy makers and scholars tend to focus on those living alone, neglecting differences within that group. We examine how their social networks contribute to subjective well-being, why some of them fare better and compare their well-being to older adults coresiding with others.MethodData are from the fourth wave of the Survey of Health and Retirement in Europe (N = 53,383). A network typology for older people living alone (N = 10,047) is constructed using a latent class analysis. Using ordinary least squares (OLS) regressions, we examined differences in subjective well-being (life satisfaction, satisfaction with social network, depression) by network type, adding adults coresiding with others (N = 43,336) as comparison group.ResultsWe find four social network types among older adults living alone. The likelihood of having “restricted” and “child-based” networks is greater in Eastern and Southern European countries, whereas the likelihood of having “friend-oriented” networks is greater in Western and Northern European countries. Across countries, only those with “restricted” networks tend to have the poorest well-being. Those with “diverse” networks have even better well-being than coresiding older adults.DiscussionOur study shows the importance of drawing distinctions within the group of older adults living alone. Most (two thirds) are not vulnerable and at risk, but fare just as well or even better than peers who coreside with others. Country-level factors shape the opportunities to build satisfactory networks, but subjective well-being depends more strongly on individual resources, including social networks, than country-level factors.
Hospital admissions in the first year of life: inequalities over three decades in a southern Brazilian city
Authors: Wehrmeister Fernando C , Victora Cesar G , Horta Bernardo L , Menezes Ana M B , Santos Iná S , Bertoldi Andréa Dâmaso , da Silva Bruna G C , Barros Fernando C ,   Pelotas Cohorts Study Group, Barros Aluisio J D , Matijasevich Alicia , Bassani Diego G , Gonçalves Helen , Murray Joseph , Tovo-Rodrigues Luciana , Assunção Maria Cecilia F , Silveira Mariangela F , Domingues Marlos Rodrigues , Hallal Pedro R C 
Published: October 2018

Abstract

Background
Hospital admissions in infancy are declining in several countries. We describe admissions to neonatal intensive care units (NICU) and other hospitalizations over a 33-year period in the Brazilian city of Pelotas.

Methods
We analysed data from four population-based birth cohorts launched in 1982, 1993, 2004 and 2015, each including all hospital births in the calendar year. NICU and other hospital admissions during infancy were reported by the mothers in the perinatal interview and at the 12-month visit, respectively. We describe these outcomes by sex of the child, family income and maternal skin colour.

Results
In 1982, NICUs did not exist in the city; admissions into NICUs increased from 2.7% of all newborns in 1993 to 6.7% in 2015, and admission rates were similar in all income groups. Hospitalizations during the first year of life fell by 29%, from 23.7% in 1982 to 16.8% in 2015, and diarrhoea admissions fell by 95.2%. Pneumonia admissions fell by 46.3% from 1993 to 2015 (no data available for 1982). Admissions due to perinatal causes increased during the period. In the poorest income quintile, total admissions fell by 33% (from 35.7% to 23.9%), but in the richest quintile these remained stable at around 10%, leading to a reduction in inequalities. Over the whole period, children born to women with black or brown skin were 30% more likely to be admitted than those of white-skinned mothers.

Conclusions
Whereas NICU admissions increased, total admissions in the first year of life declined by nearly one-third. Socioeconomic disparities were reduced, but important gaps remain.
Putting a Number on Preferences: How Numerical Attitudes Are Shaped by Ideology and Equivalency Framing
Authors: Pedersen Rasmus T , Larsen Martin V 
Published: October 2018

AbstractNumbers are ubiquitous in modern political communication and discussions. The relationship between numbers and policy attitudes is therefore a key issue for public opinion research. This article explores the degree to which voters can translate their ideological predispositions into numerical policy preferences. Further, we theorize and investigate how numerical framing can affect this translation of ideology into numerical preferences. Using a survey experiment, we show that voters’ ideological differences are reflected in their numerical preferences, but that they are also highly affected by numerical framing, specifically gain–loss framing and unit framing. These results have implications for our theoretical understanding of framing effects, and they suggest that politicians can markedly affect the attitudes of voters through strategic use of numerical framing.
The Calculus of Finite (Metric) Dissonances
Authors: Reale Steven 
Published: October 2018

Abstract“Metric dissonance” is a term borrowed from the realm of pitch relationships, but many studies of metric dissonance draw primarily from a conception of dissonance based on the relative complexities of frequency ratios while downplaying the important syntactical aspect that dissonance plays in tonal music. This article develops existing models of metric dissonance, most notably that of Harald Krebs, by formalizing them through the calculus of finite differences, thereby introducing a methodology for quantifying metric dissonance. Such a formalization not only establishes a heuristic for comparing musical passages but also suggests an experiential model for hearing metrically dissonant music.
Subfamily-Specific Specialization of RGH1/MLA Immune Receptors in Wild Barley
Authors: Maekawa Takaki , Kracher Barbara , Saur Isabel M. L. , Yoshikawa-Maekawa Makoto , Kellner Ronny , Pankin Artem , von Korff Maria , Schulze-Lefert Paul 
Published: October 2018

The barley disease resistance (R) gene locus mildew locus A (Mla) provides isolate-specific resistance against the powdery mildew fungus Blumeria graminis hordei and has been introgressed into modern cultivars from diverse germplasms, including the wild relative Hordeum spontaneum. Known Mla disease resistance specificities to B. graminis hordei appear to encode allelic variants of the R gene homolog 1 (RGH1) family of nucleotide-binding domain and leucine-rich repeat (NLR) proteins. Here, we sequenced and assembled the transcriptomes of 50 H. spontaneum accessions representing nine populations distributed throughout the Fertile Crescent. The assembled Mla transcripts exhibited rich sequence diversity, linked neither to geographic origin nor population structure, and could be grouped into two similar-sized subfamilies based on two major N-terminal coiled-coil (CC) signaling domains that are both capable of eliciting cell death. The presence of positively selected sites located mainly in the C-terminal leucine-rich repeats of both MLA subfamilies, together with the fact that both CC signaling domains mediate cell death, implies that the two subfamilies are actively maintained in the population. Unexpectedly, known MLA receptor variants that confer B. graminis hordei resistance belong exclusively to one subfamily. Thus, signaling domain divergence, potentially as adaptation to distinct pathogen populations, is an evolutionary signature of functional diversification of an immune receptor. [Formula: see text] Copyright © 2018 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Very early-onset inflammatory bowel disease: an integrated approach
Authors: Sullivan Kathleen E. , Conrad Maire , Kelsen Judith R. 
Published: October 2018

Purpose of review
Immune dysregulation disorders are among the most rapidly growing set of inborn errors of immunity. One particular subset is the category where early-onset inflammatory bowel disease (IBD) is the most common manifestation. These disorders are being increasingly appreciated although there has been minimal effort to articulate a unified approach to their diagnosis and management. This review will cover current thinking and strategies related to diagnosis and management of very early-onset IBD.

Recent findings
There is an expanding set of monogenic causes of early-onset IBD. In many cases, the precise genetic cause dictates management. Lessons learned from the management of these monogenic conditions can sometimes be extrapolated to other refractory cases of IBD.

Summary
An integrated approach to diagnosis, risk analysis, and management can include diagnostic approaches not often utilized for traditional IBD such as whole exome sequencing. Management can also include nontraditional approaches such as targeted biologics or hematopoietic cell transplantation.
Redundant Information Is Sometimes More Beneficial Than Spatial Information to Understand Speech in Noise
Authors: Dieudonné Benjamin , Francart Tom 
Published: October 2018

Objectives:
To establish a framework to unambiguously define and relate the different spatial effects in speech understanding: head shadow, redundancy, squelch, spatial release from masking (SRM), and so on. Next, to investigate the contribution of interaural time and level differences to these spatial effects in speech understanding and how this is influenced by the type of masking noise.

Design:
In our framework, SRM is uniquely characterized as a linear combination of head shadow, binaural redundancy, and binaural squelch. The latter two terms are combined into one binaural term, which we define as binaural contrast: a benefit of interaural differences. In this way, SRM is a simple sum of a monaural and a binaural term. We used the framework to quantify these spatial effects in 10 listeners with normal hearing. The participants performed speech intelligibility tasks in different spatial setups. We used head-related transfer functions to manipulate the presence of interaural time and level differences. We used three spectrally matched masker types: stationary speech-weighted noise, a competing talker, and speech-weighted noise that was modulated with the broadband temporal envelope of the competing talker.

Results:
We found that (1) binaural contrast was increased by interaural time differences, but reduced by interaural level differences, irrespective of masker type, and (2) large redundancy (the benefit of having identical information in two ears) could reduce binaural contrast and thus also reduce SRM.

Conclusions:
Our framework yielded new insights in binaural processing in speech intelligibility. First, interaural level differences disturb speech intelligibility in realistic listening conditions. Therefore, to optimize speech intelligibility in hearing aids, it is more beneficial to improve monaural signal-to-noise ratios rather than to preserve interaural level differences. Second, although redundancy is mostly ignored when considering spatial hearing, it might explain reduced SRM in some cases.
Factors Affecting Sound-Source Localization in Children With Simultaneous or Sequential Bilateral Cochlear Implants
Authors: Killan Catherine , Scally Andrew , Killan Edward , Totten Catherine , Raine Christopher 
Published: October 2018

Objectives:
The study aimed to determine the effect of interimplant interval and onset of profound deafness on sound localization in children with bilateral cochlear implants, controlling for cochlear implant manufacturer, age, and time since second implant.

Design:
The authors conducted a retrospective, observational study using routinely collected clinical data. Participants were 127 bilaterally implanted children aged 4 years or older, tested at least 12 mo post- second implant. Children used implants made by one of three manufacturers. Sixty-five children were simultaneously implanted, of whom 43% were congenitally, bilaterally profoundly deaf at 2 and 4 kHz and 57% had acquired or progressive hearing loss. Sixty-two were implanted sequentially (median interimplant interval = 58 mo, range 3–143 mo) of whom 77% had congenital and 23% acquired or progressive bilateral profound deafness at 2 and 4 kHz. Children participated in a sound-source localization test with stimuli presented in a random order from five loudspeakers at –60, –30, 0, +30, and +60 degrees azimuth. Stimuli were prerecorded female voices at randomly roved levels from 65 to 75 dB(A). Root mean square (RMS) errors were calculated. Localization data were analyzed via multivariable linear regression models, one applied to the whole group and the other to just the simultaneously implanted children.

Results:
Mean RMS error was 25.4 degrees (SD = 12.5 degrees) with results ranging from perfect accuracy to chance level (0–62.7 degrees RMS error). Compared with simultaneous implantation, an interimplant interval was associated with worse localization by 1.7 degrees RMS error per year (p < 0.001). Compared with congenital deafness, each year with hearing thresholds better than 90 dB HL at 2 and 4 kHz bilaterally before implantation led to more accurate localization by 1.3 degrees RMS error (p < 0.005). Every year post-second implant led to better accuracy by 1.6 degrees RMS error (p < 0.05). Med-El was associated with more accurate localization than Cochlear by 5.8 degrees RMS error (p < 0.01) and with more accurate localization than Advanced Bionics by 9.2 degrees RMS error (p < 0.05).

Conclusions:
Interimplant interval and congenital profound hearing loss both led to worse accuracy in sound-source localization for children using bilateral cochlear implants. Interimplant delay should therefore be minimized for children with bilateral profound hearing loss. Children presenting with acquired or progressive hearing loss can be expected to localize better via bilateral cochlear implants than their congenitally deaf peers.
Mapping 241Am Spatial Distribution Within Anatomical Bone Structures Using Digital Autoradiography
Authors: Tabatadze George , Miller Brian W. , Tolmachev Sergei Y. 
Published: October 2018

Abstract
Digital autoradiography with the ionizing radiation quantum imaging detector is used at the US Transuranium and Uranium Registries for visualizing the microdistribution of alpha particles from 241Am and quantifying the activity. The radionuclide spatial distribution was investigated within cortical and trabecular regions of bone samples from US Transuranium and Uranium Registries case 0846. Multiple specimens from the humerus proximal end, humerus proximal shaft, and clavicle acromial end were embedded in plastic, and 100‐μm-thick sections were taken and imaged using the ionizing radiation quantum imaging detector. The detector images were superimposed on the anatomical structure images to visualize 241Am distribution in cortical bone, trabecular bone, and trabecular spongiosa. Activity concentration ratios were used to characterize 241Am distribution within different bone regions. The trabecular-to-cortical bone and trabecular-spongiosa-to-cortical bone activity concentration ratios were quantified in both humerus and clavicle. The ionizing radiation quantum imaging detector results were in agreement with those obtained from radiochemical analysis of the remaining bone specimens. The results were compared with International Commission on Radiological Protection default biokinetic model predictions. Digital autoradiography was proven to be an effective method for microscale heterogeneous distribution studies where traditional counting methods are impractical.
Preganglionic Parasympathetic Denervation Rabbit Model for Innervation Studies
Authors: Toshida Hiroshi , Suto Chikako 
Published: October 2018

Purpose:
Tear secretion from the main lacrimal gland (LG) is mainly regulated by parasympathetic nerves. We performed several innervation studies to investigate lacrimation.

Methods:
In male rabbits, we performed a retrograde dye-tracing study of LG innervation, evaluated preganglionic parasympathetic denervation, and administered glial cell–derived neurotrophic factor (GDNF) in the surgical area after parasympathetic denervation.

Results:
Accumulation of fluorescent dye was observed in the pterygopalatine ganglion cells on the same side as the dye injection into the main LG. Fewer stained cells were observed in the cervical and trigeminal ganglia. After parasympathetic denervation surgery, tear secretion was decreased, and fluorescein and rose bengal staining scores were increased at day 1 after surgery and remained increased for 3 months on the denervated side only. Most of the effects in rabbits with parasympathetic denervation were not recovered by administration of GDNF.

Conclusions:
The main LG is primarily innervated by parasympathetic nerves to stimulate tear secretion. After preganglionic parasympathetic denervation, lacrimation was decreased, resulting in dry eyes, and this was maintained for at least 3 months. Administration of GDNF only minimally altered the effects of denervation.
Fuchs Endothelial Corneal Dystrophy Through the Prism of Oxidative Stress
Authors: Jurkunas Ula V. 
Published: October 2018

Abstract:
The corneal endothelium (CE) is vital for maintaining the water balance and clarity of the cornea. The CE is a cell layer that is particularly susceptible to aging because of its postmitotic arrest, high metabolic activity involving pumping of ions, and lifelong exposure to ultraviolet light. Despite gradual age-related cell loss, a sufficient number of CE cells are preserved during the lifespan of an individual. However, in conditions such as Fuchs endothelial corneal dystrophy (FECD), permanent loss of CE cells leads to corneal edema and loss of vision requiring corneal transplantation. FECD is a genetic and oxidative stress disorder manifested by abnormal cell–matrix interactions and expedited cellular aging culminating in cellular death. Because the endothelium has minimal replicative capacity in vivo and an inability to replace its genome, it is particularly prone to cumulative DNA damage acquired throughout life. In FECD, the underlying genetic defects make the CE genome even more vulnerable to this damage, to the point of causing mitochondrial dysfunction, mitochondrial membrane potential loss, and excessive mitophagy activation. Endogenous and exogenous intracellular stressors alter the synthetic footprint of CE cells, leading to endothelial–mesenchymal transition and secretion of aberrant extracellular matrix (in the form of guttae), resembling scar formation in other organs. In turn, the guttae or endothelial scars contribute to a vicious cycle of FECD pathogenesis and, by further inducing endothelial–mesenchymal transition and oxidant–antioxidant imbalance, perpetuate the molecular changes of the degenerating endothelium.
Group B Streptococcal Neonatal and Early Infancy Infections in Iceland, 1976–2015
Authors: Björnsdóttir Erla S. , Martins Elisabete R. , Erlendsdóttir Helga , Haraldsson Gunnsteinn , Melo-Cristino José , Ramirez Mário , Kristinsson Karl G. 
Published: October 2018

Background:Despite a risk-based peripartum chemoprophylaxis approach in Iceland since 1996,Streptococcus agalactiae[group B streptococci (GBS)] remains an important cause of early-onset [<7 days, early-onset disease (EOD)] and late-onset disease (LOD; 7 days to 3 months).Methods:We studied GBS invasive disease in children <1 year in Iceland in 1976–2015. Bacteria (n = 98) were characterized by susceptibility to a panel of antimicrobials, capsular serotyping, resistance genes, surface protein and pilus-locus profiling and multilocus sequence typing.Results:Both EOD and LOD increased during the early years, but while EOD subsequently decreased from 0.7/1000 live births in 1991–1995 to 0.2/1000 in 2011–2015, LOD showed a nonsignificant decrease from its peak value of 0.6/1000 in 2001–2005 to 0.4/1000 in 2006–2015. Serotype III was the most frequently found (n = 48), represented mostly by the hypervirulent lineage CC17/III/rib/PI-1+PI-2b (62%), but also by CC19/III/rib/PI-1+PI-2a (35%) frequently associated with colonization. Serotype Ia (n = 22) was represented by CC23/Ia/eps/PI-2a (68%) and CC7/Ia/bca/PI-1+PI-2b (23%) of possible zoonotic origin. Resistance to erythromycin and clindamycin was increasingly detected in the last years of the study (5 of the 9 cases were isolated after 2013), including representatives of a multiresistant CC17/III/rib/PI-2b sublineage described recently in other countries and expressing resistance to erythromycin, clindamycin and streptomycin.Conclusions:The risk-based chemoprophylaxis adopted in Iceland possibly contributed to the decline of EOD but has had limited effect on LOD. GBS causing neonatal and early infancy invasive infections in Iceland are genetically diverse, and the recent emergence of antimicrobial resistant lineages may reduce the choices for prophylaxis and therapy of these infections.