bluuebunny/crossref_metadata_2025_split huggingface dataset:
New artificial intelligence prediction model using serial prothrombin time international normalized ratio measurements in atrial fibrillation patients on vitamin K antagonists: GARFIELD-AF
Authors: Goto Shinichi , Goto Shinya , Pieper Karen S , Bassand Jean-Pierre , Camm Alan John , Fitzmaurice David A , Goldhaber Samuel Z , Haas Sylvia , Parkhomenko Alexander , Oto Ali , Misselwitz Frank , Turpie Alexander G G , Verheugt Freek W A , Fox Keith A A , Gersh Bernard J , Kakkar Ajay K 
Published: December 2019

Abstract

Aims
Most clinical risk stratification models are based on measurement at a single time-point rather than serial measurements. Artificial intelligence (AI) is able to predict one-dimensional outcomes from multi-dimensional datasets. Using data from Global Anticoagulant Registry in the Field (GARFIELD)-AF registry, a new AI model was developed for predicting clinical outcomes in atrial fibrillation (AF) patients up to 1 year based on sequential measures of prothrombin time international normalized ratio (PT-INR) within 30 days of enrolment.

Methods and results
Patients with newly diagnosed AF who were treated with vitamin K antagonists (VKAs) and had at least three measurements of PT-INR taken over the first 30 days after prescription were analysed. The AI model was constructed with multilayer neural network including long short-term memory and one-dimensional convolution layers. The neural network was trained using PT-INR measurements within days 0–30 after starting treatment and clinical outcomes over days 31–365 in a derivation cohort (cohorts 1–3; n = 3185). Accuracy of the AI model at predicting major bleed, stroke/systemic embolism (SE), and death was assessed in a validation cohort (cohorts 4–5; n = 1523). The model’s c-statistic for predicting major bleed, stroke/SE, and all-cause death was 0.75, 0.70, and 0.61, respectively.

Conclusions
Using serial PT-INR values collected within 1 month after starting VKA, the new AI model performed better than time in therapeutic range at predicting clinical outcomes occurring up to 12 months thereafter. Serial PT-INR values contain important information that can be analysed by computer to help predict adverse clinical outcomes.
Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis
Authors: Stojanović Stevan D , Fiedler Jan , Bauersachs Johann , Thum Thomas , Sedding Daniel G 
Published: December 2019

Abstract
Inflammation is a hallmark and potent driver of pathological vascular remodelling in atherosclerosis. However, current anti-inflammatory therapeutic strategies have shown mixed results. As an alternative perspective on the conundrum of chronic inflammation emerging evidence points towards a small subset of senescent cells as a critical player and central node driving atherosclerosis. Senescent cells belonging to various cell types are a dominant and chronic source of a large array of pro-inflammatory cytokines and various additional plaque destabilizing factors, being involved with various aspects of atherosclerosis pathogenesis. Antagonizing these key agitators of local chronic inflammation and plaque instability may provide a causative and multi-purpose therapeutic strategy to treat atherosclerosis. Anti-senescence treatment options with translational potential are currently in development. However, several questions and challenges remain to be addressed before these novel treatment approaches may enter the clinical setting.
Improved brain perfusion after electrical cardioversion of atrial fibrillation
Authors: Gardarsdottir Marianna , Sigurdsson Sigurdur , Aspelund Thor , Gardarsdottir Valdis Anna , Forsberg Lars , Gudnason Vilmundur , Arnar David O 
Published: December 2019

Abstract

Aims
Atrial fibrillation (AF) has been associated with reduced brain volume, cognitive impairment, and reduced cerebral blood flow. The causes of reduced cerebral blood flow in AF are unknown, but no reduction was seen in individuals without the arrhythmia in a previous study. The aim of this study was to test the hypothesis that brain perfusion, measured with magnetic resonance imaging (MRI), improves after cardioversion of AF to sinus rhythm (SR).

Methods and results
All patients undergoing elective cardioversion at our institution were invited to participate. A total of 44 individuals were included. Magnetic resonance imaging studies were done before and after cardioversion with both brain perfusion and cerebral blood flow measurements. However, 17 did not complete the second MRI as they had a recurrence of AF during the observation period (recurrent AF group), leaving 17 in the SR group and 10 in the AF group to complete both measurements. Brain perfusion increased after cardioversion to SR by 4.9 mL/100 g/min in the whole brain (P &lt; 0.001) and by 5.6 mL/100 g/min in grey matter (P &lt; 0.001). Cerebral blood flow increased by 58.6 mL/min (P &lt; 0.05). Both brain perfusion and cerebral blood flow remained unchanged when cardioversion was unsuccessful.

Conclusion
In this study of individuals undergoing elective cardioversion for AF, restoration, and maintenance of SR for at least 10 weeks after was associated with an improvement of brain perfusion and cerebral blood flow measured by both arterial spin labelling and phase contrast MRI. In those individuals where cardioversion was unsuccessful, there was no change in perfusion or blood flow.
Evaluating Regeneration in Heterobasidion Root Disease Infested Stands in the Lake States
Authors: Demchik Michael C , Sakalidis Monique L , Hillstrom Michael , Scanlon Kyoko , Adams Trevor A , Minnix Katherine R 
Published: December 2019

Abstract
Heterobasidion root disease (HRD) infection is becoming increasingly common in red pine plantations of the Lake States. Although stump treatment can reduce rates of overland transmission, infested stands continue to experience expansion of mortality pockets. Natural regeneration into HRD mortality pockets can assist with revegetation. The objective of this study was to determine what tree species naturally regenerate in red pine plantations impacted by HRD in Wisconsin and Michigan. We visited 49 pockets (in 31 stands) in Wisconsin and Michigan that had existing confirmed HRD infections during the fall of 2017. We surveyed the regeneration in the pocket and measured the species and basal area of overstory trees 10 m from the expanding edge of the pocket. Overall, pockets were regenerating with desirable species, some of which are susceptible to HRD. Additionally, woody invasive species were present in 39 percent of the pockets. We expect these pockets to generally fill with desirable species of regeneration, although long-term successful regeneration by susceptible species such as pines may be limited.
Interaction between P, S1 and S2 waves in multilayered periodic monoclinic media at low frequencies
Authors: Stovas Alexey , Roganov Yuriy , Roganov Vyacheslav 
Published: December 2019

SUMMARYApplication of the Floquet theorem and the matrix propagator method reduces the problem of the plane wave propagation in a periodically layered anisotropic media, to analysis of the properties of stationary envelopes of different wave modes propagating up- and downwards. We analyse the interchanging of stop- and pass-bands and their structure at low frequencies for a periodically layered medium with monoclinic symmetry. The analysis shows the effect of interaction between P,S1 and S2 wave multipliers for stop- and pass-band structure and gives insight into the wave propagation in vertically heterogeneous anisotropic media which is important in modelling and interpretation of seismic data.
Enigmatic rhodopsin mutation creates an exceptionally strong splice acceptor site
Authors: Riedmayr Lisa M , Böhm Sybille , Biel Martin , Becirovic Elvir 
Published: December 2019

AbstractThe c.620 T &gt; G mutation in rhodopsin found in the first mapped autosomal dominant retinitis pigmentosa (adRP) locus is associated with severe, early-onset RP. Intriguingly, another mutation affecting the same nucleotide (c.620 T &gt; A) is related to a mild, late-onset RP. Assuming that both mutations are missense mutations (Met207Arg and Met207Lys) hampering the ligand-binding pocket, previous work addressed how they might differentially impair rhodopsin function. Here, we investigated the impact of both mutations at the mRNA and protein level in HEK293 cells and in the mouse retina. We show that, in contrast to c.620 T &gt; A, c.620 T &gt; G is a splicing mutation, which generates an exceptionally strong splice acceptor site (SAS) resulting in a 90 bp in-frame deletion and protein mislocalization in vitro and in vivo. Moreover, we identified the core element underlying the c.620 T &gt; G SAS strength. Finally, we demonstrate that the c.620 T &gt; G SAS is very flexible in branch point choice, which might explain its remarkable performance. Based on these results, we suggest that (i) point mutations should be routinely tested for mRNA splicing to avoid dispensable analysis of mutations on protein level, which do not naturally exist. (ii) Puzzling disease courses of mutations in other genes might also correlate with their effects on mRNA splicing. (iii) Flexibility in branch point choice might be another factor influencing the SAS strength. (iv) The core splice element identified in this study could be useful for biotechnological applications requiring effective SAS.
Serologic Response of 2 Versus 3 Doses and Intradermal Versus Intramuscular Administration of a Licensed Rabies Vaccine for Preexposure Prophylaxis
Authors: Endy Timothy P , Keiser Paul B , Wang Dongliang , Jarman Richard G , Cibula Don , Fang Hengsheng , Ware Lisa , Abbott Mark , Thomas Stephen J , Polhemus Mark E 
Published: December 2019

Abstract

Background
The World Health Organization recommends intradermal (ID) administration of rabies vaccine for preexposure prophylaxis.

Methods
In a randomized trial in adults assigned to 1 of 6 treatment groups (ID vs intramuscular [IM], 2 vs 3 doses, and controls), rabies neutralizing antibody titers were measured to 1 year postvaccination.

Results
ID vaccination produced acceptable antibody levels in all subjects (2- and 3-dose groups). At day 365, acceptable levels were 40% for IM and 50% for ID 2-dose schedule, and 70% for IM and 60% for ID 3-dose schedule.

Conclusions
ID rabies vaccination induces acceptable antibody titers at a fraction of the dose.

Clinical Trials Registration
NCT02374814.
Once-daily tigecycline for outpatient parenteral antibiotic therapy: a single-centre observational study
Authors: Hughes Stephen , Chin Hui Yin , Heard Katie L , Kamranpour Pegah , Bartholomew Brent , Mughal Nabeela , Moore Luke S P 
Published: December 2019

Abstract

Background
Tigecycline has potential utility in the treatment of complex polymicrobial infections or those caused by MDR organisms in the ambulatory care setting owing to its breadth of antimicrobial coverage. Whilst licensed for twice-daily IV administration, its long half-life permits once-daily administration, which may facilitate successful outpatient parenteral antibiotic therapy (OPAT).

Methods
A retrospective case series of patients receiving once-daily tigecycline under OPAT was analysed at a single-centre NHS acute hospital (January 2016–June 2018). Patient demographics, including comorbidities, antimicrobial indication, concurrent antimicrobial therapies, treatment duration and adverse events related to treatment were recorded using medical records. Treatment outcomes were defined using the BSAC National Outcomes Registry System (NORS).

Results
A total of 25 treatment episodes (24 individual patients) were analysed. The most common indications were bone and joint infections (n = 8) and intra-abdominal infections (n = 7). MDR organisms were common, including ESBL-producing Enterobacterales (n = 13) and glycopeptide-resistant enterococci (n = 4). Median treatment duration was 18 days. Nineteen of 25 (76%) cases had complete cure of treatment, 3 patients experienced treatment-related adverse reactions necessitating cessation of therapy and 3 experienced failure due to disease progression. Eight patients experienced non-limiting adverse effects, such as nausea, vomiting and rash, and one patient had a transient rise in amylase 3 times the upper normal limit (with no evidence of pancreatitis).

Conclusions
Once-daily tigecycline can be successfully used for management of complex infections in the OPAT setting, with predominantly mild adverse effects, which can be managed with antiemetics or slow administration.
Rates of increase in gray seal (Halichoerus grypus atlantica) pupping at recolonized sites in the United States, 1988–2019
Authors: Wood Stephanie A , Murray Kimberly T , Josephson Elizabeth , Gilbert James 
Published: December 2019

AbstractGray seals were historically distributed along the northeastern coast of the United States, but bounties and lack of protection reduced numbers and they were rarely observed for most of the 20th century. Once protections were enacted, the population started to rebound. Here, we describe the recolonization and recovery of gray seals in the United States, focusing on the re-establishment of pupping sites. We fit individual generalized linear models to various time series (1988–2019) to estimate rates of increase in observed pup counts at four of the more data-rich sites. Annual rate of increase at individual sites ranged from −0.2% (95% CI: −2.3–1.9%) to 26.3% (95% CI: 21.6–31.4%). The increase in sites and number of pups born in the United States is driven by population growth and immigration from Canadian colonies and is part of a larger recovery of the Northwest Atlantic population. Wildlife protection, a healthy source population, habitat availability, and species traits that allow for dispersal and high productivity were all important factors in this recovery.
Investigation of X-ray timing and spectral properties of ESO 243-49 HLX-1 with long-term Swift monitoring
Authors: Lin Lupin Chun-Che , Hu Chin-Ping , Li Kwan-Lok , Takata Jumpei , Yen David Chien-Chang , Kwak Kyujin , Kim Young-Min , Kong Albert K H 
Published: December 2019

ABSTRACT
The long-term Swift monitoring of ESO 243–49 HLX−1 provides an opportunity to investigate the detailed timing and spectral behaviour of this hyperluminous X-ray source. Swift has detected seven outbursts since 2009 mid-August. Using different dynamical timing algorithms, we confirm an increasing trend for the time intervals between outbursts, which is manifest in the delays between the latest outbursts. The X-ray spectra of HLX−1 in quiescence can be described with a single power-law model while the thermal component dominates the X-ray emission during outburst. There is only marginal evidence for photon index (or spectral hardness) changes between quiescent states with about 1σ deviation. With the updated temporal and spectral features, we re-examine different scenarios to explain the origin of the quasi-periodic modulation of HLX−1. A significantly increasing trend without obvious stochastic fluctuations on the time-scale of the detected quasi-period may not fully support an orbital period origin as might be due to mass transfer episodes from a donor star at periastron of an extremely eccentric orbit. The outburst profile seems to be consistent with the effect of tidal-induced-precession of an accretion disc or an oscillating wind scenario in the inner disc. Based on these models, we speculate that the true orbital period is much shorter than the detected quasi-periodicity.
An extended size–luminosity relation for the reverberation-mapped AGNs: the role of the accretion rate
Authors: Yu Li-Ming , Zhao Bi-Xuan , Bian Wei-Hao , Wang Chan , Ge Xue 
Published: December 2019

ABSTRACT
For a compiled sample of 120 reverberation-mapped AGNs, the bivariate correlations of the broad-line region (BLR) size (RBLR) with the continuum luminosity at 5100 Å (L5100) and the dimensionless accretion rates ($\dot{\mathscr {M}}$) are investigated. Using our recently calibrated virial factor f, and the velocity tracer from the H β full width at half-maximum (FWHM(H β)) or the line dispersion (σH β) measured in the mean spectra, three kinds of supermassive black hole (SMBH) masses and $\dot{\mathscr {M}}$ are calculated. An extended RBLR(H β)–L5100 relation including $\dot{\mathscr {M}}$ is found to be stronger than the canonical RBLR(H β)–L5100 relation, showing smaller scatters. The observational parameters, RFe (the ratio of optical Fe ii to H β line flux) and the line profile parameter DH β ($D_{\rm H\,\beta } =\rm FWHM(H\,\beta)/\sigma _{\rm H\,\beta }$), have relations with three kinds of $\dot{\mathscr {M}}$. Using RFe and DH β to substitute $\dot{\mathscr {M}}$, extended empirical RBLR(Hβ)–L5100 relations are presented. RFe is a better ‘fix’ for the RBLR(H β)–L5100 offset than the H β shape DH β. The extended empirical RBLR(H β)–L5100 relation including RFe can be used to calculate RBLR, and thus the single-epoch SMBH mass MBH. Our measured accretion rate dependence is not consistent with the simple model of the accretion disc instability leading the BLR formation. The BLR may instead form from the inner edge of the torus, or from some other means in which BLR size is positively correlated with accretion rate and the SMBH mass.
Fundamental limits from chaos on instability time predictions in compact planetary systems
Authors: Hussain Naireen , Tamayo Daniel 
Published: December 2019

ABSTRACT
Instabilities in compact planetary systems are generically driven by chaotic dynamics. This implies that an instability time measured through direct N-body integration is not exact, but rather represents a single draw from a distribution of equally valid chaotic trajectories. In order to characterize the ‘errors’ on reported instability times from direct N-body integrations, we investigate the shape and parameters of the instability time distributions (ITDs) for ensembles of shadow trajectories that are initially perturbed from one another near machine precision. We find that in the limit where instability times are long compared to the Lyapunov (chaotic) time-scale, ITDs approach remarkably similar lognormal distributions with standard deviations ≈0.43 ± 0.16 dex, despite the instability times varying across our sample from 104 to 108 orbits. We find excellent agreement between these predictions, derived from ≈450 closely packed configurations of three planets, and a much wider validation set of $\approx 10\, 000$ integrations, as well as on $\approx 20\, 000$ previously published integrations of tightly packed five-planet systems, and a seven-planet resonant chain based on TRAPPIST-1, despite their instability time-scales extending beyond our analysed time-scale. We also test the boundary of applicability of our results on dynamically excited versions of our Solar system. These distributions define the fundamental limit imposed by chaos on the predictability of instability times in such planetary systems. It provides a quantitative estimate of the instrinsic error on an N-body instability time imprinted by chaos, approximately a factor of 3 in either direction.
The Laboratory Domestication of Zebrafish: From Diverse Populations to Inbred Substrains
Authors: Suurväli Jaanus , Whiteley Andrew R , Zheng Yichen , Gharbi Karim , Leptin Maria , Wiehe Thomas 
Published: December 2019

AbstractWe know from human genetic studies that practically all aspects of biology are strongly influenced by the genetic background, as reflected in the advent of “personalized medicine.” Yet, with few exceptions, this is not taken into account when using laboratory populations as animal model systems for research in these fields. Laboratory strains of zebrafish (Danio rerio) are widely used for research in vertebrate developmental biology, behavior, and physiology, for modeling diseases, and for testing pharmaceutic compounds in vivo. However, all of these strains are derived from artificial bottleneck events and therefore are likely to represent only a fraction of the genetic diversity present within the species. Here, we use restriction site-associated DNA sequencing to genetically characterize wild populations of zebrafish from India, Nepal, and Bangladesh, and to compare them to previously published data on four common laboratory strains. We measured nucleotide diversity, heterozygosity, and allele frequency spectra, and find that wild zebrafish are much more diverse than laboratory strains. Further, in wild zebrafish, there is a clear signal of GC-biased gene conversion that is missing in laboratory strains. We also find that zebrafish populations in Nepal and Bangladesh are most distinct from all other strains studied, making them an attractive subject for future studies of zebrafish population genetics and molecular ecology. Finally, isolates of the same strains kept in different laboratories show a pattern of ongoing differentiation into genetically distinct substrains. Together, our findings broaden the basis for future genetic, physiological, pharmaceutic, and evolutionary studies in Danio rerio.
An Analysis of E-Cigarette Marketing in New Zealand Tobacco Retail Outlets Prior to Legislative Change
Authors: Bateman Jerram , Robertson Lindsay A , Marsh Louise , Cameron Claire , Hoek Janet 
Published: December 2019

Abstract

Introduction
In 2017, the New Zealand (NZ) Government announced its intention to liberalize the sale and promotion of electronic nicotine delivery systems (ENDS), including permitting any outlet to sell ENDS. This research estimated the proportion of tobacco outlets selling ENDS prior to legislative change, documented ENDS point-of-sale (POS) marketing, and examined associations between ENDS availability and outlet type, area-level deprivation, study region, and proximity to a secondary school.

Aims and Methods
After drawing a proportional random sample of 281 tobacco outlets from two NZ regions that included convenience stores, supermarkets, and petrol stations, we conducted observational in-store assessments to record ENDS product ranges and promotions. Data were collected between October and December 2017 and analyzed using descriptive statistics and regression modeling.

Results
Of tobacco outlets sampled, 22% sold ENDS; these were typically convenience stores (85%) and located in high deprivation areas (53%). Of stores selling ENDS, products were visible at POS in 89% of stores, including 15% with self-service displays and 15% with displays adjacent to children’s products. ENDS advertising was present in 31% of the outlets and generally promoted ENDS as cheaper than smoked cigarettes.

Conclusions
Liberalizing access to ENDS could reduce harms caused by smoking; however, extensive use of POS promotions will reach children and young people as well as smokers. While reducing harm among smokers is important, policy makers also need to ensure that regulations protect children from ENDS promotions.

Implications
Careful regulation is required to ensure increases in ENDS availability are not accompanied by an increase in young people’s exposure to ENDS marketing at the POS.