bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the Simplified Magnetic Resonance Index of Activity [sMARIA] Without Gadolinium-enhanced Sequences for Crohn’s Disease
Authors: Capozzi Nunzia , Ordás Ingrid , Fernandez-Clotet Agnès , Castro-Poceiro Jesús , Rodríguez Sonia , Alfaro Ignacio , Sapena Víctor , Masamunt Maria Carme , Ricart Elena , Panés Julian , Rimola Jordi 
Published: February 2020

Abstract

Background
Gadolinium-enhanced sequences are not included in the simplified Magnetic Resonance Index of Activity [sMARIA], but in the derivation of this index readers had access to these sequences. The current study aimed to validate the sMARIA without gadolinium-enhanced sequences for assessing disease activity, severity, and response to treatment in patients with Crohn’s disease.

Methods
We prospectively included patients with active Crohn’s disease and at least one segment with severe inflammation [ulcers] at ileocolonoscopy, who required treatment with biologic drugs. Patients were evaluated by both magnetic resonance enterography [MRE] and ileocolonoscopy at baseline and 46 weeks after initiation of medical treatment. We compared the quantification of disease activity and response to treatment with sMARIA versus with ileocolonoscopy Crohn’s Disease Index of Severity [CDEIS], considered the gold standard.

Results
Data from both MRE and ileocolonoscopy 46 weeks after treatment initiation were available for 39 of the 50 patients. As in the derivation study, the optimal cutoffs were sMARIA ≥1 for predicting active disease (area under the curve [AUC] 0.92) and sMARIA ≥2 for predicting the presence of ulcers at ileocolonoscopy [AUC 0.93]. In evaluating the response to treatment, the sMARIA detected endoscopic ulcer healing at the segment level [sMARIA &lt;2] with 89.5% sensitivity and 87.5% specificity. The sMARIA decreased significantly [p &lt;0.001] in segments achieving endoscopic ulcer healing, but did not change [p = 0.222] in segments with persistent ulceration.

Conclusions
The sMARIA is accurate and reliable in quantifying disease activity and response to treatment in luminal Crohn’s disease, without the need for gadolinium-enhanced sequences.
Transitional Growth and Trade with Frictions: A Structural Estimation Framework
Authors: Anderson James E , Larch Mario , Yotov Yoto V 
Published: February 2020

Abstract
We build and estimate a structural model of transitional growth and trade in a many-country world. The gravity model of trade is combined with a capital accumulation mechanism driving transition between steady states. Trade affects growth through changes in consumer and producer prices. Simultaneously, capital accumulation affects trade directly through changes in country size and indirectly through changes in the incidence of trade costs. Theory maps to an econometric system that identifies the parameters of the model and establishes causal links between trade, capital accumulation and income. Counterfactual trade liberalisation magnifies static gains by a dynamic path multiplier of 1.8.
Multivariate stochastic dominance applied to sector-based portfolio selection
Authors: Kouaissah Noureddine , Ortobelli Lozza Sergio 
Published: February 2020

AbstractIn this study, we investigate whether sector-weighted portfolios based on alternative parametric assumptions are consistent with multivariate stochastic dominance (MSD) conditions for a class of non-satiable risk-averse investors. Focusing specifically on stable symmetric and Student’s t distributions, we propose and motivate an MSD rule to determine a partial order among sectors, based on a comparison between (i) location, (ii) dispersion parameters and (iii) either stability indices (for stable symmetric distributions) or degrees of freedom (for Student’s t distributions). The proposed MSD rule is applied to the US equity market to evaluate whether and how the derived stochastic dominance conditions are relevant to investors’ decisions. The empirical study confirms that the proposed MSD rule is effective and that the tail behaviour of returns is relevant to the optimization of portfolios for non-satiable investors.
Methodological features of clinical pharmacokinetic–pharmacodynamic studies of antibacterials and antifungals: a systematic review
Authors: McAleenan Alexandra , Ambrose Paul G , Bhavnani Sujata M , Drusano George L , Hope William W , Mouton Johan W , Higgins Julian P T , MacGowan Alasdair P 
Published: February 2020

Abstract

Background
Pharmacokinetic (PK)–pharmacodynamic (PD) indices relate measures of drug exposure to antibacterial effect. Clinical PK–PD studies aim to correlate PK–PD indices with outcomes in patients. Optimization of dosing based on pre-clinical studies means that PK–PD relationships are difficult to establish; therefore studies need to be designed and reported carefully to validate pre-clinical findings.

Objectives
To describe the methodological features of clinical antibacterial and antifungal PK–PD studies that reported the relationship between PK–PD indices and clinical or microbiological responses.

Methods
Studies published between 1980 and 2015 were identified through systematic searches. Methodological features of eligible studies were extracted.

Results
We identified 85 publications containing 97 PK–PD analyses. Most studies were small, with fewer than 100 patients. Around a quarter were performed on patients with infections due to a single specific pathogen. In approximately one-third of studies, patients received concurrent antibiotics/antifungals and in some other studies patients received other treatments that may confound the PK–PD–outcome relationship. Most studies measured antimicrobial concentrations in blood/serum and only four measured free concentrations. Most performed some form of regression, time-to-event analysis or used the Hill/Emax equation to examine the association between PK–PD index and outcome. Target values of PK–PD indices that predict outcomes were investigated in 52% of studies. Target identification was most commonly done using recursive partitioning or logistic regression.

Conclusions
Given the variability in conduct and reporting, we suggest that an agreed set of standards for the conduct and reporting of studies should be developed.
Determinants of Mammographic Breast Density by Race Among a Large Screening Population
Authors: Moore Justin Xavier , Han Yunan , Appleton Catherine , Colditz Graham , Toriola Adetunji T 
Published: February 2020

Abstract

BACKGROUND
Due to mixed reports from smaller studies, we examined associations of race with mammographic breast density and evaluated racial differences in the determinants of breast density.

METHODS
Participants included 37,839 women (23,166 non-Hispanic White, and 14,673 African American women) receiving screening mammograms at the Joanne Knight Breast Health Center at Washington University School of Medicine, St. Louis, Missouri from June 2010 to December 2015. Mammographic breast density was assessed using Breast Imaging Reporting and Data System (5th edition). To determine the association of race and participant characteristics with mammographic breast density, we used multivariable polytomous logistic regression models (reference group: almost entirely fatty).

RESULTS
African American women had increased odds of extremely dense (adjusted odds ratio (AOR) = 1.31, 95% CI = 1.13–1.52) and reduced odds of heterogeneously dense breasts (AOR= 0.91, 95% CI = 0.84 – 0.99) compared to non-Hispanic White women. Altogether, race, parity and age at first birth, age, current body mass index (BMI), BMI at age 18, menarche, family history of breast cancer, oral contraceptive use, alcohol, and menopausal status explained 33% of the variation in mammographic breast density. Among African American and non-Hispanic White women these factors explained nearly 28.6% and 33.6% of the variation in mammographic density, respectively. Current BMI provided the greatest explanation of breast density (26.2% overall, 22.2% in African American, and 26.2% in non-Hispanic White women).

CONCLUSIONS
The determinants of mammographic breast density were generally similar between African-American women and non-Hispanic white women. After adjustments for confounders, African Americans had higher likelihood of extremely dense breast but lower likelihood of heterogeneously dense breast. The greatest explanation of breast density was provided by BMI, regardless of race.
Photosynthesis research: a model to bridge fundamental science, translational products, and socio-economic considerations in agriculture
Authors: Kohli Ajay , Miro Berta , Balié Jean , d’A Hughes Jacqueline 
Published: February 2020

Abstract
Despite impressive success in molecular physiological understanding of photosynthesis, and preliminary evidence on its potential for quantum shifts in agricultural productivity, the question remains of whether increased photosynthesis, without parallel fine-tuning of the associated processes, is enough. There is a distinct lack of formal socio-economic impact studies that address the critical questions of product profiling, cost–benefit analysis, environmental trade-offs, and technological and market forces in product acceptability. When a relatively well understood process gains enough traction for translational value, its broader scientific and technical gap assessment, in conjunction with its socio-economic impact assessment for success, should be a prerequisite. The successes in the upstream basic understanding of photosynthesis should be integrated with a gap analysis for downstream translational applications to impact the farmers’ and customers’ lifestyles and livelihoods. The purpose of this review is to assess how the laboratory, the field, and the societal demands from photosynthesis could generate a transformative product. Two crucial recommendations from the analysis of the state of knowledge and potential ways forward are (i) the formulation of integrative mega-projects, which span the multistakeholder spectrum, to ensure rapid success in harnessing the transformative power of photosynthesis; and (ii) stipulating spatiotemporal, labour, and economic criteria to stage-gate deliverables.
The bZIP53–IAA4 module inhibits adventitious root development in Populus
Authors: Zhang Yan , Yang Xiaoqing , Cao Pei , Xiao Zheng’ang , Zhan Chang , Liu Meifeng , Nvsvrot Tashbek , Wang Nian 
Published: February 2020

Abstract
Adventitious roots (ARs) are important for some plants that depend on clonal propagation. In this study, we demonstrate that a salt-responsive gene module is involved in the negative regulation of AR development in poplar. In this module, the expression of bZIP53 is induced by salt stress and it encodes a transcription factor with transactivation activity. Overexpression or induced expression of bZIP53 in poplar lines resulted in inhibition of AR growth, while heterologous overexpression of bZIP53 in Arabidopsis resulted in a similar phenotype. Results from RNA-seq and RT-qPCR assays predicted IAA4-1 and IAA4-2 to be downstream genes that were regulated by bZIP53. Further investigation of protein–DNA interactions using yeast one-hybrid, electrophoretic mobility shift, dual luciferase reporter, and GUS co-expression assays also showed that IAA4-1/2 were the genes that were directly regulated by bZIP53. Induced-expression IAA4-1/2 transgenic poplar lines also showed inhibited AR growth. In addition, both poplar bZIP53 and IAA4-1/2 showed a response to salt stress. On the basis of these results, we conclude that the bZIP53–IAA4 module is involved in the negative regulation of AR development in poplar.
Functional QTL mapping and genomic prediction of canopy height in wheat measured using a robotic field phenotyping platform
Authors: Lyra Danilo H , Virlet Nicolas , Sadeghi-Tehran Pouria , Hassall Kirsty L , Wingen Luzie U , Orford Simon , Griffiths Simon , Hawkesford Malcolm J , Slavov Gancho T 
Published: February 2020

AbstractGenetic studies increasingly rely on high-throughput phenotyping, but the resulting longitudinal data pose analytical challenges. We used canopy height data from an automated field phenotyping platform to compare several approaches to scanning for quantitative trait loci (QTLs) and performing genomic prediction in a wheat recombinant inbred line mapping population based on up to 26 sampled time points (TPs). We detected four persistent QTLs (i.e. expressed for most of the growing season), with both empirical and simulation analyses demonstrating superior statistical power of detecting such QTLs through functional mapping approaches compared with conventional individual TP analyses. In contrast, even very simple individual TP approaches (e.g. interval mapping) had superior detection power for transient QTLs (i.e. expressed during very short periods). Using spline-smoothed phenotypic data resulted in improved genomic predictive abilities (5–8% higher than individual TP prediction), while the effect of including significant QTLs in prediction models was relatively minor (&lt;1–4% improvement). Finally, although QTL detection power and predictive ability generally increased with the number of TPs analysed, gains beyond five or 10 TPs chosen based on phenological information had little practical significance. These results will inform the development of an integrated, semi-automated analytical pipeline, which will be more broadly applicable to similar data sets in wheat and other crops.
An Applied Test of Knowledge Translation Methods Using a Mobile Health Solution
Authors: Armstrong Christina M , Ciulla Robert P , Williams Suzanne A , Micheel Logan J 
Published: February 2020

ABSTRACTIntroductionThe study’s objectives were to improve providers’ knowledge of mobile health core competencies; increase providers’ knowledge and clinical use of the Virtual Hope Box (VHB) mobile app as an evidence-based treatment tool; and test elements of a structured knowledge translation paradigm.Materials and Methodsknowledge translation best practices were integrated into a training workshop with the goal to increase provider adoption of the VHB. Providers were trained at three sites and provided feedback before the training, post-training, and at 3, 6, and 12 months following the training.ResultsPretraining, &lt;22% of respondents indicated that they had used the VHB in clinical practice; post-training, 89% of respondents reported their intent to use the VHB. At 3 and 6 months, 82% of evaluation respondents indicated actual use of the VHB.ConclusionsUsing a public-facing technology, this study successfully integrated knowledge translation methods within an existing provider training program. Implementation planning should be deliberate and consider a target site’s capacity for new ideas and potential adoption barriers. Lessons learned have implications for future efforts to bridge the gap between research and practice in improving the quality and impact of clinical care.
Maintaining Surgical Readiness While Deployed to Low-Volume Military Treatment Facilities: A Pilot Program for Clinical and Operational Sustainment Training in the Deployed Environment
Authors: Gurney Jennifer M , Cole Will C , Graybill John C , Shackelford Stacy A , Via Darin K 
Published: February 2020

ABSTRACTIntroductionMaintaining readiness among Army surgeons is increasingly challenging because of declining operative experience during certain deployments. Novel solutions should be considered.Materials and MethodsA pilot program was conducted to rotate surgical teams from a military treatment facility with a low volume of combat casualty care to one with a higher volume. Pre- and postrotation surveys were conducted to measure relative operative experience, trauma experience, and perceived readiness among rotators.ResultsOperative volumes and trauma volumes were increased and that perceived readiness among rotators, especially those with the fewest previous deployments, was improved.ConclusionsMaintaining readiness among Army surgeons is a difficult task, but a combination of increased trauma care while in garrison, as well as increased humanitarian care during deployments, may be helpful. Additionally, rotating providers from facilities caring for few combat casualties to facilities caring for more combat casualties may also be feasible, safe, and helpful.
Delivering Transcranial Direct Current Stimulation Away From Clinic: Remotely Supervised tDCS
Authors: Shaw Michael , Pilloni Giuseppina , Charvet Leigh 
Published: February 2020

Abstract

Introduction
To demonstrate the broad utility of the remotely supervised transcranial direct current stimulation (RS-tDCS) protocol developed to deliver at-home rehabilitation for individuals with multiple sclerosis (MS).

Methods
Stimulation delivered with the RS-tDCS protocol and paired with adaptive cognitive training was delivered to three different study groups of MS patients to determine the feasibility and tolerability of the protocol. The three studies each used consecutively increasing amounts of stimulation amperage (1.5, 2.0, and 2.5 mA, respectively) and session numbers (10, 20, and 40 sessions, respectively).

Results
High feasibility and tolerability of the stimulation were observed for n = 99 participants across three tDCS pilot studies.

Conclusions
RS-tDCS is feasible and tolerable for MS participants. The RS-tDCS protocol can be used to reach those in locations without clinic access and be paired with training or rehabilitation in locations away from the clinic. This protocol could be used to deliver tDCS paired with training or rehabilitation activities remotely to service members and veterans.
No nitrogen fractionation on 600 au scale in the Sun progenitor analogue OMC–2 FIR4
Authors: Fontani F , Quaia G , Ceccarelli C , Colzi L , López-Sepulcre A , Favre C , Kahane C , Caselli P , Codella C , Podio L , Viti S 
Published: February 2020

ABSTRACT
We show the first interferometric maps of the 14N/15N ratio obtained with the Atacama Large Millimeter Array (ALMA) towards the Solar-like forming protocluster OMC–2 FIR4. We observed N2H+, 15NNH+, N15NH+ (1–0), and N2D+(2–1) from which we derive the isotopic ratios 14N/15N and D/H. The target, OMC–2 FIR4, is one of the closest analogues of the environment in which our Sun may have formed. The ALMA images, having synthesized beam of ∼1.5 arcsec × 1.8 arcsec, i.e. ∼600 au, show that the emission of the less abundant isotopologues is distributed in several cores of ∼10 arcsec (i.e. ∼0.02 pc or 4000 au) embedded in a more extended N2H+emission. We have derived that the 14N/15N ratio does not vary from core to core, and our interferometric measurements are also consistent with single-dish observations. We also do not find significant differences between the 14N/15N ratios computed from the two 15N-bearing isotopologues, 15NNH+ and N15NH+. The D/H ratio derived by comparing the column densities of N2D+and N2H+changes by an order of magnitude from core to core, decreasing from the colder to the warmer cores. Overall, our results indicate that: (1) 14N/15N does not change across the region at core scales, and (2) 14N/15N does not depend on temperature variations. Our findings also suggest that the 14N/15N variations found in pristine Solar system objects are likely not inherited from the protocluster stage, and hence the reason has to be found elsewhere.
A census of coronal mass ejections on solar-like stars
Authors: Leitzinger M , Odert P , Greimel R , Vida K , Kriskovics L , Guenther E W , Korhonen H , Koller F , Hanslmeier A , Kővári Zs , Lammer H 
Published: February 2020

ABSTRACT
Coronal mass ejections (CMEs) may have major importance for planetary and stellar evolution. Stellar CME parameters, such as mass and velocity, have yet not been determined statistically. So far only a handful of stellar CMEs has been detected mainly on dMe stars using spectroscopic observations. We therefore aim for a statistical determination of CMEs of solar-like stars by using spectroscopic data from the ESO phase 3 and Polarbase archives. To identify stellar CMEs, we use the Doppler signal in optical spectral lines being a signature of erupting filaments that are closely correlated to CMEs. We investigate more than 3700 h of on-source time of in total 425 dF-dK stars. We find no signatures of CMEs and only few flares. To explain this low level of activity, we derive upper limits for the non-detections of CMEs and compare those with empirically modelled CME rates. To explain the low number of detected flares, we adapt a flare power law derived from EUV data to the H α regime, yielding more realistic results for H α observations. In addition, we examine the detectability of flares from the stars by extracting Sun-as-a-star H α light curves. The extrapolated maximum numbers of observable CMEs are below the observationally determined upper limits, which indicates that the on-source times were mostly too short to detect stellar CMEs in H α. We conclude that these non-detections are related to observational biases in conjunction with a low level of activity of the investigated dF-dK stars.
Characterizing low-contrast Galactic open clusters with Gaia Data Release 2
Authors: Angelo M S , Santos J F C , Corradi W J B 
Published: February 2020

ABSTRACT
In this study, we characterized 16 objects previously classified as faint or low-contrast Galactic open clusters (OCs). We employed parameters associated with the dynamical evolution of the OCs: the core (rc), tidal (rt) and half-mass (rhm) radii, age and crossing time (tcr). Relations among these parameters were exploited to draw some evolutionary connections. We also included 11 OCs with previous characterizations to provide wider coverage of the parameter space. The investigated sample spans a considerable range in age, log (t yr−1) ∼7.0–9.7, and Galactocentric distance, RG ∼ 6–11 kpc). Most of these OCs present solar metallicity. We employed Gaia Data Release 2 astrometry and photometry, and we selected member stars through a decontamination algorithm that explores the three-dimensional astrometric space (μα, μδ, ϖ) to assign membership likelihoods. Previous studies of most of these objects were based mostly on photometric information. All investigated OCs were proved to be real stellar concentrations. The relations among their parameters indicate a general disruption scenario in which OCs tend to be more concentrated as they evolve. Internal interactions sucessively drive OCs to develop more dynamically relaxed structures and make them less subject to mass loss due to tidal effects. Tidal radius tends to increase with RG in accordance with the strength of the Galactic tidal field. Besides, the correlation between rc and the dynamical ratio τdyn = age/tcr suggests two distinct evolutionary sequences, which may be a consequence of different initial formation conditions.
Structural insights into CpG-specific DNA methylation by human DNA methyltransferase 3B
Authors: Lin Chien-Chu , Chen Yi-Ping , Yang Wei-Zen , Shen James C K , Yuan Hanna S 
Published: February 2020

AbstractDNA methyltransferases are primary enzymes for cytosine methylation at CpG sites of epigenetic gene regulation in mammals. De novo methyltransferases DNMT3A and DNMT3B create DNA methylation patterns during development, but how they differentially implement genomic DNA methylation patterns is poorly understood. Here, we report crystal structures of the catalytic domain of human DNMT3B–3L complex, noncovalently bound with and without DNA of different sequences. Human DNMT3B uses two flexible loops to enclose DNA and employs its catalytic loop to flip out the cytosine base. As opposed to DNMT3A, DNMT3B specifically recognizes DNA with CpGpG sites via residues Asn779 and Lys777 in its more stable and well-ordered target recognition domain loop to facilitate processive methylation of tandemly repeated CpG sites. We also identify a proton wire water channel for the final deprotonation step, revealing the complete working mechanism for cytosine methylation by DNMT3B and providing the structural basis for DNMT3B mutation-induced hypomethylation in immunodeficiency, centromere instability and facial anomalies syndrome.