bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reliable species distributions are obtainable with sparse, patchy and biased data by leveraging over species and data types
Authors: Peel Samantha L. , Hill Nicole A. , Foster Scott D. , Wotherspoon Simon J. , Ghiglione Claudio , Schiaparelli Stefano 
Published: April 2019

AbstractNew methods for species distribution models (SDMs) utilise presence–absence (PA) data to correct the sampling bias of presence‐only (PO) data in a spatial point process setting. These have been shown to improve species estimates when both datasets are large and dense. However, is a PA dataset that is smaller and patchier than hitherto examined able to do the same? Furthermore, when both datasets are relatively small, is there enough information contained within them to produce a useful estimate of species’ distributions? These attributes are common in many applications.A stochastic simulation was conducted to assess the ability of a pooled data SDM to estimate the distribution of species from increasingly sparser and patchier datasets. The simulated datasets were varied by changing the number of presence–absence sample locations, the degree of patchiness of these locations, the number of PO observations, and the level of sampling bias within the PO observations. The performance of the pooled data SDM was compared to a PA SDM and a PO SDM to assess the strengths and limitations of each SDM.The pooled data SDM successfully removed the sampling bias from the PO observations even when the presence–absence data were sparse and patchy, and the PO observations formed the majority of the data. The pooled data SDM was, in general, more accurate and more precise than either the PA SDM or the PO SDM. All SDMs were more precise for the species responses than they were for the covariate coefficients.The emerging SDM methodology that pools PO and PA data will facilitate more certainty around species’ distribution estimates, which in turn will allow more relevant and concise management and policy decisions to be enacted. This work shows that it is possible to achieve this result even in relatively data‐poor regions.
Changes in hemostasis parameters in nonfatal methicillin‐sensitive Staphylococcus aureus bacteremia complicated by endocarditis or thromboembolic events: a prospective gender‐age adjusted cohort study
Authors: Forsblom Erik , Lepäntalo Aino , Wartiovaara‐Kautto Ulla , Ruotsalainen Eeva , Järvinen Asko 
Published: April 2019

The aim of this study was to examine the changes in hemostasis parameters in endocarditis and thromboembolic events in nonfatal methicillin‐sensitive Staphylococcus aureus bacteremia (MS‐SAB) – a topic not evaluated previously. In total, 155 patients were recruited and were categorized according to the presence of endocarditis or thromboembolic events with gender‐age adjusted controls. Patients who deceased within 90 days or patients not chosen as controls were excluded. SAB management was supervised by an infectious disease specialist. Patients with endocarditis (N = 21), compared to controls (N = 21), presented lower antithrombin III at day 4 (p < 0.05), elevated antithrombin III at day 90 (p < 0.01), prolonged activated partial thromboplastin time at days 4 and 10 (p < 0.05), and enhanced thrombin–antithrombin complex at day 4 (p < 0.01). Thromboembolic events (N = 8), compared to controls (N = 34), significantly increased thrombin–antithrombin complex at day 4 (p < 0.05). In receiver operating characteristic analysis, the changes in these hemostasis parameters at day 4 predicted endocarditis and thromboembolic events (p < 0.05). No differences in hemoglobin, thrombocyte, prothrombin fragment, thrombin time, factor VIII, D‐dimer or fibrinogen levels were observed between cases and controls. The results suggest that nonfatal MS‐SAB patients present marginal hemostasis parameter changes that, however, may have predictability for endocarditis or thromboembolic events. Larger studies are needed to further assess the connection of hemostasis to complications in SAB.
Brain metabolic alterations in patients with long‐term calcineurin inhibitor therapy after liver transplantation
Authors: Schmitz Birte , Pflugrad Henning , Tryc Anita B. , Lanfermann Heinrich , Jäckel Elmar , Schrem Harald , Beneke Jan , Barg‐Hock Hannelore , Klempnauer Jürgen , Weissenborn Karin , Ding Xiao‐Qi 
Published: April 2019

SummaryBackgroundCalcineurin inhibitor (CNI) neurotoxicity after liver transplantation might be due to impairment of the cerebral metabolism.AimsTo investigate CNI‐related alterations of brain metabolite distributions and associations between cognitive function and brain metabolism in patients with long‐term CNI treatment after liver transplantation.MethodsEighty‐two patients (19 CNI free, 34 CNI low‐dose and 29 standard‐dose CNI immunosuppression) 10 years after liver transplantation and 32 adjusted healthy controls underwent nonlocalised brain phosphorus magnetic resonance spectroscopy (MRS) and single voxel proton MRS in the parietal white matter to estimate brain metabolite contents. The MRS results were correlated with psychometric data assessing cognitive function.ResultsPhosphorus metabolite concentrations with the exception of phosphocreatine (PCr) were reduced in patients compared to controls. Particularly, patients with low‐dose CNI therapy showed a significant decrease in adenosine triphosphate (0.209 ± 0.012 vs 0.222 ± 0.010; P < 0.001) and a significant increase in PCr (0.344 ± 0.026 vs 0.321 ± 0.017; P < 0.001) compared to controls. Myo‐Inositol in the CNI free group (2.719 ± 0.549 institutional unit [iu]) was significantly lower compared to controls (3.181 ± 0.425 iu; P = 0.02), patients on low‐dose (3.130 ± 0.513 iu; P < 0.05) and standard‐dose CNI therapy (3.207 ± 0.632 iu; P < 0.02). Glutamate and glutamine levels correlated negatively with cognitive function (Repeatable Battery for the Assessment of Neuropsychological Status Total Scale: R = −0.362, P = 0.029).ConclusionLong‐term CNI therapy after liver transplantation might be associated with alterations of brain metabolites.
Granger Mediation Analysis of Multiple Time Series With an Application to Functional Magnetic Resonance Imaging
Authors: Zhao Yi , Luo Xi 
Published: April 2019

Abstract
This paper presents Granger mediation analysis, a new framework for causal mediation analysis of multiple time series. This framework is motivated by a functional magnetic resonance imaging (fMRI) experiment where we are interested in estimating the mediation effects between a randomized stimulus time series and brain activity time series from two brain regions. The independent observation assumption is thus unrealistic for this type of time-series data. To address this challenge, our framework integrates two types of models: causal mediation analysis across the mediation variables, and vector autoregressive (VAR) models across the temporal observations. We use “Granger” to refer to VAR correlations modeled in this paper. We further extend this framework to handle multilevel data, in order to model individual variability and correlated errors between the mediator and the outcome variables. Using Rubin's potential outcome framework, we show that the causal mediation effects are identifiable under our time-series model. We further develop computationally efficient algorithms to maximize our likelihood-based estimation criteria. Simulation studies show that our method reduces the estimation bias and improves statistical power, compared with existing approaches. On a real fMRI data set, our approach quantifies the causal effects through a brain pathway, while capturing the dynamic dependence between two brain regions.
Analysis of Covariance in Randomized Trials: More Precision and Valid Confidence Intervals, Without Model Assumptions
Authors: Wang Bingkai , Ogburn Elizabeth L. , Rosenblum Michael 
Published: April 2019

Abstract
“Covariate adjustment” in the randomized trial context refers to an estimator of the average treatment effect that adjusts for chance imbalances between study arms in baseline variables (called “covariates”). The baseline variables could include, for example, age, sex, disease severity, and biomarkers. According to two surveys of clinical trial reports, there is confusion about the statistical properties of covariate adjustment. We focus on the analysis of covariance (ANCOVA) estimator, which involves fitting a linear model for the outcome given the treatment arm and baseline variables, and trials that use simple randomization with equal probability of assignment to treatment and control. We prove the following new (to the best of our knowledge) robustness property of ANCOVA to arbitrary model misspecification: Not only is the ANCOVA point estimate consistent (as proved by Yang and Tsiatis, 2001) but so is its standard error. This implies that confidence intervals and hypothesis tests conducted as if the linear model were correct are still asymptotically valid even when the linear model is arbitrarily misspecified, for example, when the baseline variables are nonlinearly related to the outcome or there is treatment effect heterogeneity. We also give a simple, robust formula for the variance reduction (equivalently, sample size reduction) from using ANCOVA. By reanalyzing completed randomized trials for mild cognitive impairment, schizophrenia, and depression, we demonstrate how ANCOVA can achieve variance reductions of 4 to 32%.
Multiclass Linear Discriminant Analysis With Ultrahigh-Dimensional Features
Authors: Li Yanming , Hong Hyokyoung G. , Li Yi 
Published: April 2019

AbstractWithin the framework of Fisher's discriminant analysis, we propose a multiclass classification method which embeds variable screening for ultrahigh-dimensional predictors. Leveraging interfeature correlations, we show that the proposed linear classifier recovers informative features with probability tending to one and can asymptotically achieve a zero misclassification rate. We evaluate the finite sample performance of the method via extensive simulations and use this method to classify posttransplantation rejection types based on patients' gene expressions.
Impact of mentoring on socio‐emotional and mental health outcomes of youth with learning disabilities and attention‐deficit hyperactivity disorder
Authors: Haft Stephanie L. , Chen Tiffany , LeBlanc Chloe , Tencza Francesca , Hoeft Fumiko 
Published: April 2019

BackgroundLearning disabilities (LD) and attention‐deficit hyperactivity disorder (ADHD) are often accompanied by significant socio‐emotional impairments and mental health challenges. However, there is a lack of controlled, quantitative research on potential interventions to address this issue. The current study evaluated the impact of a near‐peer mentoring program for youth with LD/ADHD designed to promote socio‐emotional well‐being.MethodsYouth with LD/ADHD who participated in the mentoring program (Mentored; n = 99) were compared to both nonmentored youth with LD/ADHD (Control‐NM; n = 51) and typically developing youth without LD/ADHD (Control‐TD; n = 81) prementoring in the fall and postmentoring in the spring. Participants were assessed using self‐report measures of anxiety, depression, interpersonal relations, and self‐esteem.ResultsYouth with LD/ADHD showed significantly higher scores of depression and significantly lower scores of interpersonal relations compared to the Control‐TD group at fall baseline. The depression and self‐esteem scores of the Mentored group significantly decreased and increased, respectively, after mentoring. These changes were associated with mentee‐perceived mentorship quality. The Control‐NM group showed significant decreases in both self‐esteem and interpersonal relations, as well as increases in depression over time, while the Control‐TD group remained stable across all measures.ConclusionsResults suggest that mentoring shows promise as a potential intervention for youth with LD/ADHD who experience co‐occurring socio‐emotional and mental health difficulties. The study is the first, to our knowledge, to quantify the effect of a near‐peer mentoring program on youth with LD/ADHD in a design with two control groups. Implications for research and practice involving LD, ADHD, and mental health disorders are discussed.
Key Practitioner Message

LD and ADHD are associated with increased anxiety, depression, and impaired self‐esteem and interpersonal relationships.

There is a lack of research on interventions that could address the mental health problems and socio‐emotional difficulties that co‐occur with learning disabilities and ADHD.

Near‐peer mentoring is a promising intervention that can improve socio‐emotional well‐being and mental health in youth with learning disabilities and ADHD, and highlights the importance of strong interpersonal relationships as a protective factor.
Epigenome‐wide association studies in asthma: A systematic review
Authors: Edris Ahmed , den Dekker Herman T. , Melén Erik , Lahousse Lies 
Published: April 2019

AbstractObjectiveAsthma is a common chronic respiratory airway disease influenced by environmental factors and possibly their interaction with the human genome causing epigenetic changes. Epigenome‐wide association studies (EWAS) have mainly investigated DNA methylation and its association with disease or traits, exposure factors or gene expression. This systematic review aimed to identify all EWAS assessing differentially methylated sites associated with asthma in humans.DesignStructured systematic literature search following PRISMA guidelines, Newcastle‐Ottawa Scale (NOS) for cohort studies was used for bias assessment.Data SourcesWe searched PubMed and Embase databases from 2005 to 2019.Eligibility CriteriaEpigenome‐wide association studies testing association between differential methylation and asthma in humans.ResultsOverall, we identified 16 EWAS studies complying with our search criteria. Twelve studies were conducted on children, and 10 were conducted on sample sizes <150 subjects. Four hundred and nineteen CpGs were reported in children studies after correction for multiple testing. In the adult studies, thousands of differentially methylated sites were identified. Differential methylation in inflammatory‐related genes correlated with higher levels of gene expressions of inflammatory modulators in asthma. Differentially methylated genes associated with asthma included SMAD3, SERPINC1, PROK1, IL13, RUNX3 and TIGIT. Forty‐one CpGs were replicated at least once in blood samples, and 28 CpGs were replicated in nasal samples.ConclusionAlthough many differentially methylated CpGs in genes known to be involved in asthma have been identified in EWAS to date, we conclude that further studies of larger sample sizes and analyses of differential methylation between different phenotypes are needed in order to comprehensively evaluate the role of epigenetic factors in the pathophysiology and heterogeneity of asthma, and the potential clinical utility to predict or classify patients with asthma.
Embryonic extracellular vesicles as informers to the immune cells at the maternal–fetal interface
Authors: Giacomini E , Alleva E , Fornelli G , Quartucci A , Privitera L , Vanni V S , Viganò P 
Published: April 2019

SummaryExtracellular vesicle (EV) exchange is emerging as a novel method of communication at the maternal–fetal interface. The presence of the EVs has been demonstrated in the preimplantation embryo culture medium from different species, such as bovines, porcines and humans. Preimplantation embryo-derived EVs have been shown to carry molecules potentially able to modulate the local endometrial immune system. The non-classical major histocompatibility complex (MHC) class I molecule human leucocyte antigen (HLA)-G, the immunomodulatory molecule progesterone-induced blocking factor and some regulatory miRNAs species are contained in embryo-derived EV cargo. The implanted syncytiotrophoblasts are also well known to secrete EVs, with microvesicles exerting a mainly proinflammatory effect while exosomes in general mediate local immunotolerance. This review focuses on the current knowledge on the potential role of EVs released by the embryo in the first weeks of pregnancy on the maternal immune cells. Collectively, the data warrant further exploration of the dialogue between the mother and the embryo via EVs.
Protein-engineered molecules carrying GAD65 epitopes and targeting CD35 selectively down-modulate disease-associated human B lymphocytes
Authors: Manoylov I K , Boneva G V , Doytchinova I A , Mihaylova N M , Tchorbanov A I 
Published: April 2019

Summary
Type 1 diabetes mellitus is an autoimmune metabolic disorder characterized by chronic hyperglycemia, the presence of autoreactive T and B cells and autoantibodies against self-antigens. A membrane-bound enzyme on the pancreatic beta-cells, glutamic acid decarboxylase 65 (GAD65), is one of the main autoantigens in type 1 diabetes. Autoantibodies against GAD65 are potentially involved in beta-cell destruction and decline of pancreatic functions. The human complement receptor type 1 (CD35) on B and T lymphocytes has a suppressive activity on these cells. We hypothesized that it may be possible to eliminate GAD65-specific B cells from type 1 diabetes patients by using chimeric molecules, containing an anti-CD35 antibody, coupled to peptides resembling GAD65 B/T epitopes. These molecules are expected to selectively bind the anti-GAD65 specific B cells by the co-cross-linking of the immunoglobulin receptor and CD35 and to deliver a suppressive signal. Two synthetic peptides derived from GAD65 protein (GAD65 epitopes) and anti-CD35 monoclonal antibody were used for the construction of two chimeras. The immunomodulatory activity of the engineered antibodies was tested in vitro using peripheral blood mononuclear cells (PBMCs) from type 1 diabetes patients. A reduction in the number of anti-GAD65 IgG antibody-secreting plasma cells and increased percentage of apoptotic B lymphocytes was observed after treatment of these PBMCs with the engineered antibodies. The constructed chimeric molecules are able to selectively modulate the activity of GAD65-specific B lymphocytes and the production of anti-GAD65 IgG autoantibodies by co-cross-linking of the inhibitory CD35 and the B cell antigen receptor (BCR). This treatment presents a possible way to alter the autoimmune nature of these cells.
Patients with tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) are hypersensitive to Toll-like receptor 9 stimulation
Authors: Negm O H , Singh S , Abduljabbar W , Hamed M R , Radford P , McDermott E M , Drewe E , Fairclough L , Todd I , Tighe P J 
Published: April 2019

Summary
Tumour necrosis factor receptor-associated periodic syndrome (TRAPS) is a hereditary autoinflammatory disorder characterized by recurrent episodes of fever and inflammation. It is associated with autosomal dominant mutations in TNFRSF1A, which encodes tumour necrosis factor receptor 1 (TNF-R1). Our aim was to understand the influence of TRAPS mutations on the response to stimulation of the pattern recognition Toll-like receptor (TLR)-9. Peripheral blood mononuclear cells (PBMCs) and serum were isolated from TRAPS patients and healthy controls: serum levels of 15 proinflammatory cytokines were measured to assess the initial inflammatory status. Interleukin (IL)-1β, IL-6, IL-8, IL-17, IL-22, tumour necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), interferon (IFN)-γ, monocyte chemoattractant protein 1 (MCP-1) and transforming growth factor (TGF)-β were significantly elevated in TRAPS patients’ sera, consistent with constitutive inflammation. Stimulation of PBMCs with TLR-9 ligand (ODN2006) triggered significantly greater up-regulation of proinflammatory signalling intermediates [TNF receptor-associated factor (TRAF 3), IL-1 receptor-associated kinase-like 2 (IRAK2), Toll interacting protein (TOLLIP), TRAF6, phosphorylated transforming growth factor-β-activated kinase 1 (pTAK), transforming growth factor-β-activated kinase-binding protein 2 (TAB2), phosphorylated TAK 2 (pTAB2), IFN-regulatory factor 7 (IRF7), receptor interacting protein (RIP), nuclear factor kappa B (NF-κB) p65, phosphorylated NF-κB p65 (pNF-κB p65) and mitogen-activated protein kinase kinase (MEK1/2)] in TRAPS patients’ PBMCs. This up-regulation of proinflammatory signalling intermediates and raised serum cytokines occurred despite concurrent anakinra treatment and no overt clinical symptoms at time of sampling. These novel findings further demonstrate the wide-ranging nature of the dysregulation of innate immune responses underlying the pathology of TRAPS and highlights the need for novel pathway-specific therapeutic treatments for this disease.
Network analysis of a stakeholder community combatting illegal wildlife trade
Authors: Moshier Andrea , Steadman Janna , Roberts David L. 
Published: April 2019

AbstractThe illegal wildlife trade has emerged as a growing and urgent environmental issue. Stakeholders involved in the efforts to curb wildlife trafficking include nongovernmental organizations (NGOs), academia, and state government and enforcement bodies. The extent to which these stakeholders work and communicate among each other is fundamental to effectively combatting illicit trade. Using the United Kingdom as a case study, we used a social network analysis and semistructured interviews of stakeholders to assess communication relationships in the counter wildlife trafficking community. The NGOs consistently occupied 4 of the 5 most central positions in the generated networks, whereas academic institutions routinely occupied 4 of the 5 most peripheral positions. However, NGOs were the least diverse in their communication practices compared with the other stakeholder groups. Stakeholders identified personal relationships as the most important aspect of functioning communication. Participant insights also showed that stakeholder‐specific variables (e.g., ethical and confidentiality concerns), competition, and fundraising can have a confounding effect on intercommunication. Evaluating communication networks and intrastakeholder communication trends is essential to creating cohesive, productive, and efficient responses to the challenges of combatting illegal wildlife trade.Article impact statement: Communication among those combatting illegal wildlife trade is confounded by stakeholder variables (ethics, confidentiality), competition, and fundraising.
Next generation of dentists moving to amalgam‐free dentistry: Survey of posterior restorations teaching in North America
Authors: Zabrovsky Asher , Neeman Levy Tal , Bar‐On Hilit , Beyth Nurit , Ben‐Gal Gilad 
Published: April 2019

AbstractObjectivesThe dental field is gradually reducing the use of amalgam and moving towards adhesive restoration. This change is in accordance with the advancement and improvement of composite resin materials and adhesion systems. Consequently, posterior cavity preparations teaching should be re‐examined to determine whether dental schools are adapting their curriculum to fit the current trends in dentistry and what rationale supports their decisions.MethodsAn online questionnaire was constructed to assess the time dedicated to teaching composite materials and amalgam, in addition to the principles of posterior preparations, for composite restorations in North American dental schools.ResultsA total 33 schools responded to the questionnaire. A large variation was found in teaching methods and techniques of posterior restorations. The reasoning for teaching amalgam restorations was diverse as were the principles of composite resin preparation taught.ConclusionNo agreed principles of cavity preparation for resin composite restorations were found, as opposed to explicit agreement on amalgam cavity preparations. The results demonstrate a lack of clear guidelines for cavity preparation of resin composite restorations. Dental schools may benefit when a consensus on this topic is achieved.