bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide SNP Data Reveal an Overestimation of Species Diversity in a Group of Hawkmoths
Authors: Hundsdoerfer Anna K , Lee Kyung Min , Kitching Ian J , Mutanen Marko 
Published: May 2019

AbstractThe interface between populations and evolving young species continues to generate much contemporary debate in systematics depending on the species concept(s) applied but which ultimately reduces to the fundamental question of “when do nondiscrete entities become distinct, mutually exclusive evolutionary units”? Species are perceived as critical biological entities, and the discovery and naming of new species is perceived by many authors as a major research aim for assessing current biodiversity before much of it becomes extinct. However, less attention is given to determining whether these names represent valid biological entities because this is perceived as both a laborious chore and an undesirable research outcome. The charismatic spurge hawkmoths (Hyles euphorbiae complex, HEC) offer an opportunity to study this less fashionable aspect of systematics. To elucidate this intriguing systematic challenge, we analyzed over 10,000 ddRAD single nucleotide polymorphisms from 62 individuals using coalescent-based and population genomic methodology. These genome-wide data reveal a clear overestimation of (sub)species-level diversity and demonstrate that the HEC taxonomy has been seriously oversplit. We conclude that only one valid species name should be retained for the entire HEC, namely Hyles euphorbiae, and we do not recognize any formal subspecies or other taxonomic subdivisions within it. Although the adoption of genetic tools has frequently revealed morphologically cryptic diversity, the converse, taxonomic oversplitting of species, is generally (and wrongly in our opinion) accepted as rare. Furthermore, taxonomic oversplitting is most likely to have taken place in intensively studied popular and charismatic organisms such as the HEC.
An integrative approach to detect epigenetic mechanisms that putatively mediate the influence of lifestyle exposures on disease susceptibility
Authors: Richardson Tom G , Richmond Rebecca C , North Teri-Louise , Hemani Gibran , Davey Smith George , Sharp Gemma C , Relton Caroline L 
Published: May 2019

Abstract

Background
There is mounting evidence that our environment and lifestyle has an impact on epigenetic regulatory mechanisms, such as DNA methylation. It has been suggested that these molecular processes may mediate the effect of risk factors on disease susceptibility, although evidence in this regard has been challenging to uncover. Using genetic variants as surrogate variables, we have used two-sample Mendelian randomization (2SMR) to investigate the potential implications of putative changes to DNA methylation levels on disease susceptibility.

Methods
To illustrate our approach, we identified 412 CpG sites where DNA methylation was associated with prenatal smoking. We then applied 2SMR to investigate potential downstream effects of these putative changes on 643 complex traits using findings from large-scale genome-wide association studies. To strengthen evidence of mediatory mechanisms, we used multiple-trait colocalization to assess whether DNA methylation, nearby gene expression and complex trait variation were all influenced by the same causal genetic variant.

Results
We identified 22 associations that survived multiple testing (P < 1.89 × 10–7). In-depth follow-up analyses of particular note suggested that the associations between DNA methylation at the ASPSCR1 and REST/POL2RB gene regions, both linked with reduced lung function, may be mediated by changes in gene expression. We validated associations between DNA methylation and traits using independent samples from different stages across the life course.

Conclusion
Our approach should prove valuable in prioritizing CpG sites that may mediate the effect of causal risk factors on disease. In-depth evaluations of findings are necessary to robustly disentangle causality from alternative explanations such as horizontal pleiotropy.
Chronic Physical Health Conditions, Mental Health, and Sources of Support in a Longitudinal Australian Child Population Cohort
Authors: Laurens Kristin R , Green Melissa J , Dean Kimberlie , Tzoumakis Stacy , Harris Felicity , Islam Fakhrul , Kariuki Maina , Essery Claire M , Schofield Jill M , Carr Vaughan J 
Published: May 2019

Abstract

Objective
This study examined associations between chronic physical health conditions (identified from hospital records) that are subject to school health care plans, and children’s emotional, behavioral, and social functioning during early (∼5 years of age) and middle childhood (∼11 years).

Methods
Participants were 21,304 Australian children from a representative longitudinal population cohort derived by multi-agency record linkage. Hospital presentations (admitted patients and emergency department) identified children with asthma (n = 1,573), allergies and anaphylaxis (n = 738), type 1 diabetes (n = 59), epilepsy (n = 87), and any of these conditions (n = 2,275), relative to 19,029 children without these presentations. Logistic regression analyses determined associations between these exposures and (i) emotional, behavioral, social, and overall vulnerabilities reported by teachers (early childhood) and children (middle childhood), and (ii) self-reported lack of sources of support (middle childhood).

Results
Prevalence of any condition in hospital records was 7.5% by early childhood, and 10.7% by middle childhood. Relative to peers without these presentations, small increases in risk of overall problems, and selected emotional, behavioral, and social problems, were apparent for children with any condition, and asthma specifically, in early and middle childhood. Large and pervasive effects were apparent for epilepsy, limited small effects in middle childhood only for allergies and anaphylaxis, and no increases in risk associated with type 1 diabetes examined in middle childhood. No condition was associated with increased risk of lacking supports.

Conclusions
Children with hospital records of chronic conditions, particularly epilepsy and asthma, might benefit from school-based care plans that integrate their physical and mental health support needs.
The Impact of Aeroallergens on Military Readiness: A Case Report
Authors: Fajardo Kevin A , Wohltmann Wendi E 
Published: May 2019

Abstract
Seasonal aeroallergens commonly cause allergic conjunctivitis, rhinorrhea, sinusitis, and cough in sensitized individuals. These clinical symptoms are the result of IgE-mediated type I hypersensitivity reactions, which trigger the degranulaton of mast cells and basophils. In contrast, aeroallergens are not common precipitants of urticarial dermatitis, which is driven by a cell-mediated type IV hypersensitivity reaction. In this case report, we describe an Active Duty Air Force member stationed in San Antonio, TX, who presented to the dermatology clinic with a three year history of recalcitrant urticarial dermatitis found to be directly related to exposure to the pollen from the Juniperus ashei tree, also referred to as Mountain Cedar. While laboratory findings confirmed a high level of circulating IgE antibody to Mountain Cedar, the patient had no upper respiratory symptoms consistent with a typical allergic reaction. Further, his skin disease rapidly cleared within 24 hours of leaving southern Texas. Because of the recalcitrant nature of his condition upon returning home, he was considered unfit for further military service. This case not only highlights the growing link between IgE and chronic skin disease, but also the impact aeroallergens can have on the medical readiness and world-wide deployability of Airmen, Sailors, Soldiers, and Marines.
Iron supplementation in preterm and low-birth-weight infants: a systematic review of intervention studies
Authors: McCarthy Elaine K , Dempsey Eugene M , Kiely Mairead E 
Published: May 2019

Abstract

Context
Enteral iron supplementation in preterm infants is recommended to supply sufficient iron for growth and development without increasing the risk of iron overload. However, the current recommendations date from 2010 and are based on limited evidence.

Objective
This systematic review aimed to investigate the effects of enteral iron supplementation on iron status, growth, neurological development, and adverse clinical outcomes in preterm (&lt;37 weeks’ gestation) and low-birth-weight (LBW, &lt;2500 g) infants.

Data sources
The PubMed/Medline and Cochrane Library databases were searched to 31 October 2018.

Data extraction
Of the 684 records identified, 27 articles, describing 18 randomized controlled trials (RCTs) plus 4 nonrandomized interventions, were included. Using the Cochrane Collaboration’s criteria, study quality was found to be poor to fair overall.

Results
Most articles (23/27) reported iron status indices; supplementation for ≥8 weeks resulted in increased hemoglobin and ferritin concentrations and a reduction in iron deficiency and anemia. No article reported on iron overload. Growth-related parameters reported in 12 articles were not affected by supplementation. Among the 7 articles on neurological development, a positive effect on behavior at 3.5 and 7 years was observed in one Swedish RCT. No association was found between supplementation and adverse clinical outcomes in the 9 articles reporting on studies in which such data was collected.

Conclusions
Long-term iron supplementation appears to result in improved iron status and a reduction in iron deficiency and anemia in preterm and LBW infants. However, high-quality evidence regarding the long-term effects of supplementation on functional health outcomes is lacking. Iron overload has largely been ignored. Well-designed, long-term, dose-response RCTs are required to ascertain the optimal dose and delivery method for the provision of dietary iron in preterm infants, with consideration of short- and long-term health effects.

Systematic Review Registration
PROSPERO registration no. CRD42018085214.
Other-Awareness
Authors: Rowlands Mark 
Published: May 2019

Abstract
Other-awareness is the ability to recognize another as minded. This sort of ability is usually identified with mindreading: the ability to attribute mental states to another and use this attribution to predict and/or explain his or her behavior. It is unclear whether animals have mindreading abilities. However, even if they do not, there is another way of being aware of the mindedness of another. Just as there is a pre-intentional form of self-awareness, so too is there a pre-intentional form of other-awareness. In pre-intentional self-awareness, one is aware of oneself in virtue of being aware of something else in a certain way. In pre-intentional other-awareness, one is aware of the other in virtue of being aware of oneself in a certain way. Arguments are presented for the claim that many animals can be pre-intentionally other-aware.
Swapping Birth and Death: Symmetries and Transformations in Phylodynamic Models
Authors: Stadler Tanja , Steel Mike 
Published: May 2019

Abstract
Stochastic birth–death models provide the foundation for studying and simulating evolutionary trees in phylodynamics. A curious feature of such models is that they exhibit fundamental symmetries when the birth and death rates are interchanged. In this article, we first provide intuitive reasons for these known transformational symmetries. We then show that these transformational symmetries (encoded in algebraic identities) are preserved even when individuals at the present are sampled with some probability. However, these extended symmetries require the death rate parameter to sometimes take a negative value. In the last part of this article, we describe the relevance of these transformations and their application to computational phylodynamics, particularly to maximum likelihood and Bayesian inference methods, as well as to model selection.
Outcomes After Rectal Cancer Surgery: A Population-Based Study Using Quality Indicators
Authors: Youl Philippa , Philpot Shoni , Theile David E. ,   for Cancer Alliance Queensland
Published: May 2019

ABSTRACT
Quality indicators are increasingly being used to measure the safety of cancer treatments. We examined factors associated with poorer outcomes after major resection for rectal cancer over time. We linked population-based cancer registry and cancer-related procedure data for rectal cancer cases over a 15-year period. Multivariable logistic regression models were used to examine factors associated with 30- and 90-day postoperative mortality, and overall survival (OS) was estimated using the Kaplan–Meier survival function. The study included 9,222 patients who had major resection for invasive rectal cancer. Thirty-day and 90-day mortality were 2.1% and 3.8%, respectively. Risk of 30-day mortality was elevated in older patients (p < .001); patients with ≥2 comorbidities (p < .001); and those admitted as an emergency (p < .001). An approximate 45% reduction in 30-day mortality (p = .01) was observed over time. Two-year OS was 81.5%, again with significant improvements observed over time (p < .001). No significant association was observed between hospital volume and mortality or 2-year survival. A reduction in rates of postoperative mortality and improved 2-year OS were observed over time. Quality indicators are a valuable tool to monitor clinical outcomes over time and as a means of improving clinical care for all patients.
Female meiotic drive preferentially segregates derived metacentric chromosomes inDrosophila
Authors: Stewart Nicholas B. , Ahmed-Braimah Yasir H. , Cerne Daniel G. , McAllister Bryant F. 
Published: May 2019

AbstractA vast diversity of karyotypes exists within and between species, yet the mechanisms that shape this diversity are poorly understood. Here we investigate the role of biased meiotic segregation—i.e., meiotic drive—in karyotype evolution. The closely related species,Drosophila americanaandD. novamexicana, provide an ideal system to investigate mechanisms of karyotypic diversification. Since their recent divergence,D. americanahas evolved two centromeric fusions: one between the 2nd and 3rd chromosomes, and another between the X and 4th chromosomes. The 2-3 fusion is fixed inD. americana, but the X-4 fusion is polymorphic and varies in frequency along a latitudinal cline. Here we evaluate the hypothesis that these derived metacentric chromosomes segregate preferentially to the egg nucleus during female meiosis inD. americana. Using two different methods, we show that the fused X-4 chromosome is transmitted at an average frequency of ~57%, exceeding expectations of 50:50 Mendelian segregation. Three paracentric inversions are found in the vicinity of the X-4 fusion and could potentially influence chromosome segregation. Using crosses between lines with differing inversion arrangements, we show that the transmission bias persists regardless of inversion status. Transmission rates are also biased inD. americana/D. novamexicanahybrid females, favoring both the X-4 and 2-3 fused arrangements over their unfused homologs. Our results show that meiotic drive influences chromosome segregation inD. americanafavoring derived arrangements in its reorganized karyotype. Moreover, the fused centromeres are the facilitators of biased segregation rather than associated chromosomal inversions.
Biological Aging in Childhood and Adolescence Following Experiences of Threat and Deprivation: A Systematic Review and Meta-Analysis
Authors: Colich N.L. , Rosen M.L. , Williams E.S. , McLaughlin K.A. 
Published: May 2019

AbstractLife history theory argues that exposure to early-life adversity (ELA) accelerates development, although existing evidence for this varies. We present a meta-analysis and systematic review testing the hypothesis that ELA involving threat (e.g., violence exposure) will be associated with accelerated biological aging across multiple metrics, whereas exposure to deprivation (e.g., neglect, institutional rearing) and low-socioeconomic status (SES) will not. We meta-analyze 46 studies (n=64,925) examining associations of ELA with pubertal timing and cellular aging (telomere length and DNA methylation age), systematically review 19 studies (n=2276) examining ELA and neural markers of accelerated development (cortical thickness and amygdala-prefrontal cortex functional connectivity) and evaluate whether associations of ELA with biological aging vary according to the nature of adversity experienced. ELA overall was associated with accelerated pubertal timing (d=-0.12) and cellular aging (d=-0.32). Moderator analysis revealed that ELA characterized by threat (d=-0.26), but not deprivation or SES, was associated with accelerated pubertal development. Similarly, exposure to threat-related ELA was associated with accelerated cellular aging (d=-0.43), but not deprivation or SES. Systematic review revealed associations between ELA and accelerated cortical thinning, with threat-related ELA consistently associated with thinning in ventromedial prefrontal cortex, and deprivation and SES associated with thinning in frontoparietal, default, and visual networks. There was no consistent association of ELA with amygdala-PFC connectivity. These findings suggest specificity in the types of early environmental experiences associated with accelerated biological aging and highlight the importance of evaluating how accelerated aging contributes to health disparities and whether this process can be mitigated through early intervention.
An optimised protocol for isolation of RNA through laser capture microdissection of leaf material
Authors: Hua Lei , Hibberd Julian M 
Published: May 2019

AbstractLaser Capture Microdissection is a powerful tool that allows thin slices of specific cells types to be separated from one another. However, the most commonly used protocol, which involves embedding tissue in paraffin wax, results in severely degraded RNA. Yields from low abundance cell types of leaves are particularly compromised. We reasoned that the relatively high temperature used for sample embedding, and aqueous conditions associated with sample preparation prior to microdissection contribute to RNA degradation. Here we describe an optimized procedure to limit RNA degradation that is based on the use of low melting point wax as well as modifications to sample preparation prior to dissection, and isolation of paradermal, rather than transverse sections. Using this approach high quality RNA suitable for down-stream applications such as quantitative reverse transcriptase polymerase chain reactions or RNA-sequencing is recovered from microdissected bundle sheath strands and mesophyll cells of leaf tissue.
Image-based consensus molecular subtype classification (imCMS) of colorectal cancer using deep learning
Authors: Sirinukunwattana Korsuk , Domingo Enric , Richman Susan , Redmond Keara L , Blake Andrew , Verrill Clare , Leedham Simon J , Chatzipli Aikaterini , Hardy Claire , Whalley Celina , Wu Chieh-Hsi , Beggs Andrew D , McDermott Ultan , Dunne Philip , Meade Angela A , Walker Steven M , Murray Graeme I , Samuel Leslie M , Seymour Matthew , Tomlinson Ian , Quirke Philip , Maughan Tim , Rittscher Jens , Koelzer Viktor H ,   on behalf of S:CORT consortium
Published: May 2019

ABSTRACTImage analysis is a cost-effective tool to associate complex features of tissue organisation with molecular and outcome data. Here we predict consensus molecular subtypes (CMS) of colorectal cancer (CRC) from standard H&E sections using deep learning. Domain adversarial training of a neural classification network was performed using 1,553 tissue sections with comprehensive multi- omic data from three independent datasets. Image-based consensus molecular subtyping (imCMS) accurately classified CRC whole-slide images and preoperative biopsies, spatially resolved intratumoural heterogeneity and provided accurate secondary calls with higher discriminatory power than bioinformatic prediction. In all three cohorts imCMS established sensible classification in CMS unclassified samples, reproduced expected correlations with (epi)genomic alterations and effectively stratified patients into prognostic subgroups. Leveraging artificial intelligence for the development of novel biomarkers extracted from histological slides with molecular and biological interpretability has remarkable potential for clinical translation.
Development of a Confinable Gene-Drive System in the Human Disease Vector,Aedes aegypti
Authors: Li Ming , Yang Ting , Kandul Nikolay P. , Bui Michelle , Gamez Stephanie , Raban Robyn , Bennett Jared , Sánchez C. Héctor M. , Lanzaro Gregory C. , Schmidt Hanno , Lee Yoosook , Marshall John M. , Akbari Omar S. 
Published: May 2019

AbstractAedes aegypti, the principal mosquito vector for many arboviruses that causes yellow fever, dengue, Zika, and chikungunya, increasingly infects millions of people every year. With an escalating burden of infections and the relative failure of traditional control methods, the development of innovative control measures has become of paramount importance. The use of gene drives has recently sparked significant enthusiasm for the genetic control of mosquito populations, however no such system has been developed inAe. aegypti. To fill this void and demonstrate efficacy inAe. aegypti,here we develop several CRISPR-based split-gene drives for use in this vector. With cleavage rates up to 100% and transmission rates as high as 94%, mathematical models predict that these systems could spread anti-pathogen effector genes into wildAe. aegyptipopulations in a safe, confinable and reversible manner appropriate for field trials and effective for controlling disease. These findings could expedite the development of effector-linked gene drives that could safely control wild populations ofAe. aegyptito combat local pathogen transmission.Significance StatementAe. aegyptiis a globally distributed arbovirus vector spreading deadly pathogens to millions of people annually. Current control methods are inadequate and therefore new technologies need to be innovated and implemented. With the aim of providing new tools for controlling this pest, here we engineered and tested several split gene drives in this species. These drives functioned at very high efficiency and may provide a tool to fill the void in controlling this vector. Taken together, our results provide compelling path forward for the feasibility of future effector-linked split-drive technologies that can contribute to the safe, sustained control and potentially the elimination of pathogens transmitted by this species.