bluuebunny/crossref_metadata_2025_split huggingface dataset:
The paediatric developmental toolkit: Facilitating learning of child development
Authors: Young Elizabeth , Jegathesan Thivia , Park Hyeji , Zubairi Mohammad Samad 
Published: May 2020

Abstract

Background
Recent paediatric and family medicine graduates report feeling unprepared to identify and address children and youth with developmental disorders. Developmental history taking and physical examination alone limit engagement with children and youth in an interactive manner to assess development. The paediatric developmental toolkit (PDT) was developed to provide trainees with the opportunity to interact with a child in a play-based manner.

Objectives
The primary objective of this study was to determine the feasibility of PDT within clinical settings, and qualitatively explore how the PDT can be used by teachers and trainees.

Methods
Trainees and their clinical teachers participated in a qualitative study. Trainees used the PDT in clinical settings and were interviewed following their clinical encounters. Interactions between clinical teachers and trainees following the use of the PDT were also recorded. Teachers were interviewed following the trainees’ case presentations and closures of clinic visits. Trainee interviews, teacher and trainee interactions, and teacher interviews were audiotaped, transcribed, and analyzed thematically.

Results
Nine trainees (six paediatric residents, two family medicine residents, and one clinical clerk medical student) and four developmental paediatricians participated in the study. Each trainee used the PDT twice in two different clinical encounters. All residents agreed the PDT enabled them to observe a child’s developmental skills in a short period of time. Clinical teachers all felt the toolkit allowed trainees to more holistically consider a child’s development and diagnosis.

Conclusions
As medical education shifts to a competency-based education curriculum, the PDT is an innovative tool that can be used to enhance paediatric and family medicine residents’ learning of child development by enabling opportunities for interaction with children.
Arabidopsis SMN2/HEN2, Encoding DEAD-Box RNA Helicase, Governs Proper Expression of the Resistance Gene SMN1/RPS6 and Is Involved in Dwarf, Autoimmune Phenotypes of mekk1 and mpk4 Mutants
Authors: Takagi Momoko , Iwamoto Naoki , Kubo Yuta , Morimoto Takayuki , Takagi Hiroki , Takahashi Fuminori , Nishiuchi Takumi , Tanaka Keisuke , Taji Teruaki , Kaminaka Hironori , Shinozaki Kazuo , Akimitsu Kazuya , Terauchi Ryohei , Shirasu Ken , Ichimura Kazuya 
Published: May 2020

AbstractIn Arabidopsis thaliana, a mitogen-activated protein kinase pathway, MEKK1–MKK1/MKK2–MPK4, is important for basal resistance and disruption of this pathway results in dwarf, autoimmune phenotypes. To elucidate the complex mechanisms activated by the disruption of this pathway, we have previously developed a mutant screening system based on a dwarf autoimmune line that overexpressed the N-terminal regulatory domain of MEKK1. Here, we report that the second group of mutants, smn2, had defects in the SMN2 gene, encoding a DEAD-box RNA helicase. SMN2 is identical to HEN2, whose function is vital for the nuclear RNA exosome because it provides non-ribosomal RNA specificity for RNA turnover, RNA quality control and RNA processing. Aberrant SMN1/RPS6 transcripts were detected in smn2 and hen2 mutants. Disease resistance against Pseudomonas syringae pv. tomato DC3000 (hopA1), which is conferred by SMN1/RPS6, was decreased in smn2 mutants, suggesting a functional connection between SMN1/RPS6 and SMN2/HEN2. We produced double mutants mekk1smn2 and mpk4smn2 to determine whether the smn2 mutations suppress the dwarf, autoimmune phenotypes of the mekk1 and mpk4 mutants, as the smn1 mutations do. As expected, the mekk1 and mpk4 phenotypes were suppressed by the smn2 mutations. These results suggested that SMN2 is involved in the proper function of SMN1/RPS6. The Gene Ontology enrichment analysis using RNA-seq data showed that defense genes were downregulated in smn2, suggesting a positive contribution of SMN2 to the genome-wide expression of defense genes. In conclusion, this study provides novel insight into plant immunity via SMN2/HEN2, an essential component of the nuclear RNA exosome.
Validation of the Safer Opioid Prescribing Evaluation Tool (SOPET) for Assessing Adherence to the Centers for Disease Control Opioid Prescribing Guidelines
Authors: Navis Allison , George Mary-Catherine , Nmashie Alexandra , Hoang Ethan , Cedillo Gabriela , Robinson-Papp Jessica 
Published: May 2020

Abstract

Objective
In response to the opioid epidemic, the Centers for Disease Control and Prevention issued guidelines (CDCG) in 2016 for the prescription of opioids for chronic pain. To facilitate research into whether CDCG implementation will lead to reductions in opioid prescribing and improved patient safety, we sought to validate a tool that quantifies CDCG adherence based on clinical documentation.

Design
The Safe Opioid Prescribing Evaluation Tool (SOPET) was developed in four phases as part of a study to improve the implementation of the CDCG in the clinical setting. Four raters with varying levels of clinical experience and expertise were trained to use the SOPET and then used it to evaluate 21 baseline patient encounters. Intraclass correlation coefficient (ICC) estimates and their 95% confident intervals (CIs) were calculated for the total SOPET score based on a mean-rating (k = 4), absolute-agreement, two-way random-effects model. For intrarater reliability, two-way mixed-effect models were used.

Results
Inter-rater reliability was good, with an average-measures ICC of 0.82 (95% CI = 0.63–0.92). Intrarater reliability was excellent for the three raters, who were MDs, with average-measures ICCs as follows: 0.92 (95% CI = 0.81–0.97), 0.97 (95% CI = 0.92–0.99), 0.99 (95% CI = 0.99–0.99). However, the intrarater reliability for the non-MD rater was lower 0.69 (95% CI = 0.22–0.88).

Conclusions
Overall, the SOPET is useful for evaluating implementation of the CDCG in clinical documentation. It is an important first step in the design of future studies assessing whether adherence to the CDCG improves patient safety outcomes.
RADIOECOLOGICAL IMPACT AND THE ASSOCIATED HAZARDS DUE TO NORM FROM OIL AND GAS PRODUCTION FACILITY IN THE WESTERN DESERT OF EGYPT
Authors: Ebaid Yasser Y , Hassan Yasser , Elshemey Wael M 
Published: May 2020

Abstract
An oil and gas production facility in the western desert of Egypt was investigated for possible radiation risks due to the routine operation. Radium-226, Radium-228 and Potassium-40 were assessed in the soil samples collected from the adjacent soakaway pond. The average 226Ra, 228Ra and 40K activity concentrations were 881.0 ± 42.0, 966.0 ± 43.0 and 143.0 ± 8.0 Bq kg−1, respectively. Both 226Ra and 228Ra were above the world ranges, while 40K was within the world range. Water samples from the facilities effluent’s produced water showed elevated levels of both radium isotopes. The effective doses at three different points on the separator outer surfaces over the period between 1995 and 2014 were assessed. The maximum reading was 5.4 μSv h−1 on 2014. The time has significantly contributed to the enhancement of the effective dose readings. However, they are still within the expected range encountered in similar studies reported by International Atomic Energy Agency (IAEA).
The Trace Kynurenine, Cinnabarinic Acid, Displays Potent Antipsychotic-Like Activity in Mice and Its Levels Are Reduced in the Prefrontal Cortex of Individuals Affected by Schizophrenia
Authors: Ulivieri Martina , Wierońska Joanna Monika , Lionetto Luana , Martinello Katiuscia , Cieslik Paulina , Chocyk Agnieszka , Curto Martina , Di Menna Luisa , Iacovelli Luisa , Traficante Anna , Liberatore Francesca , Mascio Giada , Antenucci Nico , Giannino Giuseppe , Vergassola Matteo , Pittaluga Anna , Bruno Valeria , Battaglia Giuseppe , Fucile Sergio , Simmaco Maurizio , Nicoletti Ferdinando , Pilc Andrzej , Fazio Francesco 
Published: May 2020

Abstract
Cinnabarinic acid (CA) is a kynurenine metabolite that activates mGlu4 metabotropic glutamate receptors. Using a highly sensitive ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS-MS) method, we found that CA is present in trace amounts in human brain tissue. CA levels were largely reduced in the prefrontal cortex (PFC) of individuals affected by schizophrenia. This reduction did not correlate with age, sex, duration of the disease, and duration and type of antipsychotic medication and might, therefore, represent a trait of schizophrenia. Interestingly, systemic treatment with low doses of CA (&lt;1 mg/kg, i.p.) showed robust efficacy in several behavioral tests useful to study antipsychotic-like activity in mice and rats and attenuated MK-801-evoked glutamate release. CA failed to display antipsychotic-like activity and inhibit excitatory synaptic transmission in mice lacking mGlu4 receptors. These findings suggest that CA is a potent endogenous antipsychotic-like molecule and reduced CA levels in the PFC might contribute to the pathophysiology of schizophrenia.
Hypothetical control of postural sway
Authors: Mangalam Madhur , Kelty-Stephen Damian G. 
Published: May 2020

AbstractQuiet standing exhibits strongly intermittent variability that has inspired at least two interpretations. First, variability can be intermittent through the alternating engagement and disengagement of complementary control processes at distinct scales. A second and perhaps deeper way to interpret this intermittency is through the possibility that postural control depends on cascade-like interactions across many timescales at once, suggesting specific non-Gaussian distributional properties at different timescales. Multiscale probability density function (PDF) analysis shows that quiet standing on a stable surface exhibits a crossover from low, increasing non-Gaussianity (consistent with exponential distributions) at shorter timescales, reflecting inertial control, towards higher non-Gaussianity. Feedback-based control at medium to longer timescales yields a linear decrease characteristic of cascade dynamics. Destabilizing quiet standing with unstable surface or closed eyes serves to attenuate inertial control and to elicit more of the feedback-based control over progressively shorter timescales. The result was to strengthen the appearance of the linear decay indicating cascade dynamics. Finally, both linear and nonlinear indices of postural sway also govern the relative strength of crossover or of linear decay, suggesting that tempering of non-Gaussianity across log-timescale is a function of both extrinsic constraints and endogenous postural control. These results provide new evidence that cascading interactions across longer-timescales supporting postural corrections can even recruit shorter-timescale processes with novel task constraints that can destabilize posture.
The genetic architecture of post-zygotic reproductive isolation betweenAnopheles coluzziiandAn. quadriannulatus
Authors: Deitz Kevin C. , Takken Willem , Slotman Michel A. 
Published: May 2020

AbstractTheAnopheles gambiaecomplex is comprised of eight morphologically indistinguishable species and has emerged as a model system for the study of speciation genetics due to the rapid radiation of its member species over the past two million years. Male hybrids between mostAn. gambiaecomplex species pairs are sterile, and some genotype combinations in hybrid males cause inviability. We investigated the genetic basis of hybrid male inviability and sterility betweenAn. coluzziiandAn. quadriannulatusby measuring segregation distortion and performing a QTL analysis of sterility in a backcross population. Hybrid males were inviable if they inherited theAn. coluzziiX chromosome and were homozygous at one or more loci in 18.9 Mb region of chromosome 3. TheAn. coluzziiX chromosome has a disproportionately large effect on hybrid sterility when introgressed into anAn. quadriannulatusgenetic background. Additionally, an epistatic interaction between theAn. coluzziiX and a 1.12 Mb, pericentric region of theAn. quadriannulatus3L chromosome arm has a statistically significant contribution to the hybrid sterility phenotype. This same epistatic interaction occurs when theAn. coluzziiX is introgressed into the genetic background ofAn. arabiensis,the sister species ofAn. quadriannulatus, suggesting that this may represent one of the first Dobzhansky–Muller incompatibilities to evolve early in the radiation of theAnopheles gambiaespecies complex. We describe the additive effects of each sterility QTL, epistatic interactions between them, and genes within QTL with protein functions related to mating behavior, reproduction, spermatogenesis, and microtubule morphogenesis, whose divergence may contribute to post-zygotic reproductive isolation betweenAn. coluzziiandAn. quadriannulatus.
Estimating colocalization probability from limited summary statistics
Authors: King Emily A. , Dunbar Fengjiao , Davis Justin Wade , Degner Jacob F. 
Published: May 2020

1Abstract1.1MotivationA common approach to understanding the mechanisms of noncoding GWAS associations is to test the GWAS variant for association with lower level cellular phenotypes such as gene expression. However, significant association to gene expression will often arise from linkage disequilibrium to a separate causal variant and be unrelated to the mechanism underlying the GWAS association. Colocalization is a statistical genetic method used to determine whether the same variant is causal for multiple phenotypes and is stronger evidence for understanding mechanism than shared significance. Current colocalization methods require full summary statistics for both traits, limiting their use with the majority of reported GWAS associations (e.g. GWAS Catalog). We propose a new approximation to the popular coloc method [1] that can be applied when limited summary statistics are available, as in the common scenario where a GWAS catalog hit would be tested for colocalization with a GTEx eQTL. Our method (POint EstiMation of Colocalization - POEMColoc) imputes missing summary statistics using LD structure in a reference panel, and performs colocalization between the imputed statistics and full summary statistics for a second trait.1.2ResultsAs a test of whether we are able to approximate the posterior probability of colocalization, we apply our method to colocalization of UK Biobank phenotypes and GTEx eQTL. We show good correlation between posterior probabilities of colocalization computed from imputed and observed UK Biobank summary statistics. We perform simulations and show that the POEMColoc method can identify shared causality with similar accuracy to the coloc method. We evaluate scenarios that might reduce POEMColoc performance and show that multiple independent causal variants in a region and imputation from a limited subset of typed variants have a larger effect while mismatched ancestry in the reference panel has a modest effect.We apply POEMColoc to estimate colocalization of GWAS Catalog entries and GTEx eQTL. We find evidence for colocalization of ~ 150,000 trait-gene-tissue triplets. We find that colocalized trait-gene pairs are enriched in tissues relevant to the etiology of the disease (e.g., thyroid eQTLs are enriched in colocalized hypothyroidism GWAS signals). Further, we find that colocalized trait-gene pairs are enriched in approved drug target - indication pairs.1.3AvailabilityPOEMColoc is freely available as an R package athttps://github.com/AbbVie-ComputationalGenomics/POEMColoc
Co-expression signatures of combinatorial gene regulation
Authors: Gomez-Cano Fabio , Xu Qian , Shiu Shin-Han , Krishnan Arjun , Grotewold Erich 
Published: May 2020

AbstractGene co-expression analyses provide a powerful tool to determine gene associations. The interaction of transcription factors (TFs) with their target genes is an essential step in gene regulation, yet to what extent TFs-target gene associations are recovered in co-expression studies remains unclear. Using the wealth of data available for Arabidopsis, we show here that protein-DNA interactions are overall poor indicators of TF-target co-expression, yet the inclusion of TF-TF interaction information significantly enhance co-expression signals. These results highlight the impact of combinatorial gene control on such gene association networks. We integrated this information to predict higher-order regulatory complexes, which are difficult to identify experimentally. We demonstrate that genes strongly co-expressed with a TF are also enriched in indirect targets. Our results have significant implications on the empirical understanding of complex gene regulatory networks and transcription factor function, and the significance of co-expression from the perspective of protein-protein and protein-DNA interactions.
Native perennial and non-native annual grasses shape pathogen community composition and disease severity in a California grassland
Authors: Kendig Amy E. , Spear Erin R. , Daws S. Caroline , Flory S. Luke , Mordecai Erin A. 
Published: May 2020

AbstractThe densities of highly competent plant hosts may shape pathogen community composition and disease severity, altering disease risk and impacts. Life history and evolutionary history influence host competence: longer-lived species tend to be better defended than shorter-lived species and pathogens adapt to infect species with which they have longer evolutionary histories. It is unclear, however, how the densities of species that differ in competence due to life and evolutionary histories affect plant pathogen community composition and disease severity.We examined foliar fungal pathogens on two host groups in a California grassland: native perennial and non-native annual grasses. We first characterized pathogen community composition and disease severity on the two host groups to approximate differences in competence. We then used observational and manipulated gradients of native perennial and non-native annual grass densities to assess the effects of each host group on pathogen community composition and disease severity in 1-m2plots.Native perennial and non-native annual grasses hosted distinct pathogen communities but shared generalist pathogens. Native perennial grasses hosted pathogens with larger host ranges and experienced greater disease severity (75% higher proportions of leaves with lesions) than non-native annuals. While the relative abundances of three common pathogens tended to shift, and disease severity of native perennial grasses tended to increase with increasing densities of both host groups, these changes were not statistically significant.Synthesis.The life and evolutionary histories of grasses likely influence their competence for different pathogen species, leading to distinct pathogen communities and differences in disease severity. However, there was no evidence that the density of either host group significantly affected pathogen community composition or disease severity. Therefore, variation in competence for different pathogens likely shapes pathogen community composition and disease severity but may not interact with host density to alter disease risk and impacts at small scales.
PDIP38 is a novel adaptor-like modulator of the mitochondrial AAA+ protease CLPXP
Authors: Strack Philip R. , Brodie Erica J. , Zhan Hanmiao , Schuenemann Verena J. , Valente Liz J. , Saiyed Tamanna , Zeth Kornelius , Truscott Kaye N. , Dougan David A. 
Published: May 2020

SummaryPolymerase δ interacting protein of 38 kDa (PDIP38) was originally identified in a yeast two hybrid screen as an interacting protein of DNA polymerase delta, more than a decade ago. Since this time several subcellular locations have been reported and hence its function remains controversial. Our current understanding of PDIP38 function has also been hampered by a lack of detailed biochemical or structural analysis of this protein. Here we show, that human PDIP38 is directed to the mitochondrion, where it resides in the matrix compartment, together with its partner protein CLPX. PDIP38 is a bifunctional protein, composed of two conserved domains separated by an α-helical hinge region (or middle domain). The N-terminal (YccV-like) domain of PDIP38 forms an SH3-like β-barrel, which interacts specifically with CLPX, via the adaptor docking loop within the N-terminal Zinc binding domain (ZBD) of CLPX. In contrast, the C-terminal (DUF525) domain forms an Immunoglobin-like β-sandwich fold, which contains a highly conserved hydrophobic groove. Based on the physicochemical properties of this groove, we propose that PDIP38 is required for the recognition (and delivery to CLPXP) of proteins bearing specific hydrophobic degrons, potentially located at the termini of the target protein. Significantly, interaction with PDIP38 stabilizes the steady state levels of CLPXin vivo. Consistent with these data, PDIP38 inhibits the LONM-mediated turnover of CLPXin vitro.Collectively, our findings shed new light on the mechanistic and functional significance of PDIP38, indicating that in contrast to its initial identification as a nuclear protein, PIDP38 is abona fidemitochondrial adaptor protein for the CLPXP protease.
Sampling strategies for modelling above ground biomass using optimal imagery and LiDAR metrics
Authors: Murphy Seamus 
Published: May 2020

Disclaimer text“The author has withdrawn their manuscript due to improper referencing of validation and LiDAR datasets. The author has withdrawn the work while they perform additional analysis to explore their conclusions further. Therefore, the authors do not wish this work to be cited as reference for their project. If you have any questions, please contact the corresponding author.”
Seasonal variation in brain mu-opioid receptor availability
Authors: Sun Lihua , Tang Jing , Liljenbäck Heidi , Honkaniemi Aake , Virta Jenni , Isojärvi Janne , Karjalainen Tomi , Kantonen Tatu , Nuutila Pirjo , Hietala Jarmo , Kaasinen Valtteri , Kalliokoski Kari , Hirvonen Jussi , Scheinin Harry , Helin Semi , Eerola Kim , Savontaus Eriika , Yatkin Emrah , Rinne Juha O. , Roivainen Anne , Nummenmaa Lauri 
Published: May 2020

AbstractSeasonal rhythms influence mood and sociability. The brain μ-opioid receptor (MOR) system modulates a multitude of seasonally varying socioemotional functions, but its seasonal variation remains elusive with no previously reportedin vivoevidence. Here, we studied the seasonal effects on brain MOR availability via analysing a dataset (n=204) of [11C]carfentanil positron emission tomography (PET) scans of healthy volunteers. We found that seasonally varying daylength had an inverted U-shaped functional relationship with brain MOR availability. Brain regions sensitive to daylength spanned the socio-emotional brain circuits, where MOR availability formed a spring-like peak. Causal effect of daylength on brain MOR availability was further verified by apost hocexperiment with repeated PET imaging of rats (n=9) under seasonal photoperiodic simulation. Therefore, thein vivobrain MOR availability in normal humans shows significant seasonal variation, which aligns with expected seasonal variation in mood and suicidality.