bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of Reporting on Guideline, Protocol, or Algorithm Implementation in Adult Trauma Centers
Authors: Gotlib Conn Lesley , Nathens Avery B. , Perrier Laure , Haas Barbara , Watamaniuk Aaron , Daniel Pereira Diego , Zwaiman Ashley , Javidan Arshia P. , Soobiah Charlene , Strauss Rachel , da Luz Luis Teodoro 
Published: April 2019

Objective:
To appraise the quality of reporting on guideline, protocol, and algorithm implementations in adult trauma settings according to the Revised Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0).

Background:
At present we do not know if published reports of guideline implementations in trauma settings are of sufficient quality to facilitate replication by other centers wishing to implement the same or similar guidelines.

Methods:
A systematic review of the literature was conducted. Articles were identified through electronic databases and hand searching relevant trauma journals. Studies meeting inclusion criteria focused on a guideline, protocol, or algorithm that targeted adult trauma patients ≥18 years and/or trauma patient care providers, and evaluated the effectiveness of guideline, protocol, or algorithm implementation in terms of change in clinical practice or patient outcomes. Each included study was assessed in duplicate for adherence to the 18-item SQUIRE 2.0 criteria. The primary endpoint was the proportion of studies meeting at least 80% (score ≥15) of SQUIRE 2.0.

Results:
Of 7368 screened studies, 74 met inclusion criteria. Thirty-nine percent of studies scored ≥80% on SQUIRE 2.0. Criteria that were met most frequently were abstract (93%), problem description (93%), and specific aims (89%). The lowest scores appeared in the funding (28%), context (47%), and results (54%) criteria. No study indicated using SQUIRE 2.0 as a guideline to writing the report.

Conclusions:
Significant opportunity exists to improve the utility of guideline implementation reports in adult trauma settings, particularly in the domains of study context and the implications of context for study outcomes.
A resource-efficient tool for mixed model association analysis of large-scale data
Authors: Jiang Longda , Zheng Zhili , Qi Ting , Kemper Kathryn E. , Wray Naomi R. , Visscher Peter M. , Yang Jian 
Published: April 2019

ABSTRACTThe genome-wide association study (GWAS) has been widely used as an experimental design to detect associations between genetic variants and a phenotype. Two major confounding factors, population stratification and relatedness, could potentially lead to inflated GWAS test-statistics and thereby spurious associations. Mixed linear model (MLM)-based approaches can be used to account for sample structure. However, genome-wide association (GWA) analyses in biobank samples such as the UK Biobank (UKB) often exceed the capability of most existing MLM-based tools especially if the number of traits is large. Here, we developed an MLM-based tool (called fastGWA) that controls for population stratification by principal components and relatedness by a sparse genetic relationship matrix for GWA analyses of biobank-scale data. We demonstrated by extensive simulations that fastGWA is reliable, robust and highly resource-efficient. We then applied fastGWA to 2,173 traits on 456,422 array-genotyped and imputed individuals and 2,048 traits on 46,191 whole-exome-sequenced individuals in the UKB.
Revisiting G3BP-S149 phosphorylation and its impact on stress granule assembly
Authors: Panas Marc D. , Kedersha Nancy , Schulte Tim , Branca Rui M. , Ivanov Pavel , Anderson Paul 
Published: April 2019

AbstractStress granules (SGs) are cytoplasmic, non-membranous RNA/protein structures that assemble in response to environmental stress. G3BP is a critical SG-nucleating protein, and its ability to regulate SGs has been reported to be regulated by serine 149 phosphorylation. We now report that the constructs engineered to contain non-phosphorylatable and phosphomimetic (G3BP1-S149A and G3BP1-S149E, respectively) mutations used in many studies include additional unintended mutations (A54T/S149A and S99P/S149E) one of which (S99P) is responsible for the effects on SG assembly attributed to S149E. Specifically, the S99P mutation alone reduces SG nucleation and impairs the ability to rescue SG assembly in ΔΔG3BP1/2 U2OS KO cells, challenging the widely-stated conclusion that de-phosphorylation of serine 149 in G3BP1 promotes SG assembly. We used comparative mass spectrometry analysis of both (1) ectopically expressed GFP-G3BP1 in ΔΔG3BP1/2 U2OS KO and (2) endogenous G3BP1 in wild-type U2OS, with and without sodium arsenite treatment, in an attempt to reproduce earlier findings, but found no significant changes in S149 phosphorylation that correlate with arsenite-induced SG formation.
Coheritability and Coenvironmentability as Concepts for Partitioning the Phenotypic Correlation
Authors: Vasquez-Kool Jorge 
Published: April 2019

AbstractCentral to the study of joint inheritance of quantitative traits is the determination of the degree of association between two phenotypic characters, and to quantify the relative contribution of shared genetic and environmental components influencing such relationship. One way to approach this problem builds on classical quantitative genetics theory, where the phenotypic correlationbetween two traits is modelled as the sum of a genetic component called the coheritability (hx,y), which reflects the degree of shared genetics influencing the phenotypic correlation, and an environmental component, namely the coenvironmentability (ex,y) that accounts for all other factors that exert influence on the observed trait-trait association. Here a mathematical and statistical framework is presented on the partition of the phenotypic correlation into these components. I describe visualization tools to analyzeandex,yconcurrently, in the form of a three-dimensional (3DHER-plane) and a two-dimensional (2DHER-field) plots. A large data set of genetic parameter estimates (heritabilities, genetic and phenotypic correlations) was compiled from an extensive literature review, from which coheritability and coenvironmentability were derived, with the object to observe patterns of distribution, and tendency. Illustrative examples from a diverse set of published studies show the value of applying this partition to generate hypotheses proposing the differential contribution of shared genetics and shared environment to an observed phenotypic relationship between traits.
Prior physical synchrony enhances rapport and inter-brain synchronization during subsequent educational communication
Authors: Nozawa Takayuki , Sakaki Kohei , Ikeda Shigeyuki , Jeong Hyeonjeong , Yamazaki Shohei , dos Santos Kawata Kelssy Hitomi , dos Santos Kawata Natasha Yuriko , Sasaki Yukako , Kulason Kay , Hirano Kanan , Miyake Yoshihiro , Kawashima Ryuta 
Published: April 2019

AbstractPhysical synchrony has been suggested to have positive effects on not only concurrent but also subsequent communication, but the underlying neural processes are unclear. Using functional near-infrared spectroscopy (fNIRS) hyperscanning, we tested the effects of preceding physical synchrony on subsequent dyadic teaching-learning communication. Thirty-two pairs of participants performed two experimental sessions. In each session, they underwent a rhythmic arm movement block with synchronous or asynchronous conditions, and then taught/learned unknown words to/from each other according to a given scenario. Neural activities in their medial and left lateral prefrontal cortex (PFC) were measured and inter-brain synchronization (IBS) during the teaching-learning blocks was evaluated. Participants rated their subjective rapport during the teaching-learning blocks, and took a word memory test. The analyses revealed that (1) prior physical synchrony enhanced teacher-learner rapport; (2) prior physical synchrony also enhanced IBS in the lateral PFC; and (3) IBS changes correlated positively with rapport changes. Physical synchrony did however not affect word memory performance. These results suggest that IBS can be useful to measure the effects of social-bonding facilitation activities for educational communication.
Focused screening reveals functional effects of microRNAs differentially expressed in colorectal cancer
Authors: Sastre Danuta , Baiochi João , de Souza Lima Ildercilio Mota , dos Santos Schiavinato Josiane Lilian , Covas Dimas Tadeu , Panepucci Rodrigo Alexandre 
Published: April 2019

AbstractBackgroundColorectal cancer (CRC) is still a leading cause of death worldwide. Recent studies have pointed to an important role of microRNAs carcinogenesis. In fact, several microRNAs have been described as aberrantly expressed in CRC tissues and in the serum of patients. More specifically, microRNAs with dual roles in both cancer and stem cell survival represent a potential source of novel molecular targets in CRC due to their described functions in normal and deregulated proliferation. However, the functional outcomes of microRNA aberrant expression still need to be explored at the cellular level. Here, we aimed to investigate the effects of microRNAs involved in the control of pluripotency of stem cells in the proliferation and cell death of a colorectal cancer cell line.MethodsWe performed transfection of 31 microRNA mimics in HCT116 CRC cells. Cell proliferation and cell death were measured after 4 days of treatment using fluorescence staining in a high content screening platform. Total number of live and dead cells were automatically counted and analyzed. To reveal mRNA targets, we used an oligonucleotide microarray. Functional classification of targets was done using DAVID tool. Gene expression of potential mRNA targets was performed by qPCR.ResultsTwenty microRNAs altered the proliferation of HCT116 cells in comparison to control. Three microRNAs significantly repressed cell proliferation and induced cell death simultaneously (miR-22-3p, miR-24-3p, and miR-101-3p). Interestingly, all anti-proliferative microRNAs in our study had been previously described as poorly expressed in the CRC samples and were implicated in the disease. Microarray analysis of miR-101-3p targets revealed Wnt and cancer as pathways regulated by this microRNA. Specific repression of anti-apoptotic isoform of MCL-1, a member of the BCL-2 family, was also identified as a possible mechanism for miR-101-3p anti-proliferative/pro-apoptotic effect.ConclusionsmicroRNAs described as upregulated in CRC tend to induce proliferation in vitro, whereas microRNAs described as poorly expressed in CRC halt proliferation and induce cell death in vitro. Selective inhibition of anti-apoptotic MCL-1 contributes to anti-tumoral activity of miR-101-3p.
Targeted gene sequencing in 6994 individuals with neurodevelopmental disorder with epilepsy
Authors: Heyne Henrike O. , Artomov Mykyta , Battke Florian , Bianchini Claudia , Smith Douglas R. , Liebmann Nora , Tadigotla Vasisht , Stanley Christine M. , Lal Dennis , Rehm Heidi , Lerche Holger , Daly Mark J. , Helbig Ingo , Biskup Saskia , Weber Yvonne G. , Lemke Johannes R. 
Published: April 2019

AbstractPurposeWe aimed to gain insight into frequencies of genetic variants in genes implicated in neurodevelopmental disorder with epilepsy (NDD+E) by investigating large cohorts of patients in a diagnostic setting.MethodsWe analyzed variants in NDD+E using epilepsy gene panel sequencing performed between 2013 and 2017 by two large diagnostic companies. We compared variant frequencies in 6,994 panels to other 8,588 recently published panels as well as exome-widede novovariants in 1,942 individuals with NDD+E and 10,937 controls.ResultsGenes with highest frequencies of ultra-rare variants in NDD+E comprisedSCN1A, KCNQ2, SCN2A, CDKL5, SCN8AandSTXBP1, concordant with the two other epilepsy cohorts we investigated. Only 46% of the analysed 262 dominant and X-linked panel genes contained ultra-rare variants in patients. Among genes with contradictory evidence of association with epilepsyCACNB4, CLCN2, EFHC1, GABRD, MAGI2andSRPX2showed equal frequencies in cases and controls.ConclusionWe show that improvement of panel design increased diagnostic yield over time, but panels still display genes with low or no diagnostic yield. With our data, we hope to improve current diagnostic NDD+E panel design and provide a resource of ultra-rare variants in individuals with NDD+E to the community.
Completing missing MeSH code mappings in UMLS through alternative expert-curated sources
Authors: García del Valle Eduardo P. , Lagunes García Gerardo , Prieto Santamaría Lucia , Zanin Massimiliano , Rodríguez González Alejandro , Menasalvas Ruiz Ernestina 
Published: April 2019

AbstractThe increasing availability of biological, clinical and literary sources enables the study of diseases from a more comprehensive approach. However, the interoperability of these sources, particularly of the codes used to identify diseases, poses a major challenge. Because of its role as a hub of multiple medical vocabularies, the Unified Medical Language System (UMLS) has become one of the most widely used resources for mapping diseases from different classification systems. The coverage of these mappings, nevertheless, is still limited, so researchers must resort to other methods to fill these gaps. In this article we analyze the limitations in UMLS mappings for the main disease vocabularies and propose the exploitation of some alternative expert-curated sources to complete it. As a result, we demonstrate that this approach allows resolving more than 50% of the missing mappings for some vocabularies. All the findings are shared for validation and reuse.
Single cell transcriptome analysis reveals markers of naïve and lineage-primed hematopoietic progenitors derived from human pluripotent stem cells
Authors: Fidanza Antonella , Romanò Nicola , Ramachandran Prakash , Tamagno Sara , Lopez-Yrigoyen Martha , Taylor Alice Helen , Easterbrook Jennifer , Henderson Beth , Axton Richard , Henderson Neil Cowan , Medvinsky Alexander , Ottersbach Katrin , Forrester LM Lesley Margaret 
Published: April 2019

AbstractDuring embryogenesis the hematopoietic system develops through distinct waves that generate progenitors with increasing lineage potential, ultimately producing haematopoietic stem cells (HSCs). In vitro differentiation of human pluripotent stem cells (hPSCs) follows the early steps of haematopoietic development but the production of HSCs has proven more challenging. To study the dynamics and heterogeneity of hematopoietic progenitor cells generated in vitro from hPSCs, we performed RNA sequencing of over 10000 CD235a-CD43+single cells. We identified the transcriptome of naïve progenitors and those primed toward erythroid, megakaryocyte and leukocyte lineages, and revealed their markers by clustering, trajectory analyses and functional assays. CD44 marks naïve clonogenic progenitors that express the transcription factor, LMO4 and can be expanded upon BMP4 stimulation. Naïve progenitors give rise to primed CD326+erythroid, ICAM2+CD9+megakaryocyte, and monocyte, neutrophil and eosinophil progenitors. We have generated an online dataset of human hematopoietic progenitors and their transcriptional remodelling upon lineage priming.
Multivariate GWAS of psychiatric disorders and their cardinal symptoms reveal two dimensions of cross-cutting genetic liabilities
Authors: Mallard Travis T. , Linnér Richard K. , Grotzinger Andrew D. , Sanchez-Roige Sandra , Seidlitz Jakob , Okbay Aysu , de Vlaming Ronald , Meddens S. Fleur W. ,   Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Palmer Abraham A. , Davis Lea K. , Tucker-Drob Elliot M. , Kendler Kenneth S. , Keller Matthew C. , Koellinger Philipp D. , Harden K. Paige 
Published: April 2019

AbstractUnderstanding which biological pathways are specific versus general across diagnostic categories and levels of symptom severity is critical to improving nosology and treatment of psychopathology. Here, we combine transdiagnostic and dimensional approaches to genetic discovery for the first time, conducting a novel multivariate genome-wide association study (GWAS) of eight psychiatric symptoms and disorders broadly related to mood disturbance and psychosis. We identify two transdiagnostic genetic liabilities that distinguish between common forms of mood disturbance (major depressive disorder, bipolar II, and self-reported symptoms of depression, mania, and psychosis) versus rarer forms of serious mental illness (bipolar I, schizoaffective disorder, and schizophrenia). Biological annotation revealed divergent genetic architectures that differentially implicated prenatal neurodevelopment and neuronal function and regulation. These findings inform psychiatric nosology and biological models of psychopathology, as they suggest the severity of mood and psychotic symptoms present in serious mental illness may reflect a difference in kind, rather than merely in degree.
Behavioral flexibility is associated with changes in structure and function distributed across a frontal cortical network in macaques
Authors: Sallet Jérôme , Noonan MaryAnn P , Thomas Adam , O’Reilly Jill X , Anderson Jesper , Papageorgiou Georgios K , Neubert Franz X , Ahmed Bashir , Smith Jackson , Bell Andrew H , Buckley Mark J , Roumazeilles Léa , Cuell Steven , Walton Mark E , Krug Kristine , Mars Rogier B , Rushworth Matthew FS 
Published: April 2019

AbstractOne of the most influential accounts of central orbitofrontal cortex– that it mediates behavioral flexibility – has been challenged by the finding that discrimination reversal in macaques –the classic test of behavioral flexibility –is unaffected when lesions are made by excitotoxin injection rather than aspiration. This suggests the critical brain circuit mediating behavioral flexibility in reversal tasks lies beyond the central orbitofrontal cortex. To determine its identity a group of nine macaques were taught discrimination reversal learning tasks and its impact on grey matter was measured. Magnetic resonance imaging scans were taken before and after learning and compared with scans from two control groups each comprising ten animals. One control group learned similar discrimination tasks but which lacked any reversal component and the other control group engaged in no learning. Grey matter changes were prominent in posterior orbitofrontal cortex/anterior insula but also were found in three other frontal cortical regions: lateral orbitofrontal cortex (12o), cingulate cortex, and lateral prefrontal cortex. In a second analysis, neural activity in posterior orbitofrontal cortex/anterior insula was measured at rest and its pattern of coupling with the other frontal cortical regions was assessed. Activity coupling increased significantly in the reversal learning group in comparison to controls. In a final set of experiments we used similar structural imaging procedures and analyses to demonstrate that aspiration lesion of central orbitofrontal cortex, of the type known to affect discrimination learning, affected structure and activity in the same frontal cortical circuit. The results identify a distributed frontal cortical circuit associated with behavioral flexibility.
Quantitative proteomic alterations of human iPSC-based neuronal development indicate early onset of Rett syndrome
Authors: Varderidou-Minasian Suzy , Hinz Lisa , Hagemans Dominique , Posthuma Danielle , Altelaar Maarten , Heine Vivi M. 
Published: April 2019

AbstractRett syndrome (RTT) is a progressive neurodevelopmental disease often caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2). The mechanisms by which impaired MeCP2 induces the pathological abnormalities in the brain are not understood. To understand the molecular mechanisms involved in disease, we used an RTT patient induced pluripotent stem cell (iPSC)-based model and applied an in-depth high-resolution quantitative mass spectrometry-based analysis during early stages of neuronal development. Our data provide evidence of proteomic alteration at developmental stages long before the phase that symptoms of RTT syndrome become apparent. Differences in expression profiles became more pronounced from early to late neural stem cell phases, although proteins involved in immunity, metabolic processes and calcium signaling were already affected at initial stages. These results can help development of new biomarkers and therapeutic approaches by selectively target the affected proteins in RTT syndrome.
Comparing infiltration rates in soils managed with conventional and alternative farming methods: a meta-analysis
Authors: Basche Andrea D. , DeLonge Marcia S. 
Published: April 2019

AbstractIdentifying agricultural practices that enhance water cycling is critical, particularly with increased rainfall variability and greater risks of droughts and floods. Soil infiltration rates offer useful insights to water cycling in farming systems because they affect both yields (through soil water availability) and other ecosystem outcomes (such as pollution and flooding from runoff). For example, conventional agricultural practices that leave soils bare and vulnerable to degradation are believed to limit the capacity of soils to quickly absorb and retain water needed for crop growth. Further, it is widely assumed that farming methods such as no-till and cover crops can improve infiltration rates. Despite interest in the impacts of agricultural practices on infiltration rates, this effect has not been systematically quantified across a range of practices. To evaluate how conventional practices affect infiltration rates relative to select alternative practices (no-till, cover crops, crop rotation, introducing perennials, crop and livestock systems), we performed a meta-analysis that included 89 studies with field trials comparing at least one such alternative practice to conventional management. We found that introducing perennials (grasses, agroforestry, managed forestry) or cover crops led to the largest increases in infiltration rates (mean responses of 59.2 ± 20.9% and 34.8 ± 7.7%, respectively). Also, although the overall effect of no-till was non-significant (5.7 ± 9.7%), the practice led to increases in wetter climates and when combined with residue retention. The effect of crop rotation on infiltration rate was non-significant (18.5 ± 13.2%), and studies evaluating impacts of grazing on croplands indicated that this practice reduced infiltration rates (−21.3 ± 14.9%). Findings suggest that practices promoting ground cover and continuous roots, both of which improve soil structure, were most effective at increasing infiltration rates.
In the Body’s Eye: The Computational Anatomy of Interoceptive Inference
Authors: Allen Micah , Levy Andrew , Parr Thomas , Friston Karl J. 
Published: April 2019

AbstractA growing body of evidence highlights the intricate linkage of exteroceptive perception to the rhythmic activity of the visceral body. In parallel, interoceptive inference theories of emotion and self-consciousness are on the rise in cognitive science. However, thus far no formal theory has emerged to integrate these twin domains; instead most extant work is conceptual in nature. Here, we introduce a formal model of cardiac active inference, which explains how ascending cardiac signals entrain exteroceptive sensory perception and confidence. Through simulated psychophysics, we reproduce the defensive startle reflex and commonly reported effects linking the cardiac cycle to fear perception. We further show that simulated ‘interoceptive lesions’ blunt fear expectations, induce psychosomatic hallucinations, and exacerbate metacognitive biases. Through synthetic heart-rate variability analyses, we illustrate how the balance of arousal-priors and visceral prediction errors produces idiosyncratic patterns of physiological reactivity. Our model thus offers the possibility to computationally phenotype disordered brain-body interaction.