bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case series of pediatric survivors of anaplastic pleomorphic xanthoastrocytoma
Authors: Ronsley Rebecca , Dunham Christopher , Yip Stephen , Brown Lindsay , Zuccato Jeffrey A , Karimi Shirin , Zadeh Gelareh , Goddard Karen , Singhal Ash , Hukin Juliette , Cheng Sylvia 
Published: January 2021

Abstract

Background
Anaplastic pleomorphic xanthoastrocytoma (APXA) is a rare subtype of CNS astrocytoma. They are generally treated as high-grade gliomas; however, uncertainty exists regarding the optimal therapy. Here, we report on 3 pediatric cases of APXA.

Methods
Our institutional database was queried for cases of APXA and 3 cases were identified. Surgical samples were processed for methylation profiling and chromosomal microarray analysis. Methylation data were uploaded to the online CNS tumor classifier to determine methylation-based diagnoses to determine copy number variations (CNVs).

Results
Two patients were male, 1 female, and all were aged 12 years at diagnosis. All underwent a gross total resection (GTR) and were diagnosed with an APXA. Immunohistochemical analysis demonstrated that 2 cases were BRAF V600E positive. Methylation-based tumor classification supported the APXA diagnosis in all cases. CNV analyses revealed homozygous CKDN2A deletions in all and chromosome 9p loss in 2 cases. All patients received radiation therapy (54 Gy in 30 fractions) with concurrent temozolomide. Two patients received maintenance chemotherapy with temozolomide and lomustine for 6 cycles as per the Children’s Oncology Group ACNS0423. The third patient recurred and went on to receive a second GTR and 6 cycles of lomustine, vincristine, and procarbazine. All are alive with no evidence of disease &gt;4 years post-treatment completion (overall survival = 100%, event free survival = 67%).

Conclusions
The natural history and optimal treatment of this rare pediatric tumor are not well understood. This case series supports the use of adjuvant chemoradiotherapy in the treatment of APXA. The genetic landscape may be informative for optimizing treatment and prognosis.
Small-Area Estimation of Smoke-Free Workplace Policies and Home Rules in US Counties
Authors: Liu Benmei , Dompreh Isaac , Hartman Anne M 
Published: January 2021

Abstract

Introduction
The workplace and home are sources of exposure to secondhand smoke, a serious health hazard for nonsmoking adults and children. Smoke-free workplace policies and home rules protect nonsmoking individuals from secondhand smoke and help individuals who smoke to quit smoking. However, estimated population coverages of smoke-free workplace policies and home rules are not typically available at small geographic levels such as counties. Model-based small-area estimation techniques are needed to produce such estimates.

Methods
Self-reported smoke-free workplace policies and home rules data came from the 2014–2015 Tobacco Use Supplement to the Current Population Survey. County-level design-based estimates of the two measures were computed and linked to county-level relevant covariates obtained from external sources. Hierarchical Bayesian models were then built and implemented through Markov Chain Monte Carlo methods.

Results
Model-based estimates of smoke-free workplace policies and home rules were produced for 3134 (of 3143) US counties. In 2014–2015, nearly 80% of US adult workers were covered by smoke-free workplace policies, and more than 85% of US adults were covered by smoke-free home rules. We found large variations within and between states in the coverage of smoke-free workplace policies and home rules.

Conclusions
The small-area modeling approach efficiently reduced the variability that was attributable to small sample size in the direct estimates for counties with data and predicted estimates for counties without data by borrowing strength from covariates and other counties with similar profiles. The county-level modeled estimates can serve as a useful resource for tobacco control research and intervention.

Implications
Detailed county- and state-level estimates of smoke-free workplace policies and home rules can help identify coverage disparities and differential impact of smoke-free legislation and related social norms. Moreover, this estimation framework can be useful for modeling different tobacco control variables and applied elsewhere, for example, to other behavioral, policy, or health related topics.
Membrane voltage as a dynamic platform for spatiotemporal signaling, physiological, and developmental regulation
Authors: Klejchova Martina , Silva-Alvim Fernanda A L , Blatt Michael R , Alvim Jonas Chaves 
Published: January 2021

AbstractMembrane voltage arises from the transport of ions through ion-translocating ATPases, ion-coupled transport of solutes, and ion channels, and is an integral part of the bioenergetic “currency” of the membrane. The dynamics of membrane voltage—so-called action, systemic, and variation potentials—have also led to a recognition of their contributions to signal transduction, both within cells and across tissues. Here, we review the origins of our understanding of membrane voltage and its place as a central element in regulating transport and signal transmission. We stress the importance of understanding voltage as a common intermediate that acts both as a driving force for transport—an electrical “substrate”—and as a product of charge flux across the membrane, thereby interconnecting all charge-carrying transport across the membrane. The voltage interconnection is vital to signaling via second messengers that rely on ion flux, including cytosolic free Ca2+, H+, and the synthesis of reactive oxygen species generated by integral membrane, respiratory burst oxidases. These characteristics inform on the ways in which long-distance voltage signals and voltage oscillations give rise to unique gene expression patterns and influence physiological, developmental, and adaptive responses such as systemic acquired resistance to pathogens and to insect herbivory.
Brexit, Terrorist Attacks, and Hate Crime: A Longitudinal Analysis
Authors: Piatkowska Sylwia J , Stults Brian J 
Published: January 2021

Abstract
Drawing on theories of intergroup conflict and research on political legitimization of prejudice and crime motivated by bias, this study examines the temporal clustering of hate crimes in the aftermath of triggering events in the UK. In addition to domestic and nondomestic terrorist attacks, we consider the effects of the EU referendum widely known as Brexit. Consistent with previous work, the results reveal sharp increases of hate crimes in the aftermath of the antecedent events. However, we found that the effects of the EU referendum were more prolonged and more intense than the effects of the other triggering events. Moreover, the effects of domestic events are generally significant and stronger in magnitude than nondomestic events. Finally, the results show that the duration and decay of the effects of terrorist attacks on hate crimes generally mirror the severity of the galvanizing event. Taken together, our findings underscore the role of the EU referendum in explaining dramatic increases in crime motivated by bias. Accordingly, they are of particular importance to politicians and policy makers and have implications that go beyond the case of Brexit.
P. falciparumK13 mutations present varying degrees of artemisinin resistance and reduced fitness in African parasites
Authors: Stokes Barbara H. , Rubiano Kelly , Dhingra Satish K. , Mok Sachel , Straimer Judith , Gnädig Nina F. , Bath Jade R. , Deni Ioanna , Ward Kurt E. , Striepen Josefine , Yeo Tomas , Ross Leila S. , Legrand Eric , Ariey Frédéric , Cunningham Clark H. , Souleymane Issa M. , Gansané Adama , Nzoumbou-Boko Romaric , Ndayikunda Claudette , Kabanywanyi Abdunoor M. , Uwimana Aline , Smith Samuel J. , Kolley Olimatou , Ndounga Mathieu , Warsame Marian , Leang Rithea , Nosten François , Anderson Timothy J.C. , Rosenthal Philip J. , Ménard Didier , Fidock David A. 
Published: January 2021

AbstractThe emergence of artemisinin (ART) resistance inPlasmodium falciparumparasites, driven by K13 mutations, has led to widespread antimalarial treatment failure in Southeast Asia. In Africa, our genotyping of 3,299 isolates confirms the emergence of the K13 R561H variant in Rwanda and reveals the continuing dominance of wild-type K13 across 11 countries. We show that this mutation, along with M579I and C580Y, confers varying degrees ofin vitroART resistance in African parasites. C580Y and M579I cause substantial fitness costs, which may counter-select against their dissemination in high-transmission settings. We also define the impact of multiple K13 mutations on ART resistance and fitness in multiple Southeast Asian strains. ART susceptibility is unaltered upon editing point mutations in ferrodoxin or mdr2, earlier resistance markers. These data point to the lack of an evident biological barrier to mutant K13 mediating ART resistance in Africa, while identifying their detrimental impact on parasite growth.
The imprintedZdbf2gene finely tunes feeding and growth in neonates
Authors: Glaser Juliane , Iranzo Julian , Borensztein Maud , Marinucci Mattia , Gualtieri Angelica , Jouhanneau Colin , Teissandier Aurelie , Gaston-Massuet Carles , Bourc’his Deborah 
Published: January 2021

ABSTRACTGenomic imprinting refers to the mono-allelic and parent-specific expression of a subset of genes. While long recognized for their role in embryonic development, imprinted genes have recently emerged as important modulators of postnatal physiology, notably through hypothalamus-driven functions. Here, using mouse models of loss, gain and parental inversion of expression, we report that the paternally expressedZdbf2gene controls neonatal growth in mice, in a dose-sensitive but parent-of-origin-independent manner. We further found thatZdbf2-KO neonates failed to fully activate hypothalamic circuits that stimulate appetite, and suffered milk deprivation and diminished circulating Insulin Growth Factor 1 (IGF-1). Consequently, only half ofZdbf2-KO pups survived the first days after birth and those surviving were smaller. This study demonstrates that precise imprinted gene dosage is essential for vital physiological functions at the transition from intra- to extra-uterine life, here the adaptation to oral feeding and optimized body weight gain.
A synthetic switch based on orange carotenoid protein to control blue light responses in chloroplasts
Authors: Piccinini Luca , Cazzaniga Stefano , Iacopino Sergio , Ballottari Matteo , Giuntoli Beatrice , Licausi Francesco 
Published: January 2021

ABSTRACTSynthetic biology approaches to engineer light‐responsive system are widely used, but their applications in plants are still limited, due to the interference with endogenous photoreceptors. Cyanobacteria, such asSynechocystis spp., possess a soluble carotenoid associated protein named Orange Carotenoid binding Protein (OCP) that, when activated by blue‐green light, undergoes reversible conformational changes that enable photoprotection of the phycobilisomes. Exploiting this system, we developed a new chloroplast‐localized synthetic photoswitch based on a photoreceptor‐associated protein‐fragment complementation assay (PCA). SinceArabidopsis thalianadoes not possess the prosthetic group needed for the assembly of the OCP2 protein, we implemented the carotenoid biosynthetic pathway with a bacterial β‐carotene ketolase enzyme (crtW), to generate keto‐carotenoids producing plants. The novel photoswitch was tested and characterized in Arabidopsis protoplasts with experiments aimed to uncover its regulation by light intensity, wavelength, and its conversion dynamics. We believe that this pioneer study establishes the basis for future implementation of plastid optogenetics to regulate organelle responses, such as gene transcription or enzymatic activity, upon exposure to specific light spectra.One-sentence summaryInspired by the light-driven conformational transitions of orange carotenoid proteins of cyanobacteria, we generated a molecular device able to switch its dimeric state in response to blue light.
Loss of the Long Non-coding RNA OIP5-AS1 Exacerbates Heart Failure in a Sex-Specific Manner
Authors: Zhuang Aowen , Calkin Anna C. , Lau Shannen , Kiriazis Helen , Donner Daniel G. , Liu Yingying , Bond Simon T. , Moody Sarah C. , Gould Eleanor A.M. , Colgan Timothy D. , Carmona Sergio Ruiz , Inouye Michael , de Aguiar Vallim Thomas Q. , Tarling Elizabeth J. , Quaife-Ryan Gregory A. , Hudson James E. , Porrello Enzo R. , Gregorevic Paul , Gao Xiao-Ming , Du Xiao-Jun , McMullen Julie R. , Drew Brian G. 
Published: January 2021

AbstractBackgroundLong ncRNAs (lncRNAs) are known to influence numerous biological processes including cellular differentiation and tissue development. They are also implicated in the maintenance, health and physiological function of many tissues including the heart. Indeed, manipulating the expression of specific lncRNAs has been shown to improve pathological cardiac phenotypes such as heart failure. One lncRNA studied in various settings is OIP5-AS1 (also known as1700020I14RikandCyrano), however its role in cardiac pathologies remains mostly uncharacterised.MethodsWe used data generated from FACS sorted murine cardiomyocytes, human iPSC derived cardiomyocytes, as well as heart tissue from various animal models to investigate OIP5-AS1 expression in health and disease. Using CRISPR we engineered a global OIP5-AS1 knock out (KO) mouse model and performed cardiac pressure overload experiments to study heart failure in these animals. RNA-sequencing of left ventricles provided mechanistic insight between WT and KO mice.ResultsWe demonstrate that OIP5-AS1 expression is regulated during cardiac development and cardiac specific pathologies in both rodent and human models. Moreover, we demonstrate that global female OIP5-AS1 KO mice develop exacerbated heart failure, but male mice do not. Transcriptomics and gene set enrichment analysis suggests that OIP5-AS1 may regulate pathways that impact mitochondrial function.ConclusionsOIP5-AS1 is regulated in cardiac tissue and its deletion leads to worsening heart function under pressure overload in female mice. This may be due to impairments in mitochondrial function, highlighting OIP5-AS1 as a gene of interest in sex-specific differences in heart failure.
An agnostic study of associations between ABO and RhD blood group and phenome-wide disease risk
Authors: Dahlén Torsten , Clements Mark , Zhao Jingcheng , Olsson Martin L , Edgren Gustaf 
Published: January 2021

AbstractThere are multiple known associations between the ABO and RhD blood groups and disease. However, no systematic population-based studies elucidating associations between a large number of disease states and blood group have been conducted. Using SCANDAT3-S, a comprehensive nationwide blood donation-transfusion database, we modelled outcomes for 1,217 disease categories including 70 million person-years of follow-up, accruing from 5.1 million unique individuals. We discovered 49 and 1 associations between a disease and ABO and RhD blood group, respectively, after adjustment for multiple testing. We identified new associations such as kidney stones and blood group B as compared to O. We also expanded previous knowledge on other associations such as pregnancy-induced hypertension and blood group A and AB as compared to O and RhD positive as compared to negative. Our findings generate strong further support for previously known associations, but also indicate new interesting relations.
Dynamic dichotomy of accumbal population activity underlies cocaine sensitization
Authors: van Zessen Ruud , Flakowski Jérôme , Lüscher Christian 
Published: January 2021

AbstractLocomotor sensitization (LS) is an early behavioral adaptation to addictive drugs, driven by the increase of dopamine in the Nucleus Accumbens (NAc). However, the effect on accumbal population activity remains elusive. Here we used single cell calcium imaging to record the activity of dopamine-1-receptor (D1R) and dopamine-2-receptor (D2R) expressing spiny projection neurons (SPNs) during cocaine LS. Acute exposure to cocaine elevated D1R SPN activity and reduced D2R SPN activity, albeit with high variability between neurons. During LS, the number of D1R and D2R neurons responding in opposite directions increased. Moreover, preventing LS by inhibition of the ERK signalling pathway decreased the number of cocaine-responsive D1R SPNs, but had little effect on D2R SPNs. These results indicate that accumbal population dichotomy is dynamic and contains a subgroup of D1R SPNs that eventually drives LS. Insights into the drug-related activity dynamics provides a foundation for understanding the circuit-level addiction pathogenesis.
Biodiversity Image Quality Metadata Augments Convolutional Neural Network Classification of Fish Species
Authors: Leipzig Jeremy , Bakis Yasin , Wang Xiaojun , Elhamod Mohannad , Diamond Kelly , Dahdul Wasila , Karpatne Anuj , Maga Murat , Mabee Paula , Bart Henry L. , Greenberg Jane 
Published: January 2021

AbstractBiodiversity image repositories are crucial sources of training data for machine learning approaches to biological research. Metadata, specifically metadata about object quality, is putatively an important prerequisite to selecting sample subsets for these experiments. This study demonstrates the importance ofimage quality metadatato a species classification experiment involving a corpus of 1935 fish specimen images which were annotated with 22 metadata quality properties. A small subset of high quality images produced an F1 accuracy of 0.41 compared to 0.35 for a taxonomically matched subset of low quality images when used by a convolutional neural network approach to species identification. Using the full corpus of images revealed that image quality differed between correctly classified and misclassified images. We found the visibility of all anatomical features was the most important quality feature for classification accuracy. We suggest biodiversity image repositories consider adopting a minimal set of image quality metadata to support future machine learning projects.
Directed Functional and Structural Connectivity in a Large-Scale Model for the Mouse Cortex
Authors: Nunes Ronaldo V. , Reyes Marcelo Bussotti , Mejias Jorge F. , de Camargo Raphael Y. 
Published: January 2021

AbstractInferring the structural connectivity from electrophysiological measurements is a fundamental challenge in systems neuroscience. Directed functional connectivity measures, such as the Generalized Partial Directed Coherence (GPDC), provide estimates of the causal influence between areas. However, the relation between causality estimates and structural connectivity is still not clear. We analyzed this problem by evaluating the effectiveness of GPDC to estimate the connectivity of a ground-truth, data-constrained computational model of a large-scale network model of the mouse cortex. The model contains 19 cortical areas comprised of spiking neurons, with areas connected by long-range projections with weights obtained from a tract-tracing cortical connectome. We show that GPDC values provide a reasonable estimate of structural connectivity, with an average Pearson correlation over simulations of 0.74. Moreover, even in a typical electrophysiological recording scenario containing five areas, the mean correlation was above 0.6. These results suggest that it may be possible to empirically estimate structural connectivity from functional connectivity even when detailed whole-brain recordings are not achievable.
The evolution of interdependence in a four-way mealybug symbiosis
Authors: Garber Arkadiy I. , Kupper Maria , Laetsch Dominik R. , Weldon Stephanie R. , Ladinsky Mark S. , Bjorkman Pamela J. , McCutcheon John P. 
Published: January 2021

AbstractMealybugs are insects that maintain intracellular bacterial symbionts to supplement their nutrientpoor plant sap diets. Some mealybugs have a single betaproteobacterial endosymbiont, aCandidatusTremblaya species (hereafterTremblaya) that alone provides the insect with its required nutrients. Other mealybugs have two nutritional endosymbionts that together provide these nutrients, whereTremblayahas gained a gammaproteobacterial partner that resides in the cytoplasm ofTremblaya. Previous work had established thatPseudococcus longispinusmealybugs maintain not one but two species of gammaproteobacterial endosymbionts along withTremblaya. Preliminary genomic analyses suggested that these two gammaproteobacterial endosymbionts have large genomes with features consistent with a relatively recent origin as insect endosymbionts, but the patterns of genomic complementarity between members of the symbiosis and their relative cellular locations were unknown. Here, using long-read sequencing and various types of microscopy, we show that the two gammaproteobacterial symbionts ofP. longispinusare mixed together withinTremblayacells, and that their genomes are somewhat reduced in size compared to their closest non-endosymbiotic relatives. Both gammaproteobacterial genomes contain thousands of pseudogenes, consistent with a relatively recent shift from a free-living to endosymbiotic lifestyle. Biosynthetic pathways of key metabolites are partitioned in complex interdependent patterns among the two gammaproteobacterial genomes, theTremblayagenome, and horizontally acquired bacterial genes that are encoded on the mealybug nuclear genome. Although these two gammaproteobacterial endosymbionts have been acquired recently in evolutionary time, they have already evolved co-dependencies with each other,Tremblaya, and their insect host.SignificanceMealybugs are sap-feeding insects that house between one and three bacterial endosymbionts to supplement their nutritionally poor diets. Many mealybug-bacteria relationships were established tens or hundreds of millions of years ago, and these ancient examples show high levels host-endosymbiont genomic and metabolic integration. Here, we describe the complete genomes and cellular locations for two bacterial endosymbiont which have recently transitioned from a free-living to an intracellular state. Our work reveals the rapid emergence of metabolic interdependence between these two nascent endosymbionts, their partner bacterial co-symbiont in whose cytoplasm they reside, and their insect host cell. Our work confirms that intracellular bacteria rapidly adapt to a host-restricted lifestyle through breakage or loss of redundant genes.
Resequencing 250 soybean accessions: new insights into genes associated with agronomic traits and genetic networks
Authors: Yang Chunming , Yan Jun , Jiang Shuqin , Li Xia , Min Haowei , Wang Xiangfeng , Hao Dongyun 
Published: January 2021

AbstractLimited knowledge on genomic diversity and the functional genes associated with soybean variety traits has resulted in slow breeding progress. We sequenced the genome of 250 soybean landraces and cultivars from China, America and Europe, and investigated their population structure, genetic diversity and architecture and selective sweep regions of accessions. We identified five novel agronomically important genes and studied the effects of functional mutations in respective genes. We found candidate genes GSTT1, GL3 and GSTL3 associated with isoflavone content, CKX3 associated with yield traits, and CYP85A2 associated with both architecture and yield traits. Our phenotype-gene network analysis revealed that hub nodes play a role in complex phenotypic associations. In this work, we describe novel agronomic trait associated genes and a complex genetic network, providing a valuable resource for future soybean molecular breeding.