bluuebunny/crossref_metadata_2025_split huggingface dataset:
Withdrawal Symptoms From E-Cigarette Abstinence Among Adult Never-Smokers: A Pilot Experimental Study
Authors: Hughes John R , Peters Erica N , Callas Peter W , Peasley-Miklus Catherine , Oga Emmanuel , Etter Jean-Francois , Morley Nicholas 
Published: August 2019

Abstract

Introduction
Use of e-cigarettes among never-smokers has substantially increased; yet there are few descriptions of the consequences of such use. We assessed whether adult never-smokers can have withdrawal from cessation of e-cigarettes.

Methods
In an un-blinded pre-post clinical trial, 30 never-smoker daily e-cigarette users used their own nicotine-containing e-cigarette for 7 days followed by 6 days of biologically confirmed abstinence. Participants monitored symptoms of nicotine withdrawal nightly via an Interactive Voice Response system. They attended three lab visits/week to provide expired carbon monoxide and urine samples to determine compliance.

Findings
Abstinence increased all the DSM5 symptoms of tobacco withdrawal and this occurred in the majority of participants. The increase in severity of withdrawal was small and rarely impaired functioning.

Conclusions
Our finding suggests that withdrawal symptoms can occur in never-smokers who stop e-cigarettes abruptly. However, the severity of withdrawal appears to be small and may not be of clinical or regulatory significance. Although our sample size was small and thus replication tests of our results are indicated, it may be prudent to warn never-smokers that withdrawal symptoms may occur.

Implications
This study indicates that withdrawal symptoms can occur in never-smokers who are daily e-cigarette users. However, the severity of withdrawal from e-cigarette abstinence in never-smokers appears to be small and may not be of clinical or regulatory significance. Given our small sample size, replication of our results is warranted. Nevertheless, it might be prudent to warn never-smokers of addiction to e-cigarettes.
Clinical Trial Registration = NCT02825459
Nasal polyp epithelial atypia and exposure to nickel and copper
Authors: Perić A , Vukomanović Đurđević B 
Published: August 2019

Abstract

Background
Possible factors for cell atypia in nasal mucosa include noxious chemicals: ammonia, formaldehyde and heavy metals.

Aims
Case presentation of a nasal polyp with epithelial dysplasia in a worker exposed to nickel and copper salt dust.

Case report
A 27-year-old man complained of impaired nasal breathing and mild right-sided epistaxis. He was exposed to copper and nickel salt dust for 6 years. Clinical examination showed a polypoid lesion arising from the right middle turbinate. Histopathological examination of the excised lesion showed high-grade epithelial dysplasia. Duration of exposure and concentration of heavy metals in serum suggest the biological plausibility of exposure to these factors and development of epithelial dysplasia in the nasal mucosa.

Conclusion
Epithelial dysplasia may occasionally be noted in inflammatory nasal polyps, especially in workers exposed to heavy metals.
The composition of the perinatal intestinal microbiota in horse
Authors: Husso A , Jalanka J , Alipour MJ , Huhti P , Kareskoski M , Pessa-Morikawa T , Iivanainen A , Niku M 
Published: August 2019

AbstractThe establishment of the intestinal microbiota is critical for the digestive and immune systems. We studied the early development of the microbiota in horse, a hindgut fermenter, from birth until 7 days of age, by qPCR and 16S rRNA gene amplicon sequencing. To evaluate initial sources of foal microbiota, we characterized dam fecal, vaginal and oral microbiotas. We utilised an amplicon sequence variant (ASV) based pipeline to maximize resolution and reproducibility. Stringent ASV filtering based on prevalence and abundance in samples and controls purged reagent contaminants while preserving intestinal taxa. The newborn rectum contained small amounts of diverse bacterial DNA, with a profile closer to mare feces and vagina than mouth. 24 hours after birth, the intestine was colonized by Firmicutes and Proteobacteria, some foals dominated by a single genus. At day 7, the phylum-level composition resembled adult feces but genera were different. The mare vaginal microbiota contributed to 24 h and 7 day microbiotas. It contained few lactobacilli, withCorynebacterium,Porphyromonas,CampylobacterandHelcococcusas the most abundant genera. In the oral mucosa,Gemellawas extremely abundant. Our observations suggest that bacteria or bacterial components translocate to the equine fetus, but the intestinal microbiota changes rapidly after birth.
Migrant semipalmated sandpipers (Calidris pusilla) have over four decades steadily shifted towards safer stopover locations
Authors: Hope David D. , Lank David B. , Smith Paul A. , Paquet Julie , Ydenberg Ronald C. 
Published: August 2019

ABSTRACTPeregrine falcons (Falco peregrinus) have undergone a steady hemisphere-wide recovery since the ban on DDT in 1973, resulting in an ongoing increase in the level of danger posed for migrant birds, such as Arctic-breeding sandpipers. We anticipate that in response migrant semipalmated sandpipers (Calidris pusilla) have adjusted migratory behaviour, including a shift in stopover site usage towards locations offering greater safety from falcon predation.We assessed semipalmated sandpiper stopover usage within the Atlantic Canada Shorebird Survey dataset. Based on 3,030 surveys (totalling ∼32M birds) made during southward migration, 1974 - 2017, at 198 stopover locations, we assessed the spatial distribution of site usage in each year (with a ‘priority matching distribution’ index, PMD) in relation to the size (intertidal area) and safety (proportion of a site’s intertidal area further than 150m of the shoreline) of each location. The PMD index value is > 1 when usage is concentrated at dangerous locations, 1.0 when usage matches location size, and < 1 when usage is concentrated at safer locations.A large majority of migrants were found at the safest sites in all years, however our analysis of the PMD demonstrated that the fraction using safer sites increased over time. In 1974, 80% of birds were found at the safest 20% of the sites, while in 2017, this had increased to 97%. A sensitivity analysis shows that the shift was made specifically towards safer (and not just larger) sites. The shift as measured by a PMD index decline cannot be accounted for by possible biases inherent in the data set. We conclude that the data support the prediction that increasing predator danger has induced a shift by southbound migrant semipalmated sandpipers to safer sites.
Genomic history and ecology of the geographic spread of rice
Authors: Gutaker Rafal M. , Groen Simon C. , Bellis Emily S. , Choi Jae Y. , Pires Inês S. , Bocinsky R. Kyle , Slayton Emma R. , Wilkins Olivia , Castillo Cristina C. , Negrão Sónia , Oliveira M. Margarida , Fuller Dorian Q. , d’Alpoim Guedes Jade A. , Lasky Jesse R. , Purugganan Michael D. 
Published: August 2019

ABSTRACTRice (Oryza sativa) is one of the world’s most important food crops. We reconstruct the history of rice dispersal in Asia using whole-genome sequences of >1,400 landraces, coupled with geographic, environmental, archaeobotanical and paleoclimate data. We also identify extrinsic factors that impact genome diversity, with temperature a leading abiotic factor. Originating ∼9,000 years ago in the Yangtze Valley, rice diversified into temperate and tropical japonica during a global cooling event ∼4,200 years ago. Soon after, tropical rice reached Southeast Asia, where it rapidly diversified starting ∼2,500 yBP. The history of indica rice dispersal appears more complicated, moving into China ∼2,000 yBP. Reconstructing the dispersal history of rice and its climatic correlates may help identify genetic adaptation associated with the spread of a key domesticated species.One sentence summaryWe reconstructed the ancient dispersal of rice in Asia and identified extrinsic factors that impact its genomic diversity.
In uteroestrogenic endocrine disruption alters the stroma to increase extracellular matrix density and mammary gland stiffness
Authors: Wormsbaecher Clarissa , Hindman Andrea R. , Avendano Alex , Cortes Marcos , Bushman Andrew , Onua Lotanna , Kovalchin Claire E. , Murphy Alina R. , Helber Hannah L. , Shapiro Ali , Voytovitch Kyle , Kuang Xingyan , Song Jonathan W. , Burd Craig J. 
Published: August 2019

AbstractIn uteroendocrine disruption is linked to increased risk of breast cancer later in life. Despite numerous studies establishing this linkage, the long-term molecular changes that predispose mammary cells to carcinogenic transformation are unknown. Several lines of evidence indicate the stroma mediates endocrine disruption following early-life (orin utero)exposure. Herein, we utilized BPA as a model of estrogenic endocrine disruption to analyze the long-term consequences in the stroma. Using RNA-seq transcriptional profiling of adult primary fibroblasts isolated from female mice exposed to BPAin utero, we identified deregulated genes associated with the extracellular matrix. Specifically, multiple collagen genes had increased expression in exposed mice. In line with the transcriptional data, collagen deposition is increased in adult BPA-exposed mice. We further demonstratein vitrothat fibroblasts exposed to BPAin uteroremodel a collagen matrix, thereby decreasing permeability of the collagen matrix. These alterations to the mammary gland resulted in increased gland stiffness in the adult mice. Our data connects early life endocrine disruption to breast density. Interestingly, increased collagen deposition and gland stiffness were not observed in the developing glands of younger mice, suggesting risk factors for breast cancer continue to develop throughout life following these exposures. Finally, we assessed whetherin uteroexposure to two other endocrine disruptors, BPS and DES, also increase breast stiffness in adult mice. While DES increased breast stiffness, BPS did not, suggesting this BPA alternative may in fact pose less breast cancer risk than its predecessor. As breast stiffness, extracellular matrix density, and collagen deposition have been directly linked to breast cancer risk, these data mechanistically link endocrine disruptor exposures and molecular alterations to increased disease susceptibility in the gland.
A template-matching algorithm for laminar identification of cortical recording sites from evoked response potentials
Authors: Matteucci Giulio , Riggi Margherita , Zoccolan Davide 
Published: August 2019

AbstractIn recent years, the advent of the so-called silicon probes has made it possible to homogeneously sample spikes and local field potentials (LFPs) from a regular grid of cortical recording sites. In principle, this allows inferring the laminar location of the sites based on the spatiotemporal pattern of LFPs recorded along the probe, as in the well-known current source-density (CSD) analysis. This approach, however, has several limitations, since it relies on visual identification of landmark features (i.e., current sinks and sources) by human operators – features that can be absent from the CSD pattern if the probe does not span the whole cortical thickness, thus making manual labelling harder. Furthermore, as any manual annotation procedure, the typical CSD-based workflow for laminar identification of recording sites is affected by subjective judgment undermining the consistency and reproducibility of results. To overcome these limitations, we developed an alternative approach, based on finding the optimal match between the LFPs recorded along a probe in a given experiment and a template LFP profile that was computed using 18 recording sessions, in which the depth of the recording sites had been recovered through histology. We show that this method can achieve an accuracy of 79 µm in recovering the cortical depth of recording sites and a 76% accuracy in inferring their laminar location. As such, our approach provides an alternative to CSD that, being fully automated, is less prone to the idiosyncrasies of subjective judgment and works reliably also for recordings spanning a limited cortical stretch.New and noteworthyKnowing the depth and laminar location of the microelectrodes used to record neuronal activity from the cerebral cortex is crucial to properly interpret the recorded patterns of neuronal responses. Here we present an innovative approach that allows inferring such properties with high accuracy and in an automated way (i.e., without the need of visual inspection and manual annotation) from the evoked response potentials (ERPs) elicited by sensory (e.g., visual) stimuli.
Re-annotation of the Theileria parva genome refines 53% of the proteome and uncovers essential components of N-glycosylation, a conserved pathway in many organisms
Authors: Tretina Kyle , Pelle Roger , Orvis Joshua , Gotia Hanzel T. , Ifeonu Olukemi O. , Kumari Priti , Palmateer Nicholas C. , Iqbal Shaikh B.A. , Fry Lindsay , Nene Vishvanath M. , Daubenberger Claudia , Bishop Richard P. , Silva Joana C. 
Published: August 2019

AbstractBackgroundThe apicomplexan parasite Theileria parva causes a livestock disease called East coast fever (ECF), with millions of animals are at risk in sub-Saharan East and Southern Africa, the geographic distribution of T. parva. Over a million bovines die each year of ECF, with a tremendous economic burden to pastoralists in endemic countries. Comprehensive, accurate parasite genome annotation can facilitate the discovery of novel chemotherapeutic targets for disease treatment, as well as elucidate the biology of the parasite. However, genome annotation remains a significant challenge because of limitations in the quality and quantity of the data being used to inform the location and function of protein-coding genes and, when RNA data are used, the underlying biological complexity of the processes involved in gene expression. Here, we apply our recently published RNAseq dataset derived from the schizont life-cycle stage of T. parva to update structural and functional gene annotations across the entire nuclear genome.ResultsThe re-annotation effort lead to evidence-supported updates in over half of all protein-coding sequence (CDS) predictions, including exon changes, gene merges and gene splitting, an increase in average CDS length of approximately 50 base pairs, and the identification of 128 new genes. Among the new genes identified were those involved in N-glycosylation, a process previously thought not to exist in this organism and a potentially new chemotherapeutic target pathway for treating ECF. Alternatively-spliced genes were identified, and antisense and multi-gene family transcription were extensively characterized.ConclusionsThe process of re-annotation led to novel insights into the organization and expression profiles of protein-coding sequences in this parasite, and uncovered a minimal N-glycosylation pathway that changes our current understanding of the evolution of this post-translation modification in apicomplexan parasites.
Multigenerational exposure to elevated temperatures leads to a reduction in standard metabolic rate in the wild
Authors: Pilakouta Natalie , Killen Shaun S. , Kristjánsson Bjarni K. , Skúlason Skúli , Lindström Jan , Metcalfe Neil B. , Parsons Kevin J. 
Published: August 2019

AbstractIn light of global climate change, there is a pressing need to understand and predict the capacity of populations to respond to rising temperatures. Metabolic rate is a key trait that is likely to influence the ability to cope with climate change. Yet, empirical and theoretical work on metabolic rate responses to temperature changes has so far produced mixed results and conflicting predictions.Our study addresses this issue using a novel approach of comparing fish populations in geothermally warmed lakes and adjacent ambient-temperature lakes in Iceland. This unique ‘natural experiment’ provides repeated and independent examples of populations experiencing contrasting thermal environments for many generations over a small geographic scale, thereby avoiding the confounding factors associated with latitudinal or elevational comparisons. Using Icelandic sticklebacks from three warm and three cold habitats, we measured individual metabolic rates across a range of acclimation temperatures to obtain reaction norms for each population.We found a general pattern for a lower standard metabolic rate in sticklebacks from warm habitats when measured at a common temperature, as predicted by Krogh’s rule. Metabolic rate differences between warm- and cold-habitat sticklebacks were more pronounced at more extreme acclimation temperatures, suggesting the release of cryptic genetic variation upon exposure to novel conditions, which can reveal hidden evolutionary potential. We also found a stronger divergence in metabolic rate between thermal habitats in allopatry than sympatry, indicating that gene flow may constrain physiological adaptation when dispersal between warm and cold habitats is possible.In sum, our study suggests that fish may diverge toward a lower standard metabolic rate in a warming world, but this might depend on connectivity and gene flow between different thermal habitats.
BRAin INteractive Sequencing Analysis Tool (BRAIN-SAT); facilitating interactive transcriptome analyses (http://brainsat.eu/)
Authors: Dubbelaar M.L. , Brummer M.L. , Meijer M. , Eggen B.J.L. , Boddeke H.W.G.M. 
Published: August 2019

AbstractOver the last decade, a large number of glia transcriptome studies has been published. New technologies and platforms have been developed to allow access and interrogation of the published data. The increase in large transcriptomic data sets allows for innovative in silico analyses to address biological questions. Here we present BRAIN-SAT, the follow-up of our previous database GOAD, with several new features available on an interactive platform that enables access to recent, high quality bulk and single cell RNA-Seq data. The combination of several functions including gene searches, differential and quantitative expression analysis and a single cell expression analysis feature enables the exploration of published data sets at different levels. These different functionalities can be used for researchers and research companies in the neuroscience field to evaluate and visualize gene expression levels in a set of relevant publications. Here, we present a new platform with easy access to published gene expression studies for data exploration and gene of interest searches.
Multiple separate cases of pseudogenized meiosis genes Msh4 and Msh5 in Eurotiomycete fungi: associations with Zip3 sequence evolution and homothallism, but not Pch2 losses
Authors: Savelkoul Elizabeth , Toll Cynthia , Benassi Nathan , Logsdon John M. 
Published: August 2019

AbstractThe overall process of meiosis is conserved in many species, including some lineages that have lost various ancestrally present meiosis genes. The extent to which individual meiosis gene losses are independent from or dependent on one another is largely unknown. Various Eurotiomycete fungi were investigated as a case system of recent meiosis gene losses after BLAST and synteny comparisons found Msh4, Msh5, Pch2, and Zip3 to be either pseudogenized or undetected inAspergillus nidulansyet intact in congeners such asA. fumigatus. Flanking gene-targeted degenerate PCR primers applied to 9 additionalAspergillusspecies found (i) Msh4, Msh5, and Zip3 pseudogenized inA. rugulosus(sister taxon toA. nidulans) but intact in all other amplified sequences; and (ii) Pch2 not present at the syntenic locus in most of the 9 species. Topology tests suggested two independent Pch2 losses in genusAspergillus, neither directly coinciding with pseudogenization of the other three genes. TheA. nidulans-A. conjunctusclade Pch2 loss was not associated with significant Ka/Kschanges for Msh4, Msh5, or Zip3; this suggests against prior Pch2 loss directly altering sequence evolution constraints on these three genes. By contrast, Zip3 Ka/Kstended to be elevated in several other Eurotiomycete fungi with independently pseudogenized Msh4 and Msh5 (Talaromyces stipitatus,Eurotium herbariorum). The coinciding Ka/Kselevation and/or clear pseudogenization of Zip3 in taxa with pseudogenized Msh4 and Msh5 is consistent with some degree of molecular coevolution. Possible molecular, environmental, and life history variables (e.g., homothallism) that may be associated with these numerous independent meiosis gene losses (Msh4: 3, Msh5: 3, Zip3: ≥ 1, Pch2: 4) are discussed.
The meninges enhance leukemia survival in cerebral spinal fluid
Authors: Basile Patrick , Jonart Leslie M. , Ebadi Maryam , Johnson Kimberly , Kerfeld Morgan , Gordon Peter M. 
Published: August 2019

AbstractCentral nervous system (CNS) relapse is a common cause of treatment failure in patients with acute lymphoblastic leukemia (ALL) despite current CNS-directed therapies that are also associated with significant short and long-term toxicities. Herein, we showed that leukemia cells exhibit decreased proliferation, elevated reactive oxygen species (ROS), and increased cell death in CSF both in vitro and in vivo. However, interactions between leukemia and meningeal cells mitigated these adverse effects. This work expands our understanding of the pathophysiology of CNS leukemia and suggests novel therapeutic approaches for more effectively targeting leukemia cells in the CNS.
Single-cell RNA Profiling Identifies Diverse Cellular Responses to EWSR1-FLI1 Down-regulation in Ewing Sarcoma
Authors: Khoogar Roxane , Lawlor Elizabeth R. , Chen Yidong , Ignatius Myron , Kitagawa Katsumi , Huang Tim H.-M. , Houghton Peter J. 
Published: August 2019

ABSTRACTSingle-cell analyses provide insight into time dependent behaviors in response to dynamic changes of oncogene expression. We developed an unbiased approach to study gene expression variation using a model of cellular dormancy induced via EWSR1-FLI1 down-regulation in Ewing sarcoma (EWS) cells. We propose that variation in the expression of EWSR1-FLI1 over time determines cellular responses. Cell state and functions were assigned using random forest feature selection in combination with machine learning. Notably, three distinct expression profiles were uncovered contributing to Ewing sarcoma cell heterogeneity. Our predictive model identified ∼1% cells in a dormant-like state and ∼2-4% with higher stem-like and neural stem-like features in an exponentially proliferating EWS cell line and EWS xenografts. Following oncogene knockdown, cells re-entering the proliferative cycle have greater stem-like properties, whereas for those remaining quiescent, FAM134B-dependent dormancy provides a survival mechanism. We also show cell cycle heterogeneity related to EWSR1-FLI1 expression as an independent feature driving cancer heterogeneity, and drug resistance.SIGNIFICANCEWe show that time-dependent changes induced by suppression of oncogenic EWSR1-FLI1 induces dormancy, with different subpopulation dynamics, including stem-like characteristics and prolonged dormancy. Cells with these characteristics are identified in exponentially growing cell populations and confer drug resistance, and could potentially contribute to metastasis or late recurrence in patients.