bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why Westerners Are Dissatisfied: A Cross-Sectional Study Identifying State-Level Factors Associated with Variation in Private Health Insurance Satisfaction
Authors: McLeod Megan , Berinstein Jeffrey A. , Steiner Calen A. , Cushing Kelly , Cohen Mekelburg Shirley A. , Higgins Peter D.R. 
Published: August 2019

AbstractImportanceLarge regional variations in consumer satisfaction with private health insurance plans have been observed, but the factors driving this variation are unknown.ObjectiveTo identify explanatory state-level and insurance family-level predictors of satsifaction with private health insurance.DesignCross-sectional study examining regional and state variations in consumer health insurance plan satisfaction using National Committee for Quality Assurance data from 2015 to 2018, state-level health data and parent insurance family.SettingUS PopulationParticipantsPrivately insured individuals.ExposureOne of 2176 private health insurance plans.Main OutcomeConsumer satisfaction with the health insurance plan on a 0-5 scale.RESULTSConsumer satisfaction with health insurance was consistently lowest in the West (p<0.0001). Lower private health insurance plan satisfaction was associated with the percentage of the population without a place of usual medical care, the percentage of the state population that is Hispanic, and the percentage of the population reporting any mental illness. Factors associated with increasing insurance satisfaction included higher healthcare spending per capita, a higher number of for-profit beds per capita, and an increased cancer death rate. Increased consumer satisfaction was associated with the Kaiser and Anthem insurance plan families.Conclusions and RelevanceState and insurer family factors are predictive of private health insurance plan satisfaction. Potentially modifiable factors include access to primary care, healthcare spending per capita, and numbers of for-profit hospital beds. This information will help consumers hold insurance providers accountable to provide higher quality and more desirable coverage and provide actionable items to improve health insurance satisfaction.
Factors associated with opioid cessation: a machine learning approach
Authors: Cox Jiayi W. , Sherva Richard M. , Lunetta Kathryn L. , Saitz Richard , Kon Mark , Kranzler Henry R. , Gelernter Joel E. , Farrer Lindsay A. 
Published: August 2019

AbstractBackground and AimsPeople with opioid use disorder (OUD) can stop using opioids on their own, with help from groups and with treatment, but there is limited research on the factors that influence opioid cessation.MethodsWe employed multiple machine learning prediction algorithms (LASSO, random forest, deep neural network, and support vector machine) to assess factors associated with ceasing opioid use in a sample comprised of African Americans (AAs) and European Americans (EAs) who met DSM-5 criteria for mild to severe OUD. Values for several thousand demographic, alcohol and other drug use, general health, and behavioral variables, as well as diagnoses for other psychiatric disorders, were obtained for each participant from a detailed semi-structured interview.ResultsSupport vector machine models performed marginally better on average than those derived using other machine learning methods with maximum prediction accuracies of 75.4% in AAs and 79.4% in EAs. Subsequent stepwise regression analyses that considered the 83 most highly ranked variables across all methods and models identified less recent cocaine use (p<5×10−8), a shorter duration of opioid use (p<5×10−6), and older age (p<5×10−9) as the strongest independent predictors of opioid cessation. Factors related to drug use comprised about half of the significant independent predictors, with other predictors related to non-drug use behaviors, psychiatric disorders, overall health, and demographics.ConclusionsThese proof-of-concept findings provide information that can help develop strategies for improving OUD management and the methods we applied provide a framework for personalizing OUD treatment.
Extreme genome selection towards complete antimicrobial resistance in a nosocomial strain ofStenotrophomonas maltophiliacomplex
Authors: Kumar Sanjeet , Bansal Kanika , Patil Prashant P. , Kaur Amandeep , Kaur Satinder , Gautam Vikas , Patil Prabhu B. 
Published: August 2019

ABSTRACTWe report first complete genome sequence and analysis of an extreme drug resistance (XDR) nosocomialStenotrophomonas maltophiliathat is resistant to the mainstream drugs i.e. trimethoprim/sulfamethoxazole (TMP/SXT) and levofloxacin. Taxonogenomic analysis revealed it to be a novel genomospecies of theStenotrophomonas maltophiliacomplex (Smc). Comprehensive genomic investigation revealed fourteen dynamic regions (DRs) exclusive to SM866, consisting of diverse antibiotic resistance genes, efflux pumps, heavy metal resistance, various transcriptional regulators etc. Further, resistome analysis of Smc clearly depicted SM866 to be an enriched strain, having diversified resistome consisting ofsul1andsul2genes. Interestingly, SM866 does not have any plasmid but it harbors two diverse super-integrons of chromosomal origin. Apart from genes for sulfonamide resistance (sul1andsul2), both of these integrons harbor an array of antibiotic resistance genes linked to ISCR (IS91-like elements common regions) elements. These integrons also harbor genes encoding resistance to commonly used disinfectants like quaternary ammonium compounds and heavy metals like mercury. Hence, isolation of a novel strain belonging to a novel sequence type (ST) and genomospecies with diverse array of resistance from a tertiary care unit of India indicates extent and nature of selection pressure driving XDRs in hospital settings. There is an urgent need to employ complete genome based investigation using emerging technologies for tracking emergence of XDR at the global level and designing strategies of sanitization and antibiotic regime.Impact StatementThe hospital settings in India have one of the highest usage of antimicrobials and heavy patient load. Our finding of a novel clinical isolate ofS. maltophiliacomplex with two super-integrons harbouring array of antibiotic resistance genes along with antimicrobials resistance genes indicates the extent and the nature of selection pressures in action. Further, the presence of ISCR type of transposable elements on both integrons not only indicates its propensity to transfer resistome but also their chromosomal origin suggests possibilities for further genomic/phenotypic complexities. Such complex cassettes and strain are potential threat to global health care. Hence, there is an urgent need to employ cost-effective long read technologies to keep vigilance on novel and extreme antimicrobial resistance pathogens in populous countries. There is also need for surveillance for usage of antimicrobials for hygiene and linked/rapid co-evolution of extreme drug resistance in nosocomial pathogens. Our finding of the chromosomal encoding XDR will shed a light on the need of hour to understand the evolution of an opportunistic nosocomial pathogen belonging toS. maltophilia.RepositoriesComplete genome sequence ofStenotrophomonas maltophiliaSM866: CP031058
Low FoxO expression inDrosophilasomatosensory neurons protects dendrite growth under nutrient restriction
Authors: Poe Amy R. , Xu Yineng , Zhang Christine , Li Kailyn , Labib David , Han Chun 
Published: August 2019

ABSTRACTDuring prolonged nutrient restriction, developing animals redistribute vital nutrients to favor brain growth at the expense of other organs. InDrosophila, such brain sparing relies on a glia-derived growth factor to sustain proliferation of neural stem cells. However, whether other aspects of neural development are also spared under nutrient restriction is unknown. Here we show that dynamically growing somatosensory neurons in theDrosophilaperipheral nervous system exhibit organ sparing at the level of arbor growth: Under nutrient stress, sensory dendrites preferentially grow as compared to neighboring non-neural tissues, resulting in dendrite overgrowth. Underlying this neuronal nutrient-insensitivity is the lower expression of the stress sensor FoxO in neurons. Consequently, nutrient restriction suppresses Tor signaling less and does not induce autophagy in neurons. Preferential dendrite growth is functional desirable because it results in heightened animal responses to sensory stimuli, indicative of a potential survival advantage under environmental challenges.
Gene copy number is associated with phytochemistry inCannabis sativa
Authors: Vergara Daniela , Huscher Ezra L. , Keepers Kyle G. , Givens Robert M. , Cizek Christian G. , Torres Anthony , Gaudino Reggie , Kane Nolan C. 
Published: August 2019

AbstractGene copy number variation is known to be important in nearly every species where it has been examined. Alterations in gene copy number may provide a fast way of acquiring diversity, allowing rapid adaptation under strong selective pressures, and may also be a key component of standing genetic variation within species.Cannabis sativaplants produce a distinguishing set of secondary metabolites, the cannabinoids, many having medicinal utility. Two major cannabinoids -- THCA and CBDA -- are products of a three-step biochemical pathway. Using genomic data for 69Cannabiscultivars from diverse lineages within the species, we found that genes encoding the synthases in this pathway vary in copy number, and that the cannabinoid paralogs may be differentially expressed. We also found that copy number partially explains variation in cannabinoid content levels amongCannabisplants.
Berberine delays onset of collagen induced arthritis through T cell suppression
Authors: Vita Alexandra A. , Aljobaily Hend , Lyons David O. , Pullen Nicholas A. 
Published: August 2019

ABSTRACTPrevious evidence suggests that berberine (BBR), a clinically relevant plant-derived alkaloid, alleviates symptoms of clinically apparent collagen induced arthritis (CIA), and may have a prophylactic role fromin vitrostudies. Thus, we used a CIA model to determine if BBR merits further exploration as a prophylactic treatment for rheumatoid arthritis. Mice were treated with either 1 mg/kg/day of BBR or a vehicle (PBS) control via IP injections from day 0 to day 28, were left untreated (CIA control), or were in a non-arthritic control group. Incidence of arthritis in BBR mice was 40%, compared to 90% in the CIA and 80% in the PBS controls. Populations of B cells and T cells from the spleens and draining lymph nodes were examined from mice across treatment groups on day 14 and from the remaining mice on day 28 when arthritic signs and symptoms were expected to be apparent. BBR-treated mice had significantly reduced populations of CD4+T cells, CXCR5+Tfhcells, and an increased proportion of Tregat both day 14 and day 28 endpoints, as well as decreased CD28+and CD154+CD4+T cells at day 14. BBR-treated mice also experienced a significant reduction of CD19+B cells in LNs at day 28. Additionally, BBR treatment resulted in significantly lower anti-collagen type II-specific (anti-CII) IgG2a and anti-CII total IgG serum concentrations. These results indicate a potential role for BBR as a prophylactic supplement, and that its effect may be mediated through T cell suppression, which indirectly affects B cell activity.
Measuring Perceptual Distance of Organismal Color Pattern using the Features of Deep Neural Networks
Authors: Wham Drew C. , Ezray Briana , Hines Heather M. 
Published: August 2019

ABSTRACTA wide range of research relies upon the accurate and repeatable measurement of the degree to which organisms resemble one another. Here, we present an unsupervised workflow for analyzing the relationships between organismal color patterns. This workflow utilizes several recent advancements in deep learning based computer vision techniques to calculate perceptual distance. We validate this approach using previously published datasets surrounding diverse applications of color pattern analysis including mimicry, population differentiation, heritability, and development. We demonstrate that our approach is able to reproduce the biologically relevant color pattern relationships originally reported in these studies. Importantly, these results are achieved without any task-specific training. In many cases, we were able to reproduce findings directly from original photographs or plates with minimum standardization, avoiding the need for intermediate representations such as a cartoonized images or trait matrices. We then present two artificial datasets designed to highlight how this approach handles aspects of color patterns, such as changes in pattern location and the perception of color contrast. These results suggest that this approach will generalize well to support the study of a wide range of biological processes in a diverse set of taxa while also accommodating a variety of data formats, preprocessing techniques, and study designs.
Shared neural codes for eye-gaze and valence
Authors: Pryluk Raviv , Shohat Yosef , Morozov Anna , Friedman Dafna , Taub Aryeh H. , Paz Rony 
Published: August 2019

AbstractThe eye-gaze of others is a prominent social cue in primates and crucial for communication1-7, and atypical processing occurs in several conditions as autism-spectrum-disorder (ASD)1,9-14. The neural mechanisms that underlie eye-gaze remain vague, and it is still debated if these computations developed in dedicated neural circuits or shared with non-social elements. In many species, eye-gaze signals a threat and elicits anxiety, yet can also serve as a predictor for the outcome of the encounter: negative or positive2,4,8. Here, we hypothesized and find that neural codes overlap between eye-gaze and valence. Monkeys participated in a modified version of the human-intruder-test8,15 that includes direct and averted eye-gaze and interleaved with blocks of aversive and appetitive conditioning16,17. We find that single-neurons in the amygdala encode gaze18, whereas neurons in the anterior-cingulate-cortex encode the social context19,20 but not gaze. We identify a shared amygdala circuitry where neural responses to averted and direct gaze parallel the responses to appetitive and aversive value, correspondingly. Importantly, we distinguish two shared coding mechanisms: a shared-intensity scheme that is used for gaze and the unconditioned-stimulus, and a shared-activity scheme that is used for gaze and the conditioned-stimulus. The shared-intensity points to overlap in circuitry, whereas the shared-activity requires also correlated activity. Our results demonstrate that eye-gaze is coded as a signal of valence, yet also as the expected value of the interaction. The findings may suggest new insights into the mechanisms that underlie the malfunction of eye-gaze in ASD and the comorbidity with impaired social skills and anxiety.
A CRISPR-based method for measuring the essentiality of a gene
Authors: You Yan , Ramachandra Sharmila G. , Jin Tian 
Published: August 2019

AbstractThe CRISPR/Cas9 system is a powerful method of editing genes by randomly introducing errors into the target sites. Here, we describe a CRISPR-based test for gene essentiality (CRISPR-E test) that allows the identification of essential genes. Specifically, we use sgRNA-mediated CRISPR/Cas9 to target the open reading frame of a gene in the genome and analyze the in-frame (3n) and frameshift (3n+1 and 3n+2) mutations on the target region of the gene in surviving cells. If the gene is non-essential, the cells would carry both in-frame (3n) and frameshift (3n+1 and 3n+2) mutations. In contrast, the cells would carry only in-frame (3n) mutations if the targeted gene is essential, and this selective elimination of frameshift (3n+1 and 3n+2) mutations of the gene indicate its essentiality. As a proof of concept, we have used this CRISPR-E test in the model organism Dictyostelium discoideum to demonstrate that Dync1li1 is an essential gene while KIF1A and fAR1 are not. We further propose a simple method for quantifying the essentiality of a gene using the CRISPR-E test.One Sentence SummaryCRISPR-E measures a gene’s essentiality
Motor-mediated clustering at microtubule plus ends facilitates protein transfer to a bio-mimetic cortex
Authors: Taberner Núria , Dogterom Marileen 
Published: August 2019

AbstractPolarized protein distributions at the cortex play an important role in the spatial organization of cells. In S. pombe, growing microtubule ends contribute to the establishment and maintenance of such distributions by delivering specific factors to membrane receptors at the poles of the cell. It is however unclear how microtubule plus-end tracking of proteins favours protein accumulation at the cell cortex compared to proteins arriving directly from the cytoplasm. To address this question, we developed an in vitro assay, where microtubules were made to deliver His-tagged plus-end tracking proteins to functionalized microchamber walls. We found that motor-mediated protein clusters formed at microtubule ends were able to transfer to the walls, but non-clustered proteins were not. We further show that this transfer mechanism leads to preferential cluster accumulation at chamber poles, when microtubules are confined to elongated microfabricated chambers with sizes and shapes similar to S. pombe.
ARAD9-dependent cell cycle arrest in response to unresolved recombination intermediates inSaccharomyces cerevisiae
Authors: Kaur Hardeep , Krishnaprasad GN , Lichten Michael 
Published: August 2019

AbstractInSaccharomyces cerevisiae, the conserved Sgs1-Top3-Rmi1 helicase-decatenase regulates homologous recombination by limiting accumulation of recombination intermediates that are precursors of crossovers.In vitrostudies have suggested that the dissolution of double-Holliday junction joint molecules by Sgs1-driven convergent junction migration and Top3-Rmi1 mediated strand decatenation could be responsible for this. To ask if dissolution occursin vivo, we conditionally depleted Sgs1 and/or Rmi1 during return to growth, a procedure where recombination intermediates formed during meiosis are resolved when cells resume the mitotic cell cycle. Sgs1 depletion during return to growth delayed joint molecule resolution, but ultimately most were resolved and cells divided normally. In contrast, Rmi1 depletion resulted in delayed and incomplete joint molecule resolution, and most cells did not divide.rad9Δmutation restored cell division in Rmi1-depleted cells, indicating that the DNA damage checkpoint caused this cell cycle arrest. Restored cell division inrad9Δ, Rmi1-depleted cells frequently produced anucleate cells, consistent with the suggestion that persistent recombination intermediates prevented chromosome segregation. Our findings indicate that Sgs1-Top3-Rmi1 actsin vivo, as it doesin vitro, to promote recombination intermediate resolution by dissolution. They also indicate that, in the absence of Top3-Rmi1 activity, unresolved recombination intermediates persist and activate the DNA damage response, which is usually thought to be activated by much earlier DNA damage-associated lesions.
Detecting Inversions with PCA in the Presence of Population Structure
Authors: Nowling Ronald J. , Manke Krystal R. , Emrich Scott J. 
Published: August 2019

ABSTRACTChromosomal inversions are associated with reproductive isolation and adaptation in insects such as Drosophila melanogaster and the malaria vectors Anopheles gambiae and Anopheles coluzzii. While methods based on read alignment have been useful in humans for detecting inversions, these methods are less successful in insects due to long repeated sequences at the breakpoints. Alternatively, inversions can be detected using principal component analysis (PCA) of single nucleotide polymorphisms (SNPs). We apply PCA-based inversion detection to a simulated data set and real data from multiple insect species, which vary in complexity from a single inversion in samples drawn from a single population to analyzing multiple overlapping inversions occurring in closely-related species, samples of which that were generated from multiple geographic locations. We show empirically that proper analysis of these data can be challenging when multiple inversions or populations are present, and that our alternative framework is more robust in these more difficult scenarios.
Bound-state diffusion due to binding to flexible polymers in a selective biofilter
Authors: Maguire L. , Betterton M. D. , Hough L. E. 
Published: August 2019

ABSTRACTSelective biofilters are used by cells to control the transport of proteins, nucleic acids, and other macromolecules. Biological filters demonstrate both high specificity and rapid motion or high flux of proteins. In contrast, high flux comes at the expense of selectivity in many synthetic filters. Binding can lead to selective transport in systems in which the bound particle can diffuse, but the mechanisms that lead to bound diffusion remain unclear. Previous theory has proposed a molecular mechanism of bound-state mobility based only on transient binding to flexible polymers. However, this mechanism has not been directly tested in experiments. We demonstrate that bound mobility via tethered diffusion can be engineered into a synthetic gel using protein fragments derived from the nuclear pore complex. The resulting bound-state diffusion is quantitatively consistent with theory. Our results suggest that synthetic biological filters can be designed to to take advantage of tethered diffusion to give rapid, selective transport.SIGNIFICANCEBiological filters control the passage of proteins and other macromolecules between compartments of living systems. Determination of molecular mechanisms giving selective transport would enable the design of both selective filters and particles designed to penetrate biological barriers for drug delivery. One such mechanism arises from transient binding to dynamic polymer tethers. We designed a biomaterial which supports this type of tethered diffusion, demonstrating the potential to engineer bio-inspired filters.
Cellular heterogeneity and lineage restriction during mouse digit tip regeneration at single cell resolution
Authors: Johnson Gemma L. , Masias Erick J. , Lehoczky Jessica A. 
Published: August 2019

ABSTRACTInnate regeneration following digit tip amputation is one of the few examples of epimorphic regeneration in mammals. Digit tip regeneration is mediated by the blastema, the same structure invoked during limb regeneration in some lower vertebrates. By genetic lineage analyses in mice, the digit tip blastema has been defined as a population of heterogeneous, lineage restricted progenitor cells. These previous studies, however, do not comprehensively evaluate blastema heterogeneity or address lineage restriction of closely related cell types. In this report we present single cell RNA sequencing of over 38,000 cells from mouse digit tip blastemas and unamputated control digit tips and generate an atlas of the cell types participating in digit tip regeneration. We define the differentiation trajectories of vascular, monocytic, and fibroblastic lineages over regeneration, and while our data confirm broad lineage restriction of progenitors, our analysis reveals an early blastema fibroblast population expressing a novel regeneration-specific gene,Mest.