bluuebunny/crossref_metadata_2025 huggingface dataset:
The Problem With Mechanistic Risk of Bias Assessments in Evidence Synthesis of Observational Studies and a Practical Alternative: Assessing the Impact of Specific Sources of Potential Bias
Authors: Savitz David A , Wellenius Gregory A , Trikalinos Thomas A
Published: May 2019

The trustworthiness of individual studies is routinely characterized in systemic reviews by evaluating risk of bias, often by mechanistically applying standardized algorithms. However, such instruments prioritize the repeatability of the process over a more thoughtful and informative but necessarily somewhat more subjective approach. In mechanistic risk of bias assessments, the focus is on determining whether specific biases are present, but these assessments do not provide insights into the direction, magnitude, and relative importance of individual biases. In such assessments, all potential biases are naively treated as equally important threats to validity and equally important across all research topics, potentially leading to inappropriate conclusions about the overall strength of the available evidence. Instead, risk of bias assessments be should focused on identifying a few of the most likely influential sources of bias, based on methodologic and subject matter expertise, classifying each specific study on the basis of on how effectively it has addressed each potential bias, and determining whether results differ across studies in relation to susceptibility to each hypothesized source of bias. This approach provides insight into the potential impact of each specific bias, identifies a subset of studies likely to best approximate the causal effect, and suggests design features needed to improve future research.
SureTypeSC—a Random Forest and Gaussian mixture predictor of high confidence genotypes in single-cell data
Authors: Vogel Ivan , Blanshard Robert C , Hoffmann Eva R
Published: May 2019

Motivation

Accurate genotyping of DNA from a single cell is required for applications such as de novo mutation detection, linkage analysis and lineage tracing. However, achieving high precision genotyping in the single-cell environment is challenging due to the errors caused by whole-genome amplification. Two factors make genotyping from single cells using single nucleotide polymorphism (SNP) arrays challenging. The lack of a comprehensive single-cell dataset with a reference genotype and the absence of genotyping tools specifically designed to detect noise from the whole-genome amplification step. Algorithms designed for bulk DNA genotyping cause significant data loss when used for single-cell applications.

Results

In this study, we have created a resource of 28.7 million SNPs, typed at high confidence from whole-genome amplified DNA from single cells using the Illumina SNP bead array technology. The resource is generated from 104 single cells from two cell lines that are available from the Coriell repository. We used mother–father–proband (trio) information from multiple technical replicates of bulk DNA to establish a high quality reference genotype for the two cell lines on the SNP array. This enabled us to develop SureTypeSC—a two-stage machine learning algorithm that filters a substantial part of the noise, thereby retaining the majority of the high quality SNPs. SureTypeSC also provides a simple statistical output to show the confidence of a particular single-cell genotype using Bayesian statistics.

Availability and implementation

The implementation of SureTypeSC in Python and sample data are available in the GitHub repository: https://github.com/puko818/SureTypeSC

Supplementary information

Supplementary data are available at Bioinformatics online.
Country Is Yarning to Me: Worldview, Health and Well-Being Amongst Australian First Nations People
Authors: Terare Mareese , Rawsthorne Margot
Published: May 2019

Health inequalities experienced by Australian First Nations People are amongst the most marked in the world, with First Nations People dying some ten years earlier than non-Indigenous Australians. The failure of existing responses to health inequalities suggests new knowledges and questions that need to be explored. It is likely that these new knowledges sit outside of western research or practice paradigms. Through the Indigenous practice of yarning, the importance of worldview and Country emerged as an under-acknowledged social determinant of Australian First Nations People well-being. Yarning is a process of storytelling that involves both sound and silence. It requires embodied deep listening through which stories emerge that create new knowledge and understanding. We anchor our learning by re-telling John’s creation story, a story of healing through discovering his Aboriginal Worldview through reconnecting to Country. Country for First Nations People is more than a physical place; it is a place of belonging and a way of believing. We argue for the recognition of trauma, recognition of diversity and the use of yarning in social work practice. We conclude that reconnecting to Aboriginal Worldview provides hopeful insights into the well-being of Australia’s First Nations People and the social determinants of health.
Stability-Indicating Chromatographic Methods for the Investigation of Ritodrine Hydrochloride Stability and Characterization of the Oxidative Degradation Product
Authors: Rashed Noha Salem , Abdallah Ola Mostafa , El-Olemy Ahmed , Eldin Asmaa Ibrahim Hosam
Published: May 2019

Two simple and sensitive chromatographic methods were developed and validated for quantitative determination of ritodrine hydrochloride in presence of its oxidative degradation product. The first method depends on densitomeric determination of thin-layer chromatograms of the intact drug in presence of its oxidative degradate. Excellent separation was achieved at 220 nm using a mobile phase of dichloromethane–methanol–glacial acetic acid (15 : 5 : 0.25, v/v/v). The second was an HPLC method, in which efficient separation was carried out on C18 column (150 × 4.6 × 5 μm) using a mobile phase consisting of water: acetonitrile (70,30, v/v) at a flow rate of 1 mL min−1 and UV detection at 220 nm. Beer’s law was obeyed in the range of 0.025–0.3 μg/spot and 5–40 μg mL−1 of the intact drug using the two methods, respectively. The proposed methods were validated according to International Conference on Harmonization guidelines and successfully applied for the determination of ritodrine hydrochloride in bulk powder, laboratory prepared mixtures and pharmaceutical dosage form with good accuracy and precision. The results obtained were compared with those of the reported method and were found to be in good agreement.
Risk of dementia in stroke-free patients diagnosed with atrial fibrillation: data from a population-based cohort
Authors: Kim Dongmin , Yang Pil-Sung , Yu Hee Tae , Kim Tae-Hoon , Jang Eunsun , Sung Jung-Hoon , Pak Hui-Nam , Lee Myung-Yong , Lee Moon-Hyoung , Lip Gregory Y H , Joung Boyoung
Published: May 2019

Aims

Atrial fibrillation (AF) is generally regarded as a risk factor for dementia, though longitudinal studies assessing the association between AF and dementia have shown inconsistent results. This study aimed to determine the effect of AF on the risk of developing dementia using a longitudinal, community-based, and stroke-free elderly cohort.

Methods and results

The association of incident AF with the development of incident dementia was assessed from 2005 to 2012 in 262 611 dementia- and stroke-free participants aged ≥60 years in the Korea National Health Insurance Service-Senior cohort. Incident AF was observed in 10 435 participants over an observational period of 1 629 903 person-years (0.64%/year). During the observational period, the incidence of dementia was 4.1 and 2.7 per 100 person-years in the incident AF and propensity score-matched AF-free groups, respectively. After adjustment, the risk of dementia was significantly increased by incident AF with a hazard ratio (HR) of 1.52 [95% confidence interval (CI) 1.43–1.63], even after censoring for stroke (1.27, 95% CI 1.18–1.37). Incident AF increased the risk of both Alzheimer (HR 1.31, 95% CI 1.20–1.43) and vascular dementia (HR 2.11, 95% CI 1.85–2.41). Among patients with incident AF, oral anticoagulant use was associated with a preventive effect on dementia development (HR 0.61, 95% CI 0.54–0.68), and an increasing CHA2DS2-VASc score was associated with a higher risk of dementia.

Conclusion

Incident AF was associated with an increased risk of dementia, independent of clinical stroke in an elderly population. Oral anticoagulant use was linked with a decreased incidence of dementia.
Knowledge, Skills, Craft? The Skilled Worker in West German Industry and the Resilience of Vocational Training, 1970–2000
Authors: Raphael Lutz
Published: May 2019

The spread of computer technology in West German industry during the 1980s and 1990s dramatically changed the demand for skilled and unskilled work in manufacturing. As a result the knowledge used in production was redefined and reformers pushed for radical reform in vocational and general education. In these decades a corporate agreement across trade unions, associations of employers and state bureaucracy brought about a series of adaptive reforms of existing apprenticeships and the creation of new apprenticeships in new branches. This survival of the dual system is analysed as part of the strategies of modernizing West German manufacturing industries. Both employers and trade unions defended the central role of skilled workers in the new system of flexible quality production that developed during this period of rapid technological change. Data from the Socio-Economic Panel and from other sources enable analysis of the social effects of this economically successful strategy. They show the large-scale use of skilled workers in industrial production and their opportunities for upward mobility and additional qualifications. At the same time unskilled workers, and unskilled migrant workers in particular, experienced greater risks of unemployment and increased job uncertainty.
The Second Act: Seeking Best Practices for Encore Worker Management
Authors: Boyle Pam A
Published: May 2019

Background and Objectives

The Baby Boomers are the largest generation in history, and as they reach the traditional retirement age of 65, many leave the workforce and seek encore jobs. This exodus of Boomers creates a knowledge gap that the Gen X and Millennial generations lack the numbers and often the experience to fill. As the knowledge gap increases, managers can recruit and hire encore workers to fill the gap and retain human capital. This article answers the question: What processes can managers implement to close knowledge gaps by hiring or retaining Boomers seeking encore jobs?

Research Design and Methods

This article examined the factors for filling knowledge gaps with encore workers and the necessary processes for hiring or retaining encore workers to attain organizational goals. A systematic review of 32 published articles and four dissertations was conducted using Super’s amended career development theory. A thematic analysis approach was used to examine the evidence.

Results

The findings led to the development of best practices to guide managers who want to hire encore workers to close the knowledge gap, and increase organizational knowledge capital.

Discussion and Implications

Baby Boomers are responsible for finding and sustaining encore worker positions, but managers can support Boomers through best practices including skills assessments, revised HR policies, reverse-mentoring programs, and training opportunities for managers and encore workers.
Impaired mitochondrial maturation of sulfite oxidase in a patient with severe sulfite oxidase deficiency
Authors: Bender Daniel , Kaczmarek Alexander Tobias , Santamaria-Araujo Jose Angel , Stueve Burkard , Waltz Stephan , Bartsch Deniz , Kurian Leo , Cirak Sebahattin , Schwarz Guenter
Published: May 2019

Sulfite oxidase (SO) is encoded by the nuclear SUOX gene and catalyzes the final step in cysteine catabolism thereby oxidizing sulfite to sulfate. Oxidation of sulfite is dependent on two cofactors within SO, a heme and the molybdenum cofactor (Moco), the latter forming the catalytic site of sulfite oxidation. SO localizes to the intermembrane space of mitochondria where both—pre-SO processing and cofactor insertion—are essential steps during SO maturation. Isolated SO deficiency (iSOD) is a rare inborn error of metabolism caused by mutations in the SUOX gene that lead to non-functional SO. ISOD is characterized by rapidly progressive neurodegeneration and death in early infancy. We diagnosed an iSOD patient with homozygous mutation of SUOX at c.1084G>A replacing Gly362 to serine. To understand the mechanism of disease, we expressed patient-derived G362S SO in Escherichia coli and surprisingly found full catalytic activity, while in patient fibroblasts no SO activity was detected, suggesting differences between bacterial and human expression. Moco reconstitution of apo-G362S SO was found to be approximately 90-fold reduced in comparison to apo-WT SO in vitro. In line, levels of SO-bound Moco in cells overexpressing G362S SO were significantly reduced compared to cells expressing WT SO providing evidence for compromised maturation of G362S SO in cellulo. Addition of molybdate to culture medium partially rescued impaired Moco binding of G362S SO and restored SO activity in patient fibroblasts. Thus, this study demonstrates the importance of the orchestrated maturation of SO and provides a first case of Moco-responsive iSOD.
PTEN modulates gene transcription by redistributing genome-wide RNA polymerase II occupancy
Authors: Abbas Ata , Padmanabhan Roshan , Romigh Todd , Eng Charis
Published: May 2019

Control of gene expression is one of the most complex yet continuous physiological processes impacting cellular homeostasis. RNA polymerase II (Pol II) transcription is tightly regulated at promoter-proximal regions by intricate dynamic processes including Pol II pausing, release into elongation and premature termination. Pol II pausing is a phenomenon where Pol II complex pauses within 30–60 nucleotides after initiating the transcription. Negative elongation factor (NELF) and DRB sensitivity inducing factor (DSIF) contribute in the establishment of Pol II pausing, and positive transcription elongation factor b releases (P-TEFb) paused complex after phosphorylating DSIF that leads to dissociation of NELF. Pol II pausing is observed in most expressed genes across the metazoan. The precise role of Pol II pausing is not well understood; however, it’s required for integration of signals for gene regulation. In the present study, we investigated the role of phosphatase and tensin homolog (PTEN) in genome-wide transcriptional regulation using PTEN overexpression and PTEN knock-down models. Here we identify that PTEN alters the expression of hundreds of genes, and its restoration establishes genome-wide Pol II promoter-proximal pausing in PTEN null cells. Furthermore, PTEN re-distributes Pol II occupancy across the genome and possibly impacts Pol II pause duration, release and elongation rate in order to enable precise gene regulation at the genome-wide scale. Our observations demonstrate an imperative role of PTEN in global transcriptional regulation that will provide a new direction to understand PTEN-associated pathologies and its management.
Conversations on the Frontier: Finding the Dialogic in Nineteenth-century Anthropological Archives
Authors: Gibson Jason , Gardner Helen
Published: May 2019

While anthropological archives tend to be named after the collector of the material, they are often the product of conversations and long-term engagements with informants. Focusing on the concept of the dialogic, this article contends that these materials ought to be equally conceived as co-productions, often made via complex, asymmetrical researcher/researched engagements. We specifically home in on the dialogic traces left in the archive of the nineteenth century Australian ethnographer A. W. Howitt and his various conversations with an Aboriginal man named Ienbin. We argue that by being attentive to the dialogic aspects of ethnographic sources we can recognize that the Indigenous or anthropological knowledge contained within them is to a significant degree co-constructed in as much as it emerges from social encounter and interaction. More than merely acknowledging the agency of Indigenous informants we propose a more dynamic reading of these texts as products of discursive interactions and shifting relationships.
The Cost of Inflammatory Bowel Disease: An Initiative From the Crohn’s & Colitis Foundation
Authors: Park K T , Ehrlich Orna G , Allen John I , Meadows Perry , Szigethy Eva M , Henrichsen Kim , Kim Sandra C , Lawton Rachel C , Murphy Sean M , Regueiro Miguel , Rubin David T , Engel-Nitz Nicole M , Heller Caren A
Published: May 2019

Background

The Crohn’s & Colitis Foundation’s Cost of Inflammatory Bowel Disease (IBD) Care Initiative seeks to quantify the wide-ranging health care costs affecting patients living with IBD. We aimed to (1) describe the annualized direct and indirect costs of care for patients with Crohn’s disease (CD) or ulcerative colitis (UC), (2) determine the longitudinal drivers of these costs, and (3) characterize the cost of care for newly diagnosed patients.

Methods

We analyzed the Optum Research Database from the years 2007 to 2016, representing commercially insured and Medicare Advantage–insured patients in the United States. Inclusion for the study was limited to those who had continuous enrollment with medical and pharmacy benefit coverage for at least 24 months (12 months before through 12 months after the index date of diagnosis). The value of patient time spent on health care was calculated as number of workplace hours lost due to health care encounters multiplied by the patients’ estimated average wage derived from the Bureau of Labor Statistics. Comparisons between IBD patients and non-IBD patients were analyzed based on demographics, health plan type, and length of follow-up. We used generalized linear models to estimate the association between total annual costs and various patient variables.

Results

There were 52,782 IBD patients (29,062 UC; 23,720 CD) included in the analysis (54.1% females). On a per-annual basis, patients with IBD incurred a greater than 3-fold higher direct cost of care compared with non-IBD controls ($22,987 vs $6956 per-member per-year paid claims) and more than twice the out-of-pocket costs ($2213 vs $979 per-year reported costs), with all-cause IBD costs rising after 2013. Patients with IBD also experienced significantly higher costs associated with time spent on health care as compared with controls. The burden of costs was most notable in the first year after initial IBD diagnosis (mean = $26,555). The study identified several key drivers of cost for IBD patients: treatment with specific therapeutics (biologics, opioids, or steroids); ED use; and health care services associated with relapsing disease, anemia, or mental health comorbidity.

Conclusion

The costs of care for IBD have increased in the last 5 years and are driven by specific therapeutics and disease features. In addition, compared with non-IBD controls, IBD patients are increasingly incurring higher costs associated with health care utilization, out-of-pocket expenditures, and workplace productivity losses. There is a pressing need for cost-effective strategies to address these burdens on patients and families affected by IBD.
Modeling the Effects of Resource-Driven Immune Defense on Parasite Transmission in Heterogeneous Host Populations
Authors: Hall Richard J
Published: May 2019

Individuals experience heterogeneous environmental conditions that can affect within-host processes such as immune defense against parasite infection. Variation among individuals in parasite shedding can cause some hosts to contribute disproportionately to population-level transmission, but we currently lack mechanistic theory that predicts when environmental conditions can result in large disease outbreaks through the formation of immunocompromised superspreading individuals. Here, I present a within-host model of a microparasite’s interaction with the immune system that links an individual host’s resource intake to its infectious period. For environmental scenarios driving population-level heterogeneity in resource intake (resource scarcity and resource subsidy relative to baseline availability), I generate a distribution of infectious periods and simulate epidemics on these heterogeneous populations. I find that resource scarcity can result in large epidemics through creation of superspreading individuals, while resource subsidies can reduce or prevent transmission of parasites close to their invasion threshold by homogenizing resource allocation to immune defense. Importantly, failure to account for heterogeneity in competence can result in under-prediction of outbreak size, especially when parasites are close to their invasion threshold. More generally, this framework suggests that differences in conditions experienced by individual hosts can lead to superspreading via differences in resource allocation to immune defense alone, even in the absence of other heterogeneites such as host contacts.
New developments in innovation and entrepreneurial ecosystems
Authors: Feldman Maryann , Siegel Donald S , Wright Mike
Published: May 2019

In this article, we provide a rationale for this Special Section on innovation and entrepreneurial ecosystems. We also present a summary of the papers presented in the Special Section, highlighting research questions, theories, data and methods, and principal findings and conclusions. A research agenda is also identified, involving multi-level research on agents, institutions, and regions on the context, process, and impact of innovation and entrepreneurial ecosystems.
Eliminating mcr-1-harbouring plasmids in clinical isolates using the CRISPR/Cas9 system
Authors: Wang Pengxia , He Dongmei , Li Baiyuan , Guo Yunxue , Wang Weiquan , Luo Xiongjian , Zhao Xuanyu , Wang Xiaoxue
Published: May 2019

Objectives

To eliminate mcr-1-harbouring plasmids and MDR plasmids in clinical Escherichia coli isolates.

Methods

Plasmid pMBLcas9 expressing Cas9 was constructed and used to clone target single-guide RNAs (sgRNAs) for plasmid curing. The recombinant plasmid pMBLcas9-sgRNA was transferred by conjugation into two clinical E. coli isolates. The curing efficiency of different sgRNAs targeting conserved genes was tested. The elimination of targeted plasmids and the generation of transposase-mediated recombination of p14EC033a variants were characterized by PCR and DNA sequencing.

Results

In this study, four native plasmids in isolate 14EC033 and two native plasmids in isolate 14EC007 were successfully eliminated in a step-by-step manner using pMBLcas9. Moreover, two native plasmids in 14EC007 were simultaneously eliminated by tandemly cloning multiple sgRNAs in pMBLcas9, sensitizing 14EC007 to polymyxin and carbenicillin. In 14EC033 with two mcr-1-harbouring plasmids, IncI2 plasmid p14EC033a and IncX4 plasmid p14EC033b, a single mcr-1 sgRNA mediated the loss of p14EC033b and generated a mutant p14EC033a in which the mcr-1 gene was deleted. An insertion element, IS5, located upstream of mcr-1 in p14EC033a was responsible for transposase-mediated recombination, resulting in mcr-1 gene deletion instead of plasmid curing.

Conclusions

CRISPR/Cas9 can be used to efficiently sensitize clinical isolates to antibiotics in vitro. For isolates with multiple plasmids, the CRISPR/Cas9 approach can either remove each plasmid in a stepwise manner or simultaneously remove multiple plasmids in one step. Moreover, this approach can be used to delete multiple gene copies by using only one sgRNA. However, caution must be exercised to avoid unwanted recombination events during genetic manipulation.
A new species of alvinocaridid shrimp Rimicaris Williams & Rona, 1986 (Decapoda: Caridea) from hydrothermal vents on the Mariana Back Arc Spreading Center, northwestern Pacific
Authors: Komai Tomoyuki , Giguère Thomas
Published: May 2019

A new species of the alvinocaridid shrimp genus RimicarisWilliams & Rona, 1986, R. falkoraen. sp., is described and illustrated based on material from deep-sea hydrothermal vents (3,630–3,912 m deep) on the Mariana Back Arc Spreading Centre, northwestern Pacific, representing the tenth described species of the genus. The new species is morphologically most similar to R. paulexa (Martin & Shank, 2005), but the presence of numerous short setae scattered on the carapace surface, the relatively long antennular stylocerite usually reaching the distal margin of article 2 of the antennular peduncle and the spiniform posteromesial projection of the uropodal protopod distinguish the new species from all congeners. Genetic analysis using the barcoding region of the mitochondrial COI gene supports the recognition of the species as new.
Temperature Limits for the Brown Wheat Mite, in Colorado
Authors: Sitz Rachael A , Peirce Erika S , Luna Emily K , Cockrell Darren M , Newhard Laura , Peairs Frank B
Published: May 2019

Brown wheat mites, Petrobia latens (Müller 1776, Acari: Tetranychidae), are sporadic yet economically damaging pests of winter cereals. In Colorado, their life history is closely tied to the development of winter wheat, where they are present in the field from crop planting in late September through harvest in early June. In order to withstand winter months, these mites are able to survive cold temperatures. However, the mechanisms of cold hardening and their temperature limits are unknown. This research documents the seasonal supercooling points of the brown wheat mite. Their seasonal average supercooling point stayed consistent throughout the year, never varying more than a degree from the overall average supercooling point of −17°C. The greatest variation in supercooling point was seen in the spring, during which supercooling point temperatures ranged from −9.2 to −25.5°C. We also documented the upper and lower lethal temperatures for the brown wheat mite. When comparing small nymphs to large nymph and adult stages, small nymphs were slightly more cold tolerant (lethal temperature estimates required to kill 99% of the population [LT99] were −30.8 and −30.6°C, respectively), but less heat tolerant (LT99 was 50 and 56°C, respectively).
Conventional Sampling Plan for Scouting Neoleucinodes elegantalis (Lepidoptera: Crambidae) Eggs on Tomato Fruits
Authors: Silva Ézio M , Crespo André L B , Farias Elizeu S , Bacci Leandro , Queiroz Renan B , Picanço Marcelo C
Published: May 2019

The small tomato borer, Neoleucinodes elegantalis (Guenée), is an important pest of tomato (Solanum lycopersicum L.) in South and Central America. This pest is a potential threat for many tomato-producing areas and was listed in 2014 as an A1 quarantine pest by the European and Mediterranean Plant Protection Organization. Soon after hatching, the neonate N. elegantalis larvae penetrate the fruits where they feed until pupation. Therefore, effective N. elegantalis management relies on the timely scouting of egg densities to allow decision-making prior to penetration of neonates into fruits. This study aimed to develop a conventional sampling plan for scouting N. elegantalis eggs on tomato plants. The most representative and precise sampling unit was the most basal fruit cluster for plants bearing up to three clusters (S1 plants). For plants with more than three fruit clusters (S2 plants), the most representative and precise sampling unit was the combination of the second and third fruit clusters. Among the four variables evaluated (eggs/fruit, egg masses/fruit, percentage fruit with eggs, and percentage clusters with eggs), the percentage of clusters with eggs was the most economical for N. elegantalis sampling based on the number of samples and cost required. For this variable, the number of samples determined at the 25% error level was 42 and 36 samples for S1 and S2 plants, respectively. The sampling plan developed for scouting N. elegantalis is fast, reflects pest infestation in tomato fields, and costs less than US$1.50 per field scouted.
Associations Between Boys’ Early Childhood Exposure to Family and Neighborhood Poverty and Body Mass Index in Early Adolescence
Authors: Hails Katherine A , Shaw Daniel S
Published: May 2019

Objective

To test relations between exposure to poverty, in the forms of family income and neighborhood deprivation, during three developmental stages, and children’s body mass index (BMI) in early adolescence.

Methods

Data came from a longitudinal sample of racially diverse, urban, low-income boys. Interactions between family income to needs and census-derived neighborhood deprivation at three developmental stages—early childhood (18 and 24 months), preschool-to-school entry (3.5 and 6 years), and school-age (8 and 10 years)—were tested in relation to BMI at age 11.

Results

There was a significant interaction whereby higher income predicted lower BMI only in the context of low levels of neighborhood deprivation in early childhood. In high-deprivation neighborhoods, higher income was associated with risk for overweight/obesity in early adolescence. This pattern was found to be specific to income and neighborhood deprivation measured in early childhood.

Conclusions

Findings have implications for policy relevant to obesity prevention. More research on associations between early exposure to poverty and later risk for obesity on low-income samples is warranted, as the relationship is likely complex and influenced by many different factors, including the family and neighborhood food environments and child health behaviors.
Ongoing astrometric microlensing events from VVV and Gaia
Authors: McGill P , Smith L C , Evans N W , Belokurov V , Lucas P W
Published: May 2019

We extend predictive microlensing event searches using the Vista Variables in the Via Lactea survey and the second Gaia data release. We identify two events with maxima in 2019 that require urgent follow-up. First, we predict that the nearby M2 dwarf L 338-152 will align with a background source with a closest approach of $35^{+35}_{-23}$ mas on 2019 November $16^{+28}_{-27}$ d. This will cause a peak astrometric shift and photometric amplification of the background source of $2.7^{+3.5}_{-1.5}$ mas and $5.6^{+143.2}_{-5.2}$ mmag, respectively. This event should be astrometrically detectable by both the Hubble Space Telescope (HST) and the Spectro-Polarimetric High-contrast Exoplanet Research instrument on the Very Large Telescope. Secondly, we predict that the likely K dwarf NLTT 45128 will lens a background source with a closest approach of $105.3^{+12.2}_{-11.7}$ mas on 2019 September $26^{+15}_{-15}$ d. This will produce a peak astrometric shift of $0.329^{+0.065}_{-0.059}$ mas. NLTT 45128 is only 3.6 mag brighter than the background source which makes it an excellent candidate for follow-up with HST. Characterization of these signals will allow direct gravitational masses to be inferred for both L 338-152 and NLTT 45128 with an estimated precision of ∼9 and ∼13 per cent, respectively.
A Fast Likelihood Method to Reconstruct and Visualize Ancestral Scenarios
Authors: Ishikawa Sohta A , Zhukova Anna , Iwasaki Wataru , Gascuel Olivier
Published: May 2019

The reconstruction of ancestral scenarios is widely used to study the evolution of characters along phylogenetic trees. One commonly uses the marginal posterior probabilities of the character states, or the joint reconstruction of the most likely scenario. However, marginal reconstructions provide users with state probabilities, which are difficult to interpret and visualize, whereas joint reconstructions select a unique state for every tree node and thus do not reflect the uncertainty of inferences.

We propose a simple and fast approach, which is in between these two extremes. We use decision-theory concepts (namely, the Brier score) to associate each node in the tree to a set of likely states. A unique state is predicted in tree regions with low uncertainty, whereas several states are predicted in uncertain regions, typically around the tree root. To visualize the results, we cluster the neighboring nodes associated with the same states and use graph visualization tools. The method is implemented in the PastML program and web server.

The results on simulated data demonstrate the accuracy and robustness of the approach. PastML was applied to the phylogeography of Dengue serotype 2 (DENV2), and the evolution of drug resistances in a large HIV data set. These analyses took a few minutes and provided convincing results. PastML retrieved the main transmission routes of human DENV2 and showed the uncertainty of the human-sylvatic DENV2 geographic origin. With HIV, the results show that resistance mutations mostly emerge independently under treatment pressure, but resistance clusters are found, corresponding to transmissions among untreated patients.
RAB35 depletion affects spindle formation and actin-based spindle migration in mouse oocyte meiosis
Authors: Zhang Yu , Wan Xiang , Wang Hong-Hui , Pan Meng-Hao , Pan Zhen-Nan , Sun Shao-Chen
Published: May 2019

Mammalian oocyte maturation involves a unique asymmetric cell division, in which meiotic spindle formation and actin filament-mediated spindle migration to the oocyte cortex are key processes. Here, we report that the vesicle trafficking regulator, RAB35 GTPase, is involved in regulating cytoskeleton dynamics in mouse oocytes. RAB35 GTPase mainly accumulated at the meiotic spindle periphery and cortex during oocyte meiosis. Depletion of RAB35 by morpholino microinjection led to aberrant polar body extrusion and asymmetric division defects in almost half the treated oocytes. We also found that RAB35 affected SIRT2 and αTAT for tubulin acetylation, which further modulated microtubule stability and meiotic spindle formation. Additionally, we found that RAB35 associated with RHOA in oocytes and modulated the ROCK–cofilin pathway for actin assembly, which further facilitated spindle migration for oocyte asymmetric division. Importantly, microinjection of Myc-Rab35 cRNA into RAB35-depleted oocytes could significantly rescue these defects. In summary, our results suggest that RAB35 GTPase has multiple roles in spindle stability and actin-mediated spindle migration in mouse oocyte meiosis.
The glucocorticoid receptor DNA-binding domain recognizes RNA hairpin structures with high affinity
Authors: Parsonnet Nicholas V , Lammer Nickolaus C , Holmes Zachariah E , Batey Robert T , Wuttke Deborah S
Published: May 2019

The glucocorticoid receptor (GR) binds the noncoding RNA Gas5 via its DNA-binding domain (DBD) with functional implications in pro-apoptosis signaling. Here, we report a comprehensive in vitro binding study where we have determined that GR-DBD is a robust structure-specific RNA-binding domain. GR-DBD binds to a diverse range of RNA hairpin motifs, both synthetic and biologically derived, with apparent mid-nanomolar affinity while discriminating against uniform dsRNA. As opposed to dimeric recognition of dsDNA, GR-DBD binds to RNA as a monomer and confers high affinity primarily through electrostatic contacts. GR-DBD adopts a discrete RNA-bound state, as assessed by NMR, distinct from both free and DNA-bound. NMR and alanine mutagenesis suggest a heightened involvement of the C-terminal α-helix of the GR-DBD in RNA-binding. RNA competes for binding with dsDNA and occurs in a similar affinity range as dimer binding to the canonical DNA element. Given the prevalence of RNA hairpins within the transcriptome, our findings strongly suggest that many RNAs have potential to impact GR biology.
Tobacco Cessation in Affordable Care Act Medicaid Expansion States Versus Non-expansion States
Authors: Bailey Steffani R , Marino Miguel , Ezekiel-Herrera David , Schmidt Teresa , Angier Heather , Hoopes Megan J , DeVoe Jennifer E , Heintzman John , Huguet Nathalie
Published: May 2019

Introduction

Community health centers (CHCs) care for vulnerable patients who use tobacco at higher than national rates. States that expanded Medicaid eligibility under the Affordable Care Act (ACA) provided insurance coverage to tobacco users not previously Medicaid-eligible, thereby potentially increasing their odds of receiving cessation assistance. We examined if tobacco users in Medicaid expansion states had increased quit rates, cessation medications ordered, and greater health care utilization compared to patients in non-expansion states.

Methods

Using electronic health record (EHR) data from 219 CHCs in 10 states that expanded Medicaid as of January 1, 2014, we identified patients aged 19–64 with tobacco use status documented in the EHR within 6 months prior to ACA Medicaid expansion and ≥1 visit with tobacco use status assessed within 24 months post-expansion (January 1, 2014 to December 31, 2015). We propensity score matched these patients to tobacco users from 108 CHCs in six non-expansion states (n = 27 670 matched pairs; 55 340 patients). Using a retrospective observational cohort study design, we compared odds of having a quit status, cessation medication ordered, and ≥6 visits within the post-expansion period among patients in expansion versus non-expansion states.

Results

Patients in expansion states had increased adjusted odds of quitting (adjusted odds ratio [aOR] = 1.35, 95% confidence interval [CI]: 1.28–1.43), having a medication ordered (aOR = 1.53, 95% CI: 1.44–1.62), and having ≥6 follow-up visits (aOR = 1.34, 95% CI: 1.28–1.41) compared to patients from non-expansion states.

Conclusions

Increased access to insurance via the ACA Medicaid expansion likely led to increased quit rates within this vulnerable population.

Implications

CHCs care for vulnerable patients at higher risk of tobacco use than the general population. Medicaid expansion via the ACA provided insurance coverage to a large number of tobacco users not previously Medicaid-eligible. We found that expanded insurance coverage was associated with increased cessation assistance and higher odds of tobacco cessation. Continued provision of insurance coverage could lead to increased quit rates among high-risk populations, resulting in improvements in population health outcomes and reduced total health care costs.
Reduced Transplacental Transfer of Antimalarial Antibodies in Kenyan HIV-Exposed Uninfected Infants
Authors: Ray Jessica E , Dobbs Katherine R , Ogolla Sidney O , Daud Ibrahim I , Vulule John , Sumba Peter O , Rochford Rosemary , Dent Arlene E
Published: May 2019

Background

Altered neonatal immune responses may contribute to the increased morbidity observed in HIV-exposed but uninfected (HEU) infants compared with HIV-unexposed uninfected (HUU) infants. We sought to examine the effects of prenatal HIV and malaria exposure on maternal and neonatal plasma cytokine profiles and transplacental antibody transfer.

Methods

Forty-nine HIV+ and 50 HIV- women and their HIV-uninfected neonate pairs from Kenya were assessed. All HIV+ mothers received combination antiretroviral therapy. Maternal plasma and cord blood plasma samples at delivery were tested for 12 cytokines, total IgG, and IgG specific to 4 vaccine antigens and 14 Plasmodium falciparum antigens.

Results

HIV+ mothers had lower levels of all 12 plasma cytokines at delivery compared with HIV- mothers, but there were no differences between HEU and HUU neonates. There were no differences in the cord-to-maternal ratios (CMRs) of vaccine-specific IgG between HIV+/HEU and HIV-/HUU maternal–neonate pairs. HIV+/HEU maternal–neonate pairs had significantly lower CMRs for 3 antimalarial IgGs—merozoite surface protein 9, circumsporozoite protein, and erythrocyte binding antigen 181—which remained statistically significant after adjustment for malaria in pregnancy.

Conclusions

In a cohort of optimally treated HIV-infected pregnant women, maternal HIV infection was associated with reduced transplacental transfer of antimalarial antibodies.
Nobeyama 45 m mapping observations toward Orion A. II. Classification of cloud structures and variation of the 13CO/C18O abundance ratio due to far-UV radiation
Authors: Ishii Shun , Nakamura Fumitaka , Shimajiri Yoshito , Kawabe Ryohei , Tsukagoshi Takashi , Dobashi Kazuhito , Shimoikura Tomomi
Published: May 2019

We present results of the classification of cloud structures toward the Orion A Giant Molecular Cloud based on wide-field 12CO (J = 1–0), 13CO (J = 1–0), and C18O (J = 1–0) observations using the Nobeyama 45 m radio telescope. We identified 78 clouds toward Orion A by applying Spectral Clustering for Interstellar Molecular Emission Segmentation (SCIMES) to the data cube of the column density of 13CO. Well-known subregions such as OMC-1, OMC-2/3, OMC-4, OMC-5, NGC 1977, L1641-N, and the dark lane south filament (DLSF) are naturally identified as distinct structures in Orion A. These clouds can also be classified into three groups: the integral-shaped filament, the southern regions of Orion A, and the other filamentary structures in the outer parts of Orion A and the DLSF. These groups show differences in scaling relations between the physical properties of the clouds. We derived the abundance ratio between 13CO and C18O, $X_{^{13}\mathrm{CO}}/X_{\mathrm{C}^{18}\mathrm{O}}$, which ranges from 5.6 to 17.4 on median over the individual clouds. The significant variation of $X_{^{13}\mathrm{CO}}/X_{\mathrm{C}^{18}\mathrm{O}}$ is also seen within a cloud in both the spatial and velocity directions and the ratio tends to be high at the edge of the cloud. The values of $X_{^{13}\mathrm{CO}}/X_{\mathrm{C}^{18}\mathrm{O}}$ decrease from 17 to 10 with the median of the column densities of the clouds at the column density of $N_{\mathrm{C^{18}O}} \gtrsim 1 \times 10^{15}\:$cm−2 or visual extinction of AV ≳ 3 mag under the strong far-ultraviolet (FUV) environment of G0 > 103, whereas it is almost independent of the column density in the weak FUV radiation field. These results are explained if the selective photodissociation of C18O is enhanced under a strong FUV environment and it is suppressed in the dense part of the clouds.
Chaucer and Crusader Ethics: Youth, Love, and the Material World
Authors: Elias Marcel
Published: May 2019

In this essay, I argue that the Squire’s portrait in the Canterbury Tales is indebted to fourteenth-century crusade discourse, and that the ideological differences between the Knight and the Squire are well understood in relation to contemporary debates on the ethics of crusaders. Drawing upon diverse literary and historical sources, I focus on three rhetorical juxtapositions, which, I argue, Chaucer appropriated from contemporary critics of the morals and conduct of crusaders: between aged wisdom and youthful passion to admonish their military intemperance; between love of God and love of the world, often couched in terms of chivalric love-service, to decry their vainglorious motives; and between humble and ostentatious attire to denounce their excessive attachment to the material world. The evaluative relation between the two pilgrims, established in the General Prologue, is developed in the Knight’s Tale and the Squire’s Tale. Within the Squire’s scope of experience, key episodes of the Knight’s Tale fulfil the role of cautionary exempla in a vein similar to those extensively deployed in writings on and by crusaders to illustrate the benefits and dangers of specific attitudes and behaviours. The Squire’s Tale, drawing upon the motif of the ‘noble infidel’, further exposes the deficiencies of the crusading philosophy of which its teller is a symbol.
Highly diverse mesophotic reef fish communities in Raja Ampat, West Papua
Authors: Andradi-Brown Dominic A. , Beer Angela J. E. , Colin Luigi , Hastuti  , Head Catherine E. I. , Hidayat Nur Ismu , Lindfield Steven J , Mitchell Catherine R. , Pada Defy N. , Piesinger Nikola M. , Purwanto  , Ahmadia Gabby N.
Published: May 2019

Mesophotic coral ecosystems (MCEs; reefs 30-150 m depth) are poorly studied, with existing research heavily geographically biased away from the most species-rich reef regions. Yet, MCEs are of high interest because of their unique species and potential to act as refuges from the impacts of fishing. Using baited remote underwater video systems, we surveyed reef fish communities from 2 to 85 m depths throughout the Raja Ampat archipelago in West Papua, Indonesia – an area considered the heart of the Coral Triangle where coral reef biodiversity is greatest. We sought to provide the first assessment of fish communities across this depth gradient in the region and identify whether human population density and market access differently affected fish abundance based on depth. Here we show that—similar to shallow reefs—Raja Ampat MCEs are exceptionally diverse, with 152 fish species recorded at depths greater than 40 m. We found that fish community structures were highly depth driven, with declines in fish abundance at increased depth. In contrast to previous studies elsewhere in the world, we found that the proportion of planktivores declined across the shallow reef to MCE depth gradient. While greater human population density correlated with lower Epinephelidae and Lutjanidae abundance (two key fisheries families), we did not find evidence that MCEs provide a depth refuge from fishing. Surprisingly, we also found that fish abundance declined at greater distances from the major regional market – likely caused by historical fisheries pressure in more remote areas. These results both expand upon and contrast some previously established MCE-depth patterns and human impact patterns on fish communities, suggesting that regional context and historical pressures matters. Our findings highlight the need for future MCE studies within the Coral Triangle region.
Unique Transcription Factor Functions Regulate Epigenetic and Transcriptional Dynamics During Cardiac Reprogramming
Authors: Stone Nicole R. , Gifford Casey A. , Thomas Reuben , Pratt Karishma J. B. , Samse-Knapp Kaitlen , Mohamed Tamer M. A. , Radzinsky Ethan M. , Schricker Amelia , Yu Pengzhi , Ivey Kathryn N. , Pollard Katherine S. , Srivastava Deepak
Published: May 2019

Direct lineage conversion, whereby a somatic cell assumes a new cellular identity, can be driven by ectopic expression of combinations of lineage-enriched transcription factors. To determine the molecular mechanisms by which expression of Gata4, Mef2c, and Tbx5 (GMT) induces direct reprogramming from a cardiac fibroblast toward an induced cardiomyocyte, we performed a comprehensive transcriptomic and epigenomic interrogation of the reprogramming process. Single cell RNA sequencing indicated that a reprogramming trajectory was acquired within 48 hours of GMT introduction, did not require cell division, and was limited mainly by successful expression of GMT. Evaluation of chromatin accessibility by ATAC-seq supported the expression dynamics and revealed widespread chromatin remodeling at early stages of the reprogramming process. Chromatin immunoprecipitation followed by sequencing of each factor alone or in combinations revealed that GMT bind DNA individually and in combination, and that ectopic expression of either Mef2c or Tbx5 is sufficient in some contexts to increase accessibility. We also find evidence for cooperative facilitation and refinement of each factor’s binding in a combinatorial setting. A random-forest classifier that integrated the observed gene expression dynamics with regions of dynamic chromatin accessibility suggested Tbx5 binding is a primary driver of gene expression changes and revealed additional transcription factor motifs co-segregating with reprogramming factor motifs, suggesting new factors that may be involved in the reprogramming process. These results begin to explain the mechanisms by which transcription factors normally expressed in multiple germ layers can function combinatorially to direct lineage conversion.