bluuebunny/crossref_metadata_2025 huggingface dataset:
Mineral gels with a condensed dispersed phase
Authors: Sakharov P A , Khvatov A V , Belenko E V
Published: September 2020

In the modern oil industry, water-polymer gels are widely used as drilling fluids. The main structural and mechanical units of these gels are macromolecules that participate in the construction of a single spatial structural grid due to donor-acceptor or ion bonds. The purpose of this work is to study the possibility of obtaining mineral hydrogels that combine high structural and mechanical characteristics characteristic of polymer hydrogels, but differ in the pseudoplastic flow model in combination with stability in the harsh thermobaric conditions of oil wells. Condensed hydrogels can potentially solve the most important problem in the production of liquid and gaseous minerals, which is to preserve the natural ecological balance and ensure the normal mode of biological self-purification of biogeocenoses in the areas of oil field development and disposal of drilling waste.
Interaction of Neighborhood and Genetic Risk on Waist Circumference in African-American Adults: A Longitudinal Study
Authors: McDaniel Tyler , Wilson Dawn K , Coulon M Sandra , Sweeney Allison M , Van Horn M Lee
Published: September 2020

Background

Understanding determinants of metabolic risk has become a national priority given the increasingly high prevalence rate of this condition among U.S. adults.

Purpose

This study’s aim was to assess the impact of gene-by-neighborhood social environment interactions on waist circumference (WC) as a primary marker of metabolic risk in underserved African-American adults. Based on a dual-risk model, it was hypothesized that those with the highest genetic risk and who experienced negative neighborhood environment conditions would demonstrate higher WC than those with fewer risk factors.

Methods

This study utilized a subsample of participants from the Positive Action for Today’s Health environmental intervention to improve access and safety for walking in higher-crime neighborhoods, who were willing to provide buccal swab samples for genotyping stress-related genetic pathways. Assessments were conducted with 228 African-American adults at baseline, 12, 18, and 24 months.

Results

Analyses indicated three significant gene-by-environment interactions on WC outcomes within the sympathetic nervous system (SNS) genetic pathway. Two interactions supported the dual-risk hypotheses, including the SNS genetic risk-by-neighborhood social life interaction (b = −0.11, t(618) = −2.02, p = .04), and SNS genetic risk-by-informal social control interaction (b = −0.51, t(618) = −1.95, p = .05) on WC outcomes. These interactions indicated that higher genetic risk and lower social-environmental supports were associated with higher WC. There was also one significant SNS genetic risk-by-neighborhood satisfaction interaction (b = 1.48, t(618) = 2.23, p = .02) on WC that was inconsistent with the dual-risk pattern.

Conclusions

Findings indicate that neighborhood and genetic factors dually influence metabolic risk and that these relations may be complex and warrant further study.

Trial Registration

NCT01025726.
Experimental Test of the Educational Impact of the Newly Proposed FDA Graphic Cigarette Warnings Among U.S. Adults
Authors: Magnan Renee E , Hamilton W Kyle , Shorey-Fennell Bethany , Cameron Linda D
Published: September 2020

Background

In August 2019, the U.S. Food and Drug Administration proposed a set of 13 new graphic warnings for cigarette packaging and advertisements.

Purpose

We evaluated these warnings relative to text-only equivalents for their ability to educate the public regarding harms of smoking and influence outcomes associated with quitting.

Methods

In an experimental within-subjects design, U.S. adult nonsmokers, smokers, and dual smoker/electronic cigarette (e-cigarette) users (N = 412) recruited from an online internet platform evaluated the newly proposed graphic warnings and corresponding text-only warnings on understandability, perceived new knowledge, worry elicited about the content of the warning, discouragement from smoking, and encouragement to use e-cigarettes.

Results

Graphic warnings were generally rated as providing better understanding, more new knowledge, eliciting more worry about harms of smoking, and providing more discouragement from smoking relative to text-only warnings.

Conclusions

The newly proposed graphic warnings could influence important responses to warnings associated with motivation to reduce smoking.
Comparing the Individual and Combined Effects of Ant Attendance and Wing Formation on Aphid Body Size and Reproduction
Authors: Nelson Annika S , Mooney Kailen A
Published: September 2020

Species employ multiple strategies to deal with stressful environments, but these strategies often incur costs. Aphids frequently utilize multiple predator avoidance strategies, including attracting mutualist ants for protection and dispersing by producing winged forms. While both strategies can be physiologically costly, the magnitudes of these costs have not been previously compared. In this study, we experimentally manipulated ant attendance in the field and measured the individual and interactive effects of ant attendance and wing formation on body size and reproduction of the ant-tended aphid Cinara schwarzii (Wilson) (Hemiptera: Aphididae). Aphid adult body size was smaller in the presence of ants (18%), but controlling for body size, there were no differences in embryo number or size. In contrast, wing formation did not affect adult body size but strongly reduced embryo number (46%) and size (8%). Although ant attendance reduced C. schwarzii wing formation, ant attendance and wing formation acted independently on aphid body size and reproduction. For comparison, we confirmed that the manipulation of ant presence had no effect on body size or reproduction of the untended co-existing congener Cinara solitaria (Gillette and Palmer) (Hemiptera: Aphididae). Complementing our empirical study, a meta-analysis of 78 responses from 24 publications showed that wing formation consistently and significantly reduces aphid body size and reproduction (37%), while the effects of ant attendance showed a mean positive effect (9%) that did not significantly differ from zero. Together, our empirical study and meta-analysis provide strong evidence for costs of wing formation but not ant attendance for aphids.
Identification of pan-cancer Ras pathway activation with deep learning
Authors: Li Xiangtao , Li Shaochuan , Wang Yunhe , Zhang Shixiong , Wong Ka-Chun
Published: September 2020

The identification of hidden responders is often an essential challenge in precision oncology. A recent attempt based on machine learning has been proposed for classifying aberrant pathway activity from multiomic cancer data. However, we note several critical limitations there, such as high-dimensionality, data sparsity and model performance. Given the central importance and broad impact of precision oncology, we propose nature-inspired deep Ras activation pan-cancer (NatDRAP), a deep neural network (DNN) model, to address those restrictions for the identification of hidden responders. In this study, we develop the nature-inspired deep learning model that integrates bulk RNA sequencing, copy number and mutation data from PanCanAltas to detect pan-cancer Ras pathway activation. In NatDRAP, we propose to synergize the nature-inspired artificial bee colony algorithm with different gradient-based optimizers in one framework for optimizing DNNs in a collaborative manner. Multiple experiments were conducted on 33 different cancer types across PanCanAtlas. The experimental results demonstrate that the proposed NatDRAP can provide superior performance over other benchmark methods with strong robustness towards diagnosing RAS aberrant pathway activity across different cancer types. In addition, gene ontology enrichment and pathological analysis are conducted to reveal novel insights into the RAS aberrant pathway activity identification and characterization. NatDRAP is written in Python and available at https://github.com/lixt314/NatDRAP1.
Early ontogeny defines the diversification of primary vascular bundle systems in angiosperms
Authors: Claßen-Bockhoff Regine , Franke Doris , Krähmer Hansjörg
Published: September 2020

Understanding vascular bundle systems in angiosperms is a challenge. On the one hand, the vascular tissue is extremely important in reconstructing the evolution and survivability of plants, but on the other hand, it forms a complicated three-dimensional system of controversially discussed phylogenetic and ontogenetic origin. To increase clarity, in this paper we briefly summarize histological, phylogenetic and molecular aspects of primary vascular bundle formation in angiosperms, adding histological data on early stages of vascular bundle formation, proposing a concept combining the different views and providing simplified illustrations to improve the understanding of primary vascular systems in angiosperms. Based on the auxin hypothesis, vascular bundle formation is stimulated by the development of leaf primordia. Provascular domains appear at the base of the leaf primordia and develop into two directions (leaf, internode). The low vs. high number of internodal bundles, their circular vs. scattered arrangement and the open vs. closed bundle construction in eudicots vs. monocots can be deduced to be due to processes below the shoot apical meristem. The most important processes distinguishing monocots from eudicots are the isolated bundle initiation outside the primary meristem, the enormous expansion of the leaf bases associated with a high number of vascular bundles and the early onset of primary thickening passively dislocating vascular bundles.
Structural Neuroplastic Responses Preserve Functional Connectivity and Neurobehavioural Outcomes in Children Born Without Corpus Callosum
Authors: Siffredi Vanessa , Preti Maria G , Kebets Valeria , Obertino Silvia , Leventer Richard J , McIlroy Alissandra , Wood Amanda G , Anderson Vicki , Spencer-Smith Megan M , Van De Ville Dimitri
Published: September 2020

The corpus callosum is the largest white matter pathway in the brain connecting the two hemispheres. In the context of developmental absence (agenesis) of the corpus callosum (AgCC), a proposed candidate for neuroplastic response is strengthening of intrahemispheric pathways. To test this hypothesis, we assessed structural and functional connectivity in a uniquely large cohort of children with AgCC (n = 20) compared with typically developing controls (TDC, n = 29), and then examined associations with neurobehavioral outcomes using a multivariate data-driven approach (partial least squares correlation, PLSC). For structural connectivity, children with AgCC showed a significant increase in intrahemispheric connectivity in addition to a significant decrease in interhemispheric connectivity compared with TDC, in line with the aforementioned hypothesis. In contrast, for functional connectivity, children with AgCC and TDC showed a similar pattern of intrahemispheric and interhemispheric connectivity. In conclusion, we observed structural strengthening of intrahemispheric pathways in children born without corpus callosum, which seems to allow for functional connectivity comparable to a typically developing brain, and were relevant to explain neurobehavioral outcomes in this population. This neuroplasticity might be relevant to other disorders of axonal guidance, and developmental disorders in which corpus callosum alteration is observed.
Eco-evolutionary feedbacks mediated by bacterial membrane vesicles
Authors: Zlatkov Nikola , Nadeem Aftab , Uhlin Bernt Eric , Wai Sun Nyunt
Published: September 2020

Bacterial membrane vesicles (BMVs) are spherical extracellular organelles whose cargo is enclosed by a biological membrane. The cargo can be delivered to distant parts of a given habitat in a protected and concentrated manner. This review presents current knowledge about BMVs in the context of bacterial eco-evolutionary dynamics among different environments and hosts. BMVs may play an important role in establishing and stabilizing bacterial communities in such environments; for example, bacterial populations may benefit from BMVs to delay the negative effect of certain evolutionary trade-offs that can result in deleterious phenotypes. BMVs can also perform ecosystem engineering by serving as detergents, mediators in biochemical cycles, components of different biofilms, substrates for cross-feeding, defense systems against different dangers and enzyme-delivery mechanisms that can change substrate availability. BMVs further contribute to bacteria as mediators in different interactions, with either other bacterial species or their hosts. In short, BMVs extend and deliver phenotypic traits that can have ecological and evolutionary value to both their producers and the ecosystem as a whole.
Mortality among uranium miners in North America and Europe: the Pooled Uranium Miners Analysis (PUMA)
Authors: Richardson D B , Rage E , Demers P A , Do M T , DeBono N , Fenske N , Deffner V , Kreuzer M , Samet J , Wiggins C , Schubauer-Berigan M K , Kelly-Reif K , Tomasek L , Zablotska L B , Laurier D
Published: September 2020

Background

The Pooled Uranium Miners Analysis (PUMA) study draws together information from cohorts of uranium miners from Canada, the Czech Republic, France, Germany and the USA.

Methods

Vital status and cause of death were ascertained and compared with expectations based upon national mortality rates by computing standardized mortality ratios (SMRs) overall and by categories of time since first hire, calendar period of first employment and duration of employment as a miner.

Results

There were 51 787 deaths observed among 118 329 male miners [SMR = 1.05; 95% confidence interval (CI): 1.04, 1.06]. The SMR was elevated for all cancers (n = 16 633, SMR = 1.23; 95% CI: 1.21, 1.25), due primarily to excess mortality from cancers of the lung (n = 7756, SMR = 1.90; 95% CI: 1.86, 1.94), liver and gallbladder (n = 549, SMR = 1.15; 95% CI: 1.06, 1.25), larynx (n = 229, SMR = 1.10; 95% CI: 0.97, 1.26), stomach (n = 1058, SMR = 1.08; 95% CI: 1.02, 1.15) and pleura (n = 39, SMR = 1.06; 95% CI: 0.75, 1.44). Lung-cancer SMRs increased with duration of employment, decreased with calendar period and persisted with time since first hire. Among non-malignant causes, the SMR was elevated for external causes (n = 3362, SMR = 1.41; 95% CI: 1.36, 1.46) and respiratory diseases (n = 4508, SMR = 1.32; 95% CI: 1.28, 1.36), most notably silicosis (n = 814, SMR = 13.56; 95% CI: 12.64, 14.52), but not chronic obstructive pulmonary disease (n = 1729, SMR = 0.98; 95% CI: 0.93, 1.02).

Conclusions

Whereas there are important obstacles to the ability to detect adverse effects of occupational exposures via SMR analyses, PUMA provides evidence of excess mortality among uranium miners due to a range of categories of cause of death. The persistent elevation of SMRs with time since first hire as a uranium miner underscores the importance of long-term follow-up of these workers.
An Extension of BCOV Invariant
Authors: Zhang Yeping
Published: September 2020

Bershadsky, Cecotti, Ooguri, and Vafa constructed a real-valued invariant for Calabi–Yau manifolds, which is called the BCOV invariant. In this paper, we consider a pair $(X,Y)$, where $X$ is a compact Kähler manifold and $Y\in \big |K_X^m\big |$ with $m\in{\mathbb{Z}}\backslash \{0,-1\}$. We extend the BCOV invariant to such pairs. If $m=-2$ and $X$ is a rigid del Pezzo surface, the extended BCOV invariant is equivalent to Yoshikawa’s equivariant BCOV invariant. If $m=1$, the extended BCOV invariant is well behaved under blowup. It was conjectured that birational Calabi–Yau three-folds have the same BCOV invariant. As an application of our extended BCOV invariant, we show that this conjecture holds for Atiyah flops.
Trends in Burn Injuries in Northern Israel During the COVID-19 Lockdown
Authors: Kruchevsky Dani , Arraf Maher , Levanon Shir , Capucha Tal , Ramon Yitzchak , Ullmann Yehuda
Published: September 2020

Coronavirus disease 2019 obliged many countries to apply lockdown policies to contain the spread of infection. The restrictions in Israel included limitations on movement, reduction of working capacity, and closure of the educational system. The present study focused on patients treated at a referral center for burns in northern Israel. Their goal was to investigate temporal variations in burn injuries during this period. Data were retrospectively extracted from the medical records of burn patients treated at our hospital between March 14, 2020 and April 20, 2020 (ie, the period of aggravated lockdown). Data from this period were compared with that from paralleling periods between 2017 and 2019. During the lockdown and paralleling periods, 178 patients were treated for burn injuries, of whom 44% were under 18. Although no restrictions were enforced during the virus outbreak period with regard to seeking medical care, we noticed a decrease in the number of patients admitted to the emergency room for all reasons. Of particular interest was a 66% decrease in the number of adult burn patients (P < .0001). Meanwhile, among the pediatric population, no significant decrease was observed. Nonetheless, subgroups with higher susceptibility to burn injuries included children aged 2 to 5 years (56.3% vs 23.8%, P = .016) and female patients from all pediatric age groups (57.1% vs 25%, P = .027). These findings may be explained by the presumably busier kitchen and dining areas during the lockdown. Overall, the study results can assist with building a stronger understanding of varying burn injuries and with developing educational and preventive strategies.
High-Quality SNP Linkage Maps Improved QTL Mapping and Genome Assembly inPopulus
Authors: Tong Chunfa , Yao Dan , Wu Hainan , Chen Yuhua , Yang Wenguo , Zhao Wei
Published: September 2020

With the advances in high-throughput sequencing technologies and the development of new software for extracting single nucleotide polymorphisms (SNPs) across a mapping population, it is possible to construct high-quality genetic maps with thousands of SNPs in outbred forest trees. Two parent-specific linkage maps were constructed with restriction site-associated DNA sequencing data from an F1 hybrid population derived from Populus deltoides and Populus simonii, and applied in QTL mapping and genome assembly. The female P. deltoides map contained 4018 SNPs, which were divided into 19 linkage groups under a wide range of LOD thresholds from 7 to 55. The male P. simonii map showed similar characteristics, consisting of 2097 SNPs, which also belonged to 19 linkage groups under LOD thresholds of 7 to 29. The SNP order of each linkage group was optimal among different ordering results from several available software. Moreover, the linkage maps allowed the detection of 39 QTLs underlying tree height and 47 for diameter at breast height. In addition, the linkage maps improved the anchoring of 689 contigs of P. simonii to chromosomes. The 2 parental genetic maps of Populus are of high quality, especially in terms of SNP data quality, the SNP order within linkage groups, and the perfect match between the number of linkage groups and the karyotype of Populus, as well as the excellent performances in QTL mapping and genome assembly. Both approaches for extracting and ordering SNPs could be applied to other species for constructing high-quality genetic maps.
Activity overlap of carnivores, their potential wild prey, and temporal segregation, with livestock in a Biosphere Reserve in the Chihuahuan Desert
Authors: Durán-Antonio Jessica , González-Romero Alberto , Sosa Vinicio J
Published: September 2020

Daily activity is an important aspect of animal behavior and depends both on nutritional and reproductive demands. It also can be modified by—among other factors—interspecific competition, the need to minimize the risk of predation, and human disturbance, such as the presence of cattle. We studied the activity patterns and degree of overlap among carnivores, their potential wild prey, and livestock, in a Biosphere Reserve in the Chihuahuan Desert. There was no temporal segregation among the carnivores. Carnivores synchronized their activity with that of their main prey, the black-tailed jackrabbit (Lepus californicus). In contrast, we did observe temporal segregation between the puma (Puma concolor), coyote (Canis latrans), and bobcat (Lynx rufus), with mule deer (Odocoileus hemionus). There was little activity overlap between predators and livestock (Bos taurus, Equus caballus). However, to avoid conflict resulting from livestock predation we suggest increasing and improving surveillance, and that calves and females close to calving be sheltered. More studies on the multi-niche interactions of livestock and their wild predators are needed to understand daily activity overlap in different seasons, and to better understand the mechanisms of coexistence in protected areas in order to make sound management recommendations to cattle growers and park rangers.
The re-emergence of Zika in Brazil in 2020: a case of Guillain Barré Syndrome during the low season for arboviral infections
Authors: Akrami Kevan M , de Nogueira Betania Mara Freitas , do Rosário Mateus Santana , de Moraes Laise , Cordeiro Marli Tenório , Haddad Rodrigo , Gomes Lillian Nunes , de Pádua Carvalho Isabele , dos Reis Pimentel Ellen , de Jesus Silva Jéssica , de Oliveira Francisco Marcos Vinícius Lima , de Siqueira Isadora Cristina , Farias Daniel , Barral-Netto Manoel , Barral Aldina , Boaventura Viviane , Khouri Ricardo
Published: September 2020

Zika virus cases in Brazil have diminished since emergence in 2015. We report Guillain Barré Syndrome caused by Zika and possible Chikungunya co-infection during an expected low arboviral season. This case highlights the importance of clinical vigilance for Zika in those with neurological syndromes outside typical arboviral season.
Polyteam semantics
Authors: Hannula Miika , Kontinen Juha , Virtema Jonni
Published: September 2020

Team semantics is the mathematical framework of modern logics of dependence and independence in which formulae are interpreted by sets of assignments (teams) instead of single assignments as in first-order logic. In order to deepen the fruitful interplay between team semantics and database dependency theory, we define Polyteam Semantics in which formulae are evaluated over a family of teams. We begin by defining a novel polyteam variant of dependence atoms and give a finite axiomatization for the associated implication problem. We relate polyteam semantics to team semantics and investigate in which cases logics over the former can be simulated by logics over the latter. We also characterize the expressive power of poly-dependence logic by properties of polyteams that are downwards closed and definable in existential second-order logic ($\textsf{ESO}$). The analogous result is shown to hold for poly-independence logic and all $\textsf{ESO}$-definable properties. We also relate poly-inclusion logic to greatest fixed point logic.
Effectiveness of Electronic Cigarettes in Smoking Cessation: A Systematic Review and Meta-analysis
Authors: Grabovac Igor , Oberndorfer Moritz , Fischer Jismy , Wiesinger Winfried , Haider Sandra , Dorner Thomas Ernst
Published: September 2020

Introduction

Reports of the effectiveness of e-cigarettes (ECs) for smoking cessation vary across different studies making implementation recommendations hard to attain. We performed a systematic review and meta-analysis to assess the current evidence regarding effectiveness of ECs for smoking cessation.

Methods

PubMed, PsycInfo, and Embase databases were searched for randomized controlled trials comparing nicotine ECs with non-nicotine ECs or with established smoking cessation interventions (nicotine replacement therapy [NRT] and or counseling) published between 1 January 2014 and 27 June 2020. Data from eligible studies were extracted and used for random-effects meta-analyses (PROSPERO registration number: CRD42019141414).

Results

The search yielded 13 950 publications with 12 studies being identified as eligible for systematic review (N = 8362) and 9 studies for random-effects meta-analyses (range: 30–6006 participants). The proportion of smokers achieving abstinence was 1.71 (95 CI: 1.02–2.84) times higher in nicotine EC users compared with non-nicotine EC users. The proportion of abstinent smokers was 1.69 (95 CI: 1.25–2.27) times higher in EC users compared with participants receiving NRT. EC users showed a 2.04 (95 CI: 0.90–4.64) times higher proportion of abstinent smokers in comparison with participants solely receiving counseling.

Conclusions

Our results suggest that nicotine ECs may be more effective in smoking cessation when compared with placebo ECs or NRT. When compared with counseling alone, nicotine ECs are more effective short term, but its effectiveness appears to diminish with later follow-ups. Given the small number of studies, heterogeneous design, and the overall moderate to low quality of evidence, it is not possible to offer clear recommendations.

Implications

The results of this study do not allow for a conclusive argument. However, pooling current evidence points toward a potential for ECs as a smoking cessation tool. Though, given the overall quality of evidence, future studies should aim for more clarity in terms of interventions and larger study populations.
Transdisciplinary research outcomes based on the Transdisciplinary Research on Energetics and Cancer II initiative experience
Authors: Hohl Sarah D , Knerr Sarah , Gehlert Sarah , Neuhouser Marian L , Beresford Shirley A A , Unger Joseph M , Fishman Paul A , Thompson Beti
Published: September 2020

Intractable public health problems are influenced by interacting multi-level factors. Dynamic research approaches in which teams of scientists collaborate beyond traditional disciplinary, institutional, and geographic boundaries have emerged as promising strategies to address pressing public health priorities. However, little prior work has identified, defined, and characterized the outcomes of transdisciplinary (TD) research undertaken to address public health problems. Through a mixed methods approach, we identify, define, and characterize TD outcomes and their relevance to improving population health using the Transdisciplinary Research on Energetics and Cancer (TREC) II initiative as a case example. In Phase I, TREC II leadership (n = 10) identified nine initial TD outcomes. In Phase II (web-based survey; n = 23) and Phase III (interviews; n = 26; and focus groups, n = 23) TREC members defined and characterized each outcome. The resulting nine outcomes are described. The nine complementary TD outcomes can be used as a framework to evaluate progress toward impact on complex public health problems. Strategic investment in infrastructure that supports team development and collaboration, such as a coordination center, cross-center working groups, annual funded developmental projects, and face-to-face meetings, may foster achievement of these outcomes. This exploratory work provides a basis for the future investigation and development of quantitative measurement tools to assess the achievement of TD outcomes that are relevant to solving multifactorial public health problems.
A Review of the Functional Roles of the Zebrafish Aryl Hydrocarbon Receptors
Authors: Shankar Prarthana , Dasgupta Subham , Hahn Mark E , Tanguay Robyn L
Published: September 2020

Over the last 2 decades, the zebrafish (Danio rerio) has emerged as a stellar model for unraveling molecular signaling events mediated by the aryl hydrocarbon receptor (AHR), an important ligand-activated receptor found in all eumetazoan animals. Zebrafish have 3 AHRs—AHR1a, AHR1b, and AHR2, and studies have demonstrated the diversity of both the endogenous and toxicological functions of the zebrafish AHRs. In this contemporary review, we first highlight the evolution of the zebrafish ahr genes, and the characteristics of the receptors including developmental and adult expression, their endogenous and inducible roles, and the predicted ligands from homology modeling studies. We then review the toxicity of a broad spectrum of AHR ligands across multiple life stages (early stage, and adult), discuss their transcriptomic and epigenetic mechanisms of action, and report on any known interactions between the AHRs and other signaling pathways. Through this article, we summarize the promising research that furthers our understanding of the complex AHR pathway through the extensive use of zebrafish as a model, coupled with a large array of molecular techniques. As much of the research has focused on the functions of AHR2 during development and the mechanism of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) toxicity, we illustrate the need to address the considerable knowledge gap in our understanding of both the mechanistic roles of AHR1a and AHR1b, and the diverse modes of toxicity of the various AHR ligands.
Tobacco Smoke Exposure Exacerbated Crystalline Silica-Induced Lung Toxicity in Rats
Authors: Sager Tina M , Umbright Christina M , Mustafa Gul Mehnaz , Yanamala Naveena , Leonard Howard D , McKinney Walter G , Kashon Michael L , Joseph Pius
Published: September 2020

Smoking may modify the lung response to silica exposure including cancer and silicosis. Nevertheless, the precise role of exposure to tobacco smoke (TS) on the lung response to crystalline silica (CS) exposure and the underlying mechanisms need further clarification. The objectives of the present study were to determine the role of TS on lung response to CS exposure and the underlying mechanism(s). Male Fischer 344 rats were exposed by inhalation to air, CS (15 mg/m3, 6 h/day, 5 days), TS (80 mg/m3, 3 h/day, twice weekly, 6 months), or CS (15 mg/m3, 6 h/day, 5 days) followed by TS (80 mg/m3, 3 h/day, twice weekly, 6 months). The rats were euthanized 6 months and 3 weeks following initiation of the first exposure and the lung response was assessed. Silica exposure resulted in significant lung toxicity as evidenced by lung histological changes, enhanced neutrophil infiltration, increased lactate dehydrogenase levels, enhanced oxidant production, and increased cytokine levels. The TS exposure alone had only a minimal effect on these toxicity parameters. However, the combined exposure to TS and CS exacerbated the lung response, compared with TS or CS exposure alone. Global gene expression changes in the lungs correlated with the lung toxicity severity. Bioinformatic analysis of the gene expression data demonstrated significant enrichment in functions, pathways, and networks relevant to the response to CS exposure which correlated with the lung toxicity detected. Collectively our data demonstrated an exacerbation of CS-induced lung toxicity by TS exposure and the molecular mechanisms underlying the exacerbated toxicity.
Development of High-Resolution DNA Melting Analysis for Simultaneous Detection of Potato Mop-Top Virus and Its Vector, Spongospora subterranea, in Soil
Authors: Nie Xianzhou , Singh Mathuresh , Chen Dahu , Gilchrist Cassandra , Soqrat Yasmine , Shukla Manisha , Creelman Alexa , Dickison Virginia , Nie Bihua , Lavoie Jacques , Bisht Vikram
Published: September 2020

In this study, a set of duplex reverse transcription PCR (RT-PCR)–mediated high-resolution DNA melting (HRM) analyses for simultaneous detection of potato mop-virus (PMTV) and its protist vector, Spongospora subterranea f. sp. subterranea (Sss), was developed. The infestation of soil by PMTV was detected with a tobacco-based baiting system. Total RNA extracted from the soil led to successful RT-PCR gel electrophoresis detection of both PMTV and Sss. To facilitate more efficient detection, newly designed primer pairs for PMTV RNA species (i.e., RNA-Rep, RNA-CP, and RNA-TGB) were analyzed together with the existing Sss primers via real-time RT-PCR. The resulting amplicons exhibited melting profiles that could be readily differentiated. Under duplex RT-PCR format, all PMTV and Sss primer combinations led to successful detection of respective PMTV RNA species and Sss in the samples by HRM analyses. When the duplex HRM assay was applied to soil samples collected from six fields at four different sites in New Brunswick, Canada, positive detection of PMTV or Sss was found in 63 to 100% samples collected from fields in which PMTV-infected tubers had been observed. In contrast, the samples from fields where neither PMTV- nor Sss-infected tubers had been observed resulted in negative detection by the assay. Bait tobacco bioassay for PMTV and Sss produced similar results. Of the soil samples collected from PMTV-infested fields, 63 to 83% and 100% led to PMTV and Sss infections in the bait tobacco plants, respectively, whereas no PMTV- or Sss-infected plants were obtained from soil samples collected from PMTV- and Sss-free fields.
Imaging of the Ribs: From A to BX
Authors: Chadwick Nicholson S. , Hoover Kevin , Haar Peter J. , Hayes Curtis W.
Published: September 2020

The ribs are evaluated by radiologists of all subspecialties. A recent informal review of intradepartmental consults by the musculoskeletal radiology section at our institution revealed that approximately 20% of all queries involved the ribs. To educate radiologists further, an organized review of the rib in medical imaging was performed. The aims of this article are to expose radiologists to important clinical conditions in which the rib can be involved and to provide essential information to guide diagnosis and management. In the event that biopsy is indicated, we characterize three types of lesions and provide techniques for maximizing diagnostic yield.
A Novel Surgical Technique for the Management of Cerebrospinal Fluid Gusher Encountered During Cochlear Implantation
Authors: Tolisano Anthony M. , Wick Cameron C. , Kutz Joe Walter
Published: September 2020

Cerebrospinal fluid (CSF) gusher encountered during cochlear implantation are most commonly encountered in the setting of an inner ear abnormality. Repair of the gusher is essential to prevent CSF egress postoperatively and to decrease the risk of meningitis. Various methods to repair a CSF gusher have been described, including tight packing of the cochleostomy with fascia, lumbar drainage, and Eustachian tube packing with ear canal overclosure. We describe a novel and simple technique using a fascia ring placed around the cochlear implantation electrode (Cochlear Corporation, CI522) as a means to treat CSF gusher. The fascia is slid down the electrode after insertion, allowing circumferential coverage of the defect. The following video will provide an overview of patients at risk for CSF gusher and demonstrate the technique described above.

SDC video link: http://links.lww.com/MAO/B52.
Role of Nurse Practitioners in Caring for Patients With Complex Health Needs
Authors: Fraze Taressa K. , Briggs Adam D.M. , Whitcomb Elizabeth K. , Peck Kristen A. , Meara Ellen
Published: September 2020

Objective:

The objective of this study was to estimate trends in the percentage of Medicare beneficiaries cared for by nurse practitioners from 2012 to 2017, to characterize beneficiaries cared for by nurse practitioners in 2017, and to examine how the percentage of beneficiaries cared for by nurse practitioners varies by practice characteristics.

Design:

An observational study of 2012–2017 Medicare fee-for-service beneficiaries’ ambulatory visits. We computed the percentage of beneficiaries with 1 or more ambulatory visits from nurse practitioners and the percentage of beneficiaries receiving the plurality of their ambulatory visits from a nurse practitioner versus a physician (ie, predominant provider). We compared beneficiary demographics, clinical characteristics, and utilization by the predominant provider. We then characterized the predominant provider by practice characteristics.

Key Results:

In 2017, 28.9% of beneficiaries received any care from a nurse practitioner and 8.0% utilized nurse practitioners as their predominant provider—an increase from 4.4% in 2012. Among beneficiaries cared for by nurse practitioners in 2017, 25.9% had 3 or more chronic conditions compared with 20.8% of those cared for by physicians. Beneficiaries cared for in practices owned by health systems were more likely to have a nurse practitioner as their predominant provider compared with those attending practices that were independently owned (9.3% vs. 7.0%).

Conclusions:

Nurse practitioners are caring for Medicare beneficiaries with complex needs at rates that match or exceed their physician colleagues. The growing role of nurse practitioners, especially in health care systems, warrants attention as organizations embark on payment and delivery reform.
Learning by Doing: Design and Evaluation of a Quality Improvement Curriculum for Pediatric Hospitalists
Authors: Szymusiak John , McCormick Andrew
Published: September 2020

Introduction:

Quality improvement (QI) is a core competency for Pediatric Hospital Medicine (PHM) and required for maintenance of certification, but many hospitalists lack QI training. This project set out to increase a PHM faculty’s QI knowledge and comfort participating in QI projects, while concurrently applying the skills learned to a QI project in the hospital.

Methods:

We designed a 4-session curriculum utilizing principles of adult learning. Faculty immediately applied learned concepts to a QI project to increase the percentage of patients who were seen by an attending and billed for on the same day as admission to the PHM service. Attitudinal data and scores on the validated Quality Improvement Knowledge Application Tool- Revised knowledge assessment were compared precurriculum and postcurriculum. A manifest content analysis was carried out for qualitative questions.

Results:

Twenty faculty (83%) completed the preassessment; 15 (63%) completed the postassessment. Respondents showed statistically significant improvements in their perceived ability to participate in QI projects and their Quality Improvement Knowledge Application Tool- Revised scores. The group completed a QI project that increased revenue for the division. Faculty appreciated that the curriculum was applied to a real QI project and felt they would use the new skills in their daily practice.

Discussion:

This curricular model based on adult learning theory, with immediate application to a real QI project, conclusively showed attitudinal, knowledge-based, and hospital system-level improvements, and was well received by faculty.
Feasibility of Integrating Canine Olfaction with Chemical and Microbial Profiling of Urine to Detect Lethal Prostate Cancer
Authors: Guest Claire , Harris Rob , Sfanos Karen S. , Shrestha Eva , Partin Alan W. , Trock Bruce , Mangold Leslie , Bader Rebecca , Kozak Adam , Mclean Scott , Simons Jonathan , Soule Howard , Johnson Thomas , Lee Wen-Yee , Gao Qin , Aziz Sophie , Stathatou Patritsia , Thaler Stephen , Foster Simmie , Mershin Andreas
Published: September 2020

Prostate cancer is the second leading cause of cancer death in men in the developed world. A more sensitive and specific detection strategy for lethal prostate cancer beyond serum prostate specific antigen (PSA) population screening is urgently needed. Diagnosis by canine olfaction, using dogs trained to detect cancer by smell, has been shown to be both specific and sensitive. While dogs themselves are impractical as scalable diagnostic sensors, machine olfaction for cancer detection is testable. However, studies bridging the divide between clinical diagnostic techniques, artificial intelligence, and molecular analysis remains difficult due to the significant divide between these disciplines. We tested the clinical feasibility of a cross-disciplinary, integrative approach to early prostate cancer biosensing in urine using trained canine olfaction, volatile organic compound (VOC) analysis by gas chromatography-mass spectroscopy (GC-MS) artificial neural network (ANN)-assisted examination, and microbial profiling in a double-blinded pilot study. Two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. Biopsy-negative controls were used to assess canine specificity as prostate cancer biodetectors. Urine samples were simultaneously analyzed for their VOC content in headspace via GC-MS and urinary microbiota content via 16S rDNA Illumina sequencing. In addition, the dogs’ diagnoses were used to train an ANN to detect significant peaks in the GC-MS data. The canine olfaction system was 71% sensitive and between 70-76% specific at detecting Gleason 9 prostate cancer. We have also confirmed VOC differences by GC-MS and microbiota differences by 16S rDNA sequencing between cancer positive and biopsy-negative controls. Furthermore, the trained ANN identified regions of interest in the GC-MS data, informed by the canine diagnoses. Methodology and feasibility are established to inform larger-scale studies using canine olfaction, urinary VOCs, and urinary microbiota profiling to develop machine olfaction diagnostic tools. Scalable multi-disciplinary tools may then be compared to PSA screening for earlier, non-invasive, more specific and sensitive detection of clinically aggressive prostate cancers in urine samples.
High-throughput discovery and characterization of human transcriptional effectors
Authors: Tycko Josh , DelRosso Nicole , Hess Gaelen T. , Aradhana  , Banerjee Abhimanyu , Mukund Aditya , Van Mike V. , Ego Braeden K. , Yao David , Spees Kaitlyn , Suzuki Peter , Marinov Georgi K. , Kundaje Anshul , Bassik Michael C. , Bintu Lacramioara
Published: September 2020

Thousands of proteins localize to the nucleus; however, it remains unclear which contain transcriptional effectors. Here, we develop HT-recruit - a pooled assay where protein libraries are recruited to a reporter, and their transcriptional effects are measured by sequencing. Using this approach, we measure gene silencing and activation for thousands of domains. We find a relationship between repressor function and evolutionary age for the KRAB domains, discover Homeodomain repressor strength is collinear withHoxgenetic organization, and identify activities for several Domains of Unknown Function. Deep mutational scanning of the CRISPRi KRAB maps the co-repressor binding surface and identifies substitutions that improve stability/silencing. By tiling 238 proteins, we find repressors as short as 10 amino acids. Finally, we report new activator domains, including a divergent KRAB. Together, these results provide a resource of 600 human proteins containing effectors and demonstrate a scalable strategy for assigning functions to protein domains.
Evolution of kinase polypharmacology across HSP90 drug discovery
Authors: Antolin Albert A. , Clarke Paul A. , Collins Ian , Workman Paul , Al-Lazikani Bissan
Published: September 2020

Most small molecules interact with several target proteins but this polypharmacology is seldom comprehensively investigated or explicitly exploited during drug discovery. Here, we use computational and experimental methods to systematically characterize the kinase cross-pharmacology of representative HSP90 inhibitors. We demonstrate that the resorcinol clinical candidates ganetespib and, to a lesser extent, luminespib, display unique off-target kinase pharmacology as compared to other HSP90 inhibitors. We also demonstrate that polypharmacology evolved during the optimisation to discover luminespib and that the hit, leads and clinical candidate all have different polypharmacological profiles. We conclude that the submicromolar target inhibition of protein kinases by ganetespib may have potential clinical significance and we recommend the computational and experimental characterization of polypharmacology earlier in drug discovery projects to unlock new multi-target drug design opportunities.
Does offspring demand affect parental life-history trade-offs?
Authors: Mäenpää M.I. , Smiseth P.T.
Published: September 2020

Life-history trade-offs between the number and size of offspring produced, and the costs of reproduction on future reproduction and survival can all be affected by different levels of parental effort. Because of these trade-offs the parents and the offspring have different optima for the amount of care given to the current brood, which leads to a conflict between parents and offspring. The offspring, as well as the parents, have the ability to affect parental effort, and thus changes in offspring traits have the potential to cause reproductive costs on the parents. Here, we used a repeated cross-fostering design to manipulate offspring demand during juvenile development in the burying beetleNicrophorus vespilloidesto examine whether responding to offspring begging incurs reproductive costs to the parent. After a manipulated first reproductive event, we gave each experimental female, that had been exposed to different levels of offspring demand, a chance to breed again, and monitored their survival. We found that larval demand influences the trade-off between the size and number of offspring produced, but has no impact on the reproductive costs through future reproduction or survival of the parent. The parents do, however, pay an overall fecundity cost for the general success of their first broods, but this cost was not related to the changes in the levels of larval begging. Other traits, including survival showed no costs of reproduction. Survival and the number of larvae successfully raised in the second broods correlated positively, indicating differences in the individual quality of the parents.
Glycosyltransferase POMGNT1 deficiency affects N-cadherin-mediated cell-cell adhesion
Authors: Noor Sina Ibne , Hoffmann Marcus , Rinis Natalie , Bartels Markus F. , Winterhalter Patrick , Hoelscher Christina , Hennig René , Himmelreich Nastassja , Thiel Christian , Ruppert Thomas , Rapp Erdmann , Strahl Sabine
Published: September 2020

Defects in proteinO-mannosylation lead to severe congenital muscular dystrophies known as α-dystroglycanopathy. A hallmark of these diseases is the loss of theO-mannose-bound matriglycan on α-dystroglycan, which leads to a reduction in cell adhesion to the extracellular matrix. Mutations in proteinO-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1), which is crucial for the elongation ofO-mannosyl glycans, are mainly associated with muscle-eye-brain (MEB) disease. In addition to defects in cell-extracellular matrix adhesion, aberrant cell-cell adhesion has occasionally been observed in response to defects in POMGNT1. However, direct molecular mechanisms are largely unknown. We used POMGNT1 knock-out HEK293T cells and fibroblasts from a MEB patient to gain a deeper insight into the molecular changes in POMGNT1 deficiency. A combination of biochemical and molecular biological techniques with proteomics, glycoproteomics and glycomics revealed that a lack of POMGNT1 activity strengthens cell-cell adhesion. We demonstrate that the altered intrinsic adhesion properties are due to an increased abundance of N-cadherin (N-Cdh). In addition, site-specific changes in theN-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions. We found that in POMGNT1 deficient cells ERK1/2 and p38 signaling pathways are activated and transcriptional changes that are comparable to the epithelial-mesenchymal transition (EMT) are triggered, defining a possible molecular mechanism underlying the observed phenotype. Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general, and suggests a previously underestimated impact of changes inO-mannosylation onN-glycosylation.