bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDK-Mediator and FBXL19 prime developmental genes for activation by promoting atypical regulatory interactions
Authors: Feldmann Angelika , Dimitrova Emilia , Kenney Alexander , Lastuvkova Anna , Klose Robert J 
Published: January 2020

Abstract
Appropriate developmental gene regulation relies on the capacity of gene promoters to integrate inputs from distal regulatory elements, yet how this is achieved remains poorly understood. In embryonic stem cells (ESCs), a subset of silent developmental gene promoters are primed for activation by FBXL19, a CpG island binding protein, through its capacity to recruit CDK-Mediator. How mechanistically these proteins function together to prime genes for activation during differentiation is unknown. Here we discover that in mouse ESCs FBXL19 and CDK-Mediator support long-range interactions between silent gene promoters that rely on FBXL19 for their induction during differentiation and gene regulatory elements. During gene induction, these distal regulatory elements behave in an atypical manner, in that the majority do not acquire histone H3 lysine 27 acetylation and no longer interact with their target gene promoter following gene activation. Despite these atypical features, we demonstrate by targeted deletions that these distal elements are required for appropriate gene induction during differentiation. Together these discoveries demonstrate that CpG-island associated gene promoters can prime genes for activation by communicating with atypical distal gene regulatory elements to achieve appropriate gene expression.
Germline cancer predisposition variants and pediatric glioma: a population-based study in California
Authors: Muskens Ivo S , de Smith Adam J , Zhang Chenan , Hansen Helen M , Morimoto Libby , Metayer Catherine , Ma Xiaomei , Walsh Kyle M , Wiemels Joseph L 
Published: January 2020

AbstractBackgroundPediatric astrocytoma constitutes a majority of malignant pediatric brain tumors. Previous studies that investigated pediatric cancer predisposition have primarily been conducted in tertiary referral centers and focused on cancer predisposition genes. In this study, we investigated the contribution of rare germline variants to risk of malignant pediatric astrocytoma on a population level.MethodsDNA samples were extracted from neonatal dried bloodspots from 280 pediatric astrocytoma patients (predominantly high grade) born and diagnosed in California and were subjected to whole-exome sequencing. Sequencing data were analyzed using agnostic exome-wide gene-burden testing and variant identification for putatively pathogenic variants in 175 a priori candidate cancer-predisposition genes.ResultsWe identified 33 putatively pathogenic germline variants among 31 patients (11.1%) which were located in 24 genes largely involved in DNA repair and cell cycle control. Patients with pediatric glioblastoma were most likely to harbor putatively pathogenic germline variants (14.3%, N = 9/63). Five variants were located in tumor protein 53 (TP53), of which 4 were identified among patients with glioblastoma (6.3%, N = 4/63). The next most frequently mutated gene was neurofibromatosis 1 (NF1), in which putatively pathogenic variants were identified in 4 patients with astrocytoma not otherwise specified. Gene-burden testing also revealed that putatively pathogenic variants in TP53 were significantly associated with pediatric glioblastoma on an exome-wide level (odds ratio, 32.8, P = 8.04 × 10−7).ConclusionA considerable fraction of pediatric glioma patients, especially those of higher grade, harbor a putatively pathogenic variant in a cancer predisposition gene. Some of these variants may be clinically actionable or may warrant genetic counseling.
Patterns of Care and Age-Specific Impact of Extent of Resection and Adjuvant Radiotherapy in Pediatric Pineoblastoma
Authors: Jin Michael C , Prolo Laura M , Wu Adela , Azad Tej D , Shi Siyu , Rodrigues Adrian J , Soltys Scott G , Pollom Erqi L , Li Gordon , Hiniker Susan M , Grant Gerald A 
Published: January 2020

Abstract

BACKGROUND
Pediatric pineoblastomas are highly aggressive tumors that portend poor outcomes despite multimodal management. Controversy remains regarding optimal disease management.

OBJECTIVE
To evaluate patterns of care and optimal clinical management of pediatric pineoblastoma.

METHODS
A total of 211 pediatric (age 0-17 yr) histologically confirmed pineoblastoma patients diagnosed between 2004 and 2015 were queried from the National Cancer Database. Wilcoxon rank-sum statistics and chi-squared analyses were used to compare continuous and categorical variables, respectively. Univariable and multivariable Cox regressions were used to evaluate prognostic impact of covariates. Propensity-score matching was used to balance baseline characteristics.

RESULTS
Older patients (age ≥ 4 yr) experienced improved overall survival compared to younger patients (age < 4 yr) (hazard ratio [HR] = 0.41; 95% CI 0.25-0.66). Older patients (adjusted odds ratio [aOR] = 5.21; 95% CI 2.61-10.78) and those residing in high-income regions (aOR = 3.16; 95% CI 1.21-8.61) received radiotherapy more frequently. Radiotherapy was independently associated with improved survival in older (adjusted HR [aHR] = 0.31; 95% CI 0.12-0.87) but not younger (aHR = 0.64; 95% CI 0.20-1.90) patients. The benefits of radiotherapy were more pronounced in patients receiving surgery than in those not receiving surgery (aHR [surgical patients] = 0.23; 95% CI 0.08-0.65; aHR [nonsurgical patients] = 0.46; 95% CI 0.22-0.97). Older patients experienced improved outcomes associated with aggressive resection (P = .041); extent of resection was not associated with survival in younger patients (P = .880).

CONCLUSION
Aggressive tumor resection was associated with improved survival only in older pediatric patients. Radiotherapy was more effective in patients receiving surgery. Age-stratified approaches might allow for improved disease management of pediatric pineoblastoma.
Adult Social Environments and the Use of Combustible and Electronic Cigarettes: Opportunities for Reducing Smoking in the 30s
Authors: Kosterman Rick , Epstein Marina , Bailey Jennifer A , Oesterle Sabrina , Furlong Madeline , Hawkins J David 
Published: January 2020

Abstract

Introduction
Reducing cigarette use is a major public health goal in the United States. Questions remain, however, about the potential for the social environment in the adult years—particularly in the 30s and beyond—to influence cigarette use. This study tested pathways hypothesized by the social development model to understand the extent to which social environmental factors at age 33 (eg, involvement with smokers or with physically active people) contribute to changes in cigarette use from age 30 to age 39. Both combustible and electronic cigarette use were investigated.

Methods
Data were from the Seattle Social Development Project, a longitudinal study of 808 diverse participants with high retention. Self-reports assessed social developmental constructs, combustible and electronic cigarette use, and demographic measures across survey waves.

Results
At age 30, 32% of the sample reported past-month cigarette use. Using structural equation modeling, results showed high stability in cigarette use from age 30 to 39. After accounting for this stability, cigarette-using social environments at age 33 predicted personal beliefs or norms about smoking (eg, acceptability and social costs), which in turn predicted combustible cigarette use at age 39. Cigarette-using environments, however, directly predicted electronic cigarette use at age 39, with no significant role for beliefs about smoking.

Conclusions
Cigarette use was highly stable across the 30s, but social environmental factors provided significant partial mediation of this stability. Pathways were different for combustible and electronic cigarette use, however, with personal smoking norms playing an important role for the former but not the latter.

Implications
This study addresses the need for longitudinal investigation of social mechanisms and cigarette use in the 30s. Findings reinforce efforts to prevent the uptake of cigarettes prior to the 30s because, once started, smoking is highly stable. But social environmental factors remain viable intervention targets in the 30s to disrupt this stability. Addressing personal norms about smoking’s acceptability and social costs is likely a promising approach for combustible cigarette use. Electronic cigarettes, however, present a new challenge in that many perceived social costs of cigarette use do not readily translate to this relatively recent technology.
The Use of a Novel Perfusion-Based Human Cadaveric Model for Simulation of Dural Venous Sinus Injury and Repair
Authors: Strickland Ben A , Ravina Kristine , Kammen Alexandra , Chang Stephanie , Rutkowski Martin , Donoho Daniel A , Minneti Mike , Jackanich Anna , Bakhsheshian Joshua , Zada Gabriel 
Published: January 2020

Abstract

BACKGROUND
Dural sinus injuries are potentially serious complications associated with acute blood loss. It is imperative that neurosurgery trainees are able to recognize and manage this challenging scenario.

OBJECTIVE
To assess the feasibility of a novel perfusion-based cadaveric simulation model to provide the fundamentals of dural sinus repair to neurosurgical trainees.

METHODS
A total of 10 perfusion-based human cadaveric models underwent superior sagittal sinus (SSS) laceration. Neurosurgery residents were instructed to achieve hemostasis by any method in the first trial and then repeated the trial after watching the instructional dural flap technique video. Trials were timed until hemostasis and control of the region of injury was achieved. Pre- and post-trial questionnaires were administered to assess trainee confidence levels.

RESULTS
The high-flow extravasation of the perfusion-based cadaveric model mimicked similar conditions and challenges encountered during acute SSS injury. Mean ± standard deviation time to hemostasis was 341.3 ± 65 s in the first trial and 196.9 ± 41.8 s in the second trial (P < .0001). Mean trainee improvement time was 144.4 s (42.3%). Of the least-experienced trainees with longest repair times in the initial trial, a mean improvement time of 188.3 s (44.8%) was recorded. All participants reported increased confidence on post-trial questionnaires following the simulation (median pretrial confidence of 2 vs post-trial confidence of 4, P = .002).

CONCLUSION
A perfusion-based human cadaveric model accurately simulates acute dural venous sinus injury, affording neurosurgical trainees the opportunity to hone management skills in a simulated and realistic environment.
Prospective observational study to evaluate the use of musculoskeletal ultrasonography in rheumatoid arthritis management: the ECHO study
Authors: Stein Michael , Vaillancourt Julie , Rampakakis Emmanouil , Sampalis John S 
Published: January 2020

Abstract

Objectives
Since the creation of the Canadian Rheumatology Ultrasonography Society, an increasing number of rheumatologists has been trained in the use of musculoskeletal US (MSUS). We compared the effectiveness of MSUS to routine care (RC) as a disease management tool in patients with moderate-to-severe RA requiring a treatment change due to lack of efficacy. The predictive value of MSUS was also assessed.

Methods
This was a prospective, two-cohort, quasi-experimental study. Patients were managed either with MSUS (within the Canadian Rheumatology Ultrasonography Society) or as per RC for up to 1 year. Main outcomes included Clinical Disease Activity Index low disease activity/remission, DAS28 low disease activity/remission, MSUS scores, patient satisfaction and perception of participation in disease management.

Results
A total of 383 patients were enrolled (MSUS: n = 171; RC: n = 212). At baseline, a greater proportion of MSUS patients were treated with a biologic DMARD (50.3 vs 36.8%; P = 0.008) while more patients treated per RC received a non-biologic DMARD (84.2 vs 91.5%; P = 0.027). During follow-up, a greater number of RA treatment modifications was applied in the MSUS group compared with RC [adjusted incidence rate ratio (95% CI): 1.4 (1.1, 1.8)], including steroids, non-biologic DMARDs and biologic DMARDs. Regarding clinical and patient-reported outcomes, no remarkable differences were observed between groups. However, throughout the study, 50–80% of MSUS patients in clinical remission has a MSUS synovitis score of ≥1, and 37–73% an erosion score of ≥1. Significant associations were observed between baseline synovitis and joint erosion during follow-up.

Conclusion
MSUS assessments can be useful in detecting subclinical levels of inflammation and predicting future joint deterioration, thus allowing optimization of RA treatment and patient care.
Public health in genetic spaces: a statistical framework to optimize cluster-based outbreak detection
Authors: Chato Connor , Kalish Marcia L , Poon Art F Y 
Published: January 2020

Abstract
Genetic clustering is a popular method for characterizing variation in transmission rates for rapidly evolving viruses, and could potentially be used to detect outbreaks in ‘near real time’. However, the statistical properties of clustering are poorly understood in this context, and there are no objective guidelines for setting clustering criteria. Here, we develop a new statistical framework to optimize a genetic clustering method based on the ability to forecast new cases. We analysed the pairwise Tamura-Nei (TN93) genetic distances for anonymized HIV-1 subtype B pol sequences from Seattle (n = 1,653) and Middle Tennessee, USA (n = 2,779), and northern Alberta, Canada (n = 809). Under varying TN93 thresholds, we fit two models to the distributions of new cases relative to clusters of known cases: 1, a null model that assumes cluster growth is strictly proportional to cluster size, i.e. no variation in transmission rates among individuals; and 2, a weighted model that incorporates individual-level covariates, such as recency of diagnosis. The optimal threshold maximizes the difference in information loss between models, where covariates are used most effectively. Optimal TN93 thresholds varied substantially between data sets, e.g. 0.0104 in Alberta and 0.016 in Seattle and Tennessee, such that the optimum for one population would potentially misdirect prevention efforts in another. For a given population, the range of thresholds where the weighted model conferred greater predictive accuracy tended to be narrow (±0.005 units), and the optimal threshold tended to be stable over time. Our framework also indicated that variation in the recency of HIV diagnosis among clusters was significantly more predictive of new cases than sample collection dates (ΔAIC &gt; 50). These results suggest that one cannot rely on historical precedence or convention to configure genetic clustering methods for public health applications, especially when translating methods between settings of low-level and generalized epidemics. Our framework not only enables investigators to calibrate a clustering method to a specific public health setting, but also provides a variable selection procedure to evaluate different predictive models of cluster growth.
Evolution of ecological structure of anole communities in tropical rain forests from north-western South America
Authors: Moreno-Arias Rafael A , Bloor Paul , Calderón-Espinosa Martha L 
Published: January 2020

AbstractThe coexistence of several anoles in the same place is attributed to differential partitioning of resources. Although several mainland and island communities show a similar structure, differences in life-history traits, absence of niche complementarity, higher food supply and higher numbers of predators in mainland environments support the idea that predation, rather than competition, is a more important structuring force in mainland than in island anole communities. To analyse the pattern of ecological structure in mainland anole communities, we studied communities in three tropical rain forests of north-western South America to obtain data about the use of resources on three niche axes [spatial, thermal and morphological (as a proxy of diet)] for 17 species of anoles. We analysed the patterns of niche overlap for each axis and found that overlap on the dietary axis was less than the overlap on the other axes, indicating that species using similar spatial or thermal resources diverge strongly in their diet. In addition, we identified a niche complementarity among niche axes, suggesting that intraspecific competition is also an important process in those communities. Finally, this study revealed a similar ecological structure in different communities of mainland rain-forest anoles, which share seven ecomorphs, suggesting ecological adaptation and convergence in mainland anoles.
Motor cortex beta oscillations reflect motor skill learning ability after stroke
Authors: Espenhahn Svenja , Rossiter Holly E , van Wijk Bernadette CM , Redman Nell , Rondina Jane M , Diedrichsen Joern , Ward Nick S 
Published: January 2020

AbstractRecovery of skilled movement after stroke is assumed to depend on motor learning. However, the capacity for motor learning and factors that influence motor learning after stroke have received little attention. In this study we firstly compared motor skill acquisition and retention between well-recovered stroke patients and age- and performance-matched healthy controls. We then tested whether beta oscillations (15–30Hz) from sensorimotor cortices contribute to predicting training-related motor performance.Eighteen well-recovered chronic stroke survivors (mean age 64±8 years, range 50–74 years) and twenty age- and sex-matched healthy controls were trained on a continuous tracking task and subsequently retested after initial training (45–60 min and 24 hours later). Scalp EEG was recorded during the performance of a simple motor task before each training and retest session. Stroke patients demonstrated capacity for motor skill learning, but it was diminished compared to age- and performance-matched healthy controls. Further, although the properties of beta oscillations prior to training were comparable between stroke patients and healthy controls, stroke patients did show less change in beta measures with motor learning. Lastly, although beta oscillations did not help to predict motor performance immediately after training, contralateral (ipsilesional) sensorimotor cortex post-movement beta rebound (PMBR) measured after training helped predict future motor performance, 24 hours after training. This finding suggests that neurophysiological measures such as beta oscillations can help predict response to motor training in chronic stroke patients and may offer novel targets for therapeutic interventions.
Succinate can shuttle reducing power from the hypoxic retina to the O2-rich pigment epithelium
Authors: Bisbach Celia M. , Hass Daniel T. , Robbings Brian M. , Rountree Austin M. , Sadilek Martin , Sweet Ian R. , Hurley James B. 
Published: January 2020

AbstractWhen O2is plentiful, the mitochondrial electron transport chain uses it as a terminal electron acceptor. However, the mammalian retina thrives within a hypoxic niche in the eye. We find that mitochondria in retinas adapt to their hypoxic environment by relying on the “reverse” succinate dehydrogenase reaction, where fumarate accepts electrons instead of O2. Reverse succinate dehydrogenase activity produces succinate and is enhanced by down-regulation of cytochrome oxidase subunits. Retinas can export the succinate to the neighboring retinal pigment epithelium/choroid complex. There, succinate stimulates O2consumption several fold and enhances synthesis and release of malate. Malate released from the pigment epithelium can be imported into the retina, where it is converted to fumarate and again used to accept electrons in the reverse succinate dehydrogenase reaction. Our findings show how a malate/succinate shuttle can sustain these two tissues by transferring reducing power from an O2-poor tissue (retina) to an O2-rich one (retinal pigment epithelium/choroid).
Graph biased feature selection of genes is better than random for many genes
Authors: Crawford Jake , Greene Casey S. 
Published: January 2020

AbstractRecent work suggests that gene expression dependencies can be predicted almost as well by using random networks as by using experimentally derived interaction networks. We hypothesize that this effect is highly variable across genes, as useful and robust experimental evidence exists for some genes but not others. To explore this variation, we take thek-core decomposition of the STRING network, and compare it to a degree-matched random model. We show that when low-degree nodes are removed, expression dependencies in the remaining genes can be predicted better by the resulting network than by the random model.
Ancient BED-domain-containing immune receptor from wild barley confers widely effective resistance to leaf rust
Authors: Chen Chunhong , Clark Bethany , Martin Matthew , Matny Oadi , Steffenson Brian J , Franckowiak Jerome D , Mascher Martin , Singh Davinder , Perovic Dragan , Richardson Terese , Periyannan Sambasivam , Lagudah Evans S , Park Robert F , Dracatos Peter M 
Published: January 2020

AbstractLeaf rust, caused byPuccinia hordeiis a devastating fungal disease affecting barley (Hordeum vulgaresubsp.vulgare) production globally. Race-specific resistance (R) genes have been deployed widely; however, their durability is often compromised due to the rapid emergence of virulentP. hordeiraces, prompting the search for new sources of broad-spectrum resistance. Here we report on the cloning ofRph15, a broadly effective resistance gene derived from the wild progenitorHordeum vulgaresubsp.spontaneum. We demonstrate using introgression mapping, mutation and complementation thatRph15encodes a coiled-coil nucleotide-binding leucine-rich repeat (NLR) protein with an integrated Zinc-finger BED (ZF-BED) domain. The allelic variation at theRph15locus was assessed using barley exome capture data that traced its origin to the western region of the Fertile Crescent bordering Jordan and Israel. To unravel the genetic relationship of two other leaf rust resistance genes (Rph14andRph16) mapped at similar locus on chromosome 2H, we re-sequenced theRph15gene from the near-isogenic line forRph15(Bowman+Rph15) and the two donor accessions ofRph14(PI 584760) andRph16, (PI 405292, Hs 680). Both whole genome and Sanger sequencing confirmed that Hs 680 carriedRph15, whileRph14in PI 584760 was an independent locus. A perfect diagnostic KASP marker was developed and validated to permit efficient introduction ofRph15into cultivated barley.