bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oleoresin defenses in conifers: chemical diversity, terpene synthases and limitations of oleoresin defense under climate change
Authors: Celedon Jose M. , Bohlmann Jörg 
Published: June 2019

SummaryConifers have evolved complex oleoresin terpene defenses against herbivores and pathogens. In co‐evolved bark beetles, conifer terpenes also serve chemo‐ecological functions as pheromone precursors, chemical barcodes for host identification, or nutrients for insect‐associated microbiomes. We highlight the genomic, molecular and biochemical underpinnings of the large chemical space of conifer oleoresin terpenes and volatiles. Conifer terpenes are predominantly the products of the conifer terpene synthase (TPS) gene family. Terpene diversity is increased by cytochromes P450 of the CYP720B class. Many conifer TPS are multiproduct enzymes. Multisubstrate CYP720B enzymes catalyse multistep oxidations. We summarise known terpenoid gene functions in various different conifer species with reference to the annotated terpenoid gene space in a spruce genome. Overall, biosynthesis of terpene diversity in conifers is achieved through a system of biochemical radiation and metabolic grids. Expression of TPS and CYP720B genes can be specific to individual cell types of constitutive or traumatic resin duct systems. Induced terpenoid transcriptomes in resin duct cells lead to dynamic changes of terpene composition and quantity to fend off herbivores and pathogens. While terpenoid defenses have contributed much to the evolutionary success of conifers, under new conditions of climate change, these defences may become inconsequential against range‐expanding forest pests.
Oral cancer‐associated fibroblasts predict poor survival: Systematic review and meta‐analysis
Authors: Graizel Diana , Zlotogorski‐Hurvitz Ayelet , Tsesis Igor , Rosen Eyal , Kedem Ron , Vered Marilena 
Published: June 2019

AbstractObjectivesTo perform systematic review and meta‐analysis on correlations between cancer‐associated fibroblasts (CAFs) and the risk of death for patients with oral squamous cell carcinoma.Subjects and methodsEnglish literature (1966–2018) was systematically analyzed for studies that immunohistochemically assessed CAF density by alpha‐smooth muscle actin and presented 5 year survival rates by Kaplan–Meier plots. Mean age of patients, proportion of male/female patients, and male/female majority (>50% male/female patients) per study were also collected. Significance level for statistical models was p < 0.05.ResultsMeta‐analysis comprised 11 studies/1,040 patients. Univariate Cox regressions showed that high CAF density was a negative prognostic factor in studies with female and male majority [OR 5.329 (95% CI 3.223–8.811), p < 0.001, and OR 2.208 (95% CI 1.717–2.839), p < 0.001, respectively]. High CAF density with male majority was associated with a more favorable prognosis [OR 0.996 (95% CI 0.979–1.013), p < 0.001]. Multivariate Cox regressions showed that death risk was significantly higher among patients with high CAF density compared to low CAF [OR 2.741 (95% CI 2.220–3.384) p < 0.001]. High mean age and male proportion were significantly protective [OR 0.940 (95% CI 0.925–9.955), p < 0.001, OR 0.125 (95% CI 0.018–0.867), p = 0.035), respectively].ConclusionsCAFs increased death risk, male majority, and higher mean age were protective. A clinically validated cutoff for CAF density could serve as a reliable prognostic tool.
Commotio cordis and L‐type calcium channel mutation: Is there a link?
Authors: Creta Antonio , Hanington Oliver , Lambiase Pier D. 
Published: June 2019

AbstractCommotio cordis is a rare phenomenon when ventricular fibrillation and sudden death occurs with a blunt, nonpenetrating blow to the chest. Individual susceptibility to commotio cordis has been demonstrated in swine models, and might be present in humans as well. We report a case of commotio cordis in an adolescent with a heterozygous mutation on the gene CACNA1C, encoding for an L‐type calcium channel expressed in the heart. This genetic mutation has been previously associated with a phenotype of long‐QT syndrome; however, this was not demonstrated in our patient despite extensive investigations. To the best of our knowledge, this is the first report of commotio cordis in which an ion‐channel gene mutation involved in repolarization abnormalities has been documented. This finding might corroborate the hypothesis that a genetic predisposition plays a role in the individual susceptibility to this rare cause of cardiac arrest.
Age Versus Socialization in Understanding Attitudes Toward Economic Reforms in China
Authors: Harmel Robert , Yeh Yao‐Yuan , Liu Xinsheng 
Published: June 2019

ObjectiveThe objective of this research is to address the roles of age and socialization in explanation for attitudes toward economic reforms in China.MethodUsing data from the China Survey 2008 and the China Governance and Policy Survey of 2016, this note reports age/cohort‐related differences in both abstract and concrete attitudes toward economic reforms, and addresses two competing (or complementary) explanations for those differences, one attributing differences to life cycle and the other attributing differences to the different environments within which Chinese adults were socialized.ResultsWhile socialization/generation explanations seem to apply for the more abstract “market reform would bring chaos” attitudes, an age/life‐cycle explanation alone seems sufficient to explain attitudes toward the more concrete subject of “privatization.”ConclusionConsistent with our literature‐based theoretical expectations, “life cycle” tends to explain more concrete attitudes while “socialization”—in early and/or lifelong forms—is a more potent explanation for abstract attitudes.
Comparison of automated vs manual analysis of corneal endothelial cell density and morphology in normal and corneal endothelial dystrophy‐affected dogs
Authors: Miyagi Hidetaka , Stanley Amelia A. , Chokshi Tanvi J. , Pasqualino Carina Y. , Hoehn Alyssa L. , Murphy Christopher J. , Thomasy Sara M. 
Published: June 2019

AbstractObjectiveTo determine the efficacy of automated imaging software of the Nidek ConfoScan 4 confocal biomicroscope at analyzing canine corneal endothelial cell density and morphology in health and disease, by comparing to a manual analysis method.Animal studiedNineteen eyes of 10 dogs were evaluated and include three Beagles, three Jack Russell Terriers, and four miscellaneous breeds. Twelve clinically normal and seven eyes affected with corneal endothelial dystrophy (CED) were scanned and analyzed.ProceduresEndothelial cell density (ECD), mean and standard deviation (SD) of cell area, percent polymegathism, mean and SD of the number of cell sides, and percent pleomorphism were calculated using automated and manual methods for each scan.ResultsThe automated analysis showed significantly greater ECD in comparison with the manual frame method due to misidentification of cell domains in CED‐affected dogs. No significant differences in ECD were observed between normal and CED‐affected dogs in automated analysis, while CED‐affected dogs showed significantly lower ECD in manual frame method and planimetry. Using both automated and manual methods, CED‐affected dogs showed greater variability of cell area or the number of cell sides than normal dogs.ConclusionThe automated imaging software is unable to accurately identify cell borders in CED‐affected dogs resulting in inaccurate estimates of ECD. Thus, manual analysis is recommended for use in clinical trials assessing adverse events associated with novel medical treatments and/or surgical procedures.
How CEO Wealth Affects the Riskiness of a Firm
Authors: Mandal Sonik , Swartz Charlie , Guha Sanjib , Jr. Carl B. McGowan 
Published: June 2019

The objective of this paper is to analyze the relationship between the ownership level of managers and the risk averse behavior of the firm. We measure the ownership level of the managers by the ratio of their ownership of the company relative to their total wealth for a sample of 69 individuals from the Forbes 400 list of the wealthiest individuals in the world for the period from 2001-11 using an unbalanced panel data analysis. The dependent variable is the Altman Z-score of each firm and we further test these relationships using financial leverage. The independent variables are delta and Vega of the option portfolio of the manager, R&D for the firm, total assets, the age of the manager, the tenure of the manager, stock holding of the manager, CEO/Chair duality of the manager and firma age. The Z-score is statistically significantly related to size, CEO age, CEO wealth, and duality. Financial leverage is not statistically significantly related to any of the independent variables.
Mantle earthquakes in the Himalayan collision zone
Authors: Schulte-Pelkum Vera , Monsalve Gaspar , Sheehan Anne F. , Shearer Peter , Wu Francis , Rajaure Sudhir 
Published: June 2019

AbstractEarthquakes are known to occur beneath southern Tibet at depths up to ∼95 km. Whether these earthquakes occur within the lower crust thickened in the Himalayan collision or in the mantle is a matter of current debate. Here we compare vertical travel paths expressed as delay times between S and P arrivals for local events to delay times of P-to-S conversions from the Moho in receiver functions. The method removes most of the uncertainty introduced in standard analysis from using velocity models for depth location and migration. We show that deep seismicity in southern Tibet is unequivocally located beneath the Moho in the mantle. Deep seismicity in continental lithosphere occurs under normally ductile conditions and has therefore garnered interest in whether its occurrence is due to particularly cold temperatures or whether other factors are causing embrittlement of ductile material. Eclogitization in the subducting Indian crust has been proposed as a cause for the deep seismicity in this area. Our observation of seismicity in the mantle, falling below rather than within the crustal layer with proposed eclogitization, requires revisiting this concept and favors other embrittlement mechanisms that operate within mantle material.
Serious infection risk in rheumatoid arthritis compared with non-inflammatory rheumatic and musculoskeletal diseases: a US national cohort study
Authors: Mehta Bella , Pedro Sofia , Ozen Gulsen , Kalil Andre , Wolfe Frederick , Mikuls Ted , Michaud Kaleb 
Published: June 2019

ObjectivesTo identify serious infection (SI) risk by aetiology and site in patients with rheumatoid arthritis (RA) compared with those with non-inflammatory rheumatic and musculoskeletal diseases (NIRMD).MethodsPatients participating in FORWARD from 2001 to 2016 were assessed for SIs; defined by infections requiring hospitalisation, intravenous antibiotics or followed by death. SIs were categorised by aetiology and site. SI risk was assessed through Cox proportional hazards models. Best models were selected using machine learning Least Absolute Shrinkage and Selection Operator (LASSO) methodology.ResultsAmong 20 361 patients with RA and 6176 patients with NIRMD, 1600 and 276 first SIs were identified, respectively. Incidence of SIs was higher in RA compared with NIRMD (IRR = 1.5; 95% CI 1.2 to 1.5). The risk persisted after adjusting using the LASSO model (HR 1.7; 95% CI 1.5 to 1.8), but attenuated when additionally adjusted for glucocorticoid use (HR 1.3; 95% CI 1.2 to 1.5). SI risk was significantly higher in RA versus NIRMD for bacterial infections as well as for respiratory, skin, bone, joint, bloodstream infections and sepsis irrespective of glucocorticoid use. Compared with NIRMD, SI risk was significantly increased in patients with RA who were in moderate and high disease activity but was similar to those in low disease activity/remission (p trend < 0.001).ConclusionsThe risk of all SIs, particularly bacterial, respiratory, bloodstream, sepsis, skin, bone and joint infections are significantly increased in patients with RA compared with patients with NIRMD. This infection risk appears to be greatest in those with higher RA disease activity.
A Generalized Parallel Task Model for Recurrent Real-Time Processes
Authors: Bonifaci Vincenzo , Wiese Andreas , Baruah Sanjoy K. , Marchetti-Spaccamela Alberto , Stiller Sebastian , Stougie Leen 
Published: June 2019

A model is considered for representing recurrent precedence-constrained tasks that are to execute on multiprocessor platforms. A recurrent task is specified as a directed acyclic graph (DAG), a period, and a relative deadline. Each vertex of the DAG represents a sequential job, while the edges of the DAG represent precedence constraints between these jobs. All the jobs of the DAG are released simultaneously and need to complete execution within the specified relative deadline of their release. Each task may release jobs in this manner an unbounded number of times, with successive releases occurring at least the specified period apart. Conditional control structures are also allowed. The scheduling problem is to determine whether a set of such recurrent tasks can be scheduled to always meet all deadlines upon a specified number of identical processors.
This problem is shown to be computationally intractable, but amenable to efficient approximate solutions. Earliest Deadline First (EDF) and Deadline Monotonic (DM) are shown to be good approximate global scheduling algorithms. Polynomial and pseudo-polynomial time schedulability tests, of differing effectiveness, are presented for determining whether a given task set can be scheduled by EDF or DM to always meet deadlines on a specified number of processors.
Periatrial Fat Quality Predicts Atrial Fibrillation Ablation Outcome
Authors: Ciuffo Luisa , Nguyen Hieu , Marques Mateus Diniz , Aronis Konstantinos N. , Sivasambu Bhradeev , de Vasconcelos Henrique D. , Tao Susumu , Spragg David D. , Marine Joseph E. , Berger Ronald D. , Lima Joao A.C. , Calkins Hugh , Ashikaga Hiroshi 
Published: June 2019

Background:
Previous studies showed that the quantity of the left atrial (LA) periatrial fat tissue predicts recurrence after catheter ablation of atrial fibrillation (AF). We hypothesized that the quality of the LA periatrial fat tissue, measured by the mean computed tomography attenuation, predicts recurrence after AF ablation independent of the quantity of the LA periatrial fat tissue.

Methods:
We included 143 consecutive patients with drug-refractory AF referred for the first catheter ablation of AF (62.2±10 years, 40% nonparoxysmal AF). All participants had a preablation cardiac computed tomography. We measured the quantity of the LA periatrial fat tissue by the area (millimeter square) and the quality by the mean computed tomography attenuation (Hounsfield units) in a standard 4-chamber view.

Results:

Patients with AF recurrence after ablation (n=57) had a significantly larger fat area (167.6 [interquartile range, 124.1–255] versus 145.4 [95.6–229.3] mm
2
;
P
=0.018) and a higher fat attenuation (−92.0±9.8 versus −96.5±9.4 Hounsfield units;
P
=0.006) than those without recurrence (controls). LA fat attenuation was correlated with LA fat volume and LA bipolar voltage by invasive mapping and was associated with AF recurrence after adjusting for clinical risk factors, including body mass index, AF type, LA dimension, and fat area (hazard ratio, 2.65;
P
=0.001).

Conclusions:
The quality of the LA periatrial fat tissue is an independent predictor of recurrence after the first AF ablation. Assessment of LA periatrial fat attenuation can improve AF ablation outcomes by refining patient selection.
Noninferiority Designed Cardiovascular Trials in Highest-Impact Journals
Authors: Bikdeli Behnood , Welsh John W. , Akram Yasir , Punnanithinont Natdanai , Lee Ike , Desai Nihar R. , Kaul Sanjay , Stone Gregg W. , Ross Joseph S. , Krumholz Harlan M. 
Published: June 2019

Background:
Noninferiority trials are increasingly being performed. However, little is known about their methodological quality. We sought to characterize noninferiority cardiovascular trials published in the highest-impact journals, features that may bias results toward noninferiority, features related to reporting of noninferiority trials, and the time trends.

Methods:

We identified cardiovascular noninferiority trials published in
JAMA
,
Lancet
, or
New England Journal of Medicine
from 1990 to 2016. Two independent reviewers extracted the data. Data elements included the noninferiority margin and the success of studies in achieving noninferiority. The proportion of trials showing major or minor features that may have affected the noninferiority inference was determined. Major factors included the lack of presenting the results in both intention-to-treat and per-protocol/as-treated cohorts, α>0.05, the new intervention not being compared with the best alternative, not justifying the noninferiority margin, and exclusion or loss of ≥10% of the cohort. Minor factors included suboptimal blinding, allocation concealment, and others.

Results:

From 2544 screened studies, we identified 111 noninferiority cardiovascular trials. Noninferiority margins varied widely: risk differences of 0.4% to 25%, hazard ratios of 1.05 to 2.85, odds ratios of 1.1 to 2.0, and relative risks of 1.1 to 1.8. Eighty-six trials claimed noninferiority, of which 20 showed superiority, whereas 23 (21.1%) did not show noninferiority, of which 8 also demonstrated inferiority. Only 7 (6.3%) trials were considered low risk for all the major and minor biasing factors. Among common major factors for bias, 41 (37%) did not confirm the findings in both intention-to-treat and per-protocol/as-treated cohorts and 4 (3.6%) reported discrepant results between intention-to-treat and per-protocol analyses. Forty-three (38.7%) did not justify the noninferiority margin. Overall, 27 (24.3%) underenrolled or had >10% exclusions. Sixty trials (54.0%) were open label. Allocation concealment was not maintained or unclear in 11 (9.9%). Publication of noninferiority trials increased over time (
P
<0.001). Fifty-two (46.8%) were published after 2010 and had a lower risk of methodological or reporting limitations for major (
P
=0.03) and minor factors (
P
=0.002).

Conclusions:
Noninferiority trials in highest-impact journals commonly conclude noninferiority of the tested intervention, but vary markedly in the selected noninferiority margin, and frequently have limitations that may impact the inference related to noninferiority.
Influence of Intracerebral Hemorrhage Location on Outcomes in Patients With Severe Intraventricular Hemorrhage
Authors: Eslami Vahid , Tahsili-Fahadan Pouya , Rivera-Lara Lucia , Gandhi Dheeraj , Ali Hasan , Parry-Jones Adrian , Nelson Lilli S. , Thompson Richard E. , Nekoobakht-Tak Saman , Dlugash Rachel , McBee Nichol , Awad Isaam , Hanley Daniel F. , Ziai Wendy C. ,   on behalf of the CLEAR III Investigators
Published: June 2019

Background and Purpose—
We investigated the prognostic significance of spontaneous intracerebral hemorrhage location in presence of severe intraventricular hemorrhage.

Methods—
We analyzed diagnostic computed tomography scans from 467/500 (excluding primary intraventricular hemorrhage) subjects from the CLEAR (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage) III trial. We measured intracerebral hemorrhage engagement with specific anatomic regions, and estimated association of each region with blinded assessment of dichotomized poor stroke outcomes: mortality, modified Rankin Scale score of 4 to 6, National Institutes of Health Stroke Scale score of >4, stroke impact scale score of <60, Barthel Index <86, and EuroQol visual analogue scale score of <50 and <70 at days 30 and 180, respectively, using logistic regression models.

Results—
Frequency of anatomic region involvement consisted of thalamus (332 lesions, 71.1% of subjects), caudate (219, 46.9%), posterior limb internal capsule (188, 40.3%), globus pallidus/putamen (127, 27.2%), anterior limb internal capsule (108, 23.1%), and lobar (29, 6.2%). Thalamic location was independently associated with mortality (days 30 and 180) and with poor outcomes on most stroke scales at day 180 on adjusted analysis. Posterior limb internal capsule and globus pallidus/putamen involvement was associated with increased odds of worse disability at days 30 and 180. Anterior limb internal capsule and caudate locations were associated with decreased mortality on days 30 and 180. Anterior limb internal capsule lesions were associated with decreased long-term morbidity.

Conclusions—
Acute intracerebral hemorrhage lesion topography provides important insights into anatomic correlates of mortality and functional outcomes even in severe intraventricular hemorrhage causing obstructive hydrocephalus. Models accounting for intracerebral hemorrhage location in addition to volumes may improve outcome prediction and permit stratification of benefit from aggressive acute interventions.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00784134.
Big Data Approaches to Phenotyping Acute Ischemic Stroke Using Automated Lesion Segmentation of Multi-Center Magnetic Resonance Imaging Data
Authors: Wu Ona , Winzeck Stefan , Giese Anne-Katrin , Hancock Brandon L. , Etherton Mark R. , Bouts Mark J.R.J. , Donahue Kathleen , Schirmer Markus D. , Irie Robert E. , Mocking Steven J.T. , McIntosh Elissa C. , Bezerra Raquel , Kamnitsas Konstantinos , Frid Petrea , Wasselius Johan , Cole John W. , Xu Huichun , Holmegaard Lukas , Jiménez-Conde Jordi , Lemmens Robin , Lorentzen Eric , McArdle Patrick F. , Meschia James F. , Roquer Jaume , Rundek Tatjana , Sacco Ralph L. , Schmidt Reinhold , Sharma Pankaj , Slowik Agnieszka , Stanne Tara M. , Thijs Vincent , Vagal Achala , Woo Daniel , Bevan Stephen , Kittner Steven J. , Mitchell Braxton D. , Rosand Jonathan , Worrall Bradford B. , Jern Christina , Lindgren Arne G. , Maguire Jane , Rost Natalia S. ,   on behalf of the MRI-GENIE and GISCOME Investigators
Published: June 2019

Background and Purpose—
We evaluated deep learning algorithms’ segmentation of acute ischemic lesions on heterogeneous multi-center clinical diffusion-weighted magnetic resonance imaging (MRI) data sets and explored the potential role of this tool for phenotyping acute ischemic stroke.

Methods—
Ischemic stroke data sets from the MRI-GENIE (MRI-Genetics Interface Exploration) repository consisting of 12 international genetic research centers were retrospectively analyzed using an automated deep learning segmentation algorithm consisting of an ensemble of 3-dimensional convolutional neural networks. Three ensembles were trained using data from the following: (1) 267 patients from an independent single-center cohort, (2) 267 patients from MRI-GENIE, and (3) mixture of (1) and (2). The algorithms’ performances were compared against manual outlines from a separate 383 patient subset from MRI-GENIE. Univariable and multivariable logistic regression with respect to demographics, stroke subtypes, and vascular risk factors were performed to identify phenotypes associated with large acute diffusion-weighted MRI volumes and greater stroke severity in 2770 MRI-GENIE patients. Stroke topography was investigated.

Results—

The ensemble consisting of a mixture of MRI-GENIE and single-center convolutional neural networks performed best. Subset analysis comparing automated and manual lesion volumes in 383 patients found excellent correlation (ρ=0.92;
P
<0.0001). Median (interquartile range) diffusion-weighted MRI lesion volumes from 2770 patients were 3.7 cm
3
(0.9–16.6 cm
3
). Patients with small artery occlusion stroke subtype had smaller lesion volumes (
P
<0.0001) and different topography compared with other stroke subtypes.

Conclusions—
Automated accurate clinical diffusion-weighted MRI lesion segmentation using deep learning algorithms trained with multi-center and diverse data is feasible. Both lesion volume and topography can provide insight into stroke subtypes with sufficient sample size from big heterogeneous multi-center clinical imaging phenotype data sets.