bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a decerebrate model for investigating mechanisms mediating viscero-sympathetic reflexes in the spinalized rat
Authors: Reynolds Christian A. , O’Leary Donal S. , Ly Cheng , Smith Scott A. , Minic Zeljka 
Published: March 2019

Autonomic dysreflexia (AD) often occurs in individuals living with spinal cord injury (SCI) and is characterized by uncontrolled hypertension in response to otherwise innocuous stimuli originating below the level of the spinal lesion. Visceral stimulation is a predominant cause of AD in humans and effectively replicates the phenotype in rodent models of SCI. Direct assessment of sympathetic responses to viscerosensory stimulation in spinalized animals is challenging and requires invasive surgical procedures necessitating the use of anesthesia. However, administration of anesthesia markedly affects viscerosensory reactivity, and the effects are exacerbated following spinal cord injury (SCI). Therefore, the major goal of the present study was to develop a decerebrate rodent preparation to facilitate quantification of sympathetic responses to visceral stimulation in the spinalized rat. Such a preparation enables the confounding effect of anesthesia to be eliminated. Sprague-Dawley rats were subjected to SCI at the fourth thoracic segment. Four weeks later, renal sympathetic nerve activity (RSNA) responses to visceral stimuli were quantified in urethane/chloralose-anesthetized and decerebrate preparations. Visceral stimulation was elicited via colorectal distension (CRD) for 1 min. In the decerebrate preparation, CRD produced dose-dependent increases in mean arterial pressure (MAP) and RSNA and dose-dependent decreases in heart rate (HR). These responses were significantly greater in magnitude among decerebrate animals when compared with urethane/chloralose-anesthetized controls and were markedly attenuated by the administration of urethane/chloralose anesthesia after decerebration. We conclude that the decerebrate preparation enables high-fidelity quantification of neuronal reactivity to visceral stimulation in spinalized rats. NEW & NOTEWORTHY In animal models commonly used to study spinal cord injury, quantification of sympathetic responses is particularly challenging due to the increased susceptibility of spinal reflex circuits to the anesthetic agents generally required for experimentation. This constitutes a major limitation to understanding the mechanisms mediating regionally specific neuronal responses to visceral activation in chronically spinalized animals. In the present study, we describe a spinalized, decerebrate rodent preparation that facilitates quantification of sympathetic reactivity in response to visceral stimuli following spinal cord injury. This preparation enables reliable and reproducible quantification of viscero-sympathetic reflex responses resembling those elicited in conscious animals and may provide added utility for preclinical evaluation of neuropharmacological agents for the management of autonomic dysreflexia.
Intratumoral Genetic and Functional Heterogeneity in Pediatric Glioblastoma
Authors: Hoffman Mary , Gillmor Aaron H. , Kunz Daniel J. , Johnston Michael J. , Nikolic Ana , Narta Kiran , Zarrei Mehdi , King Jennifer , Ellestad Katrina , Dang Ngoc Ha , Cavalli Florence M.G. , Kushida Michelle M. , Coutinho Fiona J. , Zhu Yuankun , Luu Betty , Ma Yussanne , Mungall Andrew J. , Moore Richard , Marra Marco A. , Taylor Michael D. , Pugh Trevor J. , Dirks Peter B. , Strother Douglas , Lafay-Cousin Lucie , Resnick Adam C. , Scherer Stephen , Senger Donna L. , Simons Benjamin D. , Chan Jennifer A. , Morrissy A. Sorana , Gallo Marco 
Published: March 2019

Abstract

Pediatric glioblastoma (pGBM) is a lethal cancer with no effective therapies. To understand the mechanisms of tumor evolution in this cancer, we performed whole-genome sequencing with linked reads on longitudinally resected pGBM samples. Our analyses showed that all diagnostic and recurrent samples were collections of genetically diverse subclones. Clonal composition rapidly evolved at recurrence, with less than 8% of nonsynonymous single-nucleotide variants being shared in diagnostic-recurrent pairs. To track the origins of the mutational events observed in pGBM, we generated whole-genome datasets for two patients and their parents. These trios showed that genetic variants could be (i) somatic, (ii) inherited from a healthy parent, or (iii) de novo in the germlines of pGBM patients. Analysis of variant allele frequencies supported a model of tumor growth involving slow-cycling cancer stem cells that give rise to fast-proliferating progenitor-like cells and to nondividing cells. Interestingly, radiation and antimitotic chemotherapeutics did not increase overall tumor burden upon recurrence. These findings support an important role for slow-cycling stem cell populations in contributing to recurrences, because slow-cycling cell populations are expected to be less prone to genotoxic stress induced by these treatments and therefore would accumulate few mutations. Our results highlight the need for new targeted treatments that account for the complex functional hierarchies and genomic heterogeneity of pGBM.

Significance:
This work challenges several assumptions regarding the genetic organization of pediatric GBM and highlights mutagenic programs that start during early prenatal development.
IFNγ, a Double-Edged Sword in Cancer Immunity and Metastasis
Authors: Liu Chengfei , Gao Allen C. 
Published: March 2019

Abstract
IFNγ has antitumorigenic effects; however, the findings of IFNγ in promoting the tumor cell survival and inducing adaptive immune resistance via CD4+ T-cell loss and programmed death ligand 1 (PD-L1) upregulation challenge this concept. Lo and colleagues determined that IFNγ induces epithelial–mesenchymal transition (EMT) by regulating the turnover of miRNA in prostate cancer, emphasizing the duplicitous effects of IFNγ. IFIT5, an IFN-induced tetratricopeptide repeat (IFIT) family member, was found to form a complex with the exoribonuclease-XRN1 to process miRNA maturation. These findings unveil a new IFNγ–STAT1–IFIT5–miRNA–EMT pathway in prostate cancer progression. The biphasic effects of IFNγ in prostate cancer raise concerns about its therapeutic application, which need to be evaluated in future studies.
See related article by Lo et al., p. 1098
N-Terminal Pro-B-Type Natriuretic Peptide Levels for Risk Prediction in Patients With Heart Failure and Preserved Ejection Fraction According to Atrial Fibrillation Status
Authors: Kristensen Søren L. , Mogensen Ulrik M. , Jhund Pardeep S. , Rørth Rasmus , Anand Inder S. , Carson Peter E. , Desai Akshay S. , Pitt Bertram , Pfeffer Marc A. , Solomon Scott D. , Zile Michael R. , Køber Lars , McMurray John J. V. ,   On behalf of the I-Preserve and TOPCAT investigators
Published: March 2019

Background
NT-proBNP (N-terminal pro-B-type natriuretic peptide) is useful in diagnosis and prognostication in heart failure (HF). We examined the relationship between NT-proBNP and outcomes in patients with HF and preserved ejection fraction, with and without atrial fibrillation (AF).

Methods and Results

Among 3835 HF with preserved ejection fraction patients enrolled in the I-Preserve (Irbesartan in Heart Failure With Preserved Systolic Function trial) or TOPCAT trial (Treatment of Preserved Cardiac Function in Heart Failure With an Aldosterone Antagonist), 719 (19%) patients had AF on their baseline ECG. Median (Q1–Q3) levels of NT-proBNP were 1286 pg/mL (778–2072) in those with AF and 288 pg/mL (122–704) in those without (
P
<0.001). We analyzed patients using 4 NT-proBNP bands: <400, 400 to 999 (reference), 1000 to 1999, and ≥2000 pg/mL. The event rates for the primary composite outcome of cardiovascular death or HF hospitalization were higher in patients with AF versus patients without or those without without AF in the lowest NT-proBNP band (<400 pg/mL; 8.0 versus 3.2 per 100 patient-years), whereas for the higher bands the opposite was true (1000–1999 pg/mL; 11.4 versus 13.2 per 100 patient-years and ≥2000 pg/mL; 17.4 versus 25.6 per 100 patient-years). In adjusted analyses, higher NT-proBNP levels were less predictive of HF hospitalization than mortality in patients with AF compared with those without.

Conclusions
Event rates in HF with preserved ejection fraction patients without AF and with NT-proBNP <400 pg/mL are low. Among patients with NT-proBNP ≥400 pg/mL, the relationship between NT-proBNP and outcomes differs with lower absolute risk in patients who have AF compared with those who do not have AF.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifiers: NCT00094302 and NCT00095238.
Association Between Hospital Recognition for Resuscitation Guideline Adherence and Rates of Survival for In-Hospital Cardiac Arrest
Authors: Khera Rohan , Tang Yuanyuan , Link Mark S. , Krumholz Harlan M. , Girotra Saket , Chan Paul S. ,   for the American Heart Association Get With The Guidelines–Resuscitation Investigators
Published: March 2019

Background
Hospitals participating in the national Get With The Guidelines–Resuscitation registry receive an award for high rates of adherence to quality metrics for in-hospital cardiac arrest. We sought to evaluate whether awards based on these quality metrics can be considered a proxy for performance on cardiac arrest survival.

Methods and Results

Among 195 hospitals with continuous participation in Get With The Guidelines–Resuscitation between 2012 and 2015, we identified 78 that received an award (Gold or Silver) for ≥85% compliance for all 4 metrics for in-hospital cardiac arrest—time to chest compressions, ≤1 minute; time to defibrillation, ≤2 minutes; device confirmation of endotracheal tube placement; and a monitored/witnessed arrest—for at least 12 consecutive months during 2014 to 2015. Award hospitals had higher cardiac arrest volumes than nonaward hospitals but otherwise had similar site characteristics. During 2014 to 2015, award hospitals had higher rates of return of spontaneous circulation for in-hospital cardiac arrest than nonaward hospitals (median [interquartile range], 71% [64%–77%] versus 66% [59%–74%]; Spearman ρ, 0.19;
P
=0.009). However, rates of risk-standardized survival to discharge at award hospitals (median, 25% [interquartile range, 22%–30%]) were similar to nonaward hospitals (median, 24% [interquartile range, 12%–27%]; Spearman ρ, 0.13;
P
=0.06). Among hospitals in the best tertile for survival to discharge in 2014 to 2015, 55.4% (36/65) did not receive an award, with poor discrimination of high-performing hospitals by award status (C statistic, 0.53). Similarly, there was only a weak association between hospitals’ award status in 2014 to 2015 and their rates of survival to discharge in the preceding 2-year period (Spearman ρ, 0.16;
P
=0.03).

Conclusions
The current recognition mechanism within a national registry for in-hospital cardiac arrest captures hospital performance on return of spontaneous circulation but is not well correlated with survival to discharge. This suggests that current awards for resuscitation quality may not adequately capture hospital performance on overall survival—the outcome of greatest interest to patients.
Metabolic Risk Factors and Left Ventricular Diastolic Function in Middle‐Aged Chinese Living in the Tibetan Plateau
Authors: Zheng Congyi , Chen Zuo , Zhang Linfeng , Wang Xin , Dong Ying , Wang Jiali , Shao Lan , Tian Ye , Wang Zengwu , Zhao Tianming , Fan Guohui , Jia Xiuyun , Gao Runlin , Guo Yanfei , Tong Yaqi , Chen Yundai , Duan Peng , Li Nanfang , Suo Feiya , Cao Mei , He Liu , Kang Yuting , Li Suning , Zhang Zugui 
Published: March 2019

Background

Data regarding the metabolic risk factors clustering on the risk of left ventricular diastolic dysfunction (
LVDD
) are lacking among people living at high altitude and under hypoxic conditions. In this study, we explored the association between metabolic risk factor clustering and
LVDD
among the Tibetan population of China.

Methods and Results

We conducted a cross‐sectional survey in a representative sample of 1963 Tibetans in 2014 to 2016. Grading
LVDD
was based on recommendations for the evaluation of
LV
diastolic function by echocardiography (2009). The prevalence of
LVDD
among 1963 participants (mean age: 51.51 years, 41.11% male) was 34.39%. Odds ratios (95%
CI
) of
LVDD
for the 1, 2, and 3 to 5 risk factors clustering were 1.45 (0.96–2.17), 2.68 (1.8–3.98), and 2.9 (1.9–4.43), respectively (
P
for trend <0.001). The association between metabolic risk factors clustering and
LVDD
was much more pronounced in the middle‐aged group than in the elderly (
P
for interaction=0.0170). High altitude was one of the major independent risk factors for
LVDD
; however, habitation altitude had no significant effect on the association between metabolic risk factors and
LVDD
(
P
for interaction=0.1022). The multivariable dominance analysis indicated that abdominal obesity, hypertension, and elevated blood glucose were the significant contributors to
LVDD
.

Conclusions

There was a significant positive association between the metabolic risk factor clustering number and
LVDD
among a population living at high altitude, especially in middle‐aged adults. However, habitation altitude itself has no significant effect on the association between metabolic risk factors and
LVDD
.
A Horn for Phemius
Authors: Morgan Harry 
Published: March 2019

Abstract
In 51 BC, Titus Pomponius Atticus wrote to his friend Cicero with an unusual request: his musician Phemius needed a new instrument—a special ‘horn’ (κέρας) that could only be found in the region of Cilicia where Cicero was serving as governor. Several months later, the object in question was finally tracked down and an order placed. What exactly was this elusive piece of musical exotica, and why was Atticus so eager to get his hands on it? This article states a case for identifying Phemius’ κέρας with the Phrygian aulos/tibia, a species of pipe noted for its resonant ox-horn bell. Atticus’ acquisition of the ‘Phrygian pipe’ provides a revealing counterpoint to the often stereotyped depictions of musical entertainment (symphoniae) that we find in contemporary literature. It therefore presents an effective model for re-evaluating the place of musical culture in late Republican elite society.
Does the End Justify the Means? A Media Analysis of Invasive Pig and Fox Management
Authors: Thompson Beatrice Emma , Grace Melanie Elyse , Foster Bridget Clare , Harrison Claire Louise , Graham Sonia 
Published: March 2019

Abstract
Growing numbers of researchers and animal rights advocates are concerned about the welfare of invasive nonhuman animals, and new government policies echo these concerns. Past survey research, however, shows that the general public defines invasive animal welfare differently than scientists and animal rights advocates. There is little social research that investigates how differing views on the acceptability of invasive animal controls are reconciled in public fora. This article examines how invasive animal control is represented in two newspapers—The Sydney Morning Herald and The Land—in New South Wales, Australia, focusing on the management of invasive foxes and pigs. The findings revealed that efficacy is emphasized more than humaneness, especially among farmers and peri-urban residents, suggesting a disjuncture between new policies and landholders’ values. Views of indigenous land managers and amenity migrants are rarely represented yet they need to be actively engaged to ensure effective policy change.
Enhanced Latent Heating over the Tibetan Plateau as a Key to the Enhanced East Asian Summer Monsoon Circulation under a Warming Climate
Authors: He Chao , Wang Ziqian , Zhou Tianjun , Li Tim 
Published: March 2019

AbstractCoupled climate system models consistently show that the low-level southerly wind associated with the East Asian summer monsoon (EASM) is enhanced under anthropogenic greenhouse gas forcing, and the enhanced EASM was attributed to the enhanced land–sea thermal contrast by previous studies. Based on a comparison of the global warming scenarios with the present-day climate in an ensemble of 30 coupled models from phase 5 of the Coupled Model Intercomparison Project (CMIP5), we show evidence that changes in land–sea thermal contrast cannot explain the enhanced EASM circulation in terms of the seasonality. Indeed, the enhanced low-level southerly wind over East Asia is associated with a large-scale anomalous cyclone around the Tibetan Plateau (TP), and numerical simulation by the Linear Baroclinic Model suggests that the enhanced latent heating over the TP associated with enhanced precipitation is responsible for this low-level cyclone anomaly and the enhanced EASM circulation projected by the coupled models. Moisture budget analysis shows that enhanced hydrological recycling and enhanced vertical moisture advection due to increased specific humidity have the largest contribution to the increased precipitation over the TP, and more than half of the intermodel uncertainty in the projected change of EASM circulation is associated with the uncertainty in the changes of precipitation over the TP. Therefore, the TP plays an essential role in enhancing the EASM circulation under global warming through enhanced latent heating over the TP.
Understanding the Impacts of Soil Moisture Initial Conditions on NWP in the Context of Land–Atmosphere Coupling
Authors: Santanello Jr. Joseph A. , Lawston Patricia , Kumar Sujay , Dennis Eli 
Published: March 2019

Abstract
The role of soil moisture in NWP has gained more attention in recent years, as studies have demonstrated impacts of land surface states on ambient weather from diurnal to seasonal scales. However, soil moisture initialization approaches in coupled models remain quite diverse in terms of their complexity and observational roots, while assessment using bulk forecast statistics can be simplistic and misleading. In this study, a suite of soil moisture initialization approaches is used to generate short-term coupled forecasts over the U.S. Southern Great Plains using NASA’s Land Information System (LIS) and NASA Unified WRF (NU-WRF) modeling systems. This includes a wide range of currently used initialization approaches, including soil moisture derived from “off the shelf” products such as atmospheric models and land data assimilation systems, high-resolution land surface model spinups, and satellite-based soil moisture products from SMAP. Results indicate that the spread across initialization approaches can be quite large in terms of soil moisture conditions and spatial resolution, and that SMAP performs well in terms of heterogeneity and temporal dynamics when compared against high-resolution land surface model and in situ soil moisture estimates. Case studies are analyzed using the local land–atmosphere coupling (LoCo) framework that relies on integrated assessment of soil moisture, surface flux, boundary layer, and ambient weather, with results highlighting the critical role of inherent model background biases. In addition, simultaneous assessment of land versus atmospheric initial conditions in an integrated, process-level fashion can help address the question of whether improvements in traditional NWP verification statistics are achieved for the right reasons.
Minimally Important Difference in the Foot and Ankle Outcome Score Among Patients Undergoing Hallux Valgus Surgery
Authors: Desai Sameer , Peterson Alexander C. , Wing Kevin , Younger Alastair , Crump Trafford , Liu Guiping , Veljkovic Andrea , Penner Murray , Sutherland Jason M. 
Published: March 2019

Background: Patient-reported outcomes are increasingly used as measures of effectiveness of interventions. To make the tools more useful, therapeutic thresholds known as minimally important differences have been developed. The objective of this study was to calculate minimally important differences for the domains of the Foot and Ankle Outcome Score for hallux valgus surgery. Methods: The study was based on a retrospective analysis of patients newly scheduled for bunion correction surgery and completing patient-reported outcomes between October 2013 and January 2018. This study used anchor- and distribution-based approaches to calculate the minimally important difference for the instrument’s 5 domains. Confidence intervals were calculated for each approach. There were 91 participants included in the study. Results: Using anchor- and distribution-based approaches, the minimally important difference for the pain domain ranged from 5.8 to 10.2, from 0.3 to 6.9 for the symptoms domain, 8.3 to 10.3 for the activities of daily living domain, 7.4 to 11.1 for the quality of life domain, and from 7.0 to 15.7 for the sports and recreation domain. Small differences in the activities of daily living domain may be more clinically important for patients with better function. Discussion: The range of minimally important difference values for each domain indicate how the Foot and Ankle Outcome Score corresponded to bunion correction surgery. The sports and recreation domain showed considerable variability in the range of values and may be associated with the domain’s lack of responsiveness. Overall, most minimally important difference values for the domains of FAOS ranged from above 4 to below 16. Level of Evidence: Level III, retrospective comparative series.
Maternal ABO Blood Type and Factors Associated With Preeclampsia Subtype
Authors: Burgess Adriane , Johnson Teresa S. , Simanek Amanda , Bell Theodore , Founds Sandra 
Published: March 2019

Background: The pathophysiology of preeclampsia remains unclear. The disorder is heterogeneous, and the pathophysiology may vary by subtype. Identification of relevant biomarkers will help to better elucidate the pathophysiologic basis of each preeclampsia subtype. Blood type may be a biomarker that allows risk identification for preeclampsia. Objective: The purpose of this study was to investigate the associations among maternal ABO blood type and preeclampsia subtype and fetal growth restriction (FGR). Method: Medical records of 126 women with early-onset preeclampsia (≤33 6/7 weeks’ gestation), 126 women with late-onset preeclampsia (≥34 0/7 weeks’ gestation), and 259 controls who gave birth between January 2012 and June 2016 were retrospectively abstracted from a large suburban tertiary referral center in South Central Pennsylvania for this hospital-based case–control study. Results: Women with AB blood type had >3 times the odds of late-onset preeclampsia (odds ratio [ OR] = 3.35, 95% confidence interval (CI) = [1.02, 11.05]) compared to those with O blood type. Among women with early-onset preeclampsia, those with B blood type had 5 times the odds of having a growth-restricted fetus than did women with O blood type ( OR = 5.44, 95% CI [1.65, 17.94]). Discussion: Our findings suggest that AB blood type may be an important risk factor for late-onset preeclampsia and that among women with early-onset preeclampsia, those with B blood type have increased odds of FGR. These findings warrant further study in women and their offspring to identify the pathophysiologic processes that may link ABO blood type, preeclampsia subtype, and FGR.