bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncogenic Properties of the Antisense lncRNA COMET in BRAF- and RET-Driven Papillary Thyroid Carcinomas
Authors: Esposito Roberta , Esposito Daniela , Pallante Pierlorenzo , Fusco Alfredo , Ciccodicola Alfredo , Costa Valerio 
Published: March 2019

Abstract

RET rearrangements as well as BRAF and RAS mutations drive differential pathway activation in papillary thyroid carcinomas, leading to different tumor phenotypes and prognoses. Although The Cancer Genome Atlas Consortium has identified tumor subgroups based on protein-coding gene signatures, neither expression of long noncoding RNAs (lncRNA) nor their correlation with specific tumor-driving mutations and rearrangements have been systematically assessed. Here, we reanalyzed our RNA-sequencing data using a de novo discovery approach to identify lncRNAs and define tumor subtype-specific signatures of annotated lncRNAs. Among them, we identified COMET (Correlated-to-MET), a natural antisense transcript that was highly expressed in carcinomas harboring BRAFV600E mutation or RET gene rearrangements (i.e., BRAF-like tumors) and induced the downstream MAPK pathway. In papillary thyroid carcinomas, COMET was part of a coexpression network including different oncogenes belonging to the MAPK pathway, and its expression highly correlated with MET expression. Depletion of COMET resulted in reduced expression of genes within this network, including the MET oncogene. COMET repression inhibited viability and proliferation of tumor cells harboring BRAFV600E somatic mutation or RET oncogene rearrangement and dramatically reduced motility and invasiveness of tumor cells. Moreover, silencing COMET markedly increased sensitivity to vemurafenib, a common inhibitor of mutated B-raf. Collectively, our results suggest COMET as a new target to improve drug-based cancer therapies, especially in BRAF-mutated and MET-addicted papillary thyroid carcinomas.

Significance:
These results highlight the oncogenic role of lncRNA COMET in thyroid and indicate it as a potential new target to overcome vemurafenib resistance in BRAF-mutated and MET-addicted carcinomas.
Identidade étnica ou Identidades étnicas? A italianidade em Oswaldo Truzzi
Authors: Almeida Renata Geraissati Castro de 
Published: March 2019

Resenha do livro: TRUZZI, Oswaldo Mario Serra. Italianidade no interior paulista – percursos e descaminhos de uma identidade étnica (1880-1950). São Paulo: Editora Unesp, 2016.
O livro Italianidade no interior paulista: percursos e descaminhos de uma identidade étnica (1880-1950) publicado em 2016, pelo professor da Universidade Federal de São Carlos, Oswaldo Truzzi, tem por objetivo compreender como se deu o processo de estruturação de uma identidade étnica do grupo de indivíduos que emigraram da Itália, no recorte temporal que abrange dos anos de 1880 a 1950. O autor, com uma relevante carreira nos estudos migratórios, elenca três ocasiões que se constituíram em marcos para uma mudança neste sentimento. São elas: os momentos iniciais da imigração e a construção da “italianidade” fora da Itália; a emergência do fascismo na Itália; e o Estado Novo. Ao perscrutar as diversas camadas sobrepostas na identidade italiana, visou mostrá-la como um processo histórico constantemente negociado, em que ora ocorre a aceitação, ora a resistência à assimilação. A pertinência de seu livro está em historicizar o termo “italianidade” mostrando seus desafios e particularidades em diferentes temporalidades.
A Escravidão na imprensa: política antiescravista e escravista no Rio de Janeiro, século XIX
Authors: Oliveira Felipe Garcia de 
Published: March 2019

O texto é uma resenha da obra: YOUSSEF, Alain El. Imprensa e Escravidão. Política e tráfico negreiro no Império do Brasil (Rio de Janeiro, 1822- 1850) São Paulo: Intermeios/Fapesp, 2016.
Activity patterns of the small and medium felid (Mammalia: Carnivora: Felidae) guild in northeastern India
Authors: Mukherjee Shomita , Singh Priya , Silva André Pinto , Ri Chandan , Kakati Kashmira , Borah Binod , Tapi Tana , Kadur Sandesh , Choudhary Prafull , Srikant Shikha , Nadig Surabhi , Navya R. , Björklund Mats , Ramakrishnan Uma 
Published: March 2019

Fifteen extant species of cats inhabit India, and the northeastern region of the country is among the richest with nine species. Among these are the “standard four”, an assemblage of Clouded Leopard Neofelis nebulosa, Asiatic Golden Cat Catopuma temminckii, Marbled Cat Pardofelis marmorata, and Leopard Cat Prionailurus bengalensis, which also occur across southeastern Asia. Within India, despite several surveys in this region, very little information exists on the ecology of this assemblage to explain their co-occurrence. In this paper, we put together data from several independent camera trapping studies over 10 sites across northeastern India to examine and interpret diel activity patterns of this group. While we present results for all the four species, we focus on two species, the Marbled Cat and Leopard Cat, which are of very similar body size and are potential competitors. We used kernel density estimates to measure diel activity patterns of all four species and overlap in activity between Marbled Cat and Leopard Cat at the regional scale as well as the point scale. We obtained 783 captures of the standard four from >27,500 trap nights. The Asiatic Golden Cat and Marbled Cat were strongly diurnal, Clouded Leopard largely crepuscular and nocturnal, and Leopard Cat largely nocturnal. The degree of overlap between Marbled Cat and Leopard Cat activity was low and in consensus with other studies across southeastern Asia. We interpret this as the differing niche spaces of the two cats due to their specific pre-existing adaptations, not restricted to the effects of competition. The point scale analysis when both cats are captured at the same location and separately show no shift in activity pattern, supporting our hypothesis of pre-existing differences in resources, such as food, playing a major role in facilitating co-existence. Our study, however, is preliminary and additional information with robust analysis is required to test this finding.
Abstract 146: Performance of a Chromogenic Thrombin Generation Assay in the Thrombophilia Screening in 597 Unselected Patients with a History of VenousThromboembolism
Authors: Toulon Pierre , Martin-Toutain Isabelle , Ankri Annick 
Published: March 2019

The HemosIL ThromboPath assay (Instrumentation Laboratory) is a chromogenic assay designed to globally evaluate the functionality of the protein C (PC) pathway. It is based on the ability of endogenous APC generated after activation of PC by a snake venom extract (Protac) to reduce the thrombin generation induced by a reagent containing tissue factor. Briefly, optical density is measured after addition of a thrombin-specific chromogenic substrate in the presence (OD A) or absence (OD B) of Protac. Test results are expressed as the Protac-Induced Coagulation Inhibition percentage (PICI%) that corresponds to the ratio [OD B-OD A]/OD B x 100. A normal test result corresponds to a PICI% above a cut-off level defined as the mean-1 SD of the values measured in 30 healthy controls. To determine the performance of that assay, we retrospectively tested frozen plasma samples from 597 consecutive patients referred for screening of biological risk factors for venous thrombosis (209 M and 388 F, mean age=45.6 years, range 15-100). None was on vitamin K-antagonist or had evidence of liver failure. PICI% was significantly lower in patients who presented with than in those without any PC pathway abnormality [median=69.0% (range: 15.3-96.8), n=101 vs. 89.8 (range: 38.5-98.0), n=496; p<0.0001]. All carriers of the Factor V Leiden mutation (32 heterozygotes, and 1 homozygote) had a PICI% below the cut-off level (88.5%). The same applied to all patients with either a PC deficiency (n=14) or a lupus anticoagulant (n=8). The test sensitivity to congenital and acquired PS deficiency was 97.7% (n=45/46). 41.5% of the patients without abnormality of the PC pathway had a decreased test result (n=206/496). The overall test sensitivity to tested thrombophilia was 99.0% (95%CI=94.6-100), its specificity 58.5% (95%CI=54.0-62.9), its negative predictive value (NPV) 99.7% (95%CI=98.1-100) and its PPV 32.7% (95%CI=27.4-38.2).
The high sensitivity of the HemosIL ThromboPath assay to PC pathway abnormalities together with a high NPV, closed to 100%, associated with a normal test result, suggest the potential interest of that assay as part of the screening strategy of PC pathway abnormalities. In that connection, the economic impact of its introduction is currently evaluated.
Abstract 221: Crif1 deficiency-induced Mitochondrial Dysfunction Stimulates Endothelial Inflammation
Authors: Kim Cuk Seong , Choi Su-jung , Kim Seonhee , Song Hee Jung 
Published: March 2019

CR6 interacting factor 1 (CRIF1) deficiency impairs mitochondrial oxidative phosphorylation complexes, contributing to increased mitochondrial and cellular reactive oxygen species (ROS) production. CRIF1 downregulation has also been revealed to decrease sirtuin 1 (SIRT1) expression and impair vascular function. Inhibition of SIRT1 disturbs oxidative energy metabolism and stimulates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B)-induced inflammation. Therefore, we hypothesized that both CRIF1 deficiency-induced mitochondrial ROS production and SIRT1 reduction play stimulatory roles in vascular inflammation. Plasma levels and mRNA expression of proinflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6) were markedly elevated in endothelium-specific CRIF1-knockout mice and CRIF1-silenced endothelial cells, respectively. Moreover, CRIF1 deficiency-induced vascular adhesion molecule-1 (VCAM-1) expression was consistently attenuated by the antioxidant N-acetyl-cysteine and NF-κB inhibitor (BAY11). We next showed that siRNA-mediated CRIF1 downregulation markedly activated NF-κB. SIRT1 overexpression not only rescued CRIF1 deficiency-induced NF-κB activation but also decreased inflammatory cytokines (TNF-α, IL-1β, and IL-6) and VCAM-1 expression levels in endothelial cells.
These results strongly suggest that CRIF1 deficiency promotes endothelial cell inflammation by increasing VCAM-1 expression, elevating inflammatory cytokines levels, and activating the transcription factor NF-κB, all of which were inhibited by SIRT1 overexpression.
Abstract 556: Structural Characterization of Distinct Subparticles of Human High-density Lipoproteins Isolated from Plasma
Authors: Melchior John T , Street Scott E , Shah Amy S , Jerome W. Jay , Hart Rachel , Heinecke Jay W , He Yi , Andraski Allison B , Furtado Jeremy D , Sacks Frank M , Davidson W. Sean 
Published: March 2019

High-density lipoproteins (HDL) play a critical role in lipid transport and the maintenance of vascular homeostasis. HDL consists of a heterogeneous population of particles that vary in size, composition, and functionality. HDL is proteomically diverse; it can host at least 95 different proteins and structure-function studies suggest that specific protein complements on the surface of the particles are responsible for the broad spectrum of HDL function.
The goal of this study was to isolate and fully characterize specific subspecies of HDL based on their protein complement and particle size. We built upon our previous studies where we segregated lipoproteins using immunoaffinity chromatography using antibodies specific to the two major scaffold proteins of HDL; apolipoprotein (apo)A-I and apoA-II. Two populations were obtained directly from plasma that either had both apoA-I and apoA-II (LpA-I/A-II) or just apoA-I with no apoA-II (LpA-I). These subpopulations were further fractionated using size exclusion chromatography using four superdex columns in series.

We observed at least three distinctly sized particles within the LpA-I/A-II subfraction and two distinctly sized particles in the LpA-I subfraction which all elute in the size range of HDL. We successfully isolated the “large” and “small” subpopulations observed in the LpA-I subfraction and compositional analysis revealed profound proteomic differences between the two populations. Particles in the larger fraction were enriched in more common apolipoprotiens important for lipid metabolic processes such as apoL-I, apoD, apoM and apoE. Conversely, the smaller LpA-I particles were enriched in proteins important for immune response and complement activation. Using multiple cross-linking reagents, we have mapped the protein-protein interactions on each of these subpopulations to begin generating detailed structural models of these particles
in silico
.
Disability-Adjusted Life Years Following Adult Out-of-Hospital Cardiac Arrest in the United States
Authors: Coute Ryan A. , Nathanson Brian H. , Panchal Ashish R. , Kurz Michael C. , Haas Nathan L. , McNally Bryan , Neumar Robert W. , Mader Timothy J. ,   for the CARES Surveillance Group
Published: March 2019

Background
Disability-adjusted life years (DALY) are a common public health metric used to consistently estimate and compare health loss because of both fatal and nonfatal disease burden. The annual number of DALY because of adult out-of-hospital cardiac arrest (OHCA) in the United States is unknown. Our objective was to estimate the DALY after adult nontraumatic, emergency medical services–treated OHCA, and to compare OHCA DALY to other leading causes of death and disability in the US.

Methods and Results
The DALY were calculated as the sum of years of life lost and years lived with disability. The years of life lost were calculated using all adult nontraumatic emergency medical services–treated OHCA with complete data from the national Cardiac Arrest Registry to Enhance Survival database for 2016, and actuarial data for remaining life expectancy at the age of death. Cerebral performance category scores from the Cardiac Arrest Registry to Enhance Survival database and previously established disability weights were used to estimate years lived with disability. The cohort’s calculated DALY were extrapolated to a national level to estimate total US DALY. Data were reported as total, mean, and DALY per 100 000 individuals. A total of 59 752 OHCA met study inclusion criteria. The DALY for the study population were 1 194 993 (years of life lost, 1 194 069; years lived with disability, 924) in 2016. The estimated total DALY following adult nontraumatic emergency medical services–treated OHCA in the US were 4 354  192 (years of life lost, 4 350  825; years lived with disability, 3365) for the index year 2016. The rate of OHCA DALY were 1347 per 100 000 population, which ranked third in the US behind ischemic heart disease (2447) and low back and neck pain (1565). Sensitivity analyses yielded similar findings.

Conclusions
Adult nontraumatic OHCA is a leading cause of annual DALY in the US and should be a focus of public health policy and resources.
Detecting Anomalies Among Practice Sites Within Multicenter Trials
Authors: Berkowitz Seth A. , Rudolph Kara E. , Basu Sanjay 
Published: March 2019

Background:
Recent multisite trials reveal striking heterogeneities in results between trial sites. These may be because of population differences indicating different treatment benefits among different types of participants or site anomalies, such as failures to adhere to study protocols that could negatively affect study validity. We sought to determine whether a new data analysis strategy—transportability methods—could suggest site anomalies not readily identified through standard methods.

Methods and Results:

We applied transportability methods to 2 large, multicenter cardiovascular disease treatment trials: the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist; n=3445) comparing spironolactone to placebo for heart failure (for which site anomalies were suspected) and the ACCORD BP trial (Action to Control Cardiovascular Risk in Diabetes–Blood Pressure; n=4733) comparing intensive-to-standard blood pressure treatment (for which site anomalies were not suspected). The transportability methods give expected results by standardizing from one site to another using data on participant covariates. The difference between the expected and observed results was assessed using calibration tests to identify whether treatment-effect differences between sites could be explained by participant population characteristics. Standard regression methods did not detect heterogeneities in TOPCAT between Russia/Georgia study sites suspected of study protocol violations and sites in the Americas (
P
=0.12 for difference in primary cardiovascular outcome;
P
=0.20 for difference in total mortality). The transportability methods, however, detected the difference between Russia/Georgia sites and sites in the Americas (
P
<0.001) and found that measured participant characteristics did not explain the between-site discrepancies. The transport methods found no such discrepancies between sites in ACCORD BP, suggesting participant characteristics explained between-site differences.

Conclusions:
Transportability methods may be superior to standard approaches for detecting anomalies within multicenter randomized trials and assist data monitoring boards to determine whether important treatment-effect heterogeneities can be attributed to participant differences or potentially to site performance differences requiring further investigation.
Interrelationships Between American Heart Association's Life's Simple 7, ECG Silent Myocardial Infarction, and Cardiovascular Mortality
Authors: Ahmad Muhammad Imtiaz , Chevli Parag Anilkumar , Barot Harsh , Soliman Elsayed Z. 
Published: March 2019

Background
We examined the interrelationships among cardiovascular health (CVH), assessed by the American Heart Association's Life's Simple 7 (LS7) health metrics, silent myocardial infarction (SMI), and cardiovascular disease (CVD) mortality.

Methods and Results
This analysis included 6766 participants without a history of coronary heart disease from the Third Report of the National Health and Nutrition Examination Survey. Poor, intermediate, and ideal CVH were defined as an LS7 score of 0 to 4, 5 to 9, and 10 to 14, respectively. SMI was defined as ECG evidence of myocardial infarction without a clinical diagnosis of myocardial infarction. Cox proportional hazard analysis was used to examine the association of baseline CVH with CVD death stratified by SMI status on follow‐up. In multivariable logistic regression models, ideal CVH was associated with 69% lower odds of SMI compared with poor CVH. During a median follow‐up of 14 years, 907 CVD deaths occurred. In patients without SMI, intermediate CVH (hazard ratio, 1.41; 95% CI, 1.14–1.74) and poor CVH (hazard ratio, 2.77; 95% CI, 2.10–3.66) were associated with increased risk of CVD mortality, compared with ideal CVH. However, in the presence of SMI, the magnitude of these associations almost doubled (hazard ratio, 2.17 [95% CI, 1.42–3.32] for intermediate CVH and hazard ratio, 6.28 [95% CI, 3.02–13.07] for poor CVH). SMI predicted a significant increased risk of CVD mortality in the intermediate and poor CVH subgroups but a nonsignificant increased risk in the ideal CVH subgroup.

Conclusions
Ideal CVH is associated with a lower risk of SMI, and concomitant presence of SMI and poor CVH is associated with a worse prognosis. These novel findings underscore the potential role of maintaining ideal CVH in preventing future CVD outcomes.
Dominant Interannual Covariations of the East Asian–Australian Land Precipitation during Boreal Winter
Authors: Liu Lin , Guo Jianping , Chen Wen , Wu Renguang , Wang Lin , Gong Hainan , Liu Bo , Chen Dandan , Li Jian 
Published: March 2019

AbstractThe present study applies the empirical orthogonal function (EOF) method to investigate the interannual covariations of East Asian–Australian land precipitation (EAALP) during boreal winter based on observational and reanalysis datasets. The first mode of EAALP variations is characterized by opposite-sign anomalies between East Asia (EA) and Australia (AUS). The second mode features an anomaly pattern over EA similar to the first mode, but with a southwest–northeast dipole structure over AUS. El Niño–Southern Oscillation (ENSO) is found to be a primary factor in modulating the interannual variations of land precipitation over EA and western AUS. By comparison, the Indian Ocean subtropical dipole mode (IOSD) plays an important role in the formation of precipitation anomalies over northeastern AUS, mainly through a zonal vertical circulation spanning from the southern Indian Ocean (SIO) to northern AUS. In addition, the ENSO-independent cold sea surface temperature (SST) anomalies in the western North Pacific (WNP) impact the formation of the second mode. Using the atmospheric general circulation model ECHAM5, three 40-yr numerical simulation experiments differing in specified SST forcings verify the impacts of the IOSD and WNP SST anomalies. Further composite analyses indicate that the dominant patterns of EAALP variability are largely determined by the out-of-phase and in-phase combinations of ENSO and IOSD. These results suggest that in addition to ENSO, IOSD should be considered as another crucial factor influencing the EAALP variability during the boreal winter, which has large implications for improved prediction of EAALP land precipitation on the interannual time scale.
Enhancing the Structure of the WRF-Hydro Hydrologic Model for Semiarid Environments
Authors: Lahmers Timothy M. , Gupta Hoshin , Castro Christopher L. , Gochis David J. , Yates David , Dugger Aubrey , Goodrich David , Hazenberg Pieter 
Published: March 2019

Abstract
In August 2016, the National Weather Service Office of Water Prediction (NWS/OWP) of the National Oceanic and Atmospheric Administration (NOAA) implemented the operational National Water Model (NWM) to simulate and forecast streamflow, soil moisture, and other model states throughout the contiguous United States. Based on the architecture of the WRF-Hydro hydrologic model, the NWM does not currently resolve channel infiltration, an important component of the water balance of the semiarid western United States. Here, we demonstrate the benefit of implementing a conceptual channel infiltration function (from the KINEROS2 semidistributed hydrologic model) into the WRF-Hydro model architecture, configured as NWM v1.1. After calibration, the updated WRF-Hydro model exhibits reduced streamflow errors for the Walnut Gulch Experimental Watershed (WGEW) and the Babocomari River in southeast Arizona. Model calibration was performed using NLDAS-2 atmospheric forcing, available from the NOAA National Centers for Environmental Prediction (NCEP), paired with precipitation forcing from NLDAS-2, NCEP Stage IV, or local gauge precipitation. Including channel infiltration within WRF-Hydro results in a physically realistic hydrologic response in the WGEW, when the model is forced with high-resolution, gauge-based precipitation in lieu of a national product. The value of accounting for channel loss is also demonstrated in the Babocomari basin, where the drainage area is greater and the cumulative effect of channel infiltration is more important. Accounting for channel infiltration loss thus improves the streamflow behavior simulated by the calibrated model and reduces evapotranspiration bias when gauge precipitation is used as forcing. However, calibration also results in increased high soil moisture bias, which is likely due to underlying limitations of the NWM structure and calibration methodology.