bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver
Authors: Im Hwi-Jin , Kim Hyeong-Geug , Lee Jin-Seok , Kim Hyo-Seon , Cho Jung-Hyo , Jo Il-Joo , Park Sung-Joo , Son Chang-Gue 
Published: February 2016

AbstractLiver metastasis is the main cause of death from colorectal cancer. Alcohol consumption impacts liver function and is suggested to be an independent risk factor for liver metastasis of colorectal cancer, but no experimental evidence supporting this hypothesis has been demonstrated to date. In this study, we investigated the effect of alcohol intake on liver metastasis. We examined colon cancer cell spread from the spleen in mice provided with water (control group), alcohol for 4 weeks before tumor injection (prealcohol), alcohol for 3 weeks after tumor injection (postalcohol), or alcohol throughout the 7-week study (alcohol). Alcohol intake significantly increased hepatic metastatic burden in the prealcohol (2.4-fold, P &lt; 0.001), postalcohol (2.0-fold, P &lt; 0.01), and alcohol groups (2.2-fold, P &lt; 0.001). A fluorescence-based metastasis tracking assay also confirmed an alcohol-induced increase in the abundance of tumor cells in the liver (2.5-fold, P &lt; 0.001). Investigation of the host microenvironment revealed an alcohol-induced inflammatory response marked by elevated TNFα, IL1β, IL6, and IFNγ protein levels, as well as increased expression of intercellular molecule-1 (ICAM1) in hepatic tissues after 4 weeks of alcohol consumption. Moreover, the peripheral blood of mice provided with alcohol for 4 weeks exhibited reduced natural killer and CD8+ T-cell counts. Collectively, our findings suggest that chronic alcohol consumption accelerates liver metastasis of colorectal cancer cells through alterations to the liver microenvironment and inactivation of immune surveillance. Cancer Res; 76(7); 1698–704. ©2016 AACR.
Distinct Subtypes of Gastric Cancer Defined by Molecular Characterization Include Novel Mutational Signatures with Prognostic Capability
Authors: Li Xiangchun , Wu William K.K. , Xing Rui , Wong Sunny H. , Liu Yuexin , Fang Xiaodong , Zhang Yanlin , Wang Mengyao , Wang Jiaqian , Li Lin , Zhou Yong , Tang Senwei , Peng Shaoliang , Qiu Kunlong , Chen Longyun , Chen Kexin , Yang Huanming , Zhang Wei , Chan Matthew T.V. , Lu Youyong , Sung Joseph J.Y. , Yu Jun 
Published: February 2016

Abstract
Gastric cancer is not a single disease, and its subtype classification is still evolving. Next-generation sequencing studies have identified novel genetic drivers of gastric cancer, but their use as molecular classifiers or prognostic markers of disease outcome has yet to be established. In this study, we integrated somatic mutational profiles and clinicopathologic information from 544 gastric cancer patients from previous genomic studies to identify significantly mutated genes (SMG) with prognostic relevance. Gastric cancer patients were classified into regular (86.8%) and hypermutated (13.2%) subtypes based on mutation burden. Notably, TpCpW mutations occurred significantly more frequently in regular, but not hypermutated, gastric cancers, where they were associated with APOBEC expression. In the former group, six previously unreported (XIRP2, NBEA, COL14A1, CNBD1, ITGAV, and AKAP6) and 12 recurrent mutated genes exhibited high mutation prevalence (≥3.0%) and an unexpectedly higher incidence of nonsynonymous mutations. We also identified two molecular subtypes of regular-mutated gastric cancer that were associated with distinct prognostic outcomes, independently of disease staging, as confirmed in a distinct patient cohort by targeted capture sequencing. Finally, in diffuse-type gastric cancer, CDH1 mutation was found to be associated with shortened patient survival, independently of disease staging. Overall, our work identified previously unreported SMGs and a mutation signature predictive of patient survival in newly classified subtypes of gastric cancer, offering opportunities to stratify patients into optimal treatment plans based on molecular subtyping. Cancer Res; 76(7); 1724–32. ©2016 AACR.
HDAC Inhibition Induces MicroRNA-182, which Targets RAD51 and Impairs HR Repair to Sensitize Cells to Sapacitabine in Acute Myelogenous Leukemia
Authors: Lai Tsung-Huei , Ewald Brett , Zecevic Alma , Liu Chaomei , Sulda Melanie , Papaioannou Dimitrios , Garzon Ramiro , Blachly James S. , Plunkett William , Sampath Deepa 
Published: February 2016

AbstractPurpose: The double-strand breaks elicited by sapacitabine, a clinically active nucleoside analogue prodrug, are repaired by RAD51 and the homologous recombination repair (HR) pathway, which could potentially limit its toxicity. We investigated the mechanism by which histone deacetylase (HDAC) inhibitors targeted RAD51 and HR to sensitize acute myelogenous leukemia (AML) cells to sapacitabine.Experimental Design: Chromatin immunoprecipitation identified the role of HDACs in silencing miR-182 in AML. Immunoblotting, gene expression, overexpression, or inhibition of miR-182 and luciferase assays established that miR-182 directly targeted RAD51. HR reporter assays, apoptotic assays, and colony-forming assays established that the miR-182, as well as the HDAC inhibition–mediated decreases in RAD51 inhibited HR repair and sensitized cells to sapacitabine.Results: The gene repressors, HDAC1 and HDAC2, became recruited to the promoter of miR-182 to silence its expression in AML. HDAC inhibition induced miR-182 in AML cell lines and primary AML blasts. miR-182 targeted RAD51 protein both in luciferase assays and in AML cells. Overexpression of miR-182, as well as HDAC inhibition–mediated induction of miR-182 were linked to time- and dose-dependent decreases in the levels of RAD51, an inhibition of HR, increased levels of residual damage, and decreased survival after exposure to double-strand damage-inducing agents.Conclusions: Our findings define the mechanism by which HDAC inhibition induces miR-182 to target RAD51 and highlights a novel pharmacologic strategy that compromises the ability of AML cells to conduct HR, thereby sensitizing AML cells to DNA-damaging agents that activate HR as a repair and potential resistance mechanism. Clin Cancer Res; 22(14); 3537–49. ©2016 AACR.
Integrative Genomic Analyses Yield Cell-Cycle Regulatory Programs with Prognostic Value
Authors: Cheng Chao , Lou Shaoke , Andrews Erik H. , Ung Matthew H. , Varn Frederick S. 
Published: February 2016

AbstractLiposarcoma is the second most common form of sarcoma, which has been categorized into four molecular subtypes, which are associated with differential prognosis of patients. However, the transcriptional regulatory programs associated with distinct histologic and molecular subtypes of liposarcoma have not been investigated. This study uses integrative analyses to systematically define the transcriptional regulatory programs associated with liposarcoma. Likewise, computational methods are used to identify regulatory programs associated with different liposarcoma subtypes, as well as programs that are predictive of prognosis. Further analysis of curated gene sets was used to identify prognostic gene signatures. The integration of data from a variety of sources, including gene expression profiles, transcription factor–binding data from ChIP-Seq experiments, curated gene sets, and clinical information of patients, indicated discrete regulatory programs (e.g., controlled by E2F1 and E2F4), with significantly different regulatory activity in one or multiple subtypes of liposarcoma with respect to normal adipose tissue. These programs were also shown to be prognostic, wherein liposarcoma patients with higher E2F4 or E2F1 activity associated with unfavorable prognosis. A total of 259 gene sets were significantly associated with patient survival in liposarcoma, among which &gt;50% are involved in cell cycle and proliferation.Implications: These integrative analyses provide a general framework that can be applied to investigate the mechanism and predict prognosis of different cancer types. Mol Cancer Res; 14(4); 332–43. ©2016 AACR.
Durable Benefits of Cellular Postconditioning: Long‐Term Effects of Allogeneic Cardiosphere‐Derived Cells Infused After Reperfusion in Pigs with Acute Myocardial Infarction
Authors: Kanazawa Hideaki , Tseliou Eleni , Dawkins James F. , De Couto Geoffrey , Gallet Romain , Malliaras Konstantinos , Yee Kristine , Kreke Michelle , Valle Ileana , Smith Rachel R. , Middleton Ryan C. , Ho Chak‐Sum , Dharmakumar Rohan , Li Debiao , Makkar Raj R. , Fukuda Keiichi , Marbán Linda , Marbán Eduardo 
Published: February 2016

Background

Infusion of allogeneic cardiosphere‐derived cells (allo‐
CDC
s) postreperfusion elicits cardioprotective cellular postconditioning in pigs with acute myocardial infarction. However, the long‐term effects of allo‐
CDC
s have not been assessed. We performed a placebo‐controlled pivotal study for long‐term evaluation, as well as shorter‐term mechanistic studies.

Methods and Results

Minipigs underwent 1.5‐hour mid‐left anterior descending balloon occlusion followed by reperfusion and were randomized to receive intracoronary allo‐
CDC
s or vehicle 30 minutes postreperfusion. Left ventriculography (
LVG
) demonstrated preserved ejection fraction (
EF
) and attenuation of
LV
remodeling in
CDC
‐treated pigs. Pigs underwent cardiac magnetic resonance imaging (
MRI
) and
LVG
1 hour and 8 weeks after therapy to evaluate efficacy.
MRI
showed improvement of
EF
and attenuation of
LV
remodeling immediately after allo‐
CDC
infusion. In addition, allo‐
CDC
s improved regional function and decreased hypertrophy 2 months post‐treatment. Histological analysis revealed increased myocardial salvage index, enhanced vascularity, sustained reductions in infarct size/area at risk and scar transmurality, and attenuation of collagen deposition in the infarct zone of allo‐
CDC
‐treated pigs at 2 months. Allo‐
CDC
s did not evoke lymphohistiocytic infiltration or systemic humoral memory response. Short‐term experiments designed to probe mechanism revealed antiapoptotic effects of allo‐
CDC
s on cardiomyocytes and increases in cytoprotective macrophages, but no increase in overall inflammatory cell infiltration 2 hours after cell therapy.

Conclusions

Allo‐
CDC
infusion postreperfusion is safe, improves cardiac function, and attenuates scar size and remodeling. The favorable effects persist for at least 2 months after therapy. Thus, cellular postconditioning confers not only acute cardioprotection, but also lasting structural and functional benefits.
Impact of an Emergency Department Observation Unit Management Algorithm for Atrial Fibrillation
Authors: Bellew Shawna D. , Bremer Merri L. , Kopecky Stephen L. , Lohse Christine M. , Munger Thomas M. , Robelia Paul M. , Smars Peter A. 
Published: February 2016

Background
Atrial fibrillation (AF) is a common, growing, and costly medical condition. We aimed to evaluate the impact of a management algorithm for symptomatic AF that used an emergency department observation unit on hospital admission rates and patient outcomes.

Methods and Results

This retrospective cohort study compared 563 patients who presented consecutively in the year after implementation of the algorithm, from July 2013 through June 2014 (intervention group), with 627 patients in a historical cohort (preintervention group) who presented consecutively from July 2011 through June 2012. All patients who consented to have their records used for chart review were included if they had a primary final emergency department diagnosis of
AF
. We observed no significant differences in age, sex, vital signs, body mass index, or
CHADS
2 (congestive heart failure, hypertension, age, diabetes mellitus, and prior stroke or transient ischemic attack) score between the preintervention and intervention groups. The rate of inpatient admission was significantly lower in the intervention group (from 45% to 36%;
P
<0.001). The groups were not significantly different with regard to rates of return emergency department visits (19% versus 17%;
P
=0.48), hospitalization (18% versus 16%;
P
=0.22), or adverse events (2% versus 2%;
P
=0.95) within 30 days. Emergency department observation unit admissions were 40% (
P
<0.001) less costly than inpatient hospital admissions of ≤1 day's duration.

Conclusions

Implementation of an emergency department observation unit
AF
algorithm was associated with significantly decreased hospital admissions without increasing the rates of return emergency department visits, hospitalization, or adverse events within 30 days.
miR‐342‐5p Is a Notch Downstream Molecule and Regulates Multiple Angiogenic Pathways Including Notch, Vascular Endothelial Growth Factor and Transforming Growth Factor β Signaling
Authors: Yan Xian‐Chun , Cao Jing , Liang Liang , Wang Li , Gao Fang , Yang Zi‐Yan , Duan Juan‐Li , Chang Tian‐Fang , Deng San‐Ming , Liu Yuan , Dou Guo‐Rui , Zhang Jian , Zheng Qi‐Jun , Zhang Ping , Han Hua 
Published: February 2016

Background

Endothelial cells (
EC
s) form blood vessels through angiogenesis that is regulated by coordination of vascular endothelial growth factor (
VEGF
), Notch, transforming growth factor β, and other signals, but the detailed molecular mechanisms remain unclear.

Methods and Results

Small
RNA
sequencing initially identified miR‐342‐5p as a novel downstream molecule of Notch signaling in
EC
s. Reporter assay, quantitative reverse transcription polymerase chain reaction and Western blot analysis indicated that miR‐342‐5p targeted endoglin and modulated transforming growth factor β signaling by repressing
SMAD
1/5 phosphorylation in
EC
s. Transfection of miR‐342‐5p inhibited
EC
proliferation and lumen formation and reduced angiogenesis in vitro and in vivo, as assayed by using a fibrin beads–based sprouting assay, mouse aortic ring culture, and intravitreal injection of miR‐342‐5p agomir in P3 pups. Moreover, miR‐342‐5p promoted the migration of
EC
s, accompanied by reduced endothelial markers and increased mesenchymal markers, indicative of increased endothelial–mesenchymal transition. Transfection of endoglin at least partially reversed endothelial–mesenchymal transition induced by miR‐342‐5p. The expression of miR‐342‐5p was upregulated by transforming growth factor β, and inhibition of miR‐342‐5p attenuated the inhibitory effects of transforming growth factor β on lumen formation and sprouting by
EC
s. In addition,
VEGF
repressed miR‐342‐5p expression, and transfection of miR‐342‐5p repressed
VEGFR
2 and
VEGFR
3 expression and
VEGF
‐triggered Akt phosphorylation in
EC
s. miR‐342‐5p repressed angiogenesis in a laser‐induced choroidal neovascularization model in mice, highlighting its clinical potential.

Conclusions
miR‐342‐5p acts as a multifunctional angiogenic repressor mediating the effects and interaction among angiogenic pathways.
A Review of Merged High-Resolution Satellite Precipitation Product Accuracy during the Tropical Rainfall Measuring Mission (TRMM) Era
Authors: Maggioni Viviana , Meyers Patrick C. , Robinson Monique D. 
Published: February 2016

AbstractA great deal of expertise in satellite precipitation estimation has been developed during the Tropical Rainfall Measuring Mission (TRMM) era (1998–2015). The quantification of errors associated with satellite precipitation products (SPPs) is crucial for a correct use of these datasets in hydrological applications, climate studies, and water resources management. This study presents a review of previous work that focused on validating SPPs for liquid precipitation during the TRMM era through comparisons with surface observations, both in terms of mean errors and detection capabilities across different regions of the world. Several SPPs have been considered: TMPA 3B42 (research and real-time products), CPC morphing technique (CMORPH), Global Satellite Mapping of Precipitation (GSMaP; both the near-real-time and the Motion Vector Kalman filter products), PERSIANN, and PERSIANN–Cloud Classification System (PERSIANN-CCS). Topography, seasonality, and climatology were shown to play a role in the SPP’s performance, especially in terms of detection probability and bias. Regions with complex terrain exhibited poor rain detection and magnitude-dependent mean errors; low probability of detection was reported in semiarid areas. Winter seasons, usually associated with lighter rain events, snow, and mixed-phase precipitation, showed larger biases.
Convection-Permitting Regional Weather Modeling with COSMO-EULAG: Compressible and Anelastic Solutions for a Typical Westerly Flow over the Alps
Authors: Kurowski Marcin J. , Wojcik Damian K. , Ziemianski Michal Z. , Rosa Bogdan , Piotrowski Zbigniew P. 
Published: February 2016

A comparison between anelastic and compressible convection-permitting weather forecasts for the Alpine region is presented. This involves mesoscale simulation of a typical westerly flow accompanied by a passage of frontal systems as well as intense airmass convection and orographic convection. The limited-area model employing a 2.2-km horizontal grid length is driven by time-dependent boundary conditions from a coarse-resolution model. The results obtained with the anelastic and the compressible model versions show good agreement. Validations of the 10-m wind, 2-m temperature, 2-m dewpoint temperature, total cloud cover, and surface precipitation against observations for a seven-member forecast ensemble reveal only minor differences between the two configurations. The sensitivity study demonstrates only a small impact of realistic pressure perturbations (about a reference profile) on the solutions. Overall, anelastic approximation proves remarkably accurate in simulating moist mesoscale dynamics. The study has been conducted using a newly developed hybrid limited-area nonhydrostatic version of the Consortium for Small-Scale Modeling (COSMO) model. This version facilitates the use of two alternative dynamical cores: compressible (original) and anelastic (new). The new dynamical core, which is based on the Euler–Lagrangian (EULAG) solver, aims at integrating atmospheric flow equations at resolutions higher than O(1) km for steep orography. A coupler has been developed to merge the EULAG dynamical core with the COSMO numerical weather prediction framework.
Strategies of Self-Proclaimed Pro-Life Groups in Argentina
Authors: Morán Faúndes José Manuel , Peñas Defago María Angélica 
Published: February 2016

Over the past few decades political processes recognizing and broadening sexual and reproductive rights have produced a reaction from conservative sectors seeking to block those gains. Although the Catholic Church hierarchy and some Evangelical churches have led the opposition to these rights, various sectors of civil society have begun to foment resistance to pluralist sexual politics. In Argentina self-proclaimed pro-life nongovernmental organizations have become important in the local context, using channels legitimized by contemporary democracy. While they initially devoted themselves primarily to the issue of abortion through activities associated with assistencialism and cultural impact, their actions since the 1990s have diversified, entering into the politico-institutional field and aiming at other issues associated with the country’s sexual policy. The movement and religion overlap at many levels and are separate in others. The complexity of the relationship between them requires rethinking of the normative frameworks through which progress on sexual and reproductive rights in Latin America is usually theorized. The separation of religion and politics under the paradigm of laicism can be insufficient to guarantee sexual pluralism in our societies. En las últimas décadas, los procesos políticos por el reconocimiento y ampliación de los derechos sexuales y reproductivos han generado la reacción de sectores conservadores que buscan obstaculizar dichas conquistas. Si bien la jerarquía católica y algunas iglesias evangélicas han protagonizado el rechazo a estos derechos, distintos sectores de la sociedad civil han comenzado también a activar una resistencia a las políticas sexuales pluralistas. En Argentina las organizaciones no-gubernamentales autodenominadas pro-vida han adquirido relevancia en el contexto local, utilizando los canales legitimados por la democracia contemporánea. Mientras las primeras se abocaron centralmente a la temática del aborto desde acciones asociadas al asistencialismo y al impacto cultural, a partir de los noventa sus acciones se han diversificado, entrando al campo político-institucional y orientándose a otros temas asociados a la política sexual del país. Este movimiento y la religión se superponen en muchos niveles y se separan en otros. La complejidad que reviste su relación implica repensar los marcos normativos mediante los cuales se ha solido teorizar el avance en los derechos sexuales y reproductivos en América Latina. La separación de la religión y la política bajo el paradigma de la laicidad puede resultar una estrategia insuficiente para garantizar el pluralismo sexual al interior de nuestras sociedades.
The African-Americanization of the Black Diaspora in Globalization or the Contemporary Capitalist World-system
Authors: Mocombe Paul C. 
Published: February 2016

This article puts forth the argument that people of African descent in the contemporary capitalist world-system under American hegemony, that is, globalization, are ever so slowly becoming African-Americanized because of the ideological and material influence of the black underclass via hip-hop culture and work and the Protestant ethic and the spirit of capitalism promulgated throughout the diaspora by black American charismatic liberal bourgeois Protestant preachers like TD Jakes, Creflo Dollar, etc. The latter, representatives of the black bourgeoisie, given their material wealth, have become the bearers of ideological and linguistic domination in black America, and are seeking to do the same in the African diaspora. I am, therefore, suggesting that contemporarily the evolution of black diasporic practical consciousness in the capitalist world-system under American hegemony has to be examined against the backdrop of this class dualism as well as the cultural and religious heritage of the black American people responsible for its inception in globalization or the contemporary capitalist world-system under American hegemony.