bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lesion location, stability, and pretreatment management: factors affecting outcomes of endovascular treatment for vertebrobasilar atherosclerosis
Authors: Alexander Matthew D , Rebhun Jeffrey M , Hetts Steven W , Kim Anthony S , Nelson Jeffrey , Kim Helen , Amans Matthew R , Settecase Fabio , Dowd Christopher F , Halbach Van V , Higashida Randall T , Cooke Daniel L 
Published: March 2015

Background and purposeThe proper role of endovascular treatment of cervicocerebral atherosclerosis is unclear. Posterior circulation disease has not been investigated as extensively as disease in the anterior circulation. In this study, we characterized the rates of technical success, transient ischemic attack, stroke, and death or disability, for both acute and elective endovascular treatment of atherosclerosis in the vertebrobasilar system.MethodsWe identified patients with atherosclerosis of the vertebrobasilar circulation who underwent endovascular intervention at our hospital through retrospective medical record review, and evaluated the association between lesion and treatment features and subsequent stroke, death, or disability at 30 days and 1 year.ResultsWe identified 136 lesions in 122 patients, including 13 interventions for acute strokes. Technical success was achieved in 123 of 136 cases (90.4%). Elective procedures had higher rates of technical success (6.5% vs 15.4%, p=0.21) and better clinical outcomes. In multivariate analysis, intracranial lesions were associated with more disability (modified Rankin Scale score >2) at 30 days (OR 7.1, p=0.01) and 1 year (OR 10, p=0.03). Patients with non-hypoperfusion related symptoms had fewer strokes at follow-up at 1 year when treated after an asymptomatic interval of >10 days compared with those treated within 10 days of the presenting symptoms (OR 0.2, p=0.03). Statin treatment prior to intervention was associated with favorable outcomes across several examined endpoints. Preoperative antiplatelet treatment was associated with lower rates of disability at 30 days and 1 year (OR 0.1, p<0.01 and OR 0.07, p=0.01, respectively), and preoperative anticoagulation treatment was associated with higher rates of death at 30 days, particularly when prescribed for reasons other than atrial fibrillation (OR 6.4, p=0.01).ConclusionsEndovascular treatment of symptomatic vertebrobasilar atherosclerosis can be performed safely and with good outcomes. Technical results were better for those with extracranial disease while clinical outcomes were more favorable in those patients with non-progressive symptoms in the subacute period and those receiving statin therapy.
The role of the petrophysical characteristics on the durability and conservation of some porous calcarenites from Southern Italy
Authors: Calia A. , Lettieri M. , Mecchi A. , Quarta G. 
Published: March 2015

Abstract
Highly porous and soft calcarenites, often called ‘calcareous tuffs’, are commonly found throughout Southern Italy and are traditionally used as building materials. The petrophysical features of some of them were determined, focusing on the microstructure (fabric and porosimetric characteristics) and on the properties related to water absorption, drying and water vapour permeability; the compressive strength was also measured. The mineralogical composition was analysed and a variable presence of clay minerals was found for the different varieties. Diverse levels of damage under a salt crystallization test were related to the mineralogical, petrographic and porosimetric features, the latter being a source of the heterogeneity of the investigated stones. Results of laboratory tests and observations of decay in the field suggest protection against water penetration as the primary requirement for slowing down the decay of such highly porous and soft stones. Some water-repellent products were tested for effectiveness in reducing water absorption and for compatibility with the original stones’ properties. Their use in the presence of salts was taken into account, including the performances of the treated stones under the salt crystallization test. Treatment issues were found to be strongly influenced by the porosimetric characteristics of the studied materials.
Geoethics and seismic risk perception: the case of the Pollino area, Calabria, southern Italy and comparison with communities of the past
Authors: De Pascale F. , Bernardo M. , Muto F. , Tripodi V. 
Published: March 2015

Abstract
This work is a synthesis of research into seismic risk perception in the Pollino area (southern Italy). Over the last 3 years, there has been an ongoing earthquake swarm affecting this area that straddles the border between the regions of Calabria and Basilicata. The perception of seismic risk is an important element in environmental planning. If land is considered in terms of reciprocal interaction between humans and their physical space, Geoethics can find a synthesis between humanistic and scientific knowledge with regard to the theme of disasters. Geoethics can especially help in terms of educating the population of an area about integrated risk management. It is believed that improved communications, awareness of risk complexity and levels of preparation would increase a community's resilience and allow for more effective planning. With this premise, a questionnaire was given to students in primary and secondary education, and to a sample of adults in some of the villages affected by the Pollino earthquake swarm. A comparison with people's mental representation of risk regarding great earthquakes of the past, such as those of Calabria in 1783, helps us to clarify the relationship between an extreme event and a disaster.
Geotourism: an opportunity to enhance geoethics and boost geoheritage appreciation
Authors: Allan Mamoon 
Published: March 2015

Abstract
Geotourism (tourism with a geological purpose) has great potential to sustain and conserve our geological heritage, which represents the collective memory of Mother Nature. It involves a sustainable, viable and responsible tourism development that enhances the wellbeing of the local communities. It further provides a holistic tourism experience, and offers opportunities for visitors and hosts to gain knowledge about the values of the geological tourism attractions. In addition, it is based on the best practice of geoethics for different parties involved in geological tourism activities. However, this paper will explore the role of geotourism as a geoconservation and geoeducation tool, and will investigate the role of geotourism operations in promoting the culture of geoethics in different geological tourism practices.
IDH2 and NPM1 Mutations Cooperate to Activate Hoxa9/Meis1 and Hypoxia Pathways in Acute Myeloid Leukemia
Authors: Ogawara Yoko , Katsumoto Takuo , Aikawa Yukiko , Shima Yutaka , Kagiyama Yuki , Soga Tomoyoshi , Matsunaga Hironori , Seki Takahiko , Araki Kazushi , Kitabayashi Issay 
Published: March 2015

Abstract
IDH1 and IDH2 mutations occur frequently in acute myeloid leukemia (AML) and other cancers. The mutant isocitrate dehydrogenase (IDH) enzymes convert α-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), which dysregulates a set of α-KG–dependent dioxygenases. To determine whether mutant IDH enzymes are valid targets for cancer therapy, we created a mouse model of AML in which mice were transplanted with nucleophosmin1 (NPM)+/− hematopoietic stem/progenitor cells cotransduced with four mutant genes (NPMc, IDH2/R140Q, DNMT3A/R882H, and FLT3/ITD), which often occur simultaneously in human AML patients. Conditional deletion of IDH2/R140Q blocked 2-HG production and maintenance of leukemia stem cells, resulting in survival of the AML mice. IDH2/R140Q was necessary for the engraftment or survival of NPMc+ cells in vivo. Gene expression analysis indicated that NPMc increased expression of Hoxa9. IDH2/R140Q also increased the level of Meis1 and activated the hypoxia pathway in AML cells. IDH2/R140Q decreased the 5hmC modification and expression of some differentiation-inducing genes (Ebf1 and Spib). Taken together, our results indicated that IDH2 mutation is critical for the development and maintenance of AML stem-like cells, and they provided a preclinical justification for targeting mutant IDH enzymes as a strategy for anticancer therapy. Cancer Res; 75(10); 2005–16. ©2015 AACR.
Nitrostyrene Derivatives Act as RXRα Ligands to Inhibit TNFα Activation of NF-κB
Authors: Zeng Zhiping , Sun Zhe , Huang Mingfeng , Zhang Weidong , Liu Jie , Chen Liqun , Chen Fan , Zhou Yuqi , Lin Jiacheng , Huang Fengyu , Xu Lin , Zhuang Zixing , Guo Shangjie , Alitongbieke Gulimiran , Xie Guobin , Xu Yang , Lin Bingzhen , Cao Xihua , Su Ying , Zhang Xiao-kun , Zhou Hu 
Published: March 2015

Abstract
Retinoid X receptor alpha (RXRα) and its N-terminally truncated version, tRXRα, are widely implicated in cancer development and represent intriguing targets for cancer prevention and treatment. Successful manipulation of RXRα and tRXRα requires the identification of their modulators that could produce therapeutic effects. Here, we report that a class of nitrostyrene derivatives bind to RXRα by a unique mechanism, of which the nitro group of nitrostyrene derivatives and Cys432 of RXRα are required for binding. The binding results in the potent activation of Gal4-DBD-RXRα-LBD transactivation. However, the binding inhibits the transactivation of RXRα homodimer, which might be due to the distinct conformation of RXRα homodimer induced by these nitrostyrene derivatives. Two RXRα point mutants with Cys432 substituted with Tyr and Trp, respectively, could mimic the bindings of two nitrostyrene derivatives and have the ability of autotransactivation. In studying the functional consequences of the binding, we show that these nitrostyrene derivatives could potently inhibit the TNFα/NFκB signaling pathway in a tRXRα-dependent manner. tRXRα promotes TNFα-induced NF-κB activation through its interaction with TRAF2 and enhances TNFα-induced ubiquitination of RIP1, which is strongly inhibited by nitrostyrene derivatives. The inhibition of TNFα-induced NF-κB activation results in the synergistic effect of the combination of nitrostyrene derivatives and TNFα on the induction of cancer cell apoptosis. Together, our results show a new class of RXRα modulators that induce apoptosis of cancer cells through their unique binding mode and new mechanism of action. Cancer Res; 75(10); 2049–60. ©2015 AACR.
TLR5 Ligand–Secreting T Cells Reshape the Tumor Microenvironment and Enhance Antitumor Activity
Authors: Geng Degui , Kaczanowska Sabina , Tsai Alexander , Younger Kenisha , Ochoa Augusto , Rapoport Aaron P. , Ostrand-Rosenberg Sue , Davila Eduardo 
Published: March 2015

Abstract
The tumor microenvironment counters antitumor T-cell responses, in part, by blunting their activation and infiltration. Ligands that engage Toll-like receptors (TLR) on T cells and antigen-presenting cells can act as potent immune adjuvants. In this study, we show how tumor-reactive T cells engineered to secrete bacterial flagellin, a TLR5 ligand (TLR5L), can engender a costimulatory signal that augments antitumor activity. Human T cells engineered to express TLR5L along with DMF5, a T-cell receptor that recognizes the melanoma antigen MART-127–35 (DMF5TLR5L T cells), displayed increased proliferation, cytokine production, and cytolytic activity against melanoma cells. In a xenogenetic model, adoptive transfer of DMF5TLR5L T cells reduced tumor growth kinetics and prolonged mouse survival. In a syngeneic model, similarly engineered melanoma-reactive T cells (pmelTLR5L) displayed a relative increase in antitumor activity against established tumors, compared with unmodified T cells. In this model, we documented increased T-cell infiltration associated with increased levels of CCR1 and CXCR3 levels on T cells, a reduction in PD-1+Lag3+ T cells and CD11+Gr1+ myeloid-derived suppressor cells, and changes in the chemokine/cytokine profile of tumors. Our findings show how T cell–mediated delivery of a TLR agonist to the tumor site can contribute to antitumor efficacy, in the context of adoptive T-cell immunotherapy. Cancer Res; 75(10); 1959–71. ©2015 AACR.
Oncogenic HRAS Activates Epithelial-to-Mesenchymal Transition and Confers Stemness to p53-Deficient Urothelial Cells to Drive Muscle Invasion of Basal Subtype Carcinomas
Authors: He Feng , Melamed Jonathan , Tang Moon-shong , Huang Chuanshu , Wu Xue-Ru 
Published: March 2015

Abstract
Muscle-invasive urothelial carcinomas of the bladder (MIUCB) exhibit frequent receptor tyrosine kinase alterations, but the precise nature of their contributions to tumor pathophysiology is unclear. Using mutant HRAS (HRAS*) as an oncogenic prototype, we obtained evidence in transgenic mice that RTK/RAS pathway activation in urothelial cells causes hyperplasia that neither progresses to frank carcinoma nor regresses to normal urothelium through a period of one year. This persistent hyperplastic state appeared to result from an equilibrium between promitogenic factors and compensatory tumor barriers in the p19–MDM2–p53–p21 axis and a prolonged G2 arrest. Conditional inactivation of p53 in urothelial cells of transgenic mice expressing HRAS* resulted in carcinoma in situ and basal-subtype MIUCB with focal squamous differentiation resembling the human counterpart. The transcriptome of microdissected MIUCB was enriched in genes that drive epithelial-to-mesenchymal transition, the upregulation of which is associated with urothelial cells expressing multiple progenitor/stem cell markers. Taken together, our results provide evidence for RTK/RAS pathway activation and p53 deficiency as a combinatorial theranostic biomarker that may inform the progression and treatment of urothelial carcinoma. Cancer Res; 75(10); 2017–28. ©2015 AACR.
Nerve–Cancer Cell Cross-talk: A Novel Promoter of Tumor Progression
Authors: Jobling Phillip , Pundavela Jay , Oliveira Sonia M.R. , Roselli Séverine , Walker Marjorie M. , Hondermarck Hubert 
Published: March 2015

Abstract
Recent studies have revealed the essential role played by nerves in tumor progression. Nerves have been shown to infiltrate the tumor microenvironment and actively stimulate cancer cell growth and dissemination. This mechanism involves the release of neurotransmitters, such as catecholamines and acetylcholine, directly into the vicinity of cancer and stromal cells to activate corresponding membrane receptors. Conversely, the secretion of neurotrophic growth factors by cancer cells drives the outgrowth of nerves in solid tumors. This reciprocal interaction between nerves and cancer cells provides new insights into the cellular and molecular bases of tumorigenesis and points to the potential utility of antineurogenic therapies. This review will discuss our evolving understanding of the cross-talk between nerves and cancer cells. Cancer Res; 75(9); 1777–81. ©2015 AACR.
A YAP/TAZ-Regulated Molecular Signature Is Associated with Oral Squamous Cell Carcinoma
Authors: Hiemer Samantha E. , Zhang Liye , Kartha Vinay K. , Packer Trevor S. , Almershed Munirah , Noonan Vikki , Kukuruzinska Maria , Bais Manish V. , Monti Stefano , Varelas Xaralabos 
Published: March 2015

Abstract
Oral squamous cell carcinoma (OSCC) is a prevalent form of cancer that develops from the epithelium of the oral cavity. OSCC is on the rise worldwide, and death rates associated with the disease are particularly high. Despite progress in understanding the mutational and expression landscape associated with OSCC, advances in deciphering these alterations for the development of therapeutic strategies have been limited. Further insight into the molecular cues that contribute to OSCC is therefore required. Here, we show that the transcriptional regulators YAP (YAP1) and TAZ (WWTR1), which are key effectors of the Hippo pathway, drive protumorigenic signals in OSCC. Regions of premalignant oral tissues exhibit aberrant nuclear YAP accumulation, suggesting that dysregulated YAP activity contributes to the onset of OSCC. Supporting this premise, we determined that nuclear YAP and TAZ activity drives OSCC cell proliferation, survival, and migration in vitro, and is required for OSCC tumor growth and metastasis in vivo. Global gene expression profiles associated with YAP and TAZ knockdown revealed changes in the control of gene expression implicated in protumorigenic signaling, including those required for cell cycle progression and survival. Notably, the transcriptional signature regulated by YAP and TAZ significantly correlates with gene expression changes occurring in human OSCCs identified by The Cancer Genome Atlas (TCGA), emphasizing a central role for YAP and TAZ in OSCC biology.
Implications: This study defines a YAP/TAZ-regulated transcriptional program in OSCC and reveals novel roles for nuclear YAP/TAZ activity in the onset and progression of this cancer. Mol Cancer Res; 13(6); 957–68. ©2015 AACR.
Relations Between Aortic Stiffness and Left Ventricular Structure and Function in Older Participants in the Age, Gene/Environment Susceptibility-Reykjavik Study
Authors: Bell Vanessa , Sigurdsson Sigurdur , Westenberg Jos J.M. , Gotal John D. , Torjesen Alyssa A. , Aspelund Thor , Launer Lenore J. , Harris Tamara B. , Gudnason Vilmundur , de Roos Albert , Mitchell Gary F. 
Published: March 2015

Background—
Left ventricular (LV) contraction displaces the aortic annulus and produces a force that stretches the ascending aorta. We hypothesized that aortic stiffening increases this previously ignored component of LV load and may contribute to hypertrophy. Conversely, aortic stretch-related work represents stored energy that may facilitate early diastolic filling.

Methods and Results—

We performed MRI of the aorta and LV in 347 participants (72–91 years old, 189 women) in the Age, Gene/Environment Susceptibility-Reykjavik Study to examine relations of aortic stretch with LV structure and function. Aortic stiffness was evaluated as the product of Young’s modulus and aortic wall thickness. Force was computed from Young’s modulus and longitudinal aortic strain; work was the integrated product of force and annulus displacement during systole. LV mass and dynamic volume were measured using the area–length method. Filling was assessed from time-resolved LV volume curves. In multivariable models that adjusted for age, sex, height, weight, end-diastolic LV volume, augmentation index, end-systolic pressure, and cardiovascular disease risk factors, higher aortic stiffness was associated with increased LV mass (β=3.0±0.8% per SD,
P
<0.001; sex interaction,
P
=0.8). Greater stretch-related aortic work was associated with enhanced early filling in men (β=4.0±0.8 mL/SD;
P
<0.001), but not in women (β=−0.4±0.7 mL/SD;
P
=0.6).

Conclusions—
Higher aortic stiffness was associated with higher LV mass, independently of pressure. Higher stretch-related work was associated with greater early diastolic filling in men only. Impaired diastolic recovery of energy stored by systolic proximal aortic stretch may contribute to increased susceptibility to diastolic dysfunction in women.
Vascular Signal Transducer and Activator of Transcription-3 Promotes Angiogenesis and Neuroplasticity Long-Term After Stroke
Authors: Hoffmann Christian J. , Harms Ulrike , Rex Andre , Szulzewsky Frank , Wolf Susanne A. , Grittner Ulrike , Lättig-Tünnemann Gisela , Sendtner Michael , Kettenmann Helmut , Dirnagl Ulrich , Endres Matthias , Harms Christoph 
Published: March 2015

Background—
Poststroke angiogenesis contributes to long-term recovery after stroke. Signal transducer and activator of transcription-3 (Stat3) is a key regulator for various inflammatory signals and angiogenesis. It was the aim of this study to determine its function in poststroke outcome.

Methods and Results—

We generated a tamoxifen-inducible and endothelial-specific Stat3 knockout mouse model by crossbreeding Stat3
floxed/KO
and Tie2-Cre
ERT2
mice. Cerebral ischemia was induced by 30 minutes of middle cerebral artery occlusion. We demonstrated that endothelial Stat3 ablation did not alter lesion size 2 days after ischemia but did worsen functional outcome at 14 days and increase lesion size at 28 days. At this late time point vascular Stat3 expression and phosphorylation were still increased in wild-type mice. Gene array analysis of a CD31-enriched cell population of the neurovascular niche showed that endothelial Stat3 ablation led to a shift toward an antiangiogenic and axon growth-inhibiting micromilieu after stroke, with an increased expression of Adamts9. Remodeling and glycosylation of the extracellular matrix and microglia proliferation were increased, whereas angiogenesis was reduced.

Conclusions—
Endothelial Stat3 regulates angiogenesis, axon growth, and extracellular matrix remodeling and is essential for long-term recovery after stroke. It might serve as a potent target for stroke treatment after the acute phase by fostering angiogenesis and neuroregeneration.
The Dependence of QPF on the Choice of Boundary- and Surface-Layer Parameterization for a Lake-Effect Snowstorm
Authors: Conrick Robert , Reeves Heather Dawn , Zhong Shiyuan 
Published: March 2015

AbstractSix forecasts of a lake-effect-snow event off Lake Erie were conducted using the Weather Research and Forecasting Model to determine how the quantitative precipitation forecast (QPF) was affected when the boundary- and surface-layer parameterization schemes were changed. These forecasts showed strong variability, with differences in liquid-equivalent precipitation maxima in excess of 20 mm over a 6-h period. The quasi-normal scale elimination (QNSE) schemes produced the highest accumulations, and the Mellor–Yamada–Nakanishi–Niino (MYNN) schemes produced the lowest. Differences in precipitation were primarily due to different sensible heat flux FH and moisture flux FQ off the lake, with lower FH and FQ in MYNN leading to comparatively weak low-level instability and, consequently, reduced ascent and production of hydrometeors. The different FH and FQ were found to have two causes. In QNSE, the higher FH and FQ were due to the decision to use a Prandtl number PR of 0.72 (all other schemes use a PR of 1). In MYNN, the lower FH and FQ were due to the manner in which the similarity stability function for heat ψh is functionally dependent on the temperature gradient between the surface and the lowest model layer. It is not known what assumptions are more accurate for environments that are typical for lake-effect snow, but comparisons with available observations and Rapid-Update-Cycle analyses indicated that MYNN had the most accurate results.