bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Prospective Study of Physical Activity and Breast Cancer Incidence in African-American Women
Authors: Rosenberg Lynn , Palmer Julie R. , Bethea Traci N. , Ban Yulun , Kipping-Ruane Kristen , Adams-Campbell Lucile L. 
Published: August 2014

AbstractBackground: Physical activity has been associated with reduced risk of breast cancer. Evidence on the association in African Americans is limited.Methods: With prospective data from the Black Women's Health Study, we assessed vigorous exercise and walking in relation to incidence of invasive breast cancer overall (n = 1,364), estrogen receptor–positive (ER+, n = 688) cancer, and estrogen receptor–negative (ER−, n = 405) cancer, based on 307,672 person-years of follow-up of 44,708 African-American women ages 30 years or older at enrollment. Cox proportional hazards models estimated incidence rate ratios (IRR) and 95% confidence intervals (CI).Results: Vigorous exercise at baseline was inversely associated with overall breast cancer incidence (Ptrend = 0.05): the IRR for ≥7 h/wk relative to &lt;1 h/wk was 0.74 (95% CI, 0.57–0.96). The association did not differ by ER status. Brisk walking for ≥7 h/wk was associated with a reduction similar to that for vigorous exercise. Vigorous exercise at the age of 30 years, 21 years, or in high school was not associated with breast cancer incidence. Sitting for long periods at work or watching TV was not significantly associated with breast cancer incidence.Conclusion: High levels of vigorous exercise or brisk walking may be associated with a reduction in incidence of breast cancer in African-American women.Impact: These results provide informative data on a potential modifiable risk factor, exercise, for breast cancer in African-American women. Cancer Epidemiol Biomarkers Prev; 23(11); 2522–31. ©2014 AACR.
Cancer Prevention and Control Interventions Using Social Media: User-Generated Approaches
Authors: Cavallo David N. , Chou Wen-Ying Sylvia , McQueen Amy , Ramirez Amelie , Riley William T. 
Published: August 2014

Abstract
Social media are now used by a majority of American internet users. Social media platforms encourage participants to share information with their online social connections and exchange user-generated content. Significant numbers of people are already using social media to share health-related information. As such, social media provide an opportunity for “user-generated” cancer control and prevention interventions that employ users' behavior, knowledge, and existing social networks for the creation and dissemination of interventions. These interventions also enable novel data collection techniques and research designs that will allow investigators to examine real-time behavioral responses to interventions. Emerging social media-based interventions for modifying cancer-related behaviors have been applied to such domains as tobacco use, diet, physical activity, and sexual practices, and several examples are discussed for illustration purposes. Despite some promising early findings, challenges including inadequate user engagement, privacy concerns, and lack of internet access among some groups need to be addressed in future research. Recommendations for advancing the field include stronger partnerships with commercial technology companies, utilization of rapid and adaptive designs to identify successful strategies for user engagement, rigorous and iterative efficacy testing of these strategies, and inclusive methods for intervention dissemination. Cancer Epidemiol Biomarkers Prev; 23(9); 1953–6. ©2014 AACR.
TGFβ Induces “BRCAness” and Sensitivity to PARP Inhibition in Breast Cancer by Regulating DNA-Repair Genes
Authors: Liu Liang , Zhou Weiying , Cheng Chun-Ting , Ren Xiubao , Somlo George , Fong Miranda Y. , Chin Andrew R. , Li Hui , Yu Yang , Xu Yang , O'Connor Sean Timothy Francis , O'Connor Timothy R. , Ann David K. , Stark Jeremy M. , Wang Shizhen Emily 
Published: August 2014

Abstract
Transforming growth factor beta (TGFβ) proteins are multitasking cytokines, in which high levels at tumor sites generally correlate with poor prognosis in human patients with cancer. Previously, it was reported that TGFβ downregulates the expression of ataxia telangiectasia–mutated (ATM) and mutS homolog 2 (MSH2) in breast cancer cells through an miRNA-mediated mechanism. In this study, expression of a panel of DNA-repair genes was examined, identifying breast cancer 1, early onset (BRCA1) as a target downregulated by TGFβ through the miR181 family. Correlations between the expression levels of TGFβ1 and the miR181/BRCA1 axis were observed in primary breast tumor specimens. By downregulating BRCA1, ATM, and MSH2, TGFβ orchestrates DNA damage response in certain breast cancer cells to induce a “BRCAness” phenotype, including impaired DNA-repair efficiency and synthetic lethality to the inhibition of poly (ADP-ribose) polymerase (PARP). Xenograft tumors with active TGFβ signaling exhibited resistance to the DNA-damaging agent doxorubicin but increased sensitivity to the PARP inhibitor ABT-888. Combination of doxorubicin with ABT-888 significantly improved the treatment efficacy in TGFβ-active tumors. Thus, TGFβ can induce “BRCAness” in certain breast cancers carrying wild-type BRCA genes and enhance the responsiveness to PARP inhibition, and the molecular mechanism behind this is characterized.
Implications: These findings enable better selection of patients with sporadic breast cancer for PARP interventions, which have exhibited beneficial effects in patients carrying BRCA mutations. Mol Cancer Res; 12(11); 1597–609. ©2014 AACR.
Caffeic Acid Directly Targets ERK1/2 to Attenuate Solar UV-Induced Skin Carcinogenesis
Authors: Yang Ge , Fu Yang , Malakhova Margarita , Kurinov Igor , Zhu Feng , Yao Ke , Li Haitao , Chen Hanyong , Li Wei , Lim Do Young , Sheng Yuqiao , Bode Ann M. , Dong Ziming , Dong Zigang 
Published: August 2014

Abstract
Caffeic acid (3,4-dihydroxycinnamic acid) is a well-known phenolic phytochemical present in coffee and reportedly has anticancer activities. However, the underlying molecular mechanisms and targeted proteins involved in the suppression of carcinogenesis by caffeic acid are not fully understood. In this study, we report that caffeic acid significantly inhibits colony formation of human skin cancer cells and EGF-induced neoplastic transformation of HaCaT cells dose-dependently. Caffeic acid topically applied to dorsal mouse skin significantly suppressed tumor incidence and volume in a solar UV (SUV)–induced skin carcinogenesis mouse model. A substantial reduction of phosphorylation in mitogen-activated protein kinase signaling was observed in mice treated with caffeic acid either before or after SUV exposure. Caffeic acid directly interacted with ERK1/2 and inhibited ERK1/2 activities in vitro. Importantly, we resolved the cocrystal structure of ERK2 complexed with caffeic acid. Caffeic acid interacted directly with ERK2 at amino acid residues Q105, D106, and M108. Moreover, A431 cells expressing knockdown of ERK2 lost sensitivity to caffeic acid in a skin cancer xenograft mouse model. Taken together, our results suggest that caffeic acid exerts chemopreventive activity against SUV-induced skin carcinogenesis by targeting ERK1 and 2. Cancer Prev Res; 7(10); 1056–66. ©2014 AACR.
Nature of Tumor Control by Permanently and Transiently Modified GD2 Chimeric Antigen Receptor T Cells in Xenograft Models of Neuroblastoma
Authors: Singh Nathan , Liu Xiaojun , Hulitt Jessica , Jiang Shuguang , June Carl H. , Grupp Stephan A. , Barrett David M. , Zhao Yangbing 
Published: August 2014

Abstract
Chimeric antigen receptor (CAR) therapy has begun to demonstrate success as a novel treatment modality for hematologic malignancies. The success observed thus far has been with T cells permanently engineered to express chimeric receptors. T cells engineered using RNA electroporation represent an alternative with the potential for similar efficacy and greater safety when initially targeting novel antigens. Neuroblastoma is a common pediatric solid tumor with the potential to be targeted using immunotherapy. We performed xenograft studies in NSG mice in which we assessed the efficacy of both permanently modified and transiently modified CAR T cells directed against the neuroblastoma antigen GD2 in both local and disseminated disease models. Disease response was monitored by tumor volume measurement and histologic examination, as well as in vivo bioluminescence. RNA-modified GD2 CAR T cells mediated rapid tumor destruction when delivered locally. A single infusion of lentivirally modified GD2 CAR T cells resulted in long-term control of disseminated disease. Multiple infusions of RNA GD2 CAR T cells slowed the progression of disseminated disease and improved survival, but did not result in long-term disease control. Histologic examination revealed that the transiently modified cells were unable to significantly penetrate the tumor environment when delivered systemically, despite multiple infusions of CAR T cells. Thus, we demonstrate that RNA-modified GD2 CAR T cells can mediate effective antitumor responses in vivo, and permanently modified cells are able to control disseminated neuroblastoma in xenograft mice. Lack of long-term disease control by RNA-engineered cells resulted from an inability to penetrate the tumor microenvironment. Cancer Immunol Res; 2(11); 1059–70. ©2014 AACR.
Cooperation between human fibrocytes and endothelial colony-forming cells increases angiogenesis via the CXCR4 pathway
Authors: Dorfmüller Peter , Guerin Coralie , Bieche Ivan , Badoual Cécile , Boscolo Elisa , Kambouchner Marianne , Cazes Aurélie , Mercier Olaf , Humbert Marc , Gaussem Pascale , Bischoff Joyce , Israël-Biet Dominique , Smadja David 
Published: August 2014

SummaryFibrotic diseases of the lung are associated with a vascular remodelling process. Fibrocytes (Fy) are a distinct population of blood-borne cells that co-express haematopoietic cell antigens and fibroblast markers, and have been shown to contribute to organ fibrosis. The purpose of this study was to determine whether fibrocytes cooperate with endothelial colony-forming cells (ECFC) to induce angiogenesis. We isolated fibrocytes from blood of patient with idiopathic pulmonary fibrosis (IPF) and characterised them by flow cytometry, quantitative reverse transcriptase PCR (RTQ-PCR), and confocal microscopy. We then investigated the angiogenic interaction between fibrocytes and cordblood- derived ECFC, both in vitro and in an in vivo Matrigel implant model. Compared to fibroblast culture medium, fibrocyte culture medium increased ECFC proliferation and differentiation via the SDF- 1/CXCR4 pathway. IPF-Fy co-implanted with human ECFC in Matrigel plugs in immunodeficient mice formed functional microvascular beds, whereas fibroblasts did not. Evaluation of implants after two weeks revealed an extensive network of erythrocyte-containing blood vessels. CXCR4 blockade significantly inhibited this blood vessel formation. The clinical relevance of these data was confirmed by strong CXCR4 expression in vessels close to fibrotic areas in biopsy specimens from patients with IPF, by comparison with control lungs. In conclusion, circulating fibrocytes might contribute to the intense remodelling of the pulmonary vasculature in patients with idiopathic pulmonary fibrosis.
Targeted mass spectrometry analysis of neutrophil-derived proteins released during sepsis progression
Authors: Davidova Alzbeta , Mörgelin Matthias , Linder Adam , Larsen Michael , Qvortrup Klaus , Nordenfelt Pontus , Shannon Oonagh , Dzupova Olga , Holub Michal , Malmström Johan , Herwald Heiko , Malmström Erik 
Published: August 2014

SummaryEarly diagnosis of severe infectious diseases is essential for timely implementation of lifesaving therapies. In a search for novel biomarkers in sepsis diagnosis we focused on polymorphonuclear neutrophils (PMNs). Notably, PMNs have their protein cargo readily stored in granules and following systemic stimulation, an immediate increase of neutrophil-borne proteins can be observed into the circulation of sepsis patients. We applied a combination of mass spectrometry (MS) based approaches, LC-MS/MS and selected reaction monitoring (SRM), to characterise and quantify the neutrophil proteome in healthy or disease conditions. With this approach we identified a neutrophil- derived protein abundance pattern in blood plasma consisting of 20 proteins that can be used as a protein signature for severe infectious diseases. Our results also show that SRM is highly sensitive, specific, and reproducible and, thus, a promising technology to study a complex, dynamic and multifactorial disease such as sepsis.
Bleeding diathesis and gastro-duodenal ulcers in inherited cytosolic phospholipase-A2 alpha deficiency
Authors: Faioni Elena , Razzari Cristina , Zulueta Aida , Femia Eti , Fenu Lara , Trinchera Marco , Podda Gian Marco , Pugliano Mariateresa , Marongiu Francesco , Cattaneo Marco 
Published: August 2014

SummaryArachidonic acid (AA), when cleaved from phospholipids by cytosolic phospholipase A2 alpha (cPLA2a), generates eicosanoids, with pro-hemostatic, pro-inflammatory, vasoactive and gastro-protective functions. We describe a patient (27-year-old man) and his twin-sister with early-onset bleeding diathesis and recurrent gastro-intestinal (GI) ulcers. Platelet aggregation/δ-granules secretion by collagen was impaired, but normal by AA; serum levels of thromboxane (Tx) B2 and 12-hydroxyeicosatetraenoic acid, and urinary levels of 11-dehydro- TxB2 were extremely low. Patients were homozygous for 1723G>C transition in PLA2G4A gene, which changed the codon for Asp575 to His. GI ulcers affected 5/14 heterozygous (< 40 years) and 1/16 wildtype homozygous (> 60 years) family members; none had bleeding diathesis. The proband, his sister and mother also had mildly reduced factor XI levels. Platelet messenger RNA expression did not differ among subjects with different PLA2G4A genotypes. Conversely, platelet cPLA2a was undetectable by Western Blotting in the proband and his sister, and decreased in 1723G>C heterozygous subjects, suggesting that the variant is transcribed, but not translated or translated into an unstable protein. We described a syndromic form of deficiency of cPLA2a , characterised by recurrent GI ulcers and bleeding diathesis, associated with mild inherited deficiency of factor XI. Unlike other reported patients with cPLA2a deficiency, these patients had extremely low levels of platelet TxA2 biosynthesis.
Rosuvastatin Activates ATP-Binding Cassette Transporter A1–Dependent Efflux Ex Vivo and Promotes Reverse Cholesterol Transport in Macrophage Cells in Mice Fed a High-Fat Diet
Authors: Shimizu Tomohiko , Miura Shin-ichiro , Tanigawa Hiroyuki , Kuwano Takashi , Zhang Bo , Uehara Yoshinari , Saku Keijiro 
Published: August 2014

Objective—
It is controversial whether statins improve high-density lipoprotein (HDL) function, which plays an important role in reverse cholesterol transport in vivo. The aim of the present study was to clarify the effects of rosuvastatin and atorvastatin on reverse cholesterol transport in macrophage cells in vivo and their underlying mechanisms.

Approach and Results—

Male C57BL mice were divided into 3 groups (rosuvastatin, atorvastatin, and control groups) and orally administered rosuvastatin, atorvastatin, or placebo for 6 weeks under feeding with a 0.5% cholesterol+10% coconut oil diet. After administration, although there were no changes in plasma HDL cholesterol levels among the groups, plasma from the rosuvastatin group showed an increased ability to promote ATP-binding cassette transporter A1–mediated cholesterol efflux ex vivo. In addition, capillary electrophoresis revealed a shift in HDL toward the pre-β HDL fraction only in the rosuvastatin group. Mice in all 3 groups were intraperitoneally injected with
3
H-cholesterol–labeled and cholesterol-loaded macrophages and then were monitored for the appearance of
3
H-tracer in plasma and feces. The amount of
3
H-tracer excreted into feces during 48 hours in the rosuvastatin group was greater than that in the control group. Finally,
3
H-cholesteryl oleate-HDL was intravenously injected into all groups, blood samples were taken, and the count of
3
H-cholesterol was analyzed. Plasma
3
H-cholesteryl oleate-HDL changed similarly, and no differences in fractional catabolic rates were observed.

Conclusions—
Rosuvastatin enhanced the ATP-binding cassette transporter A1–dependent HDL efflux function of reverse cholesterol transport, and this finding highlights the potential of rosuvastatin for the regression of atherosclerosis.
Elevated Parathyroid Hormone, But Not Vitamin D Deficiency, Is Associated With Increased Risk of Heart Failure in Older Men With and Without Cardiovascular Disease
Authors: Wannamethee S. Goya , Welsh Paul , Papacosta Olia , Lennon Lucy , Whincup Peter H. , Sattar Naveed 
Published: August 2014

Background—
Hyperparathyroidism and low vitamin D status have been implicated in the pathogenesis of heart failure (HF). We examined the prospective associations between parathyroid hormone (PTH), circulating 25-hydroxyvitamin D, and markers of mineral metabolism and risk of incident HF in older men with and without established cardiovascular disease.

Methods and Results—
Prospective study of 3731 men aged 60 to 79 years with no prevalent HF followed up for a mean period of 13 years, in whom there were 287 incident HF cases. Elevated PTH (≥55.6 pg/mL; top quarter) was associated with significantly higher risk of incident HF after adjustment for lifestyle characteristics, diabetes mellitus, blood lipids, blood pressure, lung function, heart rate, renal dysfunction, atrial fibrillation, forced expiratory volume in 1 second, and C-reactive protein (hazards ratio, 1.66; 95% confidence interval, 1.30–2.13). The increased risk was seen in both men with and without previous myocardial infarction or stroke (hazards ratio, 1.72; 95% confidence interval, 1.07–2.76; hazards ratio, 1.70; 95% confidence interval, 1.25–2.30, respectively). Elevated PTH was significantly associated with N-terminal probrain natriuretic peptide, a marker of left ventricular wall stress. By contrast, 25-hydroxyvitamin D and other markers of mineral metabolism including serum calcium and phosphate showed no significant association with incident HF after adjustment for age.

Conclusions—
Elevated PTH, but not 25-hydroxyvitamin D or other markers of mineral metabolism, is associated with increased risk of HF in both older men with and without myocardial infarction/stroke. This increased risk was not explained by its association with known risk factors for HF. Further studies are now needed to elucidate the mechanisms underlying this association.
A Unified Convection Scheme (UNICON). Part I: Formulation
Authors: Park Sungsu 
Published: August 2014

Abstract
The author develops a unified convection scheme (UNICON) that parameterizes relative (i.e., with respect to the grid-mean vertical flow) subgrid vertical transport by nonlocal asymmetric turbulent eddies. UNICON is a process-based model of subgrid convective plumes and mesoscale organized flow without relying on any quasi-equilibrium assumptions such as convective available potential energy (CAPE) or convective inhibition (CIN) closures. In combination with a relative subgrid vertical transport scheme by local symmetric turbulent eddies and a grid-scale advection scheme, UNICON simulates vertical transport of water species and conservative scalars without double counting at any horizontal resolution.
UNICON simulates all dry–moist, forced–free, and shallow–deep convection within a single framework in a seamless, consistent, and unified way. It diagnoses the vertical profiles of the macrophysics (fractional area, plume radius, and number density) as well as the microphysics (production and evaporation rates of convective precipitation) and the dynamics (mass flux and vertical velocity) of multiple convective updraft and downdraft plumes. UNICON also prognoses subgrid cold pool and mesoscale organized flow within the planetary boundary layer (PBL) that is forced by evaporation of convective precipitation and accompanying convective downdrafts but damped by surface flux and entrainment at the PBL top. The combined subgrid parameterization of diagnostic convective updraft and downdraft plumes, prognostic subgrid mesoscale organized flow, and the feedback among them remedies the weakness of conventional quasi-steady diagnostic plume models—the lack of plume memory across the time step—allowing UNICON to successfully simulate various transitional phenomena associated with convection (e.g., the diurnal cycle of precipitation and the Madden–Julian oscillation).
Energetics of East Pacific Easterly Waves during Intraseasonal Events
Authors: Rydbeck Adam V. , Maloney Eric D. 
Published: August 2014

Abstract
The background atmospheric state of the east Pacific warm pool in which easterly waves develop varies dramatically on intraseasonal time scales. East Pacific intraseasonal variability is well known to modulate local convective and circulation patterns. Westerly (easterly) intraseasonal phases are associated with westerly (easterly) low-level wind and positive (negative) convective anomalies. This study investigates the perturbation available potential energy (PAPE) and perturbation kinetic energy (PKE) budgets of easterly waves composited during westerly, easterly, and neutral intraseasonal phases, respectively. The mechanisms, magnitudes, locations, and vertical structures of easterly waves are shown to strongly vary as a function of intraseasonal phase. Easterly waves draw energy from low-level barotropic conversion, regardless of phase, although the location and magnitude of the conversion varies strongly. During neutral and westerly intraseasonal phases, the generation of PAPE associated with perturbation diabatic heating that is subsequently converted to PKE is the dominant energy source for easterly waves. A novel and previously unrecognized result is the detection of strong barotropic generation of PKE at midlevels during westerly intraseasonal phases. This previously unidentified source of PKE at midlevels is in part due to strong intraseasonal modulation of the background midlevel winds.
Parameter Tuning and Calibration of RegCM3 with MIT–Emanuel Cumulus Parameterization Scheme over CORDEX East Asia Domain
Authors: Zou Liwei , Qian Yun , Zhou Tianjun , Yang Ben 
Published: August 2014

Abstract
In this study, the authors calibrated the performance of the Regional Climate Model, version 3 (RegCM3), with the Massachusetts Institute of Technology (MIT)–Emanuel cumulus parameterization scheme over the Coordinated Regional Climate Downscaling Experiment (CORDEX) East Asia domain by tuning seven selected parameters based on the multiple very fast simulated annealing (MVFSA) approach. The seven parameters were selected based on previous studies using RegCM3 with the MIT–Emanuel convection scheme. The results show the simulated spatial pattern of rainfall, and the probability density function distribution of daily rainfall rates is significantly improved in the optimal simulation. Sensitivity analysis suggests that the parameter relative humidity criteria (RHC) has the largest effect on the model results. Followed by an increase of RHC, an increase of total rainfall is found over the northern equatorial western Pacific, mainly contributed by the increase of explicit rainfall. The increases of the convergence of low-level water vapor transport and the associated increases in cloud water favor the increase of explicit rainfall. The identified optimal parameters constrained by total rainfall have positive effects on the low-level circulation and surface air temperature. Furthermore, the optimized parameters based on the chosen extreme case are transferable to a normal case and the model’s new version with a mixed convection scheme.