bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between FGFR-2, STAT5, and Progesterone Receptors in Breast Cancer
Authors: Cerliani Juan P. , Guillardoy Tomás , Giulianelli Sebastián , Vaque José P. , Gutkind J. Silvio , Vanzulli Silvia I. , Martins Rubén , Zeitlin Eduardo , Lamb Caroline A. , Lanari Claudia 
Published: April 2011

Abstract
Fibroblast growth factor (FGF) receptor 2 (FGFR-2) polymorphisms have been associated with an increase in estrogen receptor and progesterone receptor (PR)-positive breast cancer risk; however, a clear mechanistic association between FGFR-2 and steroid hormone receptors remains elusive. In previous works, we have shown a cross talk between FGF2 and progestins in mouse mammary carcinomas. To investigate the mechanisms underlying these interactions and to validate our findings in a human setting, we have used T47D human breast cancer cells and human cancer tissue samples. We showed that medroxyprogesterone acetate (MPA) and FGF2 induced cell proliferation and activation of ERK, AKT, and STAT5 in T47D and in murine C4-HI cells. Nuclear interaction between PR, FGFR-2, and STAT5 after MPA and FGF2 treatment was also showed by confocal microscopy and immunoprecipitation. This effect was associated with increased transcription of PRE and/or GAS reporter genes, and of PR/STAT5-regulated genes and proteins. Two antiprogestins and the FGFR inhibitor PD173074, specifically blocked the effects induced by FGF2 or MPA respectively. The presence of PR/FGFR-2/STAT5 complexes bound to the PRE probe was corroborated by using NoShift transcription and chromatin immunoprecipitation of the MYC promoter. Additionally, we showed that T47D cells stably transfected with constitutively active FGFR-2 gave rise to invasive carcinomas when transplanted into NOD/SCID mice. Nuclear colocalization between PR and FGFR-2/STAT5 was also observed in human breast cancer tissues. This study represents the first demonstration of a nuclear interaction between FGFR-2 and STAT5, as PR coactivators at the DNA progesterone responsive elements, suggesting that FGFRs are valid therapeutic targets for human breast cancer treatment. Cancer Res; 71(10); 3720–31. ©2011 AACR.
Persistent Racial Disparities in Survival After Heart Transplantation
Authors: Liu Vincent , Bhattacharya Jay , Weill David , Hlatky Mark A. 
Published: April 2011

Background—
Racial and ethnic disparities are well documented in many areas of health care, but have not been comprehensively evaluated among recipients of heart transplants.

Methods and Results—

We performed a retrospective cohort study of 39075 adult primary heart transplant recipients from 1987 to 2009 using national data from the United Network of Organ Sharing and compared mortality for nonwhite and white patients using the Cox proportional hazards model. During the study period, 8082 nonwhite and 30 993 white patients underwent heart transplantation. Nonwhite heart transplant recipients increased over time, comprising nearly 30% of transplantations since 2005. Nonwhite recipients had a higher clinical risk profile than white recipients at the time of transplantation, but had significantly higher posttransplantation mortality even after adjustment for baseline risk. Among the nonwhite group, only black recipients had an increased risk of death compared with white recipients after multivariable adjustment for recipient, transplant, and socioeconomic factors (hazard ratio, 1.34; 95% confidence interval, 1.21 to 1.47;
P
<0.001). Five-year mortality was 35.7% (95% confidence interval, 35.2 to 38.3) among black and 26.5% (95% confidence interval, 26.0 to 27.0) among white recipients. Black patients were more likely to die of graft failure or a cardiovascular cause than white patients, but less likely to die of infection or malignancy. Although mortality decreased over time for all transplant recipients, the disparity in mortality between blacks and whites remained essentially unchanged.

Conclusions—
Black heart transplant recipients have had persistently higher mortality than whites recipients over the past 2 decades, perhaps because of a higher rate of graft failure.
Associations Between Outpatient Heart Failure Process-of-Care Measures and Mortality
Authors: Fonarow Gregg C. , Albert Nancy M. , Curtis Anne B. , Gheorghiade Mihai , Heywood J. Thomas , Liu Yang , Mehra Mandeep R. , O'Connor Christopher M. , Reynolds Dwight , Walsh Mary Norine , Yancy Clyde W. 
Published: April 2011

Background—
Assessment of the quality of care for outpatients with heart failure (HF) has focused on the development and use of process-based performance measures, with the supposition that these care process measures are associated with clinical outcomes. However, this association has not been evaluated for current and emerging outpatient HF measures.

Methods and Results—

Performance on 7 HF process measures (4 current and 3 emerging) and 2 summary measures was assessed at baseline in patients from 167 US outpatient cardiology practices with patients prospectively followed up for 24 months. Participants included 15 177 patients with reduced left ventricular ejection fraction (≤35%) and chronic HF or post–myocardial infarction. Multivariable analyses were performed to assess the process-outcome relationship for each measure in eligible patients. Vital status was available for 11 621 patients. The mortality rate at 24 months was 22.1%. Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, β-blocker use, anticoagulant therapy for atrial fibrillation, cardiac resynchronization therapy, implantable cardioverter-defibrillators, and HF education for eligible patients were each independently associated with improved 24-month survival, whereas aldosterone antagonist use was not. The all-or-none and composite care summary measures were also independently associated with improved survival. Each 10% improvement in composite care was associated with a 13% lower odds of 24-month mortality (adjusted odds ratio, 0.87; 95% confidence interval, 0.84 to 0.90;
P
<0.0001).

Conclusions—
Current and emerging outpatient HF process measures are positively associated with patient survival. These HF measures may be useful for assessing and improving HF care.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00303979.
Induction of human fetal hemoglobin via the NRF2 antioxidant response signaling pathway
Authors: Macari Elizabeth R. , Lowrey Christopher H. 
Published: April 2011

AbstractAlthough hematopoietic stem cell transplantation and gene therapy have the potential to cure β-thalassemia and sickle cell disease, they are not currently available to most people with these diseases. In the near term, pharmacologic induction of fetal hemoglobin (HbF) may offer the best possibility for safe, effective, and widely available therapy. In an effort to define new pathways for targeted drug development for HbF induction, we evaluated the nuclear factor erythroid 2–related factor 2 (NRF2) antioxidant response element signaling pathway. We found that 3 well-known activators of this pathway increased γ-globin mRNA at nontoxic doses in K562 cells. Tert-butylhydroquinone (tBHQ), the most active of these compounds, increased cellular levels and nuclear translocation of NRF2 and binding of NRF2 to the γ-globin promoter. siRNA knockdown of NRF2 inhibited γ-globin induction by tBHQ. When tested in human primary erythroid cells, tBHQ induced NRF2 binding to the γ-globin promoter, increased γ-globin mRNA and HbF, and suppressed β-globin mRNA and HbA, resulting in a > 3-fold increase in the percentage of HbF. These results suggest that drugs that activate the NRF2/antioxidant response element signaling pathway have the potential to induce therapeutic levels of HbF in people with β-hemoglobinopathies.
Comparative proteomic analysis of Lactobacillus plantarumfor the identification of key proteins in bile tolerance
Authors: Hamon Erwann , Horvatovich Peter , Izquierdo Esther , Bringel Françoise , Marchioni Eric , Aoudé-Werner Dalal , Ennahar Saïd 
Published: April 2011

Abstract

Background
Lactic acid bacteria are commonly marketed as probiotics based on their putative or proven health-promoting effects. These effects are known to be strain specific but the underlying molecular mechanisms remain poorly understood. Therefore, unravelling the determinants behind probiotic features is of particular interest since it would help select strains that stand the best chance of success in clinical trials. Bile tolerance is one of the most crucial properties as it determines the ability of bacteria to survive in the small intestine, and consequently their capacity to play their functional role as probiotics. In this context, the objective of this study was to investigate the natural protein diversity within the Lactobacillus plantarum species with relation to bile tolerance, using comparative proteomics.

Results
Bile tolerance properties of nine L. plantarum strains were studied in vitro. Three of them presenting different bile tolerance levels were selected for comparative proteomic analysis: L. plantarum 299 V (resistant), L. plantarum LC 804 (intermediate) and L. plantarum LC 56 (sensitive). Qualitative and quantitative differences in proteomes were analyzed using two-dimensional electrophoresis (2-DE), tryptic digestion, liquid chromatography-mass spectrometry analysis and database search for protein identification. Among the proteins correlated with differences in the 2-DE patterns of the bacterial strains, 15 have previously been reported to be involved in bile tolerance processes. The effect of a bile exposure on these patterns was investigated, which led to the identification of six proteins that may be key in the bile salt response and adaptation in L. plantarum: two glutathione reductases involved in protection against oxidative injury caused by bile salts, a cyclopropane-fatty-acyl-phospholipid synthase implicated in maintenance of cell envelope integrity, a bile salt hydrolase, an ABC transporter and a F0F1-ATP synthase which participate in the active removal of bile-related stress factors.

Conclusions
These results showed that comparative proteomic analysis can help understand the differential bacterial properties of lactobacilli. In the field of probiotic studies, characteristic proteomic profiles can be identified for individual properties that may serve as bacterial biomarkers for the preliminary selection of strains with the best probiotic potential.
The novel curcumin analog FLLL32 decreases STAT3 DNA binding activity and expression, and induces apoptosis in osteosarcoma cell lines
Authors: Fossey Stacey L , Bear Misty D , Lin Jiayuh , Li Chenglong , Schwartz Eric B , Li Pui-Kai , Fuchs James R , Fenger Joelle , Kisseberth William C , London Cheryl A 
Published: April 2011

Abstract

Background
Curcumin is a naturally occurring phenolic compound shown to have a wide variety of antitumor activities; however, it does not attain sufficient blood levels to do so when ingested. Using structure-based design, a novel compound, FLLL32, was generated from curcumin. FLLL32 possesses superior biochemical properties and more specifically targets STAT3, a transcription factor important in tumor cell survival, proliferation, metastasis, and chemotherapy resistance. In our previous work, we found that several canine and human osteosarcoma (OSA) cell lines, but not normal osteoblasts, exhibit constitutive phosphorylation of STAT3. Compared to curcumin, we hypothesized that FLLL32 would be more efficient at inhibiting STAT3 function in OSA cells and that this would result in enhanced downregulation of STAT3 transcriptional targets and subsequent death of OSA cells.

Methods
Human and canine OSA cells were treated with vehicle, curcumin, or FLLL32 and the effects on proliferation (CyQUANT®), apoptosis (SensoLyte® Homogeneous AMC Caspase- 3/7 Assay kit, western blotting), STAT3 DNA binding (EMSA), and vascular endothelial growth factor (VEGF), survivin, and matrix metalloproteinase-2 (MMP2) expression (RT-PCR, western blotting) were measured. STAT3 expression was measured by RT-PCR, qRT- PCR, and western blotting.

Results
Our data showed that FLLL32 decreased STAT3 DNA binding by EMSA. FLLL32 promoted loss of cell proliferation at lower concentrations than curcumin leading to caspase-3- dependent apoptosis, as evidenced by PARP cleavage and increased caspase 3/7 activity; this could be inhibited by treatment with the pan-caspase inhibitor Z-VAD-FMK. Treatment of OSA cells with FLLL32 decreased expression of survivin, VEGF, and MMP2 at both mRNA and protein levels with concurrent decreases in phosphorylated and total STAT3; this loss of total STAT3 occurred, in part, via the ubiquitin-proteasome pathway.

Conclusions
These data demonstrate that the novel curcumin analog FLLL32 has biologic activity against OSA cell lines through inhibition of STAT3 function and expression. Future work with FLLL32 will define the therapeutic potential of this compound in vivo.
Sociodemographic and occupational risk factors associated with the development of different burnout types: the cross-sectional University of Zaragoza study
Authors: Montero-Marín Jesús , García-Campayo Javier , Fajó-Pascual Marta , Carrasco José Miguel , Gascón Santiago , Gili Margarita , Mayoral-Cleries Fermín 
Published: April 2011

AbstractBackgroundThree different burnout types have been described: The "frenetic" type describes involved and ambitious subjects who sacrifice their health and personal lives for their jobs; the "underchallenged" type describes indifferent and bored workers who fail to find personal development in their jobs and the "worn-out" in type describes neglectful subjects who feel they have little control over results and whose efforts go unacknowledged. The study aimed to describe the possible associations between burnout types and general sociodemographic and occupational characteristics.MethodsA cross-sectional study was carried out on a multi-occupational sample of randomly selected university employees (n = 409). The presence of burnout types was assessed by means of the "Burnout Clinical Subtype Questionnaire (BCSQ-36)", and the degree of association between variables was assessed using an adjusted odds ratio (OR) obtained from multivariate logistic regression models.ResultsIndividuals working more than 40 hours per week presented with the greatest risk for "frenetic" burnout compared to those working fewer than 35 hours (adjusted OR = 5.69; 95% CI = 2.52-12.82;p< 0.001). Administration and service personnel presented the greatest risk of "underchallenged" burnout compared to teaching and research staff (adjusted OR = 2.85; 95% CI = 1.16-7.01;p= 0.023). Employees with more than sixteen years of service in the organisation presented the greatest risk of "worn-out" burnout compared to those with less than four years of service (adjusted OR = 4.56; 95% CI = 1.47-14.16;p= 0.009).ConclusionsThis study is the first to our knowledge that suggests the existence of associations between the different burnout subtypes (classified according to the degree of dedication to work) and the different sociodemographic and occupational characteristics that are congruent with the definition of each of the subtypes. These results are consistent with the clinical profile definitions of burnout syndrome. In addition, they assist the recognition of distinct profiles and reinforce the idea of differential characterisation of the syndrome for more effective treatment.
A study protocol for the evaluation of occupational mutagenic/carcinogenic risks in subjects exposed to antineoplastic drugs: a multicentric project
Authors: Moretti Massimo , Bonfiglioli Roberta , Feretti Donatella , Pavanello Sofia , Mussi Francesca , Grollino Maria G , Villarini Milena , Barbieri Anna , Ceretti Elisabetta , Carrieri Mariella , Buschini Annamaria , Appolloni Massimo , Dominici Luca , Sabatini Laura , Gelatti Umberto , Bartolucci Giovanni B , Poli Paola , Stronati Laura , Mastrangelo Giuseppe , Monarca Silvano 
Published: April 2011

Abstract

Background
Some industrial hygiene studies have assessed occupational exposure to antineoplastic drugs; other epidemiological investigations have detected various toxicological effects in exposure groups labeled with the job title. In no research has the same population been studied both environmentally and epidemiologically. The protocol of the epidemiological study presented here uses an integrated environmental and biological monitoring approach. The aim is to assess in hospital nurses preparing and/or administering therapy to cancer patients the current level of occupational exposure to antineoplastic drugs, DNA and chromosome damage as cancer predictive effects, and the association between the two.

Methods/Design
About 80 healthy non-smoking female nurses, who job it is to prepare or handle antineoplastic drugs, and a reference group of about 80 healthy non-smoking female nurses not occupationally exposed to chemicals will be examined simultaneously in a cross-sectional study. All the workers will be recruited from five hospitals in northern and central Italy after their informed consent has been obtained.
Evaluation of surface contamination and dermal exposure to antineoplastic drugs will be assessed by determining cyclophosphamide on selected surfaces (wipes) and on the exposed nurses' clothes (pads). The concentration of unmetabolized cyclophosphamide as a biomarker of internal dose will be measured in end-shift urine samples from exposed nurses.
Biomarkers of effect and susceptibility will be assessed in exposed and unexposed nurses: urinary concentration of 8-hydroxy-2-deoxyguanosine; DNA damage detected using the single-cell microgel electrophoresis (comet) assay in peripheral white blood cells; micronuclei and chromosome aberrations in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e. glutathione S-transferases) will also be analysed.
Using standardized questionnaires, occupational exposure will be determined in exposed nurses only, whereas potential confounders (medicine consumption, lifestyle habits, diet and other non-occupational exposures) will be assessed in both groups of hospital workers.
Statistical analysis will be performed to ascertain the association between occupational exposure to antineoplastic drugs and biomarkers of DNA and chromosome damage, after taking into account the effects of individual genetic susceptibility, and the presence of confounding exposures.

Discussion
The findings of the study will be useful in updating prevention procedures for handling antineoplastic drugs.
Systems analysis of endothelial cell plasma membrane proteome of rat lung microvasculature
Authors: Li Yan , Massey Kerri , Witkiewicz Halina , Schnitzer Jan E 
Published: April 2011

Abstract

Background
Endothelial cells line all blood vessels to form the blood-tissue interface which is critical for maintaining organ homeostasis and facilitates molecular exchange. We recently used tissue subcellular fractionation combined with several multi-dimensional mass spectrometry-based techniques to enhance identification of lipid-embedded proteins for large-scale proteomic mapping of luminal endothelial cell plasma membranes isolated directly from rat lungs in vivo. The biological processes and functions of the proteins expressed at this important blood-tissue interface remain unexplored at a large scale.

Results
We performed an unbiased systems analysis of the endothelial cell surface proteome containing over 1800 proteins to unravel the major functions and pathways apparent at this interface. As expected, many key functions of plasma membranes in general (i.e., cell surface signaling pathways, cytoskeletal organization, adhesion, membrane trafficking, metabolism, mechanotransduction, membrane fusion, and vesicle-mediated transport) and endothelial cells in particular (i.e., blood vessel development and maturation, angiogenesis, regulation of endothelial cell proliferation, protease activity, and endocytosis) were significantly overrepresented in this proteome. We found that endothelial cells express multiple proteins that mediate processes previously reported to be restricted to neuronal cells, such as neuronal survival and plasticity, axon growth and regeneration, synaptic vesicle trafficking and neurotransmitter metabolic process. Surprisingly, molecular machinery for protein synthesis was also detected as overrepresented, suggesting that endothelial cells, like neurons, can synthesize proteins locally at the cell surface.

Conclusion
Our unbiased systems analysis has led to the potential discovery of unexpected functions in normal endothelium. The discovery of the existence of protein synthesis at the plasma membrane in endothelial cells provides new insight into the blood-tissue interface and endothelial cell surface biology.
Nanostructured titania films sensitized by quantum dot chalcogenides
Authors: Kontos Athanassios G , Likodimos Vlassis , Vassalou Eleni , Kapogianni Ioanna , Raptis Yannis S , Raptis Costas , Falaras Polycarpos 
Published: April 2011

AbstractThe optical and structural properties of cadmium and lead sulfide nanocrystals deposited on mesoporous TiO2 substrates via the successive ionic layer adsorption and reaction method were comparatively investigated by reflectance, transmittance, micro-Raman and photoluminescence measurements. Enhanced interfacial electron transfer is evidenced upon direct growth of both CdS and PbS on TiO2 through the marked quenching of their excitonic emission. The optical absorbance of CdS/TiO2 can be tuned over a narrow spectral range. On the other side PbS/TiO2 exhibits a remarkable band gap tunability extending from the visible to the near infrared range, due to the distinct quantum size effects of PbS quantum dots. However, PbS/TiO2 suffers from severe degradation upon air exposure. Degradation effects are much less pronounced for CdS/TiO2 that is appreciably more stable, though it degrades readily upon visible light illumination.
Atomic scale investigation of silicon nanowires and nanoclusters
Authors: Roussel Manuel , Chen Wanghua , Talbot Etienne , Lardé Rodrigue , Cadel Emmanuel , Gourbilleau Fabrice , Grandidier Bruno , Stiévenard Didier , Pareige Philippe 
Published: April 2011

AbstractIn this study, we have performed nanoscale characterization of Si-clusters and Si-nanowires with a laser-assisted tomographic atom probe. Intrinsic and p-type silicon nanowires (SiNWs) are elaborated by chemical vapor deposition method using gold as catalyst, silane as silicon precursor, and diborane as dopant reactant. The concentration and distribution of impurity (gold) and dopant (boron) in SiNW are investigated and discussed. Silicon nanoclusters are produced by thermal annealing of silicon-rich silicon oxide and silica multilayers. In this process, atom probe tomography (APT) provides accurate information on the silicon nanoparticles and the chemistry of the nanolayers.