bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract SY05-03: microRNAs, EMT, and cancer stem cells
Authors: Brabletz Thomas 
Published: August 2012

Abstract
We have shown, that in particular tumor cells at the invasive front undergo an epithelial-mesenchymal transition (EMT) and aberrantly express EMT-associated transcriptional repressors, like ZEB1. The amount of such cells strongly correlates with metastasis formation and poor clinical outcome. Strikingly, metastases show again a differentiated phenotype, indicating a mesenchymal-epithelial re-transition (MET) and a support a regulatory role of the tumor environment for malignant tumor progression.
We described that the EMT-activator ZEB1 is a crucial promoter of metastasis and demonstrated that ZEB1 inhibits expression of cell polarity factors and the microRNA-200 family, whose members are strong inducers of epithelial differentiation. These results indicate that ZEB1 triggers a microRNA-mediated feedback-loop, which stabilizes EMT and promotes dissemination of cancer cells. Moreover we detected that in addition ZEB1 is necessary for the tumor initiating capacity of pancreatic and colorectal cancer cells. ZEB1 inhibits expression of miR-200c, miR-203 and miR-183, which cooperate to suppress expression of stem cell factors, as demonstrated for the polycomb repressor Bmi1.
We propose that ZEB1 links EMT-activation and stemness-maintenance by suppressing stemness-inhibiting microRNAs and thereby is a promoter of mobile, migrating cancer stem cells. Notably, these cells also acquired a drug-resistance phenotype. Thus, targeting the ZEB1 - miR-200 feedback loop might be a promising treatment option for fatal tumors, such as pancreatic cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY05-03. doi:1538-7445.AM2012-SY05-03
Abstract SY07-03: The ubiquitin-based response to DNA double-strand breaks
Authors: Durocher Daniel 
Published: August 2012

Abstract
The chromatin-based response to DNA double-strand breaks (DSBs) is characterized by the accumulation of DNA repair factors and DNA damage signaling molecules within a large domain that surrounds the lesion. This response is largely dependent on ATM-dependent phosphorylation but also on chromatin ubiquitylation. Indeed, the RNF8 and RNF168 E3 ubiquitin ligases are necessary for the accumulation of proteins such as 53BP1, BRCA1 and RAD18 at sites of DNA damage. The critical importance of this pathway is manifested by the observation that biallelic mutations in the RNF168 gene results in an ataxia-telangiectasia-like syndrome referred to as RIDDLE. We are interested in understanding how this pathway is regulated and how ubiquitin-dependent protein interactions orchestrate the hierarchy of protein recruitment at sites of DNA lesions. I will present our current understanding on the regulation and organization of this signaling cascade and I will contend that DNA double-strand break signaling will be a useful system for deciphering the contribution of non-degradative ubiquitylation in cell signaling.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY07-03. doi:1538-7445.AM2012-SY07-03
Abstract SY08-02: Gene regulatory network models identify targets for mammary tumor normalization
Authors: Brock Amy 
Published: August 2012

Abstract
The majority of breast cancer therapeutics aim at slowing tumor expansion through selective killing of tumor cells. Given the enormous plasticity of cells (highlighted by recent advances in the iPS field), we have instead sought to induce a cell state transition from a mammary tumor cell phenotype to a normal mammary epithelial cell state. We have tackled the critical problem of identifying target genes for the normalization or differentiation of mammary tumor cells by employing a systems biology approach that integrates computational modeling with in vivo and in vitro studies. In vivo gene expression data of mammary tumor progression in the FVB C3(1) SV40Tag transgenic mouse model were collected at multiple time points as the disease progressed from normal gland to DCIS-like lesions to invasive carcinoma. Gene regulatory network models predicted novel transcription factor targets that appeared critical to the rise of the tumor phenotype. These putative gene targets were then assessed in a 3D spheroid assay. RNAi inhibition of two computationally predicted transcription factors reverted mammary tumor cells to a normalized mammary epithelial cell phenotype, with appropriate apical/basal polarization, lumen formation and reduced proliferative index. Validated targets were then tested in vivo. This integrated strategy has pinpointed transcription factors for RNAi therapeutic targeting in vivo but importantly, the method is not limited to breast cancer and may be useful for many different tumor types. In summary, our major advance has been the demonstration that a gene regulatory network reverse engineering approach can identify genes that are causatively involved in cancer progression and that represent viable therapeutic differentiation targets.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY08-02. doi:1538-7445.AM2012-SY08-02
Abstract SY41-01: Tumor-endothelial transdifferentiation
Authors: Verma Inder M. , Soda Yasushi , Friedmann-Morvinski Dinorah , Pastorino Sandra , Kesari Santosh 
Published: August 2012

Abstract
Glioblastoma (GBM) is the most malignant brain tumor and highly resistant to intensive combination therapies and anti-VEGF therapies. To assess the resistance mechanism to anti-VEGF therapy, we examined the vessels of GBMs in tumors that were induced by the transduction of p53+/− heterozygous mice with lentiviral vectors containing oncogenes and the marker GFP in the hippocampus of GFAP-Cre recombinase (Cre) mice. We were surprised to observe GFP+ vascular endothelial cells (ECs). Transplantation of mouse GBM cells revealed that the tumor-derived endothelial cells (TDECs) originated from tumor-initiating cells and did not result from cell fusion of ECs and tumor cells. An in vitro differentiation assay suggested that hypoxia is an important factor in the differentiation of tumor cells to ECs and is independent of VEGF. TDEC formation was not only resistant to an anti-VEGF receptor inhibitor in mouse GBMs but it led to an increase in their frequency. A xenograft model of human GBM spheres from clinical specimens and direct clinical samples from patients with GBM also showed the presence of TDECs. We suggest that the TDEC is an important player in the resistance to anti-VEGF therapy, and hence a potential target for GBM therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY41-01. doi:1538-7445.AM2012-SY41-01
Rescue Screens with Secreted Proteins Reveal Compensatory Potential of Receptor Tyrosine Kinases in Driving Cancer Growth
Authors: Harbinski Fred , Craig Vanessa J. , Sanghavi Sneha , Jeffery Douglas , Liu Lijuan , Sheppard Kelly Ann , Wagner Sabrina , Stamm Christelle , Buness Andreas , Chatenay-Rivauday Christian , Yao Yao , He Feng , Lu Chris X. , Guagnano Vito , Metz Thomas , Finan Peter M. , Hofmann Francesco , Sellers William R. , Porter Jeffrey A. , Myer Vic E. , Graus-Porta Diana , Wilson Christopher J. , Buckler Alan , Tiedt Ralph 
Published: August 2012

Abstract
The overall power of kinase inhibitors is substantially overshadowed by the acquisition of drug resistance. To address this issue, we systematically assessed the potential of secreted proteins to induce resistance to kinase inhibitors. To this end, we developed a high-throughput platform for screening a cDNA library encoding 3,432 secreted proteins in cellular assays. Using cancer cells originally dependent on either MET, FGFR2, or FGFR3, we observed a bypass of dependence through ligand-mediated activation of alternative receptor tyrosine kinases (RTK). Our findings indicate a broad and versatile potential for RTKs from the HER and FGFR families as well as MET to compensate for loss of each other. We further provide evidence that combined inhibition of simultaneously active RTKs can lead to an added anticancer effect.
Significance: Although initial tumor responses to kinase inhibitors can be significant, therapeutic benefit is often limited by the emergence of resistance (e.g., as a consequence of mutations in the drug target or through activation of alternative pathways to bypass dependence on the original target). Because the activation of alternative growth-promoting kinases by stimulation with their cognate ligands can constitute such a bypass mechanism, the identification of growth factors as possible mediators of resistance to kinase inhibitors is of clinical interest. Cancer Discov; 2(10); 948–59. ©2012 AACR.
This article is highlighted in the In This Issue feature, p. 857.
Prognostic Value of Right Ventricular Longitudinal Peak Systolic Strain in Patients With Pulmonary Hypertension
Authors: Haeck Marlieke L.A. , Scherptong Roderick W.C. , Marsan Nina Ajmone , Holman Eduard R. , Schalij Martin J. , Bax Jeroen J. , Vliegen Hubert W. , Delgado Victoria 
Published: August 2012

Background—
Right ventricular (RV) function is an important prognostic marker in patients with pulmonary hypertension. The present evaluation assessed the prognostic value of RV longitudinal peak systolic strain (LPSS) in patients with pulmonary hypertension.

Methods and Results—

A total of 150 patients with pulmonary hypertension of different etiologies (mean age, 59±15 years; 37.3% male) were evaluated. RV fractional area change and tricuspid annular plane systolic excursion index were evaluated with 2-dimensional echocardiography. RV LPSS was assessed with speckle-tracking echocardiography. The patient population was categorized according to a RV LPSS value of –19%. Among several clinical and echocardiographic parameters, the significant determinants of all-cause mortality were evaluated. There were no significant differences in age, sex, pulmonary hypertension cause and left ventricular ejection fraction between patients with RV LPSS <−19% and patients with RV LPSS ≥−19%. However, patients with RV LPSS ≥−19% had significantly worse New York Heart Association functional class (2.7±0.6 versus 2.3±0.8;
P
=0.003) and lower tricuspid annular plane systolic excursion (16±4 mm versus 18±3 mm;
P
<0.001) than their counterparts. During a median follow-up of 2.6 years, 37 patients died. RV LPSS was a significant determinant of all-cause mortality (HR, 3.40; 95% CI, 1.19–9.72;
P
=0.02).

Conclusions—
In patients with pulmonary hypertension, RV LPSS is significantly associated with all-cause mortality. RV LPSS may be a valuable parameter for risk stratification of these patients. Future studies are needed to confirm these results in the pulmonary hypertension subgroups.
Ascending-Ramp Biphasic Waveform Has a Lower Defibrillation Threshold and Releases Less Troponin I Than a Truncated Exponential Biphasic Waveform
Authors: Huang Jian , Walcott Gregory P. , Ruse Richard B. , Bohanan Scott J. , Killingsworth Cheryl R. , Ideker Raymond E. 
Published: August 2012

Background—
We tested the hypothesis that the shape of the shock waveform affects not only the defibrillation threshold but also the amount of cardiac damage.

Methods and Results—
Defibrillation thresholds were determined for 11 waveforms—3 ascending-ramp waveforms, 3 descending-ramp waveforms, 3 rectilinear first-phase biphasic waveforms, a Gurvich waveform, and a truncated exponential biphasic waveform—in 6 pigs with electrodes in the right ventricular apex and superior vena cava. The ascending, descending, and rectilinear waveforms had 4-, 8-, and 16-millisecond first phases and a 3.5-millisecond rectilinear second phase that was half the voltage of the first phase. The exponential biphasic waveform had a 60% first-phase and a 50% second-phase tilt. In a second study, we attempted to defibrillate after 10 seconds of ventricular fibrillation with a single ≈30-J shock (6 pigs successfully defibrillated with 8-millisecond ascending, 8-millisecond rectilinear, and truncated exponential biphasic waveforms). Troponin I blood levels were determined before and 2 to 10 hours after the shock. The lowest-energy defibrillation threshold was for the 8-milliseconds ascending ramp (14.6±7.3 J [mean±SD]), which was significantly less than for the truncated exponential (19.6±6.3 J). Six hours after shock, troponin I was significantly less for the ascending-ramp waveform (0.80±0.54 ng/mL) than for the truncated exponential (1.92±0.47 ng/mL) or the rectilinear waveform (1.17±0.45 ng/mL).

Conclusions—
The ascending ramp has a significantly lower defibrillation threshold and at ≈30 J causes 58% less troponin I release than the truncated exponential biphasic shock. Therefore, the shock waveform affects both the defibrillation threshold and the amount of cardiac damage.
Climate Variability and Trends in Bolivia
Authors: Seiler Christian , Hutjes Ronald W. A. , Kabat Pavel 
Published: August 2012

AbstractClimate-related disasters in Bolivia are frequent, severe, and manifold and affect large parts of the population, economy, and ecosystems. Potentially amplified through climate change, natural hazards are of growing concern. To better understand these events, homogenized daily observations of temperature (29 stations) and precipitation (68 stations) from 1960 to 2009 were analyzed in this study. The impact of the positive (+) and negative (−) phases of the three climate modes (i) Pacific decadal oscillation (PDO), (ii) El Niño–Southern Oscillation (ENSO) with El Niño (EN) and La Niña (LN) events, and (iii) Antarctic Oscillation (AAO) were assessed. Temperatures were found to be higher during PDO(+), EN, and AAO(+) in the Andes. Total amounts of rainfall, as well as the number of extreme events, were higher during PDO(+), EN, and LN in the lowlands. During austral summer [December–February (DJF)], EN led to drier conditions in the Andes with more variable precipitation. Temperatures increased at a rate of 0.1°C per decade, with stronger increases in the Andes and in the dry season. Rainfall totals increased from 1965 to 1984 [12% in DJF and 18% in June–August (JJA)] and decreased afterward (−4% in DJF and −10% in JJA), following roughly the pattern of PDO. Trends of climate extremes generally corresponded to trends of climate means. Findings suggest that Bolivia’s climate will be warmer and drier than average in the near-term future. Having entered PDO(−) in 2007, droughts and LN-related floods can be expected in the lowlands, while increasing temperatures suggest higher risks of drought in the Andes.
Underwater Radiance Distributions Measured with Miniaturized Multispectral Radiance Cameras
Authors: Antoine David , Morel André , Leymarie Edouard , Houyou Amel , Gentili Bernard , Victori Stéphane , Buis Jean-Pierre , Buis Nicolas , Meunier Sylvain , Canini Marius , Crozel Didier , Fougnie Bertrand , Henry Patrice 
Published: August 2012

AbstractMiniaturized radiance cameras measuring underwater multispectral radiances in all directions at high-radiometric accuracy (CE600) are presented. The camera design is described, as well as the main steps of its optical and radiometric characterization and calibration. The results show the excellent optical quality of the specifically designed fish-eye objective. They also show the low noise and excellent linearity of the complementary metal oxide semiconductor (CMOS) detector array that is used. Initial results obtained in various oceanic environments demonstrate the potential of this instrument to provide new measurements of the underwater radiance distribution from the sea surface to dimly lit layers at depth. Excellent agreement is obtained between nadir radiances measured with the camera and commercial radiometers. Comparison of the upwelling radiance distributions measured with the CE600 and those obtained with another radiance camera also shows a very close agreement. The CE600 measurements allow all apparent optical properties (AOPs) to be determined from integration of the radiance distributions and inherent optical properties (IOPs) to be determined from inversion of the AOPs. This possibility represents a significant advance for marine optics by tying all optical properties to the radiometric standard and avoiding the deployment of complex instrument packages to collect AOPs and IOPs simultaneously (except when it comes to partitioning IOPs into their component parts).
Bullying in childhood and religious/spiritual status in adulthood among internal medicine outpatients
Authors: Sansone Randy A , Kelley Amy R , Forbis Jeremy S 
Published: August 2012

Background: Bullying in childhood is ubiquitous and associated with a number of identified negative outcomes in both childhood and adulthood. However, the relationship between being bullied in childhood and religious/spiritual status in adulthood has never been explored. Method: Using a cross-sectional sample of 324 consecutive internal medicine outpatients and a survey methodology, we examined relationships between ‘When you were growing up, were you ever a victim of bullying?’ and (1) self-perceived extent of religiosity/spirituality and (2) religiosity/spirituality as assessed by scores on the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp-12). Results: While bullying status in childhood was not related to either the self-perceived extent of religiosity or spirituality, it did evidence negative statistically significant relationships with seven of 12 FACIT-Sp-12 scales, as well as the overall composite score. Conclusions: According to these data, bullying in childhood is associated with lower religious/spiritual well-being in adulthood; however, this study was not designed to examine a causal relationship.
Second-Look Arthroscopic Assessment of Arthroscopic Single-Bundle Posterior Cruciate Ligament Reconstruction
Authors: Yang Jae-Hyuk , Yoon Jung-Ro , Jeong Hyeon-Il , Hwang Dae-Hee , Woo Sung-Jong , Kwon Jae-Ho , Nha Kyung-Wook 
Published: August 2012

Background: Although controversy continues over the choice of graft tissue, including autografts, allografts, and synthetic ligaments, for posterior cruciate ligament (PCL) reconstruction, the use of a mixed graft consisting of a hamstring (semitendinosus and gracilis) autograft plus tibialis anterior allograft tendon has not been studied in detail. Hypothesis: Outcomes of PCL reconstructions performed with a mixed graft would be superior to those using solely an Achilles tendon allograft in terms of functional knee scores, posterior stability, and the graft appearance. Study design: Cohort study; Level of evidence, 2. Methods: Fifty-eight patients who underwent isolated single-bundle PCL reconstruction using an arthroscopic trans-septal portal with remnant preservation technique were evaluated. They were divided into group A (mixed tendon; n = 30) and group B (Achilles tendon; n = 28). Knee function was evaluated using the Lysholm knee score, Tegner activity score, and the International Knee Documentation Committee (IKDC) grading scale. Anteroposterior stability was measured using the Telos stress view. Twenty patients (66.7%) from group A and 21 patients (75.0%) from group B underwent hardware removal and a second-look arthroscopic examination. Results: The Lysholm knee scores in groups A and B increased from a respective average of 43 and 50 preoperatively to 90 and 88 at follow-up. The IKDC grade and Tegner activity scores were also significantly improved in both groups. Stability was improved in both groups, with an average posterior laxity of 3.0 mm (group A) and 3.3 mm (group B) at follow-up ( P > .05). However, there were 4 intraoperative complications in group B: 2 bone fractures and 2 graft pullouts during precyclic tensioning. Second-look arthroscopy revealed a partial tear in 8 cases (40%) from group A and 15 cases (71.4%) from group B ( P = .03). All of the partial tears were located in the femoral aperture area. Complete synovial coverage was demonstrated in 10 patients (50%) from group A and 5 patients (23.8%) from group B ( P = .04). However, clinical outcomes and stability were not affected by the arthroscopic graft appearance. Conclusion: Satisfactory results were obtained for groups A and B in patients who underwent reconstruction for isolated PCL injury. However, 4 intraoperative complications (14.3%) were encountered with use of the Achilles tendon allograft (group B), with a relative higher rate of partial tear and less synovialization in the femoral aperture area.
Arthroscopic Accessibility of the Talus Quantified by Computed Tomography Simulation
Authors: van Bergen Christiaan J.A. , Tuijthof Gabriëlle J.M. , Maas Mario , Sierevelt Inger N. , van Dijk C. Niek 
Published: August 2012

Background: Anterior ankle arthroscopy is the preferred surgical approach for the treatment of osteochondral defects of the talus (OCDs). However, the ankle is a congruent joint with limited surgical access. Purpose: The dual purpose of this study was (1) to quantify the anterior arthroscopic reach (defined as the proportion of the talar dome articular surface located anterior to the anterior distal tibial rim) with the ankle in full plantar flexion and (2) to identify predictive factors of the arthroscopic reach. Study Design: Descriptive laboratory study. Methods: Computed tomography scans were obtained of 59 ankles (57 patients aged 33 ± 11 years) in full plantar flexion in a nonmetallic 3-dimensional footplate. The arthroscopic reach of both the medial and lateral talar domes was assessed on sagittal reconstructions using a custom-made software routine. Intraobserver and interobserver reliability were calculated by intraclass correlation coefficients (ICCs). Various predictive factors of the arthroscopic reach were analyzed by multivariate linear regression analysis. Results: The arthroscopic reach was 48.2% ± 6.7% (range, 26.7%-60.7%) of the medial talar dome and 47.8% ± 6.5% (range, 31.2%-65.1%) of the lateral talar dome ( P = .62). The intraobserver and interobserver reliability of both measurements were excellent (ICC, .99). The clinical plantarflexion angle was a statistically significant predictive factor of both the medial and lateral arthroscopic reaches (ie, increased plantar flexion corresponded to increased area of access), while joint laxity, gender, and age were not predictive. Conclusion: Almost half of the talar dome is accessible anterior to the anterior distal tibial rim. The plantarflexion angle is an independent predictive factor of the arthroscopic reach both medially and laterally. Clinical Relevance: These results may facilitate preoperative planning of the surgical approach for OCDs.
Hybrids, Political Economy, and Macroeconomics
Authors: Braunstein Elissa 
Published: August 2012

In this piece I comment on Nancy’s Folbre’s David Gordon Memorial Lecture for the 2012 Allied Social Science Associations meetings, focusing on the strengths of how she combines Marxian sensibilities with neoclasscial analytical tools, the advantages of her proposed definition of political economy, and extending her call for developing a macroeconomic approach to human capital. JEL codes: B50; E11; E24