bluuebunny/crossref_metadata_2025_split huggingface dataset:
β-Catenin Signaling Is a Critical Event in ErbB2-Mediated Mammary Tumor Progression
Authors: Schade Babette , Lesurf Robert , Sanguin-Gendreau Virginie , Bui Tung , Deblois Geneviève , O'Toole Sandra A. , Millar Ewan K.A. , Zardawi Sara J. , Lopez-Knowles Elena , Sutherland Robert L. , Giguère Vincent , Kahn Michael , Hallett Michael , Muller William J. 
Published: May 2013

Abstract
Although ERBB2 amplification and overexpression is correlated with poor outcome in breast cancer, the molecular mechanisms underlying the aggressive nature of these tumors has not been fully elucidated. To investigate this further, we have used a transgenic mouse model of ErbB2-driven tumor progression (ErbB2KI model) that recapitulates clinically relevant events, including selective amplification of the core erbB2 amplicon. By comparing the transcriptional profiles of ErbB2KI mammary tumors and human ERBB2-positive breast cancers, we show that ErbB2KI tumors possess molecular features of the basal subtype of ERBB2-positive human breast cancer, including activation of canonical β-catenin signaling. Inhibition of β-catenin–dependent signaling in ErbB2KI-derived tumor cells using RNA interference impaired tumor initiation and metastasis. Furthermore, treatment of ErbB2KI or human ERBB2-overexpressing tumor cells with a selective β-catenin/CBP inhibitor significantly decreased proliferation and ErbB2 expression. Collectively, our data indicate that ERBB2-mediated breast cancer progression requires β-catenin signaling and can be therapeutically targeted by selective β-catenin/CBP inhibitors. Cancer Res; 73(14); 4474–87. ©2013 AACR.
Associations between Weight in Early Adulthood, Change in Weight, and Breast Cancer Risk in Postmenopausal Women
Authors: Krishnan Kavitha , Bassett Julie K. , MacInnis Robert J. , English Dallas R. , Hopper John L. , McLean Catriona , Giles Graham G. , Baglietto Laura 
Published: May 2013

AbstractBackground: Adult weight is positively associated with postmenopausal breast cancer but few studies have investigated whether there are associations with weight and body mass index (BMI) in early adulthood, or subsequent weight change.Methods: A total of 14,441 postmenopausal women from the Melbourne Collaborative Cohort Study (MCCS) were followed for 16.5 years (mean) and 668 incident breast cancers were identified. Hazard ratios (HRs) were estimated using Cox regression.Results: Weight and BMI at 18 to 21 years were not associated with risk of any type of breast cancer and there was no variation by age. Women with the greatest increase in weight and BMI had higher risk at older ages [HR per 5 kg/m2 gain in BMI = 1.24; 95% confidence interval (CI), 1.11–1.40], although the test for homogeneity by age was not significant. At older ages, the association was stronger for progesterone (PR) positive disease compared with PR negative disease (HR per 5 kg/m2 gain in BMI, 1.43; 95% CI, 1.23–1.66; test for homogeneity by PR status, P &lt; 0.01) and for diseases that were positive for both estrogen (ER) and PR (HR per 5 kg/m2 gain in BMI, 1.45; 95% CI, 1.24–1.69; test for homogeneity by ER/PR status, P = 0.02). HRs were also greater for HER2− and luminal A tumors, but the P values for homogeneity by tumor subgroups were not significant.Conclusion: Early adulthood weight is not associated with risk of postmenopausal breast cancer. Greater weight gain during adulthood might be associated with increased risk for older women (&gt;69 years) and this association might vary by tumor hormone receptor status.Impact: Further studies need to investigate the impact of increase in weight during adulthood on postmenopausal breast cancer risk and the potential variation by age or tumor characteristics. Cancer Epidemiol Biomarkers Prev; 22(8); 1409–16. ©2013 AACR.
Single-Nucleotide Polymorphisms in Nucleotide Excision Repair Genes, Cigarette Smoking, and the Risk of Head and Neck Cancer
Authors: Wyss Annah B. , Herring Amy H. , Avery Christy L. , Weissler Mark C. , Bensen Jeannette T. , Barnholtz-Sloan Jill S. , Funkhouser William K. , Olshan Andrew F. 
Published: May 2013

AbstractBackground: Cigarette smoking is associated with increased head and neck cancer (HNC) risk. Tobacco-related carcinogens are known to cause bulky DNA adducts. Nucleotide excision repair (NER) genes encode enzymes that remove adducts and may be independently associated with HNC, as well as modifiers of the association between smoking and HNC.Methods: Using population-based case–control data from the Carolina Head and Neck Cancer Epidemiology (CHANCE) Study (1,227 cases and 1,325 controls), race-stratified (White, African American), conventional, and hierarchical logistic regression models were used to estimate ORs with 95% intervals (I) for the independent and joint effects of cigarette smoking and 84 single-nucleotide polymorphisms (SNP) from 15 NER genes on HNC risk.Results: The odds of HNC were elevated among ever cigarette smokers and increased with smoking duration and frequency. Among Whites, rs4150403 on ERCC3 was associated with increased HNC odds (AA+AG vs. GG; OR, 1.28; 95% CI, 1.01–1.61). Among African Americans, rs4253132 on ERCC6 was associated with decreased HNC odds (CC+CT vs. TT; OR, 0.62; 95% CI, 0.45–0.86). Interactions between ever cigarette smoking and three SNPs (rs4253132 on ERCC6, rs2291120 on DDB2, and rs744154 on ERCC4) suggested possible departures from additivity among Whites.Conclusions: We did not find associations between some previously studied NER variants and HNC. We did identify new associations between two SNPs and HNC and three suggestive cigarette–SNP interactions to consider in future studies.Impact: We conducted one of the most comprehensive evaluations of NER variants, identifying a few SNPs from biologically plausible candidate genes associated with HNC and possibly interacting with cigarette smoking. Cancer Epidemiol Biomarkers Prev; 22(8); 1428–45. ©2013 AACR.
Comparison of Associations of Body Mass Index, Abdominal Adiposity, and Risk of Colorectal Cancer in a Large Prospective Cohort Study
Authors: Keimling Marlen , Renehan Andrew G. , Behrens Gundula , Fischer Beate , Hollenbeck Albert R. , Cross Amanda J. , Leitzmann Michael F. 
Published: May 2013

AbstractBackground: Increased body mass index (BMI) is an established colorectal cancer risk factor. High waist circumference or waist-hip-ratio (WHR) may better reflect an abnormal metabolic state and be more predictive of colorectal cancer risk than BMI.Methods: We examined BMI, waist circumference, WHR, and hip circumference in relation to colorectal cancer risk among 203,177 participants followed for 10 years. We derived standardized colorectal cancer risk estimates for each anthropometric parameter and compared predictive characteristics (Harrell's C-index). In women, we examined whether hormone replacement therapy (HRT) use modified the associations between anthropometric measures and colorectal cancer.Results: We ascertained 2,869 colorectal cancers. In men, increased colon cancer risks were associated with BMI [HR per SD, 1.14; 95% confidence interval (CI), 1.08–1.20], waist circumference (HR per SD, 1.17; 95% CI, 1.08–1.27), and WHR (HR per SD, 1.09; 95% CI, 1.04–1.14). In women, anthropometric variables were unrelated to colon cancer. For men and women, anthropometric variables were unrelated to rectal cancer. Compared with BMI, waist circumference and WHR did not materially influence colon cancer prediction models [C-index changes: −0.0041 and 0.0046 (men); 0.0004 and 0.0005 (women)]. In current HRT users, colon cancer was inversely or suggestively inversely associated with waist circumference (HR per SD, 0.78; 95% CI, 0.63–0.97) and WHR (HR per SD, 0.88; 95% CI, 0.76–1.01), but positively related to hip circumference (HR per SD, 1.39; 95% CI, 1.13–1.71).Conclusion: BMI, waist circumference, and WHR show comparable positive associations with colon cancer in men. Associations between anthropometric measures and colon cancer are weak or null in women, but there is some evidence for effect modification by HRT.Impact: These findings may improve our understanding of the relation of adiposity to colorectal cancer. Cancer Epidemiol Biomarkers Prev; 22(8); 1383–94. ©2013 AACR.
The Prognostic Value of MicroRNAs Varies with Patient Race/Ethnicity and Stage of Colorectal Cancer
Authors: Bovell Liselle C. , Shanmugam Chandrakumar , Putcha Balananda-Dhurjati K. , Katkoori Venkat R. , Zhang Bin , Bae Sejong , Singh Karan P. , Grizzle William E. , Manne Upender 
Published: May 2013

AbstractPurpose: MicroRNAs (miRNA) have potential prognostic value for colorectal cancers; however, their value based on patient race/ethnicity and pathologic stage has not been determined. The goal was to ascertain the prognostic value of 5 miRNAs with increased expression in colorectal cancers of African American (black) and non-Hispanic Caucasian (white) patients.Experimental Design: TaqMan quantitative real-time PCR was used to quantify expression of miR-20a, miR-21, miR-106a, miR-181b, and miR-203 in paired normal and tumor colorectal cancer archival tissues collected from 106 black and 239 white patients. The results were correlated with overall survival based on patient race/ethnicity and pathologic stage. Because decisions about adjuvant therapy are important for stage III colorectal cancers, and because miR-181b seemed to have prognostic value only for stage III black patients, we assessed its prognostic value in a separate cohort of 36 stage III colorectal cancers of blacks.Results: All 5 miRNAs had higher expression in colorectal cancers (&gt;1.0-fold) than in corresponding normal tissues. High expression of miR-203 was associated with poor survival of whites with stage IV colorectal cancers (HR = 3.00; 95% CI, 1.29–7.53), but in blacks it was an indicator of poor survival of patients with stages I and II colorectal cancers (HR = 5.63; 95% CI, 1.03–30.64). Increased miR-21 expression correlated with poor prognosis for white stage IV patients (HR = 2.50; 95% CI, 1.07–5.83). In both test and validation cohorts, high miR-181b expression correlated with poor survival of only black patients with stage III colorectal cancers (HR = 1.94; 95% CI, 1.03–3.67).Conclusion: These preliminary findings suggest that the prognostic value of miRNAs in colorectal cancers varies with patient race/ethnicity and stage of disease. Clin Cancer Res; 19(14); 3955–65. ©2013 AACR.
Developing Standards for Breakthrough Therapy Designation in Oncology
Authors: Horning Sandra J. , Haber Daniel A. , Selig Wendy K.D. , Ivy S. Percy , Roberts Samantha A. , Allen Jeff D. , Sigal Ellen V. , Sawyers Charles L. 
Published: May 2013

Abstract
In July 2012, Congress passed the Food and Drug Administration Safety and Innovation Act (FDASIA). The Advancing Breakthrough Therapies for Patients Act was incorporated into a Title of FDASIA to expedite clinical development of new, potential “breakthrough” drugs or treatments that show dramatic responses in early-phase studies. Using this regulatory pathway, once a promising new drug candidate is designated as a “Breakthrough Therapy”, the U.S. Food and Drug Administration (FDA) and sponsor would collaborate to determine the best path forward to abbreviate the traditional three-phase approach to drug development. The breakthrough legislation requires that an FDA guidance be drafted that details specific requirements of the bill to aid FDA in implementing requirements of the Act. In this article, we have proposed criteria to define a product as a Breakthrough Therapy, and discussed critical components of the development process that would require flexibility in order to enable expedited development of a Breakthrough Therapy. Clin Cancer Res; 19(16); 4297–304. ©2013 AACR.
Case Studies of Tropical Cyclones and Phytoplankton Blooms over Atlantic and Pacific Regions
Authors: Merritt-Takeuchi Ashley M. , Chiao Sen 
Published: May 2013

Abstract
This study investigates phytoplankton blooms following the passage of tropical cyclones in the Atlantic and Pacific Ocean basins. The variables of sea surface temperature (SST), chlorophyll (Chl-a), precipitation, and storm surface winds were monitored for two case studies, Typhoon Xangsane (2006) and Hurricane Earl (2010). Strong near-surface wind from tropical cyclones creates internal friction, which causes deep nutrient enriched waters to displace from the bottom of the ocean floor up toward the surface. In return, the abundance of upwelled nutrients near the surface provides an ideal environment for the growth of biological substances such as chlorophyll and phytoplankton. The inverse correlation coefficients of SST and Chl-a for this study are −0.67 and −0.26 for Xangsane and Earl, respectively. This suggests that, regardless of ocean basin, changing sea surface temperature and chlorophyll concentrations can be correlated to various characteristics of tropical cyclones including precipitation and surface wind, which in combination results in an increase of phytoplankton.
Clustering of Maxima: Spatial Dependencies among Heavy Rainfall in France
Authors: Bernard Elsa , Naveau Philippe , Vrac Mathieu , Mestre Olivier 
Published: May 2013

Abstract
One of the main objectives of statistical climatology is to extract relevant information hidden in complex spatial–temporal climatological datasets. To identify spatial patterns, most well-known statistical techniques are based on the concept of intra- and intercluster variances (like the k-means algorithm or EOFs). As analyzing quantitative extremes like heavy rainfall has become more and more prevalent for climatologists and hydrologists during these last decades, finding spatial patterns with methods based on deviations from the mean (i.e., variances) may not be the most appropriate strategy in this context of studying such extremes. For practitioners, simple and fast clustering tools tailored for extremes have been lacking. A possible avenue to bridging this methodological gap resides in taking advantage of multivariate extreme value theory, a well-developed research field in probability, and to adapt it to the context of spatial clustering. In this paper, a novel algorithm based on this plan is proposed and studied. The approach is compared and discussed with respect to the classical k-means algorithm throughout the analysis of weekly maxima of hourly precipitation recorded in France (fall season, 92 stations, 1993–2011).
Differentiating Arytenoid Dislocation and Recurrent Laryngeal Nerve Paralysis by Arytenoid Movement in Laryngoscopic Video
Authors: Zhuang Peiyun , Nemcek Steven , Surender Ketan , Hoffman Matthew R. , Zhang Fan , Chapin William J. , Jiang Jack J. 
Published: May 2013

ObjectiveTo present a new method of quantifying arytenoid movement during inspiration and determine if it can be used to distinguish arytenoid dislocation from vocal fold paralysis.Study DesignCase series with chart review.SettingRetrospective study conducted in a university laboratory based on university hospital data.Subjects and MethodsEndoscopic videos from 8 patients with dislocation and 5 patients with vocal fold paralysis diagnosed by electromyography were included. Vector analysis measured cuneiform movement, an indirect measurement of arytenoid movement, during 1 inspiration. Measurements normalized and not normalized to vocal fold length were evaluated. Interrater reliability (2 raters) and intrarater reliability (1 rater performing the analysis twice) were evaluated using intraclass correlation coefficient (ICC) analysis. Raters were blinded to subject group during analysis.ResultsPixel‐valued cuneiform movement was 81.16 ± 25.62 for dislocation and 30.22 ± 23.60 for paralysis (P =. 019). Unitless cuneiform movement was 0.58 ± 0.17 for dislocation and 0.24 ± 0.18 for paralysis (P =. 030). Interrater ICC was 0.942 for pixel‐valued measurements and 0.962 for unitless measurements. Intrarater ICC was 0.909 for pixel‐valued measurements and 0.881 for unitless measurements.ConclusionsBoth pixel‐valued and unitless measures of arytenoid movement were significantly greater in arytenoid dislocation than vocal fold paralysis. Pixel‐valued measurements were included to demonstrate the ability to make quantitative comparisons across subjects without precise knowledge of camera precision, provided position is approximately stable, as each measurement is inherently normalized by vocal tract length. Future studies will apply this new method of evaluating vocal fold immobility disorders on a larger scale and incorporate a more diverse group of etiologies.
The missing link: Enhanced functional connectivity between amygdala and visceroceptive cortex in migraine
Authors: Hadjikhani Nouchine , Ward Noreen , Boshyan Jasmine , Napadow Vitaly , Maeda Yumi , Truini Andrea , Caramia Francesca , Tinelli Emanuele , Mainero Caterina 
Published: May 2013

Background Migraine is a neurovascular disorder in which altered functional connectivity between pain-modulating circuits and the limbic system may play a role. Cortical spreading depression (CSD), which underlies migraine aura (MWA), induces C-fos expression in the amygdala. The role of CSD and amygdala connectivity in migraine without aura (MwoA) is less clear and may differentiate migraine from other chronic pain disorders. Methods Using resting-state functional MRI, we compared functional connectivity between the amygdala and the cortex in MWA and MWoA patients as well as in healthy subjects and in two other chronic pain conditions not associated with CSD: trigeminal neuralgia (TGN) and carpal tunnel syndrome (CTS). Results Amygdala connectivity in both MWA and MWoA was increased to the visceroceptive insula relative to all other groups examined. Conclusion The observed increased connectivity within the limbic/viscerosensory network, present only in migraineurs, adds to the evidence of a neurolimbic pain network dysfunction and may reflect repetitive episodes of CSD leading to the development of migraine pain.
Perturbation of fetal hematopoiesis in a mouse model of Down syndrome’s transient myeloproliferative disorder
Authors: Birger Yehudit , Goldberg Liat , Chlon Timothy M. , Goldenson Benjamin , Muler Inna , Schiby Ginette , Jacob-Hirsch Jasmin , Rechavi Gideon , Crispino John D. , Izraeli Shai 
Published: May 2013

Key Points
Transient expansion of fetal megaerythroid progenitors in ERG/Gata1s mouse is biologically similar to Down syndrome TMD. The N-terminal domain of GATA1 and the downregulation of ERG expression are essential for normal fetal erythropoiesis.
Arginine68 is an essential residue for the C-terminal cleavage of human Atg8 family proteins
Authors: Liu Chao , Ma Haijie , Wu Jiaxue , Huang Qiang , Liu Jun O , Yu Long 
Published: May 2013

Abstract

Background
Autophagy is a conserved cellular process that degrades and recycles cytoplasmic components via a lysosomal pathway. The phosphatidylethanolamine (PE)-conjugation of the Atg8 protein plays an important role in the yeast autophagy process. In humans, six Atg8 homologs, including MAP1LC3A, MAP1LC3B, MAP1LC3C (refer to LC3A, LC3B, and LC3C hereafter), GABARAP, GABARAPL1, and GABARAPL2 have been reported. All of them can be conjugated to PE through a ubiquitin-like conjugation system, and be located to autophagosomes.

Results
In this study, we found 3 new alternative splicing isoforms in LC3B, GABARAP, and GABARAPL1, (designated as LC3B-a, GABARAP-a and GABARAPL1-a, respectively). None of them can go through the PE-conjugation process and be located to autophagosomes. Interestingly, compared with LC3B, LC3B-a has a single amino acid (Arg68) deletion due to the NAGNAG alternative splicing in intron 3. Through structural simulations, we found that the C-terminal tail of LC3B-a is less mobile than that of LC3B, thus affecting its C-terminal cleavage by human ATG4 family proteins. Furthermore, we found that Arg68 is an essential residue facilitating the interaction between human Atg8 family proteins and ATG4B by forming a salt bridge with Asp171 of ATG4B. Depletion of this salt bridge reduces autophagosomes formation and autophagic flux under both normal and nutrition starvation conditions.

Conclusions
These results suggest Arg68 is an essential residue for the C-terminal cleavage of Atg8 family proteins during the autophagy process.
Enzymatically active Rho and Rac small-GTPases are involved in the establishment of the vacuolar membrane after Toxoplasma gondii invasion of host cells
Authors: Na Ren-Hua , Zhu Guo-Hui , Luo Ji-Xuan , Meng Xiao-Jing , Cui Liwang , Peng Hong-Juan , Chen Xiao-guang , Gomez-Cambronero Julian 
Published: May 2013

Abstract

Background
GTPases are the family of hydrolases that bind and hydrolyze guanosine triphosphate. The large Immunity-related GTPases and the small GTPase ADP-ribosylation factor-6 in host cells are known to accumulate on the parasitophorous vacuole membrane (PVM) of Toxoplasma gondii and play critical roles in this parasite infection, but these GTPases cannot explain the full extent of infection.

Results
In this research, RhoA and Rac1 GTPases from the host cell were found to accumulate on the PVM regardless of the virulence of the T. gondii strains after T. gondii invasion, and this accumulation was dependent on their GTPase activity. The real-time micrography of T. gondii tachyzoites invading COS-7 cells overexpressing CFP-RhoA showed that this GTPase was recruited to the PVM at the very beginning of the invasion through the host cell membrane or from the cytosol. Host cell RhoA and Rac1 were also activated after T. gondii tachyzoites invasion, which was needed for host cell cytoskeleton reorganization to facilitate intracellular pathogens invasion. The decisive domains for the RhoA accumulation on the PVM included the GTP/Mg2+ binding site, the mDia effector interaction site, the G1 box, the G2 box and the G5 box, respectively, which were related to the binding of GTP for enzymatic activity and mDia for the regulation of microtubules. The recruited CFP-RhoA on the PVM could not be activated by epithelial growth factor (EGF) and no translocation was observed, unlike the unassociated RhoA in the host cell cytosol that migrated to the cell membrane towards the EGF activation spot. This result supported the hypothesis that the recruited RhoA or Rac1 on the PVM were in the GTP-bound active form. Wild-type RhoA or Rac1 overexpressed cells had almost the same infection rates by T. gondii as the mock-treated cells, while RhoA-N19 or Rac1-N17 transfected cells and RhoA, Rac1 or RhoA + Rac1 siRNA-treated cells showed significantly diminished infection rates compared to mock cells.

Conclusions
The accumulation of the RhoA and Rac1 on the PVM and the requisite of their normal GTPase activity for efficient invasion implied their involvement and function in T. gondii invasion.