bluuebunny/crossref_metadata_2025_split huggingface dataset:
Helicobacter pylori Protein–Specific Antibodies and Risk of Colorectal Cancer
Authors: Epplein Meira , Pawlita Michael , Michel Angelika , Peek Richard M. , Cai Qiuyin , Blot William J. 
Published: September 2013

Abstract
Background: There is biologic plausibility as to why infection with Helicobacter pylori, the leading cause of gastric cancer, may also increase the risk of colorectal cancer, but the epidemiologic findings have been inconsistent. We assessed the association of H. pylori protein–specific infection and colorectal cancer risk in the prospective cohort, the Southern Community Cohort Study.
Methods: Multiplex serology was used to measure antibodies to 15 H. pylori proteins in prediagnostic blood among 188 incident colorectal cancer cases and 370 controls matched by age, race, sex, and blood collection timing. Conditional logistic regression was used to calculate ORs and 95% confidence intervals (CI).
Results: Overall H. pylori prevalence was not associated with colorectal cancer risk (OR, 1.03; 95% CI, 0.59–1.77). However, seropositivity to any of five specific H. pylori proteins (VacA, HP231, HP305, NapA, and HcpC) was associated with a significant 60% to 80% increase in odds of risk. These associations became even stronger when limited to colon cancer risk, particularly for the known H. pylori toxin VacA (OR, 2.24; 95% CI, 1.22–4.11), including a significant, positive dose–response association by VacA antibody levels in quartiles (P &lt; 0.05). Associations with VacA seropositivity were especially strong for early-onset and late-stage cancers.
Conclusions: The findings raise the hypothesis that individuals with high levels of antibodies to specific H. pylori proteins may be at higher risk of colon cancer.
Impact: Further investigation of the H. pylori–colorectal cancer association is warranted to determine the possibility of protein-specific antibody levels as a risk biomarker. Cancer Epidemiol Biomarkers Prev; 22(11); 1964–74. ©2013 AACR.
Efficacy of BET Bromodomain Inhibition in Kras-Mutant Non–Small Cell Lung Cancer
Authors: Shimamura Takeshi , Chen Zhao , Soucheray Margaret , Carretero Julian , Kikuchi Eiki , Tchaicha Jeremy H. , Gao Yandi , Cheng Katherine A. , Cohoon Travis J. , Qi Jun , Akbay Esra , Kimmelman Alec C. , Kung Andrew L. , Bradner James E. , Wong Kwok-Kin 
Published: September 2013

Abstract
Purpose: Amplification of MYC is one of the most common genetic alterations in lung cancer, contributing to a myriad of phenotypes associated with growth, invasion, and drug resistance. Murine genetics has established both the centrality of somatic alterations of Kras in lung cancer, as well as the dependency of mutant Kras tumors on MYC function. Unfortunately, drug-like small-molecule inhibitors of KRAS and MYC have yet to be realized. The recent discovery, in hematologic malignancies, that bromodomain and extra-terminal (BET) bromodomain inhibition impairs MYC expression and MYC transcriptional function established the rationale of targeting KRAS-driven non–small cell lung cancer (NSCLC) with BET inhibition.
Experimental Design: We performed functional assays to evaluate the effects of JQ1 in genetically defined NSCLC cell lines harboring KRAS and/or LKB1 mutations. Furthermore, we evaluated JQ1 in transgenic mouse lung cancer models expressing mutant kras or concurrent mutant kras and lkb1. Effects of bromodomain inhibition on transcriptional pathways were explored and validated by expression analysis.
Results: Although JQ1 is broadly active in NSCLC cells, activity of JQ1 in mutant KRAS NSCLC is abrogated by concurrent alteration or genetic knockdown of LKB1. In sensitive NSCLC models, JQ1 treatment results in the coordinate downregulation of the MYC-dependent transcriptional program. We found that JQ1 treatment produces significant tumor regression in mutant kras mice. As predicted, tumors from mutant kras and lkb1 mice did not respond to JQ1.
Conclusion: Bromodomain inhibition comprises a promising therapeutic strategy for KRAS-mutant NSCLC with wild-type LKB1, via inhibition of MYC function. Clinical studies of BET bromodomain inhibitors in aggressive NSCLC will be actively pursued. Clin Cancer Res; 19(22); 6183–92. ©2013 AACR.
Overcoming IGF1R/IR Resistance through Inhibition of MEK Signaling in Colorectal Cancer Models
Authors: Flanigan Sara A. , Pitts Todd M. , Newton Timothy P. , Kulikowski Gillian N. , Tan Aik Choon , McManus Martine C. , Spreafico Anna , Kachaeva Maria I. , Selby Heather M. , Tentler John J. , Eckhardt S. Gail , Leong Stephen 
Published: September 2013

Abstract
Purpose: Results from clinical trials involving resistance to molecularly targeted therapies have revealed the importance of rational single-agent and combination treatment strategies. In this study, we tested the efficacy of a type 1 insulin-like growth factor receptor (IGF1R)/insulin receptor (IR) tyrosine kinase inhibitor, OSI-906, in combination with a mitogen–activated protein (MAP)–ERK kinase (MEK) 1/2 inhibitor based on evidence that the MAP kinase pathway was upregulated in colorectal cancer cell lines that were resistant to OSI-906.
Experimental Design: The antiproliferative effects of OSI-906 and the MEK 1/2 inhibitor U0126 were analyzed both as single agents and in combination in 13 colorectal cancer cell lines in vitro. Apoptosis, downstream effector proteins, and cell cycle were also assessed. In addition, the efficacy of OSI-906 combined with the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886) was evaluated in vivo using human colorectal cancer xenograft models.
Results: The combination of OSI-906 and U0126 resulted in synergistic effects in 11 of 13 colorectal cancer cell lines tested. This synergy was variably associated with apoptosis or cell-cycle arrest in addition to molecular effects on prosurvival pathways. The synergy was also reflected in the in vivo xenograft studies following treatment with the combination of OSI-906 and selumetinib.
Conclusions: Results from this study demonstrate synergistic antiproliferative effects in response to the combination of OSI-906 with an MEK 1/2 inhibitor in colorectal cancer cell line models both in vitro and in vivo, which supports the rational combination of OSI-906 with an MEK inhibitor in patients with colorectal cancer. Clin Cancer Res; 19(22); 6219–29. ©2013 AACR.
Dual CDK4/CDK6 Inhibition Induces Cell-Cycle Arrest and Senescence in Neuroblastoma
Authors: Rader JulieAnn , Russell Mike R. , Hart Lori S. , Nakazawa Michael S. , Belcastro Lili T. , Martinez Daniel , Li Yimei , Carpenter Erica L. , Attiyeh Edward F. , Diskin Sharon J. , Kim Sunkyu , Parasuraman Sudha , Caponigro Giordano , Schnepp Robert W. , Wood Andrew C. , Pawel Bruce , Cole Kristina A. , Maris John M. 
Published: September 2013

Abstract
Purpose: Neuroblastoma is a pediatric cancer that continues to exact significant morbidity and mortality. Recently, a number of cell-cycle proteins, particularly those within the Cyclin D/CDK4/CDK6/RB network, have been shown to exert oncogenic roles in neuroblastoma, suggesting that their therapeutic exploitation might improve patient outcomes.
Experimental Procedures: We evaluated the effect of dual CDK4/CDK6 inhibition on neuroblastoma viability using LEE011 (Novartis Oncology), a highly specific CDK4/6 inhibitor.
Results: Treatment with LEE011 significantly reduced proliferation in 12 of 17 human neuroblastoma-derived cell lines by inducing cytostasis at nanomolar concentrations (mean IC50 = 307 ± 68 nmol/L in sensitive lines). LEE011 caused cell-cycle arrest and cellular senescence that was attributed to dose-dependent decreases in phosphorylated RB and FOXM1, respectively. In addition, responsiveness of neuroblastoma xenografts to LEE011 translated to the in vivo setting in that there was a direct correlation of in vitro IC50 values with degree of subcutaneous xenograft growth delay. Although our data indicate that neuroblastomas sensitive to LEE011 were more likely to contain genomic amplification of MYCN (P = 0.01), the identification of additional clinically accessible biomarkers is of high importance.
Conclusions: Taken together, our data show that LEE011 is active in a large subset of neuroblastoma cell line and xenograft models, and supports the clinical development of this CDK4/6 inhibitor as a therapy for patients with this disease. Clin Cancer Res; 19(22); 6173–82. ©2013 AACR.
Escalating Regulation of 5T4-Specific IFN-γ+ CD4+ T Cells Distinguishes Colorectal Cancer Patients from Healthy Controls and Provides a Target for In Vivo Therapy
Authors: Scurr Martin , Bloom Anja , Pembroke Tom , Srinivasan Rohit , Brown Clare , Smart Kathryn , Bridgeman Hayley , Davies Mike , Hargest Rachel , Phillips Simon , Christian Adam , Hockey Tom , Gallimore Awen , Godkin Andrew 
Published: September 2013

Abstract
The relationship between the adaptive CD4+ T-cell response and human cancer is unclear. The oncofetal antigen 5T4 is expressed in many human carcinomas, including colorectal cancer cells, but has limited expression on normal tissues. We previously identified anti-5T4 CD4+ T cells in a proportion of patients with colorectal cancer, and we extended this study to examine whether the quality or quantity of the T-cell response reflects tumor stage. An overlapping peptide library spanning 5T4 was used as a target to enumerate cognate IFN-γ+ CD4+ T cells [measured as spot-forming cells (SFC)/105 cultured T cells] in peripheral blood–derived lymphocytes following a 14-day in vitro culture period comparing patients preoperatively (n = 27) to healthy controls (n = 17). Robust 5T4-specific T-cell responses were present in 100% of healthy donors. There was a steady loss of T-cell responses with advancing tumors with a significant negative correlation from stage I to III (P = 0.008). The predictability of the decline meant &lt;200 SFC/105 were only found in subjects with stage III colorectal cancer. The mechanism of loss of T-cell response is independent of HLA-DR type or patient age but does correspond to increases in Foxp3+ regulatory T cells (Treg). Using low-dose cyclophosphamide to reduce the proportion of Tregs in vivo resulted in increased anti-5T4 T-cell responses in patients with colorectal cancer. The selective loss of 5T4-specific IFN-γ+ CD4+ T-cell responses implies a link between tumor stage and antitumor Th1 effector function; depleting Tregs can enhance such responses. Cancer Immunol Res; 1(6); 416–25. ©2013 AACR.
Randomized Trial of Conventional Transseptal Needle Versus Radiofrequency Energy Needle Puncture for Left Atrial Access (the TRAVERSE‐LA Study)
Authors: Hsu Jonathan C. , Badhwar Nitish , Gerstenfeld Edward P. , Lee Randall J. , Mandyam Mala C. , Dewland Thomas A. , Imburgia Kourtney E. , Hoffmayer Kurt S. , Vedantham Vasanth , Lee Byron K. , Tseng Zian H. , Scheinman Melvin M. , Olgin Jeffrey E. , Marcus Gregory M. 
Published: September 2013

Background

Transseptal puncture is a critical step in achieving left atrial (
LA
) access for a variety of cardiac procedures. Although the mechanical
B
rockenbrough needle has historically been used for this procedure, a needle employing radiofrequency (
RF
) energy has more recently been approved for clinical use. We sought to investigate the comparative effectiveness of an
RF
versus conventional needle for transseptal
LA
access.

Methods and Results

In this prospective, single‐blinded, controlled trial, 72 patients were randomized in a 1:1 fashion to an
RF
versus conventional (
BRK
‐1) transseptal needle. In an intention‐to‐treat analysis, the primary outcome was time required for transseptal
LA
access. Secondary outcomes included failure of the assigned needle, visible plastic dilator shavings from needle introduction, and any procedural complication. The median transseptal puncture time was 68% shorter using the
RF
needle compared with the conventional needle (2.3 minutes [interquartile range {
IQR
}, 1.7 to 3.8 minutes] versus 7.3 minutes [
IQR
, 2.7 to 14.1 minutes],
P
=0.005). Failure to achieve transseptal
LA
access with the assigned needle was less common using the
RF
versus conventional needle (0/36 [0%] versus 10/36 [27.8%],
P
<0.001). Plastic shavings were grossly visible after needle advancement through the dilator and sheath in 0 (0%)
RF
needle cases and 12 (33.3%) conventional needle cases (
P
<0.001). There were no differences in procedural complications (1/36 [2.8%] versus 1/36 [2.8%]).

Conclusions

Use of an
RF
needle resulted in shorter time to transseptal
LA
access, less failure in achieving transseptal
LA
access, and fewer visible plastic shavings.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
01209260.
Recurrent Processing Enhances Visual Awareness but Is Not Necessary for Fast Categorization of Natural Scenes
Authors: Koivisto Mika , Kastrati Granit , Revonsuo Antti 
Published: September 2013

Abstract
Humans are rapid in categorizing natural scenes. Electrophysiological recordings reveal that scenes containing animals can be categorized within 150 msec, which has been interpreted to indicate that feedforward flow of information from V1 to higher visual areas is sufficient for visual categorization. However, recent studies suggest that recurrent interactions between higher and lower levels in the visual hierarchy may also be involved in categorization. To clarify the role of recurrent processing in scene categorization, we recorded EEG and manipulated recurrent processing with object substitution masking while the participants performed a go/no-go animal/nonanimal categorization task. The quality of visual awareness was measured with a perceptual awareness scale after each trial. Masking reduced the clarity of perceptual awareness, slowed down categorization speed for scenes that were not clearly perceived, and reduced the electrophysiological difference elicited by animal and nonanimal scenes after 150 msec. The results imply that recurrent processes enhance the resolution of conscious representations and thus support categorization of stimuli that are difficult to categorize on the basis of the coarse feedforward representations alone.
Embodied Comprehension of Stories: Interactions between Language Regions and Modality-specific Neural Systems
Authors: Chow Ho Ming , Mar Raymond A. , Xu Yisheng , Liu Siyuan , Wagage Suraji , Braun Allen R. 
Published: September 2013

AbstractThe embodied view of language processing proposes that comprehension involves multimodal simulations, a process that retrieves a comprehender's perceptual, motor, and affective knowledge through reactivation of the neural systems responsible for perception, action, and emotion. Although evidence in support of this idea is growing, the contemporary neuroanatomical model of language suggests that comprehension largely emerges as a result of interactions between frontotemporal language areas in the left hemisphere. If modality-specific neural systems are involved in comprehension, they are not likely to operate in isolation but should interact with the brain regions critical to language processing. However, little is known about the ways in which language and modality-specific neural systems interact. To investigate this issue, we conducted a functional MRI study in which participants listened to stories that contained visually vivid, action-based, and emotionally charged content. Activity of neural systems associated with visual-spatial, motor, and affective processing were selectively modulated by the relevant story content. Importantly, when functional connectivity patterns associated with the left inferior frontal gyrus (LIFG), the left posterior middle temporal gyrus (pMTG), and the bilateral anterior temporal lobes (aTL) were compared, both LIFG and pMTG, but not the aTL, showed enhanced connectivity with the three modality-specific systems relevant to the story content. Taken together, our results suggest that language regions are engaged in perceptual, motor, and affective simulations of the described situation, which manifest through their interactions with modality-specific systems. On the basis of our results and past research, we propose that the LIFG and pMTG play unique roles in multimodal simulations during story comprehension.
A Dorsal Visual Route Necessary for Global Form Perception: Evidence from Neuropsychological fMRI
Authors: Lestou Vaia , Lam Judith Mi Lin , Humphreys Katie , Kourtzi Zoe , Humphreys Glyn W. 
Published: September 2013

Abstract
Hierarchical models of visual processing assume that global pattern recognition is contingent on the progressive integration of local elements across larger spatial regions, operating from early through intermediate to higher-level cortical regions. Here, we present results from neuropsychological fMRI that refute such models. We report two patients, one with lesions to intermediate ventral regions and the other with damage around the intraparietal sulcus (IPS). The patient with ventral damage showed normal behavioral and BOLD responses to global Glass patterns. The patient with IPS damage was impaired in discriminating global patterns and showed a lack of significant responses to these patterns in intermediate visual regions spared by the lesion. However, this patient did show BOLD activity to translational patterns, where local element relations are important. These results suggest that activation of intermediate ventral regions is not necessary to code global patterns; instead global patterns are coded in a heterarchical fashion. High-level regions of dorsal cortex are necessary to generate global pattern coding in intermediate ventral regions; in contrast, local integration processes are not sufficient.
Attention to Detail: Why Considering Task Demands Is Essential for Single-Trial Analysis of BOLD Correlates of the Visual P1 and N1
Authors: Warbrick Tracy , Arrubla Jorge , Boers Franks , Neuner Irene , Shah N. Jon 
Published: September 2013

Abstract
Single-trial fluctuations in the EEG signal have been shown to temporally correlate with the fMRI BOLD response and are valuable for modeling trial-to-trial fluctuations in responses. The P1 and N1 components of the visual ERP are sensitive to different attentional modulations, suggesting that different aspects of stimulus processing can be modeled with these ERP parameters. As such, different patterns of BOLD covariation for P1 and N1 informed regressors would be expected; however, current findings are equivocal. We investigate the effects of variations in attention on P1 and N1 informed BOLD activation in a visual oddball task. Simultaneous EEG-fMRI data were recorded from 13 healthy participants during three conditions of a visual oddball task: Passive, Count, and Respond. We show that the P1 and N1 components of the visual ERP can be used in the integration-by-prediction method of EEG-fMRI data integration to highlight brain regions related to target detection and response production. Our data suggest that the P1 component of the ERP reflects changes in sensory encoding of stimulus features and is more informative for the Passive and Count conditions. The N1, on the other hand, was more informative for the Respond condition, suggesting that it can be used to model the processing of stimulus, meaning specifically discriminating one type of stimulus from another, and processes involved in integrating sensory information with response selection. Our results show that an understanding of the underlying electrophysiology is necessary for a thorough interpretation of EEG-informed fMRI analysis.
Generic Inhibition of the Selected Movement and Constrained Inhibition of Nonselected Movements during Response Preparation
Authors: Labruna Ludovica , Lebon Florent , Duque Julie , Klein Pierre-Alexandre , Cazares Christian , Ivry Richard B. 
Published: September 2013

AbstractPrevious studies have identified two inhibitory mechanisms that operate during action selection and preparation. One mechanism, competition resolution, is manifest in the inhibition of the nonselected response and attributed to competition between candidate actions. The second mechanism, impulse control, is manifest in the inhibition of the selected response and is presumably invoked to prevent premature response. To identify constraints on the operation of these two inhibitory mechanisms, we manipulated the effectors used for the response alternatives, measuring changes in corticospinal excitability with motor-evoked potentials to TMS. Inhibition of the selected response (impulse control) was independent of the task context, consistent with a model in which this form of inhibition is automatically triggered as part of response preparation. In contrast, inhibition of the nonselected response (competition resolution) was context-dependent. Inhibition of the nonselected response was observed when the response alternatives involved movements of the upper limbs but was absent when one response alternative involved an upper limb and the other involved a lower limb. Interestingly, competition resolution for pairs of upper limbs did not require homologous effectors, observed when a left index finger response was pitted with either a nonhomologous right index finger movement or a right arm movement. These results argue against models in which competition resolution is viewed as a generic or fully flexible process, as well as models based on strong anatomical constraints. Rather, they are consistent with models in which inhibition for action selection is constrained by the similarity between the potential responses, perhaps reflecting an experience-dependent mechanism sensitive to the past history of competitive interactions.
The Assimilation of Observations from the Advanced Microwave Sounding Unit over Sea Ice in the French Global Numerical Weather Prediction System
Authors: Karbou Fatima , Rabier Florence , Prigent Catherine 
Published: September 2013

Abstract
The aim of this study is to test the feasibility of assimilating microwave observations from the Advanced Microwave Sounding Units (AMSU-A and AMSU-B) through the implementation of an appropriate parameterization of sea ice emissivity. AMSU observations are relevant to the description of air temperature and humidity, and their assimilation into numerical weather prediction (NWP) helps better constrain models in regions where very few observations are assimilated. A sea ice emissivity model suitable for AMSU-A and AMSU-B data is described in this paper and its impact is studied through two assimilation experiments run during the period of the Arctic winter. The first experiment is representative of the operational version of the Météo-France NWP model whereas the second simulation uses the sea ice emissivity parameterization and assimilates a selection of AMSU channels above polar regions. The assimilation of AMSU observations over sea ice is shown to have a significant effect on atmospheric analyses (in particular those of temperature and humidity). The effect on temperature induces a warming in the lower troposphere, especially around 850 hPa. This leads to an increase in the Arctic inversion strength over the ice cap by almost 2 K. An improvement in medium-range forecasts is also noticed when the NWP model assimilates AMSU observations over sea ice.