bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic and Predictive Values of the Immunoscore in Patients with Rectal Cancer
Authors: Anitei Maria-Gabriela , Zeitoun Guy , Mlecnik Bernhard , Marliot Florence , Haicheur Nacilla , Todosi Ana-Maria , Kirilovsky Amos , Lagorce Christine , Bindea Gabriela , Ferariu Dan , Danciu Mihai , Bruneval Patrick , Scripcariu Viorel , Chevallier Jean-Marc , Zinzindohoué Franck , Berger Anne , Galon Jérôme , Pagès Franck 
Published: April 2014

Abstract
Purpose: To determine whether the tumor immune infiltrate, as recently evaluated with the Immunoscore methodology, could be a useful prognostic marker in patients with rectal cancers.
Experimental design: The influence of the immune infiltrate on patient's outcome was investigated in patients with or without preoperative chemoradiation therapy (pCRT). The density of total (CD3+) and cytotoxic (CD8+) T lymphocytes was evaluated by immunohistochemistry and quantified by a dedicated image analysis software in surgical specimens of patients with rectal cancer (n = 111) who did not receive pCRT and in tumor biopsies performed before pCRT from additional 55 patients. The results were correlated with tumor recurrence, patient's survival, and response to pCRT.
Results: The densities of CD3+ and CD8+ lymphocytes and the associated Immunoscore (from I0 to I4) were significantly correlated with differences in disease-free and overall survival (HR, 1.81 and 1.72, respectively; all P &lt; 0.005). Cox multivariate analysis supports the advantage of the Immunoscore compared with the tumor–node–metastasis (TNM) staging in predicting recurrence and survival (all P &lt; 0.001). Lymph node ratio added information in a prognostic model (all P &lt; 0.05). In addition, high infiltration of CD3+ and CD8+ lymphocytes in tumor biopsies was associated with downstaging of the tumor after pCRT (CD3+ cells; Fisher exact test P = 0.01).
Conclusions: The Immunoscore could be a useful prognostic marker in patients with rectal cancer treated by primary surgery. The determination of the immune infiltrate in biopsies before treatment could be a valuable information for the prediction of response to pCRT. Clin Cancer Res; 20(7); 1891–9. ©2014 AACR.
KRAS Codon 12 and 13 Mutations in Relation to Disease-Free Survival in BRAF–Wild-Type Stage III Colon Cancers from an Adjuvant Chemotherapy Trial (N0147 Alliance)
Authors: Yoon Harry H. , Tougeron David , Shi Qian , Alberts Steven R. , Mahoney Michelle R. , Nelson Garth D. , Nair Suresh G. , Thibodeau Stephen N. , Goldberg Richard M. , Sargent Daniel J. , Sinicrope Frank A. ,   for the Alliance for Clinical Trials in Oncology
Published: April 2014

Abstract
Purpose: We examined the prognostic impact of specific KRAS mutations in patients with stage III colon adenocarcinoma receiving adjuvant FOLFOX alone or combined with cetuximab in a phase III trial (N0147). Analysis was restricted to BRAF–wild-type tumors, because BRAF mutation was associated with poor prognosis, and BRAF and KRAS mutations are mutually exclusive.
Experimental Design: The seven most common KRAS mutations in codon 12 and codon 13 were examined in 2,478 BRAF–wild-type tumors. Because KRAS mutations in codon 12 (n = 779) or 13 (n = 220) were not predictive of adjuvant cetuximab benefit, study arms were pooled for analysis. Disease-free survival (DFS) was evaluated by HRs using Cox models.
Results: KRAS mutations in codon 12 (multivariate HR, 1.52; 95% confidence interval, CI, 1.28–1.80; P &lt; 0.0001) or codon 13 (multivariate HR, 1.36; 95% CI, 1.04–1.77; P = 0.0248) were significantly associated with shorter DFS compared with patients with wild-type KRAS/BRAF tumors, independent of covariates. KRAS codon 12 mutations were independently associated with proficient mismatch repair (P &lt; 0.0001), proximal tumor site (P &lt; 0.0001), low grade, age, and sex, whereas codon 13 mutations were associated with proximal site (P &lt; 0.0001).
Conclusion: KRAS mutations in either codon 12 or 13 are associated with inferior survival in patients with resected stage III colon cancer. These data highlight the importance of accurate molecular characterization and the significant role of KRAS mutations in both codons in the progression of this malignancy in the adjuvant setting. Clin Cancer Res; 20(11); 3033–43. ©2014 AACR.
Inhibition of mTOR Signaling Reduces PELP1-Mediated Tumor Growth and Therapy Resistance
Authors: Gonugunta Vijay K. , Sareddy Gangadhara R. , Krishnan Samaya Rajeshwari , Cortez Valerie , Roy Sudipa Saha , Tekmal Rajeshwar Rao , Vadlamudi Ratna K. 
Published: April 2014

Abstract
Proline, Glutamic acid-, and Leucine-rich Protein 1 (PELP1) is a proto-oncogene that modulates estrogen receptor (ER) signaling. PELP1 expression is upregulated in breast cancer, contributes to therapy resistance, and is a prognostic marker of poor survival. In a subset of breast tumors, PELP1 is predominantly localized in the cytoplasm and PELP1 participates in extranuclear signaling by facilitating ER interactions with Src and phosphoinositide 3-kinase (PI3K). However, the mechanism by which PELP1 extranuclear actions contributes to cancer progression and therapy resistance remains unclear. In this study, we discovered that PELP1 cross-talked with the serine/threonine protein kinase mTOR and modulated mTOR signaling. PELP1 knockdown significantly reduced the activation of mTOR downstream signaling components. Conversely, PELP1 overexpression excessively activated mTOR signaling components. We detected the presence of the mTOR signaling complex proteins in PELP1 immunoprecipitates. mTOR-targeting drugs (rapamycin and AZD8055) significantly reduced proliferation of PELP1-overexpressed breast cancer cells in both in vitro and in vivo xenograft tumor models. MCF7 cells that uniquely retain PELP1 in the cytoplasm showed resistance to hormonal therapy and mTOR inhibitors sensitized PELP1cyto cells to hormonal therapy in xenograft assays. Notably, immunohistochemical studies using xenograft tumors derived from PELP1 overexpression model cells showed increased mTOR signaling and inhibition of mTOR rendered PELP1-driven tumors to be highly sensitive to therapeutic inhibition. Collectively, our data identified the PELP1–mTOR axis as a novel component of PELP1 oncogenic functions and suggest that mTOR inhibitor(s) will be effective chemotherapeutic agents for downregulating PELP1 oncogenic functions. Mol Cancer Ther; 13(6); 1578–88. ©2014 AACR.
Natural Compound Alternol Induces Oxidative Stress–Dependent Apoptotic Cell Death Preferentially in Prostate Cancer Cells
Authors: Tang Yuzhe , Chen Ruibao , Huang Yan , Li Guodong , Huang Yiling , Chen Jiepeng , Duan Lili , Zhu Bao-Ting , Thrasher J. Brantley , Zhang Xu , Li Benyi 
Published: April 2014

Abstract
Prostate cancers at the late stage of castration resistance are not responding well to most of current therapies available in clinic, reflecting a desperate need of novel treatment for this life-threatening disease. In this study, we evaluated the anticancer effect of a recently isolated natural compound, Alternol, in multiple prostate cancer cell lines with the properties of advanced prostate cancers in comparison to prostate-derived nonmalignant cells. As assessed by trypan blue exclusion assay, significant cell death was observed in all prostate cancer cell lines except DU145 but not in nonmalignant (RWPE-1 and BPH1) cells. Further analyses revealed that Alternol-induced cell death was an apoptotic response in a dose- and time-dependent manner, as evidenced by the appearance of apoptosis hallmarks such as caspase-3 processing and PARP cleavage. Interestingly, Alternol-induced cell death was completely abolished by reactive oxygen species scavengers N-acetylcysteine and dihydrolipoic acid. We also demonstrated that the proapoptotic Bax protein was activated after Alternol treatment and was critical for Alternol-induced apoptosis. Animal xenograft experiments in nude mice showed that Alternol treatment largely suppressed tumor growth of PC-3 xenografts but not Bax-null DU-145 xenografts in vivo. These data suggest that Alternol might serve as a novel anticancer agent for patients with late-stage prostate cancer. Mol Cancer Ther; 13(6); 1526–36. ©2014 AACR.
Early Adult to Midlife Cardiovascular Risk Factors and Cognitive Function
Authors: Yaffe Kristine , Vittinghoff Eric , Pletcher Mark J. , Hoang Tina D. , Launer Lenore J. , Whitmer Rachel A. , Coker Laura H. , Sidney Stephen 
Published: April 2014

Background—
Studies have linked midlife and late-life cardiovascular risk factors (CVRFs) to cognitive function, yet little is known about CVRF exposure in early adulthood and subsequent cognitive function. In addition, most studies rely on single assessments of CVRFs, which may not accurately reflect long-term exposure. We sought to determine the association between cumulative exposure to CVRFs from early to middle adulthood and cognitive function at midlife.

Methods and Results—

In a prospective study of 3381 adults (age, 18–30 years at baseline) with 25 years of follow-up, we assessed cognitive function at year 25 (2010–2011) with the Digit Symbol Substitution Test, Stroop Test, and Rey Auditory Verbal Learning Test analyzed with standardized
z
scores. The primary predictor was 25-year cumulative exposure estimated by areas under the curve for resting systolic and diastolic blood pressures, fasting blood glucose, and total cholesterol. Higher cumulative systolic and diastolic blood pressures and fasting blood glucose were consistently associated with worse cognition on all 3 tests. These associations were significant primarily for exposures above recommended guidelines; cognitive test
z
scores were between 0.06 and 0.30 points less, on average, for each 1-SD increase in risk factor area under the curve after adjustment for age, race, sex, and education (
P
<0.05 for all). Fewer significant associations were observed for cholesterol.

Conclusions—
Cumulative exposure to CVRFs from early to middle adulthood, especially above recommended guidelines, was associated with worse cognition in midlife. The meaning of this association and whether it warrants more aggressive treatment of CVRFs earlier in life require further investigation.
The Modern Privilege of Life
Authors: Ziarek Krzysztof 
Published: April 2014

Abstract
This essay reconsiders the notion of “world” by looking critically at the idiom of life dominating current critical debates. Showing how and why life should be displaced from the privileged position it has assumed in modernity, it examines Arendt’s and Heidegger’s comments on the world. In The Human Condition, Arendt provides an interesting philosophical and cultural account of the rise of life to prominence in the modern age, pointing out its detrimental effects on the understanding of the world and human action. Heidegger, on the other hand, executes, through his idiomatic approach to mortality, perhaps the most radical displacement of life in an attempt to rethink and bring to eminence being and the event of the world. At stake is a different experience of the world and a change in the understanding of the human, situating the human (and) life always already in response to the nonrepeatable event of being.
Leaf Area Index Variation for Crop, Pasture, and Tree in Response to Climatic Variation in the Goulburn–Broken Catchment, Australia
Authors: Tesemma Zelalem K. , Wei Yongping , Western Andrew W. , Peel Murray C. 
Published: April 2014

Abstract
Previous studies have reported relationships between mean annual climatic variables and mean annual leaf area index (LAI), but the seasonal and spatial variability of this relationship for different vegetation cover types in different climate zones have rarely been explored in Australia. The authors developed simple models using remotely sensed LAI data from the Moderate Resolution Imaging Spectroradiometer (MODIS) and gridded climatic data from the Australian Water Availability Project. They were able to relate seasonal and annual LAI of three different land cover types (tree, pasture, and crop) with climatic variables for the period 2000–09 in the Goulburn–Broken catchment, Australia. Strong relationships were obtained between annual LAI of crop, pasture, and tree with annual precipitation (R2 = 0.70, 0.65, and 0.82, respectively). Monthly LAI of each land cover type also showed a strong relationship (R2 = 0.92, 0.95, and 0.95) with the difference between precipitation P and reference crop evapotranspiration (PET; P − PET) for crop, pasture, and tree. Independent model calibration and validation showed good agreement with remotely sensed MODIS LAI. The results from the application of the developed model on the future impact of climate change suggest that under all climate scenarios crop, pasture, and tree showed consistent decreases in mean annual LAI. For the future climate change scenarios considered, crop showed a decline of 7%–38%, pasture showed a decline of 5%–24%, and tree showed a decline of 2%–11% from the historical mean annual. These results can be used to assess the impacts of future climatic and land cover changes on water resources by coupling them with hydrological models.
A Global Surface Ocean fCO2 Climatology Based on a Feed-Forward Neural Network
Authors: Zeng J. , Nojiri Y. , Landschützer P. , Telszewski M. , Nakaoka S. 
Published: April 2014

Abstract
A feed-forward neural network is used to create a monthly climatology of the sea surface fugacity of CO2 (fCO2) on a 1° × 1° spatial resolution. Using 127 880 data points from 1990 to 2011 in the track-gridded database of the Surface Ocean CO2 Atlas version 2.0 (Bakker et al.), the model yields a global mean fCO2 increase rate of 1.50 μatm yr−1. The rate was used to normalize multiple years’ fCO2 observations to the reference year of 2000. A total of 73 265 data points from the normalized data were used to model the global fCO2 climatology. The model simulates monthly fCO2 distributions that agree well with observations and yields an anthropogenic CO2 update of −1.9 to −2.3 PgC yr−1. The range reflects the uncertainty related to using different wind products for the flux calculation. This estimate is in good agreement with the recently derived best estimate by Wanninkhof et al. The model product benefits from a finer spatial resolution compared to the product of Lamont–Doherty Earth Observatory (Takahashi et al.), which is currently the most frequently used product. It therefore has the potential to improve estimates of the global ocean CO2 uptake. The method’s benefits include but are not limited to the following: (i) a fixed structure is not required to model fCO2 as a nonlinear function of biogeochemical variables, (ii) only one neural network configuration is sufficient to model global fCO2 in all seasons, and (iii) the model can be extended to produce global fCO2 maps at a higher resolution in time and space as long as the required data for input variables are available.
Social Process of Adaptation to Environmental Changes: How Eastern African Societies Intervene between Crops and Climate
Authors: Mwongera Caroline , Boyard-Micheau Joseph , Baron Christian , Leclerc Christian 
Published: April 2014

Abstract
Studies on climate change can only be conducted on a long time scale, and observing how societies adapt their sowing practices to climate variability is challenging and costly. As an alternative, a space and time substitution design was used, changes in space corresponding to that induced in time by environmental change. On the eastern slope of Mount Kenya, the Tharaka community, originating from the lowlands (750 m), moved up to the midlands (950 m) with their lowland-adapted resources, whereas the Mwimbi, originating from wetter upland (1100 m), moved down to the midlands with their highland-adapted genetic resources. A weather station was installed at 950 and 1100 m, and a logistic model was used to analyze the probability of sowing failure as a function of the length of dry spells after sowing. A total of 1691 plots in 40 surveyed farms were surveyed to compare the Mwimbi and Tharaka during 2 yr and four growing seasons, controlling crops and altitude. Although seed-sowing practices were similar in both communities, the relative risk of sowing failure was 3.3 times more for the Mwimbi than for the Tharaka during the Short Rains, and 1.5 times more during the Long Rains. This difference can be explained by within-community seed exchanges, as Tharaka seeds, originally from the lowlands, are adapted to drier conditions, whereas Mwimbi seeds are adapted to wetter conditions. The findings suggest an impact of historical and social factors on the mitigation of sowing failure risk. Thus, they must be considered as an integral part of the adaptation process to climate variability and change.
Family and Community Influences on Diabetes-Related Dietary Change in a Low-Income Urban Neighborhood
Authors: Pollard Suzanne L. , Zachary Drew A. , Wingert Katherine , Booker Sara S. , Surkan Pamela J. 
Published: April 2014

Purpose The purpose of this study is to explore the influence of the social environment, including family and community relationships, on diabetes-related dietary change behaviors in a low-income, predominantly African American community with limited access to healthy foods. Methods Study methods included interviews and focus groups with adults with diabetes and family members of individuals with diabetes in a low-income African American community. In this analysis, interview participants included 11 participants with diabetes, one with prediabetes, and 8 family members or close friends with diabetes. Information from 4 participants with diabetes and 6 with family members with diabetes was included from 6 focus groups. Transcripts were analyzed via thematic iterative coding influenced by social cognitive theory to understand the influence of family and community relationships on dietary change. Results Participants’ social environments strongly influenced diet-related behavioral change. Family members without diabetes provided reinforcements for dietary change for those with diabetes by preparing healthy food and monitoring intake, as well as by adopting dietary changes made by those with diabetes. Family and community members served as sources of observational learning about the potential impacts of diabetes and enhanced behavioral capability for dietary change among people with diabetes by providing dietary advice and strategies for making healthy choices. Conclusions This study demonstrates the ways in which family and community members can influence dietary change in people with diabetes. Interventions targeting diabetes management should incorporate families and communities as sources of information, learning, and support.
Partnering With Families to Refine and Expand a Diabetes Intervention for Mexican Americans
Authors: McEwen Marylyn Morris , Murdaugh Carolyn 
Published: April 2014

Purpose The purpose of this study was to refine and expand a culturally tailored individual-level diabetes self-management intervention to a family-level intervention. Methods Using community-based participatory research principles, Mexican American adults (n = 12) with type 2 diabetes mellitus (T2DM) and family members (n = 12) in the United States–Mexico border region participated in 6 focus group interviews, conducted by bilingual, bicultural facilitators. Facilitators and barriers to T2DM management were identified. Transcripts were analyzed using qualitative content analysis. Results Through an iterative analysis process, 5 categories represented participants with T2DM: (1) strategies my family can use to support our managing T2DM, (2) be sensitive to my challenges, (3) stop telling me what to eat or do, (4) how can we peacefully coexist, and (5) I feel supported. Categories identified by family members were (1) changing behaviors together, (2) sharing not controlling, (3) supporting positive behaviors, and (4) your behaviors frustrate me. Conclusions The family was reinforced as a major influence for successful T2DM management. Family support requires that families value and develop knowledge and skills for T2DM management. This family intervention builds on family assets and relationships, shifting from traditional externally motivated individual models to create a shared commitment to manage T2DM among Mexican American adults.
Prevalence of Complications from Adult Tonsillectomy and Impact on Health Care Expenditures
Authors: Seshamani Meena , Vogtmann Emily , Gatwood Justin , Gibson Teresa B. , Scanlon Dennis 
Published: April 2014

ObjectiveTo provide information on the prevalence of common complications of adult tonsillectomy and associated health care utilization and expenditures.Study DesignRetrospective analysis of a large insurance database.SettingData from the MarketScan Commercial Claims and Encounters Database.Subjects and MethodsTreated prevalence rates for post‐tonsillectomy complications were calculated for 36,210 patients with employer‐sponsored insurance who had an outpatient tonsillectomy between 2002 and 2007. The relationships with various patient characteristics were examined using multivariate logistic regression. Postoperative emergency department (ED) visits and hospitalizations and total per capita health care expenditures were analyzed.ResultsThis analysis suggests that of adult patients who undergo a tonsillectomy, 20% will have a complication, 10% will visit an ED, and approximately 1.5% will be admitted to a hospital within 14 days of the tonsillectomy. Six percent were treated for postoperative hemorrhage, 2% for dehydration, and 11% for ENT pain within 14 days of surgery. Patients with comorbidities, prior peritonsillar abscess, or an increased number of antibiotic prescriptions in the past year were significantly more likely to develop complications. Three out of 4 patients with postoperative hemorrhage went to the ED (4.63% of all patients), and 50% had a procedural intervention (3.09% overall). The average cost associated with a tonsillectomy was $3832 if no complication. If there was a complication within 14 days, hemorrhage was the most expensive ($6388 vs $5753 for dehydration and $4708 for ENT pain).ConclusionsComplications of adult outpatient tonsillectomies are common and may be associated with significant morbidity, health care utilization, and expenditures.
Rapid Systematic Review of the Epley Maneuver for Treating Posterior Canal Benign Paroxysmal Positional Vertigo
Authors: van Duijn Jeroen G. , Isfordink Liz M. , Nij Bijvank Jenny A. , Stapper Carlijne W. , van Vuren Annelies J. , Wegner Inge , Kortekaas Marlous F. , Grolman Wilko 
Published: April 2014

ObjectiveThe aim of this study was to compare watchful waiting to the Epley maneuver as a management option for patients with posterior canal benign paroxysmal positional vertigo (p‐BPPV) regarding symptom relief.Data SourcesPubMed, Embase, and The Cochrane Library.MethodsA systematic search was conducted. Studies reporting original study data were included. Relevance and risk of bias (RoB) of the selected articles were assessed. Studies with low relevance, high RoB, or both were excluded. Absolute risk differences and their 95% confidence intervals (CIs) were extracted for the included studies.ResultsA total of 1448 unique studies were retrieved. Eight of these satisfied the eligibility criteria. At 1‐week follow‐up, all included studies reported a clinically relevant effect in favor of the Epley maneuver regarding symptom relief (absolute risk differences ranging from 20% [95% CI, 5%‐37%] to 59% [95% CI, 32%‐76%]) or conversion to a negative Dix–Hallpike (absolute risk differences ranging from 17% [95% CI, –5%‐37%] to 64% [95% CI, 29%‐79%]). At 1‐month follow‐up, the results of the included studies diverged further. Absolute risk differences ranged from 6% (95% CI, –24%‐35%) more symptom relief in favor of watchful waiting to 79% (95% CI, 56%‐88%) in favor of the Epley maneuver.Conclusion and RecommendationsAll data of the selected studies show a benefit in favor of the Epley maneuver at 1‐week follow‐up in the management of p‐BPPV. The Epley maneuver should be considered in all patients with p‐BPPV.