bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulmonary Inflammatory Myofibroblastic Tumor Expressing a Novel Fusion, PPFIBP1–ALK: Reappraisal of Anti-ALK Immunohistochemistry as a Tool for Novel ALK Fusion Identification
Authors: Takeuchi Kengo , Soda Manabu , Togashi Yuki , Sugawara Emiko , Hatano Satoko , Asaka Reimi , Okumura Sakae , Nakagawa Ken , Mano Hiroyuki , Ishikawa Yuichi 
Published: March 2011

Abstract
Purpose: The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been used in patients with lung cancer or inflammatory myofibroblastic tumor (IMT), both types harboring ALK fusions. However, detection of some ALK fusions is problematic with conventional anti-ALK immunohistochemistry because of their low expression. By using sensitive immunohistochemistry, therefore, we reassessed “ALK-negative” IMT cases defined with conventional immunohistochemistry (approximately 50% of all examined cases).
Experimental Design: Two cases of ALK-negative IMT defined with conventional anti-ALK immunohistochemistry were further analyzed with sensitive immunohistochemistry [the intercalated antibody-enhanced polymer (iAEP) method].
Results: The two “ALK-negative” IMTs were found positive for anti-ALK immunohistochemistry with the iAEP method. 5′-rapid amplification of cDNA ends identified a novel partner of ALK fusion, protein-tyrosine phosphatase, receptor-type, F polypeptide-interacting protein-binding protein 1 (PPFIBP1) in one case. The presence of PPFIBP1–ALK fusion was confirmed with reverse transcriptase PCR, genomic PCR, and FISH. We confirmed the transforming activities of PPFIBP1–ALK with a focus formation assay and an in vivo tumorigenicity assay by using 3T3 fibroblasts infected with a recombinant retrovirus encoding PPFIBP1–ALK. Surprisingly, the fusion was also detected by FISH in the other case.
Conclusions: Sensitive immunohistochemical methods such as iAEP will broaden the potential value of immunohistochemistry. The current ALK positivity rate in IMT should be reassessed with a more highly sensitive method such as iAEP to accurately identify those patients who might benefit from ALK-inhibitor therapies. Novel ALK fusions are being identified in various tumors in addition to IMT, and thus a reassessment of other “ALK-negative” cancers may be required in the forthcoming era of ALK-inhibitor therapy. Clin Cancer Res; 17(10); 3341–8. ©2011 AACR.
Determinants of Mitotic Catastrophe on Abrogation of the G2 DNA Damage Checkpoint by UCN-01
Authors: On Kin Fan , Chen Yue , Tang Ma Hoi , Chow Jeremy P.H. , Poon Randy Y.C. 
Published: March 2011

AbstractGenotoxic stress such as ionizing radiation halts entry into mitosis by activation of the G2 DNA damage checkpoint. The CHK1 inhibitor 7-hydroxystaurosporine (UCN-01) can bypass the checkpoint and induce unscheduled mitosis in irradiated cells. Precisely, how cells behave following checkpoint abrogation remains to be defined. In this study, we tracked the fates of individual cells after checkpoint abrogation, focusing in particular on whether they undergo mitotic catastrophe. Surprisingly, while a subset of UCN-01–treated cells were immediately eliminated during the first mitosis after checkpoint abrogation, about half remained viable and progressed into G1. Both the delay of mitotic entry and the level of mitotic catastrophe were dependent on the dose of radiation. Although the level of mitotic catastrophe was specific for different cell lines, it could be promoted by extending the mitosis. In supporting this idea, weakening of the spindle-assembly checkpoint, by either depleting MAD2 or overexpressing the MAD2-binding protein p31comet, suppressed mitotic catastrophe. Conversely, delaying of mitotic exit by depleting either p31comet or CDC20 tipped the balance toward mitotic catastrophe. These results underscore the interplay between the level of DNA damage and the effectiveness of the spindle-assembly checkpoint in determining whether checkpoint-abrogated cells are eliminated during mitosis. Mol Cancer Ther; 10(5); 784–94. ©2011 AACR.
Circulating Levels of Vitamin D and Colon and Rectal Cancer: The Physicians' Health Study and a Meta-analysis of Prospective Studies
Authors: Lee Jung Eun , Li Haojie , Chan Andrew T. , Hollis Bruce W. , Lee I-Min , Stampfer Meir J. , Wu Kana , Giovannucci Edward , Ma Jing 
Published: March 2011

AbstractIt remains unknown whether increased risk with low levels of vitamin D is present for colon and/or rectal cancer. To investigate the association between circulating vitamin D levels and colon and rectal cancer, we examined the associations between plasma levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and colon and rectal cancer in the Physicians' Health Study and then conducted a meta-analysis of eight prospective studies of circulating levels of 25(OH)D and colon and rectal cancers, including the Physicians' Health Study. Study-specific ORs and 95% CIs were pooled by using a random-effects model. A total of 1,822 colon and 868 rectal cancers were included in the meta-analysis. We observed a significant inverse association for colorectal cancer (OR = 0.66; 95% CI, 0.54–0.81), comparing top versus bottom quantiles of circulating 25(OH)D levels. The inverse association was stronger for rectal cancer (OR = 0.50 for top versus bottom quantiles; 95% CI, 0.28–0.88) than colon cancer (OR = 0.77; 95% CI, 0.56–1.07; P value for difference between colon and rectal cancer = 0.20). These data suggest an inverse association between circulating 25(OH)D levels and colorectal cancer, with a stronger association for rectal cancer. Cancer Prev Res; 4(5); 735–43. ©2011 AACR.
Effects of Tomato- and Soy-Rich Diets on the IGF-I Hormonal Network: A Crossover Study of Postmenopausal Women at High Risk for Breast Cancer
Authors: McLaughlin John M. , Olivo-Marston Susan , Vitolins Mara Z. , Bittoni Marisa , Reeves Katherine W. , Degraffinreid Cecilia R. , Schwartz Steven J. , Clinton Steven K. , Paskett Electra D. 
Published: March 2011

Abstract
To determine whether dietary modifications with tomato products and/or a soy supplement affected circulating levels of insulin-like growth factor (IGF)-1 and other markers of cell signaling in postmenopausal women at risk for developing breast cancer. Eligible and consented postmenopausal women at high risk for developing breast cancer were enrolled in a 26-week, two-arm (tomato and soy, 10 weeks each) longitudinal dietary intervention study in which each woman served as her own control. Changes in biochemical endpoints including IGF-I, IGF-binding protein (IGFBP)-3, estradiol, sex hormone–binding globulin (SHBG), C-peptide, and insulin were measured for each intervention arm. Carotenoid and isoflavone levels were measured to assess adherence. Significant increases in carotenoid and isoflavone levels during the tomato and soy study arms, respectively, suggested that women were adherent to both arms of the intervention. The tomato-rich diet had little effect on cell-signaling biomarkers previously associated with breast cancer risk. However, results of the soy intervention showed that concentrations of IGF-I and IGFBP-3 increased by 21.6 and 154.7 μmol/L, respectively (P = 0.001 for both) and SHBG decreased by 5.4 μmol/L (P &lt; 0.001) after consumption of the soy protein supplement. Increased soy protein intake may lead to small, but significant, increases in IGF-I and IGFBP-3. Soy consumption also led to a significant decrease in SHBG, which has been hypothesized to promote, rather than prevent, cancer growth. Previous epidemiologic studies, however, have confirmed protective effect of soy on breast cancer. Additional investigation about the effect of soy on breast cancer risk and its mechanism of action is warranted. Cancer Prev Res; 4(5); 702–10. ©2011 AACR.
Enforced Expression of miR-101 Inhibits Prostate Cancer Cell Growth by Modulating the COX-2 Pathway In Vivo
Authors: Hao Yubin , Gu Xinbin , Zhao Yuan , Greene Stephen , Sha Wei , Smoot Duane T. , Califano Joseph , Wu T.-C. , Pang Xiaowu 
Published: March 2011

Abstract
It is commonly agreed that there is an association of chronic inflammation with tumorigenesis. COX-2, a key regulator of inflammation-producing prostaglandins, promotes cell proliferation and growth; thus, overexpression of COX-2 is often found in tumor tissues. Therefore, a better understanding of the regulatory mechanism(s) of COX-2 could lead to novel targeted cancer therapies. In this study, we investigated the mechanism of microRNA-101 (miR-101)-regulated COX-2 expression and the therapeutic potential of exogenous miR-101 for COX-2–associated cancer. A stably expressing exogenous miR-101 prostate cancer cell line (BPH1CmiR101) was generated by using lentiviral transduction as a tool for in vitro and in vivo studies. We found that miR-101 inhibited COX-2 posttranscriptional expression by directly binding to the 3′-untranslated region (3′-UTR) of COX-2 mRNA. The regulatory function of miR-101 was also confirmed by using antisense DNA. As a result, exogenous miR-101 is able to effectively suppress the growth of cultured prostate cancer cells and prostate tumor xenografts. The average tumor weight was significantly lower in the BPH1CmiR101 group (0.22 g) than the BPH1Cvec group (0.46 g). Expression levels of the cell growth regulators, such as cyclin proteins, PCNA (proliferating cell nuclear antigen), EGFR (epidermal growth factor receptor), were also studied. In conclusion, COX-2 is a direct target in miR-101 regulation of posttranscription. Exogenous miR-101 suppresses the proliferation and growth of prostate cancer cells in vitro and in vivo. These data suggest that exogenous miR-101 may provide a new cancer therapy by directly inhibiting COX-2 expression. Cancer Prev Res; 4(7); 1073–83. ©2011 AACR.
In Vivo Longitudinal Imaging of Experimental Human Papillomavirus Infection in Mice with a Multicolor Fluorescence Mini-Endoscopy System
Authors: Mitsunaga Makoto , Kosaka Nobuyuki , Kines Rhonda C. , Roberts Jeffrey N. , Lowy Douglas R. , Schiller John T. , Ishihara Yasushige , Hasegawa Akira , Choyke Peter L. , Kobayashi Hisataka 
Published: March 2011

Abstract
Human papillomavirus (HPV) infection is the most common sexually transmitted infection. Vaccines for HPV infection can reduce the risk of developing cervical cancer. To further improve such vaccines and to explore other methods of preventing or treating viral infection, longitudinal studies in experimental animals are desirable. Here, we describe a newly developed multicolor endoscopic fluorescence imaging system to visualize early HPV infection with fluorescent protein–encoded pseudoviruses (PsV) in the female genital tract of living mice. With this imaging method, the course of HPV PsV infection and the effects of intervention to prevent infection can be monitored in a single mouse over time. Female immunocompetent or athymic mice were pretreated with a vaginal spermicide and then HPV PsV composed of an authentic viral capsid and encapsidating green or red fluorescent protein (GFP or RFP) reporter gene was intravaginally instilled. Expression of GFP or RFP was detected 1 day after PsV challenge, which peaked after 2 or 3 days and decreasing thereafter. No fluorescence was detected in vaccine-treated immunocompetent mice. By using serial infection of the same PsV type (HPV16) encoding either GFP or RFP, different infection patterns of repeated exposure can be monitored. This method offers the ability to monitor experimental virus infections before and after intervention, thereby accelerating the development of appropriate prevention and therapy. Cancer Prev Res; 4(5); 767–73. ©2011 AACR.
Socioeconomic Status, Medicaid Coverage, Clinical Comorbidity, and Rehospitalization or Death After an Incident Heart Failure Hospitalization
Authors: Foraker Randi E. , Rose Kathryn M. , Suchindran Chirayath M. , Chang Patricia P. , McNeill Ann M. , Rosamond Wayne D. 
Published: March 2011

Background—
Among patients with heart failure (HF), early readmission or death and repeat hospitalizations may be indicators of poor disease management or more severe disease.

Methods and Results—
We assessed the association of neighborhood median household income (nINC) and Medicaid status with rehospitalization or death in the Atherosclerosis Risk in Communities cohort study (1987 to 2004) after an incident HF hospitalization in the context of individual socioeconomic status and evaluated the relationship for modification by demographic and comorbidity factors. We used generalized linear Poisson mixed models to estimate rehospitalization rate ratios and 95% CIs and Cox regression to estimate hazard ratios (HRs) and 95% CIs of rehospitalization or death. In models controlling for race and study community, sex, age at HF diagnosis, body mass index, hypertension, educational attainment, alcohol use, and smoking, patients with a high burden of comorbidity who were living in low-nINC areas at baseline had an elevated hazard of all-cause rehospitalization (HR, 1.40; 95% CI, 1.10 to 1.77), death (HR, 1.36; 95% CI, 1.02 to 1.80), and rehospitalization or death (HR, 1.36; 95% CI, 1.08 to 1.70) as well as increased rates of hospitalization compared to those with a high burden of comorbidity living in high-nINC areas. Medicaid recipients with a low level of comorbidity had an increased hazard of all-cause rehospitalization (HR, 1.19; 95% CI, 1.05 to 1.36) and rehospitalization or death (HR, 1.21; 95% CI, 1.07 to 1.37) and a higher rate of repeat hospitalizations compared to non-Medicaid recipients.

Conclusions—
Comorbidity burden appears to influence the association among nINC, Medicaid status, and rehospitalization and death in patients with HF.
A Strategy for Information Presentation in Spoken Dialog Systems
Authors: Demberg Vera , Winterboer Andi , Moore Johanna D. 
Published: March 2011

In spoken dialog systems, information must be presented sequentially, making it difficult to quickly browse through a large number of options. Recent studies have shown that user satisfaction is negatively correlated with dialog duration, suggesting that systems should be designed to maximize the efficiency of the interactions. Analysis of the logs of 2,000 dialogs between users and nine different dialog systems reveals that a large percentage of the time is spent on the information presentation phase, thus there is potentially a large pay-off to be gained from optimizing information presentation in spoken dialog systems. This article proposes a method that improves the efficiency of coping with large numbers of diverse options by selecting options and then structuring them based on a model of the user's preferences. This enables the dialog system to automatically determine trade-offs between alternative options that are relevant to the user and present these trade-offs explicitly. Multiple attractive options are thereby structured such that the user can gradually refine her request to find the optimal trade-off. To evaluate and challenge our approach, we conducted a series of experiments that test the effectiveness of the proposed strategy. Experimental results show that basing the content structuring and content selection process on a user model increases the efficiency and effectiveness of the user's interaction. Users complete their tasks more successfully and more quickly. Furthermore, user surveys revealed that participants found that the user-model based system presents complex trade-offs understandably and increases overall user satisfaction. The experiments also indicate that presenting users with a brief overview of options that do not fit their requirements significantly improves the user's overview of available options, also making them feel more confident in having been presented with all relevant options.
Beyond the Tipping Point: Understanding Perceptions of Abrupt Climate Change and Their Implications
Authors: Bellamy Rob , Hulme Mike 
Published: March 2011

Abstract
This article explores the influence of personal values and ontological beliefs on people’s perceptions of possible abrupt changes in the Earth’s climate system and on their climate change mitigation preferences. The authors focus on four key areas of risk perception: concern about abrupt climate change as distinct to climate change in general, the likelihood of abrupt climate changes, fears of abrupt climate changes, and preferences in how to mitigate abrupt climate changes. Using cultural theory as an interpretative framework, a multimethodological approach was adopted in exploring these areas: 287 respondents at the University of East Anglia (UK) completed a three-part quantitative questionnaire, with 15 returning to participate in qualitative focus groups to discuss the issues raised in more depth. Supporting the predictions of cultural theory, egalitarians’ values and beliefs were consistently associated with heightened perceptions of the risks posed by abrupt climate change. Yet many believed abrupt climate change to be capricious, irrespective of their psychometrically attributed worldviews or “ways of life.” Mitigation preferences—across all ways of life—were consistent with the “hegemonic myth” dominating climate policy, with many advocating conventional regulatory or market-based approaches. Moreover, a strong fatalistic narrative emerged from within abrupt climate change discourses, with frequent referrals to helplessness, societal collapse, and catastrophe.
The Impact of Cloud Cover on Major League Baseball
Authors: Kent Wes P. , Sheridan Scott C. 
Published: March 2011

Abstract
Although it is often suggested that direct sunlight may affect a player’s vision, no published studies have analyzed this interaction. In this research, a variety of statistical tests were utilized to study how baseball variables respond to different cloud cover conditions. Data from more than 35 000 Major League Baseball games, spanning the seasons from 1987 through 2002, were studied. Eleven baseball variables covering batting, pitching, and fielding performance were included. Overall responses were analyzed, as well as individual responses at 21 different stadiums. Home and away team performances were evaluated separately. This study then synthesized the synergistic differences in offensive production, pitching performance, and fielding performance into changes in the “home field advantage.”
Offensive production generally declines during clearer-sky daytime games compared to cloudy-sky daytime games, while pitching performance increases as conditions become clearer. Strikeouts show the strongest response in the study, increasing from 5.95 per game during cloudy-sky conditions to 6.40 per game during clear-sky conditions. The number of errors per game increases during clear-sky daytime games compared to cloudy-sky daytime games, while fly outs increase and ground outs decrease between daytime and nighttime games, regardless of the amount of cloud cover. Results at individual stadiums vary, with some stadiums displaying a very strong association between baseball performance and changes in cloud cover, while others display a weak association. All of these impacts affect the home field advantage, with the home team winning 56% of the games played under clear skies compared to 52.3% of the games played under cloudy skies.
Syndrome complex of bone marrow failure and pulmonary fibrosis predicts germline defects in telomerase
Authors: Parry Erin M. , Alder Jonathan K. , Qi Xiaodong , Chen Julian J.-L. , Armanios Mary 
Published: March 2011

Abstract
Mutations in the essential telomerase components hTERT and hTR cause dyskeratosis congenita, a bone marrow failure syndrome characterized by mucocutaneous features. Some (∼ 3%) sporadic aplastic anemia (AA) and idiopathic pulmonary fibrosis cases also carry mutations in hTERT and hTR. Even though it can affect clinical outcome, because the mutation frequency is rare, genetic testing is not standard. We examined whether the cooccurrence of bone marrow failure and pulmonary fibrosis in the same individual or family enriches for the presence of a telomerase mutation. Ten consecutive individuals with a total of 36 family members who fulfilled these criteria carried a germline mutant telomerase gene (100%). The mean age of onset for individuals with AA was significantly younger than that for those with pulmonary fibrosis (14 vs 51; P < .0001). Families displayed autosomal dominant inheritance and there was an evolving pattern of genetic anticipation, with the older generation primarily affected by pulmonary fibrosis and successive generations by bone marrow failure. The cooccurrence of AA and pulmonary fibrosis in a single patient or family is highly predictive for the presence of a germline telomerase defect. This diagnosis affects the choice of bone marrow transplantation preparative regimen and can prevent morbidity.
Impact of inhaled corticosteroid use on outcome in COPD patients admitted with pneumonia
Authors: Singanayagam A. , Chalmers J.D. , Akram A.R. , Hill A.T. 
Published: March 2011

The aim of this study was to investigate whether inhaled corticosteroid (ICS) use affects outcome in patients with chronic obstructive pulmonary disease (COPD) admitted with community-acquired pneumonia (CAP).This was a prospective, observational study of patients with spirometry-confirmed COPD presenting with a primary diagnosis of CAP in Lothian, UK. Outcome measures were compared between ICS users and non-ICS users.Of 490 patients included in the study, 76.7% were classified as ICS users. ICS users had higher Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage compared with non-ICS users (mean±sd3.2±0.8versus2.6±0.9; p<0.0001). There were no significant differences in pneumonia severity (mean±sdPneumonia Severity Index (PSI) 4.2±0.8versus4.3±0.8 (p = 0.3); mean±sdCURB-65 score 2.1±1.3versus2.3±1.3 (p = 0.07)) or markers of systemic inflammation (median C-reactive protein 148 (interquartile range 58–268) mg·L−1versus183 (IQR 85–302) mg·L−1; p = 0.08) between ICS users and non-ICS users. On multivariable analysis, after adjustment for COPD severity and PSI, ICS use was not independently associated with 30-day mortality (OR 1.71, 95% CI 0.75–3.90; p = 0.2), 6-month mortality (OR 1.62, 95% CI 0.82–3.16; p = 0.2), requirement for mechanical ventilation and/or inotropic support (OR 0.73, 95% CI 0.33–1.62; p = 0.4) or development of complicated pneumonia (OR 0.71, 95% CI 0.25–1.99; p = 0.5).Prior ICS use had no impact on outcome in patients with COPD admitted with CAP.