bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract KN01-03: Keynote Address: Personalized targeted chemoprevention: Opportunities and challenges
Authors: Hong Waun Ki 
Published: May 2012

Abstract
Epithelial cancers are a major killer worldwide. The epithelial cancers develop by a multistep process through premalignant lesions to invasive cancer at multiple sites through a process of field carcinogenesis. Unfortunately, many chemoprevention trials conducted in various disease sites have failed to demonstrate any efficacy to prevent cancer other than hormone targeted prevention trials in breast and prostate cancers.
Our group has demonstrated proof of principle of the efficacy of targeted chemopreventive agents in combination therapy reversing phenotypic changes of laryngeal premalignant lesions but observed persistent genotypic changes; thus, the obvious goal is the elimination of genetic scars to prevent cancer effectively.
The human genome project was completed in 2001 and many new genes have been discovered which have been implicated in cancer in general. A major challenge is translating these gene discoveries to clinical benefit for both prevention and therapy. Now, the hallmarks of cancer have been elucidated and we have a better understanding of the interactions between cancer cells and microenvironment and are able to integrate signaling pathways leading to cancer progression.
The other important challenge is identifying the highest risk cohort for primary and second primary cancers through clinical, epidemiologic, and genetic variables to create a risk model such that, ultimately, we can target this group with personalized targeted chemoprevention therapy.
In order to achieve the goals above, we must understand fully the molecular and genetic fingerprints of premalignant lesions from different organ sites and the alteration of pathways which are the driving force of cancer progression. These pathways can be targeted and perturbed by agents matched to alter the molecular defects.
Personalized targeted chemoprevention has enormous potential to make an impact from a public health point of view. To do this, we must first develop and validate the efficacy of personalized targeted therapy agents in metastatic settings, then migrate, in reverse fashion, into the early disease arena, such as the adjuvant setting, and then tackle premalignant lesions to eradicate aberrant clones and/or undermine clonal activity so that cancer can be either prevented or delayed.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):KN01-03.
Abstract PR-01: Vitamin D receptor expression is inversely associated with prostate cancer progression
Authors: Hendrickson Whitney , Kasperzyk Julie , Flavin Richard , Fiorentino Michelangelo , Lis Rosina , Fiore Christopher , Penney Kathryn , Ma Jing , Stampfer Meir , Loda Massimo , Mucci Lorelei , Giovannucci Edward 
Published: May 2012

Abstract
Background: Vitamin D is inversely associated with risk of several malignancies. Circulating vitamin D interacts with the vitamin D receptor (VDR) at the cellular level to inhibit proliferation, increase apoptosis and decrease angiogenesis. Thus, although vitamin D levels appear to be unrelated to total prostate cancer incidence, VDR levels in tumor tissue may influence prostate cancer prognosis.
Methods: We examined the immunohistochemical expression of VDR on archival tumor tissue from 841 prostate cancer cases diagnosed between 1982 and 2004 within two ongoing, prospective cohorts: the Physicians' Health Study and Health Professionals Follow-up Study. VDR expression was measured quantitatively using the CRi Vectra™ system. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of VDR expression with lethal prostate cancer (N=73) through 2008. On a subset of cases, we also examined correlation of tumor VDR expression with circulating 25(OH)D3 and 1alpha,25(OH)2D3 measured at baseline (N=84) in 1982 and two SNPs in VDR: Fok1 and bsm1 (N=140).
Results: Men with high tumor VDR expression had significantly lower Gleason score, lower prostate specific antigen (PSA) levels at diagnosis, and were less likely to have advanced tumor stage (p=0.008, p=0.012, p=0.001, respectively). Compared to the lowest quartile, men in the highest quartile of VDR expression were at significantly lower risk of developing lethal prostate cancer (age-adjusted HRs across quartiles Q2=0.95, 95% CI: 0.51–1.79; Q3=0.93, 95% CI: 0.49–1.76; Q4 = 0.23, 95% CI:0.09–0.55). This association was attenuated (HRQ4vsQ1 = 0.42, 95% CI: 0.16–1.09) after further adjustment for pathological tumor stage, Gleason grade, and PSA level at diagnosis. Tumors expressing high levels of VDR had modest downregulation of cell proliferation as measured by Ki67 (r=-0.11). Moreover, expression of estrogen receptor alpha (r=0.40, p&lt;0.001) and androgen receptor (r=0.41, p&lt;0.001) were positively correlated with VDR expression. Neither prediagnostic plasma vitamin D levels nor gene variants in VDR were associated with VDR protein expression in tumors.
Conclusion: In this large prospective study, men with tumors that demonstrated upregulation of VDR had significantly improved clinical features and reduced risk of lethal prostate cancer. In line with experimental studies, the positive correlation between VDR expression, and androgen receptor and estrogen receptor provides evidence that that VDR acts in an androgen- and/or estrogen-dependent manner. These data highlight the potential role of the vitamin D system in preventing prostate cancer progression.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):PR-01.
Abstract PR-03: Genetic variations in microRNA biogenesis genes as predictors for risk of second primary tumor (SPT) and/or recurrence in patients with early-stage head and neck cancer
Authors: Zhang Xiaofan , Yang Hushan , Lee J. Jack , Kim Edward , Lippman Scott M. , Khuri Fadlo R. , Spitz Margaret R. , Lotan Reuben , Hong Waun K. , Wu Xifeng 
Published: May 2012

Abstract
Second primary tumors (SPTs) and local-regional recurrence negatively impact the prognosis of patients with curatively treated early-stage head and neck cancer. Genetic variations in microRNA (miRNA) biogenesis genes have been found to be associated with the risk of multiple solid tumors. Thus, we hypothesized that these variations were also associated with the risk of SPT/recurrence in patients with early-stage head and neck cancer. We performed a nested case-control study including 150 early-stage head and neck cancer patients with SPT/recurrence and 300 patients without SPT/recurrence. We genotyped 71 tagging and potentially functional single nucleotide polymorphisms (SNPs) from eight miRNA biogenesis pathway genes (RNASEN, DGCR8, DICER1, EIF2C1, DDX20, GEMIN4, RAN, XPO5). Seven SNPs in RNASEN, one in XPO5, and one in RAN were significantly associated with the risk of SPT/recurrence. The most significant SNP was rs7735863, an intronic SNP in RANSEN. The variant-containing genotypes of this SNP were associated with a 1.72-fold increased risk (95% confidence interval [CI], 1.16–2.57; P=0.0076). A combined analysis showed that compared with the patients without any unfavorable genotypes, the SPT/recurrence risk was increased 1.50- (95% CI, 1.02–2.22) and 2.69-fold (95% CI, 1.59–4.53) for those with one and two unfavorable genotypes, respectively (P for trend&lt;0.001). Survival tree analysis further identified potential higher-order interactions and categorized the study subjects into different risk groups. Compared to the low-risk group with an event-free median survival time (MST) over 96 months, patients in the high-risk group had a 5.02-fold increased risk (95% CI, 2.70–9.31; P=3.20×10−7) and an event-free MST of 31.4 months (log rank P=1.25 − 10−7). Our results suggest that genetic polymorphisms within the miRNA biogenesis pathway may be used individually and jointly to predict the risk of SPT/recurrence of early-stage head and neck cancer patients.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):PR-03.
Dabigatran etexilate and concomitant use of non-steroidal anti-inflammatory drugs or acetylsalicylic acid in patients undergoing total hip and total knee arthroplasty: No increased risk of bleeding
Authors: Kurth Andreas , Clemens Andreas , Noack Herbert , Eriksson Bengt , Caprini Joseph , Friedman Richard 
Published: May 2012

SummaryPatients undergoing total hip or knee arthroplasty should receive anticoagulant therapy because of the high risk of venous thromboembolism. However, many are already taking non-steroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid (ASA) that can have antihaemostatic effects. We assessed the bleeding risk in patients treated with thromboprophylactic dabigatran etexilate, with and without concomitant NSAID or ASA. A post-hoc analysis was undertaken of the pooled data from trials comparing dabigatran etexilate (220 mg and 150 mg once daily) and enoxaparin. Major bleeding event (MBE) rates were determined and odds ratios (ORs) generated for patients who received study treatment plus NSAID (half-life ≤12 hours) or ASA (≤160 mg/day) versus study treatment alone. Relative risks were calculated for comparisons between treatments. Overall, 4,405/8,135 patients (54.1%) received concomitant NSAID and 386/8,135 (4.7%) received ASA.ORs for the comparison with/without concomitant NSAID were 1.05 (95% confidence interval [CI] 0.55–2.01) for 220 mg dabigatran etexilate; 1.19 (0.55–2.55) for 150 mg; and 1.32 (0.67–2.57) for enoxaparin. ORs for the comparison with/without ASA were 1.14 (0.26–5.03); 1.64 (0.36–7.49); and 2.57 (0.83–7.94), respectively. For both NSAIDs and ASA there was no significant difference in bleeding between patients with and without concomitant therapy in any treatment arm. Patients concomitantly taking NSAIDs or ASA have a similar risk of MBE to those taking dabigatran etexilate alone. No significant differences in MBE were detected between dabigatran etexilate and enoxaparin within comedication subgroups, suggesting that no increased major bleeding risk exists when dabigatran etexilate is administered with NSAID or ASA.Investigation performed at multiple centres participating in the RE-MODEL™, RE-NOVATE®, and RE-MOBILIZE® trials.
Propranolol as antiangiogenic candidate for the therapy of hereditary haemorrhagic telangiectasia
Authors: Albiñana Virginia , Recio-Poveda Lucía , Zarrabeitia Roberto , Bernabéu Carmelo , Botella Luisa 
Published: May 2012

SummaryThe β-blocker propranolol, originally designed for cardiological indications (angina, cardiac arrhythmias and high blood pressure), is nowadays, considered the most efficient drug for the treatment in infantile haemangiomas (IH), a vascular tumour that affects 5–10% of all infants. However, its potential therapeutic benefits in other vascular anomalies remain to be explored. In the present work we have assessed the impact of propranolol in endothelial cell cultures to test if this drug could be used in the vascular disease hereditary haemorrhagic telangiectasia (HHT). This rare disease is the result of abnormal angiogenesis with epistaxis, mucocutaneous and gastrointestinal telangiectases, as well as arteriovenous malformations in several organs, as clinical manifestations. Mutations in Endoglin (ENG) and ACVLR1 (ALK1) genes, lead to HHT1 and HHT2, respectively. Endoglin and ALK1 are involved in the TGF-β1 signalling pathway and play a critical role for the proper development of the blood vessels. As HHT is due to a deregulation of key angiogenic factors, inhibitors of angiogenesis have been used to normalise the nasal vasculature eliminating epistaxis derived from telangiectases. Thus, the antiangiogenic properties of propranolol were tested in endothelial cells. The drug was able to decrease cellular migration and tube formation, concomitantly with reduced RNA and protein levels of ENG and ALK1. Moreover, the drug showed apoptotic effects which could explain cell death in IH. Interestingly, propranolol showed some profibrinolytic activity, decreasing PAI-1 levels. These results suggest that local administration of propranolol in the nose mucosa to control epistaxis might be a potential therapeutic approach in HHT.
Influence of Mitral Regurgitation Repair on Survival in the Surgical Treatment for Ischemic Heart Failure Trial
Authors: Deja Marek A. , Grayburn Paul A. , Sun Benjamin , Rao Vivek , She Lilin , Krejca Michał , Jain Anil R. , Leng Chua Yeow , Daly Richard , Senni Michele , Mokrzycki Krzysztof , Menicanti Lorenzo , Oh Jae K. , Michler Robert , Wróbel Krzysztof , Lamy Andre , Velazquez Eric J. , Lee Kerry L. , Jones Robert H. 
Published: May 2012

Background—
Whether mitral valve repair during coronary artery bypass grafting (CABG) improves survival in patients with ischemic mitral regurgitation (MR) remains unknown.

Methods and Results—

Patients with ejection fraction ≤35% and coronary artery disease amenable to CABG were randomized at 99 sites worldwide to medical therapy with or without CABG. The decision to treat the mitral valve during CABG was left to the surgeon. The primary end point was mortality. Of 1212 randomized patients, 435 (36%) had none/trace MR, 554 (46%) had mild MR, 181 (15%) had moderate MR, and 39 (3%) had severe MR. In the medical arm, 70 deaths (32%) occurred in patients with none/trace MR, 114 (44%) in those with mild MR, and 58 (50%) in those with moderate to severe MR. In patients with moderate to severe MR, there were 29 deaths (53%) among 55 patients randomized to CABG who did not receive mitral surgery (hazard ratio versus medical therapy, 1.20; 95% confidence interval, 0.77–1.87) and 21 deaths (43%) among 49 patients who received mitral surgery (hazard ratio versus medical therapy, 0.62; 95% confidence interval, 0.35–1.08). After adjustment for baseline prognostic variables, the hazard ratio for CABG with mitral surgery versus CABG alone was 0.41 (95% confidence interval, 0.22–0.77;
P
=0.006).

Conclusion—
Although these observational data suggest that adding mitral valve repair to CABG in patients with left ventricular dysfunction and moderate to severe MR may improve survival compared with CABG alone or medical therapy alone, a prospective randomized trial is necessary to confirm the validity of these observations.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00023595.
Noninvasive Assessment of Myocardial Inflammation by Cardiovascular Magnetic Resonance in a Rat Model of Experimental Autoimmune Myocarditis
Authors: Moon Hyeyoung , Park Hyo Eun , Kang Jongeun , Lee Hyunseung , Cheong Chaejoon , Lim Yong Taik , Ihm Sang-Hyun , Seung Ki-Bae , Jaffer Farouc A. , Narula Jagat , Chang Kiyuk , Hong Kwan Soo 
Published: May 2012

Background—
Limited availability of noninvasive and biologically precise diagnostic tools poses a challenge for the evaluation and management of patients with myocarditis.

Methods and Results—

The feasibility of cardiovascular magnetic resonance (CMR) imaging with magneto-fluorescent nanoparticles (MNPs) for detection of myocarditis and its effectiveness in discriminating inflammation grades were assessed in experimental autoimmune myocarditis (EAM) (n=65) and control (n=10) rats. After undergoing CMR, rats were administered with MNPs, followed by a second CMR 24 hours later. Head-to-head comparison of MNP-CMR with T
2
-weighted, early and late gadolinium enhancement CMR was performed in additional EAM (n=10) and control (n=5) rats. Contrast-to-noise ratios were measured and compared between groups. Flow cytometry and microscopy demonstrated that infiltrating inflammatory cells engulfed MNPs, resulting in altered myocardial T
2
* effect. Changes in contrast-to-noise ratio between pre- and post-MNP CMR were significantly greater in EAM rats (1.08±0.10 versus 0.48±0.20;
P
<0.001). In addition, contrast-to-noise ratio measurement in MNP-CMR clearly detected the extent of inflammation (
P
<0.001) except for mild inflammation. Compared with conventional CMR, MNP-CMR provided better image contrast (CNR change 8% versus 46%,
P
<0.001) and detectability of focal myocardial inflammation. Notably, MNP-CMR successfully tracked the evolution of myocardial inflammation in the same EAM rats.

Conclusions—
Magneto-fluorescent nanoparticle CMR permitted effective visualization of myocardial inflammatory cellular infiltrates and distinction of the extent of inflammation compared with conventional CMR in a preclinical model of EAM. Magneto-fluorescent nanoparticle CMR performs best in EAM rats with at least moderate inflammatory response.
Raindrop Size Distribution and Radar Parameters in Coastal Tropical Rain Systems of Northeastern Brazil
Authors: Tenório Ricardo Sarmento , Cristina da Silva Moraes Marcia , Sauvageot Henri 
Published: May 2012

AbstractA dataset on raindrop size distribution (DSD) gathered in a coastal site of the Alagoas state in northeastern Brazil is used to analyze some differences between continental and maritime rainfall parameters. The dataset is divided into two subsets. One is composed of rainfall systems coming from the continent and moving eastward (i.e., offshore), representing the continental subset. The other is composed of rainfall systems that developed over the sea and are moving westward (i.e., inshore), representing the maritime subset. The mean conditional rain rate (i.e., for rain rate R > 0) is found to be higher for maritime (4.6 mm h−1) than for continental (3.2 mm h−1) conditions. The coefficient of variation of the conditional rain rate is lower for the maritime (1.75) than for the continental (2.25) subset. The continental and maritime DSDs display significant differences. For drop diameter D smaller than about 2 mm, the number of drops is higher for maritime rain than for continental rain. This reverses for D > 2 mm, in such a way that radar reflectivity factor Z for the maritime case is lower than for the continental case at the same rain rate. These results show that, to estimate precipitation by radar in the coastal area of northeastern Brazil, coefficients of the Z–R relation need to be adapted to the direction of motion of the rain-bearing system, inshore or offshore.
A Comparative Analysis of Upper-Ocean Heat Content Variability from an Ensemble of Operational Ocean Reanalyses
Authors: Xue Yan , Balmaseda Magdalena A. , Boyer Tim , Ferry Nicolas , Good Simon , Ishikawa Ichiro , Kumar Arun , Rienecker Michele , Rosati Anthony J. , Yin Yonghong 
Published: May 2012

Abstract
Ocean heat content (HC) is one of the key indicators of climate variability and also provides ocean memory critical for seasonal and decadal predictions. The availability of multiple operational ocean analyses (ORAs) now routinely produced around the world is an opportunity for estimation of uncertainties in HC analysis and development of ensemble-based operational HC climate indices. In this context, the spread across the ORAs is used to quantify uncertainties in HC analysis and the ensemble mean of ORAs to identify, and to monitor, climate signals. Toward this goal, this study analyzed 10 ORAs, two objective analyses based on in situ data only, and eight model analyses based on ocean data assimilation systems. The mean, annual cycle, interannual variability, and long-term trend of HC in the upper 300 m (HC300) from 1980 to 2009 are compared.
The spread across HC300 analyses generally decreased with time and reached a minimum in the early 2000s when the Argo data became available. There was a good correspondence between the increase of data counts and reduction of the spread. The agreement of HC300 anomalies among different ORAs, measured by the signal-to-noise ratio (S/N), is generally high in the tropical Pacific, tropical Indian Ocean, North Pacific, and North Atlantic but low in the tropical Atlantic and extratropical southern oceans where observations are very sparse. A set of climate indices was derived as HC300 anomalies averaged over the areas where the covariability between SST and HC300 represents the major climate modes such as ENSO, Indian Ocean dipole, Atlantic Niño, Pacific decadal oscillation, and Atlantic multidecadal oscillation.
Mechanisms Contributing to the Warming Hole and the Consequent U.S. East–West Differential of Heat Extremes
Authors: Meehl Gerald A. , Arblaster Julie M. , Branstator Grant 
Published: May 2012

Abstract
A linear trend calculated for observed annual mean surface air temperatures over the United States for the second-half of the twentieth century shows a slight cooling over the southeastern part of the country, the so-called warming hole, while temperatures over the rest of the country rose significantly. This east–west gradient of average temperature change has contributed to the observed pattern of changes of record temperatures as given by the ratio of daily record high temperatures to record low temperatures with a comparable east–west gradient. Ensemble averages of twentieth-century climate simulations in the Community Climate System Model, version 3 (CCSM3), show a slight west–east warming gradient but no warming hole. A warming hole appears in only several ensemble members in the Coupled Model Intercomparison Project phase 3 (CMIP3) multimodel dataset and in one ensemble member of simulated twentieth-century climate in CCSM3. In this model the warming hole is produced mostly from internal decadal time-scale variability originating mainly from the equatorial central Pacific associated with the Interdecadal Pacific Oscillation (IPO). Analyses of a long control run of the coupled model, and specified convective heating anomaly experiments in the atmosphere-only version of the model, trace the forcing of the warming hole to positive convective heating anomalies in the central equatorial Pacific Ocean near the date line. Cold-air advection into the southeastern United States in winter, and low-level moisture convergence in that region in summer, contribute most to the warming hole in those seasons. Projections show a disappearance of the warming hole, but ongoing greater surface temperature increases in the western United States compared to the eastern United States.
Propagating Atmospheric Patterns Associated with Midwest Winter Precipitation
Authors: Strong Courtenay , Liptak Jessica 
Published: May 2012

Abstract
For winters over eastern North America, complex Hilbert empirical orthogonal function (HEOF) analysis was used to objectively identify propagating patterns in four atmospheric fields that have potential relevance to precipitation: jet stream–level wind speed, 850-hPa moisture transport (qv), temperature advection (TA), and vorticity advection (VA). A novel phase shift method was used to show the location where each propagating pattern was most correlated with Midwest precipitation, and each of the four phase-shifted HEOF patterns was compared to its respective high-precipitation composite view. The leading HEOFs of the three transport fields (qv, TA, and VA), which collectively represented the dynamics associated with a midlatitude cyclone, accounted for almost half of Midwest precipitation variability and were associated with lake effect snow when propagating downstream from the Midwest. Correlation and spectral analyses revealed how the propagating transport patterns were related to the Pacific–North American pattern and other teleconnections. The leading HEOF of jet stream–level wind speed, which represented the tendency for the jet stream to migrate equatorward over the study region during winter, accounted for only about 4% of Midwest daily precipitation variability. In contrast, the second HEOF of jet stream–level wind speed, which represented an eastward propagating trough dynamically consistent with a midlatitude cyclone, accounted for 16% of Midwest daily precipitation variability.