bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergy Between VEGF/VEGFR Inhibitors and Chemotherapy Agents in the Phase I Clinic
Authors: Tang Chad , Hess Kenneth , Jardim Denis Leonardo F. , Gagliato Debora De Melo , Tsimberidou Apostolia M. , Falchook Gerald , Fu Siqing , Janku Filip , Naing Aung , Piha-Paul Sarina , Subbiah Vivek , Wheler Jennifer , Zinner Ralph G. , Kurzrock Razelle , Ellis Lee M. , Meric-Berstam Funda , Hong David S. 
Published: October 2014

Abstract
Purpose: We hypothesized that chemotherapy synergizes with VEGF/VEGFR (VEGF/R) inhibitors in patients with advanced solid malignancies.
Experimental Design: Patients treated on phase I protocols between December 2004 and July 2013 (n = 1,498) were included in this analysis. The primary outcome was clinical benefit, defined as stable disease ≥6 months, complete response, or partial response. Two odds ratios (OR) for achieving clinical benefit were calculated: one for patients treated with VEGF/R inhibitors (OR with VEGF/R) and another for patients treated without (OR without VEGF/R). To compare these two ORs, an interaction term was included in the multivariate model: (chemotherapy/factor of interest)×(VEGF/R). We took significant interaction terms (Pinteraction &lt; 0.05) to suggest effect modification (either synergy or antagonism) with VEGF/R inhibitors.
Results: All patients treated with VEGF/R inhibitors exhibited higher OR for clinical benefit than those who were not [OR = 1.9; 95% confidence interval (CI), 1.5–2.4; P &lt; 0.0001]. Use of chemotherapy agents concomitant with VEGF/R inhibitors was associated with significantly higher OR for clinical benefit compared with chemotherapy use without VEGF/R inhibitors [OR with VEGF/R = 1.6 (95% CI, 1.1–2.5) vs. OR without VEGF/R = 0.4 (95% CI, 0.3–0.6), Pinteraction = 0.02]. Specifically, the antimetabolite class was associated with the greatest increase in OR for clinical benefit [OR with VEGF/R = 2.7 (95% CI, 1.5–4.7) vs. OR without VEGF/R = 0.2 (95% CI 0.1–0.3), Pinteraction = 0.004].
Conclusions: VEGF/R inhibitor was found to synergize with chemotherapeutics. This effect was most pronounced with the antimetabolite class. Clin Cancer Res; 20(23); 5956–63. ©2014 AACR.
Alterations Associated with Androgen Receptor Gene Activation in Salivary Duct Carcinoma of Both Sexes: Potential Therapeutic Ramifications
Authors: Mitani Yoshitsugu , Rao Pulivarthi H. , Maity Sankar N. , Lee Yu-Chen , Ferrarotto Renata , Post Julian C. , Licitra Lisa , Lippman Scott M. , Kies Merrill S. , Weber Randal S. , Caulin Carlos , Lin Sue-Hwa , El-Naggar Adel K. 
Published: October 2014

Abstract
Purpose: To investigate the molecular events associated with the activation of androgen receptor (AR) as a potential therapeutic target in patients with salivary duct carcinoma (SDC).
Experimental Design: Comprehensive molecular and expression analysis of the AR gene in 35 tumor specimens (20 males and 15 females) and cell lines derived from SDC using Western blotting and RT-PCR, FISH analysis, and DNA sequencing was conducted. In vitro and in vivo animal studies were also performed.
Results: AR expression was detected in 70% of the tumors and was mainly nuclear and homogenous in both male and female SDCs, although variable cytoplasmic and/or nuclear localization was also found. We report the identification of ligand-independent AR splice variants, mutations, and extra AR gene copy in primary untreated SDC tumors. In contrast to prostate cancer, no AR gene amplification was observed. In vitro knockdown of AR in a female derived SDC cell line revealed marked growth inhibition in culture and in vivo androgen-independent tumor growth.
Conclusions: Our study provides new detailed information on the molecular and structural alterations associated with AR gene activation in SDC and sheds more light on the putative functional role of AR in SDC cells. On the basis of these data, we propose that patients with SDC (male and female) can be stratified for hormone-based therapy in future clinical trials. Clin Cancer Res; 20(24); 6570–81. ©2014 AACR.
Changing the Paradigms of Treatment in Peripheral T-cell Lymphoma: From Biology to Clinical Practice
Authors: O'Connor Owen A. , Bhagat Govind , Ganapathi Karthik , Pedersen Martin Bjerregaard , D'Amore Francesco , Radeski Dejan , Bates Susan E. 
Published: October 2014

AbstractDespite enormous advances in our understanding of aggressive lymphomas, it is clear that progress in the peripheral T-cell lymphomas (PTCL) has lagged well behind other B-cell malignancies. Although there are many reasons for this, the one commonly cited notes that the paradigms for diffuse large B-cell lymphoma (DLBCL) were merely applied to all patients with PTCL, the classic “one-size-fits-all” approach. Despite these challenges, progress is being made. Recently, the FDA has approved four drugs for patients with relapsed/refractory PTCL over the past 5 years, and if one counts the recent Japanese approval of the anti-CCR4 monoclonal antibody for patients with adult T-cell leukemia/lymphoma, five drugs have been approved worldwide. These efforts have led to the initiation of no fewer than four randomized clinical studies exploring the integration of these new agents into standard CHOP (cyclophosphamide–Adriamycin–vincristine–prednisone)–based chemotherapy regimens for patients with newly diagnosed PTCL. In addition, a new wave of studies are exploring the merits of novel drug combinations in the disease, an effort to build on the obvious single-agent successes. What has emerged most recently is the recognition that the PTCL may be a disease-characterized by epigenetic dysregulation, which may help explain its sensitivity to histone deacetylase (HDAC) inhibitors, and open the door for even more creative combination approaches. Nonetheless, advances made over a relatively short period of time are changing how we now view these diseases and, hopefully, have poised us to finally improve its prognosis.See all articles in this CCR Focus section, “Paradigm Shifts in Lymphoma.”Clin Cancer Res; 20(20); 5240–54. ©2014 AACR.
DNA Methylation Levels at Chromosome 8q24 in Peripheral Blood Are Associated with 8q24 Cancer Susceptibility Loci
Authors: Barry Kathryn Hughes , Moore Lee E. , Sampson Joshua , Yan Liying , Meyer Ann , Oler Andrew J. , Chung Charles C. , Wang Zhaoming , Yeager Meredith , Amundadottir Laufey , Berndt Sonja I. 
Published: October 2014

AbstractChromosome 8q24 has emerged as an important region for genetic susceptibility to various cancers, but little is known about the contribution of DNA methylation at 8q24. To evaluate variability in DNA methylation levels at 8q24 and the relationship with cancer susceptibility single nucleotide polymorphisms (SNPs) in this region, we quantified DNA methylation levels in peripheral blood at 145 CpG sites nearby 8q24 cancer susceptibility SNPs or MYC using pyrosequencing among 80 Caucasian men in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. For the 60 CpG sites meeting quality control, which also demonstrated temporal stability over a 5-year period, we calculated pairwise Spearman correlations for DNA methylation levels at each CpG site with 42 8q24 cancer susceptibility SNPs. To account for multiple testing, we adjusted P values into q values reflecting the false discovery rate (FDR). In contrast to the MYC CpG sites, most sites nearby the SNPs demonstrated good reproducibility, high methylation levels, and moderate-high between-individual variation. We observed 10 statistically significant (FDR &lt; 0.05) CpG site–SNP correlations. These included correlations between an intergenic CpG site at Chr8:128393157 and the prostate cancer SNP rs16902094 (ρ = −0.54; P = 9.7 × 10−7; q = 0.002), a PRNCR1 CpG site at Chr8:128167809 and the prostate cancer SNP rs1456315 (ρ = 0.52; P = 1.4 × 10−6; q = 0.002), and two POU5F1B CpG sites and several prostate/colorectal cancer SNPs (for Chr8:128498051 and rs6983267, ρ = 0.46; P = 2.0 × 10−5; q = 0.01). This is the first report of correlations between blood DNA methylation levels and cancer susceptibility SNPs at 8q24, suggesting that DNA methylation at this important susceptibility locus may contribute to cancer risk. Cancer Prev Res; 7(12); 1282–92. ©2014 AACR.
Dietary Tomato and Lycopene Impact Androgen Signaling- and Carcinogenesis-Related Gene Expression during Early TRAMP Prostate Carcinogenesis
Authors: Wan Lei , Tan Hsueh-Li , Thomas-Ahner Jennifer M. , Pearl Dennis K. , Erdman John W. , Moran Nancy E. , Clinton Steven K. 
Published: October 2014

Abstract
Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild-type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4 to 10 weeks of age. Eight-week-old mice underwent sham surgery, castration, or castration followed by testosterone repletion (2.5 mg/kg/d initiated 1 week after castration). Ten-week-old intact TRAMP mice exhibit early multifocal prostatic intraepithelial neoplasia. Of the 200 prostate cancer–related genes measured by quantitative NanoString, 189 are detectable, 164 significantly differ by genotype, 179 by testosterone status, and 30 by diet type (P &lt; 0.05). In TRAMP, expression of Birc5, Mki67, Aurkb, Ccnb2, Foxm1, and Ccne2 is greater compared with WT and is decreased by castration. In parallel, castration reduces Ki67-positive staining (P &lt; 0.0001) compared with intact and testosterone-repleted TRAMP mice. Expression of genes involved in androgen metabolism/signaling pathways is reduced by lycopene feeding (Srd5a1) and by tomato feeding (Srd5a2, Pxn, and Srebf1). In addition, tomato feeding significantly reduced expression of genes associated with stem cell features, Aldh1a and Ly6a, whereas lycopene feeding significantly reduced expression of neuroendocrine differentiation–related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk. Cancer Prev Res; 7(12); 1228–39. ©2014 AACR.
Validity of Acute Stroke Lesion Volume Estimation by Diffusion-Weighted Imaging–Alberta Stroke Program Early Computed Tomographic Score Depends on Lesion Location in 496 Patients With Middle Cerebral Artery Stroke
Authors: Schröder Julian , Cheng Bastian , Ebinger Martin , Köhrmann Martin , Wu Ona , Kang Dong-Wha , Liebeskind David S. , Tourdias Thomas , Singer Oliver C. , Christensen Soren , Campbell Bruce , Luby Marie , Warach Steven , Fiehler Jens , Fiebach Jochen B. , Gerloff Christian , Thomalla Götz , Albers Gregory , Davis Stephen , Donnan Geoffrey , Fisher Marc , Furlan Anthony , Grotta James , Hacke Werner , Kidwell Chelsea , Koroshetz Walter , Lees Kennedy R. , Lev Michael , Sorensen A. Gregory , Thijs Vincent , Wardlaw Joanna , Wintermark Max , Hao Qing , Kim Jong S. , Breuer Lorenz , Treszl Andras , Forkert Nils D. , Galinovic Ivana , Rosenkranz Michael , Engelhorn Tobias , Endres Matthias , Dousset Vincent 
Published: October 2014

Background and Purpose—
Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) has been used to estimate diffusion-weighted imaging (DWI) lesion volume in acute stroke. We aimed to assess correlations of DWI-ASPECTS with lesion volume in different middle cerebral artery (MCA) subregions and reproduce existing ASPECTS thresholds of a malignant profile defined by lesion volume ≥100 mL.

Methods—
We analyzed data of patients with MCA stroke from a prospective observational study of DWI and fluid-attenuated inversion recovery in acute stroke. DWI-ASPECTS and lesion volume were calculated. The population was divided into subgroups based on lesion localization (superficial MCA territory, deep MCA territory, or both). Correlation of ASPECTS and infarct volume was calculated, and receiver-operating characteristics curve analysis was performed to identify the optimal ASPECTS threshold for ≥100-mL lesion volume.

Results—

A total of 496 patients were included. There was a significant negative correlation between ASPECTS and DWI lesion volume (
r
=–0.78;
P
<0.0001). With regards to lesion localization, correlation was weaker in deep MCA region (
r
=–0.19;
P
=0.038) when compared with superficial (
r
=–0.72;
P
<0.001) or combined superficial and deep MCA lesions (
r
=–0.72;
P
<0.001). Receiver-operating characteristics analysis revealed ASPECTS≤6 as best cutoff to identify ≥100-mL DWI lesion volume; however, positive predictive value was low (0.35).

Conclusions—
ASPECTS has limitations when lesion location is not considered. Identification of patients with malignant profile by DWI-ASPECTS may be unreliable. ASPECTS may be a useful tool for the evaluation of noncontrast computed tomography. However, if MRI is used, ASPECTS seems dispensable because lesion volume can easily be quantified on DWI maps.
Feedbacks of Sea Surface Temperature to Wintertime Storm Tracks in the North Atlantic
Authors: Gan Bolan , Wu Lixin 
Published: October 2014

Abstract
In this study, the lagged maximum covariance analysis is performed on winter storm-track anomalies, represented by the meridional heat flux by synoptic-scale (2–8 days) transient eddies and sea surface temperature (SST) anomalies in the North Atlantic, which are both derived from reanalysis datasets spanning the twentieth century. The analysis shows significant seasonal and interannual coupling between storm-track and SST variations. On seasonal time scales, it is found that SST anomalies in the preceding early winter (November–December), which are expected to change the lower-tropospheric baroclinicity, can significantly influence storm tracks in early spring (March); that is, an intensification and slight northward shift of storm tracks in response to a midlatitude SST dipole, with a cold pole centered to the southeast of Newfoundland and a warm pole in the western subtropical Atlantic. This storm-track response pattern is similar to the storm-track forcing pattern in early spring, which resembles the dominant mode of storm tracks. At interannual time scales, it is found that the wintertime (January–March) storm-track and SST anomalies are mutually reinforced, manifesting as a zonal-dipole-like pattern in storm-track anomalies (with dominant negative anomalies in the downstream) coupled with a midlatitude SST monopole (with warm anomalies centered to the south and east of Newfoundland).
Satellite and Argo Observed Surface Salinity Variations in the Tropical Indian Ocean and Their Association with the Indian Ocean Dipole Mode
Authors: Du Yan , Zhang Yuhong 
Published: October 2014

Abstract
This study investigates sea surface salinity (SSS) variations in the tropical Indian Ocean (IO) using the Aquarius/Satelite de Aplicaciones Cientificas-D (SAC-D) and the Soil Moisture and Ocean Salinity (SMOS) satellite data and the Argo observations during July 2010–July 2014. Compared to the Argo observations, the satellite datasets generally provide SSS maps with higher space–time resolution, particularly in the regions where Argo floats are sparse. Both Aquarius and SMOS well captured the SSS variations associated with the Indian Ocean dipole (IOD) mode. Significant SSS changes occurred in the central equatorial IO, along the Java–Sumatra coast, and south of the equatorial IO, due to ocean circulation variations. During the negative IOD events in 2010, 2013, and 2014, westerly wind anomalies strengthened along the equator, weakening coastal upwelling off Java and Sumatra and decreasing SSS. South of the equatorial IO, an anomalous cyclonic gyre changed the tropical circulation, which favored the eastward high-salinity tongue along the equator and the westward low-saline tongue in the south. An upwelling Rossby wave favored the increase of SSS farther to the south. During the positive IOD events in 2011 and 2012, the above-mentioned processes reversed, although the decrease of SSS was weaker in magnitude.
Pyranometer Thermal Offset: Measurement and Analysis
Authors: Sanchez G. , Serrano A. , Cancillo M. L. , Garcia J. A. 
Published: October 2014

AbstractThe reliable estimation of the radiative forcing and trends in radiation requires very accurate measurements of global and diffuse solar irradiance at the earth’s surface. To improve measurement accuracy, error sources such as the pyranometer thermal offset should be thoroughly evaluated. This study focuses on the measurement and analysis of this effect in a widely used type of pyranometer. For this aim, a methodology based on capping the pyranometer has been used and different criteria for determining the thermal offset have been applied and compared. The thermal offset of unventilated pyranometers for global and diffuse irradiance has been measured under a wide range of cloud, ambient temperature, wind speed, and radiation conditions. Significant differences in absolute values and variability have been observed between daytime and nighttime, advising against correcting the thermal offset effect based only on nighttime values. Notable differences in the thermal offset between cloudy and cloud-free conditions have been also observed. The main results show that the ambient temperature, the radiation, and its direct/diffuse partitioning are the variables more related to the daytime thermal offset.
Multiscale Interactions in an Idealized Walker Cell: Simulations with Sparse Space–Time Superparameterization
Authors: Slawinska Joanna , Pauluis Olivier , Majda Andrew J. , Grabowski Wojciech W. 
Published: October 2014

Abstract
This paper discusses the sparse space–time superparameterization (SSTSP) algorithm and evaluates its ability to represent interactions between moist convection and the large-scale circulation in the context of a Walker cell flow over a planetary scale two-dimensional domain. The SSTSP represents convective motions in each column of the large-scale model by embedding a cloud-resolving model, and relies on a sparse sampling in both space and time to reduce computational cost of explicit simulation of convective processes. Simulations are performed varying the spatial compression and/or temporal acceleration, and results are compared to the cloud-resolving simulation reported previously. The algorithm is able to reproduce a broad range of circulation features for all temporal accelerations and spatial compressions, but significant biases are identified. Precipitation tends to be too intense and too localized over warm waters when compared to the cloud-resolving simulations. It is argued that this is because coherent propagation of organized convective systems from one large-scale model column to another is difficult when superparameterization is used, as noted in previous studies. The Walker cell in all simulations exhibits low-frequency variability on a time scale of about 20 days, characterized by four distinctive stages: suppressed, intensification, active, and weakening. The SSTSP algorithm captures spatial structure and temporal evolution of the variability. This reinforces the confidence that SSTSP preserves fundamental interactions between convection and the large-scale flow, and offers a computationally efficient alternative to traditional convective parameterizations.
Extreme Convection of the Near-Equatorial Americas, Africa, and Adjoining Oceans as seen by TRMM
Authors: Zuluaga Manuel D. , Houze Robert A. 
Published: October 2014

Abstract
This study documents the preferred location and diurnal cycle of extreme convective storms that occur in the tropical band containing the east Pacific Ocean, Central and South America, the Atlantic Ocean, and northern Africa. Data from the Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar show three types of convective-stratiform structures that constitute extreme convective events: deep convective cores (DCCs), wide convective cores (WCCs), and broad stratiform regions (BSRs). Interim ECMWF Re-Analysis (ERA-Interim) data show the associated synoptic environmental factors associated with the occurrence of extreme convective features. The DCC, WCC, and BSR echoes are associated with early, middle, and late stages of convective system development, respectively, and the statistics and timing of their occurrence are related to topography and life cycle behavior of the convection. Storms containing DCC occur primarily over the Sudanian savannas of Africa and near the mountains in northern South America, being diurnally controlled. Storms with WCC manifest over land, in the same regions as the DCC, but also over oceanic regions. They appear around the clock but with maximum frequency at night. They are favored in regions of midlevel synoptic-scale low pressure systems, which over the sub-Sahara are the troughs of easterly waves. Storms containing BSR maximize over oceanic regions west of Africa and South America, where they exhibit a weak diurnal cycle with a slight midmorning maximum. Off the west coast of South America, the storms with WCC and BSR have longer lifetimes enhanced by orographic lifting over the Andes. The storms with BSR in the east Pacific Ocean often develop into tropical cyclones.
A Comparative Study of Cricotracheal Resection and Staged Laryngotracheoplasty for Adult Subglottic Stenosis
Authors: Ching Harry H. , Mendelsohn Abie H. , Liu Isabelle Y. , Long Jennifer , Chhetri Dinesh K. , Berke Gerald S. 
Published: October 2014

Objective: Cricotracheal resection (CTR) and laryngotracheoplasty (LTP) are open surgical treatments for severe subglottic stenosis. This study aims to compare the applications and outcomes of these techniques. Method: Patients with subglottic stenosis at a tertiary academic institution from 2000 to 2012 were identified by diagnosis codes. Patients who underwent LTP or CTR were included. Records were reviewed for treatment data and outcomes. Patients with a history of head and neck malignancy or stenosis without cricoid involvement were excluded. Result: Sixty-one and 20 patients underwent LTP and CTR, respectively. When comparing patients receiving LTP and CTR, there was a significant difference in stenosis etiology ( P = .014). The groups were similar in Cotton-Myer grade ( P = .102). At last follow-up, 80.3% of LTP patients and 90.0% of CTR patients were decannulated. On multivariate analysis, there was a significant association between stenosis grade and decannulation in the LTP group ( P = .01). Decannulation was not associated with stenosis grade in the CTR group. In both groups, there was no significant association between decannulation and sex, stenosis etiology, or stenosis length. Conclusion: Cricotracheal resection and LTP have both shown excellent long-term decannulation rates. Etiology and stenosis grade are likely to be determining factors when recommending specific surgical interventions for subglottic stenosis.