bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Proliferation in Determining Response to Neoadjuvant Chemotherapy in Breast Cancer: A Gene Expression–Based Meta-Analysis
Authors: Stover Daniel G. , Coloff Jonathan L. , Barry William T. , Brugge Joan S. , Winer Eric P. , Selfors Laura M. 
Published: June 2016

Abstract
Purpose: To provide further insight into the role of proliferation and other cellular processes in chemosensitivity and resistance, we evaluated the association of a diverse set of gene expression signatures with response to neoadjuvant chemotherapy (NAC) in breast cancer.
Experimental Design: Expression data from primary breast cancer biopsies for 1,419 patients in 17 studies prior to NAC were identified and aggregated using common normalization procedures. Clinicopathologic characteristics, including response to NAC, were collected. Scores for 125 previously published breast cancer–related gene expression signatures were calculated for each tumor.
Results: Within each receptor-based subgroup or PAM50 subtype, breast tumors with high proliferation signature scores were significantly more likely to achieve pathologic complete response to NAC. To distinguish “proliferation-associated” from “proliferation-independent” signatures, we used correlation and linear modeling approaches. Most signatures associated with response to NAC were proliferation associated: 90.5% (38/42) in ER+/HER2− and 63.3% (38/60) in triple-negative breast cancer (TNBC). Proliferation-independent signatures predictive of response to NAC in ER+/HER2− breast cancer were related to immune activity, while those in TNBC comprised a diverse set of signatures, including immune, DNA damage, signaling pathways (PI3K, AKT, Ras, and EGFR), and “stemness” phenotypes.
Conclusions: Proliferation differences account for the vast majority of predictive capacity of gene expression signatures in neoadjuvant chemosensitivity for ER+/HER2− breast cancers and, to a lesser extent, TNBCs. Immune activation signatures are proliferation-independent predictors of pathologic complete response in ER+/HER2− breast cancers. In TNBCs, significant proliferation-independent signatures include gene sets that represent a diverse set of cellular processes. Clin Cancer Res; 22(24); 6039–50. ©2016 AACR.
Targeting Androgen Receptor Aberrations in Castration-Resistant Prostate Cancer
Authors: Sharp Adam , Welti Jonathan , Blagg Julian , de Bono Johann S. 
Published: June 2016

Abstract
Androgen receptor (AR) splice variants (SV) have been implicated in the development of metastatic castration-resistant prostate cancer and resistance to AR targeting therapies, including abiraterone and enzalutamide. Agents targeting AR-SV are urgently needed to test this hypothesis and further improve the outcome of patients suffering from this lethal disease. Clin Cancer Res; 22(17); 4280–2. ©2016 AACR.
See related article by Yang et al., p. 4466
Plk1 Inhibitors in Cancer Therapy: From Laboratory to Clinics
Authors: Gutteridge Rosie Elizabeth Ann , Ndiaye Mary Ann , Liu Xiaoqi , Ahmad Nihal 
Published: June 2016

Abstract
Polo-like kinase 1 (Plk1) overexpression has been shown to occur in a wide range of tumors, prompting research and development of Plk1 inhibitors as a means of cancer treatment. This review discusses recent advances in the development of Plk1 inhibitors for cancer management. Plk1 inhibition has been shown to cause mitotic block and apoptosis of cells with higher mitotic index and therefore higher Plk1 expression. The potential of Plk1 inhibitors as cancer therapeutics has been widely investigated. However, a complete understanding of Plk1 biology/mechanism is yet to be fully achieved. Resistance to certain chemotherapeutic drugs has been linked to Plk1 overexpression, and Plk1-mediated mitotic events such as microtubule rearrangement have been found to reduce the efficacy of chemotherapeutic agents. The Plk1 inhibitor volasertib has shown considerable promise in clinical studies, having reached phase III trials. However, preclinical success with Plk1 inhibitors has not translated well into clinical success. In our view, combined therapies targeting other relevant pathways together with Plk1 may be vital to combat issues observed with monotherapy, especially resistance. In addition, research should also be directed toward understanding the mechanisms of Plk1 and designing additional next generations of specific, potent Plk1 inhibitors to target cancer. Mol Cancer Ther; 15(7); 1427–35. ©2016 AACR.
Whole-Exome Molecular Autopsy After Exertion-Related Sudden Unexplained Death in the Young
Authors: Anderson Jason H. , Tester David J. , Will Melissa L. , Ackerman Michael J. 
Published: June 2016

Background—

Targeted postmortem genetic testing of the 4 major channelopathy-susceptibility genes (
KCNQ1
,
KCNH2
,
SCN5A
, and
RYR2
) have yielded putative pathogenic mutations in ≤30% of autopsy-negative sudden unexplained death in the young (SUDY) cases with highest yields derived from the subset of exertion-related SUDY. Here, we evaluate the role of whole-exome sequencing in exertion-related SUDY cases.

Methods and Results—

From 1998 to 2010, 32 cases of exertion-related SUDY were referred by Medical Examiners for a cardiac channel molecular autopsy. A mutational analysis of the major long-QT syndrome–susceptibility genes (
KCNQ1
,
KCNH2
, and
SCN5A
) and catecholaminergic polymorphic ventricular tachycardia–susceptibility gene (
RYR2
) identified a putative pathogenic mutation in 11 cases. Whole-exome sequencing was performed on the remaining 21 targeted gene–negative SUDY cases. After whole-exome sequencing, a gene-specific surveillance of all genes (N=100) implicated in sudden death was performed to identify putative pathogenic mutation(s). Three of these 21 decedents had a clinically actionable, pathogenic mutation (CALM2-F90L, CALM2-N98S, and PKP2-N634fs). Of the 18 remaining cases, 7 hosted at least 1 variant of unknown significance with a minor allele frequency <1:20 000. The overall yield of pathogenic mutations was higher among decedents aged 1 to 10 years (10/11, 91%) than those aged 11 to 19 years (4/21, 19%,
P
=0.0001).

Conclusions—
Molecular screening in this clinical scenario is appropriate with a pathogenic mutation detection rate of 44% using direct DNA sequencing followed by whole-exome sequencing. Only 5 of the 100 interrogated sudden death genes hosted actionable pathogenic mutations for more than one third of these exertion-related, autopsy-negative SUDY cases.
Treatment Gaps in Adults With Heterozygous Familial Hypercholesterolemia in the United States
Authors: deGoma Emil M. , Ahmad Zahid S. , O’Brien Emily C. , Kindt Iris , Shrader Peter , Newman Connie B. , Pokharel Yashashwi , Baum Seth J. , Hemphill Linda C. , Hudgins Lisa C. , Ahmed Catherine D. , Gidding Samuel S. , Duffy Danielle , Neal William , Wilemon Katherine , Roe Matthew T. , Rader Daniel J. , Ballantyne Christie M. , Linton MacRae F. , Duell P. Barton , Shapiro Michael D. , Moriarty Patrick M. , Knowles Joshua W. 
Published: June 2016

Background—
Cardiovascular disease burden and treatment patterns among patients with familial hypercholesterolemia (FH) in the United States remain poorly described. In 2013, the FH Foundation launched the Cascade Screening for Awareness and Detection (CASCADE) of FH Registry to address this knowledge gap.

Methods and Results—
We conducted a cross-sectional analysis of 1295 adults with heterozygous FH enrolled in the CASCADE-FH Registry from 11 US lipid clinics. Median age at initiation of lipid-lowering therapy was 39 years, and median age at FH diagnosis was 47 years. Prevalent coronary heart disease was reported in 36% of patients, and 61% exhibited 1 or more modifiable risk factors. Median untreated low-density lipoprotein cholesterol (LDL-C) was 239 mg/dL. At enrollment, median LDL-C was 141 mg/dL; 42% of patients were taking high-intensity statin therapy and 45% received >1 LDL-lowering medication. Among FH patients receiving LDL-lowering medication(s), 25% achieved an LDL-C <100 mg/dL and 41% achieved a ≥50% LDL-C reduction. Factors associated with prevalent coronary heart disease included diabetes mellitus (adjusted odds ratio 1.74; 95% confidence interval 1.08–2.82) and hypertension (2.48; 1.92–3.21). Factors associated with a ≥50% LDL-C reduction from untreated levels included high-intensity statin use (7.33; 1.86–28.86) and use of >1 LDL-lowering medication (1.80; 1.34–2.41).

Conclusions—
FH patients in the CASCADE-FH Registry are diagnosed late in life and often do not achieve adequate LDL-C lowering, despite a high prevalence of coronary heart disease and risk factors. These findings highlight the need for earlier diagnosis of FH and initiation of lipid-lowering therapy, more consistent use of guideline-recommended LDL-lowering therapy, and comprehensive management of traditional coronary heart disease risk factors.
Sex‐Based Disparities in Incidence, Treatment, and Outcomes of Cardiac Arrest in the United States, 2003–2012
Authors: Kim Luke K. , Looser Patrick , Swaminathan Rajesh V. , Horowitz James , Friedman Oren , Shin Ji Hae , Minutello Robert M. , Bergman Geoffrey , Singh Harsimran , Wong S. Chiu , Feldman Dmitriy N. 
Published: June 2016

Background
Recent studies have shown improving survival after cardiac arrest. However, data regarding sex‐based disparities in treatment and outcomes after cardiac arrest are limited.

Methods and Results

We performed a retrospective analysis of all patients suffering cardiac arrest between 2003 and 2012 using the Nationwide Inpatient Sample database. Annual rates of cardiac arrest, rates of utilization of coronary angiography/percutaneous coronary interventions/targeted temperature management, and sex‐based outcomes after cardiac arrest were examined. Among a total of 1 436 052 discharge records analyzed for cardiac arrest patients, 45.4% (n=651 745) were females. Women were less likely to present with ventricular tachycardia/ventricular fibrillation arrests compared with men throughout the study period. The annual rates of cardiac arrests have increased from 2003 to 2012 by 14.0% (
P
trend
<0.001) and ventricular tachycardia/ventricular fibrillation arrests have increased by 25.9% (
P
trend
<0.001). Women were less likely to undergo coronary angiography, percutaneous coronary interventions, or targeted temperature management in both ventricular tachycardia/ventricular fibrillation and pulseless electrical activity/asystole arrests. Over a 10‐year study period, there was a significant decrease in in‐hospital mortality in women (from 69.1% to 60.9%,
P
trend
<0.001) and men (from 67.2% to 58.6%,
P
trend
<0.001) after cardiac arrest. In‐hospital mortality was significantly higher in women compared with men (64.0% versus 61.4%; adjusted odds ratio 1.02,
P
<0.001), particularly in the ventricular tachycardia/ventricular fibrillation arrest cohort (49.4% versus 45.6%; adjusted odds ratio 1.11,
P
<0.001).

Conclusions
Women presenting with cardiac arrests are less likely to undergo therapeutic procedures, including coronary angiography, percutaneous coronary interventions, and targeted temperature management. Despite trends in improving survival after cardiac arrest over 10 years, women continue to have higher in‐hospital mortality when compared with men.
Predictors of Restenosis Following Carotid Angioplasty and Stenting
Authors: Zapata-Arriaza Elena , Moniche Francisco , González Alejandro , Bustamante Alejandro , Escudero-Martínez Irene , De la Torre Laviana Francisco Javier , Prieto María , Mancha Fernando , Montaner Joan 
Published: June 2016

Background and Purpose—
Restenosis after carotid angioplasty (with or without stent) is associated with increased rate of stroke and death. Our aim was to determine risk and predictive factors related to carotid restenosis post carotid angioplasty and its association to recurrent cerebrovascular events.

Methods—
All consecutive patients with carotid stenosis treated with angioplasty (n=1060) in a single University Hospital were included (from 2002 to 2013). Follow-up was done prospectively evaluating restenosis, ipsilateral stroke, or death. Restenosis was defined as a narrowing of ≥70% of a previously treated vessel evaluated by ultrasonography.

Results—

Of the 1060 patients treated, 9.2% (97) of patients experienced restenosis during follow up (median 12 [9–32] months). Occurrence of restenosis was associated with ipsilateral stroke during follow-up (
P
=0.049). After Cox regression analysis, hypertension (hazard ratio, 6.2 [1.9–19.9];
P
=0.002), impaired vasoreactivity (hazard ratio, 1.7 [1.09–2.8];
P
=0.019), and angioplasty without stent (hazard ratio, 2.9 [1.2–6.8];
P
=0.012) were independent risk predictors of >70% restenosis.

Conclusions—
Carotid restenosis after carotid angioplasty is associated with ipsilateral stroke occurrence. In our sample, hypertension, angioplasty without stent, and impaired vasoreactivity identify patients at high risk of restenosis and could help to select patients for follow-up ultrasonography imaging.
What is “Folk” about Synagogue Art?
Authors: Rodov Ilia 
Published: June 2016

This publication is a tribute to the memory of the outstanding folklorist and ethnographer Dov Noy, who passed away in 2013. In the scholarly discourse that classifies folklore by modes and media of transmission, synagogue art—as distinct from folk narrative and behavioral lore—is commonly categorized as “visual folklore.” This paper examines the approach of classifying murals and sculptural decoration in east and central European synagogues from the late seventeenth century until the Holocaust as “folk creations.” It suggests a revision of pre-established definitions in the field, in general, and in the analysis of representative folk narratives relating to synagogues, in particular.
The position of academic research into traditional Jewish visual culture, at the seam of art history and folkloristics, challenges predefined divisions of this integral cultural phenomenon into the conventional categories of separate disciplines. In the discourse classifying folklore according to the ways and media of its transmission, synagogue art—in distinction to folk narratives and behavioral lore—commonly falls into the category of “visual folklore,” defined as the visual domain of folk art and material culture. Jewish “folk art” is often attributed generally to “folk artists” and “craftsmen,” without a clear distinction between the two groups. This paper holistically examines the approaches to the murals and sculptural decoration in east and central European synagogues from the late seventeenth century until the Holocaust as visual folklore, craftsmanship, and artistic work, and outlines the part of oral lore in the programming and interpretation of synagogue art. Finally, it proposes to re-approach folk synagogue art as a medium that creates a visual environment for liturgical activity and predicates its viewers’ responses to the challenges, trials, and tribulations of daily life.
Investigation of the Spatial Variability of the Convective Boundary Layer Heights over an Isolated Mountain: Cases from the MATERHORN-2012 Experiment
Authors: Pal S. , De Wekker S. F. J. , Emmitt G. D. 
Published: June 2016

AbstractSpatiotemporal variability in the convective boundary layer height zi over complex terrain is governed by numerous factors such as land surface processes, topography, and synoptic conditions. Observational datasets to evaluate weather forecast models that simulate this variability are sparse. This study aims to investigate the zi spatial variability (along a total leg length of 1800 km) around and over a steep isolated mountain (Granite Mountain) of horizontal and vertical dimensions of 8 and 0.9 km, respectively. An airborne Doppler lidar was deployed on seven flights during the Mountain Terrain Atmospheric Modeling and Observations (MATERHORN) campaign conducted at Dugway Proving Ground (Utah) from 25 September to 24 October 2012. During the afternoon, an east–west zi gradient over the region with zi that was approximately 200 m higher on the eastern side than on the western side of Granite Mountain was observed. This gradient illustrates the impact of two different land surface properties on zi spatial variability, with a sparsely vegetated desert steppe region on the east and a dry, bare lake-bed desert with high subsurface soil moisture to the west of Granite Mountain. Additionally, the zi spatial variability was partly attributed to the impact of Granite Mountain on the downwind zi. Differences in zi were also observed by the radiosonde measurements in the afternoon but not in the morning as the zi variability in morning were modulated by the topography. The high-resolution lidar-derived zi measurements were used to estimate the entrainment zone thickness in the afternoon, with estimates ranging from 100 to 250 m.
Land Surface Climate in the Regional Arctic System Model
Authors: Hamman Joseph , Nijssen Bart , Brunke Michael , Cassano John , Craig Anthony , DuVivier Alice , Abel Mimi R. , Lettenmaier Dennis P. , Maslowski Wieslaw , Osinski Robert , Roberts Andrew , Zeng Xubin 
Published: June 2016

AbstractThe Regional Arctic System Model (RASM) is a fully coupled, regional Earth system model applied over the pan-Arctic domain. This paper discusses the implementation of the Variable Infiltration Capacity land surface model (VIC) in RASM and evaluates the ability of RASM, version 1.0, to capture key features of the land surface climate and hydrologic cycle for the period 1979–2014 in comparison with uncoupled VIC simulations, reanalysis datasets, satellite measurements, and in situ observations. RASM reproduces the dominant features of the land surface climatology in the Arctic, such as the amount and regional distribution of precipitation, the partitioning of precipitation between runoff and evapotranspiration, the effects of snow on the water and energy balance, and the differences in turbulent fluxes between the tundra and taiga biomes. Surface air temperature biases in RASM, compared to reanalysis datasets ERA-Interim and MERRA, are generally less than 2°C; however, in the cold seasons there are local biases that exceed 6°C. Compared to satellite observations, RASM captures the annual cycle of snow-covered area well, although melt progresses about two weeks faster than observations in the late spring at high latitudes. With respect to derived fluxes, such as latent heat or runoff, RASM is shown to have similar performance statistics as ERA-Interim while differing substantially from MERRA, which consistently overestimates the evaporative flux across the Arctic region.
Zonal Variations in the Southern Ocean Heat Budget
Authors: Tamsitt Veronica , Talley Lynne D. , Mazloff Matthew R. , Cerovečki Ivana 
Published: June 2016

AbstractThe spatial structure of the upper ocean heat budget in the Antarctic Circumpolar Current (ACC) is investigated using the ⅙°, data-assimilating Southern Ocean State Estimate (SOSE) for 2005–10. The ACC circumpolar integrated budget shows that 0.27 PW of ocean heat gain from the atmosphere and 0.38 PW heat gain from divergence of geostrophic heat transport are balanced by −0.58 PW cooling by divergence of Ekman heat transport and −0.09 PW divergence of vertical heat transport. However, this circumpolar integrated balance obscures important zonal variations in the heat budget. The air–sea heat flux shows a zonally asymmetric pattern of ocean heat gain in the Indian and Atlantic sectors and ocean heat loss in the Pacific sector of the ACC. In the Atlantic and Indian sectors of the ACC, the surface ocean heat gain is primarily balanced by divergence of equatorward Ekman heat transport that cools the upper ocean. In the Pacific sector, surface ocean heat loss and cooling due to divergence of Ekman heat transport are balanced by warming due to divergence of geostrophic heat advection, which is similar to the dominant heat balance in the subtropical Agulhas Return Current. The divergence of horizontal and vertical eddy advection of heat is important for warming the upper ocean close to major topographic features, while the divergence of mean vertical heat advection is a weak cooling term. The results herein show that topographic steering and zonal asymmetry in air–sea exchange lead to substantial zonal asymmetries in the heat budget, which is important for understanding the upper cell of the overturning circulation.
The Role of Springtime Arctic Clouds in Determining Autumn Sea Ice Extent
Authors: Cox Christopher J. , Uttal Taneil , Long Charles N. , Shupe Matthew D. , Stone Robert S. , Starkweather Sandy 
Published: June 2016

AbstractRecent studies suggest that the atmosphere conditions arctic sea ice properties in spring in a way that may be an important factor in predetermining autumn sea ice concentrations. Here, the role of clouds in this system is analyzed using surface-based observations from Barrow, Alaska. Barrow is a coastal location situated adjacent to the region where interannual sea ice variability is largest. Barrow is also along a main transport pathway through which springtime advection of atmospheric energy from lower latitudes to the Arctic Ocean occurs. The cloud contribution is quantified using the observed surface radiative fluxes and cloud radiative forcing (CRF) derived therefrom, which can be positive or negative. In low sea ice years enhanced positive CRF (increased cloud cover enhancing longwave radiative forcing) in April is followed by decreased negative CRF (decreased cloud cover allowing a relative increase in shortwave radiative forcing) in May and June. The opposite is true in high sea ice years. In either case, the combination and timing of these early and late spring cloud radiative processes can serve to enhance the atmospheric preconditioning of sea ice. The net CRF (April and May) measured at Barrow from 1993 through 2014 is negatively correlated with sea ice extent in the following autumn (r2 = 0.33; p < 0.01). Reanalysis data appear to capture the general timing and sign of the observed CRF anomalies at Barrow and suggest that the anomalies occur over a large region of the central Arctic Ocean, which supports the link between radiative processes observed at Barrow and the broader arctic sea ice extent.
Interaction between the Tidal and Seasonal Variability of the Gulf of Maine and Scotian Shelf Region
Authors: Katavouta Anna , Thompson Keith R. , Lu Youyu , Loder John W. 
Published: June 2016

AbstractAs part of a broader study of ocean downscaling, the seasonal and tidal variability of the Gulf of Maine and Scotian shelf, and their dynamical interaction, are investigated using a high-resolution (1/36°) circulation model. The model’s seasonal hydrography and circulation, and its tidal elevations and currents, are compared with an observed seasonal climatology, local observations, and results from previous studies. Numerical experiments with and without density stratification demonstrate the influence of stratification on the tides. The model is then used to interpret the physical mechanisms responsible for the largest seasonal variations in the M2 surface current that occur over, and to the north of, Georges Bank. The model generates a striation pattern of alternating highs and lows, aligned with Georges Bank, in the M2 surface summer maximum speed in the Gulf of Maine. The striations are consistent with observations by a high-frequency coastal radar system and can be explained in terms of a linear superposition of the barotropic tide and the first-mode baroclinic tide, generated on the north side of Georges Bank, as it propagates into the Gulf of Maine. The seasonal changes in tidal currents in the well-mixed area on Georges Bank are due to a combination of increased sea level gradients, and lower vertical viscosity, in summer.