bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA22: Molecular Imaging of androgen receptor signalling in CRPC
Authors: Larson Steven M. , Fox Joe , Morris Michael , Evans Michael , Lewis Jason , Humm John , Sawyers Charles L. , Scher Howard I. 
Published: May 2013

Abstract
Androgen receptor (AR) plays a key role in development of castrate-resistant prostate cancer (CRPC), the lethal form of the disease. For this reason we have developed Molecular Imaging (MI) methods to study AR, both in laboratory and clinic. For this work we have used a radiotracer that is highly specific for AR, a flourine-18 analog of dihydrotestoterone, (FDHT) the most abundant androgen at the tissue level in human cancers. In the laboratory for example, we have used FDHT to document AR binding of novel drugs and to determine their relative affinity and the number of AR receptor sites in human prostate cancer cell lines and xenografts. In the clinic we have imaged patients with CRPC to determine the impact of therapies on AR expression. During the course of this work we have developed quantitative kinetic models based on PET imaging and have shown the FDHT binding and uptake into cancers is AR dependent, and that the metabolites of FDHT do not bind appreciably to AR. We have compared FDHT and FDG in CRPC patients and have determined that there are an average of 17 tumors per patient (n=107), and the 90% of metabolically active tumors for FDG or FDHT express AR, but that there is a group of lesions that do not but are detected by metabolism of FDG. We have shown that drugs which target AR displace FDHT completely when used in full pharmacologic doses. So far the data is consistent with the view that this type of displacement is a necessary condition for tumor response, but clearly some patients whose AR binding is completely blocked have lesions which continue to progress through unknown mechanisms. We believe that molecular imaging using antibodies labeled with PET emitters will add greatly to our knowledge about CRPC, and studies in man with 89Zr-DFO J591, and antibody targeting PSMA are just beginning. The impact of AR signaling on PSMA expression has been shown in the laboratory to be down regulation, and we intend to explore the use of antibodies to provide a pharmacodynamic biomarker of AR signaling in man during therapy with AR blockers in the clinic.
Citation Format: Steven M. Larson, Joe Fox, Michael Morris, Michael Evans, Jason Lewis, John Humm, Charles L. Sawyers, Howard I. Scher. Molecular Imaging of androgen receptor signaling in CRPC [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr IA22.
Abstract IA25: Inflammation as the trigger of somatic epigenome defects in prostate cancer
Authors: Nelson William G. 
Published: May 2013

Abstract
Prostate cancer has achieved epidemic proportions among men in the United States (US) and developed world; inflammation of the peripheral zone of the prostate, where the cancers arise, is just as ubiquitous (1). Accumulating insights from studies of prostatic carcinogenesis, using either human biospecimens or rodent models, indicate that stressors which cause prostate inflammation, including infections, estrogens, and the diet, also cause prostate cancer (1). Chronic inflammation in the prostate peripheral zone leads to the appearance of focal atrophy lesions of the prostate epithelium, replete with corpora amylacea, cellular and nuclear atypia, and a prostate stroma infiltrated by inflammatory cells (2). These proliferative inflammatory atrophy (PIA) lesions serve as the earliest precursors to prostate cancers, where epigenetic gene silencing, telomere shortening, and activation of c-Myc expression drive neoplastic transformation (3). Gene translocations/deletions that generate fusion transcripts between androgen-regulated genes (such as TMPRSS2) and genes encoding ETS family transcription factors (such as ERG1), typically arise later, during progression to invasive prostate cancer (4). The end consequence of these acquired defects in genes and in gene function is life-threatening prostate cancer, which when lethal exhibits widespread genome and epigenome corruption. Epigenetic silencing of GSTP1, encoding an oxidant and carcinogen detoxifying enzyme, is emblematic of the earliest steps in prostatic carcinogenesis, triggered in some way by prostate hypermethylation of the GSTP1 CpG island. This acquired epigenome alteration is present in nearly all prostate cancer cases, appearing at the very initiation of transformation, with some 5–10% of proliferative inflammatory atrophy (PIA) lesions and &gt; 70% of prostatic intraepithelial neoplasia (PIN) lesions affected, and persisting throughout prostate cancer progression (3). In mouse models of prostate cancer, the mouse homologs of GSTP1, Gstp1 and Gstp2, serve as tumor suppressors, limiting progression of PIN to prostate cancer. Hopefully, such models can be used to ascertain how de novo GSTP1 methylation occurs during the pathogenesis of prostate cancer. Chronic or recurrent inflammatory processes leading to PIA appear to be the major driver of the prostate cancer epidemic in the developed world, raising the possibility that attenuation or prevention of inflammation, or of inflammatory damage to the prostate, might serve to prevent disease morbidity and mortality.
Citation Format: William G. Nelson. Inflammation as the trigger of somatic epigenome defects in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr IA25.
G34, Another Connection between MYCN and a Pediatric Tumor
Authors: Huang Miller , Weiss William A. 
Published: May 2013

Abstract
Summary: Recurrent mutations in H3F3A at K27 and G34 are frequent in pediatric glioblastoma, but it is unclear how these mutations promote tumorigenesis. In this issue of Cancer Discovery, Bjerke and colleagues identify mutations at G34 in H3F3A that result in elevated expression of MYCN as a potential mechanism in gliomagenesis. Cancer Discov; 3(5); 484–6. ©2013 AACR.
See related article by Bjerke et al., p. 512
Relationship Between ST-Segment Recovery and Clinical Outcomes After Primary Percutaneous Coronary Intervention
Authors: Farkouh Michael E. , Reiffel James , Dressler Ovidiu , Nikolsky Eugenia , Parise Helen , Cristea Ecatarina , Baran David A. , Dizon Jose , Merab Jacques P. , Lansky Alexandra J. , Mehran Roxana , Stone Gregg W. 
Published: May 2013

Background—
In patients with ST-segment elevation myocardial infarction undergoing thrombolytic therapy, the degree of ST-segment resolution (STR) correlates with long-term cardiovascular mortality. The long-term predictive value of STR after primary percutaneous coronary intervention (PCI) is less well understood. We sought to determine the long-term prognostic value of STR after primary PCI in ST-segment–elevation myocardial infarction.

Methods and Results—

In a formal substudy from the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, 2484 patients with ST-segment–elevation myocardial infarction undergoing primary PCI with interpretable baseline and 60-minute post-PCI electrocardiograms had at least 1 mm of baseline ST-segment elevation in ≥2 contiguous leads. Patients were categorized by the degree of STR at 60 minutes: (1) complete (>70%); (2) partial (30%–70%); and (3) absent (<30%). Absent, incomplete, and complete STR were achieved in 514 (20.7%), 712 (28.7%), and 1258 (50.5%) patients, respectively. STR <30% was associated with a greater likelihood of hypertension, diabetes mellitus, longer symptom onset to balloon time, lower left ventricular ejection fraction, and final thrombolysis in myocardial infarction flow <3. At 3 years, patients with STR<30% experienced a higher rate of major adverse cardiovascular events (death, reinfarction, ischemia-driven target vessel revascularization or stroke; 29.9% versus 20.1% versus 19.6%;
P
<0.0001), ischemia-driven target vessel revascularization (20.4% versus 14.0% versus 11.7%;
P
<0.001), and mortality (8.4% versus 5.0% versus 5.6%;
P
=0.03) than those with partial and complete STR, respectively. By multivariable analysis, STR<30% was an independent predictor of 3-year major adverse cardiovascular events (hazard ratio, 1.58; 95% confidence interval, 1.24–2.00;
P
=0.0002) and 3-year ischemia-driven target vessel revascularization (hazard ratio, 1.87; 95% confidence interval, 1.41–2.48;
P
<0.0001).

Conclusions—
In this large international study, absent STR 60 minutes after primary PCI was present in ≈1 in 5 patients with ST-segment–elevation myocardial infarction and was a significant independent predictor of major adverse cardiovascular events and target vessel revascularization at 3 years.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00433966
Perceived Risk of Ischemic and Bleeding Events in Acute Coronary Syndromes
Authors: Chew Derek P. , Junbo Ge , Parsonage William , Kerkar Prafulla , Sulimov Vitaly A. , Horsfall Matthew , Mattchoss Sue ,   for the Perceived Risk of Ischemic and Bleeding Events in Acute Coronary Syndrome Patients (PREDICT) Study Investigators
Published: May 2013

Background—
Acute coronary syndrome registries report the use of incomplete guideline therapies, especially among the highest risk patients. Whether this treatment gap results from misperceptions of risk by physicians is uncertain.

Methods and Results—

The Perceived Risk of Ischemic and Bleeding Events in Acute Coronary Syndrome Patients (PREDICT) study was a prospective acute coronary syndrome registry in Australia, China, India, and Russia, involving 58 hospitals between May 2009 and February 2011. In-hospital care and events up to 6 months were assessed. At least 2 clinicians involved in patient care estimated the untreated risk and change in risk with each therapy. Physician risk assessment and objective risk measures (eg, Global Registry of Acute Coronary Events [GRACE] score) for death, death/myocardial infarction, and bleeding events were compared using the c statistic and integrated discrimination improvement. In total, 1542 patients and 4230 patient-specific physician estimates were obtained. Of responding clinicians, 81.9% were cardiovascular specialists (years of practice: mean [SD], 11.5 [7.7] years). The median physician-perceived risk of 6-month death was 25% (interquartile range, 14%–35%). The GRACE score was superior to physician estimation (c statistic: GRACE score, 0.812 [95% confidence interval, 0.772–0.851] versus physician, 0.652 [95% confidence interval, 0.596–0.708];
P
<0.0001). The GRACE score added to clinician intuition improved discrimination (integrated discrimination improvement, 0.0632 [SE, 0.012];
P
<0.0001). Invasive management correlated with physician-estimated risk but not with GRACE risk. Among patients not at high risk by physician estimation, increased risk by GRACE score was associated with higher mortality (3.7% versus 0.8%;
P
<0.001).

Conclusions—
Objective risk assessment provides superior risk discrimination when compared with physician-estimated risk. Whether systematic use of objective risk stratification improves clinical outcomes should be studied in appropriately designed clinical trials.
Moyamoya Disease in a Primarily White, Midwestern US Population
Authors: Bower Regina S. , Mallory Grant W. , Nwojo Macaulay , Kudva Yogish C. , Flemming Kelly D. , Meyer Fredric B. 
Published: May 2013

Background and Purpose—
Moyamoya disease is an uncommon, cerebrovascular occlusive disease of unknown pathogenesis. Previously described Moyamoya cohorts include predominantly Asian populations or ethnically diverse North American cohorts. To gain further insight into the pathogenesis of moyamoya, we examined clinical characteristics of a primarily white, Midwestern US population

Methods—
Retrospective analysis of patients with angiographically confirmed moyamoya disease evaluated at our institution was performed. Prevalence of comorbidities, cerebrovascular risk factors, and autoimmune diseases were compared with the general population.

Results—
Ninety-four patients with moyamoya were evaluated; 72.3% were female. Ethnic composition was primarily white (85%). A significantly higher prevalence of autoimmune disease was seen, particularly type 1 diabetes mellitus (8.5% versus 0.4% in the general population) and thyroid disease (17.0% versus 8.0% in the institutional general patient population). Hyperlipidemia was also increased (27.7% versus 16.3% in the general population).

Conclusions—
This study of a unique, primarily white, Midwestern population of moyamoya patients demonstrates a significantly higher prevalence of autoimmune disease than in the general population. This supports a possible autoimmune component to the pathogenesis of moyamoya disease.
Decreased Corticospinal Tract Fractional Anisotropy Predicts Long-term Motor Outcome After Stroke
Authors: Puig Josep , Blasco Gerard , Daunis-I-Estadella Josep , Thomalla Götz , Castellanos Mar , Figueras Jaume , Remollo Sebastián , van Eendenburg Cecile , Sánchez-González Javier , Serena Joaquín , Pedraza Salvador 
Published: May 2013

Background and Purpose—
Nearly 50% of patients have residual motor deficits after stroke, and long-term motor outcome is difficult to predict. We assessed the predictive value of axonal damage to the corticospinal tract indexed by diffusion tensor imaging fractional anisotropy for long-term motor outcome.

Methods—
Consecutive patients with middle cerebral artery stroke underwent multimodal MRI, including diffusion tensor imaging ≤12 hours, 3 days, and 30 days after onset. Clinical severity, infarct volume, location of corticospinal tract damage on diffusion tensor tractography, and ratios of fractional anisotropy (rFA) between affected and unaffected sides of the corticospinal tract at the pons were evaluated. Severity of motor deficit at 2 years was categorized using the Motricity Index as no deficit (Motricity Index, 100), slight-moderate deficit (Motricity Index, 99–50), or severe deficit (Motricity Index, <50).

Results—

We evaluated 70 patients (28 women; 72±12 years). rFA values at day 30 correlated with the degree of motor deficit at 2 years (
P
<0.001). rFA at day 30 was the only independent predictor of long-term motor outcome (odds ratio, 1.60; 95% confidence interval, 1.26–2.03;
P
<0.001). The sensitivity, specificity, and positive and negative predictive values of the cutoffs rFA<0.982 for predicting slight-moderate deficit and rFA<0.689 for severe deficit were 94.4%, 84.6%, 73.9%, and 97.1%, respectively, and 100%, 83.3%, 81.3%, and 100%, respectively.

Conclusions—
rFA at day 30 is an independent predictor of long-term motor outcome after stroke.
Clinical Significance of Fluid-Attenuated Inversion Recovery Vascular Hyperintensities in Transient Ischemic Attack
Authors: Kobayashi Junpei , Uehara Toshiyuki , Toyoda Kazunori , Endo Kaoru , Ohara Tomoyuki , Fujinami Jun , Nagatsuka Kazuyuki , Minematsu Kazuo 
Published: May 2013

Background and Purpose—
Fluid-attenuated inversion recovery vascular hyperintensity (FVH) is often identified in patients with acute ischemic stroke. The purpose of this study was to determine the clinical significance of FVH in patients with transient ischemic attack (TIA).

Methods—
Consecutive inpatients with TIA who underwent MRI within 24 hours of symptom onset were studied. The frequency, relative factors, and time course of FVH were determined.

Results—

Of the 202 patients who were enrolled (76 women, mean age, 69.0±13.2 years), FVH was identified in 41 patients (20%). Multivariate analysis showed that atrial fibrillation (odds ratio, 7.14; 95% confidence interval [CI], 2.69–18.1), arterial occlusive lesion (odds ratio, 4.89; 95% CI, 3.03–12.2), and hemiparesis (odds ratio, 2.81; 95% CI, 1.17–7.48) was independently associated with FVH. Of 23 recurrence-free patients with FVH positive undergoing follow-up MRI at a median of 7 days after the onset, FVH was no longer positive in 15 patients (65%). Atrial fibrillation was more common (
P
=0.027) and arterial occlusive lesion was less common (
P
<0.001) in patients with transient FVH compared with those with persistent FVH. Within 90 days after the onset, 13 patients developed recurrent TIA or ischemic stroke. After Cox proportional hazard analysis, FVH (hazard ratio, 3.65; 95% CI, 1.09–12.7), arterial occlusive lesion (hazard ratio, 4.15; 95% CI, 1.18–17.1), and coexistence of FVH and arterial occlusive lesion (hazard ratio, 13.9; 95% CI, 3.36–71.0) were significantly associated with recurrent TIA or ischemic stroke.

Conclusions—
The presence of FVH early after symptom onset may help to diagnosis TIA, to identify the potential mechanisms of TIA and to predict recurrence risk after a TIA.
Impact of Completeness of Ascertainment of Minor Stroke on Stroke Incidence
Authors: Béjot Yannick , Mehta Ziyah , Giroud Maurice , Rothwell Peter M. 
Published: May 2013

Background and Purpose—
Reliable comparisons of stroke incidence are important. To determine the impact of systematic assessment of patients referred with transient ischemic attack on the measured incidence and severity of stroke, we compared 2 population-based studies.

Methods—
Patients with first-ever stroke ascertained during 2006 through 2010 from the Dijon Stroke Registry and the Oxford Vascular (OXVASC) Study were studied. Both studies comply with the criteria for ideal incidence studies, but the OXVASC Study also systematically assessed all patients referred with transient ischemic attack. Stroke severity was measured by the National Institutes of Health Stroke Scale.

Results—

Among 902 incident strokes in Dijon and 748 cases in the OXVASC Study, age and gender distribution were comparable, but severity was lower in the OXVASC Study (median National Institutes of Health Stroke Scale, 2 versus 6;
P
<0.001). Although overall incidence of ischemic stroke was higher in the OXVASC Study (157 versus 98 of 100 000/y; incidence rate ratio, 1.59; 95% confidence interval, 1.24–2.05;
P
<0.001), this was accounted for by a 3-fold excess incidence of stroke with National Institutes of Health Stroke Scale ≤2 in the OXVASC Study (90 versus 29/100 000/y;
P
<0.001), with no difference in incidence of more severe ischemic stroke (incidence rate ratio, 0.95; 95% confidence interval, 0.68–1.33). Of all 660 incident ischemic strokes in the OXVASC Study, 375 (56.8%) cases had an National Institutes of Health Stroke Scale ≤2, of which 232 had been ascertained in the transient ischemic attack clinic. Of these 232 minor strokes, only 71 cases had a diagnosis of definite stroke documented in the medical records by the referring physician.

Conclusions—
Reliance on routine clinical coding underestimates the incidence of minor stroke. To improve comparability of incidence studies, researchers should assess patients referred with transient ischemic attack, and all studies should stratify incidence rates by stroke severity.
Connectivity and Communication in the Achaemenid Empire
Authors: Colburn Henry P. 
Published: May 2013

Abstract
The vast territorial extent of the Achaemenid Empire is often assumed to have impeded connectivity and communication within the empire. This paper challenges the validity of this assumption. Two factors in particular favor this conclusion—the presence of an extensive road network and the high communication speed in the empire, made possible by the pirradazish service. Together, they demonstrate the enormous potential for movement and interaction throughout the empire.
Pyramidal Lead Objects: Scale Weights, Loom Weights, or Sinkers?
Authors: Kletter Raz 
Published: May 2013

Abstract
Ancient scale weights are a key to understanding weight systems and types of economy, but their definition is notoriously difficult, and scholars tend to classify as weights a wide variety of objects. The present paper reassesses a series of pyramidal lead objects from Phoenicia, dated mostly to the Hellenistic period. In the last twenty years these objects have been regarded as scale weights—in fact, forming the largest category of assumed Phoenician scale weights. In this paper it is suggested that these are not scale weights but sinkers (weights for fishing lines or nets).
The Suppression of Leonard Howell in Late Colonial Jamaica, 1932-1954
Authors: Dunkley D.A. 
Published: May 2013

Abstract
This article is about Leonard Percival Howell, the man who is widely regarded as the founder of the Rastafari movement, which started in Jamaica in 1932. The article focuses on the attempts to suppress Howell during the foundational phase of the Rastafari movement from 1932 to 1954. This was the period in which Howell began preaching the divinity of Haile Selassie I, who was crowned the emperor of Ethiopia in 1930. In 1937, Howell established the friendly organization known as the Ethiopian Salvation Society, and in 1940 started the first Rastafari community in the hills of the parish of St. Catherine, Jamaica. These and his other religio-political activities made Howell the target of one of the longest and most aggressive campaigns to suppress an anticolonial activist during the late colonial period in Jamaica. However, one of the main points of this article is that the attempts to suppress Howell, who was seen by the colonial government as seditious, implicated not just the colonial regime, but also a number of other opponents within the society. This article is an attempt to show that Howell’s suppression was not exclusively a colonial endeavor, but a society-wide campaign to undermine his leadership in order to disband the Rastafari movement. Howell advocated an anticolonialism that was seen as too revolutionary by every participant in the campaign to suppress him and his movement, and particularly aggravating was the notion that a black monarch was the fulfillment of biblical prophecy, and whose ascension signaled the start of black nationalism as a global liberation movement to end white rule over Africans and people of African descent.
paNTICA: A Fast 3D Radiative Transfer Scheme to Calculate Surface Solar Irradiance for NWP and LES Models
Authors: Wissmeier Ulrike , Buras Robert , Mayer Bernhard 
Published: May 2013

AbstractThe resolution of numerical weather prediction models is constantly increasing, making it necessary to consider three-dimensional radiative transfer effects such as cloud shadows cast into neighboring grid cells and thus affecting radiative heating. For that purpose, fast approximations are needed since three-dimensional radiative transfer solvers are computationally far too expensive. For the solar spectral range, different approaches of how to consider three-dimensional effects were presented in the past—in particular, the tilted independent column approximation (TICA), which aims at improving the calculation of the direct radiation, and the nonlocal tilted independent column approximation (NTICA), which is used to additionally correct the diffuse radiation. Here a new version of NTICA is presented that—in contrast to earlier approaches—is applicable for a variety of cloud scenes and grid resolutions and for arbitrary solar zenith angles. This new parameterization for the diffuse irradiance is then applied to the two different TICA approaches and the results are compared with a full 3D Monte Carlo calculation. It is shown that both approaches strongly improve the calculation of radiation fluxes if the new parameterization for the diffuse irradiance—what the authors call “parameterized NTICA (paNTICA)”—is applied. It is found that the method in which TICA is only applied to direct radiation yields the better results. The studies show that consideration of three-dimensional effects is inevitable if higher model resolutions are used in the future. This paper proposes ways to consider these effects and, thus, to substantially reduce the errors made with one-dimensional radiative transfer solvers.