bluuebunny/crossref_metadata_2025_split huggingface dataset:
PTP1B Contributes to Calreticulin-Induced Metastatic Phenotypes in Esophageal Squamous Cell Carcinoma
Authors: Wang Xiao-Min , Shang Li , Zhang Yu , Hao Jia-Jie , Shi Feng , Luo Wei , Zhang Tong-Tong , Wang Bo-Shi , Yang Yang , Liu Zhi-Hua , Zhan Qi-Min , Wang Ming-Rong 
Published: June 2013

Abstract
Calreticulin (CRT) is a Ca2+-binding chaperone protein that alters cellular Ca2+-homeostasis in the endoplasmic reticulum (ER). Previously it was shown that CRT was overexpressed in esophageal squamous cell carcinoma (ESCC), and elevated CRT expression promoted the migration and invasion of ESCC cells. In the present study, the mechanisms underlying the role of CRT in esophageal carcinoma progression were investigated. Critically, depletion of CRT or protein-tyrosine phosphatase 1B (PTP1B) reduced ESCC cell migration and metastasis to the lung, whereas restoration of PTP1B protein levels rescued cell migration in CRT-silenced cells. Knockdown of CRT decreased PTP1B protein expression by reducing phosphorylation at the Y694 site of STAT5A, whereas knockdown of PTP1B reduced ERK1/2 phosphorylation at T204. Immunohistochemical analysis of CRT and PTP1B expression in ESCC patient tissues was strongly correlated. Importantly, PTP1B expression was associated with poor survival in patients with CRT overexpression. Overall, these data indicate a novel signaling pathway connecting CRT, STAT5A, PTP1B, and ERK1/2 in the regulation of ESCC cell migration.
Implications: These findings suggest that PTP1B is a downstream effector of CRT signaling, promotes tumor progression, and can potentially be used as a new drug target for ESCC. Mol Cancer Res; 11(9); 986–94. ©2013 AACR.
Molecular Classification of Prostate Cancer Progression: Foundation for Marker-Driven Treatment of Prostate Cancer
Authors: Logothetis Christopher J. , Gallick Gary E. , Maity Sankar N. , Kim Jeri , Aparicio Ana , Efstathiou Eleni , Lin Sue-Hwa 
Published: June 2013

Abstract
Recently, many therapeutic agents for prostate cancer have been approved that target the androgen receptor and/or the prostate tumor microenvironment. Each of these therapies has modestly increased patient survival. A better understanding of when in the course of prostate cancer progression specific therapies should be applied, and of what biomarkers would indicate when resistance arises, would almost certainly improve survival due to these therapies. Thus, applying the armamentarium of therapeutic agents in the right sequences in the right combination at the right time is a major goal in prostate cancer treatment. For this to occur, an understanding of prostate cancer evolution during progression is required. In this review, we discuss the current understanding of prostate cancer progression, but challenge the prevailing view by proposing a new model of prostate cancer progression, with the goal of improving biologic classification and treatment strategies. We use this model to discuss how integrating clinical and basic understanding of prostate cancer will lead to better implementation of molecularly targeted therapeutics and improve patient survival.
Significance: Rapid development of drugs with efficacy against prostate cancer now makes it possible to consider applying these agents with curative intent in men with currently incurable cancers. However, when to apply these new drugs, as well as those under development, to obtain the best outcomes is a challenge that must be addressed. To meet this challenge, better classification of the disease based on the underlying molecular mechanisms of progression will facilitate the implementation of current and emerging therapies. Cancer Discov; 3(8); 849–61. ©2013 AACR.
Atrial Natriuretic Peptide–Mediated Inhibition of Microcirculatory Endothelial Ca
2+
and Permeability Response to Histamine Involves cGMP-Dependent Protein Kinase I and TRPC6 Channels
Authors: Chen Wen , Oberwinkler Heike , Werner Franziska , Gaßner Birgit , Nakagawa Hitoshi , Feil Robert , Hofmann Franz , Schlossmann Jens , Dietrich Alexander , Gudermann Thomas , Nishida Motohiro , Del Galdo Sabrina , Wieland Thomas , Kuhn Michaela 
Published: June 2013

Objective—
Histamine increases microvascular endothelial leakage by activation of complex calcium-dependent and -independent signaling pathways. Atrial natriuretic peptide (ANP) via its cGMP-forming guanylyl cyclase-A (GC-A) receptor counteracts this response. Here, we characterized the molecular mechanisms underlying this interaction, especially the role of cGMP-dependent protein kinase I (cGKI).

Approach and Results—

We combined intravital microscopy studies of the mouse cremaster microcirculation with experiments in cultured microvascular human dermal endothelial cells. In wild-type mice, ANP had no direct effect on the extravasation of fluorescent dextran from postcapillary venules, but strongly reduced the histamine-provoked vascular leakage. This anti-inflammatory effect of ANP was abolished in mice with endothelial-restricted inactivation of GC-A or cGKI. Histamine-induced increases in endothelial [Ca
2+
]
i
in vitro and of vascular leakage in vivo were markedly attenuated by the Ca
2+
-entry inhibitor SKF96365 and in mice with ablated transient receptor potential canonical (TRPC) 6 channels. Conversely, direct activation of TRPC6 with hyperforin replicated the hyperpermeability responses to histamine. ANP, via cGKI, stimulated the inhibitory phosphorylation of TRPC6 at position Thr
69
and prevented the hyperpermeability responses to hyperforin. Moreover, inhibition of cGMP degradation by the phosphodiesterase 5 inhibitor sildenafil prevented the edematic actions of histamine in wild types but not in mice with endothelial GC-A or cGKI deletion.

Conclusions—
ANP attenuates the inflammatory actions of histamine via endothelial GC-A/cGMP/cGKI signaling and inhibitory phosphorylation of TRPC6 channels. The therapeutic potential of this novel regulatory pathway is indicated by the observation that sildenafil improves systemic endothelial barrier functions by enhancing the endothelial effects of endogenous ANP.
25-Hydroxyvitamin D and Parathyroid Hormone Are Not Associated With Carotid Intima-Media Thickness or Plaque in the Multi-Ethnic Study of Atherosclerosis
Authors: Blondon Marc , Sachs Michael , Hoofnagle Andrew N. , Ix Joachim H. , Michos Erin D. , Korcarz Claudia , Gepner Adam D. , Siscovick David S. , Kaufman Joel D. , Stein James H. , Kestenbaum Bryan , de Boer Ian H. 
Published: June 2013

Objective—
Observational evidence supports independent associations of 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) with cardiovascular risk. A plausible hypothesis for these associations is accelerated development of atherosclerosis.

Approach and Results—
We evaluated cross-sectional and longitudinal associations of 25-OHD and PTH with carotid intima-media thickness (IMT) and carotid plaques among 3251 participants free of cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis. 25-OHD and PTH were measured at baseline by mass spectrometry and immunoassay, respectively. All subjects underwent a carotid ultrasound examination at baseline and 9.4 years later (median, range 8–11.1 years). Multivariable linear and logistic regressions were used to test associations of 25-OHD and PTH with the extent and progression of IMT and the prevalence and incidence of carotid plaque. Mean (SD) 25-OHD and PTH were 25.8 ng/mL (10.6) and 44.2 pg/mL (20.2), respectively. No independent associations were found between 25-OHD or PTH and IMT at baseline (increment of 1.9 μm [95% confidence interval, −5.1 to 8.9] per 10 ng/mL lower 25-OHD; increment of 0.8 μm [95% confidence interval, −3.2 to 4.8] per 10 pg/mL higher PTH) or progression of IMT (increment of 2.6 μm [95% confidence interval, −2.5 to 7.8] per 10 ng/mL lower 25-OHD, increment of 1.6 μm [95% confidence interval, −1.9 to 5.2] per 10 pg/mL higher PTH). No associations were found with the baseline prevalence of carotid plaque or the incidence of new plaques during the study period. We did not observe any interaction by race or ethnicity (White, Chinese, Black, and Hispanic).

Conclusions—
The consistent lack of association of vitamin D and PTH with carotid IMT and plaque suggests that these hormones may influence cardiovascular risk through pathways not reflected by carotid atherosclerosis.
Postdischarge Outcomes in Heart Failure Are Better for Teaching Hospitals and Weekday Discharges
Authors: McAlister Finlay A. , Au Anita G. , Majumdar Sumit R. , Youngson Erik , Padwal Raj S. 
Published: June 2013

Background—
It is unclear whether teaching status or day of discharge influences outcomes after a heart failure hospitalization.

Methods and Results—
We evaluated adults discharged after a heart failure hospitalization between 1999 and 2009 in Alberta, Canada. The primary outcome was death or nonelective readmission 30 days postdischarge. Of 12 216 patients discharged from teaching hospitals and 12 157 patients from nonteaching hospitals, 20 524 (84%) discharges occurred on weekdays. Although they had greater comorbidity and used more healthcare resources before their heart failure hospitalization, patients discharged from teaching hospitals exhibited shorter lengths of stay (adjusted ratio, 0.83; 95% confidence interval [CI], 0.80–0.86) and significantly lower rates of death or readmission in the 30 days after discharge than those discharged from nonteaching hospitals (17.4% versus 22.1%; adjusted hazard ratio [aHR], 0.83; 95% CI, 0.77–0.89). Patients discharged on weekdays were older and had greater comorbidity, yet exhibited significantly lower rates of death or readmission at 30 days than those discharged on weekends (19.5% versus 21.1%; aHR, 0.87; 95% CI, 0.80–0.94). Compared with weekend discharge from a nonteaching hospital, 30-day death/readmission rates were lower for weekday discharge from a nonteaching hospital (aHR, 0.85; 95% CI, 0.77–0.94), weekend discharge from a teaching hospital (aHR, 0.80; 95% CI, 0.69–0.92), and weekday discharge from a teaching hospital (aHR, 0.71, 95% CI, 0.63–0.79).

Conclusions—
Patients discharged from teaching hospitals or on weekdays exhibited better outcomes despite having higher risk profiles. Future studies should focus on distinguishing which discharge processes differ between teaching and nonteaching hospitals and between weekdays and weekends to define those that optimize patient outcomes.
Individual Common Carotid Artery Wall Layer Dimensions, but Not Carotid Intima–Media Thickness, Indicate Increased Cardiovascular Risk in Women With Preeclampsia
Authors: Akhter Tansim , Wikström Anna-Karin , Larsson Marita , Naessen Tord 
Published: June 2013

Background—
Preeclampsia (PE) is associated with increased risk of cardiovascular disease later in life. Ultrasound assessment of the common carotid artery intima–media thickness (IMT) during or after PE has not indicated any increased cardiovascular risk.

Methods and Results—

We used high-frequency ultrasound (22 MHz) to estimate the individual common carotid artery IMTs in 55 women at PE diagnosis and in 64 women with normal pregnancies at a similar stage. All were re-examined about 1 year postpartum. A thick intima, thin media, and high intima/media (I/M) ratio are signs of a less healthy artery wall. PE was associated with a significantly thicker mean common carotid artery intima, thinner media, and higher I/M ratio than in normal pregnancy (mean I/M difference, 0.21; 95% confidence interval, 0.17–0.25;
P
<0.0001). After adjustment for first trimester body mass index and mean arterial pressure, differences in intima thickness and I/M remained significant. About 1 year postpartum, these values had improved in both groups, but group differences remained significant (all adjusted
P
<0.0001). There were no significant differences in IMT between groups. In receiver-operating characteristic curve analysis, intima thickness and I/M were strongly predictive of prevalent PE (area under the curve, ≈0.95), whereas IMT was not (area under the curve, 0.49).

Conclusions—
The arteries of women with PE were negatively affected during pregnancy and 1 year postpartum compared with women with normal pregnancies, indicating increased cardiovascular risk. Estimation of intima thickness and I/M ratio seem preferable to estimation of common carotid artery IMT in imaging cardiovascular risk in PE. Results from this pilot study warrant further confirmation.
Coronary Endothelium-Dependent Vasoreactivity and Atheroma Volume in Subjects With Stable, Minimal Angiographic Disease Versus Non–ST-Segment–Elevation Myocardial Infarction
Authors: Puri Rishi , Nicholls Stephen J. , Nissen Steven E. , Brennan Danielle M. , Andrews Jordan , Liew Gary Y. , Nelson Adam J. , Carbone Angelo , Copus Barbara , Tuzcu E. Murat , Beltrame John F. , Worthley Stephen G. , Worthley Matthew I. 
Published: June 2013

Background—
Epicardial plaque burden and endothelial function are recognized predictors of coronary events. We aimed to investigate mechanistic relationships between atheroma volume and endothelial function in patients with non–ST-segment–elevation myocardial infarction (NSTEMI) using intravascular ultrasound.

Methods and Results—
In coronary vessels of patients with near-normal or minimal angiographic disease (n=23) and NSTEMI (n=24), intravascular ultrasound-derived measures (percent atheroma volume), arterial remodeling index, and segmental lumen volumes were performed in contiguous 5-mm epicardial segments. Repeat intravascular ultrasound imaging was performed after consecutive 5-minute intracoronary infusions (vehicle solution, 0.30 μg/min and 0.60 μg/min intracoronary salbutamol) to measure changes in segmental lumen volume (endothelium-dependent function). Male sex, diabetes mellitus, smoking, higher triglycerides, and lower high-density lipoprotein cholesterol were more prevalent in the NSTEMI group. Patients with NSTEMI demonstrated greater segmental percent atheroma volume (40.4±12 versus 27.5±14%, P<0.001), remodeling index (1.2 [1.0–1.5] versus 1.0 [0.9–1.0], P<0.001), and displayed less endothelium-dependent vasomotion (% change segmental lumen volume: 2.1±0.89 versus 5.1±0.89%, P=0.02) compared to patients with minimal angiographic disease. No significant difference in endothelial function between both groups was observed when controlling for plaque burden. Multivariate analysis for change in segmental lumen volume identified percent atheroma volume (β=−0.18, P=0.0004), high-sensitivity C-reactive protein >2 mg/L (β=−3.1, P=0.03), diabetes mellitus (β=−6.9, P<0.0001), low-density lipoprotein cholesterol levels (β=−0.04, P=0.01), and smoking (β=–3.2, P=0.01) as independent associates.

Conclusions—
Although coronary endothelial vasoreactivity is blunted in the setting of NSTEMI, this is a reflection of the greater volume of atherosclerosis and cardiovascular risk factors. Thus, the relationship between coronary endothelium-dependent vasomotor reactivity and atheroma volume remains constant irrespective of the nature of the clinical presentation.
Thrombolytic Therapy for the Treatment of Prosthetic Heart Valve Thrombosis in Pregnancy With Low-Dose, Slow Infusion of Tissue-Type Plasminogen Activator
Authors: Özkan Mehmet , Çakal Beytullah , Karakoyun Süleyman , Gürsoy Ozan Mustafa , Çevik Cihan , Kalçık Macit , Oğuz Ali Emrah , Gündüz Sabahattin , Astarcioglu Mehmet Ali , Aykan Ahmet Çağrı , Bayram Zübeyde , Biteker Murat , Kaynak Evren , Kahveci Gökhan , Duran Nilüfer Ekşi , Yıldız Mustafa 
Published: June 2013

Background—
Prosthetic valve thrombosis during pregnancy is life-threatening for mother and fetus, and the treatment of this complication is unclear. Cardiac surgery in pregnancy is associated with very high maternal and fetal mortality and morbidity. Thrombolytic therapy has rarely been used in these patients. The aim of this study is to evaluate the safety and efficacy of low-dose (25 mg), slow infusion (6 hours) of tissue-type plasminogen activator for the treatment of prosthetic valve thrombosis in pregnant women.

Methods and Results—
Between 2004 and 2012, tissue-type plasminogen activator was administered to 24 consecutive women in 25 pregnancies with 28 prosthetic valve thrombosis episodes (obstructive, n=15; nonobstructive, n=13). Mean age of the patients was 29±6 years. Thrombolytic therapy sessions were performed under transesophageal echocardiography guidance. The mean dose of tissue-type plasminogen activator used was 48.7±29.5 mg (range, 25–100mg). All episodes resulted in complete thrombus lysis after thrombolytic therapy. One patient had placental hemorrhage with preterm live birth at the 30th week, and 1 patient had minor bleeding.

Conclusions—
Low-dose, slow infusion of tissue-type plasminogen activator with repeated doses as needed is an effective therapy with an excellent thrombolytic success rate for the treatment of prosthetic valve thrombosis in pregnant women. This protocol also seems to be safer than cardiac surgery or any alternative medical strategies published to date. Thrombolytic therapy should be considered first-line therapy in pregnant patients with prosthetic valve thrombosis.
Effects of Noninvasive Brain Stimulation on Language Networks and Recovery in Early Poststroke Aphasia
Authors: Thiel Alexander , Hartmann Alexander , Rubi-Fessen Ilona , Anglade Carole , Kracht Lutz , Weiduschat Nora , Kessler Josef , Rommel Thomas , Heiss Wolf-Dieter 
Published: June 2013

Background and Purpose—
Modulation of activity in language networks using repetitive transcranial magnetic stimulation (rTMS) may possibly support recovery from poststroke aphasia. Case series and feasibility studies seem to indicate a therapeutic effect; however, randomized sham-controlled, proof-of-principle studies relating clinical effects to activation patterns are missing.

Methods—
Twenty-four patients with subacute poststroke aphasia were randomized to a 10-day protocol of 20-minute inhibitory 1 Hz rTMS over the right triangular part of the posterior inferior frontal gyrus or sham stimulation, followed by 45 minutes of speech and language therapy. Activity in language networks was measured with O-15-water positron emission tomography during verb generation before and after treatment. Language performance was assessed using the Aachen Aphasia Test battery.

Results—

The primary outcome measure, global Aachen Aphasia Test score change, was significantly higher in the rTMS group (
t
test,
P
=0.003). Increases were largest for subtest naming (
P
=0.002) and tended to be higher for comprehension, token test, and writing (
P
<0.1). Patients in the rTMS group activated proportionally more voxels in the left hemisphere after treatment than before (difference in activation volume index) compared with sham-treated patients (
t
test,
P
=0.002).There was a moderate but significant linear relationship between activation volume index change and global Aachen Aphasia Test score change (
r
2
=0.25;
P
=0.015).

Conclusions—
Ten sessions of inhibitory rTMS over the right posterior inferior frontal gyrus, in combination with speech and language therapy, significantly improve language recovery in subacute ischemic stroke and favor recruitment of left-hemispheric language networks.
Differences in Outcome and Predictors Between Ischemic and Intracerebral Hemorrhage
Authors: Bhalla Ajay , Wang Yanzhong , Rudd Anthony , Wolfe Charles D.A. 
Published: June 2013

Background and Purpose—
Few population-based studies describing functional outcome between ischemic stroke and intracerebral hemorrhage (ICH) in the short- and long-term are available. Knowledge of the natural history and factors associated with poor outcome is important in providing prognostic information and resource allocation.

Methods—
Data were collected within the population-based South London Stroke Register between 1995 and 2011. Baseline data were collection of sociodemographic factors, case mix, risk factors before stroke, and acute stroke processes, with outcomes at 7 days, 3 months, 1 year, 5 years, and 10 years after stroke. Logistic regression was used to determine factors associated with poor outcome (dead and dependency: Barthel index <15).

Results—

Age and incontinence were associated with poor outcome at 3 months, 1 year, 5 years, and 10 years in ICH, whereas age, incontinence, failed swallow, atrial fibrillation, and diabetes mellitus were associated with poor outcome in ischemic stroke. ICH was more likely to have poorer outcomes at 3 months (odds ratio, 2.2; 95% confidence interval [CI], 1.8–2.8) and 1 year (odds ratio, 2.1; 95% CI, 1.7–2.6) but not at 5 years (odds ratio, 1.1; 95% CI, 0.8–1.4) or 10 years (odd ratio, 0.8; 95% CI, 0.57–1.22); however, the improvement of functional outcome from day 7 to 3 months was significantly greater for ICH (regression coefficient: 1.8; 95% CI, 1.1–2.6;
P
<0.0001).

Conclusions—
ICH has poorer outcomes up to 5 years after stroke. The improvement of functional outcome up to 3 months was significantly greater with ICH. Identification of factors associated with poor outcome may be used for clinical predictions.
‘Marketless Trading in Hammurabi’s Time’: A Re-appraisal
Authors: Dale Gareth 
Published: June 2013

Abstract
In this article I revisit Karl Polanyi’s writings on ancient Mesopotamia. I begin by situating them in the context of his general approach to trade, markets and money in the ancient world. Next, I reconstruct his major theses on Mesopotamia, drawing upon his published works as well as unpublished documents in the Karl Polanyi and Michael Polanyi archives. Finally, I provide a critical assessment of the merits and demerits of his contribution, with reference to Assyriological research published in the decades that have elapsed since his death in 1964.
A Maghrebian Sharḥ to the Hafṭara for the Minḥa Service on the Day of Atonement
Authors: Bar-Asher Moshe 
Published: June 2013

Abstract
This article deals with the text of a sharḥ (i.e., a Judeo-Arabic translation) to the hafṭara for the afternoon service on the Day of Atonement according to the traditions of Tafilalt and Todgha in Southeast Morocco. This text is a written version of a sharḥ that was transmitted orally for generations and was finally put down in writing in Jerusalem, apparently in the 1960s. The paper discusses a few unique and innovative linguistic phenomena that characterize this text in the realms of orthography, pronunciation, syntax, and lexicon. It also examines the exegetical method that is reflected in this sharḥ and comments on three aspects of the scribe’s work in transmitting the oral tradition to writing.
Willingness to disclose a mental disorder and knowledge of disorders in others: Changes in Australia over 16 years
Authors: Reavley Nicola J , Jorm Anthony F 
Published: June 2013

Objective: To assess whether willingness to disclose experience of a mental disorder and treatment, and awareness of others’ experiences have changed over a 16-year period. Methods: In 2011, telephone interviews were carried out with 6019 Australians aged 15+. The survey interview used the same questions as those of the 1995 and 2003/4 national mental health literacy surveys, in which participants were presented with a case vignette describing either depression, depression with suicidal thoughts (2003/4 only), early schizophrenia or chronic schizophrenia (2003/4 only). Participants were asked whether they had a close friend or family member who had experienced a problem similar to that described in the vignette and whether the person received professional help. They were also asked whether they had experienced such a problem and whether they received professional help. Results: The numbers of those disclosing experiences of depression and early schizophrenia, and of having received professional help for depression, have increased since 1995. Awareness of a family member or close friend with experiences of depression and early schizophrenia also increased between these years, as did awareness that the person received professional help. Conclusions: The numbers of those disclosing experiences of and treatment for mental disorders has increased in the last 16 years. This is likely to be due to increased willingness to disclose rather than increased prevalence of disorders or increased rates of help-seeking.