bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polo-like Kinase 1: A Potential Therapeutic Option in Combination with Conventional Chemotherapy for the Management of Patients with Triple-Negative Breast Cancer
Authors: Maire Virginie , Némati Fariba , Richardson Marion , Vincent-Salomon Anne , Tesson Bruno , Rigaill Guillem , Gravier Eléonore , Marty-Prouvost Bérengère , De Koning Leanne , Lang Guillaume , Gentien David , Dumont Aurélie , Barillot Emmanuel , Marangoni Elisabetta , Decaudin Didier , Roman-Roman Sergio , Pierré Alain , Cruzalegui Francisco , Depil Stéphane , Tucker Gordon C. , Dubois Thierry 
Published: November 2012

Abstract
Breast cancers are composed of molecularly distinct subtypes with different clinical outcomes and responses to therapy. To discover potential therapeutic targets for the poor prognosis-associated triple-negative breast cancer (TNBC), gene expression profiling was carried out on a cohort of 130 breast cancer samples. Polo-like kinase 1 (PLK1) was found to be significantly overexpressed in TNBC compared with the other breast cancer subtypes. High PLK1 expression was confirmed by reverse phase protein and tissue microarrays. In triple-negative cell lines, RNAi-mediated PLK1 depletion or inhibition of PLK1 activity with a small molecule (BI-2536) induced an increase in phosphorylated H2AX, G2–M arrest, and apoptosis. A soft-agar colony assay showed that PLK1 silencing impaired clonogenic potential of TNBC cell lines. When cells were grown in extracellular matrix gels (Matrigel), and exposed to BI-2536, apoptosis was observed specifically in TNBC cancerous cells, and not in a normal cell line. When administrated as a single agent, the PLK1 inhibitor significantly impaired tumor growth in vivo in two xenografts models established from biopsies of patients with TNBC. Most importantly, the administration of BI-2536, in combination with doxorubicin + cyclophosphamide chemotherapy, led to a faster complete response compared with the chemotherapy treatment alone and prevented relapse, which is the major risk associated with TNBC. Altogether, our observations suggest PLK1 inhibition as an attractive therapeutic approach, in association with conventional chemotherapy, for the management of patients with TNBC. Cancer Res; 73(2); 813–23. ©2012 AACR.
Antitumor Activity of Saracatinib (AZD0530), a c-Src/Abl Kinase Inhibitor, Alone or in Combination with Chemotherapeutic Agents in Gastric Cancer
Authors: Nam Hyun-Jin , Im Seock-Ah , Oh Do-Youn , Elvin Paul , Kim Hwang-Phill , Yoon Young-Kwang , Min Ahrum , Song Sang-Hyun , Han Sae-Won , Kim Tae-You , Bang Yung-Jue 
Published: November 2012

Abstract
Src is a nonreceptor tyrosine kinase involved in the cross-talk and mediation of many signaling pathways that promote cell proliferation, adhesion, invasion, migration, and tumorigenesis. Increased Src activity has been reported in many types of human cancer, including gastric cancer. Therefore, this factor has been identified as a promising therapeutic target for cancer treatments, and targeting Src in gastric cancer is predicted to have potent effects. We evaluated the antitumor effect of a c-Src/Abl kinase inhibitor, saracatinib (AZD0530), alone or combined with chemotherapeutic agents in gastric cancer cell lines and a NCI-N87 xenograft model. Among 10 gastric cancer cell lines, saracatinib specifically inhibited the growth and migration/invasion of SNU216 and NCI-N87 cells. Saracatinib blocked the Src/FAK, HER family, and oncogenic signaling pathways, and it induced G1 arrest and apoptosis in SNU216 and NCI-N87 cells. Apoptosis required induction of the proapoptotic BCL2 family member Bim. Knockdown of Bim using siRNA decreased apoptosis induced by treatment with saracatinib, suggesting that Bim has an important role in saracatinib-induced apoptosis. Saracatinib enhanced the effects of lapatinib, an EGFR/HER2 dual inhibitor, in SNU216 and NCI-N87 cells. Furthermore, combined treatment with saracatinib and 5-fluorouracil (5-FU) or cisplatin exerted synergistic effects in both saracatinib-sensitive and saracatinib-resistant cells. Consistent with our in vitro findings, cotreatment with saracatinib and 5-FU resulted in enhanced antitumor activity in the NCI-N87 xenografts. These data indicate that the inhibition of Src kinase activity by saracatinib alone or in combination with other agents can be a strategy to target gastric cancer. Mol Cancer Ther; 12(1); 16–26. ©2013 AACR.
Stress Reduction in the Secondary Prevention of Cardiovascular Disease
Authors: Schneider Robert H. , Grim Clarence E. , Rainforth Maxwell V. , Kotchen Theodore , Nidich Sanford I. , Gaylord-King Carolyn , Salerno John W. , Kotchen Jane Morley , Alexander Charles N. 
Published: November 2012

Background—
Blacks have disproportionately high rates of cardiovascular disease. Psychosocial stress may contribute to this disparity. Previous trials on stress reduction with the Transcendental Meditation (TM) program have reported improvements in cardiovascular disease risk factors, surrogate end points, and mortality in blacks and other populations.

Methods and Results—

This was a randomized, controlled trial of 201 black men and women with coronary heart disease who were randomized to the TM program or health education. The primary end point was the composite of all-cause mortality, myocardial infarction, or stroke. Secondary end points included the composite of cardiovascular mortality, revascularizations, and cardiovascular hospitalizations; blood pressure; psychosocial stress factors; and lifestyle behaviors. During an average follow-up of 5.4 years, there was a 48% risk reduction in the primary end point in the TM group (hazard ratio, 0.52; 95% confidence interval, 0.29–0.92;
P
=0.025). The TM group also showed a 24% risk reduction in the secondary end point (hazard ratio, 0.76; 95% confidence interval, 0.51–0.1.13;
P
=0.17). There were reductions of 4.9 mmHg in systolic blood pressure (95% confidence interval −8.3 to –1.5 mmHg;
P
=0.01) and anger expression (
P
<0.05 for all scales). Adherence was associated with survival.

Conclusions—
A selected mind–body intervention, the TM program, significantly reduced risk for mortality, myocardial infarction, and stroke in coronary heart disease patients. These changes were associated with lower blood pressure and psychosocial stress factors. Therefore, this practice may be clinically useful in the secondary prevention of cardiovascular disease.

Clinical Trial Registration—

URL:
www.clinicaltrials.gov
Unique identifier: NCT01299935.
Lifestyle Risk Factors for Ischemic Stroke and Transient Ischemic Attack in Young Adults in the Stroke in Young Fabry Patients Study
Authors: von Sarnowski Bettina , Putaala Jukka , Grittner Ulrike , Gaertner Beate , Schminke Ulf , Curtze Sami , Huber Roman , Tanislav Christian , Lichy Christoph , Demarin Vida , Basic-Kes Vanja , Ringelstein E. Bernd , Neumann-Haefelin Tobias , Enzinger Christian , Fazekas Franz , Rothwell Peter M. , Dichgans Martin , Jungehulsing Gerhard J. , Heuschmann Peter U. , Kaps Manfred , Norrving Bo , Rolfs Arndt , Kessler Christof , Tatlisumak Turgut 
Published: November 2012

Background and Purpose—
Although many stroke patients are young or middle-aged, risk factor profiles in these age groups are poorly understood.

Methods—
The Stroke in Young Fabry Patients (sifap1) study prospectively recruited a large multinational European cohort of patients with cerebrovascular events aged 18 to 55 years to establish their prevalence of Fabry disease. In a secondary analysis of patients with ischemic stroke or transient ischemic attack, we studied age- and sex-specific prevalences of various risk factors.

Results—
Among 4467 patients (median age, 47 years; interquartile range, 40–51), the most frequent well-documented and modifiable risk factors were smoking (55.5%), physical inactivity (48.2%), arterial hypertension (46.6%), dyslipidemia (34.9%), and obesity (22.3%). Modifiable less well-documented or potentially modifiable risk factors like high-risk alcohol consumption (33.0%) and short sleep duration (20.6%) were more frequent in men, and migraine (26.5%) was more frequent in women. Women were more often physically inactive, most pronouncedly at ages <35 years (18–24: 38.2%; 25–34: 51.7%), and had high proportions of abdominal obesity at age 25 years or older (74%). Physical inactivity, arterial hypertension, dyslipidemia, obesity, and diabetes mellitus increased with age.

Conclusions—
In this large European cohort of young patients with acute ischemic cerebrovascular events, modifiable risk factors were highly prevalent, particularly in men and older patients. These data emphasize the need for vigorous primary and secondary prevention measures already in young populations targeting modifiable lifestyle vascular risk factors.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique Identifier: NCT00414583.
Analysis of a Coordinated Stroke Center and Regional Stroke Network on Access to Acute Therapy and Clinical Outcomes
Authors: Rymer Marilyn M. , Armstrong Edward P. , Walker Gary , Pham Sissi , Kruzikas Denise 
Published: November 2012

Background and Purpose—
Compare access and outcomes in a tertiary care community hospital (Saint Luke’s Neuroscience Institute) and its stroke network to hospitals in 3 national databases.

Methods—
Retrospective analysis of ischemic stroke patients (2005, 2007, 2010) in Saint Luke’s (n=1576), Get With The Guidelines-Stroke (n=423 809), Premier (n=91 598), and Merci Registry (n=966). Study measures were use of computed tomography scans and tissue plasminogen activator (tPA), symptomatic intracranial hemorrhage, discharge disposition, discharge National Institutes of Health Stroke Scale scores, and 90-day modified Rankin Scores.

Results—

Saint Luke’s increased access to care with higher tPA use than other hospitals (17.2% received intravenous tPA therapy compared with 5.8% at Get With The Guidelines–Stroke hospitals,
P
<0.001; 22.1% of Saint Luke’s patients received tPA by any route compared with 3.5% of Premier patients,
P
<0.001). Use of intravenous tPA within 4.5 hours of onset was associated with more discharges to home (odds ratio, 2.123; 95% confidence interval, 1.394–3.246) and improved National Institutes of Health Stroke Scale scores (
P
=0.001). Saint Luke’s patients also were more likely than those in other hospitals to receive computed tomography scans (99.4% vs 58.6% at Premier hospitals). Embolectomy at Saint Luke’s was associated with better outcomes than peer hospitals, and treatment at Saint Luke’s was independently associated with more discharges to home (odds ratio, 3.92; 95% confidence interval, 1.84–8.32). In 2010, symptomatic intracranial hemorrhages after tPA therapy was similar for Saint Luke’s patients and Premier patients (2.2% vs 1.5%;
P
=0.590).

Conclusions—
Regionally coordinated stroke programs can substantially improve access and patient outcomes.
Prestroke Modified Rankin Stroke Scale Has Moderate Interobserver Reliability and Validity in an Acute Stroke Setting
Authors: Fearon Patrica , McArthur Kate S. , Garrity Kevin , Graham Laura J. , McGroarty Geraldine , Vincent Sarah , Quinn T. J. 
Published: November 2012

Background and Purpose—
The modified Rankin Scale (mRS) is the recommended functional outcome assessment in stroke trials. Utility of mRS may be limited by interobserver variability. prestroke function, described using mRS, is often used as trial entry criterion. We assessed the reliability and validity of prestroke mRS in acute stroke.

Methods—
We present two complementary analyses of the properties of prestroke mRS: (1) Paired interviewers (trained in mRS) performed independently a blinded assessment of mRS and prestroke mRS. Interobserver variability was described using percentage agreement and weighted (kw) κ statistics with 95% confidence interval (95% CI). Validity was assessed by comparing prestroke mRS with other markers of function (comorbidity; medication count; need for carers). (2) We further assessed validity using a larger retrospective dataset. We compared prestroke mRS with Charlson comorbidity index (CCI) and the Rockwood frailty index. Rank correlation coefficient or Fisher exact test were used as appropriate.

Results—
Paired interviewers assessed 74 stroke survivors. Median standard mRS was 4 (interquartile range [IQR], 2–4), median prestroke mRS was 1 (IQR, 0–3; range, 0–4). Reliability for standard mRS interview was 56% agreement, kw=0.55 (95% CI, 0.39–0.71). Reliability for prestroke mRS was 70%, kw=0.70 (95% CI, 0.53–0.87). The retrospective dataset described 231 subjects. In this data set, Spearman Rho for prestroke mRS and frailty index was J. 0.82 (95% CI, 0.78–0.86); CCI 0.50 (95% CI, 0.40–0.59); patient age 0.45 (95% CI, 0.34–0.54); medication count 0.28 (95% CI, 0.15–0.40). There was no association between need for carers and prestroke mRS (p=0.10).

Conclusions—
Interobserver reliability of prestroke mRS is limited but comparable with standard mRS. Poor correlation of prestroke mRS with certain markers of function suggests limited validity. Our data would suggest that relying on mRS alone may be a suboptimal measure of prestroke function and could potentially bias trial samples.
Prevalence of Poststroke Cognitive Impairment
Authors: Douiri Abdel , Rudd Anthony G. , Wolfe Charles D.A. 
Published: November 2012

Background and Purpose—
Stroke is a common long-term condition with an increasing incidence as the population ages. This study evaluates temporal changes in the prevalence of cognitive impairment after first-ever stroke stratified by sociodemography, vascular risk factors, and stroke subtypes, up to 15 years after stroke.

Methods—
Data were collected between 1995 and 2010 (n=4212) from the community-based South London Stroke Register covering an inner-city multiethnic population of 271 817 inhabitants. Patients were assessed for cognitive function using Abbreviated Mental Test or Mini-Mental State Examination at the onset, 3 months, and annually thereafter. All estimates were age adjusted to the European standard.

Results—
The overall prevalence of cognitive impairment 3 months after stroke and at annual follow-up remained relatively unchanged at 22% (24% [95% CI, 21.2–27.8] at 3 months; 22% [17.4–26.8] at 5 years to 21% [3.6–63.8] at 14 years). In multivariate analyses, the poststroke prevalence ratio of cognitive impairment increased with older age (2% [1–3] for each year of age), ethnicity (2.2 [1.65–2.89]-fold higher among black group) and socioeconomic status (42% [8–86] increased among manual workers). A significant, progressive trend of cognitive impairment was observed among patients with small vessel occlusion and lacunar infarction (average annual percentage change: 10% [7.9–12.8] and 2% [0.3–2.7], respectively, up to 5 years after stroke).

Conclusions—
The prevalence of cognitive impairment after stroke remains persistently high over time, with variations being predominantly explained by sociodemographic characteristics. Given population growth and ageing demographics, effective preventive strategies and poststroke surveillance are needed to manage survivors with cognitive impairment.
Secondary Signal Change and an Apparent Diffusion Coefficient Decrease of the Substantia Nigra After Striatal Infarction
Authors: Nakajima Makoto , Inatomi Yuichiro , Okigawa Takashi , Yonehara Toshiro , Hirano Teruyuki 
Published: November 2012

Background and Purpose—
Diffusion-weighted imaging can depict secondary signal change of the substantia nigra of patients with ipsilateral striatal infarction via a decrease in the apparent diffusion coefficient (ADC). Clinical predictors of this phenomenon remain unclear.

Methods—
We assessed 98 stroke patients with acute ischemic lesions in the hemilateral basal ganglia, external capsule, or internal capsule. The ADC values of the bilateral substantia nigra obtained from a follow-up MRI, various clinical factors, and patients’ outcome were analyzed. Nineteen patients who underwent a follow-up MRI within 3 days were excluded from analysis because none of them demonstrated a significant ADC change of substantia nigra.

Results—
Of 79 patients, 21 (26.6%) revealed a decreased ADC in the substantia nigra. Ischemic lesions in the globus pallidus (odds ratio 12.90) and the presence of emboligenic diseases (odds ratio 6.95) were independent predictors for an ADC decrease in the substantia nigra. The clinical outcome 3 months after stroke onset was not different between patients with an ADC decrease and patients without.

Conclusions—
A reduction of ADC in the substantia nigra after acute striatal infarction was more frequently observed when the globus pallidus was affected or when the patient had emboligenic diseases, however, did not necessarily relate to the patient’s clinical outcome.
Examining Mechanisms of Variability within the Pacific Storm Track: Upstream Seeding and Jet-Core Strength
Authors: Penny Sandra M. , Battisti David S. , Roe Gerard H. 
Published: November 2012

Abstract
This paper examines how variations in two mechanisms, upstream seeding and jet-core strength, relate to storminess within the cold season (October–April) Pacific storm track. It is found that about 17% of observed storminess covaries with the strength of the upstream wave source, and the relationship is robust throughout the cold season and for both the Pacific and Atlantic basins. Further analyses of the intraseasonal variability in the strength and structure of the wintertime [December–February (DJF)] Pacific jet stream draw upon both Eulerian-variance and feature-tracking statistics to diagnose why winter months with a strong-core jet stream have weaker storminess than those with a weak-core jet stream. Contrary to expectations, it is shown that the basic spatial patterns actually conform to a simple linear picture: regions with a weaker jet have weaker storminess. The overall decrease in storminess is most strongly linked to the weaker amplitude of individual storms in strong-core months. Previously proposed mechanisms are evaluated in the context of these new results. Last, this analysis provides further evidence that the midwinter suppression in storminess over the North Pacific Ocean is primarily due to a notable lack of storminess upstream of the Pacific storm track in the heart of winter.
Behaviour change potential for energy saving in non-domestic buildings: Development and pilot-testing of a benchmarking tool
Authors: Ucci M , Domenech T , Ball A , Whitley T , Wright C , Mason D , Corrin K , Milligan A , Rogers A , Fitzsimons D , Gaggero C , Westaway A 
Published: November 2012

Due to recent studies and government policies, designers and facilities managers are becoming increasingly aware of the role of occupant behaviour in energy conservation in buildings. While the use of post-occupancy surveys and benchmark tools is widespread in the built environment, there is limited research on assessing environmental and energy saving behaviours – particularly in non-domestic buildings. This article focuses on the development and pilot-testing of a novel benchmarking tool for the assessment of behaviour change potential for energy saving in the workplace, with findings from an industrial case study comprising a manufacturing and office environment. Beyond the findings of the case study, the article aims to provide a methodological framework for an easy-to-use benchmarking tool of user-behaviour within the context of energy saving in factories and offices. Practical Implications: This article discusses the development and pilot-testing of a novel questionnaire-based benchmarking tool for the assessment of behaviour change potential for energy saving in office and industrial settings. Its application to a case-study from the manufacturing sector demonstrates that the tool is easy to use, and it provides valuable insights on areas for improvement in energy use within non-domestic buildings, with a focus on user behaviour and management approaches. The tool can be used in applied research, for example in intervention studies for comparison within the same organisation (before and after), and/or for benchmarking against the performance of similar organisations.
The Impact of Point-of-Care A1C Testing on Provider Compliance and A1C Levels in a Primary Setting
Authors: Egbunike Veronica , Gerard Sally 
Published: November 2012

Purpose The purpose of the research was to investigate the impact of point-of-care (POC) A1C testing among patients with type 2 diabetes in a primary care setting. Methods This study used a pretest-posttest design with data from patient charts matched for age, sex, race, body mass index, insurance status, and the number of comorbidities. A random sample of charts of patients with type 2 diabetes in the primary care setting was reviewed 6 months and 3 months pre- and post-implementation of the POC A1C testing. Results There was a significant difference in the number of A1Cs documented in the medical record pre- versus post-implementation of POC A1C. There was also a significant difference in A1C values pre- versus post-implementation. There was also a difference in the treatment changes pre- versus post-implementation of POC A1C. Conclusion Point-of-care A1C testing represents an opportunity for improved care of people with diabetes. The significance of this improvement will become more critical as the number of people with type 2 diabetes continues to increase.
Management of patients with spontaneous intracranial hypotension causing altered level of consciousness: Report of two cases and review of literature
Authors: Ghavanini Amer A , Scott Courtney A , Chan David K , Tang-Wai David F 
Published: November 2012

Background Decreased level of consciousness is a rare neurological manifestation of spontaneous intracranial hypotension (SIH), which typically presents with orthostatic headache. The optimal management of this uncommon presentation remains uncertain. Methods We analyzed the presentation, management and outcome of two patients in our institution and reviewed 22 patients reported in the literature with SIH and decreased level of consciousness, defined as any decrease in the patient’s Glasgow Coma Scale score. Results There were 20 male and four female patients (M:F ratio of 5:1) with an average age of 52 years (range 37 to 68 years). There was a variable time interval of up to many months between the initial presentation of SIH and changes in the level of consciousness. An epidural autologous blood patch was eventually successful in 79% of the patients, although up to three trials were necessary in seven of these patients. Intrathecal saline infusion used as a temporizing measure resulted in excellent response within hours in five out of six patients who received this treatment. Drainage of the subdural collection either did not result in any sustained improvement or resulted in clinical deterioration in 12 out of 12 patients who received this treatment. Conclusions In the absence of a clinical trial because of the rarity of this entity, the treatment of SIH complicated by decreased level of consciousness remained controversial in the past. However, current collective experience supports early treatment of patients with SIH and decreased level of consciousness with one or more epidural blood patches. Fibrin glue and surgical duroplasty are the next steps in the management of patients in whom epidural blood patches fail. Drainage of the subdural collections may be detrimental.