bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indirect laminate veneer: a conservative novel approach
Authors: Prajapati Paranjay , Sethuraman Rajesh , Naveen Y G , Patel Jayanti R 
Published: August 2013

Various treatment options and materials are available for restoration of an endodontically treated tooth. Laminate veneer is conservative treatment usually employed for aesthetic correction or improvement. The indirect composite is available in a wide range of shades and specific characterisation is easily performed chair side in the operatory area, which makes it a quick procedure and time saving for both the patient and the dentist. The physical properties and optical properties are good enough to use it as indirect restorative material, so in this particular case it was the material of choice for fabrication of laminate veneer on anterior tooth. In this case, the endodontically treated tooth with a fractured incisal edge was restored with indirect composite material.
Determinants of death anxiety in patients with advanced cancer
Authors: Neel Caroline , Lo Chris , Rydall Anne , Hales Sarah , Rodin Gary 
Published: August 2013

ObjectiveTo examine the presence of death anxiety in patients with advanced cancer and to identify the psychosocial and disease-related factors associated with it.DesignCross-sectional analysis of baseline data from a phase 2 pilot intervention trial.SettingPrincess Margaret Cancer Centre, University Health Network, Toronto, Canada.Participants60 adult outpatients with metastatic breast, endocrine, gastrointestinal, gynaecological, genitourinary and lung cancer.Main outcome measureDeath anxiety, as measured by the Death and Dying Distress Scale (DADDS).ResultsThirty-two per cent of the sample reported death anxiety of at least moderate severity. The most distressing concern involved fears about the impact of one's death on others, and the least distressing concerns were related to dying alone or suddenly. According to regression analyses, death anxiety was negatively associated with self-esteem, b=−1.73, CI0.95(−2.57 to −0.90) and positively associated with physical symptom burden, b=1.38, CI0.95(0.44 to 2.31), having children under 18 years of age in the family, b=13.3, CI0.95(2.15 to 24.5), and age, b=0.40, CI0.95(0.0023 to 0.79). The physical symptoms most strongly associated with death anxiety were changes in physical appearance, b=18.8, CI0.95(8.21 to29.5), and pain, b=10.1, CI0.95(0.73 to 19.5).ConclusionsThe findings suggest that death anxiety in patients with advanced cancer is common and determined by the interaction of individual factors, family circumstances and physical suffering. Multidimensional interventions that take into account these and other factors may be most likely to be effective to alleviate this death-related distress.
Genomic profiling of plasma cell disorders in a clinical setting: integration of microarray and FISH, after CD138 selection of bone marrow
Authors: Berry Nadine Kaye , Bain Nicole L , Enjeti Anoop K , Rowlings Philip 
Published: August 2013

AimTo evaluate the role of whole genome comparative genomic hybridisation microarray (array-CGH) in detecting genomic imbalances as compared to conventional karyotype (GTG-analysis) or myeloma specific fluorescence in situ hybridisation (FISH) panel in a diagnostic setting for plasma cell dyscrasia (PCD).MethodsA myeloma-specific interphase FISH (i-FISH) panel was carried out on CD138 PC-enriched bone marrow (BM) from 20 patients having BM biopsies for evaluation of PCD. Whole genome array-CGH was performed on reference (control) and neoplastic (test patient) genomic DNA extracted from CD138 PC-enriched BM and analysed.ResultsComparison of techniques demonstrated a much higher detection rate of genomic imbalances using array-CGH. Genomic imbalances were detected in 1, 19 and 20 patients using GTG-analysis, i-FISH and array-CGH, respectively. Genomic rearrangements were detected in one patient using GTG-analysis and seven patients using i-FISH, while none were detected using array-CGH. I-FISH was the most sensitive method for detecting gene rearrangements and GTG-analysis was the least sensitive method overall. All copy number aberrations observed in GTG-analysis were detected using array-CGH and i-FISH.ConclusionsWe show that array-CGH performed on CD138-enriched PCs significantly improves the detection of clinically relevant and possibly novel genomic abnormalities in PCD, and thus could be considered as a standard diagnostic technique in combination with IGH rearrangement i-FISH.
Histological evaluation of preoperative mediastinoscopy lymph node biopsies in non-small cell lung cancer
Authors: Dhaliwal Catharine Ann , Andrews Timothy D , Walker William S , Wallace William A 
Published: August 2013

IntroductionDespite the advent of PET scanning and endoscopic minimally invasive methods of sampling mediastinal lymph nodes, surgical assessment, particularly by mediastinoscopy, remains an important tool for staging non-small cell lung cancer.MethodsWe carried out a retrospective review of mediastinoscopic lymph node biopsies taken at The Royal Infirmary of Edinburgh between 1996 and 2006 and performed additional histological investigations on select cases.ResultsIn total, 89/802 (11%) patients had a negative mediastinoscopy but final resection stage of N2/N3. Within this group, 41/89 (46%) patients had positive resection lymph nodes in stations potentially accessible to biopsy at mediastinoscopy. Of these, 30 (34%) patients had had the metastatic station sampled at mediastinoscopy. Further histopathological examination (multiple levels and pancytokeratin immunohistochemistry) of these original biopsies detected micrometastases in two cases, one of which, in retrospect, had been missed on the original section at the time of reporting. Isolated tumour cells were detected by immunohistochemistry in another two cases.ConclusionsRoutine examination of additional levels and immunohistochemical staining of mediastinal lymph nodes biopsies is not required and would not improve the overall negative predictive value of the procedure.
Systematic differences among never, occasional and moderate alcohol users in southern China, and its use in alcohol research: a cross-sectional study
Authors: Yeung S L Au , Jiang C Q , Zhang W S , Lam T H , Cheng K K , Leung G M , Schooling C M 
Published: August 2013

BackgroundWestern observational studies show moderate alcohol use, compared with never use, positively associated with health. Moderate users differ systematically from others, making these observations vulnerable to confounding. Observations from other contexts may help distinguish whether these associations are confounded. To assess whether southern Chinese would provide a more suitable setting to examine the association of moderate alcohol use with health, we compared never alcohol users with moderate alcohol users and occasional users in this setting.MethodsWe used age-adjusted multinomial regression to assess sex-stratified associations of alcohol use (never, occasional (<1 occasion/week), moderate (≤140 g ethanol/week for women and ≤210 g for men)) with health attributes and indicators in the Guangzhou Biobank Cohort Study (2003–2008) (n=26 361).ResultsAmong men, moderate alcohol users, when compared with never users, had slightly lower socioeconomic position and unhealthier lifestyle. Conversely, occasional alcohol users, when compared with never users, had higher socioeconomic position and healthier lifestyle. Among women, when compared with never users, both occasional and moderate users had higher socioeconomic position and healthier lifestyle. However, all alcohol users for both sexes, when compared with never users, were more likely to be ever smokers and to be exposed to secondhand smoke.ConclusionsObservations in alcohol epidemiology may be affected by confounding due to contextually specific systematic differences. Results from a particular setting should not be interpreted as causal unless they are verified in different populations and, preferably, in non-observational studies.
Characterization and Clinical Relevance of ALDHbright Populations in Prostate Cancer
Authors: Le Magnen Clémentine , Bubendorf Lukas , Rentsch Cyrill A. , Mengus Chantal , Gsponer Joel , Zellweger Tobias , Rieken Malte , Thalmann George N. , Cecchini Marco G. , Germann Markus , Bachmann Alexander , Wyler Stephen , Heberer Michael , Spagnoli Giulio C. 
Published: August 2013

Abstract
Purpose: High aldehyde dehydrogenase (ALDH) has been suggested to selectively mark cells with high tumorigenic potential in established prostate cancer cell lines. However, the existence of cells with high ALDH activity (ALDHbright) in primary prostate cancer specimens has not been shown so far. We investigated the presence, phenotype, and clinical significance of ALDHbright populations in clinical prostate cancer specimens.
Experimental Design: We used ALDEFLUOR technology and fluorescence-activated cell-sorting (FACS) staining to identify and characterize ALDHbright populations in cells freshly isolated from clinical prostate cancer specimens. Expression of genes encoding ALDH-specific isoforms was evaluated by quantitative real-time PCR in normal prostate, benign prostatic hyperplasia (BPH), and prostate cancer tissues. ALDH1A1-specific expression and prognostic significance were assessed by staining two tissue microarrays that included more than 500 samples of BPH, prostatic intraepithelial neoplasia (PIN), and multistage prostate cancer.
Results: ALDHbright cells were detectable in freshly excised prostate cancer specimens (n = 39) and were mainly included within the EpCAM(+) and Trop2(+) cell populations. Although several ALDH isoforms were expressed to high extents in prostate cancer, only ALDH1A1 gene expression significantly correlated with ALDH activity (P &lt; 0.01) and was increased in cancers with high Gleason scores (P = 0.03). Most importantly, ALDH1A1 protein was expressed significantly more frequently and at higher levels in advanced-stage than in low-stage prostate cancer and BPH. Notably, ALDH1A1 positivity was associated with poor survival (P = 0.02) in hormone-naïve patients.
Conclusions: Our data indicate that ALDH contributes to the identification of subsets of prostate cancer cells of potentially high clinical relevance. Clin Cancer Res; 19(19); 5361–71. ©2013 AACR.
Emergence of Polyclonal FLT3 Tyrosine Kinase Domain Mutations during Sequential Therapy with Sorafenib and Sunitinib in FLT3-ITD–Positive Acute Myeloid Leukemia
Authors: Baker Sharyn D. , Zimmerman Eric I. , Wang Yong-Dong , Orwick Shelley , Zatechka Douglas S. , Buaboonnam Jassada , Neale Geoffrey A. , Olsen Scott R. , Enemark Eric J. , Shurtleff Sheila , Rubnitz Jeffrey E. , Mullighan Charles G. , Inaba Hiroto 
Published: August 2013

Abstract
Purpose: To evaluate the clinical activity of sequential therapy with sorafenib and sunitinib in FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD)-positive acute myelogenous leukemia (AML) and monitor the emergence of secondary FLT3 tyrosine kinase domain (TKD) mutations during treatment.
Experimental Design: Six children with relapsed/refractory AML were treated with sorafenib in combination with clofarabine and cytarabine, followed by single-agent sorafenib if not a candidate for transplantation. Sunitinib was initiated after sorafenib relapse. Bone marrow samples were obtained for assessment of FLT3 TKD mutations by deep amplicon sequencing. The phase of secondary mutations with ITD alleles was assessed by cloning and sequencing of FLT3 exons 14 through 20. Identified mutations were modeled in Ba/F3 cells, and the effect of kinase inhibitors on FLT3 signaling and cell viability was assessed.
Results: Four patients achieved complete remission, but 3 receiving maintenance therapy with sorafenib relapsed after 14 to 37 weeks. Sunitinib reduced circulating blasts in two patients and marrow blasts in one. Two patients did not respond to sorafenib combination therapy or sunitinib. FLT3 mutations at residues D835 and F691 were observed in sorafenib resistance samples on both ITD-positive and -negative alleles. Deep sequencing revealed low-level mutations and their evolution during sorafenib treatment. Sunitinib suppressed leukemic clones with D835H and F691L mutations, but not D835Y. Cells expressing sorafenib-resistant FLT3 mutations were sensitive to sunitinib in vitro.
Conclusions: Sunitinib has activity in patients that are resistant to sorafenib and harbor secondary FLT3 TKD mutations. The use of sensitive methods to monitor FLT3 mutations during therapy may allow individualized treatment with the currently available kinase inhibitors. Clin Cancer Res; 19(20); 5758–68. ©2013 AACR.
Relationship Among Circulating Inflammatory Proteins, Platelet Gene Expression, and Cardiovascular Risk
Authors: McManus David D. , Beaulieu Lea M. , Mick Eric , Tanriverdi Kahraman , Larson Martin G. , Keaney John F. , Benjamin Emelia J. , Freedman Jane E. 
Published: August 2013

Objective—
Cardiovascular disease is a complex disorder influenced by interactions of genetic variants with environmental factors. However, there is no information from large community-based studies examining the relationship of circulating cell–specific RNA to inflammatory proteins. In light of the associations among inflammatory biomarkers, obesity, platelet function, and cardiovascular disease, we sought to examine the relationships of C-reactive protein (CRP) and interleukin-6 (IL-6) to the expression of key inflammatory transcripts in platelets.

Approach and Results—

We quantified circulating levels of CRP and IL-6 in 1625 participants of the Framingham Heart Study (FHS) Offspring cohort examination 8 (mean age, 66.6±6.6 years; 46% men). We measured the expression of 15 relevant genes by high-throughput quantitative reverse transcriptase polymerase chain reaction from platelet-derived RNA and used multivariable regression to relate serum concentrations of CRP and IL-6 with gene expression. Levels of CRP and IL-6 were associated with 10 of the 15 platelet-derived inflammatory transcripts,
ALOX5
,
CRP
,
IFIT1
,
IL6
,
PTGER2
,
S100A9
,
SELENBP1
,
TLR2
,
TLR4
, and
TNFRSF1B
(
P
<0.001). Associations between platelet mRNA expression with CRP and IL-6 persisted after multivariable adjustment for potentially confounding factors. Six genes positively associated with CRP or IL-6 in the FHS sample were also upregulated in megakaryocytes in response to CRP or IL-6 exposure.

Conclusions—
Our data highlight the strong connection between the circulating inflammatory biomarkers CRP and IL-6 and platelet gene expression, adjusting for cardiovascular disease risk factors. Our results also suggest that body weight may directly influence these associations.
The Role of Shear-Induced Transforming Growth Factor-β Signaling in the Endothelium
Authors: Walshe Tony E. , dela Paz Nathaniel G. , D’Amore Patricia A. 
Published: August 2013

Objective—
Vascular endothelial cells (ECs) are continuously exposed to blood flow that contributes to the maintenance of vessel structure and function; however, the effect of hemodynamic forces on transforming growth factor-β (TGF-β) signaling in the endothelium is poorly described. We examined the potential role of TGF-β signaling in mediating the protective effects of shear stress on ECs.

Approach and Results—
Human umbilical vein ECs (HUVECs) exposed to shear stress were compared with cells grown under static conditions. Signaling through the TGF-β receptor ALK5 was inhibited with SB525334. Cells were examined for morphological changes and harvested for analysis by real-time polymerase chain reaction, Western blot analysis, apoptosis, proliferation, and immunocytochemistry. Shear stress resulted in ALK5-dependent alignment of HUVECs as well as attenuation of apoptosis and proliferation compared with static controls. Shear stress led to an ALK5-dependent increase in TGF-β3 and Krüppel-like factor 2, phosphorylation of endothelial NO synthase, and NO release. Addition of the NO donor S-nitroso-N-acetylpenicillamine rescued the cells from apoptosis attributable to ALK5 inhibition under shear stress. Knockdown of TGF-β3, but not TGF-β1, disrupted the HUVEC monolayer and prevented the induction of Krüppel-like factor 2 by shear.

Conclusions—
Shear stress of HUVECs induces TGF-β3 signaling and subsequent activation of Krüppel-like factor 2 and NO, and represents a novel role for TGF-β3 in the maintenance of HUVEC homeostasis in a hemodynamic environment.
β
1
-Adrenergic Receptor and Sphingosine-1-Phosphate Receptor 1 (S1PR1) Reciprocal Downregulation Influences Cardiac Hypertrophic Response and Progression to Heart Failure
Authors: Cannavo Alessandro , Rengo Giuseppe , Liccardo Daniela , Pagano Gennaro , Zincarelli Carmela , De Angelis Maria Carmen , Puglia Roberto , Di Pietro Elisa , Rabinowitz Joseph E. , Barone Maria Vittoria , Cirillo Plinio , Trimarco Bruno , Palmer Timothy M. , Ferrara Nicola , Koch Walter J. , Leosco Dario , Rapacciuolo Antonio 
Published: August 2013

Background—

The sphingosine-1-phosphate receptor 1 (S1PR1) and β
1
-adrenergic receptor (β1AR) are G-protein–coupled receptors expressed in the heart. These 2 receptors have opposing actions on adenylyl cyclase because of differential G-protein coupling. Importantly, both of these receptors can be regulated by the actions of G-protein–coupled receptor kinase-2, which triggers desensitization and downregulation processes. Although classic signaling paradigms suggest that simultaneous activation of β1ARs and S1PR1s in a myocyte would simply result in opposing action on cAMP production, in this report we have uncovered a direct interaction between these 2 receptors, with regulatory involvement of G-protein–coupled receptor kinase-2.

Methods and Results—
In HEK (human embryonic kidney) 293 cells overexpressing both β1AR and S1PR1, we demonstrated that β1AR downregulation can occur after stimulation with sphingosine-1-phosphate (an S1PR1 agonist), whereas S1PR1 downregulation can be triggered by isoproterenol (a β-adrenergic receptor agonist) treatment. This cross talk between these 2 distinct G-protein–coupled receptors appears to have physiological significance, because they interact and show reciprocal regulation in mouse hearts undergoing chronic β-adrenergic receptor stimulation and in a rat model of postischemic heart failure.

Conclusions—
We demonstrate that restoration of cardiac plasma membrane levels of S1PR1 produces beneficial effects that counterbalance the deleterious β1AR overstimulation in heart failure.
Coronary Artery Bypass Graft Surgery Using the Radial Artery as a Secondary Conduit Improves Patient Survival
Authors: Lin John , Cheng Wen , Czer Lawrence S. , De Robertis Michele A. , Mirocha James , Ruzza Andrea , Kass Robert M. , Khoynezhad Ali , Ramzy Danny , Esmailian Fardad , Trento Alfredo 
Published: August 2013

Background

The clinical benefits of the left internal thoracic artery–to–left anterior descending coronary artery graft are well established in coronary artery bypass graft surgery (
CABG
). However, limited data are available regarding the long‐term outcome of the radial artery (
RA
) as a secondary conduit over the established standard of the saphenous venous graft.

Methods and Results

We compared the 12‐year survival outcome in a set of propensity‐matched
CABG
patients who received either the
RA
or the saphenous vein as a secondary conduit. A multivariable logistic regression that included 18 baseline characteristics was used to define the propensity of receiving an RA graft. The propensity model resulted in 260 matched pairs who underwent first‐time isolated
CABG
from 1996 to 2001 with similar preoperative characteristics (C statistic=0.86). The cumulative 12‐year survival estimated by use of the
K
aplan–
M
eier method was higher for the
RA
graft patients (hazard ratio 0.76;
P
=0.03). This survival advantage was especially significant in diabetics (
P
=0.005), in women (
P
=0.02), and in the elderly (
P
=0.04.) The protective effect appeared beginning at year 5 post surgical intervention.

Conclusion

The RA as a secondary conduit provided superior long‐term survival after
CABG
, especially in diabetic patients, women, and the elderly. This effect was most pronounced >5 years after surgery.
Ultra-Early Intravenous Stroke Thrombolysis
Authors: Strbian Daniel , Ringleb Peter , Michel Patrik , Breuer Lorenz , Ollikainen Jyrki , Murao Kei , Seiffge David J. , Jung Simon , Obach Victor , Weder Bruno , Eskandari Ashraf , Gensicke Henrik , Chamorro Angel , Mattle Heinrich P. , Engelter Stefan , Leys Didier , Numminen Heikki , Köhrmann Martin , Hacke Werner , Tatlisumak Turgut 
Published: August 2013

Background and Purpose—
We previously reported increased benefit and reduced mortality after ultra-early stroke thrombolysis in a single center. We now explored in a large multicenter cohort whether extra benefit of treatment within 90 minutes from symptom onset is uniform across predefined stroke severity subgroups, as compared with later thrombolysis.

Methods—
Prospectively collected data of consecutive ischemic stroke patients who received IV thrombolysis in 10 European stroke centers were merged. Logistic regression tested association between treatment delays, as well as excellent 3-month outcome (modified Rankin scale, 0–1), and mortality. The association was tested separately in tertiles of baseline National Institutes of Health Stroke Scale.

Results—

In the whole cohort (n=6856), shorter onset-to-treatment time as a continuous variable was significantly associated with excellent outcome (
P
<0.001). Every fifth patient had onset-to-treatment time≤90 minutes, and these patients had lower frequency of intracranial hemorrhage. After adjusting for age, sex, admission glucose level, and year of treatment, onset-to-treatment time≤90 minutes was associated with excellent outcome in patients with National Institutes of Health Stroke Scale 7 to 12 (odds ratio, 1.37; 95% confidence interval, 1.11–1.70;
P
=0.004), but not in patients with baseline National Institutes of Health Stroke Scale>12 (odds ratio, 1.00; 95% confidence interval, 0.76–1.32;
P
=0.99) and baseline National Institutes of Health Stroke Scale 0 to 6 (odds ratio, 1.04; 95% confidence interval, 0.78–1.39;
P
=0.80). In the latter, however, an independent association (odds ratio, 1.51; 95% confidence interval, 1.14–2.01;
P
<0.01) was found when considering modified Rankin scale 0 as outcome (to overcome the possible ceiling effect from spontaneous better prognosis of patients with mild symptoms). Ultra-early treatment was not associated with mortality.

Conclusions—
IV thrombolysis within 90 minutes is, compared with later thrombolysis, strongly and independently associated with excellent outcome in patients with moderate and mild stroke severity.