bluuebunny/crossref_metadata_2025_split huggingface dataset:
The social difficulties of cancer patients of South Asian Indian and Pakistani origin: a cross-sectional questionnaire and interview study
Authors: Dharni Nimarta , Hanif Naheed , Bradley Chris , Velikova Galina , Stark Dan , Wright Penny 
Published: August 2011

ObjectivesTo evaluate, in a sample of patients of South Asian (SA) origin, the acceptability of introducing assessment of social difficulties in everyday practice, examine the range and severity of reported social difficulties and inquire about their management.DesignA cross-sectional study in which participants completed the Social Difficulties Inventory (SDI-21) in English, Urdu, Punjabi or Hindi followed by a semi-structured interview.ParticipantsParticipants comprised 26 men and 29 women of SA origin ranging between 18 and 80 years of age. The commonest primary languages were Urdu (n=17) and Punjabi (n=17). English was the primary language of three participants. A range of cancer diagnoses and stages of disease were represented.SettingPatients were recruited from outpatient haematology and oncology clinics in Bradford, Airedale and Leeds hospitals.ResultsSA cancer patients welcomed routine assessment of social difficulties as part of their cancer care. They reported higher levels of social distress than found in earlier studies of white British patients. The majority managed their social difficulties themselves with little discussion with the clinical team, although, at times, this would have been welcomed. SA patients lacked information and were unaware of the support available to them, especially when language was a barrier.ConclusionsIntroduction of routine assessment of social difficulties into cancer care will require not only relevant and accessible screening tools such as the SDI-21, but also staff trained to respond to the difficulties disclosed, with knowledge of information sources and supportive care services when patients request these.
Plasma dioxin levels and cause-specific mortality in an occupational cohort of workers exposed to chlorophenoxy herbicides, chlorophenols and contaminants
Authors: Boers Daisy , Portengen Lützen , Turner Wayman E , Bueno-de-Mesquita H Bas , Heederik Dick , Vermeulen Roel 
Published: August 2011

BackgroundWe recently reported increased risks for all cancers and urinary cancers in workers exposed to chlorophenoxy herbicides using data from the Dutch herbicide cohort study. These risks could not be linked to the qualitative exposure proxies available. Here, we re-investigate exposure–response relationships using a (semi)quantitative measure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure.MethodsPlasma TCDD levels of 187 workers were used to develop a predictive model for TCDD exposure. Cox proportional hazards model was used to investigate associations between time-varying TCDD exposure and cause-specific mortality. Sensitivity analyses were performed to assess the impact of key assumptions in exposure assessment.ResultsPredicted TCDD levels were associated with mortality from all causes (HR 1.08; 95% CI 1.03 to 1.13), ischaemic heart disease (IHD; HR 1.19; 95% CI 1.08 to 1.32) and non-Hodgkin's lymphoma (NHL; HR 1.36; 95% CI 1.06 to 1.74). No relationships were found between TCDD exposure and mortality from all cancers, respiratory or urinary cancers, which were previously linked to qualitative proxies of TCDD exposure in this cohort. Sensitivity analyses showed that results were relatively robust to slight changes in exposure estimation.ConclusionsModelled TCDD exposure does not explain the previously reported increased risks for cancer mortality in this cohort except for a possible association with NHL. A small increase in ischaemic heart disease was observed, however we cannot exclude that this finding was due to residual confounding. Although risk estimates for some of the rarer outcomes were still rather imprecise, we do not expect more precise estimates from longer follow-up of this cohort due to the long time-span since last exposure to TCDD.
Long-term occupational outcomes of endotoxin exposure and the effect of exposure cessation
Authors: Skogstad Marit , Sikkeland Liv Ingunn Bjoner , Øvstebø Reidun , Haug Kari Bente Foss , Heldal Kari Kulvik , Skare Øivind , Kongerud Johny , Kierulf Peter , Eduard Wijnand 
Published: August 2011

ObjectiveTo study the possible respiratory and haematological effects of endotoxin exposure to bacterial single-cell protein (BSCP) in workers during a follow-up period of 5 years including 4 years of exposure and 1 year without exposure.MethodsThe study included 28 workers examined in 2002–2005 and 1 year after exposure termination in 2007. The arithmetic mean endotoxin exposure was 5800–11 000 EU/m3among the high exposure group and 390 EU/m3in the low exposure group. Assessment of lung function included spirometry and gas diffusion in 2003, 2004 and 2007. Rhinometry was performed in 2004 and 2007. Blood analysis included leukocyte cell count and measurement of the acute phase proteins: C-reactive protein, interleukin-6, eosinophilic cationic protein, macrophage inflammatory protein-1α, monocyte chemoattractant protein-1, chemoattractant protein RANTES, platelet-derived growth factor BB, fibrinogen and D-dimer.ResultsIn the low exposure group, but not in the high exposure group, there were significant improvements in both forced vital capacity (FVC) (290 ml) and forced expiratory volume in 1 s (FEV1) (180–210 ml) (p=0.004–0.03) 1 year after the end of exposure. The number of leukocytes and eosinophilic cationic protein and D-dimer levels increased significantly with increasing endotoxin exposures and decreased significantly 1 year after exposure termination. Changes in acute phase proteins suggested exposure-related tolerance.ConclusionsAn inflammatory tendency during an exposure period of 4 years seems to reverse 1 year after cessation of exposure to endotoxins from a single species. Lung function improved significantly among workers exposed to low levels of endotoxin but not among the highly exposed workers.
Mitochondrial and cytosolic calcium in rat hearts under high-K+ cardioplegia and pyruvate: mechano-energetic performance
Authors: Consolini A.E. , Ragone M.I. , Bonazzola P. 
Published: August 2011

High-K+-cardioplegia (CPG) and pyruvate (Pyr) are used as cardioprotective agents. Considering that mitochondria play a critical role in cardiac dysfunction, we investigated the effect of CPG on mitochondrial Ca2+ uptake and sarcorreticular (SR) calcium handling. Cytosolic and mitochondrial Ca2+, as well as mitochondrial membrane potential (ΔΨm) were assessed in rat cardiomyocytes by confocal microscopy. Mechano-calorimetrical correlation was studied in perfused hearts. CPG did not modify JC-1 (ΔΨm), but transiently increased, by up to 1.8 times, the Fura-2 (intracellular Ca concentration, [Ca2+]i) and Rhod-2 (mitochondrial free Ca concentration [Ca2+]m) fluorescence of resting cells, with exponential decays. The addition of 5 µmol·L–1 thapsigargin (Tpg) increased the Rhod-2 fluorescence in a group of cells without any effect on the Fura-2 signal. In rat hearts perfused with CPG, 1 µmol·L–1 Tpg decreased resting heat rate (ΔHr: –0.44 ± 0.07 mW·g–1), while the addition of 5 µmol·L–1 KB-R7943 increased resting pressure (ΔrLVP by +5.26 ± 1.10 mm Hg; 1 mm Hg = 133.322 Pa). The addition of 10 mmol·L–1 Pyr to CPG increased Hr (+3.30 ± 0.24 mW·g–1) and ΔrLVP (+2.2 ± 0.4 mm Hg), which are effects potentiated by KB-R7943. The results suggest that under CPG, (i) there was an increase in [Ca2+]i and [Ca2+]m (without changing ΔΨm) that decayed by exothermic removal mechanisms; (ii) mitochondrial Ca2+ uptake contributed to the removal of cytosolic Ca2+, in a process that was potentiated by inhibition of sarco–endoplasmic reticulum Ca2+-ATPase (SERCA), and reduced by KB-R7943; (iii) under these conditions, SERCA represents the main energetic consumer; (iv) Pyr increased the energetic performance of hearts,mainly by inducing mitochondrial metabolism.
A Phase I Pharmacokinetic and Pharmacodynamic Study of Dalotuzumab (MK-0646), an Anti-Insulin-like Growth Factor-1 Receptor Monoclonal Antibody, in Patients with Advanced Solid Tumors
Authors: Atzori Francesco , Tabernero Josep , Cervantes Andrés , Prudkin Ludmila , Andreu Jordi , Rodríguez-Braun Edith , Domingo Amparo , Guijarro Jorge , Gamez Cristina , Rodon Jordi , Di Cosimo Serena , Brown Holly , Clark Jason , Hardwick James S. , Beckman Robert A. , Hanley William D. , Hsu Karl , Calvo Emiliano , Roselló Susana , Langdon Ronald B. , Baselga José 
Published: August 2011

Abstract
Purpose: Insulin-like growth factor-1 receptor (IGF-1R) mediates cellular processes in cancer and has been proposed as a therapeutic target. Dalotuzumab (MK-0646) is a humanized IgG1 monoclonal antibody that binds to IGF-1R preventing receptor activation. This study was designed to evaluate the safety and tolerability of dalotuzumab, determine the pharmacokinetic (PK) and pharmacodynamic (PD) profiles, and identify a recommended phase II dose.
Experimental Design: Patients with tumors expressing IGF-1R protein were allocated to dose-escalating cohorts of three or more patients each and received intravenous dalotuzumab weekly, every 2 or 3 weeks. Plasma was collected for PK analysis. Paired baseline and on-treatment skin and tumor biopsy samples were collected for PD analyses.
Results: Eighty patients with chemotherapy-refractory solid tumors were enrolled. One dose-limiting toxicity was noted, but a maximum-tolerated dose was not identified. Grade 1 to 3 hyperglycemia, responsive to metformin, occurred in 15 (19%) patients. At dose levels or more than 5 mg/kg, dalotuzumab mean terminal half-life was 95 hours or more, mean Cmin was more than 25 μg/mL, clearance was constant, and serum exposures were approximately dose proportional. Decreases in tumor IGF-1R, downstream receptor signaling, and Ki67 expression were observed. 18F-Fluorodeoxy-glucose positron emission tomography metabolic responses occurred in three patients. One patient with Ewing's sarcoma showed a mixed radiologic response. The recommended phase II doses were 10, 20, and 30 mg/kg for the weekly, every other week, and every third week schedules, respectively.
Conclusions: Dalotuzumab was generally well-tolerated, exhibited dose-proportional PK, inhibited IGF-1R pathway signaling and cell proliferation in treated tumors, and showed clinical activity. The low clearance rate and long terminal half-life support more extended dosing intervals. Clin Cancer Res; 17(19); 6304–12. ©2011 AACR.
Phase II Trial of Dasatinib in Patients with Metastatic Breast Cancer Using Real-Time Pharmacodynamic Tissue Biomarkers of Src Inhibition to Escalate Dosing
Authors: Herold Christina I. , Chadaram Vijaya , Peterson Bercedis L. , Marcom P. Kelly , Hopkins Judith , Kimmick Gretchen G. , Favaro Justin , Hamilton Erika , Welch Renee A. , Bacus Sarah , Blackwell Kimberly L. 
Published: August 2011

AbstractPurpose: A phase II study of dasatinib, an inhibitor of multiple oncogenic tyrosine kinases including Src, was conducted to evaluate 16-week progression-free rate and tolerability in patients with previously treated metastatic breast cancer (MBC). Real-time assessment of potential tissue biomarkers of Src inhibition was used to optimize dosing.Experimental Design: Eligibility criteria required that patients have measurable MBC, biopsiable tumor, and unlimited prior therapies. For the analysis of change in protein biomarkers of Src inhibition, focal adhesion kinase, paxillin, and p-Src, patients underwent metastatic biopsies at baseline and 4 weeks. Patients who tolerated the starting dose of dasatinib (50 or 70 mg orally twice daily) for the first 28-day cycle, and displayed suboptimal Src inhibition, were escalated to a higher dose (70 or 100 mg).Results: The trial was closed early with 31 patients because of a statistical boundary that required at least 4 (13%) patients without disease progression to continue accrual. These 31 patients had a median of 2 prior lines of chemotherapy for MBC. The most notable toxicity was pleural effusions in 16 patients (52%). Twenty patients had evaluable metastatic biopsies. None of the tumors showed the predefined optimal level of Src inhibition at week 4.Conclusions: Single-agent dasatinib did not exhibit significant antitumor activity in patients with heavily pretreated MBC. There were no clinically meaningful decreases before and after dasatinib exposure between exploratory tissue biomarkers of Src inhibition which may be attributable to challenges in defining biomarker endpoints for multitargeted tyrosine kinase inhibitors. Clin Cancer Res; 17(18); 6061–70. ©2011 AACR.
Lung Cancer Risk Prediction to Select Smokers for Screening CT—a Model Based on the Italian COSMOS Trial
Authors: Maisonneuve Patrick , Bagnardi Vincenzo , Bellomi Massimo , Spaggiari Lorenzo , Pelosi Giuseppe , Rampinelli Cristiano , Bertolotti Raffaella , Rotmensz Nicole , Field John K. , DeCensi Andrea , Veronesi Giulia 
Published: August 2011

Abstract
Screening with low-dose helical computed tomography (CT) has been shown to significantly reduce lung cancer mortality but the optimal target population and time interval to subsequent screening are yet to be defined. We developed two models to stratify individual smokers according to risk of developing lung cancer. We first used the number of lung cancers detected at baseline screening CT in the 5,203 asymptomatic participants of the COSMOS trial to recalibrate the Bach model, which we propose using to select smokers for screening. Next, we incorporated lung nodule characteristics and presence of emphysema identified at baseline CT into the Bach model and proposed the resulting multivariable model to predict lung cancer risk in screened smokers after baseline CT. Age and smoking exposure were the main determinants of lung cancer risk. The recalibrated Bach model accurately predicted lung cancers detected during the first year of screening. Presence of nonsolid nodules (RR = 10.1, 95% CI = 5.57–18.5), nodule size more than 8 mm (RR = 9.89, 95% CI = 5.84–16.8), and emphysema (RR = 2.36, 95% CI = 1.59–3.49) at baseline CT were all significant predictors of subsequent lung cancers. Incorporation of these variables into the Bach model increased the predictive value of the multivariable model (c-index = 0.759, internal validation). The recalibrated Bach model seems suitable for selecting the higher risk population for recruitment for large-scale CT screening. The Bach model incorporating CT findings at baseline screening could help defining the time interval to subsequent screening in individual participants. Further studies are necessary to validate these models. Cancer Prev Res; 4(11); 1778–89. ©2011 AACR.
Functional Viability Profiles of Breast Cancer
Authors: Brough Rachel , Frankum Jessica R. , Sims David , Mackay Alan , Mendes-Pereira Ana M. , Bajrami Ilirjana , Costa-Cabral Sara , Rafiq Rumana , Ahmad Amar S. , Cerone Maria Antonietta , Natrajan Rachael , Sharpe Rachel , Shiu Kai-Keen , Wetterskog Daniel , Dedes Konstantine J. , Lambros Maryou B. , Rawjee Teeara , Linardopoulos Spiros , Reis-Filho Jorge S. , Turner Nicholas C. , Lord Christopher J. , Ashworth Alan 
Published: August 2011

Abstract
The design of targeted therapeutic strategies for cancer has largely been driven by the identification of tumor-specific genetic changes. However, the large number of genetic alterations present in tumor cells means that it is difficult to discriminate between genes that are critical for maintaining the disease state and those that are merely coincidental. Even when critical genes can be identified, directly targeting these is often challenging, meaning that alternative strategies such as exploiting synthetic lethality may be beneficial. To address these issues, we have carried out a functional genetic screen in &gt;30 commonly used models of breast cancer to identify genes critical to the growth of specific breast cancer subtypes. In particular, we describe potential new therapeutic targets for PTEN-mutated cancers and for estrogen receptor–positive breast cancers. We also show that large-scale functional profiling allows the classification of breast cancers into subgroups distinct from established subtypes.
Significance: Despite the wealth of molecular profiling data that describe breast tumors and breast tumor cell models, our understanding of the fundamental genetic dependencies in this disease is relatively poor. Using high-throughput RNA interference screening of a series of pharmacologically tractable genes, we have generated comprehensive functional viability profiles for a wide panel of commonly used breast tumor cell models. Analysis of these profiles identifies a series of novel genetic dependencies, including that of PTEN-null breast tumor cells upon mitotic checkpoint kinases, and provides a framework upon which additional dependencies and candidate therapeutic targets may be identified. Cancer Discovery; 1(3); 260–73. © 2011 AACR.
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Impact of Sirolimus-Eluting Stent Fracture on 4-Year Clinical Outcomes
Authors: Umeda Hisashi , Kawai Tomoko , Misumida Naoki , Ota Tomoyuki , Hayashi Kazutaka , Iwase Mitsunori , Izawa Hideo , Sugino Shigeo , Shimizu Takeshi , Takeichi Yasushi , Ishiki Ryoji , Inagaki Haruo , Ozaki Yukio , Murohara Toyoaki 
Published: August 2011

Background—
Although stent fracture (SF) after sirolimus-eluting stent (SES) implantation has been recognized as one of the predisposing factors of in-stent restenosis, it remains uncertain whether SF can increase the risk of major adverse cardiac events (MACE), especially beyond 1 year after SES implantation. The aim of this study was to assess the impact of SF relative to non-SF on 4-year clinical outcomes after treatment with SES of comparable unselected lesions.

Methods and Results—

A total of 874 lesions in 793 patients undergoing SES implantation and subsequent angiography 6 to 9 months after index procedure were analyzed. At 6- to 9-month angiographic follow-up, SF was identified in 70 of 874 lesions (8.0%). In-stent late loss was significantly higher in SF lesions versus non-SF lesions (0.42±0.59 mm versus 0.13±0.49 mm,
P
<0.001), resulting in a significantly higher in-stent restenosis rate (21.4% versus 4.1%,
P
<0.001). At 4 years, SF versus non-SF was associated with a significantly higher MACE rate (23.2% versus 12.6%,
P
=0.014), mainly driven by significantly higher target-lesion revascularization (18.8% versus 10.2%,
P
=0.029) rate. Adverse effects of SF on clinical outcomes occurred mostly within the first year (17.4% versus 6.6%,
P
=0.001), with similar MACE rate between 1 and 4 years (5.8% versus 5.9%,
P
=0.611). No significant differences between SF versus non-SF patients were observed in the cumulative frequency of very late stent thrombosis (2.9% versus 1.4%,
P
=0.281), death (0% versus 2.1%,
P
=0.252), or myocardial infarction (5.8% versus 2.9%,
P
=0.165).

Conclusions—
SF of SES was associated with higher MACE rate up to 1 year, mainly driven by higher target-lesion revascularization, whereas no significant association was evident between years 1 and 4.
Contribution of Subregions of Human Frontal Cortex to Novelty Processing
Authors: Løvstad Marianne , Funderud Ingrid , Lindgren Magnus , Endestad Tor , Due-Tønnessen Paulina , Meling Torstein , Voytek Bradley , Knight Robert T. , Solbakk Anne-Kristin 
Published: August 2011

Abstract
Novelty processing was studied in patients with lesions centered in either OFC or lateral pFC (LPFC). An auditory novelty oddball ERP paradigm was applied with environmental sounds serving as task irrelevant novel stimuli. Lesions to the LPFC as well as the OFC resulted in a reduction of the frontal Novelty P3 response, supporting a key role of both frontal subdivisions in novelty processing. The posterior P3b to target sounds was unaffected in patients with frontal lobe lesions in either location, indicating intact posterior cortical target detection mechanisms. LPFC patients displayed an enhanced sustained negative slow wave (NSW) to novel sounds not observed in OFC patients, indicating prolonged resource allocation to task-irrelevant stimuli after LPFC damage. Both patient groups displayed an enhanced NSW to targets relative to controls. However, there was no difference in behavior between patients and controls suggesting that the enhanced NSW to targets may index an increased resource allocation to response requirements enabling comparable performance in the frontal lesioned patients. The current findings indicate that the LPFC and OFC have partly shared and partly differential contributions to the cognitive subcomponents of novelty processing.
Two Hemispheres for Better Memory in Old Age: Role of Executive Functioning
Authors: Angel Lucie , Fay Séverine , Bouazzaoui Badiâa , Isingrini Michel 
Published: August 2011

Abstract
This experiment explored the functional significance of age-related hemispheric asymmetry reduction associated with episodic memory and the cognitive mechanisms that mediate this brain pattern. ERPs were recorded while young and older adults performed a word-stem cued-recall task. Results confirmed that the parietal old/new effect was of larger latency and reduced magnitude and less lateralized in the older group than the young group. Correlational and regression analyses indicated that the degree of laterality of brain activity determines the accuracy of memory performance and mediates age-related differences in memory performance among older participants. They also confirmed a cascade model in which the individual level of executive functioning of older adults mediates age-related differences in the degree of lateralization of brain activity, which in turn mediates age-related differences in memory performance.
Frontal Oscillatory Dynamics Predict Feedback Learning and Action Adjustment
Authors: van de Vijver Irene , Ridderinkhof K. Richard , Cohen Michael X 
Published: August 2011

Abstract
Frontal oscillatory dynamics in the theta (4–8 Hz) and beta (20–30 Hz) frequency bands have been implicated in cognitive control processes. Here we investigated the changes in coordinated activity within and between frontal brain areas during feedback-based response learning. In a time estimation task, participants learned to press a button after specific, randomly selected time intervals (300–2000 msec) using the feedback after each button press (correct, too fast, too slow). Consistent with previous findings, theta-band activity over medial frontal scalp sites (presumably reflecting medial frontal cortex activity) was stronger after negative feedback, whereas beta-band activity was stronger after positive feedback. Theta-band power predicted learning only after negative feedback, and beta-band power predicted learning after positive and negative feedback. Furthermore, negative feedback increased theta-band intersite phase synchrony (a millisecond resolution measure of functional connectivity) among right lateral prefrontal, medial frontal, and sensorimotor sites. These results demonstrate the importance of frontal theta- and beta-band oscillations and intersite communication in the realization of reinforcement learning.