bluuebunny/crossref_metadata_2025_split huggingface dataset:
A workplace intervention for sick-listed employees with distress: results of a randomised controlled trial
Authors: van Oostrom Sandra H , van Mechelen Willem , Terluin Berend , de Vet Henrica C W , Knol Dirk L , Anema Johannes R 
Published: April 2010

ObjectivesTo evaluate the effectiveness of a participatory workplace intervention compared with usual care for sick-listed employees with distress, with regard to return to work (RTW) within the 12-month follow-up.MethodsEmployees with distress and sick-listed for 2–8 weeks were randomised to a workplace intervention (n=73) or to usual care (n=72). The participatory workplace intervention is a stepwise process involving the sick-listed employee and their supervisor, aimed at reducing obstacles for RTW by reaching consensus about an action plan for RTW. Outcome variables were lasting RTW, cumulative sickness absence and stress-related symptoms.ResultsOverall, an HR of 0.99 (95% CI 0.70 to 1.39) indicated no effect of the workplace intervention on lasting RTW. However, the workplace intervention significantly reduced the time until lasting RTW for employees who at baseline intended to return to work despite symptoms with an HR of 2.05 (95% CI 1.22 to 3.45). Employees who intended to return to work despite symptoms returned to work after 55 days in the workplace intervention group and 120 days in the usual care group. No such effect of the intervention was found for employees without baseline intentions to return to work despite symptoms (HR=0.78, 95% CI 0.47 to 1.28).ConclusionsNo overall effect of the participatory workplace intervention on lasting RTW was found. The workplace intervention appeared effective on lasting RTW for employees who at baseline intended to return to work despite symptoms. For employees who showed no baseline intention to return to work, the intervention did not have any effect. Other approaches are needed for this subgroup.This trial has been registered at the Dutch National Trial RegisterISRCTN92307123.
Hydraulic conductivity and consolidation response of mixtures of mine waste rock and tailings
Authors: Wickland Benjamin E. , Wilson G. Ward , Wijewickreme Dharma 
Published: April 2010

Hydraulic conductivity and consolidation behaviour are examined for an alternative mine waste disposal technique. One type of waste rock, one type of tailings, and mixtures of the same waste rock and tailings were tested in bench-scale and column studies. Specimens 150 mm in diameter were tested for hydraulic conductivity by falling-head method alternated with one-dimensional consolidation, specimens 300 mm in diameter were tested for one-dimensional consolidation response, and specimens 1 m in diameter were tested for self-weight consolidation behaviour in 6 m high columns. Deformation of mixtures under one-dimensional loading was similar to that of waste rock alone and much less than that of tailings alone. Hydraulic conductivity of mixtures was similar to that of tailings alone and independent of specimen diameter. Mixture behaviour was attributed to a homogeneous structure including waste rock in particle-to-particle contact and a continuous, saturated matrix of tailings. The results indicate that mixing waste rock and tailings can produce dense deposits with values of hydraulic conductivity that are orders of magnitude lower than those of waste rock alone, thereby limiting fluxes through the waste and the associated potential for acid rock drainage. Mixture deposits will also have less consolidation-related settlement than tailings, thus improving stability and aiding reclamation.
Three-dimensional ground displacements from static pipe bursting in stiff clay
Authors: Brachman R. W.I. , McLeod H. A. , Moore I. D. , Take W. A. 
Published: April 2010

Three-dimensional ground surface displacements from 20 m long static pipe-bursting experiments are reported. These experiments were conducted with firm-to-stiff clay backfill in a trench with very stiff clay sidewalls at three different burial depths. Multiple digital cameras and image analysis were used to quantify the surface response as the expander progressed through the original pipe. The experiments quantified the upward surface movement as the expander approached, the effect of burial depth on maximum uplift, and the final amount of uplift after it decreased to a residual displacement. The experiments also quantified the axially forward ground surface movement as the expander approached, reaching maximum just ahead of the expander, and decreasing to almost zero after the expander had passed by. Lateral movements of the ground surface away from the centreline are also reported, which were essentially zero at the centre line, increasing to a maximum and then decreasing with distance from the centreline. The three different burial depths produced in effect the same width of vertical surface response with the displacements contained within 1.5 m on either side of the centreline, suggesting that the very stiff clay trench walls had a dominant influence on the measured displacements.
Engineering burstsort
Authors: Sinha Ranjan , Wirth Anthony 
Published: April 2010

Burstsort is a trie-based string sorting algorithm that distributes strings into small buckets whose contents are then sorted in cache. This approach has earlier been demonstrated to be efficient on modern cache-based processors [Sinha & Zobel, JEA 2004]. In this article, we introduce improvements that reduce by a significant margin the memory requirement of Burstsort: It is now less than 1% greater than an in-place algorithm. These techniques can be applied to existing variants of Burstsort, as well as other string algorithms such as for string management.
We redesigned the buckets, introducing sub-buckets and an index structure for them, which resulted in an order-of-magnitude space reduction. We also show the practicality of moving some fields from the trie nodes to the insertion point (for the next string pointer) in the bucket; this technique reduces memory usage of the trie nodes by one-third. Importantly, the trade-off for the reduction in memory use is only a very slight increase in the running time of Burstsort on real-world string collections. In addition, during the bucket-sorting phase, the string suffixes are copied to a small buffer to improve their spatial locality, lowering the running time of Burstsort by up to 30%. These memory usage enhancements have enabled the copy-based approach [Sinha et al., JEA 2006] to also reduce the memory usage with negligible impact on speed.
Preclinical Evidence that Use of TRAIL in Ewing's Sarcoma and Osteosarcoma Therapy Inhibits Tumor Growth, Prevents Osteolysis, and Increases Animal Survival
Authors: Picarda Gaëlle , Lamoureux François , Geffroy Loïc , Delepine Pascal , Montier Tristan , Laud Karine , Tirode Franck , Delattre Olivier , Heymann Dominique , Rédini Françoise 
Published: April 2010

Abstract
Purpose: Osteosarcoma and Ewing's sarcoma are high-grade neoplasms typically arising in the bones of children and adolescents. Despite improvement in therapy, the five-year survival rate is only 20% for patients not responding to treatment or presenting with metastases. Among new therapeutic strategies, the efficacy of tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily with strong antitumoral activity and minimal toxicity to most normal cells and tissues, was investigated by complementary approaches both in vitro and in preclinical models.
Experimental design: The sensitivity of osteosarcoma and Ewing’s sarcoma cell lines to TRAIL was investigated in vitro by determining TRAIL receptor expression together with TRAIL effects on cell viability and apoptosis. Complementary preclinical studies were carried out in respective tumor models by inoculation of osteosarcoma or Ewing’s sarcoma tumor cells in paraosseous location. In addition, a model of lung nodule dissemination was developed by i.v. injection of osteosarcoma cells.
Results: In vitro, both osteosarcoma and Ewing’s sarcoma cells that express the TRAIL death receptors were highly sensitive to TRAIL-induced caspase-8–mediated apoptosis. TRAIL administered in vivo by nonviral gene therapy inhibited primary bone tumor incidence and growth by 87% and prevented tumor-induced osteolysis, leading to a significant 2-fold increase in animal survival 40 days after tumor induction. Furthermore, TRAIL inhibited tumor nodule dissemination in lungs and increased survival in an osteosarcoma model.
Conclusion: These findings suggest that TRAIL is a promising candidate for the development of new therapeutic strategies in the most frequent malignant primary bone tumors. Clin Cancer Res; 16(8); 2363–34. ©2010 AACR.
RAS Mutations Contribute to Evolution of Chronic Myelomonocytic Leukemia to the Proliferative Variant
Authors: Ricci Clara , Fermo Elisa , Corti Stefania , Molteni Mauro , Faricciotti Alessio , Cortelezzi Agostino , Lambertenghi Deliliers Giorgio , Beran Miloslav , Onida Francesco 
Published: April 2010

Abstract
Purpose: The biological and clinical heterogeneity of chronic myelomonocytic leukemia features renders its classification difficult. Moreover, because of the limited knowledge of the mechanisms involved in malignant evolution, chronic myelomonocytic leukemia remains a diagnostic and therapeutic challenge and a poor prognosis disease. We aimed to verify the biological and clinical significance of the discrimination, based on the leukocyte count, between myelodysplastic chronic myelomonocytic leukemia (MD-CMML) and myeloproliferative chronic myelomonocytic leukemia (MP-CMML).
Experimental Design: Peripheral blood samples from 22 patients classified as MD-CMML and 18 as MP-CMML were collected at different time points during disease course, and patients' clinical characteristics were examined. RAS mutational screening was done by sequencing and, for each substitution identified, a highly selective allele-specific PCR was set up to screen all specimens.
Results: MP-CMML patients showed a significantly poorer survival (P = 0.003) and a higher frequency of RAS mutations (P = 0.033) by sequencing compared with MD-CMML. Overall, five MD-CMML patients progressed to myeloproliferative disease: in two, allele-specific PCR unveiled low levels of the RAS mutations predominating in the myeloproliferative phase at the time of myelodysplastic disease, documenting for the first time the expansion of a RAS mutated clone in concomitance with chronic myelomonocytic leukemia evolution. Moreover, one of the progressed patients harbored the FLT3-ITD and two MP-CMML patients presented with the JAK2 V617F substitution. All these lesions were mutually exclusive.
Conclusions: Our results strongly suggest RAS mutations to function as a secondary event that contributes to development of the chronic myelomonocytic leukemia variant with the poorer prognosis (MP-CMML) and therefore advise their detection to be implemented in chronic myelomonocytic leukemia diagnostics and monitoring. Clin Cancer Res; 16(8); 2246–56. ©2010 AACR.
T-Cell Receptor Gene–Modified T Cells with Shared Renal Cell Carcinoma Specificity for Adoptive T-Cell Therapy
Authors: Leisegang Matthias , Turqueti-Neves Adriana , Engels Boris , Blankenstein Thomas , Schendel Dolores J. , Uckert Wolfgang , Noessner Elfriede 
Published: April 2010

AbstractPurpose: Adoptive therapy with genetically engineered T cells carrying redirected antigen specificity is a new option for the treatment of cancer. This approach is not yet available for metastatic renal cell carcinoma (RCC), due to the scarcity of therapeutically useful reagents. We analyzed tumor-infiltrating lymphocytes (TIL) from RCC to identify T-cell specificities with shared tumor-specific recognition to develop T-cell receptor (TCR)-engineered T lymphocytes for adoptive therapy of RCC.Experimental Design: We established a T-cell clone from TIL that recognized a human leukocyte antigen (HLA)-A2–restricted tumor antigen. The TCR α- and β-chain genes were isolated, modified by codon optimization and murinization, and retrovirally transduced into peripheral blood lymphocytes (PBL). A TCR-expressing indicator line (B3Z-TCR53) was established to screen for antigen prevalence in RCC, other malignancies, and normal cell counterparts.Results: TCR53-engineered PBL recapitulated the specificity of the TIL and showed tumor-specific HLA-A2–restricted effector activities (IFN-γ, tumor necrosis factor-α, interleukin-2, macrophage inflammatory protein-1β, cytotoxicity). PBL-TCR53 of healthy donors and RCC patients exhibited similar transduction efficiency, expansion, and polyfunctional profile. Using B3Z-TCR53 cells, 130 tumor and normal cells were screened and shared TCR53 peptide: MHC expression was found in &gt;60% of RCC and 25% of tumor lines of other histology, whereas normal tissue cells were not recognized.Conclusions: To date, TCR53 is the only TCR with shared HLA-A2–restricted recognition of RCC. It fulfills the criteria for utilization in TCR gene therapy and advances T cell–based immunotherapy to patients with RCC and other malignancies expressing the TCR ligand. Clin Cancer Res; 16(8); 2333–43. ©2010 AACR.
Phase I/II Study of Inhaled Doxorubicin Combined with Platinum-Based Therapy for Advanced Non–Small Cell Lung Cancer
Authors: Otterson Gregory A. , Villalona-Calero Miguel A. , Hicks William , Pan Xueliang , Ellerton John A. , Gettinger Scott N. , Murren John R. 
Published: April 2010

Abstract
Purpose: We have shown the feasibility of administering inhaled doxorubicin to patients with cancer. This study evaluated inhaled doxorubicin combined with cisplatin and docetaxel in patients with non–small cell lung cancer. The principal objective was to determine safety and, secondarily, efficacy.
Experimental Design: Patients who had chemo-naïve advanced non–small cell lung cancer were enrolled in the study. Adequate organ and pulmonary function was required: diffusing capacity for carbon monoxide/forced expiratory volume in 1 second/forced vital capacity ≥50%, resting/exercise O2 saturation ≥90%/85%. In phase I, doxorubicin was escalated: dose level 1 (6 mg/m2) and level 2 (7.5 mg/m2). Escalation was permitted if ≤2 of 6 patients experienced pulmonary dose-limiting toxicity (grade 2 Radiation Therapy Oncology Group lung morbidity; resting O2 saturation of &lt;85%; decrease in diffusing capacity for carbon monoxide, forced vital capacity, or forced expiratory volume in 1 second of ≥20% from baseline or ≤30% of predicted; or grade 3 Common Terminology Criteria for Adverse Events version 3.0 pulmonary toxicity). Doses of cisplatin and docetaxel were 75 mg/m2. Treatments and pulmonary function tests were repeated every 21 days, with up to eight cycles for responding patients.
Results: Twenty-eight patients were treated at level 1 and eight patients at level 2. Doxorubicin was escalated to 7.5 mg/m2, however, after two patients developed pulmonary dose-limiting toxicity; the remainder were treated at 6.0 mg/m2. Twenty-four evaluable patients received at least two courses or had progressive disease following the first course at the phase II dose. Toxicity was associated with i.v. chemotherapy although one patient had delayed pulmonary toxicity responding to corticosteroids and oxygen. Seven (29%) evaluable patients responded (six partial responses and one complete response) and 13 (54%) patients had stable disease for up to eight cycles.
Conclusion: Although this combination was safe, the primary objective was not met and will not be pursued further. Clin Cancer Res; 16(8); 2466–73. ©2010 AACR.
Establishment and Characterization of a Panel of Human Uveal Melanoma Xenografts Derived from Primary and/or Metastatic Tumors
Authors: Némati Fariba , Sastre-Garau Xavier , Laurent Cécile , Couturier Jérôme , Mariani Pascale , Desjardins Laurence , Piperno-Neumann Sophie , Lantz Olivier , Asselain Bernard , Plancher Corine , Robert Delphine , Péguillet Isabelle , Donnadieu Marie-Hélène , Dahmani Ahmed , Bessard Marie-Andrée , Gentien David , Reyes Cécile , Saule Simon , Barillot Emmanuel , Roman-Roman Sergio , Decaudin Didier 
Published: April 2010

Abstract
Purpose: Uveal melanoma is the most common primary intraocular malignant tumor in adults and is defined by a poor natural outcome, as 50% of patients die from metastases. The aim of this study was to develop and characterize a panel of human uveal melanoma xenografts transplanted into immunodeficient mice.
Experimental Design: Ninety tumor specimens were grafted into severe combined immunodeficient mice, and 25 transplantable xenografts were then established (28%). Relationship between tumor graft and clinical, biological, and therapeutic features of the patients included were investigated. Characterization of 16 xenografts included histology, molecular analyses by immunohistochemistry, genetic alteration analysis (single-nucleotide polymorphism), and specific tumor antigen expression by quantitative reverse transcription-PCR. Pharmacologic characterization (chemosensitivity) was also done in four models using two drugs, temozolomide and fotemustine, currently used in the clinical management of uveal melanoma.
Results: Take rate of human uveal melanoma was 28% (25 of 90). Tumor take was independent of size, histologic parameters, or chromosome 3 monosomy but was significantly higher in metastatic tumors. Interestingly, in vivo tumor growth was prognostic for a lower metastasis-free survival in patients with primary tumors. A high concordance between the patients' tumors and their corresponding xenografts was found for all parameters tested (histology, genetic profile, and tumor antigen expression). Finally, the four xenografts studied displayed different response profiles to chemotherapeutic agents.
Conclusions: Based on these results, this panel of 16 uveal melanoma xenografts represents a useful preclinical tool for both pharmacologic and biological assessments. Clin Cancer Res; 16(8); 2352–62. ©2010 AACR.
Trifluorothymidine Resistance Is Associated with Decreased Thymidine Kinase and Equilibrative Nucleoside Transporter Expression or Increased Secretory Phospholipase A2
Authors: Temmink Olaf H. , Bijnsdorp Irene V. , Prins Henk-Jan , Losekoot Nienke , Adema Auke D. , Smid Kees , Honeywell Richard J. , Ylstra Bauke , Eijk Paul P. , Fukushima Masakazu , Peters Godefridus J. 
Published: April 2010

AbstractTrifluorothymidine (TFT) is part of the novel oral formulation TAS-102, which is currently evaluated in phase II studies. Drug resistance is an important limitation of cancer therapy. The aim of the present study was to induce resistance to TFT in H630 colon cancer cells using two different schedules and to analyze the resistance mechanism. Cells were exposed either continuously or intermittently to TFT, resulting in H630-cTFT and H630-4TFT, respectively. Cells were analyzed for cross-resistance, cell cycle, protein expression, and activity of thymidine phosphorylase (TP), thymidine kinase (TK), thymidylate synthase (TS), equilibrative nucleoside transporter (hENT), gene expression (microarray), and genomic alterations. Both cell lines were cross-resistant to 2′-deoxy-5-fluorouridine (&gt;170-fold). Exposure to IC75-TFT increased the S/G2-M phase of H630 cells, whereas in the resistant variants, no change was observed. The two main target enzymes TS and TP remained unchanged in both TFT-resistant variants. In H630-4TFT cells, TK protein expression and activity were decreased, resulting in less activated TFT and was most likely the mechanism of TFT resistance. In H630-cTFT cells, hENT mRNA expression was decreased 2- to 3-fold, resulting in a 5- to 10-fold decreased TFT-nucleotide accumulation. Surprisingly, microarray-mRNA analysis revealed a strong increase of secretory phospholipase-A2 (sPLA2; 47-fold), which was also found by reverse transcription-PCR (RT-PCR; 211-fold). sPLA2 inhibition reversed TFT resistance partially. H630-cTFT had many chromosomal aberrations, but the exact role of sPLA2 in TFT resistance remains unclear. Altogether, resistance induction to TFT can lead to different mechanisms of resistance, including decreased TK protein expression and enzyme activity, decreased hENT expression, as well as (phospho)lipid metabolism. Mol Cancer Ther; 9(4); 1047–57. ©2010 AACR.
Natural Immunity Enhances the Activity of a DR5 Agonistic Antibody and Carboplatin in the Treatment of Ovarian Cancer
Authors: El-Gazzar Ahmed , Perco Paul , Eckelhart Eva , Anees Mariam , Sexl Veronika , Mayer Bernd , Liu Yanxin , Mikulits Wolfgang , Horvat Reinhard , Pangerl Thomas , Zheng Dexian , Krainer Michael 
Published: April 2010

AbstractThe tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) induces apoptosis specifically in cancer cells with little effect on normal cells. We have previously shown that TRAIL signaling is altered in most ovarian cancer patients and that resistance to TRAIL contributes to ovarian cancer progression. In this study, we investigated whether resistance to TRAIL may be overcome by a monoclonal TRAILR2 (DR5) agonistic antibody (AD5-10). We found that the joint presence of AD5-10 with TRAIL and natural killer (NK) cells expressing TRAIL resensitizes ovarian cancer cells to apoptosis in vitro and in vivo, respectively. The combination of AD5-10 with carboplatin exerts a more than additive effect in vitro, which may at least partially be explained by the fact that carboplatin triggers DR5 expression on ovarian cancer cells. Moreover, AD5-10 restores the sensitivity of platin-resistant ovarian cancer to carboplatin in vivo. In addition, we found that TRAIL expression and NK cells are abundant in the tumor microenvironment and that depletion of NK cells abolishes the antitumor activity of AD5-10. This indicates that NK-mediated immunosurveillance against ovarian cancer might be mediated by TRAIL and that apoptosis induced by AD5-10 requires the presence of NK cells. In conclusion, this study indicates a key role and strong antitumorigenic effect of DR5 and highlights a novel link between NK-mediated immunosurveillance and activation of DR5-mediated apoptosis in ovarian cancer. Mol Cancer Ther; 9(4); 1007–18. ©2010 AACR.
Interstitial Infusion of Glioma-Targeted Recombinant Immunotoxin 8H9scFv-PE38
Authors: Luther Neal , Cheung Nai-Kong , Souliopoulos Eleni P. , Karempelas Ioannis , Bassiri Daniel , Edgar Mark A. , Guo Hong-fen , Pastan Ira , Gutin Philip H. , Souweidane Mark M. 
Published: April 2010

Abstract
Monoclonal antibodies have the potential to target therapy for high-grade gliomas. Monoclonal antibody 8H9 is specific for membrane protein B7H3 and is reactive with most human high-grade gliomas. We tested the 8H9scFv-PE38 recombinant Pseudomonas immunotoxin in a preclinical model of high-grade glioma. The half maximal inhibitory concentration (IC50) of 8H9scFv-PE38 in vitro was determined using glioblastoma cell lines U87 and U251. Maximum tolerated infusion dose of 8H9scFv-PE38 following interstitial infusion to the striatum and pons was defined using athymic rats. Maximum tolerated infusion dose of 8H9scFv-PE38 or PBS control were interstitially delivered to athymic rats xenografted with U87 in the striatum or brain stem. Radiographic response and survivals were measured and compared between treatment groups. The in vitro IC50 of 8H9scFv-PE38 for U87 was 1,265 ng/mL and, for U251, 91 ng/mL. The maximum tolerated infusion doses of interstitially infused 8H9scFv-PE38 to the striatum and brain stem were 0.75 and 1.8 μg, respectively. For rats harboring intracranial U87 xenografts, infusion of 8H9scFv-PE38 increased mean survival (striatum, 43.4 versus 24.6 days; brain stem, 80.6 versus 45.5 days; n = 28 total) and produced three long-term survivors past 120 days. None of the 14 placebo-treated animals survived &gt;54 days. Tumors also showed volumetric response to infusion of 8H9scFv-PE38 by magnetic resonance imaging. Interstitial infusion of 8H9scFv-PE38 shows potential for the treatment of hemispherical and brain stem glioma. Mol Cancer Ther; 9(4); 1039–46. ©2010 AACR.