bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myocardial injury in infants ventilated on the paediatric intensive care unit: a case control study
Authors: Clark Simon J , Eisenhut Michael , Sidaras Dorothea , Hancock Stephen W , Newland Paul , Thorburn Kent 
Published: September 2006

Abstract
Introduction
Cardiac troponin T (cTnT) has been used to assess prevalence of myocardial injury in critically ill children. The majority of studies investigated patients undergoing cardiac surgery. Myocardial injury has been associated with increased mortality. Our objectives were to investigate whether cTnT levels are elevated in infants without congenital heart disease admitted to the paediatric intensive care unit (PICU) and whether levels are associated with increased disease severity.

Methods
We measured cTnT in consecutive infants (<12 months old) without congenital heart disease admitted to the PICU and healthy infants. The Paediatric Index of Mortality (PIM) score was determined in patients on the PICU.

Results
We recruited 107 infants: 47 infants admitted to the PICU and 60 healthy controls. Controls were, with a median (interquartile range (IQR)) age of 20 (12 to 34) weeks, significantly older than cases, with a median age of 6.5 (0.3 to 20.6) weeks. CTnT levels were, with a median (IQR) of 18 (10 to 60) pg/ml, significantly higher in admissions to the PICU than in controls, with a median level of 10 (10 to 10) pg/ml (95th centile of 20 pg/ml) (p < 0.001). There was a significant positive correlation (r = 0.41, p = 0.004) between PIM score and cTnT levels. Admissions under one month old had higher cTnT levels than older patients (p = 0.013) but the PIM score was not significantly different between them. When corrected for age and weight the correlation of PIM and cTnT was no longer significant.

Conclusion
Infants on the PICU in the neonatal period have higher cTnT levels compared to older infants despite not having more severe disease.
High mobility group box-1 protein induces the migration and activation of human dendritic cells and acts as an alarmin
Authors: Yang De , Chen Qian , Yang Huan , Tracey Kevin J , Bustin Michael , Oppenheim Joost J 
Published: September 2006

AbstractHigh mobility group box-1 (HMGB1) protein is a nonhistone, DNA-binding protein that plays a critical role in regulating gene transcription. Recently, HMGB1 has also been shown to act as a late mediator of endotoxic shock and to exert a variety of proinflammatory, extracellular activities. Here, we report that HMGB1 simultaneously acts as a chemoattractant and activator of dendritic cells (DCs). HMGB1 induced the migration of monocyte-derived, immature DCs (Mo-iDCs) but not mature DCs. The chemotactic effect of HMGB1 on iDCs was pertussis toxin-inhibitable and also inhibited by antibody against the receptor of advanced glycation end products (RAGE), suggesting that HMGB1 chemoattraction of iDCs is mediated by RAGE in a Gi protein-dependent manner. In addition, HMGB1 treatment of Mo-iDCs up-regulated DC surface markers (CD80, CD83, CD86, and HLA-A, B,C), enhanced DC production of cytokines (IL-6, CXCL8, IL-12p70, and TNF-α), switched DC chemokine responsiveness from CCL5-sensitive to CCL21-sensitive, and acquired the capacity to stimulate allogeneic T cell proliferation. Based on its dual DC-attracting and -activating activities as well as its reported capacity to promote an antigen-specific immune response, we consider HMGB1 to have the properties of an immune alarmin.
IRF-1 deficiency skews the differentiation of dendritic cells toward plasmacytoid and tolerogenic features
Authors: Gabriele L , Fragale A , Borghi P , Sestili P , Stellacci E , Venditti M , Schiavoni G , Sanchez M , Belardelli F , Battistini A 
Published: September 2006

Abstract
Members of the IFN regulatory factors (IRFs) family are transcriptional regulators that play essential roles in the homeostasis and function of the immune system. Recent studies indicate a direct involvement of some members of the family in the development of different subsets of dendritic cells (DC). Here, we report that IRF-1 is a potent modulator of the development and functional maturation of DC. IRF-1-deficient mice (IRF-1−/−) exhibited a predominance of plasmacytoid DC and a selective reduction of conventional DC, especially the CD8α+ subset. IRF-1−/− splenic DC were markedly impaired in their ability to produce proinflammatory cytokines such as IL-12. By contrast, they expressed high levels of IL-10, TGF-β, and the tolerogenic enzyme indoleamine 2,3 dioxygenase. As a consequence, IRF-1−/− DC were unable to undergo full maturation and retained plasmacytoid and tolerogenic characteristics following virus infection ex vivo and in vivo. Accordingly, DC from IRF-1−/− mice were less efficient in stimulating the proliferation of allogeneic T cells and instead, induced an IL-10-mediated, suppressive activity in allogeneic CD4+CD25+ regulatory T cells. Together, these results indicate that IRF-1 is a key regulator of DC differentiation and maturation, exerting a variety of effects on the functional activation and tolerogenic potential of these cells.
MicroRNA Expression Abnormalities in Pancreatic Endocrine and Acinar Tumors Are Associated With Distinctive Pathologic Features and Clinical Behavior
Authors: Roldo Claudia , Missiaglia Edoardo , Hagan John P. , Falconi Massimo , Capelli Paola , Bersani Samantha , Calin George Adrian , Volinia Stefano , Liu Chang-Gong , Scarpa Aldo , Croce Carlo M. 
Published: September 2006

PurposeWe investigated the global microRNA expression patterns in normal pancreas, pancreatic endocrine tumors and acinar carcinomas to evaluate their involvement in transformation and malignant progression of these tumor types. MicroRNAs are small noncoding RNAs that regulate gene expression by targeting specific mRNAs for degradation or translation inhibition. Recent evidence indicates that microRNAs can contribute to tumor development and progression and may have diagnostic and prognostic value in several human malignancies.Materials and MethodsUsing a custom microarray, we studied the global microRNA expression in 12 nontumor pancreas and 44 pancreatic primary tumors, including 12 insulinomas, 28 nonfunctioning endocrine tumors, and four acinar carcinomas.ResultsOur data showed that a common pattern of microRNA expression distinguishes any tumor type from normal pancreas, suggesting that this set of microRNAs might be involved in pancreatic tumorigenesis; the expression of miR-103 and miR-107, associated with lack of expression of miR-155, discriminates tumors from normal; a set of 10 microRNAs distinguishes endocrine from acinar tumors and is possibly associated with either normal endocrine differentiation or endocrine tumorigenesis; miR-204 is primarily expressed in insulinomas and correlates with immunohistochemical expression of insulin; and the overexpression of miR-21 is strongly associated with both a high Ki67 proliferation index and presence of liver metastasis.ConclusionThese results suggest that alteration in microRNA expression is related to endocrine and acinar neoplastic transformation and progression of malignancy, and might prove useful in distinguishing tumors with different clinical behavior.
Phase II Study of Belagenpumatucel-L, a Transforming Growth Factor Beta-2 Antisense Gene-Modified Allogeneic Tumor Cell Vaccine in Non–Small-Cell Lung Cancer
Authors: Nemunaitis John , Dillman Robert O. , Schwarzenberger Paul O. , Senzer Neil , Cunningham Casey , Cutler Jodi , Tong Alex , Kumar Padmasini , Pappen Beena , Hamilton Cody , DeVol Edward , Maples Phillip B. , Liu Lily , Chamberlin Terry , Shawler Daniel L. , Fakhrai Habib 
Published: September 2006

PurposeBelagenpumatucel-L is a nonviral gene-based allogeneic tumor cell vaccine that demonstrates enhancement of tumor antigen recognition as a result of transforming growth factor beta-2 inhibition.Patients and MethodsWe performed a randomized, dose-variable, phase II trial involving stages II, IIIA, IIIB, and IV non–small-cell lung cancer patients. Each patient received one of three doses (1.25, 2.5, or 5.0 × 107cells/injection) of belagenpumatucel-L on a monthly or every other month schedule to a maximum of 16 injections. Immune function, safety, and anticancer activity were monitored.ResultsSeventy-five patients (two stage II, 12 stage IIIA, 15 stage IIIB, and 46 stage IV patients) received a total of 550 vaccinations. No significant adverse events were observed. A dose-related survival difference was demonstrated in patients who received ≥ 2.5 × 107cells/injection (P = .0069). Focusing on the 61 late-stage (IIIB and IV) assessable patients, a 15% partial response rate was achieved. The estimated probabilities of surviving 1 and 2 years were 68% and 52%, respectively for the higher dose groups combined and 39% and 20%, respectively, for the low-dose group. Immune function was explored in the 61 advanced-stage (IIIB and IV) patients. Increased cytokine production (at week 12 compared with patients with progressive disease) was observed among clinical responders (interferon gamma, P = .006; interleukin [IL] -6, P = .004; IL-4, P = .007), who also displayed an elevated antibody-mediated response to vaccine HLAs (P = .014). Furthermore, positive enzyme-linked immunospot reactions to belagenpumatucel-L showed a correlation trend (P = .086) with clinical responsiveness in patients achieving stable disease or better.ConclusionBelagenpumatucel-L is well tolerated, and the survival advantage justifies further phase III evaluation.
Loss of Heterozygosity 1p36 and 19q13 Is a Prognostic Factor for Overall Survival in Patients With Diffuse WHO Grade 2 Gliomas Treated Without Chemotherapy
Authors: Mariani Luigi , Deiana Gianluca , Vassella Erik , Fathi Ali-Reza , Murtin Christine , Arnold Marlène , Vajtai Istvan , Weis Joachim , Siegenthaler Peter , Schobesberger Martina , Reinert Michael M. 
Published: September 2006

Purpose This study was conducted to elucidate the impact of loss of heterozygosity (LOH) for chromosomes 1p36 and 19q13 on the overall survival of patients with diffusely infiltrating WHO grade 2 gliomas treated without chemotherapy. Patients and Methods We assessed the LOH status of tumors from patients harboring WHO grade 2 gliomas diagnosed between 1991 and 2000. Patients were either followed after initial biopsy or treated by surgery and/or radiation therapy (RT). Overall survival, time to malignant transformation, and progression-free survival were last updated as of March 2005. Results Of a total of 79 patients, LOH 1p36 and LOH 19q13 could be assessed in 67 and 66 patients, respectively. The median follow-up after diagnosis was 6 years. Loss of either 1p or 19q, in particular codeletion(s) at both loci, was found to positively impact on both overall survival (log-rank P < .01), progression-free survival, and survival without malignant transformation (P < .05). Tumor volume (P < .0001), neurologic deficits at diagnosis (P < .01), involvement of more than one lobe (P < .01), and absence of an oligodendroglial component (P < .05) were also predictors of shorter overall survival. The extent of surgery was similar in patients with or without LOH 1p and/or 19q; RT was more frequently resorted to for patients without than for patients with LOH 1p/19q (30% v 60%). Conclusion The presence of LOH on either 1p36 or 19q13, and in particular codeletion of both loci is a strong, nontreatment-related, prognostic factor for overall survival in patients with diffusely infiltrating WHO grade 2 gliomas.
Bcl-2 Antisense (oblimersen sodium) Plus Dacarbazine in Patients With Advanced Melanoma: The Oblimersen Melanoma Study Group
Authors: Bedikian Agop Y. , Millward Michael , Pehamberger Hubert , Conry Robert , Gore Martin , Trefzer Uwe , Pavlick Anna C. , DeConti Ronald , Hersh Evan M. , Hersey Peter , Kirkwood John M. , Haluska Frank G. 
Published: September 2006

Purpose Chemotherapy resistance in melanoma has been linked to antiapoptotic effects mediated by Bcl-2 protein. We evaluated whether targeting Bcl-2 using an antisense oligonucleotide (oblimersen sodium) could improve the efficacy of systemic chemotherapy in patients with advanced melanoma. Patients and Methods We randomly assigned chemotherapy-naïve patients with advanced melanoma to treatment with dacarbazine (1,000 mg/m2) alone or preceded by a 5-day continuous intravenous infusion of oblimersen sodium (7 mg/kg/d) every 3 weeks for up to eight cycles. Patients were stratified by Eastern Cooperative Oncology Group performance status, liver metastases, disease site, and serum lactate dehydrogenase (LDH). The primary efficacy end point was overall survival. Results Among 771 patients randomly assigned, the addition of oblimersen to dacarbazine yielded a trend toward improved survival at 24-month minimum follow-up (median, 9.0 v 7.8 months; P = .077) and significant increases in progression-free survival (median, 2.6 v 1.6 months; P < .001), overall response (13.5% v 7.5%; P = .007), complete response (2.8% v 0.8%), and durable response (7.3% v 3.6%; P = .03). A significant interaction between baseline serum LDH and treatment was observed; oblimersen significantly increased survival in patients whose baseline serum LDH was not elevated (median overall survival, 11.4 v 9.7 months; P = .02). Neutropenia and thrombocytopenia were increased in the oblimersen-dacarbazine group; however, there was no increase in serious infections or bleeding events. Conclusion The addition of oblimersen to dacarbazine significantly improved multiple clinical outcomes in patients with advanced melanoma and increased overall survival in patients without an elevated baseline serum LDH.
Gemcitabine Plus Carboplatin Compared With Carboplatin in Patients With Platinum-Sensitive Recurrent Ovarian Cancer: An Intergroup Trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG
Authors: Pfisterer Jacobus , Plante Marie , Vergote Ignace , du Bois Andreas , Hirte Hal , Lacave Angel J. , Wagner Uwe , Stähle Anne , Stuart Gavin , Kimmig Rainer , Olbricht Sigrid , Le Tien , Emerich Janusz , Kuhn Walther , Bentley James , Jackisch Christian , Lück Hans-Joachim , Rochon Justine , Zimmermann Annamaria Hayden , Eisenhauer Elizabeth 
Published: September 2006

Purpose Most patients with advanced ovarian cancer develop recurrent disease. For those patients who recur at least 6 months after initial therapy, paclitaxel platinum has shown a modest survival advantage over platinum without paclitaxel; however, many patients develop clinically relevant neurotoxicity, frequently resulting in treatment discontinuation. Thus, an alternative regimen without significant neurotoxicity was evaluated by comparing gemcitabine plus carboplatin with single-agent carboplatin in platinum-sensitive recurrent ovarian cancer patients. Methods Patients with platinum-sensitive recurrent ovarian cancer were randomly assigned to receive either gemcitabine plus carboplatin or carboplatin alone, every 21 days. The primary objective was to compare progression-free survival (PFS). Results Three hundred fifty-six patients (178 gemcitabine plus carboplatin; 178 carboplatin) were randomly assigned. Patients received a median of six cycles in both arms. With a median follow-up of 17 months, median PFS was 8.6 months (95% CI, 7.9 to 9.7 months) for gemcitabine plus carboplatin and 5.8 months (95% CI, 5.2 to 7.1 months) for carboplatin. The hazard ration (HR) for PFS was 0.72 (95% CI, 0.58 to 0.90; P = .0031). Response rate was 47.2% (95% CI, 39.9% to 54.5%) for gemcitabine plus carboplatin and 30.9% (95% CI, 24.1% to 37.7%) for carboplatin (P = .0016). The HR for overall survival was 0.96 (95% CI, 0.75 to1.23; P = .7349). While myelosuppression was significantly more common in the combination, sequelae such as febrile neutropenia or infections were uncommon. No statistically significant differences in quality of life scores between arms were noted. Conclusion Gemcitabine plus carboplatin significantly improves PFS and response rate without worsening quality of life for patients with platinum-sensitive recurrent ovarian cancer.
RRM1 Modulated In Vitro and In Vivo Efficacy of Gemcitabine and Platinum in Non–Small-Cell Lung Cancer
Authors: Bepler Gerold , Kusmartseva Irina , Sharma Swati , Gautam Ashish , Cantor Alan , Sharma Anupama , Simon George 
Published: September 2006

Purpose RRM1 encodes the regulatory subunit of ribonucleotide reductase and is a molecular target of gemcitabine. Previous studies showed increased RRM1 expression on continuous exposure of cell lines to gemcitabine and suggested improved survival for patients with low as opposed to high tumoral RRM1 expression when treated with gemcitabine-containing chemotherapy. However, the principal hypothesis that intratumoral levels of gene expression are associated with disease response has not been addressed. Patients and Methods We constructed genetically modified lung cancer cell lines with increased and decreased RRM1 expression to investigate the in vitro 50% inhibitory concentration (IC50) for gemcitabine, cisplatin, and carboplatin. A prospective phase II clinical trial in patients with locally advanced non–small-cell lung cancer was conducted with pretreatment tumor collection for determination of RRM1 and ERCC1 expression by real-time reverse transcriptase polymerase chain reaction. The levels of gene expression were correlated with tumor response after two cycles of gemcitabine and carboplatin. Results In cell lines with a genetically engineered 15-fold RRM1 expression range, the gemcitabine IC50 had a 100-fold range, and the cisplatin and carboplatin IC50 had a two-fold range. They were highest in constructs with high RRM1 expression. In the prospective clinical trial, RRM1 expression was significantly (P = .002) and inversely correlated (r = −0.498) with disease response. ERCC1 expression showed a similar trend (P = .099). Conclusion The results strongly suggest that tumoral RRM1 expression is a major predictor of disease response to gemcitabine/platinum chemotherapy. ERCC1 expression is predictive of response albeit to a lesser degree.
Detection of Subclinical Systemic Disease in Primary CNS Lymphoma by Polymerase Chain Reaction of the Rearranged Immunoglobulin Heavy-Chain Genes
Authors: Jahnke Kristoph , Hummel Michael , Korfel Agnieszka , Burmeister Thomas , Kiewe Philipp , Klasen Hermann Ayke , Müller Hans-Henning , Stein Harald , Thiel Eckhard 
Published: September 2006

Purpose To search for subclinical systemic disease in bone marrow and peripheral blood in patients with primary CNS lymphoma (PCNSL) to elucidate whether extracerebral relapse may represent a sequel of initial occult systemic disease rather than true extracerebral spread. Patients and Methods Bone marrow and peripheral-blood specimens of 24 PCNSL patients were examined using polymerase chain reaction (PCR) for analysis of clonally rearranged immunoglobulin heavy-chain (IgH) genes. Results Identical dominant PCR products were found in bone marrow aspirates, blood samples, and tumor biopsy specimens of two patients, indicating that the same tumor cell population is present in the CNS and in extracerebral sites. Follow-up IgH PCR performed in one of these patients in complete remission 24 months after diagnosis yielded a persistent monoclonal product in the blood. An oligoclonal IgH rearrangement pattern was found in the tumor specimen of two other patients, whereas bone marrow and blood samples demonstrated the same dominant PCR products. Follow-up PCR showed a persistent monoclonal amplificate in blood in one of these patients 27 months after diagnosis. Conclusion It could be demonstrated for the first time that subclinical systemic disease can be present in PCNSL patients at initial diagnosis. Our findings may have an impact on the understanding of PCNSL pathogenesis and the extent of staging and treatment.
Perception of Auditory Motion Affects Language Processing
Authors: Kaschak Michael P. , Zwaan Rolf A. , Aveyard Mark , Yaxley Richard H. 
Published: September 2006

AbstractPrevious reports have demonstrated that the comprehension of sentences describing motion in a particular direction (toward, away, up, or down) is affected by concurrently viewing a stimulus that depicts motion in the same or opposite direction. We report 3 experiments that extend our understanding of the relation between perception and language processing in 2 ways. First, whereas most previous studies of the relation between perception and language processing have focused on visual perception, our data show that sentence processing can be affected by the concurrent processing of auditory stimuli. Second, it is shown that the relation between the processing of auditory stimuli and the processing of sentences depends on whether the sentences are presented in the auditory or visual modality.
Flexible Conceptual Projection of Time Onto Spatial Frames of Reference
Authors: Torralbo Ana , Santiago Julio , Lupiáñez Juan 
Published: September 2006

AbstractFlexibility in conceptual projection constitutes one of the most challenging issues in the embodiment and conceptual metaphor literatures. We sketch a theoretical proposal that places the burden of the explanation on attentional dynamics in interaction with mental models in working memory that are constrained to be maximally coherent. A test of this theory is provided in the context of the conceptual projection of time onto the domain of space. Participants categorized words presented at different spatial locations (back–front, left–right) as referring to the past or to the future. Responses were faster when the irrelevant word location was congruent with the back–past, front–future metaphoric mapping. Moreover, when a new highly task‐relevant spatial frame of reference was introduced, it changed the projection of past and future onto space in a way that was congruent with the new frame (past was now projected to left space and future to right space), as predicted by the theory. This study shows that there is substantial flexibility in conceptual projection and opens a venue to study metaphoric variation across tasks, individuals, and cultures as the result of attentional dynamics.
An Embodied Model for Sensorimotor Grounding and Grounding Transfer: Experiments With Epigenetic Robots
Authors: Cangelosi Angelo , Riga Thomas 
Published: September 2006

AbstractThe grounding of symbols in computational models of linguistic abilities is one of the fundamental properties of psychologically plausible cognitive models. In this article, we present an embodied model for the grounding of language in action based on epigenetic robots. Epigenetic robotics is one of the new cognitive modeling approaches to modeling autonomous mental development. The robot model is based on an integrative vision of language in which linguistic abilities are strictly dependent on and grounded in other behaviors and skills. It uses simulated robots that learn through imitation the names of basic actions. Robots also learn higher order action concepts through the process of grounding transfer. The simulation demonstrates how new, higher order behavioral abilities can be autonomously built on previously grounded basic action categories following linguistic interaction with human users.
Metacognitive Control and Optimal Learning
Authors: Son Lisa K. , Sethi Rajiv 
Published: September 2006

AbstractThe notion of optimality is often invoked informally in the literature on metacognitive control. We provide a precise formulation of the optimization problem and show that optimal time allocation strategies depend critically on certain characteristics of the learning environment, such as the extent of time pressure, and the nature of the uptake function. When the learning curve is concave, optimality requires that items at lower levels of initial competence be allocated greater time. On the other hand, with logistic learning curves, optimal allocations vary with time availability in complex and surprising ways. Hence there are conditions under which optimal strategies will be relatively easy to uncover, and others in which suboptimal time allocation might be expected. The model can therefore be used to address the question of whether and when learners should be able to exercise good metacognitive control in practice.