bluuebunny/crossref_metadata_2025_split huggingface dataset:
The apoptotic machinery as a biological complex system: analysis of its omics and evolution, identification of candidate genes for fourteen major types of cancer, and experimental validation in CML and neuroblastoma
Authors: Di Pietro Cinzia , Ragusa Marco , Barbagallo Davide , Duro Laura R , Guglielmino Maria R , Majorana Alessandra , Angelica Rosario , Scalia Marina , Statello Luisa , Salito Loredana , Tomasello Luisa , Pernagallo Salvo , Valenti Salvo , D'Agostino Vito , Triberio Patrizio , Tandurella Igor , Palumbo Giuseppe A , La Cava Piera , Cafiso Viviana , Bertuccio Taschia , Santagati Maria , Li Destri Giovanni , Lanzafame Salvatore , Di Raimondo Francesco , Stefani Stefania , Mishra Bud , Purrello Michele 
Published: May 2009

AbstractBackgroundApoptosis is a critical biological phenomenon, executed under the guidance of the Apoptotic Machinery (AM), which allows the physiologic elimination of terminally differentiated, senescent or diseased cells. Because of its relevance to BioMedicine, we have sought to obtain a detailed characterization of AM Omics inHomo sapiens, namely its Genomics and Evolution, Transcriptomics, Proteomics, Interactomics, Oncogenomics, and Pharmacogenomics.MethodsThis project exploited the methodology commonly used in Computational Biology (i.e., mining of manyomicsdatabases of the web) as well as the High Throughput biomolecular analytical techniques.ResultsInHomo sapiensAM is comprised of 342 protein-encoding genes (possessing either anti- or pro-apoptotic activity, or a regulatory function) and 110 MIR-encoding genes targeting them: some have a critical role within the system (coreAM nodes), others perform tissue-, pathway-, or disease-specific functions (peripheralAM nodes). By overlapping the cancer type-specific AM mutation map in the fourteen most frequent cancers in western societies (breast, colon, kidney, leukaemia, liver, lung, neuroblastoma, ovary, pancreas, prostate, skin, stomach, thyroid, and uterus) to their transcriptome, proteome and interactome in the same tumour type, we have identified the most prominent AM molecular alterations within each class. The comparison of the fourteen mutated AM networks (both protein- as MIR-based) has allowed us to pinpoint the hubs with a general and critical role in tumour development and, conversely, in cell physiology: in particular, we found that some of these had already been used as targets for pharmacological anticancer therapy. For a better understanding of the relationship between AM molecular alterations and pharmacological induction of apoptosis in cancer, we examined the expression of AM genes in K562 and SH-SY5Y after anticancer treatment.ConclusionWe believe that our data on the Apoptotic Machinery will lead to the identification of new cancer genes and to the discovery of new biomarkers, which could then be used to profile cancers for diagnostic purposes and to pinpoint new targets for pharmacological therapy. This approach could pave the way for future studies and applications in molecular and clinical Medicine with important perspectives both for Oncology as for Regenerative Medicine.
Comparison between Flotrac-Vigileo and Bioreactance, a totally noninvasive method for cardiac output monitoring
Authors: Marqué Sophie , Cariou Alain , Chiche Jean-Daniel , Squara Pierre 
Published: May 2009

Abstract
Introduction
This study was designed to compare the clinical acceptability of two cardiac output (CO) monitoring systems: a pulse wave contour-based system (FloTrac-Vigileo) and a bioreactance-based system (NICOM), using continuous thermodilution (PAC-CCO) as a reference method.

Methods
Consecutive patients, requiring PAC-CCO monitoring following cardiac surgery, were also monitored by the two other devices. CO values obtained simultaneously by the three systems were recorded continuously on a minute-by-minute basis.

Results
Continuous recording was performed on 29 patients, providing 12,099 simultaneous measurements for each device (417 ± 107 per patient). In stable conditions, correlations of NICOM and Vigileo with PAC-CCO were 0.77 and 0.69, respectively. The bias was -0.01 ± 0.84 for NICOM and -0.01 ± 0.81 for Vigileo (NS). NICOM relative error was less than 30% in 94% of the patients and less than 20% in 79% vs. 91% and 79% for the Vigileo, respectively (NS). The variability of measurements around the trend line (precision) was not different between the three methods: 8 ± 3%, 8 ± 4% and 8 ± 3% for PAC-CCO, NICOM and Vigileo, respectively. CO changes were 7.2 minutes faster with Vigileo and 6.9 minutes faster with NICOM (P < 0.05 both systems vs. PAC-CCO, NS). Amplitude of changes was not significantly different than thermodilution. Finally, the sensitivity and specificity for predicting significant CO changes were 0.91 and 0.95 respectively for the NICOM and 0.86 and 0.92 respectively for the Vigileo.

Conclusions
This study showed that the NICOM and Vigileo devices have similar monitoring capabilities in post-operative cardiac surgery patients.
Improvements in Survival After Follicular Lymphoma by Race/Ethnicity and Socioeconomic Status: A Population-Based Study
Authors: Keegan Theresa H.M. , McClure Laura A. , Foran James M. , Clarke Christina A. 
Published: May 2009

Purpose A recent report suggested improvements in survival after follicular lymphoma (FL), but not for all racial/ethnic groups. To better understand the reasons for these FL survival differences, we examined the joint influences of diagnostic period, race/ethnicity, and neighborhood socioeconomic status (SES) on survival in a large population-based case series. Methods All patients (n = 15,937) diagnosed with FL between 1988 and 2005 in California were observed for vital status through November 2007. Overall and FL-specific survival were analyzed with Kaplan-Meier and Cox proportional hazards regression. Neighborhood SES was assigned from United States Census data using residence at diagnosis. Results Overall and FL-specific survival improved 22% and 37%, respectively, from 1988 to 1997 to 1998 to 2005, and were observed in all racial/ethnic groups. Asian/Pacific Islanders had better survival than non-Hispanic white, Hispanic, and black patients who had similar outcomes. Lower neighborhood SES was associated with worse survival in patients across all stages of disease (P for trend < .01). Patients with the lowest SES quintile had a 49% increased risk of death from all causes (hazard ratio [HR] = 1.49, 95% CI, 1.30 to 1.72) and 31% increased risk of death from FL (HR = 1.31; 95% CI, 1.06 to 1.60) than patients with the highest SES. Conclusion Evolving therapies have likely led to improvements in survival after FL. Although improvements have occurred within all racial/ethnic groups, lower neighborhood SES was significantly associated with substantially poorer survival.
Sorafenib for Treatment of Renal Cell Carcinoma: Final Efficacy and Safety Results of the Phase III Treatment Approaches in Renal Cancer Global Evaluation Trial
Authors: Escudier Bernard , Eisen Tim , Stadler Walter M. , Szczylik Cezary , Oudard Stéphane , Staehler Michael , Negrier Sylvie , Chevreau Christine , Desai Apurva A. , Rolland Frédéric , Demkow Tomasz , Hutson Thomas E. , Gore Martin , Anderson Sibyl , Hofilena Gloria , Shan Minghua , Pena Carol , Lathia Chetan , Bukowski Ronald M. 
Published: May 2009

Purpose Mature survival data and evaluation of vascular endothelial growth factor (VEGF) as a prognostic biomarker from the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) study in patients with renal cell carcinoma (RCC) are reported. Patients and Methods Nine hundred three previously treated patients were randomly assigned to receive sorafenib versus placebo. On demonstration of progression-free survival (PFS) benefit with sorafenib, patients assigned to placebo were offered sorafenib. Overall survival (OS) was determined at two planned interim analyses and one final analysis, with a secondary OS analysis conducted by censoring placebo patients who crossed over to sorafenib. The relationships between baseline VEGF level and prognosis and efficacy were evaluated. Results The final OS of patients receiving sorafenib was comparable with that of patients receiving placebo (17.8 v 15.2 months, respectively; hazard ratio [HR] = 0.88; P = .146); however, when post–cross-over placebo survival data were censored, the difference became significant (17.8 v 14.3 months, respectively; HR = 0.78; P = .029). Adverse events at 16 months after cross over were similar to those previously reported. Baseline VEGF levels correlated with Eastern Cooperative Oncology Group performance status (P < .0001), Memorial Sloan-Kettering Cancer Center score (P < .0001), and PFS and OS in univariate (PFS, P = .0013; OS, P = .0009) and multivariate (PFS, P = .0231; OS, P = .0416) analyses of placebo patients and with short OS by multivariate analysis of patients receiving sorafenib (P = .0145). Both high-VEGF (P < .01) and low-VEGF (P < .01) groups benefited from sorafenib. Conclusion Although an OS benefit was not seen on a primary intent-to-treat analysis, results of a secondary OS analysis censoring placebo patients demonstrated a survival advantage for those receiving sorafenib, suggesting an important cross-over effect. VEGF levels are prognostic for PFS and OS in RCC. The results of TARGET establish the efficacy and safety of sorafenib in advanced RCC.
Humanized Anti-CD20 Antibody, Veltuzumab, in Refractory/Recurrent Non-Hodgkin's Lymphoma: Phase I/II Results
Authors: Morschhauser Franck , Leonard John P. , Fayad Luis , Coiffier Bertrand , Petillon Marie-Odile , Coleman Morton , Schuster Stephen J. , Dyer Martin J.S. , Horne Heather , Teoh Nick , Wegener William A. , Goldenberg David M. 
Published: May 2009

Purpose This is a multicenter phase I/II dose-finding study in relapsed/refractory B-cell non-Hodgkin's lymphoma (NHL) evaluating veltuzumab, a humanized anti-CD20 antibody with structure-function differences from chimeric rituximab. Patients and Methods Eighty-two patients (median age, 64 years; 79% stage III/IV, one to nine prior treatments) received four once-weekly doses of 80 to 750 mg/m2 of veltuzumab and were assessed for safety, efficacy, pharmacodynamics, pharmacokinetics, and immunogenicity. Results Veltuzumab was well tolerated, with no grade 3 to 4 drug-related adverse events despite short infusion times (typically 2 hours initially, 1 hour subsequently at doses < 375 mg/m2). In follicular lymphoma, 24 (44%) of 55 patients had objective responses (OR), with 15 (27%) complete responses (CRs) or CRs unconfirmed (CRus) by International Working Group criteria, and with some responses occurring despite two to five prior rituximab-containing regimens, less favorable prognosis (elevated lactate dehydrogenase, tumors > 5 cm, and Follicular Lymphoma International Prognostic Index ≥ 2), and at all dose levels. The CRs/CRus were durable (median duration, 19.7 months), with five patients still ongoing (15.9 to 37.6 months duration). In marginal zone lymphoma, five (83%) of six patients had ORs, with two CRs/CRus (33%), and in diffuse large B-cell lymphoma, three (43%) of seven patients achieved partial responses. At all dose levels studied, B cells were depleted after the first infusion, veltuzumab serum half-lives were similar after the fourth infusion, and mean antibody serum levels exceeded values considered important for anti-CD20 therapy (ie, 25 μg/mL). Conclusion Veltuzumab appeared safe and active at all tested doses, encouraging further study, including dose levels less than those typically used with rituximab.
Imatinib Plasma Levels Are Correlated With Clinical Benefit in Patients With Unresectable/Metastatic Gastrointestinal Stromal Tumors
Authors: Demetri George D. , Wang Yanfeng , Wehrle Elisabeth , Racine Amy , Nikolova Zariana , Blanke Charles D. , Joensuu Heikki , von Mehren Margaret 
Published: May 2009

Purpose To study the pharmacokinetics (PK) of imatinib (IM) in patients with advanced GI stromal tumors (GISTs) treated in a randomized phase II study and to explore the potential relationship between IM plasma levels and long-term clinical outcomes. Patients and Methods Patients were randomly assigned to receive IM at 400 mg versus 600 mg daily. IM plasma levels were analyzed in a subset of patients (n = 73) for whom PK data on day 1 and at steady-state (SS, day 29) were available. IM PK was evaluated using a population PK approach. The relationship between IM plasma exposure and clinical outcome was explored by grouping patients into quartiles according to IM trough concentration (Cmin). The clinical outcome parameters evaluated include overall objective benefit rate (OOBR; complete response plus partial response plus stable disease) time to progression (TTP), and KIT genotyping. Results IM PK exposure showed a high inter-patient variability, and clinical outcomes were correlated with IM trough levels at SS. The median TTP was 11.3 months for patients in the lowest Cmin quartile (Q1, < 1,110 ng/mL) compared with more than 30 months for Q2 to Q4 (P = .0029). OOBR was also inferior in Q1 patients. In patients with GIST with KIT exon 11 mutations (n = 39), the OOBR was 67% for Q1 patients versus 100% for all others (P = .001). Conclusion In patients with advanced GIST, IM trough levels at SS were associated with clinical benefit. Patients with IM Cmin below 1,100 ng/mL showed a shorter TTP and lower rate of clinical benefit (OOBR). Further studies are justified to test whether monitoring IM plasma levels might optimize clinical outcomes for patients with GIST.
Safety and Efficacy of Patupilone in Patients With Advanced Ovarian, Primary Fallopian, or Primary Peritoneal Cancer: A Phase I, Open-Label, Dose-Escalation Study
Authors: ten Bokkel Huinink Wim W. , Sufliarsky Jozef , Smit Willem M. , Spanik Stanislav , Wagnerova Maria , Hirte Hal W. , Kaye Stan , Johri Anandhi R. , Oza Amit M. 
Published: May 2009

Purpose To evaluate the safety, maximum tolerated dose (MTD), and pharmacokinetics of patupilone administered once every 3 weeks with proactive standardized diarrhea management in patients with resistant or refractory ovarian, fallopian, or peritoneal cancer. Patients and Methods Patients received patupilone (6.5 to 11.0 mg/m2) every 3 weeks via 20-minute infusion. Adverse events, dose-limiting toxicities (DLT), MTD, and tumor response were determined. The tumor response was measured by Response Evaluation Criteria in Solid Tumors (RECIST) and cancer antigen 125 levels. Results Forty-five patients were enrolled. Adverse events were mild to moderate in intensity, and grade 3 diarrhea (13%) was the most commonly reported serious adverse event. Grade 3 peripheral neuropathy was noted in two patients (4%). Diarrhea, peripheral neuropathy, and fatigue were the most common DLTs; however, these were uncommon in the first cycle and the MTD was therefore not reached in this study. Overall response (OR; complete and partial responses; median cycles, 8) per RECIST in patients with measurable disease (n = 36) was 19.5%. Median duration of disease stabilization (complete and partial responses and stable disease) was 15.8 months. These results appear improved from a previous study in a similar patient population using a weekly schedule (2.5 mg/m2/week; N = 53; OR, 5.7%). Conclusion Patupilone once every 3 weeks was well-tolerated at doses up to 11.0 mg/m2. Patupilone demonstrated promising antitumor activity in patients with drug-resistant/refractory disease. An ongoing phase III study in this patient population is testing the 10.0 mg/m2 dose.
Multicenter Phase II Trial of Sunitinib in the Treatment of Nongastrointestinal Stromal Tumor Sarcomas
Authors: George Suzanne , Merriam Priscilla , Maki Robert G. , Van den Abbeele Annick D. , Yap Jeffrey T. , Akhurst Timothy , Harmon David C. , Bhuchar Gauri , O'Mara Margaret M. , D'Adamo David R. , Morgan Jeffrey , Schwartz Gary K. , Wagner Andrew J. , Butrynski James E. , Demetri George D. , Keohan Mary L. 
Published: May 2009

Purpose To evaluate the potential benefit of continuous daily dosing sunitinib in patients with advanced nongastrointestinal stromal tumor (GIST) sarcomas. Patients and Methods A total of 53 patients with advanced non-GIST soft tissue sarcomas received sunitinib 37.5 mg daily. Primary end point was Response Evaluation Criteria in Solid Tumors defined response. Secondary end points were stable disease at 16 and 24 weeks. [18F]-fluorodeoxyglucose positron emission tomography was performed on a subset of 24 patients at baseline and after 10 to 14 days of therapy. Results Forty-eight patients were eligible for response. One patient (desmoplastic round cell tumor [DSRCT]) achieved a confirmed partial response (PR) and remained on study for 56 weeks. Ten patients (20%) achieved stable disease for at least 16 weeks. Metabolic PR was seen in 10 (47%) of 21 of patients. Metabolic stable disease was seen in 11 (52%) of 21. There were no unexpected toxicities observed. Conclusion Sunitinib demonstrated notable evidence of metabolic response in several patients with non-GIST sarcoma. The relevance of disease control observed in subtypes with an indolent natural history is unknown, however, the durable disease control observed in DSRCT, solitary fibrous tumor, and giant cell tumor of bone suggests that future evaluation of sunitinib in these subtypes may be warranted.
Pazopanib, a Multikinase Angiogenesis Inhibitor, in Patients With Relapsed or Refractory Advanced Soft Tissue Sarcoma: A Phase II Study From the European Organisation for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group (EORTC Study 62043)
Authors: Sleijfer Stefan , Ray-Coquard Isabelle , Papai Zsuzsa , Le Cesne Axel , Scurr Michelle , Schöffski Patrick , Collin Françoise , Pandite Lini , Marreaud Sandrine , De Brauwer Annick , van Glabbeke Martine , Verweij Jaap , Blay Jean-Yves 
Published: May 2009

Purpose Given the importance of angiogenesis in soft tissue sarcoma (STS), pazopanib, an oral angiogenesis inhibitor that targets vascular endothelial growth factor receptor and platelet-derived growth factor receptor, was explored in patients with advanced STS. Patients and Methods Patients with intermediate- or high-grade advanced STS who were ineligible for chemotherapy or who had received no more than two prior cytotoxic agents for advanced disease, who had documented progression, who had adequate performance status, and who had good organ function were eligible. Pazopanib 800 mg was given daily. The primary end point was progression-free rate at 12 weeks (PFR12 weeks). Secondary end points were response, safety, and overall survival. Four different strata were studied: adipocytic STS, leiomyosarcomas, synovial sarcomas, and other STS types. A Simon two-stage design was applied (P1 = 40%; P0 = 20%; α = β = .1) for each stratum. Results One hundred forty-two patients were enrolled. The adipocytic STS stratum was closed after the first stage, given insufficient activity (PFR12 weeks, five [26%] of19). PFR12 weeks was 18 (44%) of 41 patients in the leiomyosarcoma cohort, 18 (49%) of 37 in the synovial sarcomas, and 16 (39%) of 41 in the other STS types. Compared with historical controls who were treated with second-line chemotherapy, progression-free and overall survivals were prolonged in the three cohorts in which the primary end point was reached. The most frequent drug-related toxicities were hypertension, fatigue, hypopigmentation, and nausea. Other toxicities included liver enzyme elevations, myelosuppression, and proteinuria, all of which were mostly grades 1 to 2. The most frequent grades 3 to 4 toxicities were hyperbilirubinemia (6.3%), hypertension (7.7%), and fatigue (7.7%). Conclusion Pazopanib is well tolerated in patients with relapsed, advanced STS and demonstrates interesting activity that warrants additional study in patients with leiomyosarcomas, synovial sarcomas, and other STS types.
Reading Democratically: Pedagogies of Difference and Practices of Listening in The House of Mirth and Passing
Authors: Bromell Nick 
Published: May 2009

Bromell's essay argues that Edith Wharton's The House of Mirth and Nella Larsen's Passing both represent and enact a core problem in theories of deliberative democracy: how to assess the value of differences among citizens (of race, gender, or age) when democracy is understood primarily in terms of its communicative practices. On the one hand, a deliberative democracy would appear to need some minimal “common standards” of what constitutes reasoned communication. On the other, it also seeks to allow as much genuine difference to enter into democratic deliberations as possible. What exactly does it mean for democratic citizens to communicate successfully? How should they understand the act of communication with an “Other” who is different, and how should they understand what it means to “know” this Other?
These questions animate both novels. The House of Mirth is concerned with gender difference primarily and Passing mainly with racial difference, but both are careful also to situate these differences within an explicitly acknowledged range of other differences, including those of class and sexuality. These novels depict the failed and successful communicative strategies adopted by their characters as they encounter others who are “different” and struggle to “know” and communicate with them. Both novels go beyond merely representing the problem of knowing and communicating difference to deploy sophisticated narrative methods that and pull their readers into this problem, requiring us to employ and test various strategies ourselves. They thereby offer a democratic pedagogy that encourages readers to understand that knowing an “Other” means acknowledging also that we can never completely know and fix the meaning of difference.
Identification of Rice Variety Using near Infrared Spectroscopy
Authors: Kwon Y.K. , Cho R.K. 
Published: May 2009

Current techniques for the discrimination of varieties of rice is known not to be objective because of having to depend on the naked eye of a well trained inspector. DNA fingerprint methods, based on the genetic character of rice, has been shown to be inappropriate for on-site application because the method needs a lot of labour and skilled expertise. In order to solve these problems, many researchers have tried to develop a non-destructive method which possesses speed and functionality for the inspection centre of the government. Rice consumers want tot confirm cultivation origin and its variety because they believe price or eating score has a high correlation according to them. Sometimes illegal utilisation of rice has been reported and the variety name has been mismatched with the actual rice variety due to the non-establishment of objective techniques for discrimination of rice origin and variety. On the basis of this situation, we investigated the possibility of developing a non-destructive discriminant method for the domestic rice variety in this research. At the 8th IDRC held at Chambersburg in 1996 we reported that an image processing technique using a CCD camera could discriminate the variety of rice with high accuracy in the case of quite different shaped rice but the accuracy reached 90% for similarly shaped rice. At the prsent conference, near infrared spectroscopy, which can offer internal characters of a single rice kernel, giving useful information for identifying rice variety, was introduced. We have developed several tools for measuing the NIR spectra of whole, polished rice. The spectra using a single grain cell with grinding facilities was more effective than the others in accuracy of identification after principal component analysis. In conclusion, near infrared spectroscopy can be used to identify rice varieties even though even though accuracy of identification needs to be improved.