bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haploinsufficiency for p190B RhoGAP inhibits MMTV-Neu tumor progression
Authors: Heckman-Stoddard Brandy M , Vargo-Gogola Tracy , McHenry Peter R , Jiang Vivian , Herrick Matthew P , Hilsenbeck Susan G , Settleman Jeffrey , Rosen Jeffrey M 
Published: August 2009

Abstract
Introduction
Rho signaling regulates key cellular processes including proliferation, survival, and migration, and it has been implicated in the development of many types of cancer including breast cancer. P190B Rho GTPase activating protein (RhoGAP) functions as a major inhibitor of the Rho GTPases. P190B is required for mammary gland morphogenesis, and overexpression of p190B in the mammary gland induces hyperplastic lesions. Hence, we hypothesized that p190B may play a pivotal role in mammary tumorigenesis.

Methods
To investigate the effects of loss of p190B function on mammary tumor progression, p190B heterozygous mice were crossed with an MMTV-Neu breast cancer model. Effects of p190B deficiency on tumor latency, multiplicity, growth, preneoplastic progression and metastasis were evaluated. To investigate potential differences in tumor angiogenesis between the two groups, immunohistochemistry to detect von Willebrand factor was performed and quantified. To examine gene expression of potential mediators of the angiogenic switch, an angiogenesis PCR array was utilized and results were confirmed using immunohistochemistry. Finally, reciprocal transplantation of tumor fragments was performed to determine the impact of stromal deficiency of p190B on tumor angiogenesis.

Results
P190B deficiency reduced tumor penetrance (53% of p190B+/-Neu mice vs. 100% of p190B+/+Neu mice formed tumors) and markedly delayed tumor onset by an average of 46 weeks. Tumor multiplicity was also decreased, but an increase in the number of preneoplastic lesions was detected indicating that p190B deficiency inhibited preneoplastic progression. Angiogenesis was decreased in the p190B heterozygous tumors, and expression of a potent angiogenic inhibitor, thrombospondin-1, was elevated in p190B+/-Neu mammary glands. Transplantation of p190B+/-Neu tumor fragments into wild-type recipients restored tumor angiogenesis. Strikingly, p190B+/+Neu tumor fragments were unable to grow when transplanted into p190B+/-Neu recipients.

Conclusions
These data suggest that p190B haploinsufficiency in the epithelium inhibits MMTV-Neu tumor initiation. Furthermore, p190B deficiency in the vasculature is responsible, in part, for the inhibition of MMTV-Neu tumor progression.
Admission factors associated with hospital mortality in patients with haematological malignancy admitted to UK adult, general critical care units: a secondary analysis of the ICNARC Case Mix Programme Database
Authors: Hampshire Peter A , Welch Catherine A , McCrossan Lawrence A , Francis Katharine , Harrison David A 
Published: August 2009

Abstract
Introduction
Patients with haematological malignancy admitted to intensive care have a high mortality. Adverse prognostic factors include the number of organ failures, invasive mechanical ventilation and previous bone marrow transplantation. Severity-of-illness scores may underestimate the mortality of critically ill patients with haematological malignancy. This study investigates the relationship between admission characteristics and outcome in patients with haematological malignancies admitted to intensive care units (ICUs) in England, Wales and Northern Ireland, and assesses the performance of three severity-of-illness scores in this population.

Methods
A secondary analysis of the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme Database was conducted on admissions to 178 adult, general ICUs in England, Wales and Northern Ireland between 1995 and 2007. Multivariate logistic regression analysis was used to identify factors associated with hospital mortality. The Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II and ICNARC score were evaluated for discrimination (the ability to distinguish survivors from nonsurvivors); and the APACHE II, SAPS II and ICNARC mortality probabilities were evaluated for calibration (the accuracy of the estimated probability of survival).

Results
There were 7,689 eligible admissions. ICU mortality was 43.1% (3,312 deaths) and acute hospital mortality was 59.2% (4,239 deaths). ICU and hospital mortality increased with the number of organ failures on admission. Admission factors associated with an increased risk of death were bone marrow transplant, Hodgkin's lymphoma, severe sepsis, age, length of hospital stay prior to intensive care admission, tachycardia, low systolic blood pressure, tachypnoea, low Glasgow Coma Score, sedation, PaO2:FiO2, acidaemia, alkalaemia, oliguria, hyponatraemia, hypernatraemia, low haematocrit, and uraemia. The ICNARC model had the best discrimination of the three scores analysed, as assessed by the area under the receiver operating characteristic curve of 0.78, but all scores were poorly calibrated. APACHE II had the highest accuracy at predicting hospital mortality, with a standardised mortality ratio of 1.01. SAPS II and the ICNARC score both underestimated hospital mortality.

Conclusions
Increased hospital mortality is associated with the length of hospital stay prior to ICU admission and with severe sepsis, suggesting that, if appropriate, such patients should be treated aggressively with early ICU admission. A low haematocrit was associated with higher mortality and this relationship requires further investigation. The severity-of-illness scores assessed in this study had reasonable discriminative power, but none showed good calibration.
Escalated-Dose BEACOPP in the Treatment of Patients With Advanced-Stage Hodgkin's Lymphoma: 10 Years of Follow-Up of the GHSG HD9 Study
Authors: Engert Andreas , Diehl Volker , Franklin Jeremy , Lohri Andreas , Dörken Bernd , Ludwig Wolf-Dieter , Koch Peter , Hänel Mathias , Pfreundschuh Michael , Wilhelm Martin , Trümper Lorenz , Aulitzky Walter-Erich , Bentz Martin , Rummel Mathias , Sezer Orhan , Müller-Hermelink Hans-Konrad , Hasenclever Dirk , Löffler Markus 
Published: August 2009

Purpose The HD9 trial of the German Hodgkin Study Group compared two different doses (baseline and escalated) of the bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) chemotherapy regimen in 1,196 patients with advanced-stage Hodgkin's lymphoma (HL). The previous analysis with 5 years median follow-up had indicated improved tumor control with BEACOPP escalated. Since the long-term safety and efficacy of this regimen has been debated, we report the 10-year follow-up. Patients and Methods Patients received one of three chemotherapy regimens: eight cycles of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); eight cycles of BEACOPP baseline; or eight cycles of BEACOPP escalated. Results Median follow-up was 111 months. At 10 years, freedom from treatment failure (FFTF) was 64%, 70%, and 82% with OS rates of 75%, 80%, and 86% for patients treated with COPP/ABVD (arm A), BEACOPP baseline (arm B), and BEACOPP escalated (arm C), respectively (P < .001). BEACOPP escalated was significantly better than BEACOPP baseline in terms of FFTF (P < .0001) and OS (P = .0053). A total of 74 second malignancies (6.2%) were documented, including acute myeloid leukemia (0.4%, 1.5%, and 3.0%), non-Hodgkin's lymphoma (2.7%, 1.7%, and 1.0%), and solid tumors (2.7%, 3.4%, and 1.9%). The corresponding overall secondary malignancy rates were 5.7%, 6.6%, and 6.0%, respectively. Conclusion The 10-year follow-up of the HD9 trial demonstrates a stabilized significant improvement in long-term FFTF and OS for BEACOPP escalated in advanced-stage HL. These results challenge ABVD as standard of care for this patient population.
Professionals Assess the Acceptability of Preimplantation Genetic Diagnosis and Prenatal Diagnosis for Managing Inherited Predisposition to Cancer
Authors: Julian-Reynier Claire , Chabal Françoise , Frebourg Thierry , Lemery Didier , Noguès Catherine , Puech Francis , Stoppa-Lyonnet Dominique 
Published: August 2009

Purpose Preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND) practices for inherited predisposition to cancer are heterogeneous in industrialized countries. In France, permission to perform PGD/PND must be obtained from registered Multidisciplinary Prenatal Diagnosis Teams (MPDTs). The aim of this study was to determine French professionals' attitudes about the acceptability of PGD and PND for inherited predisposition to cancer. Methods A cross-sectional survey was performed, involving self-administered questionnaires mailed to all registered cancer geneticists (CGs; n = 123) and MPDTs (n = 47) in France. Results The response rates of CGs and MPDTs were 62% and 64%, respectively; 59% and 50% of the CGs had at least discussed PGD and PND, respectively, with their consultees during the previous year. When severe cancer is liable to occur in childhood with a high penetrance and no effective methods of prevention/treatment exist, high rates of acceptability of PGD/PND were recorded (> 80%). When cancer is liable to occur before the age of 50 years but not in childhood and some form of prevention/treatment is available that preserves quality of life, PGD was rated as acceptable by one MPDT (3.3%) and 10 CGs (13.2%), and PND was rated acceptable by nine CGs (11.8%). Most respondents agreed that the acceptability of PND/PGD depends on patients' family history of cancer and their reproductive history. Conclusion With the most severe forms of inherited cancer, no differences were observed between the acceptability to practitioners of PND and PGD, but with late-onset syndromes, there is still much uncertainty. Guidelines would help to standardize the practices of professionals handling these reproductive issues.
Phase III Trial of Observation Versus Six Courses of Paclitaxel in Patients With Advanced Epithelial Ovarian Cancer in Complete Response After Six Courses of Paclitaxel/Platinum-Based Chemotherapy: Final Results of the After-6 Protocol 1
Authors: Pecorelli Sergio , Favalli Giuseppe , Gadducci Angiolo , Katsaros Dionyssios , Panici Pierluigi Benedetti , Carpi Amalia , Scambia Giovanni , Ballardini Michela , Nanni Oriana , Conte PierFranco 
Published: August 2009

Purpose To assess whether six courses of paclitaxel are effective as consolidation treatment in patients with advanced epithelial ovarian cancer who are in complete response after first-line paclitaxel/platinum–based chemotherapy. Patients and Methods Patients with stages IIb to IV disease in clinical or pathologic complete response after six courses of paclitaxel/platinum–based chemotherapy were randomly allocated to either observation (ie, control) or six courses of paclitaxel 175 mg/m2 every 3 weeks (ie, maintenance). Results Two hundred patients were randomly assigned from March 1999 to July 2006. Because of the low accrual rate, an unplanned interim analysis of futility according to the Bayesian approach was performed. Grade 2 or greater motor neurotoxicity and sensory neurotoxicity were reported in 11.3% and 28.0% of the paclitaxel-arm patients, respectively. After a median follow-up of 43.5 months, 107 patients (53%) had experienced relapse, and 48 patients (24%) had died. Two-year progression-free survival rates were 54% (95% CI, 43% to 64%) and 59% (95% CI, 49% to 69%; P = not significant) in the control and maintenance arms, respectively. Corresponding 2-year overall survival rates were 90% (95% CI, 84% to 97%) and 87% (95% CI, 80% to 94%; P = not significant), respectively. The Cox model showed that residual disease after initial surgery (macroscopic v no macroscopic residuum; hazard ratio [HR], 1.91; 95%CI, 1.21 to 3.03) and stage (IIIc to IV v others; HR, 3.10; 95% CI, 1.13 to 8.48) were independent prognostic factors for progression-free survival, whereas the treatment arm (maintenance v control) had no prognostic relevance. Conclusion A consolidation treatment with six cycles of paclitaxel does not prolong progression-free survival or overall survival in patients in complete response after first-line paclitaxel/platinum–based regimens.
Rituximab, Fludarabine, Cyclophosphamide, and Mitoxantrone: A New, Highly Active Chemoimmunotherapy Regimen for Chronic Lymphocytic Leukemia
Authors: Bosch Francesc , Abrisqueta Pau , Villamor Neus , Terol María José , González-Barca Eva , Ferra Christelle , González Diaz Marcos , Abella Eugenia , Delgado Julio , Carbonell Félix , García Marco José Antonio , Escoda Lourdes , Ferrer Secundino , Monzó Encarnación , González Yolanda , Estany Cristina , Jarque Isidro , Salamero Olga , Muntañola Ana , Montserrat Emili 
Published: August 2009

Purpose The addition of monoclonal antibodies to chemotherapy has significantly improved treatment of chronic lymphocytic leukemia (CLL). Based on excellent results with the chemotherapy-only regimen fludarabine, cyclophosphamide, and mitoxantrone (FCM), we built a new chemoimmunotherapy combination—rituximab plus FCM (R-FCM). We report a phase II clinical trial consisting of an initial treatment with R-FCM followed by rituximab maintenance. Patients and Methods Seventy-two untreated CLL patients age 70 years or younger received rituximab 500 mg/m2 on day 1 (375 mg/m2 the first cycle), fludarabine 25 mg/m2 IV on days 1 to 3, cyclophosphamide 200 mg/m2 on days 1 to 3, and mitoxantrone 6 mg/m2 IV on day 1, given at 4-week intervals with up to six cycles supported with colony-stimulating factor. Patients achieving response received maintenance with rituximab 375 mg/m2 every 3 months for 2 years. Results The overall response, minimal residual disease (MRD) –negative complete response (CR), MRD-positive CR, and partial response rates were 93%, 46%, 36%, and 11%, respectively. Severe neutropenia developed in 13% of patients. Major and minor infections were reported in 8% and 5% of cycles, respectively. Advanced clinical stage, del(17p), or increased serum β2-microglobulin levels correlated with a lower CR rate. Conclusion R-FCM is highly effective in previously untreated CLL, with an 82% CR rate and a high proportion of MRD-negative CRs (46%). Treatment toxicity is acceptable. Parameters correlating with a lower response rate were advanced clinical stage, high serum β2-microglobulin levels, and del(17p). Based on these results, R-FCM warrants further investigation in randomized clinical trials.
"There is no anachronism": Indian Dancing Girls in Ancient Carthage in Berlioz's Les Troyens
Authors: Van Rij Inge 
Published: August 2009

Abstract
Relatively early in the composition of Les Troyens Berlioz declared his intention to include a "pas d'almées with the music and dancing exactly like the Bayadères' ballet which I saw here sixteen or seventeen years ago." Despite Berlioz's claim that he had "gone into it" and "there is no anachronism," historical evidence would suggest that the presence of Indian dancing girls in Dido's Carthage is actually highly inauthentic and anachronistic. Indeed, Berlioz's immediate inspiration for the ballet in question was not ancient history but, rather, a group of Indian dancers and musicians who had visited Paris in 1838. An investigation of the context of the bayadères' performances and the reception of the dancers and their music reveals that issues of authenticity and anachronism were a constant preoccupation for their French audiences, most of whom had previously encountered bayadères only through the exoticizing lens of Western representations. Berlioz's own references to the bayadères are examined in relation to contemporary reviews and the text of a highly self-reflexive play that was performed as a prologue and that shaped audiences' responses to the bayadères' performances at the Théâtre des Variétés in Paris. Although Berlioz is generally thought to have abandoned his intention to embody the 1838 bayadères in Les Troyens, I argue that he actually retained aspects of his original Indian inspiration in the act IV ballet; moreover, an awareness of the impact of the bayadères' performances on Berlioz and his contemporaries greatly informs our appreciation of the contribution of the act IV ballet to the wider imperial subtext of Les Troyens. If, rather than simply dismissing anachronism, we are willing to embrace it as a concept fundamental to Berlioz's opera, the act IV ballet—often cut in recent productions—can be newly appreciated as occupying a significant role in the historical dialectic of Les Troyens as a whole.
Flying Leaves: Between Berlioz and Wagner
Authors: Kolb Katherine 
Published: August 2009

Abstract
This article analyzes the writings of Berlioz on Wagner and, to a lesser extent, of Wagner on Berlioz, emphasizing the covert innuendoes of their verbal sparring during the period surrounding the Tannhäuser debacle at the Paris Opéra (1860) and Berlioz's tribulations with Les Troyens (ca. 1853–63). Because Berlioz's style and subtlety have worked against him in this famous rivalry, the priority goes to him, and especially to his magnum opus as critic, the volume A travers chants (1862). A selection from thirty years of music criticism both serious and light ("flying leaves"), A travers chants reveals itself as an unconventional counterpart to Wagner's treatises; as a tactical response to Wagner, both in the reprinted review of his 1860 concerts and in the structure, themes, and allusions of the text as a whole; as an object lesson in reading Berlioz, whose engaging clarity and humor can be more deceptive, in their ironic undertones, than the thickets of Wagner's famously tangled prose. This article interrogates some of that prose, revealing Wagner's deep ambivalence toward a predecessor of intimidating prestige to whom his music is frequently indebted—as Berlioz occasionally finds coded ways of reminding him. It shows Berlioz, for his part, continually sympathetic to the younger man's practical difficulties and high artistic ideals. And it shows him eventually coming to acknowledge the power and legitimacy of his music, despite strong aversion to Wagner's harmonic idiom and to the two cardinal points of his aesthetic: an "impious" insistence on the primacy of the word; belief in a musical progress culminating in his own Gesamtkunstwerk. In a late letter wrongly omitted from the Correspondance générale (its authenticity and correct date are here established), Berlioz movingly implies the injustice of his earlier prejudice toward a practice sanctioned by his own unshakeable creed of artistic freedom.
"Vous qui faites l'endormie": The Phantom and the Buried Voices of the Paris Opéra
Authors: Newark Cormac 
Published: August 2009

Abstract
Gaston Leroux's Le Fantôme de l'Opéra (1909–10), as well as providing the model for some famous adaptations in other media, represents an important late stage in the development of a venerable French novelistic tradition: the soirée à l'Opéra. Notwithstanding his obvious lack of musical expertise (or perhaps because of it), Leroux's keen exploration of operatic reception deserves its place alongside more eminent contributors to that tradition such as Balzac, Dumas, and Flaubert. The richness of his portrayal of the institution's mythology and place in contemporary popular consciousness derives partly from his direct use of a large number of sources, which goes far beyond the conventions of the Gothic novel. These range from real and fictional operas to reportage concerning the famous fatal accident at the Opéra in 1896 and the rivalry between Christine Nilsson and Marie Miolan-Carvalho. The most significant of them, though, is the set of gramophone records buried underneath the Opéra in 1907, which was Leroux's inspiration and which emerges as the metaphorical key to interpreting the novel—if not the tradition as a whole.
The Roles of Multiple UNC-40 (DCC) Receptor-Mediated Signals in Determining Neuronal Asymmetry Induced by the UNC-6 (Netrin) Ligand
Authors: Xu Zhennan , Li Haichang , Wadsworth William G 
Published: August 2009

Abstract
The polarization of post-mitotic neurons is poorly understood. Preexisting spatially asymmetric cues, distributed within the neuron or as extracellular gradients, could be required for neurons to polarize. Alternatively, neurons might have the intrinsic ability to polarize without any preestablished asymmetric cues. In Caenorhabditis elegans, the UNC-40 (DCC) receptor mediates responses to the extracellular UNC-6 (netrin) guidance cue. For the HSN neuron, an UNC-6 ventral-dorsal gradient asymmetrically localizes UNC-40 to the ventral HSN surface. There an axon forms, which is ventrally directed by UNC-6. In the absence of UNC-6, UNC-40 is equally distributed and the HSN axon travels anteriorly in response to other cues. However, we find that a single amino acid change in the UNC-40 ectodomain causes randomly oriented asymmetric UNC-40 localization and a wandering axon phenotype. With UNC-6, there is normal UNC-40 localization and axon migration. A single UNC-6 amino acid substitution enhances the mutant phenotypes, whereas UNC-6 second-site amino acid substitutions suppress the phenotypes. We propose that UNC-40 mediates multiple signals to polarize and orient asymmetry. One signal triggers the intrinsic ability of HSN to polarize and causes randomly oriented asymmetry. Concurrently, another signal biases the orientation of the asymmetry relative to the UNC-6 gradient. The UNC-40 ectodomain mutation activates the polarization signal, whereas different forms of the UNC-6 ligand produce UNC-40 conformational changes that allow or prohibit the orientation signal.
In Utero Valvuloplasty for Pulmonary Atresia With Hypoplastic Right Ventricle: Techniques and Outcomes
Authors: Tworetzky Wayne , McElhinney Doff B. , Marx Gerald R. , Benson Carol B. , Brusseau Roland , Morash Donna , Wilkins-Haug Louise E. , Lock James E. , Marshall Audrey C. 
Published: August 2009

BACKGROUND: Prenatal intervention for fetuses with pulmonary atresia with an intact ventricular septum (PA/IVS) has the potential to alter right heart physiologic features in utero, facilitating right heart growth and improving the prospect of a biventricular outcome after birth.
METHODS: Since 2002, we have considered prenatal intervention for fetal PA/IVS in patients with (1) membranous pulmonary atresia, with identifiable pulmonary valve (PV) leaflets or membrane; (2) an intact or highly restrictive ventricular septum; and (3) right heart hypoplasia, with a tricuspid valve annulus z score of −2 or below and an identifiable but small right ventricle. Intervention was performed through direct cardiac puncture under ultrasound guidance, with percutaneous access or access through a limited laparotomy.
RESULTS: Ten fetuses underwent attempted balloon dilation of the PV in utero. The first 4 procedures were technically unsuccessful, and the most-recent 6 were technically successful. Compared with control fetuses with PA/IVS who did not undergo prenatal intervention and had univentricular outcomes after birth, the tricuspid valve annulus, right ventricle length, and PV annulus grew significantly more from midgestation to late gestation in the 6 fetuses who underwent successful interventions.
CONCLUSIONS: In utero perforation and dilation of the PV in midgestation fetuses with PA/IVS is technically feasible and may be associated with improved right heart growth and postnatal outcomes for fetuses with moderate right heart hypoplasia in midgestation. There is an important learning curve for this procedure, and much remains to be learned about the selection of appropriate fetuses for prenatal intervention.