bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of Tamoxifen Discontinuation Among Older Women With Estrogen Receptor–Positive Breast Cancer
Authors: Owusu Cynthia , Buist Diana S.M. , Field Terry S. , Lash Timothy L. , Thwin Soe Soe , Geiger Ann M. , Quinn Virginia P. , Frost Floyd , Prout Marianne , Yood Marianne Ulcickas , Wei Feifei , Silliman Rebecca A. 
Published: December 2007

Purpose Five years of adjuvant tamoxifen therapy for estrogen receptor (ER) –positive breast cancer is more effective than 2 years of use. However, information on tamoxifen discontinuation is scanty. We sought to identify predictors of tamoxifen discontinuation among older women with breast cancer. Patients and Methods Within six health care delivery systems, we identified women ≥ 65 years old diagnosed with stage I to IIB ER-positive or indeterminant breast cancer between 1990 and 1994 who had filled a prescription for adjuvant tamoxifen. We observed them for 5 years after initial tamoxifen prescription. We used automated pharmacy records to validate tamoxifen prescription information abstracted from medical records. The primary end point was tamoxifen discontinuation, operationalized as ever discontinuing tamoxifen during 5 years of follow-up. We used Cox proportional hazards to identify predictors of tamoxifen discontinuation. Results Of 961 women who were prescribed tamoxifen, 49% discontinued tamoxifen before the completion of 5 years. Discontinuers were more likely to be aged 75 to less than 80 years (v < 70 years; hazard ratio [HR] = 1.41; 95% CI, 1.06 to 1.87), be aged ≥ 80 years (HR = 2.02; 95% CI, 1.53 to 2.66), have an increase in Charlson Comorbidity Index at 3 years from diagnosis (HR = 1.52; 95% CI, 1.18 to 1.95), have an increase in the number of cardiopulmonary comorbidities at 3 years (HR = 1.75; 95% CI, 1.34 to 2.28), have indeterminant ER status (v ER-positive status; HR = 1.36; 95% CI, 1.00 to 1.85), and have received breast-conserving surgery (BCS) without radiotherapy (v mastectomy; HR = 1.62; 95% CI, 1.18 to 2.22). Conclusion Attention to nonadherence among older women at risk of discontinuation, particularly those receiving BCS without radiotherapy, might improve breast cancer outcomes for these women.
High-Dose Therapy and Autologous Stem-Cell Transplantation in Angioimmunoblastic Lymphoma: Complete Remission at Transplantation Is the Major Determinant of Outcome—Lymphoma Working Party of the European Group for Blood and Marrow Transplantation
Authors: Kyriakou Charalampia , Canals Carmen , Goldstone Anthony , Caballero Dolores , Metzner Bernd , Kobbe Guido , Kolb Hans-Jochem , Kienast Joachim , Reimer Peter , Finke Jurgen , Oberg Gunnar , Hunter Ann , Theorin Niklas , Sureda Anna , Schmitz Norbert 
Published: December 2007

Purpose Patients with angioimmunoblastic T-cell lymphoma (AITL) have poor prognoses with current conventional chemotherapy. The aim of this study was to evaluate the effect of high-dose therapy (HDT) followed by autologous stem-cell transplantation (ASCT) on patients with AITL. Patients and Methods We report a retrospective, multicenter study of 146 patients with AITL who received ASCT. The source of the stem cells was peripheral blood in 143 patients. The conditioning regimen varied, and 74% of the patients received carmustine and 1,3-bis(2-chloroethyl)-1-nitrosourea; etoposide; ara-C; and melphalan chemotherapy. Results After a median follow-up of 31 months (range, 3 to 174 months), 95 patients (65%) remained alive, and 51 patients (35%) died. Forty-two patients died as a result of disease progression, and nine died as a result of regimen-related toxicity. The cumulative incidence of nonrelapse mortality was 5% and 7% at 12 and 24 months, respectively. The actuarial overall survival (OS) was 67% at 24 months and 59% at 48 months. The cumulative incidence of relapse was estimated at 40% and 51% at 24 and 48 months, respectively. Disease status at transplantation was the major factor that impacted outcome. Patients who received a transplant during first complete remission (CR) had significantly superior progression-free survival and OS. The estimated PFS rates for patients who received their transplants in CR were 70% and 56% at 24 and 48 months, respectively; 42% and 30% for patients with chemotherapy-sensitive disease at those time points, respectively; and 23% at both time points for patients with chemotherapy-refractory disease. Conclusion This study shows that HDT and ASCT offers the possibility of long-term disease-free survival to patients with AITL. Early transplantation is necessary to achieve optimal results.
Genetic and Environmental Influence on Structural Strength of Weight-Bearing and Non–Weight-Bearing Bone: A Twin Study
Authors: Mikkola Tuija M , Sipilä Sarianna , Rantanen Taina , Sievänen Harri , Suominen Harri , Kaprio Jaakko , Koskenvuo Markku , Kauppinen Markku , Heinonen Ari 
Published: December 2007

Abstract
A bivariate genetic analysis among 217 older female twin pairs showed that, although the structural strength of tibia and radius are mainly regulated by same genetic and environmental factors, the tibia is more affected by environment.
Introduction: The habitual loading environment of the bone may modulate the relative contribution of genetic and environmental factors to bone structure. The purpose of this study was to estimate the contribution of the common and site-specific genetic and environmental factors to interindividual variation in compressive structural strength of the weight-bearing tibia and non–weight-bearing radius.
Materials and Methods: pQCT scans were obtained from both members of 103 monozygotic (MZ) and 114 dizygotic (DZ) 63- to 76-yr-old female twin pairs to estimate the compressive strength of the distal tibia and distal radius. Quantitative genetic models were used to decompose the phenotypic variance into additive genetic, shared environmental, and individual environmental effects at each bone site and to study whether these bone sites share genetic or environmental effects.
Results: The MZ and DZ twins did not differ in mean age, height, weight, or bone structural strength. The age-adjusted Cholesky model showed that additive genetic factors accounted for 83% (95% CI, 77–88%) of the variance in radial strength and 61% (95% CI, 52–69%) of the variance in tibial strength, and these were fully correlated. A shared environmental factor accounted for 15% (95% CI, 10–20%) of tibial strength. An individual environmental factor accounted for 17% (95% CI, 12–23%) of the variance in radial strength and 10% (95% CI, 5–17%) of the variance in tibial strength. The relative contribution of an individual environmental factor specific to tibial strength was 14% (95% CI, 11–18%).
Conclusions: The results suggest that, in older women, the majority of the individual differences in the compressive structural strength of the forearm and leg are regulated by genetic and environmental factors that are common to both bone sites. However, the relative importance of environmental factors was greater for the weight-bearing tibia than for the non–weight-bearing radius. Thus, the heritability of bone strength seems to vary between skeletal sites according to differences in the typical loading environment.
Long-Term Protective Effects of Zoledronic Acid on Cancellous and Cortical Bone in the Ovariectomized Rat
Authors: Gasser Jürg A , Ingold Peter , Venturiere Andrea , Shen Victor , Green Jonathan R 
Published: December 2007

Abstract
Current bisphosphonate therapies effectively prevent bone loss in postmenopausal women. We studied the effect of a single intravenous dose of ZOL in ovariectomized rats. Protection from bone loss was dose dependent, lasting for up to 32 weeks, supporting the rationale for an annual intravenous dosing regimen of ZOL for treatment of postmenopausal osteoporosis.
Introduction: Once-yearly dosing with zoledronic acid (ZOL) 5 mg can increase BMD and reduce fracture rate in postmenopausal women with low BMD. The primary objective of this study was to determine the duration of bone protective effects of a single dose of ZOL in ovariectomized rats, an animal model of postmenopausal osteopenia. Secondary objectives were to determine the effects on bone turnover and mechanical properties.
Materials and Methods: Female Wistar rats (10 per group) received single intravenous doses of ZOL 0.8, 4, 20, 100, or 500 μg/kg, alendronate 200 μg/kg, or isotonic saline 4 days before bilateral ovariectomy. Sham-operated controls were pretreated with saline. Mass and density of cancellous and cortical bone (pQCT) were measured at 4-wk intervals for 32 wk. Bone architecture (μCT), bone formation dynamics (fluorochrome label-based histomorphometry), and biomechanical strength in compression testing were also assessed at 32 wk.
Results: Ovariectomy-associated BMD loss was significantly attenuated for 32 wk by ZOL ≥4 μg/kg for total BMD, ZOL ≥20 μg/kg for cortical BMD, and ZOL ≥4 μg/kg for cancellous BMD (p &lt; 0.01 versus ovariectomized controls). Alendronate 200 μg/kg was of equivalent potency to ZOL 20 μg/kg. Ovariectomy-associated decreases in trabecular architectural parameters were dose-dependently attenuated by ZOL. Alendronate 200 μg/kg was equivalent to ZOL 20 μg/kg. The bone resorption marker TRACP5b indicated transient suppression of elevated osteoclast activity by ZOL relative to OVX-rats even at the lowest dose of 0.8 μg/kg, whereas at 100–500 μg/kg, the effect was significant relative to the OVX control for the entire duration of the study of 32 wk. Bone formation parameters were not significantly affected by ZOL 20 μg/kg but were significantly reduced by ZOL 100–500 μg/kg. Alendronate 200 μg/kg was equivalent to ZOL 100 μg/kg. ZOL produced dose-related improvements in bone strength parameters after ovariectomy. Alendronate 200 μg/kg was of similar potency to ZOL 20 μg/kg.
Conclusions: The duration and magnitude of the bone-protecting effect of a single intravenous dose of ZOL in ovariectomized rats is dose dependent and lasts for up to 32 wk. Compared with alendronate, ZOL shows 10-fold higher potency in preventing bone loss. These data support the use of an annual intravenous ZOL dosing regimen for the treatment of osteoporosis.
Nitrosylcobalamin Potentiates the Anti-Neoplastic Effects of Chemotherapeutic Agents via Suppression of Survival Signaling
Authors: Bauer Joseph A. , Lupica Joseph A. , Szugye Heidi , Morrison Bei H. , Haney Rebecca M. , Masci Rhonda K. , Lee Rebecca M. , DiDonato Joseph A. , Lindner Daniel J. 
Published: December 2007

Background
Nitrosylcobalamin (NO-Cbl) is a chemotherapeutic pro-drug derived from vitamin B12 that preferentially delivers nitric oxide (NO) to tumor cells, based upon increased receptor expression. NO-Cbl induces Apo2L/TRAIL-mediated apoptosis and inhibits survival signaling in a variety of malignant cell lines. Chemotherapeutic agents often simultaneously induce an apoptotic signal and activation of NF-κB, which has the undesired effect of promoting cell survival. The specific aims of this study were to 1) measure the anti-tumor effects of NO-Cbl alone and in combination with conventional chemotherapeutic agents, and to 2) examine the mechanism of action of NO-Cbl as a single agent and in combination therapy.

Methodology
Using anti-proliferative assays, electrophoretic mobility shift assay (EMSA), immunoblot analysis and kinase assays, we demonstrate an increase in the effectiveness of chemotherapeutic agents in combination with NO-Cbl as a result of suppressed NF-κB activation.

Results
Eighteen chemotherapeutic agents were tested in combination with NO-Cbl, in thirteen malignant cell lines, resulting in a synergistic anti-proliferative effect in 78% of the combinations tested. NO-Cbl pre-treatment resulted in decreased NF-κB DNA binding activity, inhibition of IκB kinase (IKK) enzymatic activity, decreased AKT activation, increased caspase-8 and PARP cleavage, and decreased cellular XIAP protein levels.

Conclusion
The use of NO-Cbl to inhibit survival signaling may enhance drug efficacy by preventing concomitant activation of NF-κB or AKT.
Accurate Determination and Benchmarking of Radiation Field Parameters, Relevant for Pressure Vessel Monitoring—Review of Some REDOS Project Results
Authors: Ošmera B. , Kyncl J. , Boehmer B. , Konheiser J. , Ballesteros A. , Hordosy G. , Keresztúri A. , Belousov S. , Ilieva K. , Kirilova D. , Mitev M. , Smutný V. , Polke E. , Zaritsky S. , Töre C. , Ortego P. 
Published: December 2007

Abstract
Plant life management needs a reliable estimation of radiation field parameters, including their uncertainty, to avoid the use of conservative approaches. The particular objectives of the REDOS project [1] are the improvements of the RPV monitoring, the improvement of the neutron-gamma calculation methodologies through the LR-0 engineering benchmarks for WWER-1000 and WWER-440, and the accurate determination of radiation field parameters in the vicinity and over the thickness of the RPV. This paper is mainly devoted to the comparison and analysis of the experimental and calculated LR-0 data. The LR-0 benchmark data consist of neutron spectra (WWER-440 Mock-ups) and neutron + photon spectra (WWER-1000 Mock-up) in several points from the barrel simulator to the outer surface of RPV and evaluated integral fluxes, space-energy indices, like the spectral indices and attenuation factors in measuring points.
Assessment of the Long-term Safety of Inhaled Ciclesonide on Growth in Children With Asthma
Authors: Skoner David P. , Maspero Jorge , Banerji Donald ,   and the Ciclesonide Pediatric Growth Study Group
Published: December 2007

OBJECTIVE. To assess the effects of the new inhaled corticosteroid ciclesonide on growth in children with asthma.
METHODS. We performed a multicenter, randomized, double-blind, placebo-controlled study to assess the effects of inhaled ciclesonide on growth in children with mild, persistent asthma. After a 6-month run-in period, 661 prepubertal children who were aged 5.0 to 8.5 years were randomly assigned to once-daily morning treatment for 1 year with ciclesonide 40 or 160 μg (ex-actuator) or placebo, followed by a 2-month follow-up period. The primary end point was the linear growth velocity (linear regression estimate) over the double-blind treatment period. Growth was recorded as the median of 4 stadiometer measurements. Adverse events and 10-hour overnight and 24-hour urinary free cortisol levels were also assessed.
RESULTS. Mean linear growth velocity during run-in was comparable between groups: 160 μg, 6.20 cm/year; 40 μg, 6.59 cm/year; placebo, 6.49 cm/year. Mean differences from placebo (5.75 cm/year) in growth velocity over the double-blind treatment period were −0.02 cm/year for ciclesonide 40 μg and −0.15 cm/year for ciclesonide 160 μg. Both ciclesonide treatments were noninferior to placebo with respect to growth velocity. The overall incidence of adverse events was comparable between groups, and no significant changes in 10-hour overnight or 24-hour urinary free cortisol levels were noted between groups during the double-blind treatment period.
CONCLUSIONS. Ciclesonide demonstrated no detectable effect on childhood growth velocity, even at the highest dosage, which may ease concerns about systemic adverse events.
Probability of Walking in Children With Cerebral Palsy in Europe
Authors: Beckung Eva , Hagberg Gudrun , Uldall Peter , Cans Christine ,   for Surveillance of Cerebral Palsy in Europe
Published: December 2007

OBJECTIVES. The purpose of this work was to describe walking ability in children with cerebral palsy from the Surveillance of Cerebral Palsy in Europe common database through 21 years and to examine the association between walking ability and predicting factors.
PATIENTS AND METHODS. Anonymous data on 10042 children with cerebral palsy born between 1976 and 1996 were gathered from 14 European centers; 9012 patients were eligible for the analyses.
RESULTS. Unaided walking as the primary way of walking at 5 years of age was reported for 54%, walking with assistive devices was reported for 16%, and no walking ability was reported for 30%. The proportion of children who were unable to walk was rather stable over time in all of the centers, with a mean proportion of 28%. Walking ability related significantly to cerebral palsy types, that is, spastic unilateral, spastic bilateral, dyskinetic, and ataxic cerebral palsy, as well as to IQ level, active epilepsy, and severe visual and hearing impairment. Severe cerebral palsy, defined as both the inability to walk and an IQ of &lt;50, was present in 20% of the subjects. Logistic regression revealed that intellectual capacity was the variable most associated with walking ability in all 4 of the cerebral palsy types. The presence of a severe intellectual impairment increased the risk of being unable to walk 56 times if the child had unilateral spastic cerebral palsy type and 9 times if the child had bilateral spastic cerebral palsy type.
CONCLUSIONS. The collaboration Surveillance of Cerebral Palsy in Europe provides a powerful means of monitoring trends in cerebral palsy and its functional consequences. The proportion of nonwalking in children with cerebral palsy seems to be rather stable over years and across centers despite the changes that have occurred in neonatal care across Europe. As is well known and also shown in this study, walking ability varied strongly with cerebral palsy type. Additional impairments, as well as the presence of epilepsy, correlated significantly with walking ability and, thus, the walking ability can be an indicator of total disability load.
Transcription Factor 7-Like 2 Regulates β-Cell Survival and Function in Human Pancreatic Islets
Authors: Shu Luan , Sauter Nadine S. , Schulthess Fabienne T. , Matveyenko Aleksey V. , Oberholzer José , Maedler Kathrin 
Published: December 2007

OBJECTIVE—Type 2 diabetes is characterized by impaired insulin secretion in response to increased metabolic demand. This defect in β-cell compensation seems to result from the interplay between environmental factors and genetic predisposition. Genome-wide association studies reveal that common variants in transcription factor 7-like 2 (TCF7L2) are associated with increased risk of type 2 diabetes. The aim of the present study was to establish whether TCF7L2 plays a role in β-cell function and/or survival.
RESEARCH DESIGN AND METHODS—To investigate the effects of TCFL7L2 depletion, isolated islets were exposed to TCF7L2 small interfering RNA (siRNA) versus scrambled siRNA, and β-cell survival and function were examined. For TCF7L2 overexpression, islets were cultured in glucose concentrations of 5.5–33.3 mmol/l and the cytokine mix interleukin-1β/γ-interferon with or without overexpression of TCF7L2. Subsequently, glucose-stimulated insulin secretion (GSIS), β-cell apoptosis [by transferase-mediated dUTP nick-end labeling assay and Western blotting for poly(ADP-ribose) polymerase and Caspase-3 cleavage], and β-cell proliferation (by Ki67 immunostaining) were analyzed.
RESULTS—Depleting TCF7L2 by siRNA resulted in a 5.1-fold increase in β-cell apoptosis, 2.2-fold decrease in β-cell proliferation (P &lt; 0.001), and 2.6-fold decrease in GSIS (P &lt; 0.01) in human islets. Similarly, loss of TCF7L2 resulted in impaired β-cell function in mouse islets. In contrast, overexpression of TCF7L2 protected islets from glucose and cytokine-induced apoptosis and impaired function.
CONCLUSIONS—TCF7L2 is required for maintaining GSIS and β-cell survival. Changes in the level of active TCF7L2 in β-cells from carriers of at-risk allele may be the reason for defective insulin secretion and progression of type 2 diabetes.
Defining Pancreatic Endocrine Precursors and Their Descendants
Authors: White Peter , Lee May Catherine , Lamounier Rodrigo N. , Brestelli John E. , Kaestner Klaus H. 
Published: December 2007

OBJECTIVE—The global incidence of diabetes continues to increase. Cell replacement therapy and islet transplantation offer hope, especially for severely affected patients. Efforts to differentiate insulin-producing β-cells from progenitor or stem cells require knowledge of the transcriptional programs that regulate the development of the endocrine pancreas.
RESEARCH DESIGN AND METHODS—Differentiation toward the endocrine lineage is dependent on the transcription factor Neurogenin 3 (Neurog3, Ngn3). We utilize a Neurog3–enhanced green fluorescent protein knock-in mouse model to isolate endocrine progenitor cells from embryonic pancreata (embryonic day [E]13.5 through E17.5). Using advanced genomic approaches, we generate a comprehensive gene expression profile of these progenitors and their immediate descendants.
RESULTS—A total of 1,029 genes were identified as being temporally regulated in the endocrine lineage during fetal development, 237 of which are transcriptional regulators. Through pathway analysis, we have modeled regulatory networks involving these proteins that highlight the complex transcriptional hierarchy governing endocrine differentiation.
CONCLUSIONS—We have been able to accurately capture the gene expression profile of the pancreatic endocrine progenitors and their descendants. The list of temporally regulated genes identified in fetal endocrine precursors and their immediate descendants provides a novel and important resource for developmental biologists and diabetes researchers alike.
Effects of epidural administration of dexmedetomidine on the minimum alveolar concentration of isoflurane in dogs
Authors: Campagnol Daniela , Teixeira Neto Francisco J. , Giordano Tatiana , Ferreira Tatiana H. , Monteiro Eduardo R. 
Published: December 2007

Abstract
Objective—To evaluate the effects of epidural administration of 3 doses of dexmedetomidine on isoflurane minimum alveolar concentration (MAC) and characterize changes in bispectral index (BIS) induced by nociceptive stimulation used for MAC determination in dogs.
Animals—6 adult dogs.
Procedures—Isoflurane-anesthetized dogs received physiologic saline (0.9% NaCl) solution (control treatment) or dexmedetomidine (1.5 [DEX1.5], 3.0 [DEX3], or 6.0 [DEX6] μg/kg) epidurally in a crossover study. Isoflurane MAC (determined by use of electrical nociceptive stimulation of the hind limb) was targeted to be accomplished at 2 and 4.5 hours. Changes in BIS attributable to nociceptive stimulation and cardiopulmonary data were recorded at each MAC determination.
Results—With the control treatment, mean ± SD MAC values did not change over time (1.57 ± 0.23% and 1.55 ± 0.25% at 2 and 4.5 hours, respectively). Compared with the control treatment, MAC was significantly lower at 2 hours (13% reduction) but not at 4.5 hours (7% reduction) in DEX1.5-treated dogs and significantly lower at 2 hours (29% reduction) and 4.5 hours (13% reduction) in DEX3-treated dogs. The DEX6 treatment yielded the greatest MAC reduction (31% and 22% at 2 and 4.5 hours, respectively). During all treatments, noxious stimulation increased BIS; but changes in BIS were correlated with increases in electromyographic activity.
Conclusions and Clinical Relevance—In dogs, epidural administration of dexmedetomidine resulted in dose-dependent decreases in isoflurane MAC and that effect decreased over time. Changes in BIS during MAC determinations may not represent increased awareness because of the possible interference of electromyographic activity.
Le temps de réaction à un stimulus intercalé dans une suite rythmique
Authors: Fraisse P 
Published: December 2007

To a given object, correspond a specific and a categorical reply, the quickest one (measured by a time of verbal reaction) corresponding to the most spontaneous and available reply when the subject is requested to identify the object.
This spontaneous reply corresponds to the nature of the object. When the objects are perceptively similar, and generale a generic image (tree, fish, etc.) the categorical reply is the most spontaneous, no matter how old the subject is. On the other hand, it assumes a specific nature when the objects are quite distinct and the corresponding category is more abstract and not contingent on a general perceptive shape (ex. : functional category : weapon, etc.).