bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer-Related Direct-to-Consumer Advertising: Awareness, Perceptions, and Reported Impact Among Patients Undergoing Active Cancer Treatment
Authors: Abel Gregory A. , Burstein Harold J. , Hevelone Nathanael D. , Weeks Jane C. 
Published: August 2009

Purpose Although cancer-related direct-to-consumer advertising (CR-DTCA) is prevalent, little is known about cancer patients' experiences with this controversial medium of medical communication. Methods We administered a 41-item, mailed questionnaire to consecutive patients with breast and hematologic malignancies who were undergoing active treatment at our institution. We assessed awareness of CR-DTCA within the prior year, perceptions of CR-DTCA, and CR-DTCA–prompted patient and provider behaviors. Results We received 348 completed questionnaires (response rate, 75.0%). Overall, 86.2% reported being aware of CR-DTCA, most frequently from television (77.7%). Awareness did not vary with clinical or sociodemographic factors except that patients were more likely to be aware of CR-DTCA for products specific to their cancer types (P < .0001). A majority of those aware reported that CR-DTCA made them “aware of treatments they did not know about” (62.2%), provided information in “a balanced manner” (65.2%), and helped them to have “better discussions” with their provider (56.8%). These perceptions were significantly more favorable among those who had not graduated from college (P < .05 for each). Overall, 11.2% reported that CR-DTCA made them “less confident” in their providers' judgment. Of those aware, 17.3% reported talking to their provider about an advertised medication, although less than one fifth of those reported receiving a prescription for the advertised medication. Conclusion The patients in our cohort were highly aware of CR-DTCA. CR-DTCA was found to be accessible and useful; however, it decreased some patients' confidence in their providers' judgment. CR-DTCA prompted a modest amount of patient-provider discussion but infrequent patient-reported changes in therapy.
Reduced Intensity Conditioning Compared With Myeloablative Conditioning Using Unrelated Donor Transplants in Patients With Acute Myeloid Leukemia
Authors: Ringdén Olle , Labopin Myriam , Ehninger Gerhard , Niederwieser Dietger , Olsson Richard , Basara Nadezda , Finke Juergen , Schwerdtfeger Rainer , Eder Matthias , Bunjes Donald , Gorin Norbert-Claude , Mohty Mohamad , Rocha Vanderson 
Published: August 2009

Purpose Reduced intensity conditioning regimen (RIC) is increasingly used in hematopoietic stem cell transplantation (HSCT). Unrelated donor (UD) transplants have more complications. We wanted to examine if RIC is a valid treatment option using UD in acute myeloblastic leukemia (AML). Patients and Methods Between 1999 and 2005, 401 patients with AML were treated with RIC and 1,154 received myeloablative conditioning (MAC), using UD and reported to the European Group for Blood and Marrow Transplantation Registry. Patients < and ≥ 50 years of age were analyzed separately. Results Patients receiving RIC were older, received transplants more recently, received peripheral blood stem cells more frequently, and were treated with total-body irradiation less often. In multivariable analysis, in patients younger than 50 years of age, nonrelapse mortality (NRM) was similar using RIC (hazard ratio [HR], 0.85; P = .41), relapse was increased (HR, 1.46; P = .02) and leukemia-free survival (LFS) was the same (HR, 0.88; P = .28), as compared with MAC. In patients ≥ 50 years of age, NRM was decreased in the RIC group (HR, 0.64; P = .04), relapse probability was not significantly different (HR, 1.34; P = .16) and LFS was similar (HR, 1.04; P = .79) compared with MAC. Conclusion RIC-UD transplants are associated with higher relapse in AML patients younger than 50 years of age and decreased NRM in those ≥ 50 years compared with MAC-UD. LFS was similar after both conditioning regimens, regardless of age. Therefore, RIC-UD extend the use of allotransplants for elderly patients and strategies that decrease relapse should be considered mainly in younger patients with AML.
Phase II Study of Axitinib in Sorafenib-Refractory Metastatic Renal Cell Carcinoma
Authors: Rini Brian I. , Wilding George , Hudes Gary , Stadler Walter M. , Kim Sinil , Tarazi Jamal , Rosbrook Brad , Trask Peter C. , Wood Laura , Dutcher Janice P. 
Published: August 2009

Purpose To investigate the efficacy and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3 in patients with metastatic renal cell carcinoma (mRCC) refractory to prior therapies that included, but were not limited to, sorafenib. Patients and Methods In this multicenter, open-label, phase II study, patients with sorafenib-refractory mRCC received a starting dose of axitinib 5 mg orally twice daily. A one-arm, single-stage design was used to estimate the primary end point of objective response rate (ORR), defined by RECIST (Response Evaluation Criteria in Solid Tumors). Secondary end points included safety, duration of response, progression-free survival (PFS), overall survival (OS), and patient-reported outcomes. Results Of 62 patients recruited, 100% had received prior sorafenib, and 74.2% had received two or more prior systemic treatments. The axitinib dose was titrated to greater than 5 mg twice daily in 53.2% of patients, and 35.5% of patients had the dose modified to less than 5 mg twice daily. In 62 patients evaluable for response, the ORR was 22.6%, and the median duration of response was 17.5 months. Median PFS and OS times were 7.4 months (95% CI, 6.7 to 11.0 months) and 13.6 months (95% CI, 8.4 to 18.8 months), respectively. All-causality grade 3 to 4 adverse events included hand-foot syndrome (16.1%), fatigue (16.1%), hypertension (16.1%), dyspnea (14.5%), diarrhea (14.5%), dehydration (8.1%), and hypotension (6.5%). Conclusion Axitinib has antitumor activity in patients with mRCC refractory to prior VEGF-targeted therapy, including sorafenib. Toxicities were mild to moderate and were manageable. A randomized, phase III trial to compare axitinib with sorafenib in patients who have mRCC refractory to one prior first-line therapy regimen is underway.
Phase I/II Trial of AEG35156 X-Linked Inhibitor of Apoptosis Protein Antisense Oligonucleotide Combined With Idarubicin and Cytarabine in Patients With Relapsed or Primary Refractory Acute Myeloid Leukemia
Authors: Schimmer Aaron D. , Estey Elihu H. , Borthakur Gautam , Carter Bing Z. , Schiller Gary J. , Tallman Martin S. , Altman Jessica K. , Karp Judith E. , Kassis Jeannine , Hedley David W. , Brandwein Joseph , Xu Wei , Mak Duncan H. , LaCasse Eric , Jacob Christine , Morris Stephen J. , Jolivet Jacques , Andreeff Michael 
Published: August 2009

Purpose X-linked inhibitor of apoptosis protein (XIAP) is an inhibitor of caspases 3 and 9 which are overexpressed in acute myeloid leukemia (AML) and may contribute to chemoresistance. We report on a phase I/II trial of the XIAP antisense oligonucleotide AEG35156 in combination with reinduction chemotherapy. Patients and Methods Twenty-four patients with rapidly relapsed or refractory AML were treated with escalating doses of AEG35156 (12 to 250 mg/m2) as an intravenous solution over 2 hours and 32 patients were treated with the highest planned dose of 350 mg/m2 in combination with idarubicin and high-dose cytarabine reinduction chemotherapy. Correlative studies were conducted to determine the effects of AEG35156 on levels of XIAP mRNA. Results Knockdown of XIAP mRNA during treatment increased with the dose of the antisense. All patients who received 350 mg/m2 of AEG35156 had higher than 30% target knockdown with a median maximal knockdown of 90% (range, 48% to 100%). The overall response rate was higher among the patients receiving the highest dose of AEG35156. In this group, 15 (47%) of 32 patients achieved complete response (CR)/CR with incomplete platelet count recovery (CRp) compared with only one (4%) of 24 receiving 12 to 250 mg/m2 AEG35156. Among the patients receiving 350 mg/m2 of AEG35156 in combination with chemotherapy, 10 (91%) of 11 who were refractory to a single induction chemotherapy regimen achieved CR/CRp after reinduction with AEG35156 and chemotherapy. AEG35156 was well tolerated save for two cases of peripheral neuropathy in patients receiving multiple doses of AEG35156. Conclusion At the highest dose tested, AEG35156 knocks down its target and appears very effective when combined with chemotherapy in patients with AML refractory to a single induction regimen.
Impact of Baseline BCR-ABL Mutations on Response to Nilotinib in Patients With Chronic Myeloid Leukemia in Chronic Phase
Authors: Hughes Timothy , Saglio Giuseppe , Branford Susan , Soverini Simona , Kim Dong-Wook , Müller Martin C. , Martinelli Giovanni , Cortes Jorge , Beppu Lan , Gottardi Enrico , Kim Dongho , Erben Philipp , Shou Yaping , Haque Ariful , Gallagher Neil , Radich Jerald , Hochhaus Andreas 
Published: August 2009

Purpose Nilotinib is a second-generation tyrosine kinase inhibitor indicated for the treatment of patients with chronic myeloid leukemia (CML) in chronic phase (CP; CML-CP) and accelerated phase (AP; CML-AP) who are resistant to or intolerant of prior imatinib therapy. In this subanalysis of a phase II study of nilotinib in patients with imatinib-resistant or imatinib-intolerant CML-CP, the occurrence and impact of baseline and newly detectable BCR-ABL mutations were assessed. Patients and Methods Baseline mutation data were assessed in 281 (88%) of 321 patients with CML-CP in the phase II nilotinib registration trial. Results Among imatinib-resistant patients, the frequency of mutations at baseline was 55%. After 12 months of therapy, major cytogenetic response (MCyR) was achieved in 60%, complete cytogenetic response (CCyR) in 40%, and major molecular response (MMR) in 29% of patients without baseline mutations versus 49% (P = .145), 32% (P = .285), and 22% (P = .366), respectively, of patients with mutations. Responses in patients who harbored mutations with high in vitro sensitivity to nilotinib (50% inhibitory concentration [IC50] ≤ 150 nM) or mutations with unknown nilotinib sensitivity were equivalent to those responses for patients without mutations (not significant). Patients with mutations that were less sensitive to nilotinib in vitro (IC50 > 150 nM; Y253H, E255V/K, F359V/C) had less favorable responses, as 13%, 43%, and 9% of patients with each of these mutations, respectively, achieved MCyR; none achieved CCyR. Conclusion For most patients with imatinib resistance and with mutations, nilotinib offers a substantial probability of response. However, mutational status at baseline may influence response. Less sensitive mutations that occurred at three residues defined in this study, as well as the T315I mutation, may be associated with less favorable responses to nilotinib.
Phase II Study of Sorafenib in Patients With Sunitinib-Refractory Metastatic Renal Cell Cancer
Authors: Di Lorenzo Giuseppe , Cartenì Giacomo , Autorino Riccardo , Bruni Gianni , Tudini Marianna , Rizzo Mimma , Aieta Michele , Gonnella Antonio , Rescigno Pasquale , Perdonà Sisto , Giannarini Gianluca , Pignata Sandro , Longo Nicola , Palmieri Giovannella , Imbimbo Ciro , De Laurentiis Michele , Mirone Vincenzo , Ficorella Corrado , De Placido Sabino 
Published: August 2009

Purpose No previous prospective trials have been reported with sorafenib in patients with sunitinib-refractory metastatic renal cell cancer (MRCC). We conducted a multicenter study to determine the activity and tolerability of sorafenib as second-line therapy after sunitinib progression in MRCC. Patients and Methods Between January 2006 and September 2008, 52 patients were enrolled onto this single-arm phase II study. All patients received sorafenib 400 mg orally twice a day until disease progression or intolerable toxicity. The primary end point was objective response rate (complete or partial response) evaluated every 8 weeks by use of the Response Evaluation Criteria in Solid Tumors; secondary end points were toxicity, time to progression (TTP), and overall survival (OS). Results All patients were included in response and safety analyses. Partial responses were observed in 9.6% of patients (five of 52 patients; 95% CI, 5% to 17%) after two cycles. Grade 1 to 2 fatigue, diarrhea, nausea/vomiting, rash, and neutropenia were the most common side effects, noted in 16 (30.8%), 19 (36.5%), 20 (38.5%), 19 (36.5%), and 20 patients (38.5%), respectively. The most common grade 3 toxicity was diarrhea, noted in six patients (11.5%). Median TTP was 16 weeks (range, 8 to 40 weeks), and median OS was 32 weeks (range, 16 to 64 weeks). Conclusion Although well tolerated, sorafenib shows limited efficacy in sunitinib-refractory MRCC. Further randomized trials comparing sorafenib with other drugs that target different biologic pathways are needed to define the best second-line treatment option in these patients.
Dispersion of antimony from oxidizing ore deposits
Authors: Diemar Glen A. , Filella Montserrat , Leverett Peter , Williams Peter A. 
Published: August 2009

Abstract
The solubilities of brandholzite, [Mg(H2O)6][Sb(OH)6]2, and bottinoite, [Ni(H2O)6][Sb(OH)6]2, at 25 °C in water have been measured. Solubilities are 1.95(4) × 10-3 and 3.42(11) × 10-4 mol dm-3, respectively. The incongruent dissolution of romeite, Ca2Sb2O7, and bindheimite, Pb2Sb2O7, at 25 °C in 0.100 mol dm-3 aqueous HNO3 was also investigated. Equilibrium dissolved Sb concentrations were 3.3 ± 1.0 × 10-7 and 7.7 ± 2.1 × 10-8 mol dm-3, respectively. These values have been used to re-evaluate the geochemical mobility of Sb in the supergene environment. It is concluded that the element is geochemically immobile in solution and in soils. This was in part validated by an orientation soil geochemical survey over the Bayley Park prospect near Armidale, New South Wales, Australia. Anomalous soil Sb levels are confined to within 100 m of known stibnite mineralization.
Imputation of 10-year osteoporotic fracture rates from hip fractures: A clinical validation study
Authors: Leslie William D , Lix Lisa M 
Published: August 2009

Abstract
The World Health Organization (WHO) fracture risk assessment system (FRAX) allows for calibration from country-specific fracture data. The objective of this study was to evaluate the method for imputation of osteoporotic fracture rates from hip fractures alone. A total of 38,784 women aged 47.5 years or older at the time of baseline femoral neck bone mineral density (BMD) measurement were identified in a database containing all clinical dual energy X-ray absorptiometry (DXA) results for the Province of Manitoba, Canada. Health service records were assessed for the presence of nontrauma osteoporotic fracture codes after BMD testing (431 hip, 787 forearm, 336 clinical vertebral, and 431 humerus fractures). Ten-year hip and osteoporotic fracture rates were estimated by the Kaplan-Meier method. The population was stratified by age (50 to 90 years, 5-year width strata) and again by femoral neck T-scores (−4.0 to 0.0, 0.5 SD width strata). Within each stratum, the ratio of hip to osteoporotic fractures was calculated and compared with the predicted ratio from FRAX. Increasing age was associated with greater predicted hip-to-osteoporotic ratios (youngest 0.07 versua oldest 0.41) and observed ratios (youngest 0.10 versus oldest 0.48). Lower T-scores were associated with greater predicted (highest 0.04 versus lowest 0.71) and observed ratios (highest 0.06 versus lowest 0.44). There was a strong positive correlation between predicted and observed ratios (Spearman r = 0.90–0.97, p &lt; .001). For 14 of the 18 strata, the predicted ratio was within the observed 95% confidence interval (CI). Since collection of population-based hip fracture data is considerably easier than collection of non–hip fracture data, this study supports the current emphasis on using hip fractures as the preferred site for FRAX model calibration. © 2010 American Society for Bone and Mineral Research
Defects in mesenchymal stem cell self-renewal and cell fate determination lead to an osteopenic phenotype in Bmi-1 null mice
Authors: Zhang Heng-Wei , Ding Jiong , Jin Jian-Liang , Guo Jian , Liu Jing-Ning , Karaplis Andrew , Goltzman David , Miao Dengshun 
Published: August 2009

Abstract
In parathyroid hormone–related protein 1-84 [PTHrP(1-84)] knockin mice, expression of the polycomb protein Bmi-1 is reduced and potentially can mediate the phenotypic alterations observed. We have therefore now examined the skeletal phenotype of Bmi-1−/− mice in vivo and also assessed the function of bone marrow mesenchymal stem cells (BM-MSCs) from Bmi-1−/− mice ex vivo in culture. Neonatal Bmi-1−/− mice exhibited skeletal growth retardation, with reduced chondrocyte proliferation and increased apoptosis. Osteoblast numbers; gene expression of alkaline phosphatase, type I collagen, and osteocalcin; the mineral apposition rate; trabecular bone volume; and bone mineral density all were reduced significantly; however, the number of bone marrow adipocytes and Ppar-γ expression were increased. These changes were consistent with the skeletal phenotype observed in the PTHrP(1-84) knockin mouse. The efficiency of colony-forming unit fibroblast (CFU-F) formation in bone marrow cultures was decreased, and the percentage of alkaline phosphatase–positive CFU-F and Runx2 expression were reduced. In contrast, adipocyte formation and Ppar-γ expression in cultures were increased, and expression of the polycomb protein sirtuin (Sirt1) was reduced. Reduced proliferation and increased apoptosis of BM-MSCs were associated with upregulation of senescence-associated tumor-suppressor genes, including p16, p19, and p27. Analysis of the skeletal phenotype in Bmi-1−/− mice suggests that Bmi-1 functions downstream of PTHrP. Furthermore, our studies indicate that Bmi-1 maintains self-renewal of BM-MSCs by inhibiting the expression of p27, p16, and p19 and alters the cell fate of BM-MSCs by enhancing osteoblast differentiation and inhibiting adipocyte differentiation at least in part by stimulating Sirt1 expression. Bmi-1 therefore plays a critical role in promoting osteogenesis. © 2010 American Society for Bone and Mineral Research
Short-term exposure to low-carbohydrate, high-fat diets induces low bone mineral density and reduces bone formation in rats
Authors: Bielohuby Maximilian , Matsuura Maiko , Herbach Nadja , Kienzle Ellen , Slawik Marc , Hoeflich Andreas , Bidlingmaier Martin 
Published: August 2009

Abstract
Low-carbohydrate, high-fat (LC-HF) diets are popular for inducing weight loss in adults and are also used as part of a treatment for children with epilepsy. However, potential risks and side effects remain controversial. We investigated effects of LC-HF diets on growth, bone mineral density (BMD), and turnover in growing rats fed for 4 weeks either normal chow (CH, 9% fat, 33% protein, and 58% carbohydrates), LC-HF-1 (66% fat, 33% protein, and 1% carbohydrates), or LC-HF-2 (94.5% fat, 4.2% protein, and 1.3% carbohydrates). Rats fed LC-HF diets accumulated significantly more visceral and bone marrow fat and showed increased leptin but decreased insulin-like growth-factor 1 (IGF-1). Both LC-HF diets significantly decreased body length (nose to rump), but lengths of humerus, tibia, and femur were significantly reduced with LC-HF-2 only. Peripheral quantitative computed tomography (pQCT) and micro-CT (µCT) independently revealed significant reductions in BMD of tibiae in both LC-HF groups, and tibial maximum load was impaired. Bone-formation marker N-terminal propeptide of type I procollagen was reduced in sera of LC-HF groups, whereas bone resorption marker CrossLaps remained unchanged. Real-time PCR analysis revealed significant reductions by 70% to 80% of transcription factors influencing osteoblastogenesis (Runx2, osterix, and C/EBPβ) in bone marrow of rats fed LC-HF diets. In conclusion, both LC-HF diets impaired longitudinal growth, BMD, and mechanical properties, possibly mediated by reductions in circulating IGF-1. Serum bone-formation markers as well as expression of transcription factors influencing osteoblastogenesis were reduced. This might indicate a lower rate of mesenchymal stem cells differentiating into osteoblasts, thus explaining reduced bone formation with LC-HF diets. © 2010 American Society for Bone and Mineral Research
The Etiological Moderation of Aggressive and Nonaggressive Antisocial Behavior by Age
Authors: Burt S. Alexandra , Klump Kelly L. 
Published: August 2009

AbstractA recent study has suggested that aggressive (AGG) and non-aggressive, rule-breaking (RB) antisocial behavior evidence differential and subtype-specific patterns of genetic expression during development. Namely, although genetic influences on RB increase dramatically during early- to mid-adolescence, genetic influences on AGG appear to remain stable. As no other study has examined age-related change in AGG versus RB, more research is clearly needed before any firm conclusions can be drawn. The current study thus examined whether and how age impacted genetic and environmental influences on AGG and RB in a sample of 252 10- to 15-year-old twin pairs assessed as part of the Michigan State University Twin Registry (MSUTR). Results constructively replicated and extended prior findings, indicating that while the magnitude of genetic and environmental influences on AGG remained stable across adolescence, genetic influences on RB increased dramatically with age. Such findings provide additional support for etiological distinctions within the broader construct of antisocial behavior based on the presence or absence of aggression, and offer insights into the expression of genetic influences during development.
Heritability of Testis Size
Authors: Estourgie-van Burk G. Frederiek , Bartels Meike , Delemarre-van de Waal Henriette A. , Boomsma Dorret I. 
Published: August 2009

AbstractTestis size is an important feature of male pubertal development. The genetic and environmental contributions to variation in human testis size have hardly been studied. We estimated the heritability of human testicular size in a group of mono- and dizygotic twins and their non-twin brothers (145 twins and 20 brothers from 95 families). Participants were 18 years old on average and all had reached Tanner development stage 4 or higher. Dizygotic twins and their siblings had a larger mean testis volume than monozygotic twins and their siblings. There was significant familial resemblance, with higher correlations in monozygotic twin pairs (0.59) than in dizygotic twin and sibling pairs (0.34). Heritability was estimated at 59% (95% CI = 37–75%), but a model that excluded genetic influences and attributed all familial resemblance to shared environment, fitted the data only marginally worse. The finding of larger mean testis volume in dizygotic twins may be of interest for future research into the mechanisms underlying dizygotic twinning.