bluuebunny/crossref_metadata_2025_split huggingface dataset:
American Society of Clinical Oncology Policy Statement: The Role of the Oncologist in Cancer Prevention and Risk Assessment
Authors: Zon Robin T. , Goss Elizabeth , Vogel Victor G. , Chlebowski Rowan T. , Jatoi Ismail , Robson Mark E. , Wollins Dana S. , Garber Judy E. , Brown Powel , Kramer Barnett S. 
Published: December 2008

Oncologists have a critical opportunity to utilize risk assessment and cancer prevention strategies to interrupt the initiation or progression of cancer in cancer survivors and individuals at high risk of developing cancer. Expanding knowledge about the natural history and prognosis of cancers positions oncologists to advise patients regarding the risk of second malignancies and treatment-related cancers. In addition, as recognized experts in the full spectrum of cancer care, oncologists are afforded opportunities for involvement in community-based cancer prevention activities. Although oncologists are currently providing many cancer prevention and risk assessment services to their patients, economic barriers exist, including inadequate or lack of insurance, that may compromise uniform patient access to these services. Additionally, insufficient reimbursement for existing and developing interventions may discourage patient access to these services. The American Society of Clinical Oncology (ASCO), the medical society representing cancer specialists involved in patient care and clinical research, is committed to supporting oncologists in their wide-ranging involvement in cancer prevention. This statement on risk assessment and prevention counseling, although not intended to be a comprehensive overview of cancer prevention describes the current role of oncologists in risk assessment and prevention; provides examples of risk assessment and prevention activities that should be offered by oncologists; identifies potential opportunities for coordination between oncologists and primary care physicians in prevention education and coordination of care for cancer survivors; describes ASCO's involvement in education and training of oncologists regarding prevention; and proposes improvement in the payment environment to encourage patient access to these services.
Sequential Therapy With Fludarabine, High-Dose Cyclophosphamide, and Rituximab in Previously Untreated Patients With Chronic Lymphocytic Leukemia Produces High-Quality Responses: Molecular Remissions Predict for Durable Complete Responses
Authors: Lamanna Nicole , Jurcic Joseph G. , Noy Ariela , Maslak Peter , Gencarelli Alison N. , Panageas Katherine S. , Heaney Mark L. , Brentjens Renier J. , Golde David W. , Scheinberg David A. , Zelenetz Andrew D. , Weiss Mark A. 
Published: December 2008

Purpose Modern combination strategies are active in chronic lymphocytic leukemia (CLL) but can have significant myelosuppression and immunosuppression that may require dose attenuation for safety. We explored a sequential treatment strategy to allow safe delivery of active agents at full doses. Previously, we studied sequential therapy with fludarabine followed by cyclophosphamide (F→C). In that study, cyclophosphamide consolidation improved the frequency of complete response (CR) four-fold. Subsequently, rituximab was added to this regimen (F→C→R). Patients and Methods Thirty-six previously untreated CLL patients received therapy with fludarabine 25 mg/m2 on days 1 through 5 every 4 weeks for six cycles, followed by consolidation with cyclophosphamide 3,000 mg/m2 administered every 3 weeks for three cycles, followed by consolidation with weekly rituximab 375 mg/m2 for four cycles. Evaluation for minimal residual disease included flow cytometry and a highly sensitive clonotypic polymerase chain reaction (PCR). The median age was 59 years (range, 37 to 71 years), 61% of patients had high-risk disease, and 58% had unmutated IgVH genes. Results There were 32 responses (89%), including 22 CRs (61%). Consolidation with cyclophosphamide improved responses in 13 patients (36%); nine patients (25%) further improved their response with rituximab. Twenty patients (56%) achieved flow cytometric CRs, and 12 patients (33%) achieved a molecular CR (PCR negative). Patients achieving molecular CRs had an excellent prognosis with a plateau in the response duration curve, and 90% remain in clinical CR at 5 years. For the entire group, 5-year survival rate is 71% compared with a rate of 48% with our prior F→C regimen (P = .10). Conclusion Sequential therapy with F→C→R yields improvement in quality of response, with many patients achieving a PCR-negative state.
Relevance of Breast Cancer Antiestrogen Resistance Genes in Human Breast Cancer Progression and Tamoxifen Resistance
Authors: van Agthoven Ton , Sieuwerts Anieta M. , Meijer-van Gelder Marion E. , Look Maxime P. , Smid Marcel , Veldscholte Jos , Sleijfer Stefan , Foekens John A. , Dorssers Lambert C.J. 
Published: December 2008

PurposeWe have previously identified a set of breast cancer antiestrogen resistance (BCAR) genes causing estrogen independence and tamoxifen resistance in vitro using a functional genetic screen. Here, we explored whether these BCAR genes provide predictive value for tamoxifen resistance and prognostic information for tumor aggressiveness in breast cancer patients.Patients and MethodsmRNA levels of 10 BCAR genes (AKT1, AKT2, BCAR1, BCAR3, EGFR, ERBB2, GRB7, SRC, TLE3, and TRERF1) were measured in estrogen receptor–positive breast tumors using quantitative reverse-transcriptase polymerase chain reaction. Normalized mRNA levels were evaluated for association with progression-free survival (PFS) in 242 patients receiving tamoxifen as first-line monotherapy for recurrent disease, and with distant metastasis-free survival (MFS) in 413 lymph node-negative (LNN) primary breast cancer patients who did not receive systemic adjuvant therapy.ResultsConcerning tamoxifen resistance, BCAR3, ERBB2, GRB7, and TLE3 mRNA levels were predictive for PFS, independent of traditional predictive factors. By combining GRB7 (or ERBB2) and TLE3 mRNA levels, patients could be classified in three subgroups with distinct PFS. For the evaluation of tumor aggressiveness, AKT2, EGFR, and TRERF1 mRNA levels were all significantly associated with MFS, independent of traditional prognostic factors. Using the combined AKT2 and EGFR mRNA status, four prognostic groups were identified with different MFS outcomes.ConclusionThe majority of BCAR genes, which were revealed to confer tamoxifen resistance and estrogen independence in vitro by functional screening, have clinical relevance, and associate with tamoxifen resistance and/or tumor aggressiveness in breast cancer patients.
Randomized Trial of 13-cis Retinoic Acid Compared With Retinyl Palmitate With or Without Beta-Carotene in Oral Premalignancy
Authors: Papadimitrakopoulou Vassiliki A. , Lee J. Jack , William William N. , Martin Jack W. , Thomas Margaret , Kim Edward S. , Khuri Fadlo R. , Shin Dong M. , Feng Lei , Hong Waun Ki , Lippman Scott M. 
Published: December 2008

Purpose To investigate whether retinyl palmitate (RP) alone or plus beta-carotene (BC) would be as effective and less toxic than low-dose 13-cis retinoic acid (13cRA) in treating oral premalignant lesions (OPLs) and reducing the risk of oral cancer. Patients and Methods Initially, patients were randomly assigned to receive low-dose 13cRA or BC plus RP for 3 years (plus 2 years follow-up). After other randomized trials established an adverse effect of BC on lung cancer incidence/mortality, BC was dropped (patients randomly assigned to 13cRA or RP alone). The primary end point was OPL clinical response at 3 months. Results We randomly assigned 162 eligible patients. The 3-month clinical response rate of the combined BC plus RP and RP alone arm (32.5%) was not statistically equivalent to that of 13cRA (48.1%). The clinical response rate of RP alone (20.0%) was significantly lower than that of BC plus RP (42.9%; P = .03). Similar oral cancer–free survival rates were observed across all arms. There was no significant association between 3-month OPL response and subsequent oral cancer development (P = .11). Grades 2 and higher adverse events were more common in the 13cRA than other groups (P < .0001). Conclusion This large chemoprevention trial did not establish the equivalence of RP plus BC or RP alone with low-dose 13cRA in reducing the long-term risk of oral cancer. At present, 13cRA, BC plus RP, and RP alone cannot be recommended for chemoprevention, and new, better agents are needed in this setting. Our results did not establish short-term OPL response as a surrogate end point for oral cancer–free survival.
Oregovomab Maintenance Monoimmunotherapy Does Not Improve Outcomes in Advanced Ovarian Cancer
Authors: Berek Jonathan , Taylor Peyton , McGuire William , Smith L. Mary , Schultes Birgit , Nicodemus Christopher F. 
Published: December 2008

Purpose This phase III study tested the hypothesis that the CA-125–specific murine monoclonal antibody, oregovomab, administered as a monoimmunotherapy after front-line therapy in a selected ovarian cancer population would prolong time to relapse (TTR) and, ultimately, survival. Patients and Methods Patients with stage III to IV ovarian cancer with preoperatively elevated CA-125 and objectively defined characteristics were randomly assigned 4 to 12 weeks after front-line carboplatin and paclitaxel chemotherapy to maintenance monoimmunotherapy in a fully blinded protocol. Two mg of oregovomab or placebo was infused over 20 minutes at weeks 0, 4, and 8 and then 12 weeks until recurrence or up to year 5. Patients were evaluated with serial imaging and clinical evaluation for evidence of recurrence at quarterly visits. TTR was the primary end point. Results Three hundred seventy-three patients were accrued at more than 60 centers; 251 patients were assigned to oregovomab and 120 patients were assigned to placebo. The treatment arms were well balanced. There were no differences in the clinical outcomes between treatment groups. Median TTR measured from randomization after completion of chemotherapy for the integrated study was 10.3 months (95% CI, 9.7 to 13.0 months) for oregovomab and 12.9 months (95% CI, 10.1 to 17.4 months) for placebo (P = .29, log-rank test). The treatment was well tolerated. Grade 3 to 4 toxicity was reported in 24.6% of patients in the placebo group and 20.1% of patients in the oregovomab group, respectively. Conclusion Although oregovomab has demonstrated bioactivity, the strategy of monoimmunotherapy is not effective as maintenance therapy after front-line treatment of a favorable subset of patients with advanced ovarian cancer. Future studies of this or other tumor-antigen specific immunization strategies should seek ways to further augment induced immunity.
Phase III Randomized, Placebo-Controlled, Double-Blind Trial of Risedronate for the Prevention of Bone Loss in Premenopausal Women Undergoing Chemotherapy for Primary Breast Cancer
Authors: Hines Stephanie L. , Mincey Betty Anne , Sloan Jeff A. , Thomas Sachdev P. , Chottiner Elaine , Loprinzi Charles L. , Carlson Mark D. , Atherton Pamela J. , Salim Muhammad , Perez Edith A. 
Published: December 2008

Purpose Risedronate prevents bone loss in postmenopausal women. The purpose of this study was to determine whether risedronate prevents bone loss in premenopausal women undergoing chemotherapy for breast cancer. Patients and Methods Premenopausal women undergoing chemotherapy for breast cancer were treated with oral calcium 600 mg and vitamin D 400 U daily and randomly assigned to receive oral risedronate 35 mg weekly or placebo, with all these therapies beginning within a month of the start of chemotherapy. Most chemotherapy regimens included anthracyclines, taxanes, or cyclophosphamide. Bone mineral density (BMD) was measured at baseline and 1 year. The primary end point was the change in lumbar spine (LS) BMD from baseline to 1 year. Results A total of 216 women enrolled; 170 women provided BMD data at 1 year. There was no difference in the mean change or percent change in LS BMD between groups, with a loss of 4.3% in the risedronate arm and 5.4% for placebo at 1 year (P = .18). Loss of BMD at the femoral neck and total hip were also similar between treatment groups. Risedronate was well tolerated, with no significant differences in adverse events compared with placebo, except that arthralgias and chest pain were worse in those receiving the placebos. Conclusion Risedronate did not prevent bone loss in premenopausal women undergoing adjuvant chemotherapy for breast cancer.
Decreased precision contributes to the hypoxic thermoregulatory response in lizards
Authors: Cadena Viviana , Tattersall Glenn J. 
Published: December 2008

SUMMARYThe decrease in body temperature (Tb) observed in most vertebrate classes in response to hypoxia has been attributed to a regulated decrease in set-point, protecting organs against tissue death due to oxygen depletion. Hypoxia, however, imparts particular challenges to metabolic function which may, in turn, affect thermoregulation. In ectotherms, where thermoregulation is mainly behavioural, stressors that influence the propensity to move and respond to temperature gradients are expected to have an impact on thermoregulatory control. Using low oxygen as a potent stressor,we evaluated the variability and level of thermoregulation of inland bearded dragons. To examine the source of thermoregulatory variability, we studied their behaviour in an electronically controlled temperature-choice shuttle box, a constant temperature dual-choice shuttle box, and a linear thermal gradient. A significant increase in the size of the Tbrange was observed at the lowest oxygen concentration (4% O2),reflecting a decrease in thermoregulatory precision in the temperature-choice shuttle box. This was also accompanied by a drop of ∼2–4°C in Tb, the drop being greatest in situations where Tb must be actively defended. Situations that force the lizards to continually choose temperatures, rather than passively remain at a given temperature, lead to an increase in the variability in the manifested Tb, which is further exaggerated in hypoxia. This study reveals that a decrease in thermoregulatory precision caused by a diminished propensity to move or effect appropriate thermoregulatory responses may be a contributing component in the lowering of selected body temperatures observed in many hypoxic ectotherms.
Comparison of the Effect of Denosumab and Alendronate on BMD and Biochemical Markers of Bone Turnover in Postmenopausal Women With Low Bone Mass: A Randomized, Blinded, Phase 3 Trial
Authors: Brown Jacques P , Prince Richard L , Deal Chad , Recker Robert R , Kiel Douglas P , de Gregorio Luiz H , Hadji Peyman , Hofbauer Lorenz C , Álvaro-Gracia Jose M , Wang Huei , Austin Matthew , Wagman Rachel B , Newmark Richard , Libanati Cesar , San Martin Javier , Bone Henry G 
Published: December 2008

Abstract
Denosumab is a fully human monoclonal antibody that inhibits bone resorption by neutralizing RANKL, a key mediator of osteoclast formation, function, and survival. This phase 3, multicenter, double-blind study compared the efficacy and safety of denosumab with alendronate in postmenopausal women with low bone mass. One thousand one hundred eighty-nine postmenopausal women with a T-score ≤ −2.0 at the lumbar spine or total hip were randomized 1:1 to receive subcutaneous denosumab injections (60 mg every 6 mo [Q6M]) plus oral placebo weekly (n = 594) or oral alendronate weekly (70 mg) plus subcutaneous placebo injections Q6M (n = 595). Changes in BMD were assessed at the total hip, femoral neck, trochanter, lumbar spine, and one-third radius at 6 and 12 mo and in bone turnover markers at months 1, 3, 6, 9, and 12. Safety was evaluated by monitoring adverse events and laboratory values. At the total hip, denosumab significantly increased BMD compared with alendronate at month 12 (3.5% versus 2.6%; p &lt; 0.0001). Furthermore, significantly greater increases in BMD were observed with denosumab treatment at all measured skeletal sites (12-mo treatment difference: 0.6%, femoral neck; 1.0%, trochanter; 1.1%, lumbar spine; 0.6%, one-third radius; p ≤ 0.0002 all sites). Denosumab treatment led to significantly greater reduction of bone turnover markers compared with alendronate therapy. Adverse events and laboratory values were similar for denosumab- and alendronate-treated subjects. Denosumab showed significantly larger gains in BMD and greater reduction in bone turnover markers compared with alendronate. The overall safety profile was similar for both treatments.
Effect of surface sizing on the surface chemistry of paper containing eucalyptus pulp
Authors: Teixeira Moutinho Isabel Maria , Kleen Anne Marjatta , Lopes Figueiredo Maria Margarida , Tavares Ferreira Paulo Jorge 
Published: December 2008

Abstract
The effect of different surface sizing formulations on the chemical features of surfaces of the papers produced from Eucalyptus kraft pulp was studied. The surface analysis techniques, electron spectroscopy for chemical analysis and time-of-flight secondary ion mass spectrometry were applied. An uncoated base paper, the reference material, was sized with blends of cationic starch with either co-acrylonitrile-acrylate or co-styrene-acrylate. The results of both techniques are in good agreement and complete each other. It was possible not only to detect the presence of the surface sizing agents on the paper surface but also to distinguish them and evaluate their distribution and relative concentration. In addition, it was found that application of higher amounts of the sizing formulations, at a constant ratio of 20% copolymer to starch, did not significantly change the chemical properties of the paper surfaces.
Using High Speed Video Imaging in the Study of Cracking Processes in Rock
Authors: Wong L. N. Y. , Einstein H. H. 
Published: December 2008

Abstract
This paper presents the use of a high speed video system (high speed camera) in studying the crack initiation, propagation, and coalescence in rocks. Prismatic laboratory-molded gypsum and Carrara marble specimens, which contained either a single artificial flaw or a pair of artificial flaws, were tested in uniaxial compression. The front face of the specimen was monitored by a high speed camera. By adopting an appropriate frame rate (1000 to 24 000 frames/s) and image resolution (256 by 512 to 1024 by 1024 pixels) of the high speed camera, we were able to observe the abrupt and violent cracking processes in rocks. In particular, it was possible to distinguish shear and tensile crack mechanisms, which so far was not possible and subject to many discussions in rock mechanics. Distinguishing the cracking details allowed us to record and interpret the entire cracking sequence. The aims of this paper are twofold. First, it briefly addresses the capability of the high speed camera technology to set the stage. Second, and this is the major contribution, it presents two comprehensive examples of how the interpretation of high speed videos is carried out to retrieve useful information on the cracking processes in rocks.
Serum adiponectin is associated with family history of diabetes independently of obesity and insulin resistance in healthy Korean men and women
Authors: Sull Jae Woong , Kim Hee Jin , Yun Ji Eun , Kim Grace , Park Eun Jung , Kim Soriul , Lee Hee Yeon , Jee Sun Ha 
Published: December 2008

BackgroundAdiponectin has been reported as a new risk factor for the development of diabetes. However, it is not clear whether adiponectin levels are associated with family history of diabetes (FHD).ObjectiveThe objective of this study was to measure the independent association of serum adiponectin with FHD in relation to insulin resistance and obesity.MethodsIn 2006, a cross-sectional study was conducted in which waist circumference (WC), body mass index (BMI), and serum adiponectin were measured in 5919 healthy Korean men and women. Multiple linear regression models were used to assess the association of serum adiponectin levels with FHD. The population was classified into two groups according to median values for each of the following variables: WC, BMI, and homeostasis model assessment of insulin resistance (HOMA-IR).ResultsThe positive FHD group had higher HOMA-IR and lower adiponectin levels in both men and women than those without FHD. Adiponectin levels were significantly associated with FHD in men and women respectively, after adjusting for age, BMI, and alcohol consumption (P=0.0123 and 0.0004). The relationship between adiponectin and FHD was similar between the high and low insulin resistance, BMI, and WC groups in male non-smokers and in all Korean women.ConclusionThese results confirm that adiponectin levels are associated with FHD. These data also suggest that the association of serum adiponectin with FHD may be independent of obesity and insulin resistance.
Molecular Analysis of a Large Subtelomeric Nucleotide-Binding-Site–Leucine-Rich-Repeat Family in Two Representative Genotypes of the Major Gene Pools of Phaseolus vulgaris
Authors: Geffroy Valérie , Macadré Catherine , David Perrine , Pedrosa-Harand Andrea , Sévignac Mireille , Dauga Catherine , Langin Thierry 
Published: December 2008

Abstract
In common bean, the B4 disease resistance (R) gene cluster is a complex cluster localized at the end of linkage group (LG) B4, containing at least three R specificities to the fungus Colletotrichum lindemuthianum. To investigate the evolution of this R cluster since the divergence of Andean and Mesoamerican gene pools, DNA sequences were characterized from two representative genotypes of the two major gene pools of common bean (BAT93: Mesoamerican; JaloEEP558: Andean). Sequences encoding 29 B4-CC nucleotide-binding-site–leucine-rich-repeat (B4-CNL) genes were determined—12 from JaloEEP558 and 17 from BAT93. Although sequence exchange events were identified, phylogenetic analyses revealed that they were not frequent enough to lead to homogenization of B4-CNL sequences within a haplotype. Genetic mapping based on pulsed-field gel electrophoresis separation confirmed that the B4-CNL family is a large family specific to one end of LG B4 and is present at two distinct blocks separated by 26 cM. Fluorescent in situ hybridization on meiotic pachytene chromosomes revealed that two B4-CNL blocks are located in the subtelomeric region of the short arm of chromosome 4 on both sides of a heterochromatic block (knob), suggesting that this peculiar genomic environment may favor the proliferation of a large R gene cluster.
Statistical Mechanics and the Evolution of Polygenic Quantitative Traits
Authors: Barton N H , de Vladar H P 
Published: December 2008

Abstract
The evolution of quantitative characters depends on the frequencies of the alleles involved, yet these frequencies cannot usually be measured. Previous groups have proposed an approximation to the dynamics of quantitative traits, based on an analogy with statistical mechanics. We present a modified version of that approach, which makes the analogy more precise and applies quite generally to describe the evolution of allele frequencies. We calculate explicitly how the macroscopic quantities (i.e., quantities that depend on the quantitative trait) depend on evolutionary forces, in a way that is independent of the microscopic details. We first show that the stationary distribution of allele frequencies under drift, selection, and mutation maximizes a certain measure of entropy, subject to constraints on the expectation of observable quantities. We then approximate the dynamical changes in these expectations, assuming that the distribution of allele frequencies always maximizes entropy, conditional on the expected values. When applied to directional selection on an additive trait, this gives a very good approximation to the evolution of the trait mean and the genetic variance, when the number of mutations per generation is sufficiently high (4Nμ &gt; 1). We show how the method can be modified for small mutation rates (4Nμ → 0). We outline how this method describes epistatic interactions as, for example, with stabilizing selection.