bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Abiraterone Acetate on Androgen Signaling in Castrate-Resistant Prostate Cancer in Bone
Authors: Efstathiou Eleni , Titus Mark , Tsavachidou Dimitra , Tzelepi Vassiliki , Wen Sijin , Hoang Anh , Molina Arturo , Chieffo Nicole , Smith Lisa A. , Karlou Maria , Troncoso Patricia , Logothetis Christopher J. 
Published: December 2011

Purpose Persistent androgen signaling is implicated in castrate-resistant prostate cancer (CRPC) progression. This study aimed to evaluate androgen signaling in bone marrow–infiltrating cancer and testosterone in blood and bone marrow and to correlate with clinical observations. Patients and Methods This was an open-label, observational study of 57 patients with bone-metastatic CRPC who underwent transiliac bone marrow biopsy between October 2007 and March 2010. Patients received oral abiraterone acetate (1 g) once daily and prednisone (5 mg) twice daily. Androgen receptor (AR) and CYP17 expression were assessed by immunohistochemistry, testosterone concentration by mass spectrometry, AR copy number by polymerase chain reaction, and TMPRSS2-ERG status by fluorescent in situ hybridization in available tissues. Results Median overall survival was 555 days (95% CI, 440 to 965+ days). Maximal prostate-specific antigen decline ≥ 50% occurred in 28 (50%) of 56 patients. Homogeneous, intense nuclear expression of AR, combined with ≥ 10% CYP17 tumor expression, was correlated with longer time to treatment discontinuation (> 4 months) in 25 patients with tumor-infiltrated bone marrow samples. Pretreatment CYP17 tumor expression ≥ 10% was correlated with increased bone marrow aspirate testosterone. Blood and bone marrow aspirate testosterone concentrations declined to less than picograms-per-milliliter levels and remained suppressed at progression. Conclusion The observed pretreatment androgen-signaling signature is consistent with persistent androgen signaling in CRPC bone metastases. This is the first evidence that abiraterone acetate achieves sustained suppression of testosterone in both blood and bone marrow aspirate to less than picograms-per-milliliter levels. Potential admixture of blood with bone marrow aspirate limits our ability to determine the origin of measured testosterone.
Risk Factors for Obesity in Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Green Daniel M. , Cox Cheryl L. , Zhu Liang , Krull Kevin R. , Srivastava Deo Kumar , Stovall Marilyn , Nolan Vikki G. , Ness Kirsten K. , Donaldson Sarah S. , Oeffinger Kevin C. , Meacham Lillian R. , Sklar Charles A. , Armstrong Gregory T. , Robison Leslie L. 
Published: December 2011

PurposeMany Childhood Cancer Survivor Study (CCSS) participants are at increased risk for obesity. The etiology of their obesity is likely multifactorial but not well understood.Patients and MethodsWe evaluated the potential contribution of demographic, lifestyle, treatment, and intrapersonal factors and self-reported pharmaceutical use to obesity (body mass index ≥ 30 kg/m2) among 9,284 adult (> 18 years of age) CCSS participants. Independent predictors were identified using multivariable regression models. Interrelationships were determined using structural equation modeling (SEM).ResultsIndependent risk factors for obesity included cancer diagnosed at 5 to 9 years of age (relative risk [RR], 1.12; 95% CI, 1.01 to 1.24; P = .03), abnormal Short Form–36 physical function (RR, 1.19; 95% CI, 1.06 to 1.33; P < .001), hypothalamic/pituitary radiation doses of 20 to 30 Gy (RR, 1.17; 95% CI, 1.05 to 1.30; P = .01), and paroxetine use (RR, 1.29; 95% CI, 1.08 to 1.54; P = .01). Meeting US Centers for Disease Control and Prevention guidelines for vigorous physical activity (RR, 0.90; 95% CI, 0.82 to 0.97; P = .01) and a medium amount of anxiety (RR, 0.86; 95% CI, 0.75 to 0.99; P = .04) reduced the risk of obesity. Results of SEM (N = 8,244; comparative fit index = 0.999; Tucker Lewis index = 0.999; root mean square error of approximation = 0.014; weighted root mean square residual = 0.749) described the hierarchical impact of the direct predictors, moderators, and mediators of obesity.ConclusionTreatment, lifestyle, and intrapersonal factors, as well as the use of specific antidepressants, may contribute to obesity among survivors. A multifaceted intervention, including alternative drug and other therapies for depression and anxiety, may be required to reduce risk.
Substantial Susceptibility of Chronic Lymphocytic Leukemia to BCL2 Inhibition: Results of a Phase I Study of Navitoclax in Patients With Relapsed or Refractory Disease
Authors: Roberts Andrew W. , Seymour John F. , Brown Jennifer R. , Wierda William G. , Kipps Thomas J. , Khaw Seong Lin , Carney Dennis A. , He Simon Z. , Huang David C.S. , Xiong Hao , Cui Yue , Busman Todd A. , McKeegan Evelyn M. , Krivoshik Andrew P. , Enschede Sari H. , Humerickhouse Rod 
Published: December 2011

Purpose BCL2 overexpression is a hallmark of chronic lymphocytic leukemia (CLL). The novel BH3 mimetic navitoclax (ABT-263) specifically inhibits BCL2 and related proteins BCL-xl and BCL-w, potently inducing apoptosis of CLL cells in vitro. A phase I trial in patients with CLL was conducted to evaluate the safety, pharmacokinetics, and biologic activity of oral navitoclax. Patients and Methods Twenty-nine patients with relapsed or refractory CLL received daily navitoclax for 14 days (10, 110, 200, or 250 mg/d; n = 15) or 21 days (125, 200, 250, or 300 mg/d; n = 14) of each 21-day cycle. Dose escalation decisions were informed by continual reassessment methodology. Results Lymphocytosis was reduced by more than 50% in 19 of 21 patients with baseline lymphocytosis. Among 26 patients treated with navitoclax ≥ 110 mg/d, nine (35%) achieved a partial response and seven maintained stable disease for more than 6 months. Median treatment duration was 7 months (range, 1 to ≥ 29 months). Median progression-free survival was 25 months. Activity was observed in patients with fludarabine-refractory disease, bulky adenopathy, and del(17p) CLL. Thrombocytopenia due to BCL-xl inhibition was the major dose-limiting toxicity and was dose-related. Low MCL1 expression and high BIM:MCL1 or BIM:BCL2 ratios in leukemic cells correlated with response. We determined that the navitoclax dose of 250 mg/d in a continuous dosing schedule was optimal for phase II studies. Conclusion BCL2 is a valid therapeutic target in CLL, and its inhibition by navitoclax warrants further evaluation as monotherapy and in combination in this disease.
Impact of Long-Term Serum Platinum Concentrations on Neuro- and Ototoxicity in Cisplatin-Treated Survivors of Testicular Cancer
Authors: Sprauten Mette , Darrah Thomas H. , Peterson Derick R. , Campbell M. Ellen , Hannigan Robyn E. , Cvancarova Milada , Beard Clair , Haugnes Hege S. , Fosså Sophie D. , Oldenburg Jan , Travis Lois B. 
Published: December 2011

Purpose Cisplatin-induced neurotoxicity and ototoxicity (NTX) are important adverse effects after chemotherapy for testicular cancer (TC). Although serum platinum is measurable years after therapy, its impact on NTX has not been evaluated. Patients and Methods In all, 169 cisplatin-treated survivors of TC provided blood samples at Survey I and reported NTX during Survey I (1998-2002) and Survey II (2007-2008). Serum platinum was quantified by inductively coupled plasma mass spectrometry. Patient-reported outcomes were evaluated with the Scale for Chemotherapy-Induced Neurotoxicity (SCIN), regarding the extent of symptom bother as 0, “not at all”; 1, “a little”; 2, “quite a bit”; or 3, “very much.” Summing the six symptom scores yielded a total SCIN score of 0 to 18. Categorizing total SCIN scores into quartiles yielded similar-sized groups with increasing symptoms. Multivariate ordinal logistic regression analyses evaluated associations between NTX and long-term serum platinum levels, adjusting for cisplatin dose, dosing schedule, and age. Results At Survey I, a significant four- to five-fold association with total SCIN score emerged for the highest serum platinum quartile (odds ratio [OR], 4.69; 95% CI, 1.82 to 12.08). Paresthesias and Raynaud's syndrome (hands and feet) showed significant two- to four-fold increased risks with the highest platinum quartile. At Survey II, total SCIN score remained significantly associated with the highest platinum quartile (OR, 4.28; 95% CI, 1.36 to 13.48). Paresthesias (hands and feet) and tinnitus showed significant three- to four-fold increased risks for the highest platinum quartile. Cumulative cisplatin dose was not associated with total SCIN score or individual SCIN symptoms in multivariate analyses. Conclusion Here we document a significant relationship between increasing levels of residual serum platinum and NTX severity after adjusting for initial cisplatin dose.
Safety and Efficacy of Combination Immunotherapy With Interferon Alfa-2b and Tremelimumab in Patients With Stage IV Melanoma
Authors: Tarhini Ahmad A. , Cherian John , Moschos Stergios J. , Tawbi Hussein A. , Shuai Yongli , Gooding William E. , Sander Cindy , Kirkwood John M. 
Published: December 2011

PurposeWe tested the hypothesis that the combination of tremelimumab and interferon alfa-2b acting via different and possibly synergistic mechanisms would overcome tumor immune tolerance and lead to significant and durable clinical responses.Patients and MethodsWe conducted a phase II study in which patients were administered tremelimumab 15 mg/kg/course (three cycles [one cycle = 4 weeks]) intravenously every 12 weeks. High-dose interferon alfa-2b (HDI) was administered concurrently, including intravenous induction at 20 MU/m2/d for 5 d/wk for 4 weeks followed by maintenance at 10 MU/m2/d subcutaneously three times a week for 8 weeks per course. From course 2 onward, HDI maintenance was administered subcutaneously.ResultsThirty-seven patients with American Joint Committee on Cancer stage IV (9M1a, 6M1b, and 22M1c) were enrolled. Two patients had previously treated brain metastases. Grades 3 and 4 toxicities included neutropenia (six patients; 17%), diarrhea/colitis (four patients; 11%), liver enzyme increase (four patients; 11%), rash (four patients; 11%), fatigue (15 patients; 40%), and anxiety/depression (five patients; 14%). Response data were available for 35 patients. The best objective response rate (RR; Response Evaluation Criteria in Solid Tumors) by intention to treat was 24% (90% CI, 13% to 36%; four complete responses [CRs] and five partial responses [PRs] that lasted 6, 6, > 12, > 14, > 18, 20, > 28, 30, and > 37 months, respectively). Fourteen patients (38%) had stable disease (SD) that lasted 1.5 to 21 months. The median progression-free survival was 6.4 months (95% CI, 3.3 to 12.1 months). The median overall survival (OS) was 21 months (95% CI, 9.5 to not reached). There was a weak association between therapy-induced autoimmunity and clinical benefits (CR/PR/SD; P = .0059), baseline C-reactive protein (CRP) less than or equal to 2.7× the upper limit of normal and clinical benefits (P = .0494) and improved probability of survival (P = .0032), and baseline lymphocyte count of at least 1,000/μL and response (CR/PR; P = .0183) and clinical benefits (CR/PR/SD; P = .0255). Biomarker associations were not significant after adjustment for multiple comparisons.ConclusionHDI can be administered combined with tremelimumab with acceptable toxicity and promising durable antitumor efficacy that warrant further testing in a randomized trial.
Phase III Trial Comparing Capecitabine Plus Cisplatin Versus Capecitabine Plus Cisplatin With Concurrent Capecitabine Radiotherapy in Completely Resected Gastric Cancer With D2 Lymph Node Dissection: The ARTIST Trial
Authors: Lee Jeeyun , Lim Do Hoon , Kim Sung , Park Se Hoon , Park Joon Oh , Park Young Suk , Lim Ho Yeong , Choi Min Gew , Sohn Tae Sung , Noh Jae Hyung , Bae Jae Moon , Ahn Yong Chan , Sohn Insuk , Jung Sin Ho , Park Cheol Keun , Kim Kyoung-Mee , Kang Won Ki 
Published: December 2011

Purpose The ARTIST (Adjuvant Chemoradiation Therapy in Stomach Cancer) trial was the first study to our knowledge to investigate the role of postoperative chemoradiotherapy therapy in patients with curatively resected gastric cancer with D2 lymph node dissection. This trial was designed to compare postoperative treatment with capecitabine plus cisplatin (XP) versus XP plus radiotherapy with capecitabine (XP/XRT/XP). Patients and Methods The XP arm received six cycles of XP (capecitabine 2,000 mg/m2 per day on days 1 to 14 and cisplatin 60 mg/m2 on day 1, repeated every 3 weeks) chemotherapy. The XP/XRT/XP arm received two cycles of XP followed by 45-Gy XRT (capecitabine 1,650 mg/m2 per day for 5 weeks) and two cycles of XP. Results Of 458 patients, 228 were randomly assigned to the XP arm and 230 to the XP/XRT/XP arm. Treatment was completed as planned by 75.4% of patients (172 of 228) in the XP arm and 81.7% (188 of 230) in the XP/XRT/XP arm. Overall, the addition of XRT to XP chemotherapy did not significantly prolong disease-free survival (DFS; P = .0862). However, in the subgroup of patients with pathologic lymph node metastasis at the time of surgery (n = 396), patients randomly assigned to the XP/XRT/XP arm experienced superior DFS when compared with those who received XP alone (P = .0365), and the statistical significance was retained at multivariate analysis (estimated hazard ratio, 0.6865; 95% CI, 0.4735 to 0.9952; P = .0471). Conclusion The addition of XRT to XP chemotherapy did not significantly reduce recurrence after curative resection and D2 lymph node dissection in gastric cancer. A subsequent trial (ARTIST-II) in patients with lymph node–positive gastric cancer is planned.
Educating Surgical Patients to Reduce the Risk of Venous Thromboembolism: An Audit of an Effective Strategy
Authors: Sadideen Hazim , O'Callaghan John M , Navidi Maziar , Sayegh Mazin 
Published: December 2011

Objectives Venous thromboembolism (VTE) causes approximately 25,000 deaths each year from hospital-acquired thrombosis in the UK. Patient understanding of risk factors and preventive measures is important in preventing VTE. This audit was designed to assess surgical patient awareness and understanding of VTE risk factors and prophylaxis. Design A questionnaire was designed to assess preoperative patient understanding of components of the National Institute for Health and Clinical Excellence (NICE) guidelines. Leaflets were designed to address gaps in understanding and junior doctors were given guidance on patient education. A second group of patients completed the same questionnaire after introduction of the education system. Setting Worthing Hospital, UK. Participants One hundred and twenty-one patients due to undergo major general surgery. Seventy-one participants completed the questionnaire prior to implementation of the education system, and 50 after. Main Outcome Measures Improvement in patient awareness of VTE, its risk factors and its preventative measures (in response to the education system). Results Following the introduction of a targeted VTE education system, there was a significant improvement in the awareness of VTE to 90% ( P< 0.01), its signs to 80% ( P< 0.01), and its preventative measures to 84% ( P<0.01). Conclusions Patient education is of paramount importance in reducing the risks of VTE perioperatively. A simple method of introducing patient education at pre-assessment clinic and as part of their discharge planning, for major elective surgery, is an effective system in improving patient understanding of VTE, its risk factors and the importance of prophylaxis. It may also increase compliance.
Therapeutic Options in Managing Hyponatremia: Focus on Arginine Vasopressin Receptor Antagonists
Authors: Human Theresa 
Published: December 2011

Purpose To describe the available and emerging treatment options for acute and chronic hyponatremia, including the efficacy, safety, and recommendations regarding appropriate use, monitoring, and treatment individualization. Summary Arginine vasopressin (AVP) receptor antagonists provide an opportunity to address some of the unmet medical needs of patients with hyponatremia. Traditional therapies, including diuretics, fluid restriction, and saline infusions, have variable effects, potential toxicities, and issues with patient adherence. Furthermore, these therapies are not specific to the underlying pathophysiology causing the hyponatremia. The recently approved AVP receptor antagonists target the underlying abnormal release of AVP that is very likely at the core of the physiology. Conclusion Management of hyponatremia requires balancing the benefits of therapeutic intervention for the restoration of normal serum sodium against the potential risks. The data available indicate that this new class of medications, the AVP receptor antagonists, can favorably affect serum sodium and clinical outcomes in patients with hypervolemic and euvolemic hyponatremia.
Hyponatremia's Impact on Patients and Health Systems
Authors: Patterson J. Herbert 
Published: December 2011

Purpose To define hyponatremia, discuss its incidence and epidemiology, and summarize the frequency and prognostic implications of hyponatremia in selected clinical conditions. Summary Hyponatremia is the most common electrolyte abnormality encountered in clinical practice. Hyponatremia is commonly defined as a serum sodium concentration of <136 mEq/L. There are 3 different types of hyponatremia: hypovolemia, euvolemia, and hypervolemia. Epidemiologic studies reveal that hyponatremia is a common problem in hospitalized patients whether it is present at admission or is hospital acquired. The disorder increases the risk of admission to the intensive care unit, hospital length of stay, and morbidity and mortality. Hyponatremia appears to be a marker for severe underlying disease with a poor prognosis. Congestive heart failure, pneumonia, cirrhosis, and neurologic disease are among the serious clinical conditions known to be associated with hyponatremia. Chronic hyponatremia presents its own set of challenges; even in mild disease that is often asymptomatic, patients are at heightened risk for falls, gait disturbances, attention deficits, and fracture. Conclusion Hyponatremia is the most common electrolyte disorder encountered in clinical practice and is associated with significant morbidity and mortality, especially at lower serum sodium concentrations. The disorder has a substantial impact on hospital length of stay with a direct impact on health care costs. Further, as this discussion illustrates, hyponatremia represents a significant clinical burden in all forms – mild, moderate, and severe – with subsequent clinical consequences.
Agents and artists in Central Africa
Authors: Boyd Raymond 
Published: December 2011

Abstract

Zande and Chamba-Daka are Adamawa-Ubangi (Niger-Congo) languages. The Zande agent noun is identical with the completive verb. Some agent nouns are instrumental or designate the process itself. The Chamba-Daka agent noun is a compound postposing the “infinitive” to the noun meaning ‘person’. It refers only to the subject argument of the source verb. Both languages have a semantically related compound: the “artist” noun meaning ‘owner, skillful user of (a material object)’ or ‘individual (with intrinsic attribute)’. The semantic range of the artist noun in both languages is similar. The artist noun may be formed with the “infinitive”; it then contrasts modally with the agent noun.
Pierrot L.
Authors: Pedneault-Deslauriers Julie 
Published: December 2011

Abstract
During Arnold Schoenberg's 1912–13 Pierrot lunaire tours, critics frequently described the work's Sprechstimme delivery as “hysterical” and “neurasthenic.” The essay expounds this important strand of Pierrot lunaire's reception by positioning the character of Pierrot in Paul Margueritte's pantomime Pierrot assassin de sa femme (1888) and Schoenberg's Opus 21 against Parisian and Viennese discourses on hysteria. Engaging aspects of pantomime, travesty, visual arts, medical iconography, and performance practice, I explicate how, as the medical definition of hysteria underwent important changes in etiology, symptomatology, and treatment in Freud's revisions of Jean-Martin Charcot's theories, so too did Pierrot's performance of the illness.
Early Childhood Overweight and Asthma and Allergic Sensitization at 8 Years of Age
Authors: Magnusson Jessica Öhman , Kull Inger , Mai Xiao-Mei , Wickman Magnus , Bergström Anna 
Published: December 2011

Objectives:
Our aim was to examine the associations between high BMI and changes in BMI status during the first 7 years of life and asthma and allergic sensitization at age 8 years.

Methods:
A birth cohort of newborn infants was followed for 8 years. Repeated parental questionnaires provided information on environmental exposures and health outcomes. Information on height and weight during childhood was retrieved from preschool and school health care records. The analyses included the 2075 children for whom information was available on weight and height, as well as on asthma, at age 8 years.

Results:
A high BMI (≥85th percentile) at age 1, 4, and/or 7 years was associated with an increased risk of asthma at age 8 years. However, no significant association was observed among children with high BMI at age 12 and/or 18 months (early age) or at age 4 years who developed a normal BMI by age 7 years. The risk was increased among children with high BMI at age 7 years, regardless of their earlier weight. Moreover, we observed an increased risk of sensitization to inhalant allergens among children with high BMI at age 7 years.

Conclusions:
Our study indicates that high BMI during the first 4 years does not increase the risk of asthma at school age among children who have developed a normal weight by age 7 years. However, high BMI at age 7 years is associated with an increased risk of asthma and sensitization to inhalant allergens.
Cumulative Prevalence of Arrest From Ages 8 to 23 in a National Sample
Authors: Brame Robert , Turner Michael G. , Paternoster Raymond , Bushway Shawn D. 
Published: December 2011

Objective:
To estimate the cumulative proportion of youth who self-report having been arrested or taken into custody for illegal or delinquent offenses (excluding arrests for minor traffic violations) from ages 8 to 23 years.

Methods:
Self-reported arrest history data (excluding arrests for minor traffic violations) from the National Longitudinal Survey of Youth 1997 (N = 7335) were examined from 1997 to 2008.

Results:
By age 18, the in-sample cumulative arrest prevalence rate lies between 15.9% and 26.8%; at age 23, it lies between 25.3% and 41.4%. These bounds make no assumptions at all about missing cases. If we assume that the missing cases are at least as likely to have been arrested as the observed cases, the in-sample age-23 prevalence rate must lie between 30.2% and 41.4%. The greatest growth in the cumulative prevalence of arrest occurs during late adolescence and the period of early or emerging adulthood.

Conclusions:
Since the last nationally defensible estimate based on data from 1965, the cumulative prevalence of arrest for American youth (particularly in the period of late adolescence and early adulthood) has increased substantially. At a minimum, being arrested for criminal activity signifies increased risk of unhealthy lifestyle, violence involvement, and violent victimization. Incorporating this insight into regular clinical assessment could yield significant benefits for patients and the larger community.