bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying disease-specific genes based on their topological significance in protein networks
Authors: Dezső Zoltán , Nikolsky Yuri , Nikolskaya Tatiana , Miller Jeremy , Cherba David , Webb Craig , Bugrim Andrej 
Published: March 2009

AbstractBackgroundThe identification of key target nodes within complex molecular networks remains a common objective in scientific research. The results of pathway analyses are usually sets of fairly complex networks or functional processes that are deemed relevant to the condition represented by the molecular profile. To be useful in a research or clinical laboratory, the results need to be translated to the level of testable hypotheses about individual genes and proteins within the condition of interest.ResultsIn this paper we describe novel computational methodology capable of predicting key regulatory genes and proteins in disease- and condition-specific biological networks. The algorithm builds shortest path network connecting condition-specific genes (e.g. differentially expressed genes) using global database of protein interactions from MetaCore. We evaluate the number of all paths traversing each node in the shortest path network in relation to the total number of paths going via the same node in the global network. Using these numbers and the relative size of the initial data set, we determine the statistical significance of the network connectivity provided through each node. We applied this method to gene expression data from psoriasis patients and identified many confirmed biological targets of psoriasis and suggested several new targets. Using predicted regulatory nodes we were able to reconstruct disease pathways that are in excellent agreement with the current knowledge on the pathogenesis of psoriasis.ConclusionThe systematic and automated approach described in this paper is readily applicable to uncovering high-quality therapeutic targets, and holds great promise for developing network-based combinational treatment strategies for a wide range of diseases.
The clinical effectiveness of different parenting programmes for children with conduct problems: a systematic review of randomised controlled trials
Authors: Dretzke Janine , Davenport Clare , Frew Emma , Barlow Jane , Stewart-Brown Sarah , Bayliss Sue , Taylor Rod S , Sandercock Josie , Hyde Chris 
Published: March 2009

Abstract

Background
Conduct problems are common, disabling and costly. The prognosis for children with conduct problems is poor, with outcomes in adulthood including criminal behaviour, alcoholism, drug abuse, domestic violence, child abuse and a range of psychiatric disorders.
There has been a rapid expansion of group based parent-training programmes for the treatment of children with conduct problems in a number of countries over the past 10 years. Existing reviews of parent training have methodological limitations such as inclusion of non-randomised studies, the absence of investigation for heterogeneity prior to meta-analysis or failure to report confidence intervals.
The objective of the current study was to systematically review randomised controlled trials of parenting programmes for the treatment of children with conduct problems.

Methods
Standard systematic review methods were followed including duplicate inclusion decisions, data extraction and quality assessment. Twenty electronic databases from the fields of medicine, psychology, social science and education were comprehensively searched for RCTs and systematic reviews to February 2006.
Inclusion criteria were: randomised controlled trial; of structured, repeatable parenting programmes; for parents/carers of children up to the age of 18 with a conduct problem; and at least one measure of child behaviour. Meta-analysis and qualitative synthesis were used to summarise included studies.

Results
57 RCTs were included. Studies were small with an average group size of 21. Meta-analyses using both parent (SMD -0.67; 95% CI: -0.91, -0.42) and independent (SMD -0.44; 95% CI: -0.66, -0.23) reports of outcome showed significant differences favouring the intervention group. There was insufficient evidence to determine the relative effectiveness of different approaches to delivering parenting programmes.

Conclusion
Parenting programmes are an effective treatment for children with conduct problems. The relative effectiveness of different parenting programmes requires further research.
Impact of intraoperative lung-protective interventions in patients undergoing lung cancer surgery
Authors: Licker Marc , Diaper John , Villiger Yann , Spiliopoulos Anastase , Licker Virginie , Robert John , Tschopp Jean-Marie 
Published: March 2009

Abstract
Introduction
In lung cancer surgery, large tidal volume and elevated inspiratory pressure are known risk factors of acute lung (ALI). Mechanical ventilation with low tidal volume has been shown to attenuate lung injuries in critically ill patients. In the current study, we assessed the impact of a protective lung ventilation (PLV) protocol in patients undergoing lung cancer resection.

Methods
We performed a secondary analysis of an observational cohort. Demographic, surgical, clinical and outcome data were prospectively collected over a 10-year period. The PLV protocol consisted of small tidal volume, limiting maximal pressure ventilation and adding end-expiratory positive pressure along with recruitment maneuvers. Multivariate analysis with logistic regression was performed and data were compared before and after implementation of the PLV protocol: from 1998 to 2003 (historical group, n = 533) and from 2003 to 2008 (protocol group, n = 558).

Results
Baseline patient characteristics were similar in the two cohorts, except for a higher cardiovascular risk profile in the intervention group. During one-lung ventilation, protocol-managed patients had lower tidal volume (5.3 ± 1.1 vs. 7.1 ± 1.2 ml/kg in historical controls, P = 0.013) and higher dynamic compliance (45 ± 8 vs. 32 ± 7 ml/cmH2O, P = 0.011). After implementing PLV, there was a decreased incidence of acute lung injury (from 3.7% to 0.9%, P < 0.01) and atelectasis (from 8.8 to 5.0, P = 0.018), fewer admissions to the intensive care unit (from 9.4% vs. 2.5%, P < 0.001) and shorter hospital stay (from 14.5 ± 3.3 vs. 11.8 ± 4.1, P < 0.01). When adjusted for baseline characteristics, implementation of the open-lung protocol was associated with a reduced risk of acute lung injury (adjusted odds ratio of 0.34 with 95% confidence interval of 0.23 to 0.75; P = 0.002).

Conclusions
Implementing an intraoperative PLV protocol in patients undergoing lung cancer resection was associated with improved postoperative respiratory outcomes as evidence by significantly reduced incidences of acute lung injury and atelectasis along with reduced utilization of intensive care unit resources.
Prospective Study of Factors Predicting Adherence to Medical Advice in Men With Testicular Cancer
Authors: Moynihan Clare , Norman Andy R. , Barbachano Yolanda , Burchell Louise , Huddart Robert , Dearnaley David P. , Horwich Alan 
Published: March 2009

Purpose To identify predictive factors of adherence to medical advice, specifically the likelihood of attendance to a recommended follow-up regimen in patients with newly diagnosed testicular cancer. Patients and Methods This was a prospective study measuring initially not only aspects of the doctor–patient interview, but also a range of demographic, psychological, social, and medical factors, and then recording attendance behavior on follow-up. All 209 new patients with testicular cancer referred between June 1992 and May 1995 were approached, and 184 men consented and completed questionnaires. The nonadherence end point (nonattender) was two failures to attend an outpatient appointment at least 1 month apart, despite a written reminder. Results Thirty-two participants (17%) were classified as nonattenders. No significant differences were found between attenders and nonattenders in the majority of psychosocial and medical variables that might have predicted nonadherence to medical advice. There was a highly significant association between nonattendance and a patient's perception of an unsatisfactory affective relationship with his clinician (P = .005; hazard ratio, 3.1; 95% CI, 1.4 to 6.6). Conclusion Patients who perceived an unsatisfactory affective relationship with their clinician that included an inability to trust the clinician and a perception that they were not being treated as “a person” were subsequently more likely to disregard medical advice regarding follow-up. Attention to the ways young men may wish to communicate with their clinicians is important, bearing in mind that they may not necessarily adhere to stereotypical images of masculine self-dependence.
Lack of Comprehension of Common Prostate Cancer Terms in an Underserved Population
Authors: Kilbridge Kerry L. , Fraser Gertrude , Krahn Murray , Nelson Elizabeth M. , Conaway Mark , Bashore Randall , Wolf Andrew , Barry Michael J. , Gong Debra A. , Nease Robert F. , Connors Alfred F. 
Published: March 2009

Purpose To assess the comprehension of common medical terms used in prostate cancer in patient education materials to obtain informed consent, and to measure outcomes after prostate cancer treatment. We address this issue among underserved, African-American men because of the increased cancer incidence and mortality observed in this population. Patients and Methods We reviewed patient education materials and prostate-specific quality-of-life instruments to identify technical terms describing sexual, urinary, and bowel function. Understanding of these terms was assessed in face-to-face interviews of 105, mostly African-American men, age ≥ 40, from two low-income clinics. Comprehension was evaluated using semiqualitative methods coded by two independent investigators. Demographics were collected and literacy was measured. Results Fewer than 50% of patients understood the terms “erection” or “impotent.” Only 5% of patients understood the term “incontinence” and 25% understood the term “bowel habits.” More patients recognized word roots than related terms or compound words (eg, “rectum” v “rectal urgency,” “intercourse” v “vaginal intercourse”). Comprehension of terms from all domains was statistically significantly correlated with reading level (P < .001). Median literacy level was fourth to sixth grade. Prostate cancer knowledge was poor. Many patients had difficulty locating key anatomic structures. Conclusion Limited comprehension of prostate cancer terms and low literacy create barriers to obtaining informed consent for treatment and to measuring prostate cancer outcomes accurately in our study population. In addition, the level of prostate cancer knowledge was poor. These results highlight the need for prostate cancer education efforts and outcomes measurements that consider literacy and use nonmedical language.
Phase II Studies of Gemcitabine and Cisplatin in Heavily and Minimally Pretreated Metastatic Breast Cancer
Authors: Chew Helen K. , Doroshow James H. , Frankel Paul , Margolin Kim A. , Somlo George , Lenz Heinz-Josef , Gordon Michael , Zhang Wu , Yang Dongyun , Russell Christy , Spicer Darcy , Synold Tim , Bayer Robert , Hantel Alexander , Stiff Patrick J. , Tetef Merry L. , Gandara David R. , Albain Kathy S. 
Published: March 2009

Purpose Cisplatin and gemcitabine have single-agent activity in metastatic breast cancer, and preclinical data support synergy of the combination. Two parallel, phase II trials were conducted to evaluate the response rate, response duration, and toxicities of the combination. Genetic polymorphisms were analyzed for correlation with outcomes. Patients and Methods Eligible women had measurable disease and heavily or minimally pretreated metastatic breast cancer. The heavily pretreated protocol required prior anthracycline and taxane therapy; cisplatin as part of high-dose therapy was allowed. All patients received cisplatin 25 mg/m2 on days 1 through 4 and gemcitabine 1,000 mg/m2 on days 2 and 8 of a 21-day cycle with prophylactic granulocyte colony-stimulating factor in the heavily pretreated group. Sera from a subset of patients were evaluated by polymerase chain reaction restriction fragment length polymorphism for polymorphisms in 10 genes of interest. Results Of 136 women enrolled, 74 were heavily pretreated. Both protocols accrued to their two-stage design. The response rate for both the heavily and minimally pretreated cohorts was 26%, and the median durations of response were 5.3 and 5.9 months, respectively. In a multivariate analysis, hormone receptor–negative disease was associated with a higher response rate. The most common grades 3 or 4 toxicities were thrombocytopenia (71%), neutropenia (66%), and anemia (38%). In a subset of 55 patients, the xeroderma pigmentosum group D (XPD)–751, x-ray cross-complementing group 3 (XRCC3) and cytidine deaminase polymorphisms were significantly associated with clinical outcomes. Conclusion Combination cisplatin and gemcitabine is active in metastatic breast cancer regardless of prior therapy. Genetic polymorphisms may tailor which patients benefit from this regimen.
Impact of Diabetes Mellitus on Complications and Outcomes of Adjuvant Chemotherapy in Older Patients With Breast Cancer
Authors: Srokowski Tomasz P. , Fang Shenying , Hortobagyi Gabriel N. , Giordano Sharon H. 
Published: March 2009

Purpose To evaluate whether diabetes affects patterns of adjuvant chemotherapy use, toxic effects of chemotherapy, and breast cancer outcomes. Patients and Methods By using the Surveillance, Epidemiology, and End Results–Medicare database, we identified patients aged 66 years or older who had stages I through III breast cancer that was diagnosed between 1992 and 2002. Multivariable regression analyses were performed to determine the effect of diabetes on use of chemotherapy, toxicities, and outcomes. The risks of all-cause mortality and breast cancer–specific (BCS) mortality were estimated with the Kaplan-Meier method. Results Our cohort had 70,781 men and women, of whom 14,414 (20.36%) had diabetes. Among people who received chemotherapy (n = 11,826), 21.0% were diabetics. In this group, diabetics had lower odds of receiving anthracyclines (odds ratio [OR], 0.78; 95% CI, 0.71 to 0.87) and taxanes (OR, 0.86; 95% CI, 0.75 to 0.99). Diabetes was associated with increased odds of being hospitalized for any chemotherapy toxicity (OR, 1.38; 95% CI, 1.23 to 1.56), for infection or fever (OR, 1.43; 95% CI, 1.2 to 1.7), for neutropenia (OR, 1.22; 95% CI, 1.03 to 1.45), for anemia (OR, 1.24; 95% CI, 1.05 to 1.47), and for any cause (OR, 1.32; 95% CI, 1.19 to 1.46). Patients with diabetes had higher all-cause mortality (hazard ratio [HR], 1.35; 95% CI, 1.31 to 1.39). There was a significant interaction between diabetes and chemotherapy use for BCS mortality. Diabetic and nondiabetic patients who did not receive chemotherapy had similar BCS mortality, but diabetic patients who did receive chemotherapy had higher BCS mortality than nondiabetic patients (OR, 1.20; 95% CI, 1.07 to 1.35). Conclusion In this observational, hypothesis-generating study, patients who have breast cancer and diabetes are at increased risk of chemotherapy-related toxicities compared with nondiabetic patients who are receiving chemotherapy and have higher all-cause mortality.
Patient Involvement in Decisions to Limit Treatment: The Crucial Role of Agreement Between Physician and Patient
Authors: Winkler Eva C. , Reiter-Theil Stella , Lange-Rieß Dorothee , Schmahl-Menges Nina , Hiddemann Wolfgang 
Published: March 2009

Purpose The aim of this study was to describe, first, the decision-making process concerning the limitation of life-prolonging treatment (DLT); second, the extent to which patients are actually involved in these decisions; and third, to detect medical and ethical factors that affect patient involvement. Patients and Methods This prospective qualitative study enrolled 76 patients with incurable cancer with whom the limitation of life-prolonging treatment was discussed. Embedded researchers on the wards recorded the patient's history, medical condition, type of treatment limitation discussed, patient wishes, decision-making capacity, and patient involvement using an in-depth documentation procedure. Results While the majority of patients were informed about their diagnosis, therapy, and course of disease (99%, 97%, 90%, respectively), only 47% were involved in DLT. Two thirds of the patients preferred palliative care, and one third wished to extend their lifetime. If patients preferred palliative care, they were more often in line with physicians' treatment goals than patients who were striving for longer survival (91.4% v 46.7%; P = .001). They also were involved significantly more often in DLT. Multivariate analysis showed that age, Karnofsky performance index or decision-making capacity had no impact on patient involvement. Conclusion Only half of the patients were involved in DLT. Surprisingly, the main predictor of patient involvement was not their medical condition, but agreement with physicians' palliative treatment goals. These results show that if physicians switch to comfort care in terminally ill patients and patients are not yet prepared to follow this line, treatment limitations are often decided without involving the patient.
Serum Amyloid A As a Prognostic Marker in Melanoma Identified by Proteomic Profiling
Authors: Findeisen Peter , Zapatka Marc , Peccerella Teresa , Matzk Heike , Neumaier Michael , Schadendorf Dirk , Ugurel Selma 
Published: March 2009

Purpose Currently known prognostic serum biomarkers of melanoma are powerful in metastatic disease, but weak in early-stage patients. This study was aimed to identify new prognostic biomarkers of melanoma by serum mass spectrometry (MS) proteomic profiling, and to validate candidates compared with established markers. Patients and Methods Two independent sets of serum samples from 596 melanoma patients were investigated. The first set (stage I = 102; stage IV = 95) was analyzed by matrix assisted laser desorption and ionization time of flight (MALDI TOF) MS for biomarkers differentiating between stage I and IV. In the second set (stage I = 98; stage II = 91; stage III = 87; stage IV = 103), the serum concentrations of the candidate marker serum amyloid A (SAA) and the known biomarkers S100B, lactate dehydrogenase, and C reactive protein (CRP) were measured using immunoassays. Results MALDI TOF MS revealed a peak at m/z 11.680 differentiating between stage I and IV, which could be identified as SAA. High peak intensities at m/z 11.680 correlated with poor survival. In univariate analysis, SAA was a strong prognostic marker in stage I to III (P = .043) and stage IV (P = .000083) patients. Combination of SAA and CRP increased the prognostic impact to P = .011 in early-stage (I to III) patients. Multivariate analysis revealed sex, stage, tumor load, S100B, SAA, and CRP as independent prognostic factors, with an interaction between SAA and CRP. In stage I to III patients, SAA combined with CRP was superior to S100B in predicting patients' progression-free and overall survival. Conclusion SAA combined with CRP might be used as prognostic serological biomarkers in early-stage melanoma patients, helping to discriminate low-risk patients from high-risk patients needing adjuvant treatment.
Phase II Trial of Vorinostat in Recurrent Glioblastoma Multiforme: A North Central Cancer Treatment Group Study
Authors: Galanis Evanthia , Jaeckle Kurt A. , Maurer Matthew J. , Reid Joel M. , Ames Matthew M. , Hardwick James S. , Reilly John F. , Loboda Andrey , Nebozhyn Michael , Fantin Valeria R. , Richon Victoria M. , Scheithauer Bernd , Giannini Caterina , Flynn Patrick J. , Moore Dennis F. , Zwiebel James , Buckner Jan C. 
Published: March 2009

Purpose Vorinostat, a histone deacetylase inhibitor, represents a rational therapeutic target in glioblastoma multiforme (GBM). Patients and Methods Patients with recurrent GBM who had received one or fewer chemotherapy regimens for progressive disease were eligible. Vorinostat was administered at a dose of 200 mg orally twice a day for 14 days, followed by a 7-day rest period. Results A total of 66 patients were treated. Grade 3 or worse nonhematologic toxicity occurred in 26% of patients and consisted mainly of fatigue (17%), dehydration (6%), and hypernatremia (5%); grade 3 or worse hematologic toxicity occurred in 26% of patients and consisted mainly of thrombocytopenia (22%). Pharmacokinetic analysis showed lower vorinostat maximum concentration and area under the curve (0 to 24 hours) values in patients treated with enzyme-inducing anticonvulsants, although this did not reach statistical significance. The trial met the prospectively defined primary efficacy end point, with nine of the first 52 patients being progression-free at 6 months. Median overall survival from study entry was 5.7 months (range, 0.7 to 28+ months). Immunohistochemical analysis performed in paired baseline and post-vorinostat treatment samples in a separate surgical subgroup of five patients with recurrent GBM showed post treatment increase in acetylation of histones H2B and H4 (four of five patients) and of histone H3 (three of five patients). Microarray RNA analysis in the same samples showed changes in genes regulated by vorinostat, such as upregulation of E-cadherin (P = .02). Conclusion Vorinostat monotherapy is well tolerated in patients with recurrent GBM and has modest single-agent activity. Histone acetylation analysis and RNA expression profiling indicate that vorinostat in this dose and schedule affects target pathways in GBM. Additional testing of vorinostat in combination regimens is warranted.
Randomized Phase II and Pharmacogenetic Study of Pemetrexed Compared With Pemetrexed Plus Carboplatin in Pretreated Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Smit Egbert F. , Burgers Sjaak A. , Biesma Bonne , Smit Hans J.M. , Eppinga Pier , Dingemans Anne-Marie C. , Joerger Markus , Schellens Jan H. , Vincent Andrew , van Zandwijk Nico , Groen Harry J.M. 
Published: March 2009

Purpose We performed a randomized phase II trial comparing pemetrexed with pemetrexed plus carboplatin (PC) in patients experiencing relapse after platinum-based chemotherapy. Patients and Methods Main eligibility criteria were histologic or cytologic proof of advanced non–small-cell lung cancer (NSCLC), relapse more than 3 months after platinum-based chemotherapy, normal organ function, and Eastern Cooperative Oncology Group performance status 0 to 2. Patients were randomly assigned to pemetrexed 500 mg/m2 (arm A) or carboplatin area under the curve 5 and pemetrexed 500 mg/m2 (arm B), both administered intravenously every 3 weeks. Response assessment was performed every 6 weeks; toxicity assessment was performed every 3 weeks. Primary end point was time to progression (TTP); secondary end points were objective response rate (ORR), overall survival (OS), and toxicity. The study was designed to detect a 33% decrease in the hazard of disease progression in the combination arm (α = 0.05, two-sided log-rank test). Polymorphisms of thymidylate synthase, the reduced folate carrier, γ-glutamyl hydrolase, and methylenetetrahydrofolate reductase (MTHF) were investigated in peripheral WBCs of consenting patients. Results Two hundred forty patients were enrolled. Median TTP was 2.8 months for arm A versus 4.2 months for arm B (hazard ratio, 0.67; 95% CI, 0.51 to 0.89; P = .005). Median OS was 7.6 months and 8.0 months and ORR was 4% and 9% for arms A and B, respectively. Subgroup analyses found adenocarcinoma to be associated with favorable outcome. Toxicities in both arms was negligible, with one potential toxic death in arm A. Patients with MTHFR C677T homozygous mutation had increased progression-free survival compared with patients with wild-type or heterozygous mutations (P = .03). Conclusion PC as second-line treatment for relapsed NSCLC resulted in a significant 33% reduction of the hazard of disease progression as compared with pemetrexed alone.