bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inferring modules from human protein interactome classes
Authors: Marras Elisabetta , Travaglione Antonella , Chaurasia Gautam , Futschik Matthias , Capobianco Enrico 
Published: August 2010

Abstract

Background
The integration of protein-protein interaction networks derived from high-throughput screening approaches and complementary sources is a key topic in systems biology. Although integration of protein interaction data is conventionally performed, the effects of this procedure on the result of network analyses has not been examined yet. In particular, in order to optimize the fusion of heterogeneous interaction datasets, it is crucial to consider not only their degree of coverage and accuracy, but also their mutual dependencies and additional salient features.

Results
We examined this issue based on the analysis of modules detected by network clustering methods applied to both integrated and individual (disaggregated) data sources, which we call interactome classes. Due to class diversity, we deal with variable dependencies of data features arising from structural specificities and biases, but also from possible overlaps. Since highly connected regions of the human interactome may point to potential protein complexes, we have focused on the concept of modularity, and elucidated the detection power of module extraction algorithms by independent validations based on GO, MIPS and KEGG. From the combination of protein interactions with gene expressions, a confidence scoring scheme has been proposed before proceeding via GO with further classification in permanent and transient modules.

Conclusions
Disaggregated interactomes are shown to be informative for inferring modularity, thus contributing to perform an effective integrative analysis. Validation of the extracted modules by multiple annotation allows for the assessment of confidence measures assigned to the modules in a protein pathway context. Notably, the proposed multilayer confidence scheme can be used for network calibration by enabling a transition from unweighted to weighted interactomes based on biological evidence.
NDRG2 suppresses the proliferation of clear cell renal cell carcinoma cell A-498
Authors: Ma Jian-Jun , Liao Cheng-Gong , Jiang Xue , Zhao Hua-Dong , Yao Li-Bo , Bao Ting-Yi 
Published: August 2010

Abstract

Background
Recently, the anti-tumor activity of N-myc downstream-regulated gene 2 (NDRG2) was shown decreased expression in clear cell renal cell carcinoma (CCRCC), but the role of the down-expression of NDRG2 has not been described.

Methods
The NDRG2 recombinant adenovirus plasmid was constructed. The proliferation rate and NDRG2 expression of cell infected with recombinant plasmid were mesured by MTT, Flow cytometry analysis and western blot.

Results
The CCRCC cell A-498 re-expressed NDRG2 when infected by NDRG2 recombinant adenovirus and significantly decreased the proliferation rate. Fluorescence activated cell sorter analysis showed that 25.00% of cells expressed NDRG2 were in S-phase compared to 40.67% of control cells, whereas 62.08% of cells expressed NDRG2 were in G1-phase compared to 54.39% of control cells (P < 0.05). In addition, there were much more apoptotic cells in NDRG2-expressing cells than in the controls (P < 0.05). Moreover, upregulation of NDRG2 protein was associated with a reduction in cyclin D1, cyclin E, whereas cyclinD2, cyclinD3 and cdk2 were not affected examined by western blot. Furthermore, we found that p53 could upregulate NDRG2 expression in A-498 cell.

Conclusions
We found that NDRG2 can inhibit the proliferation of the renal carcinoma cells and induce arrest at G1 phase. p53 can up-regulate the expression of NDRG2. Our results showed that NDRG2 may function as a tumor suppressor in CCRCC.
Idiopathic toe walking and sensory processing dysfunction
Authors: Williams Cylie M , Tinley Paul , Curtin Michael 
Published: August 2010

AbstractBackgroundIt is generally understood that toe walking involves the absence or limitation of heel strike in the contact phase of the gait cycle. Toe walking has been identified as a symptom of disease processes, trauma and/or neurogenic influences. When there is no obvious cause of the gait pattern, a diagnosis of idiopathic toe walking (ITW) is made. Although there has been limited research into the pathophysiology of ITW, there has been an increasing number of contemporary texts and practitioner debates proposing that this gait pattern is linked to a sensory processing dysfunction (SPD). The purpose of this paper is to examine the literature and provide a summary of what is known about the relationship between toe walking and SPD.MethodForty‐nine articles were reviewed, predominantly sourced from peer reviewed journals. Five contemporary texts were also reviewed. The literature styles consisted of author opinion pieces, letters to the editor, clinical trials, case studies, classification studies, poster/conference abstracts and narrative literature reviews. Literature was assessed and graded according to level of evidence.ResultsOnly one small prospective, descriptive study without control has been conducted in relation to idiopathic toe walking and sensory processing. A cross‐sectional study into the prevalence of idiopathic toe walking proposed sensory processing as being a reason for the difference. A proposed link between ITW and sensory processing was found within four contemporary texts and one conference abstract.ConclusionBased on the limited conclusive evidence available, the relationship between ITW and sensory processing has not been confirmed. Given the limited number and types of studies together with the growing body of anecdotal evidence it is proposed that further investigation of this relationship would be advantageous.
Who benefits most from mild therapeutic hypothermia in coronary intervention era? A retrospective and propensity-matched study
Authors: Kagawa Eisuke , Inoue Ichiro , Kawagoe Takuji , Ishihara Masaharu , Shimatani Yuji , Kurisu Satoshi , Nakama Yasuharu , Dai Kazuoki , Otani Takayuki , Ikenaga Hiroki , Morimoto Yoshimasa , Ejiri Kentaro , Oda Nozomu 
Published: August 2010

Abstract
Introduction
The aim of the present study was to investigate the impact of the time interval from collapse to return of spontaneous circulation (CPA-ROSC) in cardiac arrest patients and the types of patients who will benefit from therapeutic hypothermia.

Methods
Four hundred witnessed adult comatose survivors of out-of-hospital cardiac arrest of cardiac etiology were enrolled in the study. The favorable neurological outcome was defined as category 1 or 2 on the five-point Pittsburgh cerebral performance scale at the time of hospital discharge. A matching process based on the propensity score was performed to equalize potential prognostic factors in the hypothermia and normothermia groups, and to formulate a balanced 1:1 matched cohort study.

Results
The rate of favorable neurological outcome was higher (P < 0.05) in the hypothermia group (n = 110) than in the normothermia group in patients with CPA-ROSC of 15 to 20 minutes (64% vs. 17%), 20 to 25 minutes (70% vs. 8%), 25 to 30 minutes (50% vs. 7%), 35 to 40 minutes (27% vs. 0%) and 40 to 45 minutes (29% vs. 2%). A similar association was observed in a propensity-matched cohort, but the differences were not significant. There was no significant difference in the rate of favorable neurological outcome between the hypothermia-matched group and the normothermia-matched group. In the patients whose CPA-ROSC was greater than 15 minutes, however, the rate of favorable neurological outcome was higher in the hypothermia-matched group than in the normothermia-matched group (27% vs. 4%, P < 0.001). In multivariate analysis, the CPA-ROSC was an independent predictor of favorable neurological outcome (every 1 minute: odds ratio = 0.89, 95% confidence interval = 0.85 to 0.92, P < 0.001).

Conclusions
The CPA-ROSC is an independent predictor of neurological outcome. Therapeutic hypothermia is more beneficial in comatose survivors of cardiac arrest with CPA-ROSC greater than 15 minutes.
Qualitative Assessment of the Progesterone Receptor and HER2 Improves the Nottingham Prognostic Index Up to 5 Years After Breast Cancer Diagnosis
Authors: Van Belle Vanya , Van Calster Ben , Brouckaert Olivier , Vanden Bempt Isabelle , Pintens Saskia , Harvey Vernon , Murray Paula , Naume Björn , Wiedswang Gro , Paridaens Robert , Moerman Philippe , Amant Frederic , Leunen Karin , Smeets Ann , Drijkoningen Maria , Wildiers Hans , Christiaens Marie-Rose , Vergote Ignace , Van Huffel Sabine , Neven Patrick 
Published: August 2010

Purpose To investigate whether the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) can improve the Nottingham Prognostic Index (NPI) in the classification of patients with primary operable breast cancer for disease-free survival (DFS). Patients and Methods The analysis is based on 1,927 patients with breast cancer treated between 2000 and 2005 at the University Hospitals, Leuven. We compared performances of NPI with and without ER, PR and/or HER2. Validation was done on two external data sets containing 862 and 2,805 patients from Oslo (Norway) and Auckland (New Zealand), respectively. Results In the Leuven cohort, median follow-up was 66 months, and 13.7% of patients experienced a breast cancer–related event. Positive staining for ER, PR, and HER2 was detected, respectively, in 86.9%, 75.5%, and 11.9% of patients. Based on multivariate Cox regression modeling, the improved NPI (iNPI) was derived as NPI − PR positivity + HER2 positivity. Validation results showed a risk group reclassification of 20% to 30% of patients when using iNPI with its optimal risk boundaries versus NPI, in a majority of patients to more appropriate risk groups. An additional 10% of patients were classified into the extreme risk groups, where clinical actions are less ambiguous. Survival curves of reclassified patients resembled more closely those for patients in the same iNPI group than those for patients in the same NPI group. Conclusion The addition of PR and HER2 to NPI increases its 5-year prognostic accuracy. The iNPI can be considered as a clinically useful tool for stratification of patients with breast cancer receiving standard of care.
Cancer Patients' Roles in Treatment Decisions: Do Characteristics of the Decision Influence Roles?
Authors: Keating Nancy L. , Beth Landrum Mary , Arora Neeraj K. , Malin Jennifer L. , Ganz Patricia A. , van Ryn Michelle , Weeks Jane C. 
Published: August 2010

Purpose Patients with more active roles in decisions are more satisfied and may have better health outcomes. Younger and better educated patients have more active roles in decisions, but whether patients' roles in decisions differ by characteristics of the decision itself is unknown. Patients and Methods We surveyed a large, population-based cohort of patients with recently diagnosed lung or colorectal cancer about their roles in decisions regarding surgery, radiation therapy, and/or chemotherapy. We used multinomial logistic regression to assess whether characteristics of the decision, including evidence about the treatment's benefit, whether the decision was likely preference-sensitive (palliative therapy for metastatic cancer), and treatment modality, influenced patients' roles in that decision. Results Of 10,939 decisions made by 5,383 patients, 38.9% were patient controlled, 43.6% were shared, and 17.5% were physician controlled. When there was good evidence to support a treatment, shared control was greatest; when evidence was uncertain, patient control was greatest; and when there was no evidence for or evidence against a treatment, physician control was greatest (overall P < .001). Decisions about treatments for metastatic cancers tended to be more physician controlled than other decisions (P < .001). Conclusion Patients making decisions about treatments for which no evidence supports benefit and decisions about noncurative treatments reported more physician control, which suggests that patients may not want the responsibility of deciding on treatments that will not cure them. Better strategies for shared decision making may be needed when there is no evidence to support benefit of a treatment or when patients have terminal illnesses that cannot be cured.
Pretreatment Quality of Life As a Predictor of Distant Metastasis and Survival for Patients With Nasopharyngeal Carcinoma
Authors: Fang Fu-Min , Tsai Wen-Ling , Chien Chih-Yen , Chen Hui-Chun , Hsu Hsuan-Chih , Huang Tai-Lin , Lee Tsair-Fwu , Huang Hsuan-Ying , Lee Chien-Hung 
Published: August 2010

Purpose The purpose of this study was to examine the prognostic value of pretreatment quality of life (QoL) data on locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with nasopharyngeal carcinoma (NPC). Patients and Methods A total of 347 new patients with NPC, who were curatively treated by conformal radiotherapy from March 2003 to December 2007, were recruited. The Taiwan Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 was completed before treatment. Multivariate Cox's proportional hazards models were used to analyze the impact of clinical and QoL variables on the treatment results. Results The 5-year LRC, DMFS, and OS rates were 72.9%, 79.1%, and 68.4%, respectively. After adjusting the clinical variables, 10 QoL variables were observed to be significantly (P < .05) related to OS, and four QoL variables were related to DMFS. No QoL variable was predictive of LRC. Among the QoL variables that significantly predicted OS and DMFS, physical functioning was the most powerful predictor. A 10-point increase in the physical functioning score was associated with a 23% (95% CI, 12% to 34%) reduction in the likelihood of death and a 22% (95% CI, 9% to 36%) reduction in the likelihood of distant metastasis. Conclusion Our findings indicate that pretreatment QoL variables, especially physical functioning, provide easily available prognostic value for distant metastasis and survival in patients with NPC.
Early Treatment Failure in Intermediate-Risk Rhabdomyosarcoma: Results From IRS-IV and D9803—A Report From the Children's Oncology Group
Authors: Minn A. Yuriko , Lyden Elizabeth R. , Anderson James R. , Million Lynn , Arndt Carola A. , Brown Kenneth , Hawkins Douglas S. , Donaldson Sarah S. 
Published: August 2010

Purpose The goal of this study was to determine the frequency and clinical features of early treatment failure during induction chemotherapy before protocol radiation therapy for children with intermediate-risk rhabdomyosarcoma (RMS). Patients and Methods Patients with intermediate-risk RMS enrolled onto the Intergroup Rhabdomyosarcoma Study-IV and the Children's Oncology Group D9803 study were reviewed for an early treatment failure. Early failure was defined as failure caused by progressive disease, death as a result of progressive disease, or death as a result of other causes occurring fewer than 120 days from study entry. Patients with parameningeal site RMS with high-risk features who received radiation therapy at week 1 were excluded from analysis. Overall survival (OS) was estimated using the Kaplan-Meier method. Fisher's exact test was used to compare differences between groups. Cumulative incidence of progression was estimated. Results Of 916 patients, 20 (2.2%) were found to have an early disease progression and did not receive planned protocol radiotherapy. Three additional early failures resulted from treatment-related death without progression. Median time to failure was 48 days (range, 7 to 106 days). Nineteen (95%) of the 20 patients experienced progression at their primary site. Five-year OS was 32% (95% CI, 12% to 54%) for patients experiencing an early progression. Conclusion A small proportion of patients with intermediate-risk RMS suffer an early failure as a result of early progression (2.2%) or treatment-related mortality (0.3%). The majority of patients with early progression had a local failure. Earlier radiotherapy could potentially improve outcome by preventing early local progression.
Intensified Chemotherapy and Dose-Reduced Involved-Field Radiotherapy in Patients With Early Unfavorable Hodgkin's Lymphoma: Final Analysis of the German Hodgkin Study Group HD11 Trial
Authors: Eich Hans Theodor , Diehl Volker , Görgen Helen , Pabst Thomas , Markova Jana , Debus Jürgen , Ho Anthony , Dörken Bernd , Rank Andreas , Grosu Anca-Ligia , Wiegel Thomas , Karstens Johann Hinrich , Greil Richard , Willich Normann , Schmidberger Heinz , Döhner Hartmut , Borchmann Peter , Müller-Hermelink Hans-Konrad , Müller Rolf-Peter , Engert Andreas 
Published: August 2010

Purpose Combined-modality treatment consisting of four to six cycles of chemotherapy followed by involved-field radiotherapy (IFRT) is the standard of care for patients with early unfavorable Hodgkin's lymphoma (HL). It is unclear whether treatment results can be improved with more intensive chemotherapy and which radiation dose needs to be applied. Patients and Methods Patients age 16 to 75 years with newly diagnosed early unfavorable HL were randomly assigned in a 2 × 2 factorial design to one of the following treatment arms: four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) + 30 Gy of IFRT; four cycles of ABVD + 20 Gy of IFRT; four cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPbaseline) + 30 Gy of IFRT; or four cycles of BEACOPPbaseline + 20 Gy of IFRT. Results With a total of 1,395 patients included, the freedom from treatment failure (FFTF) at 5 years was 85.0%, overall survival was 94.5%, and progression-free survival was 86.0%. BEACOPPbaseline was more effective than ABVD when followed by 20 Gy of IFRT (5-year FFTF difference, 5.7%; 95% CI, 0.1% to 11.3%). However, there was no difference between BEACOPPbaseline and ABVD when followed by 30 Gy of IFRT (5-year FFTF difference, 1.6%; 95% CI, −3.6% to 6.9%). Similar results were observed for the radiotherapy question; after four cycles of BEACOPPbaseline, 20 Gy was not inferior to 30 Gy (5-year FFTF difference, −0.8%; 95% CI, −5.8% to 4.2%), whereas inferiority of 20 Gy cannot be excluded after four cycles of ABVD (5-year FFTF difference, −4.7%; 95% CI, −10.3% to 0.8%). Treatment-related toxicity occurred more often in the arms with more intensive therapy. Conclusion Moderate dose escalation using BEACOPPbaseline did not significantly improve outcome in early unfavorable HL. Four cycles of ABVD should be followed by 30 Gy of IFRT.
Randomized, Phase II Study of the Insulin-Like Growth Factor-1 Receptor Inhibitor IMC-A12, With or Without Cetuximab, in Patients With Cetuximab- or Panitumumab-Refractory Metastatic Colorectal Cancer
Authors: Reidy Diane Lauren , Vakiani Efsevia , Fakih Marwan G. , Saif Muhammad Wasif , Hecht Joel Randolph , Goodman-Davis Noah , Hollywood Ellen , Shia Jinru , Schwartz Jonathan , Chandrawansa Kumari , Dontabhaktuni Aruna , Youssoufian Hagop , Solit David B. , Saltz Leonard B. 
Published: August 2010

Purpose To evaluate the safety and efficacy of IMC-A12, a human monoclonal antibody (mAb) that blocks insulin-like growth factor receptor-1 (IGF-1R), as monotherapy or in combination with cetuximab in patients with metastatic refractory anti–epidermal growth factor receptor (EGFR) mAb colorectal cancer. Methods A randomized, phase II study was performed in which patients in arm A received IMC-A12 10 mg/kg intravenously (IV) every 2 weeks, while patients in arm B received this same dose of IMC-A12 plus cetuximab 500 mg/m2 IV every 2 weeks. Subsequently, arm C (same combination treatment as arm B) was added to include patients who had disease control on a prior anti-EGFR mAb and wild-type KRAS tumors. Archived pretreatment tumor tissue was obtained when possible for KRAS, PIK3CA, and BRAF genotyping, and immunohistochemistry was obtained for pAKT as well as IGF-1R. Results Overall, 64 patients were treated (median age, 61 years; range, 40 to 84 years): 23 patients in arm A, 21 in arm B, and 20 in arm C. No antitumor activity was seen in the 23 patients treated with IMC-A12 monotherapy. Of the 21 patients randomly assigned to IMC-A12 plus cetuximab, one patient (with KRAS wild type) achieved a partial response, with disease control lasting 6.5 months. Arm C (all patients with KRAS wild type), however, showed no additional antitumor activity. Serious adverse events thought possibly related to IMC-A12 included a grade 2 infusion-related reaction (2%; one of 64 patients), thrombocytopenia (2%; one of 64 patients), grade 3 hyperglycemia (2%; one of 64 patients), and grade 1 pyrexia (2%, one of 64 patients). Conclusion IMC-A12 alone or in combination with cetuximab was insufficient to warrant additional study in patients with colorectal cancer refractory to EGFR inhibitors.
Compliance with Institutional Guidelines on the Use of Vancomycin in a Medical Intensive Care Unit
Authors: Eschenauer Gregory A. , Fedewa Karen , Collins Curtis D. , Alaniz Cesar 
Published: August 2010

Purpose The University of Michigan implemented guidelines and restrictions for the use of vancomycin in 1995, based on recommendations from the Centers for Disease Control and Prevention. This study evaluated vancomycin use in the University of Michigan's Medical Intensive Care Unit (MICU), and assessed compliance with these institutional guidelines. Methods The primary objective of the study was to assess compliance with institutional guidelines. All patients admitted to the MICU who received vancomycin during the period of October 2002 through January 2003 were included in the study. Patients were identified retrospectively and patient medical records were accessed to gather pertinent information. Approval of the Institutional Review Board was obtained. Results Fifty-one patients received a total of 71 courses of vancomycin therapy (55 empiric, 16 definitive). Fifty-five (77.5%) of the 71 total courses of vancomycin therapy met institutional criteria. All courses of definitive therapy met specific criteria. Thirty-nine (71%) of the 55 courses of empiric therapy met criteria. Of the courses of empiric therapy which did not fulfill criteria, 12 were from patients exhibiting signs of sepsis and received vancomycin for more than 72 hours, and nine involved immunocompromised patients. Conclusions The implementation of guidelines and restrictions is essential to limiting and preventing resistance, but are only effective if designed with the specific hospital's patient population in mind. The results of this study suggest that immunocompromised patients may require a different approach than what is allowed by existing criteria.
Tramadol: Premature Ejaculation
Authors: Generali Joyce , Cada Dennis J. 
Published: August 2010

Off-Label Drug Uses This Hospital Pharmacy feature is extracted from Off-Label DrugFacts, a quarterly publication available from Wolters Kluwer Health. Off-Label DrugFacts is a practitioner-oriented resource for information about specific FDA-unapproved drug uses. This new guide to the literature will enable the health care professional/clinician to quickly identify published studies on off-label uses and to determine if a specific use is rational in a patient care scenario. The most relevant data are provided in tabular form, so the reader can easily identify the scope of information available. A summary of the data—including background, study design, patient population, dosage information, therapy duration, results, safety, and therapeutic considerations—precedes each table of published studies. References direct the reader to the full literature for more comprehensive information prior to patient care decisions. Direct questions or comments regarding “Off-Label Drug Uses” to hospitalpharmacy@drugfacts.com .