bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-Wide Analysis of Survival in Early-Stage Non–Small-Cell Lung Cancer
Authors: Huang Yen-Tsung , Heist Rebecca S. , Chirieac Lucian R. , Lin Xihong , Skaug Vidar , Zienolddiny Shanbeh , Haugen Aage , Wu Michael C. , Wang Zhaoxi , Su Li , Asomaning Kofi , Christiani David C. 
Published: May 2009

PurposeLung cancer, of which 85% is non–small-cell (NSCLC), is the leading cause of cancer-related death in the United States. We used genome-wide analysis of tumor tissue to investigate whether single nucleotide polymorphisms (SNPs) in tumors are prognostic factors in early-stage NSCLC.Patients and MethodsOne hundred early-stage NSCLC patients from Massachusetts General Hospital (MGH) were used as a discovery set and 89 NSCLC patients collected by the National Institute of Occupational Health, Norway, were used as a validation set. DNA was extracted from flash-frozen lung tissue with at least 70% tumor cellularity. Genome-wide genotyping was done using the high-density SNP chip. Copy numbers were inferred using median smoothing after intensity normalization. Cox models were used to screen and validate significant SNPs associated with the overall survival.ResultsCopy number gains in chromosomes 3q, 5p, and 8q were observed in both MGH and Norwegian cohorts. The top 50 SNPs associated with overall survival in the MGH cohort (P ≤ 2.5 × 10−4) were selected and examined using the Norwegian cohort. Five of the top 50 SNPs were validated in the Norwegian cohort with false discovery rate lower than 0.05 (P < .016) and all five were located in known genes: STK39, PCDH7, A2BP1, and EYA2. The numbers of risk alleles of the five SNPs showed a cumulative effect on overall survival (Ptrend= 3.80 × 10−12and 2.48 × 10−7for MGH and Norwegian cohorts, respectively).ConclusionFive SNPs were identified that may be prognostic of overall survival in early-stage NSCLC.
Placebo-Controlled Phase III Trial of Patient-Specific Immunotherapy With Mitumprotimut-T and Granulocyte-Macrophage Colony-Stimulating Factor After Rituximab in Patients With Follicular Lymphoma
Authors: Freedman Arnold , Neelapu Sattva S. , Nichols Craig , Robertson Michael J. , Djulbegovic Benjamin , Winter Jane N. , Bender John F. , Gold Daniel P. , Ghalie Richard G. , Stewart Morgan E. , Esquibel Vanessa , Hamlin Paul 
Published: May 2009

Purpose To evaluate patient-specific immunotherapy with mitumprotimut-T (idiotype keyhole limpet hemocyanin [Id-KLH]) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in CD20+ follicular lymphoma. Patients and Methods Patients with treatment-naive or relapsed/refractory disease achieving a complete response (CR), partial response (PR), or stable disease (SD) with four weekly rituximab infusions were randomly assigned to mitumprotimut-T/GM-CSF or placebo/GM-CSF, with doses given monthly for six doses, every 2 months for six doses, and then every 3 months until disease progression (PD). Randomization was stratified by prior therapy (treatment-naive or relapsed/refractory) and response to rituximab (CR/PR or SD). The primary end point was time to progression (TTP) from randomization. Results A total of 349 patients were randomly assigned; median age was 54 years, 79% were treatment naive, and 86% had stage III/IV disease. Median TTP was 9.0 months for mitumprotimut-T/GM-CSF and 12.6 months for placebo/GM-CSF (hazard ratio [HR] = 1.384; P = .019). TTP was comparable between the two arms in treatment-naive patients (HR = 1.196; P = .258) and shorter with mitumprotimut-T/GM-CSF in relapsed/refractory disease (HR = 2.265; P = .004). After adjusting for Follicular Lymphoma International Prognostic Index (FLIPI) scores, the difference in TTP between the two arms was no longer significant. Overall objective response rate, rate of response improvement, and duration of response were comparable between the two arms. Toxicity was similar in the two arms; 76% of adverse events were mild or moderate, and 94% of patients had injection site reactions. Conclusion TTP was shorter with mitumprotimut-T/GM-CSF compared with placebo/GM-CSF. This difference was possibly due to the imbalance in FLIPI scores.
Phase I Study of Concurrent Weekly Docetaxel and Repeated Samarium-153 Lexidronam in Patients With Castration-Resistant Metastatic Prostate Cancer
Authors: Tu Shi-Ming , Mathew Paul , Wong Franklin C. , Jones Donnah , Johnson Marcella M. , Logothetis Christopher J. 
Published: May 2009

Purpose Samarium-153 (153Sm) lexidronam is a bone-targeting radiopharmaceutical with a short physical half-life and a favorable toxicity profile. We evaluated the safety and feasibility of a concurrent combination of weekly docetaxel with repeated 153Sm-lexidronam in patients with castration-resistant prostate cancer (CRPC). Patients and Methods A conventional 3 + 3 dose-escalation design was used for this study. Patients were treated in three cohorts comprising two cycles of weekly docetaxel at 25, 30, and 35 mg/m2, respectively, on days 1, 8, and 15 of a 28-day cycle in combination with 153Sm (1 mCi/kg) on day 1. Unacceptable hematologic toxicity (UHT) was defined as more than 7 days delay in therapy for inadequate counts: an absolute neutrophil count (ANC) more than 1,000/μL and platelets more than 70,000/μL were required at days 8 and 15 and ANC more than 1,500/μL and platelets more than 100,000/μL were required at cycle 2, day 1. If counts had not recovered by day 56 of either combination cycle, UHT was declared. Results Eighteen patients were treated in three cohorts. Two patients in separate cohorts experienced UHT; the maximum-tolerated dose for this regimen was not reached. The median interval between 153Sm doses was 35 days (range, 27 to 57 days). The only significant toxicity was mild, transient myelosuppression. Five patients (28%) experienced grade 3 hematologic toxicity. There were no grade ≥ 4 hematologic or nonhematologic toxicities. Conclusion Two dosing cycles consisting of weekly docetaxel and monthly 153Sm-lexidronam were well tolerated and feasible in this CRPC population.
Two-Center Evaluation of Dynamic Sentinel Node Biopsy for Squamous Cell Carcinoma of the Penis
Authors: Leijte Joost A.P. , Hughes Ben , Graafland Niels M. , Kroon Bin K. , Olmos Renato A. Valdés , Nieweg Omgo E. , Corbishley Cathy , Heenan Sue , Watkin Nick , Horenblas Simon 
Published: May 2009

Purpose Sentinel node biopsy is used to evaluate the nodal status of patients with clinically node-negative penile carcinoma. Its use is not widespread, and the majority of patients with clinically node-negative disease undergo an elective inguinal lymph node dissection. Reservations about the use of sentinel node biopsy include the fact that most current results come from one institution and the supposedly long learning curve associated with the procedure. The purpose of this study was to address these issues by analyzing results from two centers and by evaluating the learning curve. Patients and Methods All patients undergoing sentinel node biopsy for penile carcinoma at two centers were included. The sentinel node identification rate, false-negative rate, and morbidity of the procedure were calculated. Results from the first 30 procedures were assessed for a potential learning curve. Results A total of 323 patients with penile squamous cell carcinoma, which included 611 clinically node-negative groins, were scheduled for sentinel node biopsy. A sentinel node was found in 572 of the 592 groins (97%) that proceeded to sentinel node biopsy. In 79 groins, a sentinel node was positive for tumor. Six inguinal node recurrences occurred after a negative sentinel node procedure, all within 15 months after sentinel node biopsy. The combined false-negative rate was 7%. Complications occurred in 4.7% of explored groins. None of the false-negative procedures occurred in the initial 30 procedures. Conclusion Sentinel node biopsy is a suitable procedure to stage clinically node-negative penile cancer, and it has a low complication rate. No learning curve was demonstrated in this study.
Initial Safety Report of NSABP C-08: A Randomized Phase III Study of Modified FOLFOX6 With or Without Bevacizumab for the Adjuvant Treatment of Patients With Stage II or III Colon Cancer
Authors: Allegra Carmen J. , Yothers Greg , O'Connell Michael J. , Sharif Saima , Colangelo Linda H. , Lopa Samia H. , Petrelli Nicholas J. , Goldberg Richard M. , Atkins James N. , Seay Thomas E. , Fehrenbacher Louis , O'Reilly Seamus , Chu Luis , Azar Catherine A. , Wolmark Norman 
Published: May 2009

Purpose The National Surgical Adjuvant Breast and Bowel Project C-08 trial was designed to investigate the safety and effectiveness of adding bevacizumab to modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen for the adjuvant treatment of patients with stage II or III colon cancer. We present safety information in advance of the planned analysis of efficacy. Patients and Methods Among 2,710 randomly assigned patients, demographic factors were balanced. Patients received modified FOLFOX6 every 2 weeks × 12 or modified FOLFOX6 plus bevacizumab (5 mg/kg every 2 weeks × 26, experimental group). Results Overall rates of grade 4 or 5 toxicities were nearly identical in the FOLFOX6 and FOLFOX6 plus bevacizumab arms (15.2% and 15.0%, respectively). Six-month mortality rates were 0.96% and 0.90% for the control and experimental groups, respectively. Grade 3+ toxicities that occurred more often in the experimental arm versus control arm included hypertension (12% v 1.8%, respectively), wound complications (abdominal incisional hernia or infusion port dehiscence/inflammation; 1.7% v 0.3%, respectively), pain (11.1% v 6.3%, respectively), and proteinuria (2.7% v 0.8%, respectively). Grade 2+ neuropathy was increased in the experimental arm versus the control arm (grade 2, 33% v 29%, respectively; grade 3, 16% v 14%, respectively; and grade 4, < 1% each). In the experimental arm versus control arm, significantly less thrombocytopenia (1.4% v 3.4%, respectively) and fewer allergic reactions (3.1% v 4.7%, respectively) were observed. Advanced age was associated with a significantly greater rate of grade 4 and 5 toxicities regardless of treatment. Conclusion Bevacizumab with modified FOLFOX6 is well tolerated in the surgical adjuvant setting in these patients. No significant increase in GI perforation, hemorrhage, arterial or venous thrombotic events, or death with the addition of bevacizumab to modified FOLFOX6 has been observed. Follow-up for potential delayed adverse effects and efficacy is ongoing.
Telavancin: A Novel Lipoglycopeptide Antibiotic
Authors: Charneski Lisa , Patel Priti N , Sym Donna 
Published: May 2009

Objective To review the pharmacology, antimicrobial activity, pharmacokinetics, clinical applications, and safety of telavancin, a new lipoglycopeptide antibiotic. Data Sources Literature was obtained from MEDLINE (1966–April 2009) and International Pharmaceutical Abstracts (1971–April 2009) using the search terms telavancin and TD-6424, and also from Theravance, Inc., and Astellas Pharma US, Inc. Study Selection And Data Extraction Available English-language articles were reviewed, as well as information obtained from Theravance, Inc., and Astellas Pharma US, Inc. Data Synthesis Telavancin has rapid bactericidal activity against gram-positive aerobic and anaerobic bacteria through multiple mechanisms of action. In vitro and Phase 2 in vivo data support the efficacy of telavancin against antibiotic-resistant gram-positive organisms. On March 4, 2008, the Food and Drug Administration (FDA) accepted as complete for review Theravance's response to the October 19, 2007, New Drug Application approvable letter for telavancin to be used as treatment for complicated skin and skin structure infections (cSSSIs) caused by gram-positive bacteria. QTc interval prolongation has been reported, although the clinical impact of this has not been determined. Drug interactions have not been identified as of yet. Conclusions Telavancin is currently under review by the FDA for the treatment of cSSSIs caused by gram-positive bacteria. The completion of Phase 3 trials will determine whether telavancin will have a role in the treatment of other infections caused by resistant gram-positive bacteria.
Role of Metformin in the Treatment of Gestational Diabetes
Authors: Wensel Terri M 
Published: May 2009

Objective To evaluate the safety and efficacy of metformin in the treatment of gestational diabetes mellitus (GDM). Data Sources A literature search was conducted via PubMed (1948–December 2008), International Pharmaceutical Abstracts (1970–December 2008), and Cochrane Library (up to 2008) using the search terms gestational diabetes and metformin. No limits were applied to the search, Reference citations from relevant publications identified were also reviewed. Study Selection And Data Extraction All articles identified from the data sources were reviewed for inclusion. Original research and retrospective cohorts were included in the review. Thirty-three articles were selected for review; 6 met the inclusion criteria. Trials evaluating the use of metformin in pregnant women with polycystic ovarian syndrome were not included. Data Synthesis Metformin has been found largely to be effective in the treatment of GDM. One retrospective study reported that preeclampsia and neonatal mortality are increased with the use of metformin. The largest randomized trial to date found that neonatal and maternal complications did not differ between patients treated with metformin and those treated with insulin; however, rates of preterm birth were increased in the metformin group. In all studies reviewed, patients treated with metformin tended to be overweight or obese and required varying doses of metformin. Conclusions Metformin appears to be effective for the treatment of GDM, but safety concerns may limit its use. Due to these concerns, insulin should remain the drug of choice if dietary measures alone fail.
Anaphylactic Reaction to Anakinra in a Rheumatoid Arthritis Patient Intolerant to Multiple Nonbiologic and Biologic Disease-Modifying Antirheumatic Drugs
Authors: Desai Ditina , Goldbach-Mansky Raphaela , Milner Joshua D , Rabin Ronald L , Hull Keith , Pucino Frank , Colburn Nona 
Published: May 2009

Objective To report a case of probable anaphylaxis due to anakinra in a patient with rheumatoid arthritis and multiple drug allergies. Case Summary A 46-year-old Indian female with rheumatoid arthritis demonstrated distinct adverse reactions to all commercially available anti–tumor necrosis factor therapies, sulfasalazine, and hydroxychloroquine. Over a 4-year period her disease remained active during therapy with methotrexate and prednisone. Biologics were added sequentially, with development of intolerable reactions, first to infliximab (urticarial rash, infusion reactions) after 3 doses, and then to etanercept (autoantibodies, worsening Raynaud's phenomenon, digital microinfarcts) after 1 year. Following 2 months of daily injections of anakinra, she experienced an immediate immunoglobulin E–mediated anaphylactic reaction within 20 minutes of an injection, as evidenced by positive testing to both anakinra and histamine with the skin prick method. The patient subsequently started adalimumab therapy, which was discontinued after the fourth dose due to the development of generalized hives. Discussion The Naranjo probability scale demonstrated a probable relationship between anaphylaxis and anakinra in this patient. Although cases of anakinra-related hypersensitivity have been reported in patients in which therapy was interrupted and then reintroduced, to our knowledge, this is the first report of anaphylaxis with continuous therapy. Conclusions This unusual case of a patient with multiple drug allergies presents a difficult clinical scenario, which was unsuccessfully managed with multiple biologic therapies on a trial-and-error basis. In the future, pharmacogenetics may help to better identify individuals at risk for multiple drug reactions and preclude unnecessary exposure to potentially harmful therapeutic options in similar patients.
Efficacy of Natural Health Products in Treating Osteoporosis: What is the Quality of Internet Patient Advice?
Authors: Whelan Anne Marie , Jurgens Tannis M , Bowles Susan K , Doyle Hayley 
Published: May 2009

Background With Canadians increasing their use of the Internet to find health-related information, especially regarding natural health products (NHPs), there is a need for high-quality, evidence-based information on Web sites to aid consumers in making informed decisions regarding the appropriate and safe use of NHPs. Objective To determine the quality of Web sites that target consumers and advocate the use of NHPs in the management of osteoporosis in postmenopausal women. Methods Web sites were identified via the Google search engine using the key words “natural treatment osteoporosis.” The first pages of the first 91 Web sites identified were assessed for relevance based on the following criteria: (1) written in English, (2) contained consumer information, and (3) claimed a benefit of a single NHP in the management of osteoporosis. This task was completed by 2 investigators; differences were resolved by consensus after discussion with the third investigator. Quality of relevant sites was assessed using an expanded DISCERN instrument that also examined the evidence supporting the claim of benefit. Additionally, readability of the sites was assessed. Results Thirty-eight Web sites met the inclusion criteria. Using the DISCERN instrument, we found that many of the sites scored low, suggesting serious or extensive shortcomings. On many Web sites, benefit claims regarding calcium, vitamin D, phytoestrogens, dehydroepiandrosterone and vitamin K were consistent with empirical evidence. However, for other NHPs, many of these same sites made effectiveness claims that were not supported by current evidence from randomized controlled trials. Twenty-five sites did not provide information as to what resources were used to support their claims. The average reading grade score was grade 11.9 (based on US school grades) and the mean Flesch Reading Ease Score was 41.7. (A higher score out of 100 indicates ease of reading.) Conclusions Due to the poor quality and content from unknown sources found on some Web sites, consumers who access Web sites for information regarding the use of NHPs in osteoporosis should do so cautiously and discuss results with their healthcare providers.
Typification of Antithamnion nipponicum Yamada et Inagaki (Antithamnieae, Ceramioideae, Ceramiaceae, Ceramiales, Rhodophyta)
Authors: Athanasiadis Athanasios 
Published: May 2009

Abstract
In the absence of type specimens, a lectotype of Antithamnion nipponicum is selected here from the original illustrations of the protologue. The lectotype is in agreement with the original description and shows characters that allow unequivocal identification with an undated Yamada specimen from a syntype locality. The latter specimen is selected here as epitype. It is concluded that Antithamnion nipponicum is a heterotypic synonym of Antithamnion pectinatum, and that the correct name of the species currently passing under the name A. nipponicum should be Antithamnion hubbsii.
Modeling of Quenching and Tempering Induced Phase Transformations in Steels
Authors: Rajeev P. T. , Jin L. , Farris T. N. , Chandrasekar S. 
Published: May 2009

Abstract
Quenching and tempering are common processes used in the manufacture of steel components. The development of simulation tools for quenching is critical for improving process performance by minimizing component distortion and maximizing service life. While modeling of quenching has received considerable attention, there has not been much work on similar tools for tempering. This paper presents an efficient simulation tool to predict microstructure, temperature, and stress evolution, and is applicable to both quenching and tempering processes. This method takes into account the temperature dependence of material properties, transformation strains, latent heats of transformation, and transformation plasticity. Furthermore, three different micromechanical approaches are implemented and studied to simulate steel as a multiphase constitutive material: the average property model, the Voigt model, and the Reuss model. These models assume that the properties of a unit volume of material can be derived, respectively, by applying the linear rule of mixtures to the material properties of its constituent phases, by assuming that all constituent phases have the same strain field, and by assuming that all constituent phases have the same stress field. The model predicts the microstructure, stress, and distortion in the heat treated component. The simulation model is implemented within the framework of the ABAQUS finite element package by taking advantage of its advanced features to incorporate user defined material properties. Given that the material properties are strongly dependent on carbon content, the simulation method is tested using experiments with modified 4320 steel plates that were carburized on one side to amplify distortion when quenched, due to martensitic phase transformation. Distorted shapes are measured and compared to model predictions for both quenching and tempering. The detailed comparisons provide confidence in the model as well as suggestions for improvement.
An Innovative Solution for Managing Waterworks Sludge: Developing an Alum Sludge-Based Multistage Constructed Wetland System for Wastewater Treatment
Authors: Zhao Y. Q. , Babatunde A. O. , Zhao X. H. 
Published: May 2009

Abstract
Waterworks sludge continues to be an inescapable by-product of the potable water treatment process. Accordingly, final disposal of the sludge remains one of the most significant pressing problems for the potable water treatment industry. The possibility of reusing the sludge as a main substrate in a novel constructed wetland system was investigated in this study. Results show that significant phosphorus (P) and other pollutants removal were achieved in the system. With a mean influent 5-day biochemical oxygen demand and chemical oxygen demand levels of 392.7 and 579.8 mg/L, respectively, a removal efficiency of 90.6 % and 71.8 %, respectively, was obtained. P removal was however exceptionally high despite the high influent mean P level of 45.3 mg P/L, which is about two to three times the level of P commonly found in sewage. This is attributable to the P adsorption capacity of the alum sludge and this highlights the benefits of its reuse in the system. The paper presents and discusses the findings from a laboratory scale research, which has potential for further large scale implementation.
Konzept eines Fahrdynamikreglers für die Längs- und Querdynamik von FahrzeugenGlobal Chassis Controller Concept for Longitudinal and Lateral Vehicle Dynamics
Authors: Kober Werner , Kreutz Marlene , Angeringer Ulrich , Horn Martin 
Published: May 2009

Zusammenfassung
Im Rahmen des vorliegenden Beitrages werden Konzepte zur Regelung von aktiven Fahrwerks- und Antriebsstrangkomponenten am Beispiel einer Hinterachslenkung und von momentenverteilenden Antriebsstrangkomponenten vorgestellt. Ausgehend von den Ansätzen für die Regelung der Längs- und Querdynamik von Fahrzeugen wird weiters eine Gesamtsystemarchitektur eines Fahrdynamikreglers dargestellt und anhand von Messergebnissen analysiert.