bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decrease of CD4-lymphocytes and apoptosis of CD14-monocytes are characteristic alterations in sepsis caused by ventilator-associated pneumonia: results from an observational study
Authors: Pelekanou Aimilia , Tsangaris Iraklis , Kotsaki Antigoni , Karagianni Vassiliki , Giamarellou Helen , Armaganidis Apostolos , Giamarellos-Bourboulis Evangelos J 
Published: November 2009

Abstract
Introduction
The present study aimed to investigate changes of the immune response between sepsis due to ventilator-associated pneumonia (VAP) and sepsis due to other types of infections.

Methods
Peripheral venous blood was sampled from 68 patients with sepsis within 24 hours of diagnosis; 36 suffered from VAP; 32 from other nosocomial infections, all well-matched for severity, age and sex. Blood monocytes were isolated and cultured with/without purified endotoxin (lipopolysaccharide (LPS)). Estimation of tumour necrosis factor alpha (TNFα) and interleukin-6 (IL-6) in cultures' supernatants was done by an enzyme immunoassay. Flow cytometry was used to determine subpopulations of mononuclear cells and apoptosis. To mimic pathogenesis of VAP, mononuclear cells of healthy volunteers were progressively stimulated with increased inocula of pathogens; apoptosis was determined.

Results
In patients with VAP, the absolute number of CD3(+)/CD4(+) lymphocytes was significantly lower (P = 0.034) and apoptosis of isolated monocytes was increased (P = 0.007) compared to other infections. TNFα and IL-6 production from LPS-stimulated monocytes was lower in patients with VAP-related sepsis than with sepsis due to other infections. Apoptosis of monocytes was induced after in vitro stimulation of mononuclear cells by a mechanism mimicking VAP.

Conclusions
Decrease of CD4-lymphocytes and immunoparalysis of monocytes are characteristic alterations of sepsis arising in the field of VAP.
Phase II Study of Erlotinib in Patients With Locally Advanced or Metastatic Papillary Histology Renal Cell Cancer: SWOG S0317
Authors: Gordon Michael S. , Hussey Michael , Nagle Raymond B. , Lara Primo N. , Mack Philip C. , Dutcher Janice , Samlowski Wolfram , Clark Joseph I. , Quinn David I. , Pan Chong-Xian , Crawford David 
Published: November 2009

Purpose Patients with advanced papillary renal cell cancer (pRCC) have poor survival after systemic therapy; the reported median survival time is 7 to 17 months. In this trial, we evaluated the efficacy of erlotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor in patients with advanced pRCC, a tumor type associated with wild-type von Hippel Lindau gene. Patients and Methods Patients with histologically confirmed, advanced, or metastatic pRCC were treated with erlotinib 150 mg orally once daily. A RECIST (Response Evaluation Criteria in Solid Tumors) response rate (RR) of ≥ 20% was considered a promising outcome. Secondary end points included overall survival and 6-month probability of treatment failure. Results Of 52 patients registered, 45 were evaluable. The overall RR was 11% (five of 45 patients; 95% CI, 3% to 24%), and the disease control rate was 64% (ie five partial response and 24 stable disease). The median overall survival time was 27 months (95% CI, 13 to 36 months). Probability of freedom from treatment failure at 6 months was 29% (95% CI, 17% to 42%). There was one grade 5 adverse event (AE) of pneumonitis, one grade 4 thrombosis, and nine other grade 3 AEs. Conclusion Although the RECIST RR of 11% did not exceed prespecified estimates for additional study, single-agent erlotinib yielded disease control and survival outcomes of interest with an expected toxicity profile. The design of future trials of the EGFR axis in pRCC should be based on preclinical or molecular data that define appropriate patient subgroups, new drug combinations, or potentially more active alternative schedules.
Fluorouracil, Epirubicin, and Cyclophosphamide With Either Docetaxel or Vinorelbine, With or Without Trastuzumab, As Adjuvant Treatments of Breast Cancer: Final Results of the FinHer Trial
Authors: Joensuu Heikki , Bono Petri , Kataja Vesa , Alanko Tuomo , Kokko Riitta , Asola Raija , Utriainen Tapio , Turpeenniemi-Hujanen Taina , Jyrkkiö Sirkku , Möykkynen Kari , Helle Leena , Ingalsuo Seija , Pajunen Marjo , Huusko Mauri , Salminen Tapio , Auvinen Päivi , Leinonen Hannu , Leinonen Mika , Isola Jorma , Kellokumpu-Lehtinen Pirkko-Liisa 
Published: November 2009

Purpose Docetaxel has not been compared with vinorelbine as adjuvant treatment of early breast cancer. Efficacy and long-term safety of a short course of adjuvant trastuzumab administered concomitantly with chemotherapy for human epidermal growth factor receptor 2 (HER2) –positive cancer are unknown. Patients and Methods One thousand ten women with axillary node–positive or high-risk node-negative breast cancer were randomly assigned to receive three cycles of docetaxel or vinorelbine, followed in both groups by three cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC). Women with HER2-positive cancer (n = 232) were further assigned to either receive or not receive trastuzumab for 9 weeks with docetaxel or vinorelbine. The median follow-up time was 62 months after random assignment. Results Women assigned to docetaxel had better distant disease–free survival (DDFS) than those assigned to vinorelbine (hazard ratio [HR] = 0.66; 95% CI, 0.49 to 0.91; P = .010). In the subgroup of HER2-positive disease, patients treated with trastuzumab tended to have better DDFS than those treated with chemotherapy only (HR = 0.65; 95% CI, 0.38 to 1.12; P = .12; with adjustment for presence of axillary nodal metastases, HR = 0.57; P = .047). In exploratory analyses, docetaxel, trastuzumab, and FEC improved DDFS compared with docetaxel plus FEC (HR = 0.32; P = .029) and vinorelbine, trastuzumab, and FEC (HR = 0.31; P = .020). The median left ventricular ejection fraction of trastuzumab-treated patients remained unaltered during the 5-year follow-up; only one woman treated with trastuzumab was diagnosed with a heart failure. Conclusion Adjuvant treatment with docetaxel improves DDFS compared with vinorelbine. A brief course of trastuzumab administered concomitantly with docetaxel is safe and effective and warrants further evaluation.
Patients' Supportive Care Needs Beyond the End of Cancer Treatment: A Prospective, Longitudinal Survey
Authors: Armes Jo , Crowe Maggie , Colbourne Lynne , Morgan Helen , Murrells Trevor , Oakley Catherine , Palmer Nigel , Ream Emma , Young Annie , Richardson Alison 
Published: November 2009

Purpose To estimate prevalence and severity of patients' self-perceived supportive care needs in the immediate post-treatment phase and identify predictors of unmet need. Patients and Methods A multicenter, prospective, longitudinal survey was conducted. Sixty-six centers recruited patients for 12 weeks. Patients receiving treatment for the following cancers were recruited: breast, prostate, colorectal, and gynecologic cancer and non-Hodgkin's lymphoma. Measures of supportive care needs, anxiety and depression, fear of recurrence, and positive and negative affect were completed at the end of treatment (T0) and 6 months later (T1). Results Of 1,850 patients given questionnaire packs, 1,425 (79%) returned questionnaires at T0, and 1,152 (62%) returned questionnaires at T1. Mean age was 61 years; and most respondents were female (69%) and had breast cancer (57%). Most patients had no or few moderate or severe unmet supportive care needs. However, 30% reported more than five unmet needs at baseline, and for 60% of these patients, the situation did not improve. At both assessments, the most frequently endorsed unmet needs were psychological needs and fear of recurrence. Logistic regression revealed several statistically significant predictors of unmet need, including receipt of hormone treatment, negative affect, and experiencing an unrelated significant event between assessments. Conclusion Most patients do not express unmet needs for supportive care after treatment. Thirty percent reported more than five moderate or severe unmet needs at both assessments. Unmet needs were predicted by hormone treatment, negative mood, and experiencing a significant event. Our results suggest that there is a proportion of survivors with unmet needs who might benefit from the targeted application of psychosocial resources.
Comparative Prognostic Value of HPV16 E6 mRNA Compared With In Situ Hybridization for Human Oropharyngeal Squamous Carcinoma
Authors: Shi Wei , Kato Hisayuki , Perez-Ordonez Bayardo , Pintilie Melania , Huang Shaohui , Hui Angela , O'Sullivan Brian , Waldron John , Cummings Bernard , Kim John , Ringash Jolie , Dawson Laura A. , Gullane Patrick , Siu Lillian , Gillison Maura , Liu Fei-Fei 
Published: November 2009

Purpose A significant proportion of oropharyngeal squamous cell carcinomas (OSCC) are associated with the human papilloma virus (HPV), particularly HPV16. The optimal method for HPV determination on archival materials however, remains unclear. We compared a quantitative real-time polymerase chain reaction (qRT-PCR) assay for HPV16 mRNA to a DNA in situ hybridization (ISH) method, and evaluated their significance for overall (OS) and disease-free (DFS) survival. Patients and Methods Matched, archival biopsies from 111 patients with OSCC were evaluated for HPV16 using a qRT-PCR for E6 mRNA and ISH for DNA. Immunohistochemistry for p16, p53, and epidermal growth factor receptor were also performed. Results HPV16 E6 mRNA was positive in 73 (66%) of 111 samples; ISH was positive in 62 of 106 samples (58%), with 86% concordance. P16 was overexpressed in 72 samples (65%), which was strongly associated with HPV16 status by either method. E6 mRNA presence or p16 overexpression were significantly associated with superior OS; E6 mRNA, HPV16 ISH, or p16 were all significantly associated with DFS. On multivariate analysis adjusted for age, stage, and treatment, positive E6 mRNA was the only independent predictor for superior OS; for DFS, p16 expression or HPV16 status determined by either method was significant. Conclusion The prevalence of HPV16 in OSCC ranges from 58% to 66%, in a recently treated Canadian cohort. Classification of HPV-positivity by HPV16 E6 mRNA, HPV16 ISH or p16 immunohistochemistry (IHC) is associated with improved DFS. However, the latter two assays are technically easier to perform; hence, HPV16 ISH or p16 IHC should become standard evaluations for all patients with OSCC.
High Risk of Recurrence for Patients With Breast Cancer Who Have Human Epidermal Growth Factor Receptor 2–Positive, Node-Negative Tumors 1 cm or Smaller
Authors: Gonzalez-Angulo Ana M. , Litton Jennifer K. , Broglio Kristine R. , Meric-Bernstam Funda , Rakkhit Ronjay , Cardoso Fatima , Peintinger Florentia , Hanrahan Emer O. , Sahin Aysegul , Guray Merih , Larsimont Denis , Feoli Francesco , Stranzl Heidi , Buchholz Thomas A. , Valero Vicente , Theriault Richard , Piccart-Gebhart Martine , Ravdin Peter M. , Berry Donald A. , Hortobagyi Gabriel N. 
Published: November 2009

Purpose To evaluate the risk of recurrence in women diagnosed with T1a and T1b, node-negative, human epidermal growth factor receptor 2 (HER2) –positive breast cancer. Methods We reviewed 965 T1a,bN0M0 breast cancers diagnosed at our institution between 1990 and 2002. Dedicated breast pathologists confirmed HER2 positivity if 3+ by immunohistochemistry or if it had a ratio of 2.0 or greater by fluorescence in situ hybridization (FISH). Patients who received adjuvant chemotherapy or trastuzumab were excluded. Kaplan-Meier product was used to calculate recurrence-free survival (RFS) and distant recurrence–free survival (DRFS). Cox proportional hazard models were fit to determine associations between HER2 status and survival after adjustment for patient and disease characteristics. Additionally, 350 breast cancers from two other institutions were used for validation. Results Ten percent of patients had HER2-positive tumors. At a median follow-up of 74 months, there were 72 recurrences. The 5-year RFS rates were 77.1% and 93.7% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). The 5-year DRFS rates were 86.4% and 97.2% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). In multivariate analysis, patients with HER2-positive tumors had higher risks of recurrence (hazard ratio [HR], 2.68; 95% CI, 1.44 to 5.0; P = .002) and distant recurrence (HR, 5.3; 95% CI, 2.23 to 12.62; P < .001) than those with HER2-negative tumors. Patients with HER2-positive tumors had 5.09 times (95% CI, 2.56 to 10.14; P < .0001) the rate of recurrences and 7.81 times (95% CI, 3.17 to 19.22; P < .0001) the rate of distant recurrences at 5 years compared with patients who had hormone receptor–positive tumors. Conclusion Patients with HER2-positive T1abN0M0 tumors have a significant risk of relapse and should be considered for systemic, anti-HER2, adjuvant therapy.
Comparison of Neurocognitive Functioning in Children Previously Randomly Assigned to Intrathecal Methotrexate Compared With Triple Intrathecal Therapy for the Treatment of Childhood Acute Lymphoblastic Leukemia
Authors: Kadan-Lottick Nina S. , Brouwers Pim , Breiger David , Kaleita Thomas , Dziura James , Northrup Veronika , Chen Lu , Nicoletti Megan , Bostrom Bruce , Stork Linda , Neglia Joseph P. 
Published: November 2009

Purpose For the majority of children with acute lymphoblastic leukemia (ALL), CNS prophylaxis consists of either intrathecal (IT) methotrexate or triple IT therapy (ie, methotrexate with both cytarabine and hydrocortisone). The long-term neurotoxicities of these two IT strategies have not yet been directly compared. Patients and Methods In this multisite study, 171 children with standard-risk ALL, age 1 to 9.99 years at diagnosis, previously randomly assigned to IT methotrexate (n = 82) or to triple IT therapy (n = 89) on CCG 1952, underwent neurocognitive evaluation by a licensed psychologist at a mean of 5.9 years after random assignment. Results Patients who received IT methotrexate had a mean Processing Speed Index that was 3.6 points lower, about one fourth of a standard deviation, than those who received triple IT therapy (P = .04) after analysis was adjusted for age, sex, and time since diagnosis. Likewise, 19.5% of children in the IT methotrexate group had a Processing Speed Index score in the below-average range compared with 6.9% in the triple IT therapy group (P = .02). Otherwise, the groups performed similarly on tests of full-scale intelligence quotient, academic achievement, attention/concentration, memory, and visual motor integration. The association of treatment with measures of cognitive functioning was not modified by sex or age at diagnosis. In the post-therapy period, there were no group differences in special education services, neurologic events, or use of psychotropic medications. Conclusion This study did not show any clinically meaningful differences in neurocognitive functioning between patients previously randomly assigned to IT methotrexate or triple IT therapy except for a small difference in processing speed in the IT methotrexate group.
Chronic Myeloid Leukemia: An Update of Concepts and Management Recommendations of European LeukemiaNet
Authors: Baccarani Michele , Cortes Jorge , Pane Fabrizio , Niederwieser Dietger , Saglio Giuseppe , Apperley Jane , Cervantes Francisco , Deininger Michael , Gratwohl Alois , Guilhot François , Hochhaus Andreas , Horowitz Mary , Hughes Timothy , Kantarjian Hagop , Larson Richard , Radich Jerald , Simonsson Bengt , Silver Richard T. , Goldman John , Hehlmann Rudiger 
Published: November 2009

Purpose To review and update the European LeukemiaNet (ELN) recommendations for the management of chronic myeloid leukemia with imatinib and second-generation tyrosine kinase inhibitors (TKIs), including monitoring, response definition, and first- and second-line therapy. Methods These recommendations are based on a critical and comprehensive review of the relevant papers up to February 2009 and the results of four consensus conferences held by the panel of experts appointed by ELN in 2008. Results Cytogenetic monitoring was required at 3, 6, 12, and 18 months. Molecular monitoring was required every 3 months. On the basis of the degree and the timing of hematologic, cytogenetic, and molecular results, the response to first-line imatinib was defined as optimal, suboptimal, or failure, and the response to second-generation TKIs was defined as suboptimal or failure. Conclusion Initial treatment was confirmed as imatinib 400 mg daily. Imatinib should be continued indefinitely in optimal responders. Suboptimal responders may continue on imatinb, at the same or higher dose, or may be eligible for investigational therapy with second-generation TKIs. In instances of imatinib failure, second-generation TKIs are recommended, followed by allogeneic hematopoietic stem-cell transplantation only in instances of failure and, sometimes, suboptimal response, depending on transplantation risk.
In Vivo Targeting of the Growth Hormone Receptor (GHR) Box1 Sequence Demonstrates that the GHR Does Not Signal Exclusively through JAK2
Authors: Barclay Johanna L. , Kerr Linda M. , Arthur Leela , Rowland Jennifer E. , Nelson Caroline N. , Ishikawa Mayumi , d'Aniello Elisabetta M. , White Mary , Noakes Peter G. , Waters Michael J. 
Published: November 2009

AbstractGH is generally believed to signal exclusively through Janus tyrosine kinases (JAK), particularly JAK2, leading to activation of signal transducers and activators of transcription (STAT), ERK and phosphatidylinositol 3-kinase pathways, resulting in transcriptional regulation of target genes. Here we report the creation of targeted knock-in mice wherein the Box1 motif required for JAK2 activation by the GH receptor (GHR) has been disabled by four Pro/Ala mutations. These mice are unable to activate hepatic JAK2, STAT3, STAT5, or Akt in response to GH injection but can activate Src and ERK1/2. Their phenotype is identical to that of the GHR−/− mouse, emphasizing the key role of JAK2 in postnatal growth and the minimization of obesity in older males. In particular, they show dysregulation of the IGF-I/IGF-binding protein axis at transcript and protein levels and decreased bone length. Because no gross phenotypic differences were evident between GHR−/− and Box1 mutants, we undertook transcript profiling in liver from 4-month-old males. We compared their transcript profiles with our 391-GHR truncated mice, which activate JAK2, ERK1/2, and STAT3 in response to GH but not STAT5a/b. This has allowed us for the first time to identify in vivo Src/ERK-regulated transcripts, JAK2-regulated transcripts, and those regulated by the distal part of the GHR, particularly by STAT5.
Peroxisome Proliferator-Activated Receptor γ Coactivator-1α Interacts with the Androgen Receptor (AR) and Promotes Prostate Cancer Cell Growth by Activating the AR
Authors: Shiota Masaki , Yokomizo Akira , Tada Yasuhiro , Inokuchi Junichi , Tatsugami Katsunori , Kuroiwa Kentaro , Uchiumi Takeshi , Fujimoto Naohiro , Seki Narihito , Naito Seiji 
Published: November 2009

AbstractThere are currently few successful therapies for castration-resistant prostate cancer (CRPC). CRPC is thought to result from augmented activation of the androgen/androgen receptor (AR) signaling pathway, which could be enhanced by AR cofactors. In this study, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) was found to be an AR cofactor. PGC-1α interacted with the N-terminal domain of AR, was involved in the N- and C-terminal interaction of AR, and enhanced the DNA-binding ability of AR to androgen-responsive elements in the prostate-specific antigen enhancer and promoter regions to increase the transcription of AR target genes. Silencing of PGC-1α suppressed cell growth of AR-expressing prostate cancer (PCa) cells by inducing cell-cycle arrest at the G1 phase, similar to inhibition of androgen/AR signaling. Furthermore, PGC-1α knock-down also suppressed cell growth in the castration-resistant LNCaP-derivatives. These findings indicate that PGC-1α is involved in the proliferation of AR-expressing PCa cells by acting as an AR coactivator. Modulation of PGC-1α expression or function may offer a useful strategy for developing novel therapeutics for PCa, including CRPC, which depends on AR signaling by overexpressing AR and its coactivators.
A Liquid Hand Blossoms
Authors: Rapaport Herman 
Published: November 2009

This essay speaks to two New Critical taboos generally held by literary critics, whatever their training. The first concerns the poet's use of a preestablished referent that functions as a sentimental attachment that carries the poem along. This is usually considered a form of cheating, a loading of the dice. The second taboo concerns the poet's tossing “sweet nothings” into a poem, delicious turns of phrase that don't mean anything.
Again, critical readers generally take this to be a cheat. My article explores why readers of poetry should be more open to the sentimental attachment and the sweet nothing, given how central they are to poetry. This article is a short section from a book I'm working on that is composed of many short pieces on all manner of topics that concern contemporary poetry.
Numerical analysis of unsteady cavitating flow in an axial inducer
Authors: Campos-Amezcua R , Khelladi S , Bakir F , Mazur-Czerwiec Z , Sarraf C , Rey R 
Published: November 2009

This article presents a numerical simulation of an unsteady cavitating flow. First, the analysis was carried out for a two-dimensional (2D) venturi-type geometry, and then for a 2D blade cascade simulating an axial inducer. The main purpose of this work is to explore the local cavitation instabilities, such as alternate blade cavitation and rotating blade cavitation, which can appear in axial inducers. The numerical simulation was performed using a commercial code based on a cell-centred finite-volume method. The cavitation model used for calculations assumes a thermal equilibrium between phases. It is based on the classical conservation equations of the vapour phase and the mixture phase, with mass transfer owing to the cavitation appearing as a source and a sink term in the vapour mass fraction equation. The mass transfer rate is derived from a simplified Rayleigh—Plesset model for bubble dynamics.
From supramolecular chemistry to nanotechnology: Assembly of 3D nanostructures
Authors: Ling Xing Yi , Reinhoudt David N. , Huskens Jurriaan 
Published: November 2009

Abstract
Fabricating well-defined and stable nanoparticle crystals in a controlled fashion receives growing attention in nanotechnology. The order and packing symmetry within a nanoparticle crystal is of utmost importance for the development of materials with unique optical and electronic properties. To generate stable and ordered 3D nanoparticle structures, nanotechnology is combined with supramolecular chemistry to control the self-assembly of 2D and 3D receptor-functionalized nanoparticles. This review focuses on the use of molecular recognition chemistry to establish stable, ordered, and functional nanoparticle structures. The host–guest complexation of β-cyclodextrin (CD) and its guest molecules (e.g., adamantane and ferrocene) are applied to assist the nanoparticle assembly. Direct adsorption of supramolecular guest- and host-functionalized nanoparticles onto (patterned) CD self-assembled monolayers (SAMs) occurs via multivalent host–guest interactions and layer-by-layer (LbL) assembly. The reversibility and fine-tuning of the nanoparticle-surface binding strength in this supramolecular assembly scheme are the control parameters in the process. Furthermore, the supramolecular nanoparticle assembly has been integrated with top-down nanofabrication schemes to generate stable and ordered 3D nanoparticle structures, with controlled geometries and sizes, on surfaces, other interfaces, and as free-standing structures.