bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toll like receptor-3 ligand poly-ICLC promotes the efficacy of peripheral vaccinations with tumor antigen-derived peptide epitopes in murine CNS tumor models
Authors: Zhu Xinmei , Nishimura Fumihiko , Sasaki Kotaro , Fujita Mitsugu , Dusak Jill E , Eguchi Junichi , Fellows-Mayle Wendy , Storkus Walter J , Walker Paul R , Salazar Andres M , Okada Hideho 
Published: February 2007

AbstractBackgroundToll-like receptor (TLR)3 ligands serve as natural inducers of pro-inflammatory cytokines capable of promoting Type-1 adaptive immunity, and TLR3 is abundantly expressed by cells within the central nervous system (CNS). To improve the efficacy of vaccine strategies directed against CNS tumors, we evaluated whether administration of a TLR3 ligand, polyinosinic-polycytidylic (poly-IC) stabilized with poly-lysine and carboxymethylcellulose (poly-ICLC) would enhance the anti-CNS tumor effectiveness of tumor peptide-based vaccinations.MethodsC57BL/6 mice bearing syngeneic CNS GL261 glioma or M05 melanoma received subcutaneous (s.c.) vaccinations with synthetic peptides encoding CTL epitopes- mEphA2 (671–679), hgp100 (25–33) and mTRP-2 (180–188) for GL261, or ovalbumin (OVA: 257–264) for M05. The mice also received intramuscular (i.m.) injections with poly-ICLC.ResultsThe combination of subcutaneous (s.c.) peptide-based vaccination and i.m. poly-ICLC administration promoted systemic induction of antigen (Ag)-specific Type-1 CTLs expressing very late activation antigen (VLA)-4, which confers efficient CNS-tumor homing of vaccine-induced CTLs based on experiments with monoclonal antibody (mAb)-mediated blockade of VLA-4. In addition, the combination treatment allowed expression of IFN-γ by CNS tumor-infiltrating CTLs, and improved the survival of tumor bearing mice in the absence of detectable autoimmunity.ConclusionThese data suggest that poly-ICLC, which has been previously evaluated in clinical trials, can be effectively combined with tumor Ag-specific vaccine strategies, thereby providing a greater index of therapeutic efficacy.
Progranulin in frontotemporal lobar degeneration and neuroinflammation
Authors: Ahmed Zeshan , Mackenzie Ian RA , Hutton Michael L , Dickson Dennis W 
Published: February 2007

Abstract
Progranulin (PGRN) is a pleiotropic protein that has gained the attention of the neuroscience community with recent discoveries of mutations in the gene for PGRN that cause frontotemporal lobar degeneration (FTLD). Pathogenic mutations in PGRN result in null alleles, and the disease is likely the result of haploinsufficiency. Little is known about the normal function of PGRN in the central nervous system apart from a role in brain development. It is expressed by microglia and neurons. In the periphery, PGRN is involved in wound repair and inflammation. High PGRN expression has been associated with more aggressive growth of various tumors. The properties of full length PGRN are distinct from those of proteolytically derived peptides, referred to as granulins (GRNs). While PGRN has trophic properties, GRNs are more akin to inflammatory mediators such as cytokines. Loss of the neurotrophic properties of PGRN may play a role in selective neuronal degeneration in FTLD, but neuroinflammation may also be important. Gene expression studies suggest that PGRN is up-regulated in a variety of neuroinflammatory conditions, and increased PGRN expression by microglia may play a pivotal role in the response to brain injury, neuroinflammation and neurodegeneration.
Increased sensitivity to cocaine-induced analgesia in Spontaneously Hypertensive Rats (SHR)
Authors: Pamplona Fabrício A , Vendruscolo Leandro F , Takahashi Reinaldo N 
Published: February 2007

Abstract
This study examined the analgesic effect of cocaine in Spontaneously Hypertensive Rats (SHR), which are considered a suitable model for the study of attention deficit hyperactivity disorder (ADHD), and in Wistar (WIS) rats of both sexes using the hot-plate test. In addition, we tested whether habituation to the unheated hot-plate apparatus, that "normalizes" the basal hypoalgesic phenotype of SHR, alters the subsequent cocaine-induced analgesia (CIA) in this strain. SHR of both sexes were hypoalgesic compared to WIS rats in the hot-plate test and showed higher sensitivity to CIA. Habituation to the unheated hot-plate reduced the basal nociceptive latency of SHR, suggesting cognitive/emotional modulation of pain in this strain, but did not alter the magnitude of CIA. The present study shows increased sensitivity to CIA in SHR, which may be related to abnormalities in the mesocorticolimbic dopaminergic system. Further studies using SHR strain may reveal new information on the neurobiological mechanisms underlying ADHD and its co-morbidity with drug addiction.
Clinical findings in two cases of atypical scrapie in sheep: a case report
Authors: Konold Timm , Davis Andrew , Bone Gemma , Bracegirdle John , Everitt Sharon , Chaplin Melanie , Saunders Ginny C , Cawthraw Saira , Simmons Marion M 
Published: February 2007

Abstract

Background
Atypical scrapie is a recently recognised form of transmissible spongiform encephalopathy of sheep that differs from classical scrapie in its neuropathological and biochemical features. Most cases are detected in apparently healthy sheep and information on the clinical presentation is limited.

Case presentation
This report describes the clinical findings in two sheep notified as scrapie suspects and confirmed as atypical scrapie cases by immunohistochemistry and Western immunoblotting. Although both sheep displayed signs suggestive of a cerebellar dysfunction there was considerable variation in the individual clinical signs, which were similar to classical scrapie.

Conclusion
Any sheep presenting with neurological gait deficits should be assessed more closely for other behavioural, neurological and physical signs associated with scrapie and their presence should lead to the suspicion of scrapie.
Decision tree modeling predicts effects of inhibiting contractility signaling on cell motility
Authors: Kharait Sourabh , Hautaniemi Sampsa , Wu Shan , Iwabu Akihiro , Lauffenburger Douglas A , Wells Alan 
Published: February 2007

Abstract

Background
Computational models of cell signaling networks typically are aimed at capturing dynamics of molecular components to derive quantitative insights from prior experimental data, and to make predictions concerning altered dynamics under different conditions. However, signaling network models have rarely been used to predict how cell phenotypic behaviors result from the integrated operation of these networks. We recently developed a decision tree model for how EGF-induced fibroblast cell motility across two-dimensional fibronectin-coated surfaces depends on the integrated activation status of five key signaling nodes, including a proximal regulator of transcellular contractile force generation, MLC (myosin light chain) [Hautaniemi et al, Bioinformatics 21: 2027 {2005}], but we have not previously attempted predictions of new experimental effects from this model.

Results
In this new work, we construct an improved decision tree model for the combined influence of EGF and fibronectin on fibroblast cell migration based on a wider spectrum of experimental protein signaling and cell motility measurements, and directly test a significant and non-intuitive a priori prediction for the outcome of a targeted molecular intervention into the signaling network: that partially reducing activation of MLC would increase cell motility on moderately adhesive surfaces. This prediction was indeed confirmed experimentally: partial inhibition of the activating MLC kinase (MLCK) upstream using the pharmacologic agent ML-7 resulted in increased motility of NR6 fibroblasts. We further extended this exciting finding by showing that partial reduction of MLC activation similarly enhanced the transmigration of the human breast carcinoma cell line MDA-213 through a Matrigel barrier.

Conclusion
These findings specifically highlight a central regulatory role for transcellular contractility in governing cell motility, while at the same time demonstrating the value of a decision tree approach to a systems "signal-response" model in discerning non-intuitive behavior arising from integrated operation a cell signaling network.
Management of bleeding following major trauma: a European guideline
Authors: Spahn Donat R , Cerny Vladimir , Coats Timothy J , Duranteau Jacques , Fernández-Mondéjar Enrique , Gordini Giovanni , Stahel Philip F , Hunt Beverley J , Komadina Radko , Neugebauer Edmund , Ozier Yves , Riddez Louis , Schultz Arthur , Vincent Jean-Louis , Rossaint Rolf 
Published: February 2007

Abstract
Introduction
Evidence-based recommendations can be made with respect to many aspects of the acute management of the bleeding trauma patient, which when implemented may lead to improved patient outcomes.

Methods
The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing guidelines for the management of bleeding following severe injury. Recommendations were formulated using a nominal group process and the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) hierarchy of evidence and were based on a systematic review of published literature.

Results
Key recommendations include the following: The time elapsed between injury and operation should be minimised for patients in need of urgent surgical bleeding control, and patients presenting with haemorrhagic shock and an identified source of bleeding should undergo immediate surgical bleeding control unless initial resuscitation measures are successful. A damage control surgical approach is essential in the severely injured patient. Pelvic ring disruptions should be closed and stabilised, followed by appropriate angiographic embolisation or surgical bleeding control, including packing. Patients presenting with haemorrhagic shock and an unidentified source of bleeding should undergo immediate further assessment as appropriate using focused sonography, computed tomography, serum lactate, and/or base deficit measurements. This guideline also reviews appropriate physiological targets and suggested use and dosing of blood products, pharmacological agents, and coagulation factor replacement in the bleeding trauma patient.

Conclusion
A multidisciplinary approach to the management of the bleeding trauma patient will help create circumstances in which optimal care can be provided. By their very nature, these guidelines reflect the current state-of-the-art and will need to be updated and revised as important new evidence becomes available.
Declining Antibiotic Prescriptions for Upper Respiratory Infections, 1993–2004
Authors: Vanderweil Stefan G. , Pelletier Andrea J. , Hamedani Azita G. , Gonzales Ralph , Metlay Joshua P. , Camargo Carlos A. 
Published: February 2007

Abstract
Objectives:
To examine antibiotic prescribing trends for U.S. emergency department (ED) visits with upper respiratory tract infections (URIs) between 1993 and 2004.
Methods:
Data were compiled from the National Hospital Ambulatory Medical Care Survey (NHAMCS). URI visits were identified by using ICD‐9‐CM code 465.9, whereas antibiotics were identified using the National Drug Code Directory class Antimicrobials. A multivariate logistic regression model revealed sociodemographic and geographic factors that were independently associated with receipt of an antibiotic prescription for URIs.
Results:
There were approximately 23.4 million ED visits diagnosed as URIs between 1993 and 2004. Although the proportion of URI diagnoses remained relatively stable (p trend = 0.26), a significant decrease in provision of antibiotic prescriptions for URIs occurred during this 12‐year period, from a maximum of 55% in 1993, to a minimum of 35% in 2004. Patients who were prescribed antibiotics were more likely to be white than African American and to have been treated in EDs located in the southern United States.
Conclusions:
Antibiotic prescribing for URIs continues to decrease, a favorable trend that suggests that national efforts to reduce inappropriate antibiotic usage are having some success. Nevertheless, the frequency of antibiotic treatment for URI in the ED remains high (35%). Future efforts to reduce inappropriate antibiotic prescribing may focus on patients and physicians in southern U.S. EDs. Additional work is needed to address continued evidence of race‐related disparities in care.
Phase II Study of Neoadjuvant Docetaxel, Vinorelbine, and Trastuzumab Followed by Surgery and Adjuvant Doxorubicin Plus Cyclophosphamide in Women With Human Epidermal Growth Factor Receptor 2–Overexpressing Locally Advanced Breast Cancer
Authors: Limentani Steven A. , Brufsky Adam M. , Erban John K. , Jahanzeb Mohammed , Lewis Deborah 
Published: February 2007

Purpose To evaluate the combination of docetaxel, vinorelbine, and trastuzumab as neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2) –overexpressing breast cancer. Patients and Methods Patients with stage IIB or III breast cancer, including inflammatory disease, and HER2 overexpression (determined by fluorescent in situ hybridization) were treated with six cycles of docetaxel 60 mg/m2 and vinorelbine 45 mg/m2 administered every 14 days with granulocyte colony-stimulating factor and quinolone prophylaxis. Trastuzumab was administered as a 4 mg/kg loading dose followed by 2 mg/kg weekly for 12 weeks. The primary efficacy end point was pathologic complete response (pCR) in the breast. Results Of 31 enrolled patients, 68% had T3 or T4 tumors and 90% were clinically node positive. Twelve patients (39%; 95% CI, 21.6% to 55.9%) achieved pCR in the breast and lymph nodes and 14 patients (45%; 95% CI, 27.6% to 62.7%) achieved pCR in the breast alone, and 19 patients (61%; 95% CI, 44.1% to 78.4%) were node negative after neoadjuvant therapy. Clinical response was documented in 29 patients (94%; 95% CI, 78.6% to 99.2%) with 26 complete responses (84%; 95% CI, 70.9% to 96.8%). The most commonly reported grade 3/4 toxicities were neutropenia (97%), febrile neutropenia (22%), anemia (6%), mucositis/stomatitis (6%), constipation (6%), and skin rash (6%). Conclusion With clinical response and pCR rates of 94% and 39%, respectively, docetaxel, vinorelbine, and trastuzumab is a highly active neoadjuvant therapy for HER2-overexpressing locally advanced breast cancer. Although well tolerated overall, significant febrile neutropenia was observed despite prophylactic measures; therefore, evaluating a similar regimen using lower docetaxel and/or vinorelbine doses is warranted.
Efficacy and Safety of Single-Agent Pertuzumab (rhuMAb 2C4), a Human Epidermal Growth Factor Receptor Dimerization Inhibitor, in Castration-Resistant Prostate Cancer After Progression From Taxane-Based Therapy
Authors: Agus David B. , Sweeney Christopher J. , Morris Michael J. , Mendelson David S. , McNeel Douglas G. , Ahmann Frederick R. , Wang Jin , Derynck Mika K. , Ng Kimmie , Lyons Benjamin , Allison David E. , Kattan Michael W. , Scher Howard I. 
Published: February 2007

Purpose Pertuzumab represents a new class of targeted anticancer agents, human epidermal growth factor receptor (HER) dimerization inhibitors. The aim of this single-arm phase II clinical study was to assess the efficacy and safety of single-agent pertuzumab in castration-resistant prostate cancer (CRPC) patients who had experienced progression after prior chemotherapy. Patients and Methods Patients received pertuzumab every 3 weeks. All castration-resistant patients had experienced progression after at least one taxane-based regimen. Patients received a loading dose of 840 mg pertuzumab (cycle 1) followed by 420 mg for subsequent cycles. The primary end point was overall response and safety. A separate retrospective analysis of actual survival time versus predicted survival time for a patient population with comparable prognostic features was performed. Results Patients were enrolled (N = 42) and treated (n = 41). No patients had complete or partial response (as defined by Response Evaluation Criteria in Solid Tumors Group or ≥ 50% decline in prostate-specific antigen). Of 30 efficacy-assessable patients, five had stable disease (SD) for at least 23 weeks; one of five had SD for 36 weeks. Pertuzumab was well tolerated; diarrhea was the most common adverse effect (61.0%, grades 1 to 3). Retrospective analysis of survival using a validated nomogram suggested that survival was prolonged with pertuzumab treatment, compared with historic controls with similar baseline prognostic features. Conclusion Pertuzumab was well tolerated and resulted in no objective responses, but several patients had SD more than 23 weeks from a heavily pretreated population. Retrospective analysis suggested prolonged median survival time with pertuzumab compared with historical controls. Thus, inhibition of HER dimerization may have clinical utility in CRPC patients.
Specific Secondary Genetic Alterations in Mantle Cell Lymphoma Provide Prognostic Information Independent of the Gene Expression–Based Proliferation Signature
Authors: Salaverria Itziar , Zettl Andreas , Beà Sílvia , Moreno Victor , Valls Joan , Hartmann Elena , Ott German , Wright George , Lopez-Guillermo Armando , Chan Wing C. , Weisenburger Dennis D. , Gascoyne Randy D. , Grogan Thomas M. , Delabie Jan , Jaffe Elaine S. , Montserrat Emili , Muller-Hermelink Hans-Konrad , Staudt Louis M. , Rosenwald Andreas , Campo Elias 
Published: February 2007

Purpose To compare the genetic relationship between cyclin D1–positive and cyclin D1–negative mantle cell lymphomas (MCLs) and to determine whether specific genetic alterations may add prognostic information to survival prediction based on the proliferation signature of MCLs. Patients and Methods Seventy-one cyclin D1–positive and six cyclin D1–negative MCLs previously characterized by gene expression profiling were examined by comparative genomic hybridization (CGH). Results Cyclin D1–negative MCLs were genetically characterized by gains of 3q, 8q, and 15q, and losses of 1p, 8p23-pter, 9p21-pter, 11q21-q23, and 13q that were also the most common alterations in conventional MCLs. Parallel analysis of CGH aberrations and locus-specific gene expression profiles in cyclin D1–positive patients showed that chromosomal imbalances had a substantial impact on the expression levels of the genes located in the altered regions. The analysis of prognostic factors revealed that the proliferation signature, the number of chromosomal aberrations, gains of 3q, and losses of 8p, 9p, and 9q predicted survival of MCL patients. A multivariate analysis showed that the gene expression-based proliferation signature was the strongest predictor for shorter survival. However, 3q gains and 9q losses provided prognostic information that was independent of the proliferative activity. Conclusion Cyclin D1–positive and –negative MCLs share the same secondary genetic aberrations, supporting the concept that they correspond to the same genetic entity. The integration of genetic information on chromosome 3q and 9q alterations into a proliferation signature-based model may improve the ability to predict survival in patients with MCL.
Magnetic Resonance Imaging in Multiple Myeloma: Diagnostic and Clinical Implications
Authors: Walker Ronald , Barlogie Bart , Haessler Jeffrey , Tricot Guido , Anaissie Elias , Shaughnessy John D. , Epstein Joshua , van Hemert Rudy , Erdem Eren , Hoering Antje , Crowley John , Ferris Ernest , Hollmig Klaus , van Rhee Frits , Zangari Maurizio , Pineda-Roman Mauricio , Mohiuddin Abid , Yaccoby Shmuel , Sawyer Jeffrey , Angtuaco Edgardo J. 
Published: February 2007

Purpose Magnetic resonance imaging (MRI) permits the detection of diffuse and focal bone marrow infiltration in the absence of osteopenia or focal osteolysis on standard metastatic bone surveys (MBSs). Patients and Methods Both baseline MBS and MRI were available in 611 of 668 myeloma patients who were treated uniformly with a tandem autologous transplantation–based protocol and were evaluated to determine their respective merits for disease staging, response assessment, and outcome prediction. Results MRI detected focal lesions (FLs) in 74% and MBS in 56% of imaged anatomic sites; 52% of 267 patients with normal MBS results and 20% of 160 with normal MRI results had FL on MRI and MBS, respectively. MRI- but not MBS-defined FL independently affected survival. Cytogenetic abnormalities (CAs) and more than seven FLs on MRI (MRI-FLs) distinguished three risk groups: 5-year survival was 76% in the absence of both more than seven MRI-FLs and CA (n = 276), 61% in the presence of one MRI-FL (n = 262), and 37% in the presence of both unfavorable parameters (n = 67). MRI-FL correlated with low albumin and elevated levels of C-reactive protein, lactate dehydrogenase, and creatinine, but did not correlate with age, beta-2-microglobulin, and CA. Resolution of MRI-FL, occurring in 60% of cases and not seen with MBS-defined FL, conferred superior survival. Conclusion MRI is a more powerful tool for detection of FLs than is MBS. MRI-FL number had independent prognostic implications; additionally, MRI-FL resolution identified a subgroup with superior survival. We therefore recommend that, in addition to MBS, MRI be used routinely for staging, prognosis, and response assessment in myeloma.
Selection on the timing of adult emergence results in altered circadian clocks in fruit flies Drosophila melanogaster
Authors: Kumar Shailesh , Kumar Dhanya , Paranjpe Dhanashree A. , R. Akarsh C. , Sharma Vijay Kumar 
Published: February 2007

SUMMARY
To investigate whether circadian clocks in fruit flies Drosophila melanogaster evolve as a consequence of selection on the timing of adult emergence, we raised four replicate populations each of early(early1..4) and late (late1..4)emerging flies by selecting for adults that emerged during the morning and the evening hours. We estimated the percentage of flies that emerged during the two selection windows to evaluate the direct response to selection, and the circadian phenotypes of adult emergence and locomotor activity rhythms under light/dark (LD) and constant darkness (DD) to assess the correlated response to selection. After 55 generations, the percentage of flies emerging during the morning window increased in the early populations, but decreased in the late populations. The percentage of flies emerging during the evening window increased in the late populations, but decreased in the early populations. The time course and waveform of emergence and locomotor activity rhythms of the selected populations diverged from each other as well as from the controls. Further, the circadian periodicity of the early populations was significantly shorter than the controls, while that of the late populations was significantly longer than the controls. The light-induced phase response curve of the selected populations differed significantly within groups as well as from the controls. Such modifications in the circadian phenotypes of the selected populations due to heritable changes in genetic architecture, in response to imposed selection pressure, suggest that the circadian clocks underlying emergence and locomotor activity rhythms in D. melanogaster evolve as a correlated response to selection on the timing of adult emergence.