bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 6-month prospective study of injury in Gaelic football
Authors: Wilson F , Caffrey S , King E , Casey K , Gissane C 
Published: December 2006

Objective:To describe the injury incidence in Gaelic football.Methods:A total of 83 players from three counties were interviewed monthly about their injury experience, during the 6 months of the playing season.Results:The injury rate was 13.5/1000 h exposure to Gaelic football (95% CI, 10.9 to 16.6). There were nearly twice as many injuries during matches (64.4%, 95% CI, 54.1 to 73.6) as in training (35.6%, 95% CI, 26.4 to 49.5). The ankle was found to be the most commonly injured site (13.3%, 95% CI, 7.8 to 21.9). The musculotendinous unit accounted for nearly 1/3 of all injuries (31.1%). The tackle accounted for 27.8% of the injuries sustained (tackler 10%, 95% CI, 5.4 to 17.9; player being tackled 17.9%, 95% CI, 11.2 to 26.9). Of total match injuries, 56.9% (95% CI, 46.1 to 67.1) were experienced in the second half as opposed to 39.7% (95% CI, 29.8 to 50.5) in the first half.Conclusions:Gaelic footballers are under considerable risk of injury. Greater efforts must be made to reduce this risk so that players miss less time from sport due to injury. Risk factors for injury in Gaelic football must now be investigated so that specific interventions may be established to reduce them.
DESIGN OF DECOUPLING ACTIVE NOISE CONTROL SYSTEMS
Authors: TARINGOO F. , POSHTAN J. , NASIRI A. , KAHAE M. H. 
Published: December 2006

In this paper a simple method for multi-channel Active Noise Control (ANC) is introduced. The proposed structure is a combination of an adaptive FIR filter, based on the FXLMS algorithm, and the ALIGN algorithm resulting in a decoupled matrix for secondary path transfer function. This structure thus converts a multi-channel ANC system to decoupled systems which results in the reduction in computational load without affecting the convergence behavior of the FXLMS system.
Pharmacokinetics, Metabolism, and Oral Bioavailability of the DNA Methyltransferase Inhibitor 5-Fluoro-2′-Deoxycytidine in Mice
Authors: Beumer Jan H. , Eiseman Julie L. , Parise Robert A. , Joseph Erin , Holleran Julianne L. , Covey Joseph M. , Egorin Merrill J. 
Published: December 2006

Abstract
Purpose: In vivo, 5-fluoro-2′-deoxycytidine (FdCyd) is rapidly and sequentially converted to 5-fluoro-2′-deoxyuridine, 5-fluorouracil, and 5-fluorouridine. The i.v. combination of FdCyd and 3,4,5,6-tetrahydrouridine (THU), a cytidine deaminase (CD) inhibitor that blocks the first metabolic step in FdCyd catabolism, is being investigated clinically for its ability to inhibit DNA methyltransferase. However, the full effects of THU on FdCyd metabolism and pharmacokinetics are unknown. We aimed to characterize the pharmacokinetics, metabolism, and bioavailability of FdCyd with and without THU in mice.
Experimental Design: We developed a sensitive high-performance liquid chromatography tandem mass spectrometry assay to quantitate FdCyd and metabolites in mouse plasma. Mice were dosed i.v. or p.o. with 25 mg/kg FdCyd with or without coadministration of 100 mg/kg THU p.o. or i.v.
Results: The oral bioavailability of FdCyd alone was ∼4%. Coadministration with THU increased exposure to FdCyd and decreased exposure to its metabolites; i.v. and p.o. coadministration of THU increased exposure to p.o. FdCyd by 87- and 58-fold, respectively. FdCyd exposure after p.o. FdCyd with p.o. THU was as much as 54% that of i.v. FdCyd with i.v. THU.
Conclusions: FdCyd is well absorbed but undergoes substantial first-pass catabolism by CD to potentially toxic metabolites that do not inhibit DNA methyltransferase. THU is sufficiently bioavailable to reduce the first-pass effect of CD on FdCyd. Oral coadministration of THU and FdCyd is a promising approach that warrants clinical testing because it may allow maintaining effective FdCyd concentrations on a chronic basis, which would be an advantage over other DNA methyltransferase inhibitors that are currently approved or in development.
Cerebrovascular Nitrosative Stress Mediates Neurovascular and Endothelial Dysfunction Induced by Angiotensin II
Authors: Girouard Helene , Park Laibaik , Anrather Josef , Zhou Ping , Iadecola Costantino 
Published: December 2006

Objective—Angiotensin II (AngII) disrupts the regulation of the cerebral circulation through superoxide, a reactive oxygen species (ROS) generated by a nox2-containing NADPH oxidase. We tested the hypothesis that AngII-derived superoxide reacts with nitric oxide (NO) to form peroxynitrite, which, in turn, contributes to the vascular dysfunction.Methods and Results—Cerebral blood flow (CBF) was monitored by laser Doppler flowmetry in the neocortex of anesthetized mice equipped with a cranial window. AngII (0.25±0.02 μg/kg/min; intravenous for 30 to 45 minutes) attenuated the cerebral blood flow (CBF) increase produced by topical application of the endothelium-dependent vasodilator acetylcholine (−43±1%) and by whisker stimulation (−47±1%). AngII also increased the nitration marker 3-nitrotyrosine (3-NT) in cerebral blood vessels, an effect dependent on NO and nox2-derived ROS. Both the cerebrovascular effects of AngII and the nitration were attenuated by pharmacological inhibition or genetic inactivation of NO synthase. The nitration inhibitor uric acid or the peroxynitrite decomposition catalyst FeTPPS abolished AngII-induced cerebrovascular nitration and prevented the cerebrovascular effects of AngII.Conclusions—These findings provide evidence that peroxynitrite, formed from NO and nox2-derived superoxide, contributes to the deleterious cerebrovascular effects of AngII. Inhibitors of peroxynitrite action may be valuable tools to counteract the deleterious cerebrovascular effects of AngII-induced hypertension.
Adenovirus-Mediated Expression of Tissue Factor Pathway Inhibitor-2 Inhibits Endothelial Cell Migration and Angiogenesis
Authors: Ivanciu Lacramioara , Gerard Robert D. , Tang Haiwang , Lupu Florea , Lupu Cristina 
Published: December 2006

Objective—Extracellular matrix (ECM) remodeling during angiogenesis is accomplished through plasmin-dependent pericellular proteolysis and through the action of matrix metalloproteinases (MMPs). Because tissue factor pathway inhibitor-2 (TFPI-2), a Kunitz-type protease inhibitor with prominent ECM localization, inhibits plasmin and MMPs activity, we investigated the role of TFPI-2 in endothelial cell (EC) migration and angiogenesis.Methods and Results—Real-time polymerase chain reaction and immunostaining showed that the expression of TFPI-2 mRNA and protein was upregulated in migrating ECs. The effect of TFPI-2 on angiogenesis was studied in mouse models of Matrigel and polyvinylalcohol sponge implants by overexpressing TFPI-2 through infection with a replication-deficient adenovirus (AdTFPI-2). Using (immuno)fluorescence and confocal microscopy we observed that TFPI-2 reduced neovascularization and promoted ECM deposition. Lateral cell migration and capillary tube formation in vitro also were impaired by TFPI-2, a process reversed by anti–TFPI-2 antibodies. Increased apoptosis occurred both in AdTFPI-2–treated ECs and in the mouse implants. Zymography and assays in the absence of plasminogen confirmed plasmin inhibition as a main mechanism through which TFPI-2 inhibits EC migration.Conclusions—Our data suggest that TFPI-2 may be an important regulator of aberrant angiogenesis associated with tumor growth/metastasis, cardiovascular diseases, chronic inflammation, or diabetes.
Serum Amyloid P and Cardiovascular Disease in Older Men and Women
Authors: Jenny Nancy Swords , Arnold Alice M. , Kuller Lewis H. , Tracy Russell P. , Psaty Bruce M. 
Published: December 2006

Objective—Serum amyloid P (SAP), a pentraxin like C-reactive protein (CRP), functions in innate immunity. However, associations of SAP with cardiovascular disease (CVD) are unknown.Methods and Results—We examined these associations in the Cardiovascular Health Study using a case–cohort design. Nonexclusive case groups were incident angina (n=523), myocardial infarction (MI; n=308), stroke (n=323), and CVD death (n=288). 786 participants had no events. SAP was correlated with CRP, CVD risk factors (obesity, blood pressure, lipids), common and internal carotid wall thickness, and ankle-brachial index (allP<0.02). In Cox regression models adjusted for age, sex, and ethnicity, a standard deviation increase in SAP (9.8 mg/L) was associated with angina (hazard ratio; 95% confidence interval 1.3; 1.2 to 1.5) and MI (1.3; 1.1 to 1.5), but not stroke (1.1; 0.9 to 1.3) or CVD death (1.1; 0.9 to 1.3). Adding CRP to the models had no significant effect on associations. Adjusting for CVD risk factors slightly attenuated SAP associations with CVD events; however, associations with angina and MI remained significant.Conclusions—Although both are pentraxins, SAP and CRP may represent different facets of inflammation. The association of SAP with CVD in these older adults further supports the role of innate immunity in atherosclerosis.
Interferon regulatory factor 3-dependent responses to lipopolysaccharide are selectively blunted in cord blood cells
Authors: Aksoy Ezra , Albarani Valentina , Nguyen Muriel , Laes Jean-Francois , Ruelle Jean-Louis , De Wit Dominique , Willems Fabienne , Goldman Michel , Goriely Stanislas 
Published: December 2006

AbstractThe synthesis of interferon-β (IFNβ) and IFN-inducible factors elicited by lipopolysaccharide (LPS) depends on the transcriptional activity of interferon regulatory factor 3 (IRF-3) downstream of Toll-like receptor-4 (TLR4). To examine the ability of human newborns to mount TLR4-mediated IRF-3–dependent responses, we analyzed the pattern of genes expressed on the addition of LPS to cord blood or cord blood monocyte-derived dendritic cells (moDCs). Expression of IFNβ and IFN-inducible genes was selectively impaired in neonatal blood and moDCs as compared with their adult counterparts. This selective defect was confirmed by microarray experiments on moDCs. Altered expression of IFN-inducible genes was related to impaired IFNβ synthesis because IFNβ signaling was functional in neonatal moDCs. However, addition of exogenous IFNβ failed to restore LPS-induced IL-12p70 synthesis which was previously shown to be defective in neonatal moDCs. Although LPS-induced IRF-3 nuclear translocation was observed both in adult and neonatal moDCs, IRF-3 DNA-binding activity and association with the coactivator CREB-binding protein (CBP) were decreased in neonatal as compared with adult moDCs. We conclude that impaired IRF-3/CBP interaction in neonatal blood cells exposed to LPS is associated with impaired expression of IFNβ and IFN-inducible genes. Because IRF-3 activity is also required for IL-12p70 synthesis, our findings provide a molecular basis for the decreased ability of LPS-stimulated neonatal moDCs to elicit Th1-type responses.
Hyperacute GVHD: risk factors, outcomes, and clinical implications
Authors: Saliba Rima M. , de Lima Marcos , Giralt Sergio , Andersson Borje , Khouri Issa F. , Hosing Chitra , Ghosh Shubhra , Neumann Joyce , Hsu Yvonne , De Jesus Jorge , Qazilbash Muzaffar H. , Champlin Richard E. , Couriel Daniel R. 
Published: December 2006

AbstractAcute graft-versus-host disease (GVHD) is a major limiting factor in allogeneic hematopoietic stem cell transplantation (HSCT), and the timing of acute GVHD may affect patient outcomes. We evaluated the incidence, risk factors, clinical manifestations, and outcomes of hyperacute GVHD, defined as that occurring within 14 days after transplantation, among 809 consecutive HSCTs at the University of Texas M. D. Anderson Cancer Center. Of 265 patients with grade II-IV acute GVHD, 27% had biopsy-proven hyperacute GVHD. Skin involvement was significantly more common (88% versus 44%) and more severe (stage III-IV, 88% versus 66%) in the hyperacute group compared with acute GVHD diagnosed after day 14. On multivariate analysis, significant risk factors for hyperacute GVHD included a mismatched related or matched unrelated donor, a myeloablative conditioning regimen, more than 5 prior chemotherapy regimens, and donor-recipient sex mismatch. Hyperacute GVHD was associated with a significantly lower response rate to first-line therapy and a higher rate of nonrelapse mortality in patients with a mismatched related or matched unrelated donor graft. In conclusion, hyperacute GVHD accounts for a substantial proportion of grade II-IV acute GVHD after HSCT. Patients at high risk or with a diagnosis of hyperacute GVHD should be included in clinical studies.
Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats
Authors: Schurgers Leon J. , Spronk Henri M. H. , Soute Berry A. M. , Schiffers Paul M. , DeMey Jo G. R. , Vermeer Cees 
Published: December 2006

Abstract
Arterial calcification (AC) is generally regarded as an independent risk factor for cardiovascular morbidity and mortality. Matrix Gla protein (MGP) is a potent inhibitor of AC, and its activity depends on vitamin K (VK). In rats, inactivation of MGP by treatment with the vitamin K antagonist warfarin leads to rapid calcification of the arteries. Here, we investigated whether preformed AC can be regressed by a VK-rich diet. Rats received a calcification-inducing diet containing both VK and warfarin (W&K). During a second 6-week period, animals were randomly assigned to receive either W&K (3.0 mg/g and 1.5 mg/g, subsequently), a diet containing a normal (5 μg/g) or high (100 μg/g) amount of VK (either K1 or K2). Increased aortic calcium concentration was observed in the group that continued to receive W&K and also in the group changed to the normal dose of VK and AC progressed. Both the VK-rich diets decreased the arterial calcium content by some 50%. In addition, arterial distensibility was restored by the VK-rich diet. Using MGP antibodies, local VK deficiency was demonstrated at sites of calcification. This is the first study in rats demonstrating that AC and the resulting decreased arterial distensibility are reversible by high-VK intake.
IRF-4 and c-Rel expression in antiviral-resistant adult T-cell leukemia/lymphoma
Authors: Ramos Juan Carlos , Ruiz Phillip , Ratner Lee , Reis Isildinha M. , Brites Carlos , Pedroso Celia , Byrne Gerald E. , Toomey Ngoc L. , Andela Valentine , Harhaj Edward W. , Lossos Izidore S. , Harrington William J. 
Published: December 2006

AbstractAdult T-cell leukemia/lymphoma (ATLL) is a generally fatal malignancy. Most ATLL patients fare poorly with conventional chemotherapy; however, antiviral therapy with zidovudine (AZT) and interferon alpha (IFN-α) has produced long-term clinical remissions. We studied primary ATLL tumors and identified molecular features linked to sensitivity and resistance to antiviral therapy. Enhanced expression of the proto-oncogene c-Rel was noted in 9 of 27 tumors. Resistant tumors exhibited c-Rel (6 of 10; 60%) more often than did sensitive variants (1 of 9; 11%). This finding was independent of the disease form. Elevated expression of the putative c-Rel target, interferon regulatory factor-4 (IRF-4), was observed in 10 (91%) of 11 nonresponders and in all tested patients with c-Rel+ tumors and occurred in the absence of the HTLV-1 oncoprotein Tax. In contrast, tumors in complete responders did not express c-Rel or IRF-4. Gene rearrangement studies demonstrated the persistence of circulating T-cell clones in long-term survivors maintained on antiviral therapy. The expression of nuclear c-Rel and IRF-4 occurs in the absence of Tax in primary ATLL and is associated with antiviral resistance. These molecular features may help guide treatment. AZT and IFN-α is a suppressive rather than a curative regimen, and patients in clinical remission should remain on maintenance therapy indefinitely.
Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents
Authors: Cairo Mitchell S. , Gerrard Mary , Sposto Richard , Auperin Anne , Pinkerton C. Ross , Michon Jean , Weston Claire , Perkins Sherrie L. , Raphael Martine , McCarthy Keith , Patte Catherine ,   on behalf of the FAB LMB96 International Study Committee
Published: December 2006

AbstractThe prognosis for higher risk childhood B-cell non-Hodgkin lymphoma has improved over the past 20 years but the optimal intensity of treatment has yet to be determined. Children 21 years old or younger with newly diagnosed B-cell non-Hodgkin lymphoma/B-cell acute lymphoblastic leukemia (B-NHL/B-ALL) with higher risk factors (bone marrow [BM] with or without CNS involvement) were randomized to standard intensity French-American-British/Lymphoma Malignancy B (FAB/LMB) therapy or reduced intensity (reduced cytarabine plus etoposide and deletion of 3 maintenance courses M2, M3, M4). All patients with CNS disease had additional high-dose methotrexate (8 g/m2) plus extra intrathecal therapy. Fifty-one percent had BM involvement, 20% had CNS involvement, and 29% had BM and CNS involvement. One hundred ninety patients were randomized. The probabilities of 4-year event-free survival (EFS) and survival (S) were 79% ± 2.7% and 82% ± 2.6%, respectively. In patients in remission after 3 cycles who were randomized to standard versus reduced-intensity therapy, the 4-year EFS after randomization was 90% ± 3.1% versus 80% ± 4.2% (one-sided P = .064) and S was 93% ± 2.7% versus 83% ± 4.0% (one-sided P = .032). Patients with either combined BM/CNS disease at diagnosis or poor response to cyclophosphamide, Oncovin [vincristine], prednisone (COP) reduction therapy had a significantly inferior EFS and S (P < .001). Standard-intensity FAB/LMB therapy is recommended for children with high-risk B-NHL (B-ALL with or without CNS involvement).
Extended follow-up of methotrexate-free immunosuppression using sirolimus and tacrolimus in related and unrelated donor peripheral blood stem cell transplantation
Authors: Cutler Corey , Li Shuli , Ho Vincent T. , Koreth John , Alyea Edwin , Soiffer Robert J. , Antin Joseph H. 
Published: December 2006

Abstract
We assessed the combination of sirolimus and tacrolimus without methotrexate after myeloablative allogeneic stem cell transplantation from 53 matched related donors (MRDs) and 30 unrelated donors (URDs). All patients received cyclophosphamide and total body irradiation conditioning followed by transplantation of mobilized peripheral blood stem cells. The median time to neutrophil engraftment was 14 days. The median time to platelet engraftment was 12 days. No differences between MRD and URD cohorts was noted. The incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD) were 20.5% and 4.8%. The cumulative incidence of chronic GVHD was 59.1%. There were no differences in acute or chronic GVHD incidence between MRD and URD cohorts. The omission of methotrexate was associated with low transplant-related toxicity, with 30-day and 100-day treatment-related mortality rates of 0% and 4.8%. Relapse-free survival at 1 and 2 years was 72.3% and 68.5%, respectively. Overall survival at 1 and 2 years was 77.1% and 72.2%, respectively. There were no differences in relapse-free or overall survival between MRD and URD cohorts. The substitution of sirolimus for methotrexate as GVHD prophylaxis is associated with rapid engraftment, a low incidence of acute GVHD, minimal transplant-related toxicity, and excellent survival. Differences between MRD and URD cohorts are not evident when effective GVHD prophylaxis is used.
Activity and safety of bortezomib in multiple myeloma patients with advanced renal failure: a multicenter retrospective study
Authors: Chanan-Khan Asher A. , Kaufman Jonathan L. , Mehta Jayesh , Richardson Paul G. , Miller Kena C. , Lonial Sagar , Munshi Nikhil C. , Schlossman Robert , Tariman Joseph , Singhal Seema 
Published: December 2006

AbstractPatients with multiple myeloma (MM) frequently present with concomitant renal dysfunction, and those requiring dialysis have particularly poor outcomes. Bortezomib is a reversible proteasome inhibitor with significant activity in MM. This retrospective case analysis evaluated the feasibility and activity of bortezomib-based therapy in MM patients (n = 24) requiring dialysis support for advanced renal failure. All but 1 patient were undergoing dialysis at the time of therapy. Patients received bortezomib alone or bortezomib-based combination therapy. Among 20 patients with available response data, overall response rate (complete response [CR] + partial response) was 75%, with 30% CR + near CR. One patient was spared dialysis, and 3 other patients became independent of dialysis following bortezomib-based treatment. These encouraging results suggest that bortezomib or bortezomib-based regimens can be used in MM patients requiring dialysis, with manageable toxicities. Further studies will more formally evaluate the impact of bortezomib-based regimens in this patient population.
Connectivity independent protein-structure alignment: a hierarchical approach
Authors: Kolbeck Bjoern , May Patrick , Schmidt-Goenner Tobias , Steinke Thomas , Knapp Ernst-Walter 
Published: December 2006

Abstract

Background
Protein-structure alignment is a fundamental tool to study protein function, evolution and model building. In the last decade several methods for structure alignment were introduced, but most of them ignore that structurally similar proteins can share the same spatial arrangement of secondary structure elements (SSE) but differ in the underlying polypeptide chain connectivity (non-sequential SSE connectivity).

Results
We perform protein-structure alignment using a two-level hierarchical approach implemented in the program GANGSTA. On the first level, pair contacts and relative orientations between SSEs (i.e. α-helices and β-strands) are maximized with a genetic algorithm (GA). On the second level residue pair contacts from the best SSE alignments are optimized. We have tested the method on visually optimized structure alignments of protein pairs (pairwise mode) and for database scans. For a given protein structure, our method is able to detect significant structural similarity of functionally important folds with non-sequential SSE connectivity. The performance for structure alignments with strictly sequential SSE connectivity is comparable to that of other structure alignment methods.

Conclusion
As demonstrated for several applications, GANGSTA finds meaningful protein-structure alignments independent of the SSE connectivity. GANGSTA is able to detect structural similarity of protein folds that are assigned to different superfamilies but nevertheless possess similar structures and perform related functions, even if these proteins differ in SSE connectivity.