bluuebunny/crossref_metadata_2025_split huggingface dataset:
A proof of concept study for the integration of robot therapy with physiotherapy in the treatment of stroke patients
Authors: Casadio Maura , Giannoni Psiche , Morasso Pietro , Sanguineti Vittorio 
Published: February 2009

Objective: To carry out a proof of concept study for integrating robot therapy with physiotherapy in the treatment of stroke patients. Design: A simple and `gentle' paradigm of robot—patient interaction was designed in order to foster the re-emergence of smooth, active control patterns in coordinated shoulder/elbow reaching movements. A haptic robot was programmed according to a strategy of minimal, progressively reduced assistance, with a double representation of targets: (i) visual (circles on a screen) and (ii) haptic (robot-generated force fields). The protocol included trials with and without vision, in order to emphasize the role of proprioceptive feedback. The training paradigm included 10 sessions and more than 5000 movements. Subjects: Ten chronic, hemiparetic subjects; four controls provided reference values for the performance measurements. Outcome measures: Four performance indicators (derived from the analysis of the reaching trajectories); clinical/functional measures (Fugl-Meyer and Ashworth scales). Results: After robot therapy reaching movements became faster and smoother. The performance in the no-vision trials was at least as good as in the vision trials. The Fugl-Meyer arm scores also increased significantly and remained approximately constant at follow-up; the Ashworth scores did not change. Conclusion: In spite of its simplicity, a limited number of `gentle' robot therapy sessions appear to be beneficial, even for severely impaired patients, although no firm conclusion can be drawn at this point. However, the study provides support material for the careful design of controlled clinical trials and for a better integration with physiotherapy.
The effect of walking mobility on the measurement of physical activity using accelerometry in multiple sclerosis
Authors: Snook Erin M , Motl Robert W , Gliottoni Rachael C 
Published: February 2009

Objective: To examine whether accelerometry provides a measure of physical activity, walking ability or both in a sample of individuals with multiple sclerosis. The secondary purpose was to examine the validity of physical activity measures in people with multiple sclerosis who have ambulatory impairments. Participants: Forty-two individuals with multiple sclerosis without ambulatory impairment (Expanded Disability Status Scale (EDSS) score ≤ 4.5) and 32 individuals with multiple sclerosis with ambulatory impairment (EDSS ≥5.0). Method: Participants completed the Multiple Sclerosis Walking Scale-12 and Performance Scales, wore an accelerometer for seven days, and completed the Godin Leisure-Time Exercise Questionnaire and short-form of the International Physical Activity Questionnaire. Results: There were significant differences between groups on scores from the five measures. There were large correlations between the accelerometer counts with scores from both the self-report measures of physical activity and the self-report measures of walking mobility in the overall sample. There were large correlations between scores from both measures of physical activity in the overall sample and the subsample with ambulatory impairment. Conclusion: Our data suggest that accelerometers are measuring both physical activity and walking mobility in individuals with multiple sclerosis, whereas self-report measures are measuring physical activity in individuals with multiple sclerosis, including those with ambulatory impairment.
A controlled trial of 6-weeks' treatment with a novel inhaled phosphodiesterase type-4 inhibitor in COPD
Authors: Vestbo J. , Tan L. , Atkinson G. , Ward J. 
Published: February 2009

Anti-inflammatory drugs are lacking in chronic obstructive pulmonary disease (COPD) and inhibitors of the phosphodiesterase type-4 (PDE4) enzyme have been suggested to be an interesting class of drugs to treat inflammation in COPD. The present authors report the findings of a phase II trial of a novel inhaled PDE4 inhibitor.Three doses, 0.1, 0.4 and 1.0 mgb.i.d., of the compound UK-500,001 were tested in a double-blind, placebo-controlled, 6-week trial in 209 patients with moderate-to-severe COPD. The primary efficacy parameter was trough forced expiratory volume in one second after 6 weeks of treatment, and secondary end-points included other lung function end-points and symptom scores assessed at 2-week intervals. The present study was stopped following a planned interim analysis for futility.No effect on the primary efficacy parameter, other measures of lung function or symptom scores was observed at any dose of UK-500,001 after 6 weeks of treatment. However, after the first 2 weeks of treatment, an improvement in a number of outcome measures in the 1.0 mgb.i.d.dose group was observed compared with placebo. The drug was well tolerated, although PDE4 inhibitor-related side-effects were observed, especially in the highest dose group.The findings of the present study question the role of inhaled phosphodiesterase type-4 inhibitors in chronic obstructive pulmonary disease.
Suberoylanilide hydroxamic acid: a potential epigenetic therapeutic agent for lung fibrosis?
Authors: Wang Z. , Chen C. , Finger S. N. , d/o Kwajah M.M S. , Jung M. , Schwarz H. , Swanson N. , Lareu R. R. , Raghunath M. 
Published: February 2009

Pulmonary fibrosis represents a fatal stage of interstitial lung diseases of known and idiopathic aetiology. No effective therapy is currently available. Based on an indication-discovery approach we present novelin vitroevidence that the histone deacetylases inhibitor suberoylanilide hydroxamic acid (SAHA), an FDA approved anti-cancer drug, has antifibrotic and anti-inflammatory potential.Human lung fibroblasts (fetal, adult and idiopathic adult pulmonary fibrosis) were treated with transforming growth factor (TGF)-β1 with or without SAHA. Collagen deposition, α-smooth muscle actin (α-SMA) expression, matrix metalloproteinase (MMP)1 activity, tissue inhibitor of MMP (TIMP)1 production, apoptosis and cell proliferation were assessed. Pro-inflammatory cytokines relevant to pulmonary fibrosis were assayed in SAHA-treated human peripheral blood mononuclear cells (PBMC) and its subpopulations.SAHA abrogated TGF-β1 effects on all the fibroblast lines by preventing their transdifferentiation into α-SMA positive myofibroblasts and increased collagen deposition without inducing apoptosis. However, MMP1 activity and TIMP1 production was modulated without a clear fibrolytic effect. SAHA also inhibited serum-induced proliferation of the fibroblast lines and caused hyperacetylation of α-tubulin and histone. Cytokine secretion was inhibited from PBMC and lymphocytes at nonapoptotic concentrations.Taken together, these data demonstrate combined antifibrotic and anti-inflammatory properties of SAHA, suggesting its therapeutic potential for pulmonary fibrosis.
Feedback dose alteration significantly affects probability of pathogen eradication in nosocomial pneumonia
Authors: Scaglione F. , Esposito S. , Leone S. , Lucini V. , Pannacci M. , Ma L. , Drusano G. L. 
Published: February 2009

Nosocomial pneumonia (NP) is associated with considerable morbidity and mortality. Data have shown that inadequate initial antibiotic therapy is a major risk for infection-attributed mortality. The aim of the present study was to measure antibiotic concentration and minimum inhibitory concentration (MIC) in infected hospitalised patients early in therapy, in order to determine whether dose alterations, in those with low drug concentrations, could affect outcomes.Only patients treated with aminoglycosides, fluoroquinolones, and β-lactams were evaluated. MICs were determined using standard National Committee for Clinical Laboratory Standards procedures. Antibiotics were assayed using validated high-performance liquid chromatographic methods. Pharmacokinetic/pharmacodynamic markers adopted were: aminoglycoside peak/MIC ratio ≥8 mg·L−1; fluoroquinolone peak/MIC ≥10 mg·L−1; β-lactam peak/MIC ≥4 mg·L−1and time that plasma levels remain above the MIC ≥70%.638 patients with NP were included in the study. In 205 patients, both drug concentration and isolate MIC were available, while in other patients, used as controls, one or both parameters were lacking. For clinical outcome, the Acute Physiology and Chronic Health Evaluation II score (p<0.0001), the presence of combination therapy (p = 0.0014) and whether both MIC and drug concentration(s) were measured (p = 0.0002) significantly affected the probability of a good outcome. For microbiological outcome, the MIC for the β-lactams (≤2 mg·L−1; p<0.0001) and whether the second drug was a fluoroquinolone or aminoglycoside (fluoroquinolones were better than aminoglycosides; p = 0.0177), as well as whether both MIC and drug concentration(s) were measured (p = 0.02), affected the probability of eradication.Measurement of drug concentrations and determination of pathogen MIC values with subsequent dose alteration significantly improves the probability of good clinical outcome and pathogen eradication in NP.
Impact of influenza vaccination on mortality risk among the elderly
Authors: Groenwold R. H. H. , Hoes A. W. , Hak E. 
Published: February 2009

Estimates of influenza vaccine effectiveness have mostly been derived from nonrandomised studies and therefore are potentially confounded. The aim of the current study was to estimate influenza vaccine effectiveness in preventing mortality among the elderly, taking both measured and unmeasured confounding into account.Information on patients aged ≥65 yrs from the computerised Utrecht General Practitioner database on eight influenza epidemic periods and summer periods was pooled to estimate influenza vaccine effectiveness in preventing mortality. Summer periods (during which no effect of vaccination was expected) were used as a reference to control for unmeasured confounding in epidemic periods.After adjustment for measured confounders using multivariable regression analysis, propensity score matching and propensity score regression analysis, influenza vaccination reduced mortality risk (odds ratios (ORs) 0.58 (95% confidence interval (CI) 0.46–0.72), 0.56 (95% CI 0.44–0.71) and 0.56 (95% CI 0.45–0.69), respectively). After additional adjustment for unmeasured confounding (as observed during summer periods), the association between influenza vaccination and mortality risk decreased (OR 0.69 (95% CI 0.52–0.92)).We conclude that after state-of-the-art adjustment for typical confounders such as age, sex and comorbidity status, unmeasured confounding still biased estimates of influenza vaccine effectiveness. After taking unmeasured confounding into account, influenza vaccination is still associated with substantial reduction in mortality risk.
A comparison on effects of normalisations in the detection of differentially expressed genes
Authors: Chiogna Monica , Massa Maria Sofia , Risso Davide , Romualdi Chiara 
Published: February 2009

AbstractBackgroundVarious normalisation techniques have been developed in the context of microarray analysis to try to correct expression measurements for experimental bias and random fluctuations. Major techniques include: total intensity normalisation; intensity dependent normalisation; and variance stabilising normalisation. The aim of this paper is to discuss the impact of normalisation techniques for two-channel array technology on the process of identification of differentially expressed genes.ResultsThrough three precise simulation plans, we quantify the impact of normalisations: (a) on the sensitivity and specificity of a specified test statistic for the identification of deregulated genes, (b) on the gene ranking induced by the statistic.ConclusionAlthough we found a limited difference of sensitivities and specificities for the test after each normalisation, the study highlights a strong impact in terms of gene ranking agreement, resulting in different levels of agreement between competing normalisations. However, we show that the combination of two normalisations, such as glog and lowess, that handle different aspects of microarray data, is able to outperform other individual techniques.
Rapid glycation with D-ribose induces globular amyloid-like aggregations of BSA with high cytotoxicity to SH-SY5Y cells
Authors: Wei Yan , Chen Lan , Chen Ji , Ge Lin , He Rong Qiao 
Published: February 2009

Abstract

Background
D-ribose in cells and human serum participates in glycation of proteins resulting in advanced glycation end products (AGEs) that affect cell metabolism and induce cell death. However, the mechanism by which D-ribose-glycated proteins induce cell death is still unclear.

Results
Here, we incubated D-ribose with bovine serum albumin (BSA) and observed changes in the intensity of fluorescence at 410 nm and 425 nm to monitor the formation of D-ribose-glycated BSA. Comparing glycation of BSA with xylose (a control for furanose), glucose and fructose (controls for pyranose), the rate of glycation with D-ribose was the most rapid. Protein intrinsic fluorescence (335 nm), Nitroblue tetrazolium (NBT) assays and Western blotting with anti-AGEs showed that glycation of BSA incubated with D-ribose occurred faster than for the other reducing sugars. Protein intrinsic fluorescence showed marked conformational changes when BSA was incubated with D-ribose. Importantly, observations with atomic force microscopy showed that D-ribose-glycated BSA appeared in globular polymers. Furthermore, a fluorescent assay with Thioflavin T (ThT) showed a remarkable increase in fluorescence at 485 nm in the presence of D-ribose-glycated BSA. However, ThT fluorescence did not show the same marked increase in the presence of xylose or glucose. This suggests that glycation with D-ribose induced BSA to aggregate into globular amyloid-like deposits. As observed by Hoechst 33258 staining, 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) activity assay, flow cytometry using Annexin V and Propidium Iodide staining and reactive oxygen species (ROS) measurements, the amyloid-like aggregation of glycated BSA induced apoptosis in the neurotypic cell line SH-SY5Y.

Conclusion
Glycation with D-ribose induces BSA to misfold rapidly and form globular amyloid-like aggregations which play an important role in cytotoxicity to neural cells.
Mismatch oligonucleotides in human and yeast: guidelines for probe design on tiling microarrays
Authors: Seringhaus Michael , Rozowsky Joel , Royce Thomas , Nagalakshmi Ugrappa , Jee Justin , Snyder Michael , Gerstein Mark 
Published: February 2009

Abstract

Background
Mismatched oligonucleotides are widely used on microarrays to differentiate specific from nonspecific hybridization. While many experiments rely on such oligos, the hybridization behavior of various degrees of mismatch (MM) structure has not been extensively studied. Here, we present the results of two large-scale microarray experiments on S. cerevisiae and H. sapiens genomic DNA, to explore MM oligonucleotide behavior with real sample mixtures under tiling-array conditions.

Results
We examined all possible nucleotide substitutions at the central position of 36-nucleotide probes, and found that nonspecific binding by MM oligos depends upon the individual nucleotide substitutions they incorporate: C→A, C→G and T→A (yielding purine-purine mispairs) are most disruptive, whereas A→X were least disruptive. We also quantify a marked GC skew effect: substitutions raising probe GC content exhibit higher intensity (and vice versa). This skew is small in highly-expressed regions (± 0.5% of total intensity range) and large (± 2% or more) elsewhere. Multiple mismatches per oligo are largely additive in effect: each MM added in a distributed fashion causes an additional 21% intensity drop relative to PM, three-fold more disruptive than adding adjacent mispairs (7% drop per MM).

Conclusion
We investigate several parameters for oligonucleotide design, including the effects of each central nucleotide substitution on array signal intensity and of multiple MM per oligo. To avoid GC skew, individual substitutions should not alter probe GC content. RNA sample mixture complexity may increase the amount of nonspecific hybridization, magnify GC skew and boost the intensity of MM oligos at all levels.
The effect of the dual Src/Abl kinase inhibitor AZD0530 on Philadelphia positive leukaemia cell lines
Authors: Gwanmesia Patricia Mambou , Romanski Annette , Schwarz Kerstin , Bacic Biserka , Ruthardt Martin , Ottmann Oliver G 
Published: February 2009

Abstract

Background
Imatinib mesylate, a selective inhibitor of Abl tyrosine kinase, is efficacious in treating chronic myeloid leukaemia (CML) and Ph+ acute lymphoblastic leukaemia (ALL). However, most advanced-phase CML and Ph+ ALL patients relapse on Imatinib therapy. Several mechanisms of refractoriness have been reported, including the activation of the Src-family kinases (SFK). Here, we investigated the biological effect of the new specific dual Src/Abl kinase inhibitor AZD0530 on Ph+ leukaemic cells.

Methods
Cell lines used included BV173 (CML in myeloid blast crisis), SEM t(4;11), Ba/F3 (IL-3 dependent murine pro B), p185Bcr-Abl infected Ba/F3 cells, p185Bcr-Abl mutant infected Ba/F3 cells, SupB15 (Ph+ ALL) and Imatinib resistant SupB15 (RTSupB15) (Ph+ ALL) cells. Cells were exposed to AZD0530 and Imatinib. Cell proliferation, apoptosis, survival and signalling pathways were assessed by dye exclusion, flow cytometry and Western blotting respectively.

Results
AZD0530 specifically inhibited the growth of, and induced apoptosis in CML and Ph+ ALL cells in a dose dependent manner, but showed only marginal effects on Ph- ALL cells. Resistance to Imatinib due to the mutation Y253F in p185Bcr-Abl was overcome by AZD0530. Combination of AZD0530 and Imatinib showed an additive inhibitory effect on the proliferation of CML BV173 cells but not on Ph+ ALL SupB15 cells. An ongoing transphosphorylation was demonstrated between SFKs and Bcr-Abl. AZD0530 significantly down-regulated the activation of survival signalling pathways in Ph+ cells, resistant or sensitive to Imatinib, with the exception of the RTSupB15.

Conclusion
Our results indicate that AZD0530 targets both Src and Bcr-Abl kinase activity and reduces the leukaemic maintenance by Bcr-Abl.
The incidence of interstitial lung disease 1995–2005: a Danish nationwide population-based study
Authors: Kornum Jette B , Christensen Steffen , Grijota Miriam , Pedersen Lars , Wogelius Pia , Beiderbeck Annette , Sørensen Henrik Toft 
Published: February 2009

AbstractBackgroundCurrent data on incidence of interstitial lung diseases (ILDs) are sparse and concerns about an increasing trend have been raised. We examined incidence rates (IRs) of ILDs and changes in IRs between 1995 and 2005.MethodsAll persons with a first-time hospital discharge or outpatient diagnosis of ILD were identified through the Danish National Registry of Patients, which covers all Danish hospitals. Crude and age-standardised IRs were computed for ILD overall, as well as stratified by ILD subcategories.ResultsA total of 21,765 patients with ILD were identified. Between 1995 and 1998 the overall standardised IR of ILD decreased from 27.14 (95% CI 25.82–28.46) per 100,000 person-years to 19.36 (95% CI 18.26–20.46) per 100,000 person-years. After 1998 the IR increased considerably, peaking at 34.34 (95% CI 32.84–35.85) per 100,000 person-years in 2002. Subsequently there was a slight decrease. The highest IR was observed in the non-specific category "Respiratory disorders in diseases classified elsewhere". By ILD subcategory, the greatest average increase during the study period was observed in "Respiratory disorders in diseases classified elsewhere".ConclusionThe incidence rate of ILD in Denmark increased during the study period, most pronounced for ILDs associated with systemic diseases.
Muscular and non-muscular contributions to maximum power cycling in children and adults: implications for developmental motor control
Authors: Korff Thomas , Hunter Elaine L. , Martin James C. 
Published: February 2009

SUMMARY
During submaximal cycling, children demonstrate a different distribution between muscular and non-muscular (gravitational and motion-dependent) forces when compared with adults. This is partly due to anthropometric differences. In this study, we tested the hypothesis that during maximum power cycling,children would construct the task (in terms of the distribution between muscular and non-muscular pedal power) similarly to adults. Eleven children(aged 8–9 years) and 13 adults (aged 20–40 years) performed a maximal isokinetic cycling task over 3 s at 115 r.p.m. Multivariate analyses of variance revealed no significant differences in normalized maximum, minimum and average positive non-muscular pedal power between children and adults(Wilks' λ=0.755, F3,20=2.17, P=0.124). Thus, maximum cycling is a developmental `self-scaling' task and age-related differences in muscular power production are not confounded by differences in anthropometry. This information is useful to researchers who wish to differentiate between muscular and non-muscular power when studying developmental motor control. In addition to the similarities in the distribution between muscular and non-muscular pedal power, we found age-related differences in the relative joint power contributions to total pedal power. In children, a significantly smaller proportion of total pedal power was generated at the ankle joint (6.1±5.4% for children and 12.6±3.2% for adults), whilst relatively more power was generated at the knee and hip joints. These results suggest that intermuscular coordination may be contributing to children's limits in maximum power production during multi-joint tasks.
Characterization of amphioxus nebulin and its similarity to human nebulin
Authors: Hanashima Akira , Kubokawa Kaoru , Kimura Sumiko 
Published: February 2009

SUMMARYIdentification of a large molecule in muscle is important but difficult to approach by protein chemistry. In this study we isolated nebulin cDNA from the striated muscle of amphioxus, and characterized the C-terminal regions of nebulins from other chordates. Although the sequence homology with that of human is only 26%, the C-terminal region of amphioxus nebulin has similar structural motifs of 35 amino acid nebulin repeats and an SH3 domain. Using in situ indirect immunofluorescence analysis with a specific antibody raised to the bacterially produced recombinant peptide, we identified that this nebulin fragment is located in the Z-line of the sarcomere, similar to human nebulin. Pull-down and co-sedimentation assays in vitro showed that the C-terminal region binds to actin, α-actinin and connectin(titin). These results suggest that the C-terminal region of amphioxus nebulin plays a similar role in maintaining striated muscle structure to that of human nebulin. This is the first report of the exact location of nebulin in amphioxus muscle.