bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timing and Dose of Statin Therapy Define Its Impact on Inflammatory and Endothelial Responses During Myocardial Infarction
Authors: Sposito Andrei C. , Santos Simone N. , de Faria Eliana Cotta , Abdalla Dulcineia S.P. , da Silva Luiza P. , Soares Alexandre A. Sousa , Japiassú André V.T. , Quinaglia e Silva Jose C. , Ramires Jose A.F. , Coelho Otavio Rizzi 
Published: March 2011

Objective—
Clinical trials of statins during myocardial infarction (MI) have differed in their therapeutic regimes and generated conflicting results. This study evaluated the role of the timing and potency of statin therapy on its potential mechanisms of benefit during MI.

Methods and Results—

ST-elevation MI patients (n=125) were allocated into 5 groups: no statin; 20, 40, or 80 mg/day simvastatin starting at admission; or 80 mg/day simvastatin 48 hours after admission. After 7 days, all patients switched their treatment to 20 mg/day simvastatin for an additional 3 weeks and then underwent flow-mediated dilation in the brachial artery. As of the second day, C-reactive protein (CRP) differed between non–statin users (12.0±4.1 mg/L) and patients treated with 20 (8.5±4.0 mg/L), 40 (3.8±2.5 mg/L), and 80 mg/day (1.4±1.5 mg/L), and the daily differences remained significant until the seventh day (
P
<0.0001). The higher the statin dose, the lower the elevation of interleukin-2 and tumor necrosis factor-α, the greater the reduction of 8-isoprostane and low-density lipoprotein(−), and the greater the increase in nitrate/nitrite levels during the first 5 days (
P
<0.001). Later initiation of statin was less effective than its early introduction in relation to attenuation of CRP, interleukin-2, tumor necrosis factor-α, 8-isoprostane, and low-density lipoprotein(−), as well as in increase in nitrate/nitrite levels (
P
<0.0001). At the 30th day, there was no longer a difference in lipid profile or CRP between groups; the flow-mediated dilation, however, was proportional to the initial statin dose and was higher for those who started the treatment early (
P
=0.001).

Conclusion—
This study demonstrates that the timing and potency of statin treatment during MI are key elements for their main mechanisms of benefit.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00906451.
Early Inflammatory Reactions in Atherosclerosis Are Induced by Proline-Rich Tyrosine Kinase/Reactive Oxygen Species–Mediated Release of Tumor Necrosis Factor-α and Subsequent Activation of the p21
Cip1
/Ets-1/p300 System
Authors: Katsume Asako , Okigaki Mitsuhiko , Matsui Akihiro , Che Jishan , Adachi Yasushi , Kishita Eigo , Yamaguchi Shinichiro , Ikeda Koji , Ueyama Tomomi , Matoba Satoaki , Yamada Hiroyuki , Matsubara Hiroaki 
Published: March 2011

Objective—
Reactive oxygen species (ROS) are involved in the initial process of atherosclerosis, whereas it remains to be determined how atherogenic stimulus causes ROS-mediated proinflammatory reactions. Here, we focused on proline-rich tyrosine kinase (PYK2)–mediated ROS generation and examined how atherogenic stimulus causes early proinflammatory reactions.

Methods and Results—

PYK2-deficient (knockout [KO]) (PYK2-KO) mice were crossbred with apolipoprotein E (ApoE)–deficient (PYK2-KO/ApoE-KO) mice. PYK2-KO/ApoE-KO mice and endothelial cells (EC) were used for the study. Aortic atherogenic lesions in PYK2-KO/ApoE-KO mice were markedly decreased (55% versus ApoE-KO) after 8 weeks of a Western diet. Aortic PYK2 was activated as early as 7 days after the Western diet, when inflammatory cells were not yet activated. Addition of the proatherogenic oxidized phospholipid lysophosphatidylcholine caused activation of endothelial PYK2. Lysophosphatidylcholine-activated PYK2 induced NADPH oxidase–mediated ROS generation and ROS-mediated synthesis of tumor necrosis factor-α (TNFα), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemotactic protein-1 (MCP-1), and p21
Cip1
/Ets-1. Neutralizing anti-TNFα antibody or knockdown of p21
Cip1
/Ets-1 system blocked the induction of VCAM-1 and MCP-1. PYK2 deficiency abolished these ROS-mediated proinflammatory reactions. Further analysis revealed that PYK2/ROS-mediated p21
Cip1
/Ets-1 activation upregulated the transcription of the MCP-1 gene in collaboration with p300 transcription coactivator.

Conclusion—

PYK2 is a key tyrosine kinase activated by high cholesterol exposure, which causes ROS-mediated TNFα release and induces TNFα-dependent expression of proinflammatory molecules via the p21
Cip1
/Ets-1/p300 transcription system.
High-Mobility Group Box-1 Mediates Toll-Like Receptor 4–Dependent Angiogenesis
Authors: Lin Qing , Yang Xiao Ping , Fang Dan , Ren Xiangrong , Zhou Hongyan , Fang Jiazhu , Liu Xialin , Zhou Shiyou , Wen Feng , Yao Xiaohong , Wang Ji Ming , Su Shao Bo 
Published: March 2011

Objective—
Inflammation is closely linked to angiogenesis, and Toll-like receptors (TLRs) are the key mediators of inflammatory responses. However, the impact of TLRs on angiogenesis is incompletely understood. In this study, we determined the involvement of TLRs in angiogenesis.

Methods and Results—

In a mouse model of alkali-induced corneal neovascularization (CNV), we found that CNV was attenuated in TLR4
−/−
but not TLR2
−/−
mice. Further study revealed that the absence of TLR4 led to decreased production of proangiogenic factors in association with reduced accumulation of macrophages at the site of wounds, which was associated with reduced expression of high-mobility group box-1 (HMGB1) protein, an endogenous ligand for TLR4. Topical application of HMGB1 to the injured cornea promoted CNV with increased macrophage accumulation in wild-type mice but not in TLR4
−/−
mice. HMGB1 treatment in vitro also promoted the production of proangiogenic factors by mouse macrophages in a TLR4-dependent manner. Furthermore, antagonists of HMGB1 and TLR4 reduced CNV and macrophage recruitment in the injured cornea of wild-type mice.

Conclusion—
Our results suggest that the release of HMGB1 in the wounds initiates TLR4-dependent responses that contribute to neovascularization. Thus, targeting HMGB1-TLR4 signaling cascade may constitute a novel therapeutic approach to angiogenesis-related diseases.
Bridging Intravenous–Intra-Arterial Rescue Strategy Increases Recanalization and the Likelihood of a Good Outcome in Nonresponder Intravenous Tissue Plasminogen Activator-Treated Patients
Authors: Rubiera Marta , Ribo Marc , Pagola Jorge , Coscojuela Pilar , Rodriguez-Luna David , Maisterra Olga , Ibarra Bernardo , Piñeiro Socorro , Meler Pilar , Romero Francisco J. , Alvarez-Sabin Jose , Molina Carlos A. 
Published: March 2011

Background and Purpose—
Safety and efficacy of the “bridging therapy” (intra-arterial [IA] reperfusion rescue for nonresponder intravenous [IV] tissue plasminogen activator [tPA]-treated patients) is a matter of debate. Our aim was to compare IV and IV–IA thrombolysis using a case–control approach.

Methods—
Consecutive patients with proximal intracranial occlusion who received IA reperfusion procedures after unsuccessful IV tPA (lack of clinical improvement and arterial recanalization 1 hour after tPA bolus) were studied (IV–IA group). They were compared with occluded vessel, clot location, stroke severity, and time to treatment-matched 1 to 2 historical patients from our prospective IV tPA database with persistent occlusion 1 hour after IV tPA (IV-NR group). Arterial occlusion and recanalization were assessed with transcranial Doppler. Clinical evaluation was assessed by National Institutes of Health Stroke Scale at baseline, 24 hours, and at discharge. Symptomatic intracranial hemorrhage was defined according to the National Institute of Neurological Disorders and Stroke trial. Functional evaluation was determined by modified Rankin Scale, being functional independency defined by modified Rankin Scale score ≤2.

Results—

Forty-two IV–IA patients were compared with 84 matched IV-NR. Mean age was 71.5±2.9 years, 58 (46%) were women, and baseline median National Institutes of Health Stroke Scale score was 20 (interquartile range, 5). Mean time from symptoms to IV tPA was 176.9±113 minutes. On transcranial Doppler, complete recanalization was significantly higher in IV–IA than control subjects (12 hours: 45.2% versus 18.1%,
P
=0.002; 24 hours: 46.3% versus 25.3%,
P
=0.016) with nonsignificant better clinical evolution at 24 hours (40.5% versus 30.1%,
P
=0.169) and discharge (52.5% versus 39.5%,
P
=0.123). Symptomatic intracranial hemorrhage was similar (IV–IA 11.9% versus IV-NR 6%,
P
=0.205). Mortality at 3 months was 50% in the IV–IA group and 35.8% in the IV-NR (
P
=0.154). Forty percent of IV–IA patients were functionally independent at 3 months and only 14.9% IV-NR (
P
=0.012).

Conclusions—
Bridging IV–IA treatment may improve recanalization and clinical outcome in nonresponder IV tPA-treated patients.
Barthel Index for Stroke Trials
Authors: Quinn Terence J. , Langhorne Peter , Stott David J. 
Published: March 2011

Background and Purpose—
Robust measures of functional outcome are required to determine treatment effects in stroke trials. Of the various measures available, the Barthel index (BI) is one of the more prevalent. We aimed to describe validity, reliability, and responsiveness (clinimetric properties) of the BI in stroke trials.

Methods—
Narrative review of published articles describing clinimetric properties or use of the BI as a stroke trial end point.

Results—
Definitive statements on properties of BI are limited by heterogeneity in methodology of assessment and in the content of “BI” scales. Accepting these caveats, evidence suggests that BI is a valid measure of activities of daily living; sensitivity to change is limited at extremes of disability (floor and ceiling effects), and reliability of standard BI assessment is acceptable. However, these data may not be applicable to contemporary multicenter stroke trials.

Conclusions—
Substantial literature describing BI clinimetrics in stroke is available; however, questions remain regarding certain properties. The “BI” label is used for a number of instruments and we urge greater consistency in methods, content, and scoring. A 10-item scale, scoring 0 to 100 with 5-point increments, has been used in several multicenter stroke trials and it seems reasonable that this should become the uniform stroke trial BI.
Dietary Vitamin D Intake Among High-Risk Adolescents With Insulin Dependent Diabetes
Authors: Janisse Heather C. , Cakan Nedim , Ellis Deborah , Brogan Kathryn 
Published: March 2011

Purpose The purpose of the present study was to describe the dietary intake of vitamin D in an urban, low income, predominantly African American sample of adolescents with insulin dependent diabetes. Methods Participants were 99 adolescents diagnosed with insulin dependent diabetes. Vitamin D intake was estimated from dietary recall data. Blood glucose levels were also assessed. Results The average daily vitamin D intake estimated from dietary recall data was 102 IUs (SD = 64.4) with 70% of adolescents consuming less than 50 IUs of vitamin D in their day. Level of vitamin D intake was a significant predictor of HbA1c levels in the current sample. Conclusions Results indicate a need for the assessment of vitamin D levels in this at-risk population, as supplementation may be indicated.
Standardized Analysis of Mandibular Osteoradionecrosis in a Rat Model
Authors: Tamplen Matthew , Trapp Kelley , Nishimura Ichiro , Armin Bob , Steinberg Michael , Beumer John , Abemayor Elliot , Nabili Vishad 
Published: March 2011

ObjectiveTo develop a rat model of mandibular osteoradionecrosis (ORN) that uses novel micro‐computed tomography bone volume analysis and detailed histology to provide a more effective, quantifiable, and standardized way to study ORN in vivo.Study DesignAnimal model.SettingAcademic medical center.Subjects and MethodsModifications to our previously published rat model of mandibular ORN were done to develop an ideal protocol consisting of 10 rats (6 experimental and 4 controls) with their left middle mandibular molar removed 7 days after either 20 Gy high dose rate brachytherapy or sham irradiation. Rats were sacrificed 21 days after extraction for landmark defined bone volume and histologic analysis.ResultsA standardized method of quantification was achieved in all samples. The radiated group (XRT) had a mean bone volume/total volume (BV/TV) of 13.8% compared to 65.9% for controls (P <. 001). There were increases in osteoclasts and fibrosis, decreases in osteoblasts, and less bone in radiated samples with a mean (SD) of 5.91 (3.77) osteoclasts/high‐powered field (HPF) and 4.00 (1.83) osteoblasts/HPF in XRT samples compared to 1.08 (1.08) osteoclasts/HPF and 22.49 (6.00) osteoblasts/HPF for controls (P <. 001).ConclusionOur updated model continues to be clinically analogous to human mandibular ORN and improves the radiologic and histologic analysis of bony defects, providing a method for quantification of bone loss. Further cell‐specific staining, including immunohistochemistry, can be used with this model to study potential cellular mechanisms of mandibular ORN and test any future therapeutic options.
Augmentation of Achilles Tendon Repair With Extracellular Matrix Xenograft
Authors: Magnussen Robert A. , Glisson Richard R. , Moorman Claude T. 
Published: March 2011

Background: Achilles tendon rupture is a frequent injury in athletes and the general public. Cases of chronic rupture or poor tendon quality secondary to tendinopathy are challenging to repair primarily. Commercially available extracellular matrix materials have been utilized in recent years to augment tendon repair. Hypothesis: Augmentation of Achilles tendon with extracellular matrix xenograft results in reduced repair site gapping and increased peak failure load in a cadaveric model featuring simulated physiologic loads. Study Design: Controlled laboratory study. Methods: Ten matched pairs of fresh-frozen human lower extremities amputated just below the knee were obtained and each Achilles tendon was sharply tenotomized. One randomly selected specimen from each matched pair underwent Achilles repair using a 4-strand Krackow technique with extracellular matrix xenograft augmentation (TissueMend Soft Tissue Repair Matrix), while the opposite tendon underwent suture repair alone as a control. Each tendon was then subjected to 1000 sinusoidal tensile loading cycles to 86 N during which repair site gapping was monitored, followed by distraction to failure. One pair was used to evaluate the effects of graft orientation and not included in the analysis. Results: Significantly less gapping was noted in the augmented tendon group at all time points after the 10th load cycle ( P < .05). The mean repair site gapping after 1000 cycles of loading was 4.0 mm (range, 3.1-5.0 mm) in the augmented group and 6.5 mm (range, 4.1-8.6 mm) in the suture-only group. The ultimate failure load was 821 N (range, 613-1021 N) in the augmented group and 392 N (range, 322-481 N) in the suture-only group ( P < .01). Conclusion: The augmentation of Achilles tendon repair with extracellular matrix xenograft decreases gapping and increases load to failure immediately after surgery in a cadaveric model. Clinical Relevance: Tendon repair augmentation may allow more aggressive early rehabilitation, particularly in cases of chronic rupture or poor tendon quality. Further work is necessary to define indications for extracellular matrix graft augmentation of tendon repairs.
Modelling of scales in traditional solo singing
Authors: Ambrazevičius Rytis 
Published: March 2011

Background in psychoacoustics The scale in freely intoned music is characterised by pitch “zones” resulting from and reflecting categorical perception. Usage of the zones depends on aspects of performance as well as on melodic context. The central pitches and pitch zones corresponding to musical scale steps can be determined from frequency histograms. This approach, however, is generally not applicable in the case of floating tonality, i.e., if the pitch of the reference tone (e.g., pitch of the tonic) is slightly altered in the course of performance. Background in ethnomusicology Archaic traditional solo singing features pre-diatonic scales which deviate from equal temperament. For instance, Alexeyev classifies embryonic scales of solo singing into three groups based on (a) contrast of voice registers and timbre (α-type), (b) gliding pitches (β-type), and (c) made of approximately equidistant steps (γ-type). Similar conceptions are also well known from early comparative musicology studies. There have been many acoustical investigations of musical scales; however, scales of archaic traditional solo singing, characterized by wide zones of intonation as well as somewhat floating tonality, have not yet been thoroughly studied. Aims This paper aims (1) to develop mathematical-statistical models based on regularities of scale perception (categorical perception and neglect of floating tonality) to quantitatively describe of an insider's emic musical scale; and (2) to study, by means of the models, the regularities of musical scales in one idiolect. Method Three mathematical-statistical models based on different assumptions of the nature of floating tonality were developed. Pitches of tones in songs belonging to one idiolect of Lithuanian traditional male solo singing were measured and reevaluated by means of the models. Results and conclusions Approximately equidistant scales as well as modern diatonic scales are found in the samples under investigation. This suggests that there are different historical layers of musical thinking manifested in the idiolect.
The neural basis of pitch and harmony in the auditory system
Authors: Langner Gerald , Ochse Michael 
Published: March 2011

Background in psychophysics Psychophysical experiments have shown that the human brain has a natural preference for harmonic sounds and relationships between musical tones. Even naïve listeners are able to distinguish harmonic from inharmonic musical intervals and, under many conditions, the pitches of octaves are confused even though their fundamental frequency differs by a factor of two. Our psychophysical investigations in Mongolian gerbils have shown that animals can also learn to differentiate musical intervals. Background in neurophysiology In order to understand pitch perception and the neuronal basis of harmonicity, we have to understand how neurons in the central auditory system process acoustic signals. It has been demonstrated that temporal processing mechanisms in the auditory brainstem are essential for these fundamental aspects of musical perception. Neurophysiological experiments have revealed that the periodicity of signal envelopes is crucial for the perception of pitch. Neuronal representations of envelope periods, which reflect the superposition of partials of harmonic sounds in the cochlea, are analysed by temporal correlation mechanisms in the central auditory system. These mechanisms also include processing of resolved partials. Aims In this paper we attempt to explain pitch perception and our preference for harmonic sounds on the basis of the temporal neuronal analysis and the spatial representation of pitch information in the brain. Conclusions As a result of cochlear analysis, frequency is mapped along a tonotopic axis in all auditory brain areas. Similarly, as a result of temporal analysis, periodicity is mapped from the midbrain to the auditory cortex. In each case, tonotopic and periodotopic axes are orthogonal to each other. One may say that spectral information, as an important aspect of timbre, is mapped along a first neural axis, periodicity (pitch) is mapped along the second neural axis of the auditory system. Finally, as a result of temporal analysis, neurons in the auditory midbrain show preferences for harmonically related sounds. The major function of the ventral nucleus of the lateral lemniscus (VNLL), which seems to have a structure reminiscent of the pitch helix of music psychology, appears to be to control and suppress these harmonic responses.
Understanding musical expressiveness using interactive multimedia platforms
Authors: Leman Marc , Camurri Antonio 
Published: March 2011

Background in musicology Understanding the gesture-based foundations of musical involvement opens a number of new perspectives for musicology, with the likely effect of a change in approach. Giving justice to the role of gesture in music calls for an integrated view of perception and action, which implies a shift from auditory-based cognition towards embodied cognition, an approach that includes the whole human body as mediator between mental processes and physical energy. Background in computing With the help of new measurement tools, new computational models of multi-modal interaction, and new interactive multimedia platforms, it becomes easier to study music from a multi-modal point of view, both in terms of scientific and artistic perspectives. Music also offers an appropriate domain for the testing and developing of interactive systems and computational models for handling non-verbal multi-modal communication. Aims In studying musical gesture, both musicology and engineering can profit from a joint collaboration. While technology provides new tools for the measurement and modelling of musical involvement, knowledge of its corporeal foundation may largely contribute to the development of technology that in turn contributes to measurement and modelling. Furthermore, this knowledge may be exploited in artistic applications. As such, the interaction between musicology and music engineering may lead to interesting developments in the domain of embodied cognition and interactive multimedia platforms. Main contribution An overview of recent work on the development of an interactive multimedia platform for the measurement and modelling of musical expressiveness is presented. The paper introduces the notion of corporeal imitation and mirroring behavior as a core concept fur understanding musical expressiveness. Implications The approach advocated in this paper implies a shift of paradigm in systematic musicology, away from an all too narrow focus on auditory perception and sound structure, towards a broader view that encompasses multi-modal musical involvement. This approach is grounded in multi-sensory integration, the coupling of perception and action, the study of motor imitation, and issues that relate to affect, emotions and subjectivity. The advantage of using a interactive multimedia platform for music research, rather than ad hoc solutions, pertains to the use of modular functionalities, which allow rapid prototyping of experimental setup, flexible modelling, and the subsequent use of results in artistic applications.