bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioavailability of Sulforaphane from Two Broccoli Sprout Beverages: Results of a Short-term, Cross-over Clinical Trial in Qidong, China
Authors: Egner Patricia A. , Chen Jian Guo , Wang Jin Bing , Wu Yan , Sun Yan , Lu Jian Hua , Zhu Jian , Zhang Yong Hui , Chen Yong Sheng , Friesen Marlin D. , Jacobson Lisa P. , Muñoz Alvaro , Ng Derek , Qian Geng Sun , Zhu Yuan Rong , Chen Tao Yang , Botting Nigel P. , Zhang Qingzhi , Fahey Jed W. , Talalay Paul , Groopman John D , Kensler Thomas W. 
Published: March 2011

Abstract
One of several challenges in design of clinical chemoprevention trials is the selection of the dose, formulation, and dose schedule of the intervention agent. Therefore, a cross-over clinical trial was undertaken to compare the bioavailability and tolerability of sulforaphane from two of broccoli sprout–derived beverages: one glucoraphanin-rich (GRR) and the other sulforaphane-rich (SFR). Sulforaphane was generated from glucoraphanin contained in GRR by gut microflora or formed by treatment of GRR with myrosinase from daikon (Raphanus sativus) sprouts to provide SFR. Fifty healthy, eligible participants were requested to refrain from crucifer consumption and randomized into two treatment arms. The study design was as follows: 5-day run-in period, 7-day administration of beverages, 5-day washout period, and 7-day administration of the opposite intervention. Isotope dilution mass spectrometry was used to measure levels of glucoraphanin, sulforaphane, and sulforaphane thiol conjugates in urine samples collected daily throughout the study. Bioavailability, as measured by urinary excretion of sulforaphane and its metabolites (in approximately 12-hour collections after dosing), was substantially greater with the SFR (mean = 70%) than with GRR (mean = 5%) beverages. Interindividual variability in excretion was considerably lower with SFR than with GRR beverage. Elimination rates were considerably slower with GRR, allowing for achievement of steady-state dosing as opposed to bolus dosing with SFR. Optimal dosing formulations in future studies should consider blends of sulforaphane and glucoraphanin as SFR and GRR mixtures to achieve peak concentrations for activation of some targets and prolonged inhibition of others implicated in the protective actions of sulforaphane. Cancer Prev Res; 4(3); 384–95. ©2011 AACR.
Obesity Is Associated with Inflammation and Elevated Aromatase Expression in the Mouse Mammary Gland
Authors: Subbaramaiah Kotha , Howe Louise R. , Bhardwaj Priya , Du Baoheng , Gravaghi Claudia , Yantiss Rhonda K. , Zhou Xi Kathy , Blaho Victoria A. , Hla Timothy , Yang Peiying , Kopelovich Levy , Hudis Clifford A. , Dannenberg Andrew J. 
Published: March 2011

Abstract
Elevated circulating estrogen levels are associated with increased risk of breast cancer in obese postmenopausal women. Following menopause, the biosynthesis of estrogens through CYP19 (aromatase)-mediated metabolism of androgen precursors occurs primarily in adipose tissue, and the resulting estrogens are then secreted into the systemic circulation. The potential links between obesity, inflammation, and aromatase expression are unknown. In both dietary and genetic models of obesity, we observed necrotic adipocytes surrounded by macrophages forming crown-like structures (CLS) in the mammary glands and visceral fat. The presence of CLS was associated with activation of NF-κB and increased levels of proinflammatory mediators (TNF-α, IL-1β, Cox-2), which were paralleled by elevated levels of aromatase expression and activity in the mammary gland and visceral fat of obese mice. Analyses of the stromal-vascular and adipocyte fractions of the mammary gland suggested that macrophage-derived proinflammatory mediators induced aromatase and estrogen-dependent gene expression (PR, pS2) in adipocytes. Saturated fatty acids, which have been linked to obesity-related inflammation, stimulated NF-κB activity in macrophages leading to increased levels of TNF-α, IL-1β, and Cox-2, each of which contributed to the induction of aromatase in preadipocytes. The discovery of the obesity → inflammation → aromatase axis in the mammary gland and visceral fat and its association with CLS may provide insight into mechanisms underlying the increased risk of hormone receptor-positive breast cancer in obese postmenopausal women, the reduced efficacy of aromatase inhibitors in the treatment of breast cancer in these women, and their generally worse outcomes. The presence of CLS may be a biomarker of increased breast cancer risk or poor prognosis. Cancer Prev Res; 4(3); 329–46. ©2011 AACR.
Curcumin Chemoprevention: The Long Road to Clinical Translation
Authors: Shureiqi Imad , Baron John A. 
Published: March 2011

AbstractCurcumin exhibits significant antitumorigenic activity in various preclinical models; data supporting its chemopreventive activity in humans, however, are lacking. To our knowledge, the first published results of a phase II chemoprevention study of curcumin are reported in this issue of the journal by Carroll and colleagues (beginning on page 354), who examined the effects of oral curcumin on various putative biomarkers of colonic tumorigenesis in smokers. This perspective discusses the potential significance and limitations of the current study findings in addressing the question of whether curcumin is clinically active as a chemopreventive agent. Cancer Prev Res; 4(3); 296–8. ©2011 AACR.
Circulating Leukocyte and Carotid Atherosclerotic Plaque Telomere Length
Authors: Huzen Jardi , Peeters Wouter , de Boer Rudolf A. , Moll Frans L. , Wong Liza S.M. , Codd Veryan , de Kleijn Dominique P.V. , de Smet Bart J.G.L. , van Veldhuisen Dirk J. , Samani Nilesh J. , van Gilst Wiek H. , Pasterkamp Gerard , van der Harst Pim 
Published: March 2011

Objective—
Shorter leukocyte telomeres are associated with atherosclerosis and predict future heart disease. The goal of the present study was to determine whether leukocyte telomere length is related to atherosclerotic plaque telomere length and whether it is associated with plaque characteristics or recurrence of disease.

Methods and Results—

Telomere length was measured by real-time quantitative polymerase chain reaction in atherosclerotic plaques and leukocytes in patients with carotid atherosclerosis undergoing carotid endarterectomy (n=684) and of leukocytes in age- and gender-balanced subjects without clinical atherosclerosis (n=780). Leukocyte telomere length was shorter in patients versus controls (0.99 [interquartile range (IQR): 0.79 to 1.26] versus 1.06 [0.80 to 1.39];
P
=0.0007). Plaque telomeres were longer than leukocyte telomeres (1.42 [IQR: 1.21 to 1.77] versus 1.01 [IQR: 0.75 to 1.34];
P
<1.00×10
−6
) and independent of age. Leukocyte and plaque telomere length were only weakly correlated (correlation coefficient
r
2
=0.04,
P
=0.03). Patients, whose plaques showed marked macrophage infiltration and large lipid core, had longer plaque telomeres (1.61 [IQR: 1.32 to 2.04] versus 1.40 [IQR: 1.15 to 1.57];
P
=0.006) and shorter leukocyte telomeres (0.88 [IQR: 0.75 to 1.20] versus 1.03 [IQR: 0.83 to 1.34];
P
=0.02). Plaque telomere length was associated with restenosis 1 year after endarterectomy (OR 1.58±0.206;
P
=0.026 per SD decrease of plaque telomere length).

Conclusion—
Leukocyte telomere length is associated with the presence of atherosclerotic carotid plaques but is not a proxy for local plaque telomere length. Plaque telomere length is related to plaque characteristics and development of restenosis following endarterectomy.
Bone Marrow–Derived Smooth Muscle–Like Cells Are Infrequent in Advanced Primary Atherosclerotic Plaques but Promote Atherosclerosis
Authors: Yu Haixiang , Stoneman Victoria , Clarke Murray , Figg Nichola , Xin Hong-Bo , Kotlikoff Michael , Littlewood Trevor , Bennett Martin 
Published: March 2011

Objective—
Although vascular smooth muscle cells (VSMCs) provide the major structural integrity of atherosclerotic plaques, their origin has been questioned. In particular, although some studies identified plaque VSMCs originating from bone marrow or peripheral blood, their frequency is controversial and their function unknown. We used genetic tracking of cell fate through smooth muscle cell (SMC)–specific LacZ reporter activity and VSMC-selective apoptosis to investigate the frequency, distribution, and role of marrow-derived VSMCs in atherogenesis.

Methods and Results—

Cultured mouse bone marrow–derived smooth muscle–like cells expressed SMC markers and functional SMC promoter-driven transgenes over time. Transplantation of apolipoprotein E (ApoE)
−/−
mice with smooth muscle myosin heavy chain–Cre/ROSA26R/ApoE
−/−
marrow showed that 0.7±0.14% cells expressed LacZ in atherosclerotic plaques, located superficially in early plaques, and in necrotic cores but not fibrous caps of advanced lesions. Cells expressing both progenitor and SMC markers showed a similar distribution and frequency. Apoptosis of marrow-derived SMC-like cells transplanted from SM22α–human diphtheria toxin receptor/ApoE
−/−
mice retarded atherogenesis, with reduced plaque macrophage content. Cultured marrow-derived SMC-like cells secreted proinflammatory cytokines and promoted macrophage migration, VSMC proliferation, and collagen synthesis.

Conclusion—
Bone marrow–derived SMC-like cells are infrequent in advanced primary atherosclerotic plaques and absent in fibrous caps. However, these cells secrete proinflammatory cytokines and mitogens and promote atherosclerosis.
Macrophage-Derived Tumor Necrosis Factor-α Is an Early Component of the Molecular Cascade Leading to Angiogenesis in Response to Aortic Injury
Authors: Ligresti Giovanni , Aplin Alfred C. , Zorzi Penelope , Morishita Ann , Nicosia Roberto F. 
Published: March 2011

Objective—
The goal of this study was to define the role of tumor necrosis factor-α (TNFα) in the cascade of gene activation that regulates aortic angiogenesis in response to injury.

Methods and Results—
Angiogenesis was studied by culturing rat or mouse aortic rings in collagen gels. Gene expression was evaluated by quantitative reverse transcription–polymerase chain reaction, microarray analysis, immunocytochemistry, and ELISA. TNFα gene disruption and recombinant TNFα or blocking antibodies against vascular endothelial growth factor (VEGF) or TNF receptors were used to investigate TNFα-mediated angiogenic mechanisms. Resident aortic macrophages were depleted with liposomal clodronate. Angiogenesis was preceded by overexpression of TNFα and TNFα-inducible genes. Studies with isolated cells showed that macrophages were the main source of TNFα. Angiogenesis, VEGF production, and macrophage outgrowth were impaired by TNFα gene disruption and promoted by exogenous TNFα. Antibody-mediated inhibition of TNF receptor 1 significantly inhibited angiogenesis. The proangiogenic effect of TNFα was suppressed by blocking VEGF or by ablating aortic macrophages. Exogenous TNFα, however, maintained a limited proangiogenic capacity in the absence of macrophages and macrophage-mediated VEGF production.

Conclusion—
Overexpression of TNFα is required for optimal VEGF production and angiogenesis in response to injury. This TNFα/VEGF-mediated angiogenic pathway requires macrophages. The residual capacity of TNFα to stimulate angiogenesis in macrophage-depleted aortic cultures implies the existence of a VEGF-independent alternate pathway of TNFα-induced angiogenesis.
Propagation of the Sinus Impulse Into the Koch Triangle and Localization, Timing, and Origin of the Multicomponent Potentials Recorded in This Area
Authors: Pandozi Claudio , Ficili Sabina , Galeazzi Marco , Lavalle Carlo , Russo Maurizio , Pandozi Angela , Venditti Franco , Pristipino Christian , Verbo Brunella , Santini Massimo 
Published: March 2011

Background—
The presence of a conduction block at the level of the Koch triangle (KT) and the origin of the multicomponent potentials inside this area are controversial issues. We investigated the propagation of the sinus impulse into the KT and the characteristics of multicomponent potentials recorded in that area in patients with and without atrioventricular nodal reentrant tachycardia (AVNRT).

Methods and Results—

Thirty-two patients (16 with AVNRT, 16 without AVNRT) underwent a sinus rhythm electroanatomic mapping of the right atrium (RA). Conduction velocities in the RA and in the KT were evaluated quantitatively on activation maps and qualitatively on isochronal and propagation maps. The presence, location, and timing of different types of multicomponent potentials were evaluated. A mean of 149±44 points were sampled in the RA, whereas a mean of 79±21 points were collected inside the KT. Propagation block at the level of crista terminalis was not found in any patient, whereas slow conduction inside the KT was found in all (median conduction velocity, 122 cm/s [110 to 135 cm/s] outside KT versus 60 cm/s [48 to 75 cm/s] inside KT;
P
<0.0001). Jackman potentials were identified inside KT in almost all the patients and were invariably found on the line of collision between the wavefronts activating the KT in opposite directions.

Conclusions—
No conduction block was detected inside the KT in patients with and without AVNRT. Conduction slowing was demonstrated during propagation of the sinus impulse inside the KT. The genesis of the Jackman potential may be related to the collision of the wavefronts activating KT in opposite directions.
Cycling Induced by Electrical Stimulation Improves Motor Recovery in Postacute Hemiparetic Patients
Authors: Ambrosini Emilia , Ferrante Simona , Pedrocchi Alessandra , Ferrigno Giancarlo , Molteni Franco 
Published: March 2011

Background and Purpose—
This study assessed whether cycling induced by functional electrical stimulation (FES) was more effective than passive cycling with placebo stimulation in promoting motor recovery and walking ability in postacute hemiparetic patients.

Methods—
In a double-blind, randomized, controlled trial, 35 patients were included and randomized to receive FES-induced cycling training or placebo FES cycling. The 4-week treatment consisted of 20 sessions lasting 25 minutes each. Primary outcome measures included the leg subscale of the Motricity Index and gait speed during a 50-meter walking test. Secondary outcomes were the Trunk Control Test, the Upright Motor Control Test, the mean work produced by the paretic leg, and the unbalance in mechanical work between paretic and nonparetic legs during voluntary pedaling. Participants were evaluated before training, after training, and at 3- to 5-month follow-up visits.

Results—

No significant differences were found between groups at baseline. Repeated-measures ANOVA (
P
<0.05) revealed significant increases in Motricity Index, Trunk Control Test, Upright Motor Control Test, gait speed, and mean work of the paretic leg after training and at follow-up assessments for FES-treated patients. No outcome measures demonstrated significant improvements after training in the placebo group. Both groups showed no significant differences between assessments after training and at follow-up. A main effect favoring FES-treated patients was demonstrated by repeated-measures ANCOVA for Motricity Index (
P
<0.001), Trunk Control Test (
P
=0.001), Upright Motor Control Test (
P
=0.005), and pedaling unbalance (
P
=0.038).

Conclusions—
The study demonstrated that 20 sessions of FES cycling training significantly improved lower extremity motor functions and accelerated the recovery of overground locomotion in postacute hemiparetic patients. Improvements were maintained at follow-up.
Safety and Tolerability of Early Noninvasive Ventilatory Correction Using Bilevel Positive Airway Pressure in Acute Ischemic Stroke
Authors: Tsivgoulis Georgios , Zhang Yi , Alexandrov Anne W. , Harrigan Mark R. , Sisson April , Zhao Limin , Brethour Mary , Cava Luis , Balucani Clotilde , Barlinn Kristian , Patterson Damon E. , Giannopoulos Sotirios , DeWolfe Jennifer , Alexandrov Andrei V. 
Published: March 2011

Background and Purpose—
Hypercapnia can induce intracranial blood-flow steal from ischemic brain tissues, and early initiation of noninvasive ventilator correction (NIVC) may improve cerebral hemodynamics in acute ischemic stroke. We sought to determine safety and tolerability of NIVC initiated on hospital admission without polysomnography study.

Subjects and Methods—

Consecutive acute ischemic stroke patients were evaluated for the presence of a proximal arterial occlusion, daytime sleepiness, or history of obstructive sleep apnea, and acceptable pulse oximetry readings while awake (96%–100% on 2 to 4 L supplemental oxygen delivered by nasal cannula). NIVC was started on hospital admission as standard of care when considered necessary by treating physicians. NIVC was initiated using bilevel positive airway pressure at 10 cmH
2
O inspiratory positive airway pressure and 5 cmH
2
O expiratory positive airway pressure in combination with 40% fraction of inspired oxygen. All potential adverse events were prospectively documented.

Results—

Among 356 acute ischemic stroke patients (median NIHSS score, 5; interquartile range, 2–13), 64 cases (18%) received NIVC (median NIHSS score, 12; interquartile range, 6–17). Baseline stroke severity was higher and proximal arterial occlusions were more frequent in NIVC patients compared to the rest (
P
<0.001). NIVC was not tolerated by 4 patients (7%). Adverse events in NIVC included vomiting (n=1), aspiration pneumonia (n=1), respiratory failure/intubation (n=1), hypotension requiring pressors (n=1), and facial skin breakdown (n=3). The in-hospital mortality rate was 13% in NIVC patients and 8% in the rest (
P
=0.195). Neurological improvement during hospitalization tended to be greater in the NIVC group (median NIHSS score decrease, 2 points; interquartile range, 0–4) compared to the rest (median NIHSS score decrease, 1; interquartile range, 0–2;
P
=0.078).

Conclusions—
In acute ischemic stroke patients with proximal arterial occlusion and excessive sleepiness or obstructive sleep apnea, NIVC can be initiated early with good tolerability and a relatively small risk of serious complications.
Visualization of Clot Lysis in a Rat Embolic Stroke Model
Authors: Walvick Ronn P. , Bråtane Bernt T. , Henninger Nils , Sicard Kenneth M. , Bouley James , Yu Zhanyang , Lo Eng , Wang Xiaoying , Fisher Marc 
Published: March 2011

Background and Purpose—
The purpose of this study was to develop a novel MRI method for imaging clot lysis in a rat embolic stroke model and to compare tissue plasminogen activator (tPA)-based clot lysis with and without recombinant Annexin-2 (rA2).

Methods—
In experiment 1 we used in vitro optimization of clot visualization using multiple MRI contrast agents in concentrations ranging from 5 to 50 μL in 250 μL blood. In experiment 2, we used in vivo characterization of the time course of clot lysis using the clot developed in the previous experiment. Diffusion, perfusion, angiography, and T1-weighted MRI for clot imaging were conducted before and during treatment with vehicle (n=6), tPA (n=8), or rA2 plus tPA (n=8) at multiple time points. Brains were removed for ex vivo clot localization.

Results—

Clots created with 25 μL Magnevist were the most stable and provided the highest contrast-to-noise ratio. In the vehicle group, clot length as assessed by T1-weighted imaging correlated with histology (
r
=0.93). Clot length and cerebral blood flow-derived ischemic lesion volume were significantly smaller than vehicle at 15 minutes after treatment initiation in the rA2 plus tPA group, whereas in the tPA group no significant reduction from vehicle was observed until 30 minutes after treatment initiation. The rA2 plus tPA group had a significantly shorter clot length than the tPA group at 60 and 90 minutes after treatment initiation and significantly smaller cerebral blood flow deficit than the tPA group at 90 minutes after treatment initiation.

Conclusions—
We introduce a novel MRI-based clot imaging method for in vivo monitoring of clot lysis. Lytic efficacy of tPA was enhanced by rA2.
Polarimetric Radar Observation Operator for a Cloud Model with Spectral Microphysics
Authors: Ryzhkov A. , Pinsky M. , Pokrovsky A. , Khain A. 
Published: March 2011

AbstractThe radar observation operator for computation of polarimetric radar variables from the output of numerical cloud models is described in its most generic form. This operator is combined with the Hebrew University of Jerusalem cloud model with spectral microphysics. The model contains 7 classes of hydrometeors and each class is represented by size distribution functions in 43 size bins. The performance of the cloud model and radar observation operator has been evaluated for the case of a hailstorm in Oklahoma on 2 February 2009. It is shown that the retrieved fields of polarimetric radar variables at C and S microwave bands are generally consistent with results of observations. The relationship between microphysical and polarimetric signatures is illustrated.
Polarimetric Doppler Radar Observations of Kelvin–Helmholtz Waves in a Winter Storm
Authors: Houser Jana Lesak , Bluestein Howard B. 
Published: March 2011

Abstract
Kelvin–Helmholtz waves were observed by the Twin Lakes, Oklahoma (KTLX), Weather Surveillance Radar-1988 Doppler (WSR-88D); the Norman, Oklahoma (KOUN), polarimetric WSR-88D; and the polarimetric Collaborative Adaptive Sensing of the Atmosphere (CASA) radars on 30 November 2006 during a winter storm in central Oklahoma. The life cycle and structure of the waves are analyzed from the radar data, and the nearby atmospheric conditions are examined. The initial perturbations associated with the waves are first evident only in the radars’ radial velocity fields. As the waves mature, perturbations become discernable in the reflectivity factor Z and spectrum width (SW) fields of both radars, and in the differential reflectivity Zdr and, to a lesser extent, the cross-correlation coefficient ρhv fields of KOUN. As the waves break and begin to dissipate, the perturbations subside.
A dual-Doppler analysis is synthesized to examine the kinematic structure of the waves and to relate the polarimetric observations to the kinematics. It is determined that Z and Zdr are enhanced in regions of upward motion (wave crests), and ρhv is reduced in the same vicinity and near the base of the wave circulations. Vertical velocity perturbations transport horizontal momentum upward and downward, inducing horizontal wind perturbations that are approximately 90° out of phase and downstream from their corresponding vertical velocity perturbations. Perturbations in Z, Zdr, and ρhv are observed in the vicinity of wave crests while SW perturbations occur predominately in and just upstream from wave troughs. It is determined that perturbations in the polarimetric variables are a result of the waves modifying local precipitation microphysics. Perturbations in Z and Zdr are hypothesized to be the result of columnar ice crystal generation whereas those in ρhv likely result from the mixing of ice crystals of various shapes and sizes. Perturbations in SW are a result of turbulent motions likely associated with wave breaking and downward advection of a strong shear layer.