bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urinary 3,3′-Diindolylmethane: A Biomarker of Glucobrassicin Exposure and Indole-3-Carbinol Uptake in Humans
Authors: Fujioka Naomi , Ainslie-Waldman Cheryl E. , Upadhyaya Pramod , Carmella Steven G. , Fritz Vincent A. , Rohwer Charles , Fan Yunhua , Rauch Diane , Le Chap , Hatsukami Dorothy K. , Hecht Stephen S. 
Published: December 2013

Abstract
Background: Brassica vegetable consumption may confer a protective effect against cancer, possibly attributable to their glucosinolates. Glucobrassicin is a predominant glucosinolate and is the precursor of indole-3-carbinol (I3C), a compound with anticancer effects. However, objective assessments of I3C uptake from Brassica vegetables have not been successful.
Methods: We conducted a randomized, crossover trial to test whether 3,3′-diindolylmethane (DIM, a metabolite of I3C) excreted in the urine after consumption of raw Brassica vegetables with divergent glucobrassicin concentrations is a marker of I3C uptake from such foods. Twenty-five subjects were fed 50 g of either raw “Jade Cross” Brussels sprouts (high glucobrassicin concentration) or “Blue Dynasty” cabbage (low glucobrassicin concentration) once daily for 3 days. All urine was collected for 24 hours after vegetable consumption each day. After a washout period, subjects crossed over to the alternate vegetable. Urinary DIM was measured using a novel liquid chromatography-electrospray ionization-tandem mass spectrometry–selected reaction monitoring (LC-ESI-MS/MS-SRM) method with [2H2]DIM as internal standard.
Results: Urinary DIM was consistently and significantly higher after Brussels sprouts feeding than after cabbage feeding, as evidenced by an average difference of 8.73 pmol/mg creatinine (95% confidence interval, 5.36–12.10; P = 0.00002).
Conclusion: We have successfully quantified urinary DIM after uptake of I3C from food, and demonstrated that differences in glucobrassicin exposure are reflected in urinary DIM levels.
Impact: Our LC-ESI-MS/MS-SRM method and the results of our study indicate urinary DIM is a measure of I3C uptake from Brassica vegetables, a finding that can be utilized in prospective epidemiologic and chemoprevention studies. Cancer Epidemiol Biomarkers Prev; 23(2); 282–7. ©2013 AACR.
The Effect of Photoimmunotherapy Followed by Liposomal Daunorubicin in a Mixed Tumor Model: A Demonstration of the Super-Enhanced Permeability and Retention Effect after Photoimmunotherapy
Authors: Sano Kohei , Nakajima Takahito , Choyke Peter L. , Kobayashi Hisataka 
Published: December 2013

Abstract
In general, de novo solid tumors are composed of phenotypically and functionally heterogeneous malignant cells. This heterogeneity interferes with the effectiveness of targeted molecular cancer therapies. Even if most of the tumor is killed by a targeted treatment, recurrences are common and can be lethal. In this study, a mixed tumor model, which is predominantly a population of epidermal growth factor receptor (EGFR)-positive A431 cells combined with a smaller population of EGFR-negative Balb3T3/DsRed cells, was established. This mixed tumor was then treated with photoimmunotherapy, a newly developed target-cell–selective cancer therapy using a monoclonal antibody (mAb)–photosensitizer (IR700 fluorescence dye) conjugate and exposure of near-infrared light. Although photoimmunotherapy successfully treated EGFR-positive A431 cells in the mixed tumor, EGFR-negative Balb/DsRed cells were not responsive. However, photoimmunotherapy also induced a large increase in tumor permeability, known as the super-enhanced permeability and retention (SUPR) effect, which allowed a 5-fold increase in the accumulation of a liposomal chemotherapy (DaunoXome) and resulted in more effective therapy than either photoimmunotherapy or liposomal daunorubicin alone. The liposomal daunorubicin, administered 1 hour after EGFR-targeted photoimmunotherapy, was homogeneously distributed, allowing delivery to tiny surviving nests of EGFR-negative Balb3T3/DsRed cells, resulting in prolonged survival of mice. Mol Cancer Ther; 13(2); 426–32. ©2013 AACR.
Antiangiogenic Therapies: Going beyond Their Limits
Authors: Moserle Lidia , Jiménez-Valerio Gabriela , Casanovas Oriol 
Published: December 2013

Abstract
Tumor growth requires induction of an angiogenic program, and targeting of this program with antiangiogenic drugs shows an impact on tumor progression. However, although they are effective at reducing angiogenesis, these therapies have not produced widespread or enduring clinical benefit, which openly exposes their limitations. Here, we describe the current limitations of these therapies, including the known mechanisms and current controversies. Further, we present some of the recent approaches to predict these limitations and strategies to overcome them. With the development of meaningful predictive biomarkers and effective treatments that impede these limitations, longer and more robust efficacies will be achieved for a wider population of patients.
Significance: The clinical benefit of antiangiogenic drugs is restricted because of intrinsic and acquired limitations. Acknowledging and understanding these limitations will not only allow the development of effective predictive biomarkers but also help in devising new therapeutic strategies that achieve longer efficacies for a wider population of patients. Cancer Discov; 4(1); 31–41. ©2013 AACR.
Mesothelin-Specific Chimeric Antigen Receptor mRNA-Engineered T Cells Induce Antitumor Activity in Solid Malignancies
Authors: Beatty Gregory L. , Haas Andrew R. , Maus Marcela V. , Torigian Drew A. , Soulen Michael C. , Plesa Gabriela , Chew Anne , Zhao Yangbing , Levine Bruce L. , Albelda Steven M. , Kalos Michael , June Carl H. 
Published: December 2013

Abstract
Off-target toxicity due to the expression of target antigens in normal tissue represents a major obstacle to the use of chimeric antigen receptor (CAR)-engineered T cells for treatment of solid malignancies. To circumvent this issue, we established a clinical platform for engineering T cells with transient CAR expression by using in vitro transcribed mRNA encoding a CAR that includes both the CD3-ζ and 4-1BB costimulatory domains. We present two case reports from ongoing trials indicating that adoptive transfer of mRNA CAR T cells that target mesothelin (CARTmeso cells) is feasible and safe without overt evidence of off-tumor on-target toxicity against normal tissues. CARTmeso cells persisted transiently within the peripheral blood after intravenous administration and migrated to primary and metastatic tumor sites. Clinical and laboratory evidence of antitumor activity was shown in both patients, and the CARTmeso cells elicited an antitumor immune response revealed by the development of novel antiself antibodies. These data show the potential of using mRNA-engineered T cells to evaluate, in a controlled manner, potential off-tumor on-target toxicities and show that short-lived CAR T cells can induce epitope spreading and mediate antitumor activity in patients with advanced cancer. Thus, these findings support the development of mRNA CAR-based strategies for carcinoma and other solid tumors. Cancer Immunol Res; 2(2); 112–20. ©2013 AACR.
Intraperitoneal Injection Improves the Uptake of Nanoparticle-Labeled High-Density Lipoprotein to Atherosclerotic Plaques Compared With Intravenous Injection
Authors: Jung Caroline , Kaul Michael G. , Bruns Oliver T. , Dučić Tanja , Freund Barbara , Heine Markus , Reimer Rudolph , Meents Alke , Salmen Sunhild C. , Weller Horst , Nielsen Peter , Adam Gerhard , Heeren Jörg , Ittrich Harald 
Published: December 2013

Background—
The aim of this study was to assess whether high-density lipoprotein (HDL) labeled with superparamagnetic iron oxide nanoparticles (SPIOs) and quantum dots was able to detect atherosclerotic lesions in mice after intravenous and intraperitoneal injection by multimodal imaging.

Methods and Results—

Nanoparticle-labeled HDLs (NP-HDLs) were characterized in vitro by dynamic light scattering and size exclusion chromatography with subsequent cholesterol and fluorescence measurements. For biodistribution and blood clearance studies, NP-HDL
SPIOs
radiolabeled with
59
Fe (NP-HDL
59Fe-SPIOs
) were injected intravenously or intraperitoneally into ApoE knockout mice (n=6), and radioactivity was measured using a gamma counter. NP-HDL accumulation within atherosclerotic plaques in vivo and ex vivo was estimated by MRI at 7 Tesla, ex vivo confocal fluorescence microscopy, x-ray fluorescence microscopy, and histological analysis (n=3). Statistical analyses were performed using a 2-tailed Student
t
-test. In vitro characterization of NP-HDL confirmed properties similar to endogenous HDL. Blood concentration time curves showed a biexponential decrease for the intravenous injection, whereas a slow increase followed by a steady state was noted for intraperitoneal injection. Radioactivity measurements showed predominant accumulation in the liver and spleen after both application approaches. NP-HDL
59Fe-SPIOs
uptake into atherosclerotic plaques increased significantly after intraperitoneal compared with intravenous injection (
P
<0.01). In vivo MRI showed an increased uptake of NP-HDL into atherosclerotic lesions after intraperitoneal injection, which was confirmed by ex vivo MRI, x-ray fluorescence microscopy, confocal fluorescence microscopy, and histological analysis.

Conclusions—
In vivo MRI and ex vivo multimodal imaging of atherosclerotic plaque using NP-HDL is feasible, and intraperitoneal application improves the uptake within vessel wall lesions compared with intravenous injection.
Perceived Stress Is Associated With Incident Coronary Heart Disease and All‐Cause Mortality in Low‐ but Not High‐Income Participants in the Reasons for Geographic And Racial Differences in Stroke Study
Authors: Redmond Nicole , Richman Joshua , Gamboa Christopher M. , Albert Michelle A. , Sims Mario , Durant Raegan W. , Glasser Stephen P. , Safford Monika M. 
Published: December 2013

Background

Perceived stress may increase risk for coronary heart disease (
CHD
) and death, but few studies have examined these relationships longitudinally. We sought to determine the association of perceived stress with incident
CHD
and all‐cause mortality.

Methods and Results

Data were from a prospective study of 24 443 participants without
CHD
at baseline from the national Reasons for Geographic And Racial Differences in Stroke (
REGARDS
) study cohort. Outcomes were expert‐adjudicated acute
CHD
and all‐cause mortality. Over a mean follow‐up of 4.2 (maximum 6.9) years, there were 659 incident
CHD
events and 1320 deaths. Analyses were stratified by income level because of significant interactions with stress. For individuals with low income, 3529 (35.4%) reported high stress, and for those with high income, 2524 (22.1%) did so. Compared with reporting no stress, those reporting the highest stress had higher risk for incident
CHD
if they reported low income (sociodemographic‐adjusted
HR
1.36, 95%
CI
: 1.04, 1.78) but not high income (sociodemographic‐adjusted
HR
0.82, 95%
CI
: 0.57, 1.16); the finding in low income individuals attenuated with adjustment for clinical and behavioral factors (
HR
1.29, 95%
CI
: 0.99, 1.69,
P
=0.06). After full adjustment, the highest stress category was associated with higher risk for death among those with low income (
HR
1.55, 95%
CI
: 1.31, 1.82) but not high income (
HR
1.13, 95%
CI
: 0.88, 1.46).

Conclusions

High stress was associated with greater risks of
CHD
and death for individuals with low but not high income.
Carotid Bifurcation Geometry Is an Independent Predictor of Early Wall Thickening at the Carotid Bulb
Authors: Bijari Payam B. , Wasserman Bruce A. , Steinman David A. 
Published: December 2013

Background and Purpose—
Lumen geometry has long been suspected as a risk factor for atherosclerosis by virtue of its influence on blood flow disturbances. Confirmation of this geometric risk hypothesis has, however, proved challenging owing to possible effects of wall thickening on geometry and unproven links between candidate geometric variables and disturbed flow. The purpose of this study was to overcome these challenges.

Methods—
The study relied on imaging and risk factor data from progressively refined subsets of the Atherosclerosis Risk in Communities (ARIC) Carotid MRI study. Group 1 (n=467) included only nonstenotic cases having sufficient quality angiography for 3-dimensional analysis. Group 2 (n=346) excluded cases from group 1 having common and internal carotid artery wall thickness above previously identified thresholds for inward remodeling. Group 3 (n=294) excluded cases from group 2 having lumen irregularities and thus was least likely to include lumen geometries influenced by wall thickening.

Results—
Multiple linear regressions showed that for group 3, bifurcation flare and proximal curvature were independent predictors of internal carotid artery wall thickness, consistent with their previously demonstrated roles in predicting disturbed flow. For the broadest group 1, flare was an independent predictor of internal carotid artery wall thickness but with a sign change in regression coefficient reflecting effects of wall thickening on lumen geometry.

Conclusions—
Carotid bifurcation geometry is an independent, albeit weak, predictor of its early wall thickening, but only when assumptions about geometric factors, and the influence of disease on them, are confronted. This highlights pitfalls of previous attempts to confirm geometric risk of atherosclerosis.
Why is the AMOC Monostable in Coupled General Circulation Models?
Authors: Liu Wei , Liu Zhengyu , Brady Esther C. 
Published: December 2013

AbstractThis paper is concerned with the question: why do coupled general circulation models (CGCM) seem to be biased toward a monostable Atlantic meridional overturning circulation (AMOC)? In particular, the authors investigate whether the monostable behavior of the CGCMs is caused by a bias of model surface climatology. First observational literature is reviewed, and it is suggested that the AMOC is likely to be bistable in the real world in the past and present. Then the stability of the AMOC in the NCAR Community Climate System Model, version 3 (CCSM3) is studied by comparing the present-day control simulation (without flux adjustment) with a sensitivity experiment with flux adjustment. It is found that the monostable AMOC in the control simulation is altered to a bistable AMOC in the flux-adjustment experiment because a reduction of the surface salinity biases in the tropical and northern North Atlantic leads to a reduction of the bias of freshwater transport in the Atlantic. In particular, the tropical bias associated with the double ITCZ reduces salinity in the upper South Atlantic Ocean and, in turn, the AMOC freshwater export, which tends to overstabilize the AMOC and therefore biases the AMOC from bistable toward monostable state. This conclusion is consistent with a further analysis of the stability indicator of two groups of IPCC Fourth Assessment Report (AR4) CGCMs: one without and the other with flux adjustment. Because the tropical bias is a common feature among all CGCMs without flux adjustment, the authors propose that the surface climate bias, notably the tropical bias in the Atlantic, may contribute significantly to the monostability of AMOC behavior in current CGCMs.
Subacute lupus erythematosus during treatment with golimumab for seronegative rheumatoid arthritis
Authors: Brunasso AMG , Aberer W , Massone C 
Published: December 2013

We report on a 52-year-old woman with a history of severe seronegative rheumatoid arthritis. Several conventional therapies and biological therapy with etanercept and infliximab had been unsuccessful. In 2010 she was given golimumab subcutaneously at a monthly dose of 50 mg. She had a negative ANA titre. After 16 months of uninterrupted therapy and sustained response, she developed skin lesions on the upper trunk, back and upper extremities, which worsened on exposure to the sun. The skin biopsy was compatible with subacute lupus erythematosus. Laboratory findings included an ANA titre 1:640, negative anti-Ro/SSA and anti-DNA antibodies. Topical corticosteroid therapy proved inadequate. The patient’s condition improved only after discontinuation of golimumab. The causal relationship between subacute cutaneous lupus erythematosus and golimumab is not dose-related and occurs with some delay (a typical feature of immunological adverse reactions). The association is likely, but not confirmed (because re-challenge was not performed). However, a clear improvement was noted after withdrawal. Based on this case, we hypothesized the aetiological role of golimumab-associated immunogenicity. TNF-α antagonist-induced lupus-like syndrome (TAILS) is a well-known side effect of this class of substances. The British Society of Rheumatology recommends discontinuation of the causal anti-TNF-α treatment in patients with TAILS.
Surgical Technique, Fusion Rates, and Planovalgus Foot Deformity Correction With Naviculocuneiform Fusion
Authors: Ajis Adam , Geary Nicholas 
Published: December 2013

Background: Arthrodesis of the naviculocuneiform (NC) joints is not a common procedure, as it is perceived by many to be less reliable or less predictable than arthrodesis of proximal or distal joints in the medial column. There is a subset of patients with planovalgus feet, cavovarus feet, and degenerative arthritis who also have an apex of deformity at the NC joints in whom fusion is indicated. The surgical technique, fusion rates, and deformity correction data for NC fusion in planovalgus feet are evaluated in this report. Methods: Twenty-eight patients (33 feet) who underwent surgery between October 2008 and November 2012 were identified who had NC fusion as their only arthrodesis procedure. Medical records and radiographs were reviewed, and time to union was calculated. Twenty patients from that group underwent NC fusion for symptomatic planovalgus feet, and their preoperative and last postoperative weight-bearing radiographs were reviewed and compared for deformity correction. All patients were operated on by the senior author or a senior foot and ankle trainee during fellowship using the same surgical technique, and all patients followed a standardized postoperative rehabilitation protocol. Results: Mean time to union for all 33 NC fusions was 21.7 ± 2 weeks (mean ± SEM). One patient underwent revision for nonunion, resulting in an arthrodesis rate of 97%. For NC fusions in those with planovalgus feet, an improvement in mean lateral talus–first metatarsal angle (Meary’s line) from 12.3 ± 1.3 degrees to 5.2 ± 1.2 degrees ( P < .05) was found. There was also a mean improvement in talonavicular coverage angle from 14.1 ± 1.8 degrees to 7.4 ± 1.3 degrees ( P < .05). There were 2 superficial wound infections that were successfully treated with oral antibiotics, there were no cases of deep vein thrombosis or pulmonary embolism, and all patients came out of cast at 6 weeks into a fixed angle boot to commence weight bearing. Patients were happy with 32 of the 33 procedures and required no further treatment for their condition. Conclusions: NC fusion was a safe and predictable procedure for any of its indications, with a fusion rate similar to that of other joints in the foot albeit with a longer time to union. For patients with symptomatic and flexible planovalgus feet, NC fusion resulted in deformity correction in multiple planes and good symptomatic relief. Level of Evidence: Level IV, retrospective case series.
Does applying technology throughout the medication use process improve patient safety with antineoplastics?
Authors: Bubalo Joseph , Warden Bruce A , Wiegel Joshua J , Nishida Tess , Handel Evelyn , Svoboda Leanne M , Nguyen Lam , Edillo P Neil 
Published: December 2013

Purpose Medical errors, in particular medication errors, continue to be a troublesome factor in the delivery of safe and effective patient care. Antineoplastic agents represent a group of medications highly susceptible to medication errors due to their complex regimens and narrow therapeutic indices. As the majority of these medication errors are frequently associated with breakdowns in poorly defined systems, developing technologies and evolving workflows seem to be a logical approach to provide added safeguards against medication errors. Summary This article will review both the pros and cons of today's technologies and their ability to simplify the medication use process, reduce medication errors, improve documentation, improve healthcare costs and increase provider efficiency as relates to the use of antineoplastic therapy throughout the medication use process. Several technologies, mainly computerized provider order entry (CPOE), barcode medication administration (BCMA), smart pumps, electronic medication administration record (eMAR), and telepharmacy, have been well described and proven to reduce medication errors, improve adherence to quality metrics, and/or improve healthcare costs in a broad scope of patients. The utilization of these technologies during antineoplastic therapy is weak at best and lacking for most. Specific to the antineoplastic medication use system, the only technology with data to adequately support a claim of reduced medication errors is CPOE. In addition to the benefits these technologies can provide, it is also important to recognize their potential to induce new types of errors and inefficiencies which can negatively impact patient care. Conclusion The utilization of technology reduces but does not eliminate the potential for error. The evidence base to support technology in preventing medication errors is limited in general but even more deficient in the realm of antineoplastic therapy. Though CPOE has the best evidence to support its use in the antineoplastic population, benefit from many other technologies may have to be inferred based on data from other patient populations. As health systems begin to widely adopt and implement new technologies it is important to critically assess their effectiveness in improving patient safety.
Thoracoscopy in the cat
Authors: Radlinsky MaryAnn 
Published: December 2013

Practical relevance: Thoracoscopy provides a minimally invasive means of diagnosis and offers many important benefits when compared with open thoracotomy. Clinical challenges: The expense of the equipment, the steep learning curve required to gain proficiency in thoracoscopic surgery, and the limitations imposed by the feline thoracic cavity, in terms of working and viewing space, are some of the challenges that have limited its uptake to date. However, it is envisaged that it will increase as a technique in feline medicine, in much the same way as laparoscopy has. Audience: This article is directed at veterinarians currently performing open thoracic surgery and the associated aftercare who concurrently are adept at endoscopic surgery. Evidence base: The article draws on the small body of literature that is available on thoracoscopy in cats, which includes reports of its use for evaluation and management of undiagnosed pleural effusion, lung lobe torsion, persistent right aortic arch and chylothorax.