bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting the Outcome of Infectious Diseases: Variability among Inbred Mice as a New and Powerful Tool for Biomarker Discovery
Authors: Martin Miriam E. , Dieter Jacquelyn A. , Luo Zheng , Baumgarth Nicole , Solnick Jay V. 
Published: October 2012

ABSTRACT

Individuals respond differently to infectious diseases. Even among inbred mice that are presumed to be genetically identical, the response to a microbial pathogen is variable, which is generally thought to reflect experimental inconsistencies, technical errors, and stochastic processes. Here we describe the remarkable observation that the variability of
Helicobacter pylori
colonization density in the stomachs of experimentally infected C57BL/6J mice is tightly correlated with weight loss and viral load after a challenge with influenza virus, though
H. pylori
infection
per se
does not affect influenza and vice versa. Since these two infectious agents are found in different tissue compartments and are detected using unrelated methods, the correlation in microbial burden must represent a biological measure of disease susceptibility among genetically nearly identical individuals and not technical or stochastic factors. We hypothesize that inbred mice represent a powerful new tool for the identification of biomarkers to predict the outcome of infectious diseases.
Unexpected Diversity and Expression of Avian Endogenous Retroviruses
Authors: Bolisetty Mohan , Blomberg Jonas , Benachenhou Farid , Sperber Göran , Beemon Karen 
Published: October 2012

ABSTRACT

Endogenous retroviruses (ERVs) were identified and characterized in three avian genomes to gain insight into early retroviral evolution. Using the computer program RetroTector to detect relatively intact ERVs, we identified 500 ERVs in the chicken genome, 150 in the turkey genome, and 1,200 in the zebra finch genome. Previous studies suggested that endogenous alpharetroviruses were present in chicken genomes. In this analysis, a small number of alpharetroviruses were seen in the chicken and turkey genomes; however, these were greatly outnumbered by beta-like, gamma-like, and alphabeta proviruses. While the avian ERVs belonged to the same major groups as mammalian ERVs, they were more heterogeneous. In particular, the beta-like viruses revealed an evolutionary continuum with the gradual acquisition and loss of betaretroviral markers and a transition from beta to alphabeta and then to alpharetroviruses. Thus, it appears that birds may resemble a melting pot for early ERV evolution. Many of the ERVs were integrated in clusters on chromosomes, often near centromeres. About 25% of the chicken ERVs were in or near cellular transcription units; this is nearly random. The majority of these integrations were in the sense orientation in introns. A higher-than-random number of integrations were >100 kb from the nearest gene. Deep-sequencing studies of chicken embryo fibroblasts revealed that about 20% of the 500 ERVs were transcribed and translated. A subset of these were also transcribed
in vivo
in chickens, showing tissue-specific patterns of expression.

IMPORTANCE
Studies of avian endogenous retroviruses (ERVs) have given us a glimpse of an earlier retroviral world. Three different classes of ERVs were observed with many features of mammalian retroviruses, as well as some important differences. Many avian ERVs were transcribed and translated.
Serum Glutamate Levels Correlate with Gleason Score and Glutamate Blockade Decreases Proliferation, Migration, and Invasion and Induces Apoptosis in Prostate Cancer Cells
Authors: Koochekpour Shahriar , Majumdar Sunipa , Azabdaftari Gissou , Attwood Kristopher , Scioneaux Ray , Subramani Dhatchayini , Manhardt Charles , Lorusso Giovanni D. , Willard Stacey S. , Thompson Hillary , Shourideh Mojgan , Rezaei Katayoon , Sartor Oliver , Mohler James L. , Vessella Robert L. 
Published: October 2012

Abstract
Purpose: During glutaminolysis, glutamine is catabolized to glutamate and incorporated into citric acid cycle and lipogenesis. Serum glutamate levels were measured in patients with primary prostate cancer or metastatic castrate-resistant prostate cancer (mCRPCa) to establish clinical relevance. The effect of glutamate deprivation or blockade by metabotropic glutamate receptor 1 (GRM1) antagonists was investigated on prostate cancer cells' growth, migration, and invasion to establish biologic relevance.
Experimental Design: Serum glutamate levels were measured in normal men (n = 60) and patients with primary prostate cancer (n = 197) or mCRPCa (n = 109). GRM1 expression in prostatic tissues was examined using immunohistochemistry (IHC). Cell growth, migration, and invasion were determined using cell cytotoxicity and modified Boyden chamber assays, respectively. Apoptosis was detected using immunoblotting against cleaved caspases, PARP, and γ-H2AX.
Results: Univariate and multivariate analyses showed significantly higher serum glutamate levels in Gleason score ≥ 8 than in the Gleason score ≤ 7 and in African Americans than in the Caucasian Americans. African Americans with mCRPCa had significantly higher serum glutamate levels than those with primary prostate cancer or benign prostate. However, in Caucasian Americans, serum glutamate levels were similar in normal research subjects and patients with mCRPC. IHC showed weak or no expression of GRM1 in luminal acinar epithelial cells of normal or hyperplastic glands but high expression in primary or metastatic prostate cancer tissues. Glutamate deprivation or blockade decreased prostate cancer cells' proliferation, migration, and invasion and led to apoptotic cell death.
Conclusions: Glutamate expression is mechanistically associated with and may provide a biomarker of prostate cancer aggressiveness. Clin Cancer Res; 18(21); 5888–901. ©2012 AACR.
Restoration of miR-200c to Ovarian Cancer Reduces Tumor Burden and Increases Sensitivity to Paclitaxel
Authors: Cittelly Diana M. , Dimitrova Irina , Howe Erin N. , Cochrane Dawn R. , Jean Annie , Spoelstra Nicole S. , Post Miriam D. , Lu Xian , Broaddus Russell R. , Spillman Monique A. , Richer Jennifer K. 
Published: October 2012

AbstractA therapeutic intervention that could decrease tumor burden and increase sensitivity to chemotherapy would have a significant impact on the high morbidity rate associated with ovarian cancer. miRNAs have emerged as potential therapeutic candidates due to their ability to downregulate multiple targets involved in tumor progression and chemoresistance. miRNA-200c (miR-200c) is downregulated in ovarian cancer cell lines and stage III ovarian tumors, and low miR-200c correlates with poor prognosis. miR-200c increases sensitivity to taxanes in vitro by targeting class III β-tubulin gene (TUBB3), a tubulin known to mediate chemoresistance. Indeed, we find that patients with tumors having low TUBB3 had significantly prolonged survival (average survival 52.73 ± 4.08 months) as compared with those having high TUBB3 (average survival 42.56 ± 3.19 months). miR-200c also targets TrkB, a mediator of resistance to anoikis. We show that restoration of miR-200c to ovarian cancer cells results in increased anoikis sensitivity and reduced adherence to biologic substrates in vitro. Because both chemo- and anoikis-resistance are critical steps in the progression of ovarian cancer, we sought to determine how restoration of miR-200c affects tumor burden and chemosensitivity in an in vivo preclinical model of ovarian cancer. Restoration of miR-200c in an intraperitoneal xenograft model of human ovarian cancer results in decreased tumor formation and tumor burden. Furthermore, even in established tumors, restoration of miR-200c, alone or in combination with paclitaxel, results in significantly decreased tumor burden. Our study suggests that restoration of miR-200c immediately before cytotoxic chemotherapy may allow for a better response or lower effective dose. Mol Cancer Ther; 11(12); 2556–65. ©2012 AACR.
STAT3-RANTES Autocrine Signaling Is Essential for Tamoxifen Resistance in Human Breast Cancer Cells
Authors: Yi Eun Hee , Lee Chang Seok , Lee Jin-Ku , Lee Young Ju , Shin Min Kyung , Cho Chung-Hyun , Kang Keon Wook , Lee Jung Weon , Han Wonshik , Noh Dong-Young , Kim Yong-Nyun , Cho Ik-Hyun , Ye Sang-kyu 
Published: October 2012

Abstract
The acquisition of tamoxifen resistance is a major therapeutic problem in breast cancer. We developed a tamoxifen-resistant MCF-7 (TRM-7) cell line to elucidate the molecular mechanisms and factors associated with acquisition of such resistance. We showed that phosphorylation of STAT3 at tyrosine 705 (Y705) and RANTES expression are increased in response to tamoxifen in human breast cancer cells. On the basis of these results, we hypothesize that upregulated STAT3 phosphorylation and RANTES may be correlated with the development of drug resistance. Here, we showed that STAT3 and RANTES contribute to the maintenance of drug resistance. STAT3 phosphorylation is constitutively retained via a RANTES autocrine loop, which in turn upregulates anti-apoptotic signals in TRM-7 cells. STAT3–RANTES autocrine signaling affected expression of anti-apoptotic BCL-2 family genes and prevented TRM-7 cells from undergoing programmed cell death by inhibiting PARP and caspase-9 cleavage. Subsequently, blockade of STAT3 and RANTES in TRM-7 cells resulted in reduction of anti-apoptotic signals, which was rescued by exogenous RANTES treatment; drug resistance was also restored. Taken together, our results suggested that STAT3–RANTES autocrine signaling is essential for maintenance of drug resistance and inhibition of programmed cell death. These mechanisms of STAT3–RANTES autocrine signaling suggest a novel strategy for management of patients with tamoxifen-resistant tumors. Mol Cancer Res; 11(1); 31–42. ©2012 AACR.
Mapping and Ablation of the Pulmonary Veins and Cavo-Tricuspid Isthmus With a Magnetic Resonance Imaging–Compatible Externally Irrigated Ablation Catheter and Integrated Electrophysiology System
Authors: Ganesan Anand N. , Selvanayagam Joseph B. , Mahajan Rajiv , Grover Suchi , Nayyar Sachin , Brooks Anthony G. , Finnie John , Sunnarborg Daniel , Lloyd Thomas , Chakrabarty Adhiraj , Abed Hany S. , Sanders Prashanthan 
Published: October 2012

Background—
Magnetic resonance imaging (MRI)–guided interventional electrophysiology (EP) has rapidly emerged as a promising alternative to x-ray–guided ablation. We aimed to evaluate an externally irrigated MRI-compatible ablation catheter and integrated EP pacing and recording system, testing the feasibility of pulmonary vein and cavo-tricuspid isthmus ablation.

Methods and Results—
Externally irrigated MRI-compatible ablation and diagnostic EP catheters and an integrated EP recording system (Imricor Medical Systems, Burnsville, MN) were tested in n=11 sheep in a 1.5-T MRI scanner. Power-controlled (40 W, 120-second duration) lesions were formed at the pulmonary vein and cavo-tricuspid isthmus. Real-time intracardiac electrograms were recorded during MRI. Steady-state free precession non–breath-hold images were repeatedly acquired to guide catheter navigation. Lesion visualization was performed using noncontrast (T2-weighted turbo spin echo pulse sequence) and gadolinium-diethylene triamine pentaacetic acid–enhanced T1-weighted imaging (inversion-recovery gradient echo pulse sequence). Catheters were able to be visualized and navigated under cardiovascular magnetic resonance guidance. In total, 8±2.5 lesions (radiofrequency time, 16±4.2 minutes) were formed at the pulmonary vein ostia, and 6.5±1.3 lesions (radiofrequency time, 13±2.2 minutes) were formed at the cavo-tricuspid isthmus, with the end point of bidirectional block. The mean procedure time was 150±55 minutes. Lesion visualization with both T2W imaging and contrast-enhanced imaging correlated with sites of injury at autopsy.

Conclusions—
These data demonstrate the feasibility of using multiple catheters, an integrated EP pacing and recording system, and externally irrigated ablation with cardiovascular magnetic resonance guidance to undertake clinically relevant biatrial mapping and ablation.
Cardiac Magnetic Resonance T2 Mapping in the Monitoring and Follow-up of Acute Cardiac Transplant Rejection
Authors: Usman Asad A. , Taimen Kirsi , Wasielewski Marie , McDonald Jennifer , Shah Saurabh , Giri Shivraman , Cotts William , McGee Edwin , Gordon Robert , Collins Jeremy D. , Markl Michael , Carr James C. 
Published: October 2012

Background—
Acute rejection is a major factor impacting survival in the first 12 months after cardiac transplantation. Transplant monitoring requires invasive techniques. Cardiac magnetic resonance (CMR), noninvasive testing, has been used in monitoring heart transplants. Prolonged T2 relaxation has been related to transplant edema and possibly rejection. We hypothesize that prolonged T2 reflects transplant rejection and that quantitative T2 mapping will concur with the pathological and clinical findings of acute rejection.

Methods and Results—

Patients were recruited within the first year after transplantation. Biopsies were graded according to the International Society for Heart Lung Transplant system for cellular rejection with immunohistochemistry for humoral rejection. Rejection was also considered if patients presented with signs and symptoms of hemodynamic compromise without biopsy evidence of rejection who subsequently improved with treatment. Patients underwent a novel single-shot T2-prepared steady-state free precession 4-chamber and 3 short axis sequences and regions of interest were drawn overlying T2 maps by 2 independent blinded reviewers. A total of 74 (68 analyzable) CMRs T2 maps in 53 patients were performed. There were 4 cellular, 2 humoral, and 2 hemodynamic rejection cases. The average T2 relaxation time for grade 0R (n=46) and grade 1R (n=17) was 52.5±2.2 and 53.1±3.3 ms (mean±SD), respectively. The average T2 relaxation for grade 2R (n=3) was 59.6±3.1 ms and 3R (n=1) was 60.3 ms (all
P
value <0.05 compared with controls). The T2 average in humoral rejection cases (n=2) was 59.2±3.3 ms and the hemodynamic rejection (n=2) was 61.1±1.8 ms (
P
<0.05 versus controls). The average T2 relaxation time for all-cause rejection versus no rejection is 60.1±2.1 versus 52.8±2.7 ms (
P
<0.05). All rejection cases were rescanned 2.5 months after treatment and demonstrated T2 normalization with average of 51.4±1.6 ms. No difference was found in ventricular function between nonrejection and rejection patients, except in ventricular mass 107.8±10.3 versus 127.5±10.4 g (
P
< 0.05).

Conclusions—
Quantitative T2 mapping offers a novel noninvasive tool for transplant monitoring, and these initial findings suggest potential use in characterizing rejections. Given the limited numbers, a larger multi-institution study may help elucidate the benefits of T2 mapping as an adjunctive tool in routine monitoring of cardiac transplants.
Important Differences in Mode of Death Between Men and Women With Heart Failure Who Would Qualify for a Primary Prevention Implantable Cardioverter-Defibrillator
Authors: Rho Robert W. , Patton Kristen K. , Poole Jeanne E. , Cleland John G. , Shadman Ramin , Anand Inder , Maggioni Aldo Pietro , Carson Peter E. , Swedberg Karl , Levy Wayne C. 
Published: October 2012

Background—
Whether sex differences in implantable cardioverter-defibrillator (ICD) benefit exist remains unanswered. We evaluated sex differences in mode of death among a large cohort of ambulatory heart failure patients who meet criteria for a primary prevention ICD.

Methods and Results—

Patients from 5 trials or registries were included if they met American College of Cardiology/American Heart Association/Heart Rhythm Society guideline criteria for implantation of a primary prevention ICD. We investigated the potential sex differences in total deaths and total deaths by mode of death. The relationship between the estimated total mortality and mode of death by percentage of total mortality was also analyzed by sex. The Seattle Heart Failure Model was used to estimate total mortality in this analysis. A total of 8337 patients (1685 [20%] women) met inclusion criteria. One-year mortality was 10.8±0.3%. In women, the age-adjusted all-cause mortality was 24% lower (hazard ratio [HR], 0.76; confidence interval [CI], 0.68–0.85;
P
<0.0001), the risk of sudden death was 32% lower (HR, 0.68; CI, 0.58–0.68;
P
<0.0001), but no significant difference in pump failure death was observed. Throughout a range of total mortality risk, women had a 20% lower all-cause mortality (HR, 0.80; CI, 0.71–0.89;
P
<0.001) and 30% fewer deaths that were sudden (HR, 0.70; CI, 0.59–0.82;
P
<0.0001) compared with men.

Conclusions—
Women with heart failure have a lower mortality than men, and fewer of those deaths are sudden throughout a spectrum of all-cause mortality risk. These data provide a plausible reason for and thus support the possibility that sex differences in ICD benefit may exist.
Efficacy and Safety of the Novel Oral Anticoagulants in Atrial Fibrillation
Authors: Dentali Francesco , Riva Nicoletta , Crowther Mark , Turpie Alexander G.G. , Lip Gregory Y.H. , Ageno Walter 
Published: October 2012

Background—
Novel oral anticoagulants (NOACs) have been proposed as alternatives to vitamin K antagonists for the prevention of stroke and systemic embolism in patients with atrial fibrillation. Individually, NOACs were at least noninferior to vitamin K antagonists, but a clear superiority in overall and vascular mortality was not consistently proven.

Methods and Results—

We performed a meta-analysis of phase II and phase III randomized, controlled trials comparing NOACs with vitamin K antagonists in patients with atrial fibrillation. The MEDLINE and EMBASE databases, supplemented with conference abstract books and
www.clinicaltrials.gov
, were searched up to the first week of July 2012 with no language restriction. Two reviewers performed independent article review and study quality assessment. Data on overall and cardiovascular mortality, stroke or systemic embolism, ischemic stroke, major and intracranial bleeding, and myocardial infarction were collected. NOACs were pooled to perform a comparison with vitamin K antagonists, calculating pooled relative risks (RRs) and associated 95% confidence intervals (CIs). We retrieved 12 studies (3 administering dabigatran, 4 administering rivaroxaban, 2 administering apixaban, and 3 administering edoxaban) enrolling a total of 54 875 patients. NOACs significantly reduced total mortality (5.61% versus 6.02%; RR, 0.89; 95% CI, 0.83–0.96), cardiovascular mortality (3.45% versus 3.65%; RR, 0.89; 95% CI, 0.82–0.98), and stroke/systemic embolism (2.40% versus 3.13%; RR, 0.77; 95% CI, 0.70–0.86). There was a trend toward reduced major bleeding (RR, 0.86; 95% CI, 0.72–1.02) with a significant reduction of intracranial hemorrhage (RR, 0.46; 95% CI, 0.39–0.56). No difference in myocardial infarction was observed.

Conclusions—
NOACs are associated with an overall clinical benefit compared with vitamin K antagonists. Additional research is required to confirm these findings outside the context of randomized trials.
Tropical rock coasts
Authors: Moses Cherith A. 
Published: October 2012

Rock coasts are widespread in the tropics and exhibit particular morphologies that may be specific to their tropical, micro-tidal location. Notches are particularly well developed, often linked to onshore cliffs and fronted by subhorizontal platforms. Through a review of previously published data across the tropics, average cliff face erosion rates are calculated as 2.15 ± 2.62 mm a−1, intertidal erosion rates 3.03 ± 7.50 mm a−1 and subtidal erosion rates 0.96 ± 0.44 mm a−1. Intertidal erosion rates are variable within and across latitudinal ranges: within 10°N and S of the equator average rates are 1.42 ± 1.22 mm a−1; between latitudes of 10°and 20°, 0.88 ± 1.16 mm a−1 and between latitudes of 20°and 30°, 2.04 ± 2.57 mm a−1. A consideration of temporal variations in intertidal erosion rates provides insights into the potential impacts of climate change on the erosion dynamics of rock coasts in the tropics. This paper highlights some of the interactions over time and space between process and measurement that continue to limit our understanding of, and ability to model, the erosion dynamics of tropical rock coasts. It concludes by identifying potentially fruitful areas for future research.
Effect of feed and roller contact start point on strain and residual stress distribution in dome forming of steel tube by spinning at an elevated temperature
Authors: Zoghi Hamed , Fallahi Arezoodar Alireza , Sayeaftabi Mojtaba 
Published: October 2012

Tube spinning, without mandrel, is a common process used for manufacturing pressure vessels, e.g. CNG (Compressed Natural Gas) capsules for automotive industry and fire extinguishers. The process is carried out at an elevated temperature for forming a dome on thick wall steel tube ends. Two of the most important control parameters in the process are the “roller contact start point” (RCSP) and spinning feed (pitch), both of them highly affecting the process time and deformation behavior of the tubes and therefore success and quality of the product. In this article, using a three-dimensional dynamic explicit finite element model, the effects of these parameters are investigated on circumferential, axial and radial (thickness) strains of the formed tube in three thickness layers of the tube wall. The model is also verified by experiment. While circumferential strain is shown to be independent of the feed, axial and thickness strains are highly affected by both the feed and roller contact start point. It is shown that when the roller contact start point distance from the free end of the tube increases, there is a risk of indentation instead of normal bending behavior. It is also shown that axial strain has an inverse relation with feed, i.e. decreasing the feed results in further elongation of the tube. On the other hand, thickness strain increases by increasing the feed, so bigger thicknesses are expected in domes manufactured by higher feeds. In addition, it is shown that increasing the feed results in a decrease of the equivalent strain. The amount of residual stress (regardless of the temperature change) increases with increasing feed and its distribution is more uniform for higher distances of the contact start point from the free end.
Real-Life Outcomes of Maraviroc-Based Regimens in HIV-1-Infected Individuals
Authors: Babiker Zahir Osman Eltahir , Douthwaite Sam Thomas , Collier Lucy Elizabeth , Pennell Ashley , Uriel Alison J. , Wilkins Edmund 
Published: October 2012

Purpose: The use of maraviroc in our unit was reviewed with regard to efficacy and safety and also reviewed with regard to how our experience reflects the data presented in clinical trials. Methods: We utilized the pharmacy dispensary system to identify any patient dispensed maraviroc and conducted a case note review. Results: We identified 27 patients who have been prescribed maraviroc as part of their antiretroviral treatment. In all, 81% were men and 81% were white British. There were 26 treatment-experienced patients and 1 treatment-naive patient. At the time of switching to maraviroc, 17 patients had detectable HIV viral loads and 10 had HIV RNA levels <40 copies/mL. At completion, 6 undetectable patients maintained undetectability and 10 viremically detectable patients achieved viral suppression. Maraviroc was discontinued in 18.5% of patients and the only adverse drug reaction reported was a rash. Conclusions: The experience of using maraviroc by our study participants shows similarity in terms of efficacy and safety to the MERIT and MOTIVATE clinical trials.