bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutralization of Prolactin Receptor Function by Monoclonal Antibody LFA102, a Novel Potential Therapeutic for the Treatment of Breast Cancer
Authors: Damiano Jason S. , Rendahl Katherine G. , Karim Christopher , Embry Millicent G. , Ghoddusi Majid , Holash Jocelyn , Fanidi Abdallah , Abrams Tinya J. , Abraham Judith A. 
Published: December 2012

Abstract
Numerous lines of evidence suggest that the polypeptide hormone prolactin (PRL) may contribute to breast and prostate tumorigenesis through its interactions with the prolactin receptor (PRLR). Here, we describe the biologic properties of LFA102, a humanized neutralizing monoclonal antibody directed against the extracellular domain of PRLR. This antibody was found to effectively antagonize PRL-induced signaling in breast cancer cells in vitro and in vivo and to block PRL-induced proliferation in numerous cell line models, including examples of autocrine/paracrine PRL activity. A single administration of LFA102 resulted in regression of PRL-dependent Nb2-11 tumor xenografts and significantly prolonged time to progression. Finally, LFA102 treatment significantly inhibited PRLR signaling as well as tumor growth in a carcinogen-induced, estrogen receptor-positive rat mammary cancer model as a monotherapy and enhanced the efficacy of the aromatase inhibitor letrozole when administered in combination. The biologic properties of LFA102, elucidated by the preclinical studies presented here, suggest that this antibody has the potential to be a first-in-class, effective therapeutic for the treatment of PRL-dependent cancers. Mol Cancer Ther; 12(3); 295–305. ©2012 AACR.
Cardiac-Specific Overexpression of Melanoma Differentiation–Associated Gene-5 Protects Mice From Lethal Viral Myocarditis
Authors: Philip Joseph , Xu Zhaohui , Bowles Neil E. , Vallejo Jesus G. 
Published: December 2012

Background—

Viral myocarditis is among the most common causes of heart failure in children and young adults. The RNA helicase melanoma differentiation–associated gene-5 (MDA5) is critical for host antiviral responses against members of the
Picornaviridae
family, such as encephalomyocarditis virus (EMCV). MDA5-knockout mice are highly susceptible to EMCV infection and develop significant myocardial injury and left ventricular dysfunction. However, the mechanisms by which MDA5 signaling within cardiac myocytes contributes to the host response against viral infection have not been defined.

Methods and Results—
We generated cardiac-specific MDA5 transgenic (alpha-myosin heavy chain [αMHC]-MDA5) mice. These mice showed increased baseline cardiac expression of antiviral cytokines and increased cellular infiltration but no alterations in cardiac function and structure. αMHC-MDA5 mice were less susceptible to EMCV infection and had a significantly lower cardiac viral load compared with littermate control mice. The severity of myocarditis, prevalence of cardiac myocyte apoptosis, and cleavage of caspase 3 after EMCV infection were attenuated in αMHC-MDA5 mice. Furthermore, αMHC-MDA5 mice were protected against EMCV-induced myocardial dysfunction.

Conclusions—
Our data suggest that myocardial MDA5 may be a key molecule in protecting the heart from direct viral injury and myocardial dysfunction.
AAV9.I-1c Delivered via Direct Coronary Infusion in a Porcine Model of Heart Failure Improves Contractility and Mitigates Adverse Remodeling
Authors: Fish Kenneth M. , Ladage Dennis , Kawase Yoshiaki , Karakikes Ioannis , Jeong Dongtak , Ly Hung , Ishikawa Kiyotake , Hadri Lahouaria , Tilemann Lisa , Muller-Ehmsen Jochen , Samulski R. Jude , Kranias Evangelia G. , Hajjar Roger J. 
Published: December 2012

Background—

Heart failure is characterized by impaired function and disturbed Ca
2+
homeostasis. Transgenic increases in inhibitor-1 activity have been shown to improve Ca
2
cycling and preserve cardiac performance in the failing heart. The aim of this study was to evaluate the effect of activating the inhibitor (I-1c) of protein phosphatase 1 (I-1) through gene transfer on cardiac function in a porcine model of heart failure induced by myocardial infarction.

Methods and Results—

Myocardial infarction was created by a percutaneous, permanent left anterior descending artery occlusion in Yorkshire Landrace swine (n=16). One month after myocardial infarction, pigs underwent intracoronary delivery of either recombinant adeno-associated virus type 9 carrying I-1c (n=8) or saline (n=6) as control. One month after myocardial infarction was created, animals exhibited severe heart failure demonstrated by decreased ejection fraction (46.4±7.0% versus sham 69.7±8.5%) and impaired (d
P
/d
t
)
max
and (d
P
/d
t
)
min
. Intracoronary injection of AAV9.I-1c prevented further deterioration of cardiac function and led to a decrease in scar size.

Conclusions—
In this preclinical model of heart failure, overexpression of I-1c by intracoronary in vivo gene transfer preserved cardiac function and reduced the scar size.
Predictors of New-Onset Heart Failure
Authors: Ho Jennifer E. , Lyass Asya , Lee Douglas S. , Vasan Ramachandran S. , Kannel William B. , Larson Martin G. , Levy Daniel 
Published: December 2012

Background—
About one half of patients with heart failure (HF) have preserved ejection fraction (HFPEF) rather than reduced ejection fraction (HFREF). The differences in risk factors predisposing to the 2 subtypes of HF are poorly understood. We sought to identify clinical predictors of new-onset HF and to explore differences in HFPEF versus HFREF.

Methods and Results—

We studied new-onset HF cases between 1981 and 2008 in Framingham Heart Study participants, classified into HFPEF and HFREF (ejection fraction >45% versus ≤45%). We used Cox multivariable regression to examine predictors of 8-year risk of incident HF and competing-risks analysis to identify predictors that differed between HFPEF and HFREF. Among 6340 participants (60±12 years) with 97 808 person-years of follow-up, 512 developed incident HF. Of 457 participants with left ventricular ejection fraction evaluation at the time of HF diagnosis, 196 (43%) were classified as HFPEF and 261 (56%) as HFREF. Fourteen predictors of overall HF were identified. Older age, diabetes mellitus, and a history of valvular disease predicted both types of HF (
P
≤0.0025 for all). Higher body mass index, smoking, and atrial fibrillation predicted HFPEF only, whereas male sex, higher total cholesterol, higher heart rate, hypertension, cardiovascular disease, left ventricular hypertrophy, and left bundle-branch block predicted risk of HFREF.

Conclusions—
Although multiple risk factors preceded overall HF, distinct clusters of risk factors determine risk for new-onset HFPEF versus HFREF. This knowledge may enable the design of clinical trials of targeted prevention and the introduction of therapeutic strategies for prevention of HF and its 2 major subtypes.
Concomitant Use of Antiplatelet Therapy with Dabigatran or Warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) Trial
Authors: Dans Antonio L. , Connolly Stuart J. , Wallentin Lars , Yang Sean , Nakamya Juliet , Brueckmann Martina , Ezekowitz Michael , Oldgren Jonas , Eikelboom John W. , Reilly Paul A. , Yusuf Salim 
Published: December 2012

Background—
The Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial showed that dabigatran etexilate 150 mg BID was superior and dabigatran etexilate 110 mg BID was noninferior to warfarin in preventing stroke and systemic embolism in patients with atrial fibrillation. In this subgroup analysis, we assess the efficacy and safety of dabigatran in patients who did and did not receive concomitant antiplatelets.

Methods and Results—

All comparisons used a Cox proportional hazards model with adjustments made for risk factors for bleeding. A time-dependent analysis was performed when comparing patients with concomitant antiplatelets with those without. Of 18 113 patients, 6952 (38.4%) received concomitant aspirin or clopidogrel at some time during the study. Dabigatran etexilate 110 mg BID was noninferior to warfarin in reducing stroke and systemic embolism, whether patients received antiplatelets (hazard ratio [HR], 0.93; 95% confidence interval [95% CI], 0.70–1.25) or not (HR, 0.87; 95% CI, 0.66–1.15; interaction
P
=0.738). There were fewer major bleeds than warfarin in both subgroups (HR, 0.82; 95% CI, 0.67–1.00 for patients who used antiplatelets; HR, 0.79; 95% CI, 0.64–0.96 for patients who did not; interaction
P
=0.794). Dabigatran etexilate 150 mg BID reduced the primary outcome of stroke and systemic embolism in comparison with warfarin. This effect seemed attenuated among patients who used antiplatelets (HR, 0.80; 95% CI, 0.59–1.08) in comparison with those who did not (HR, 0.52; 95% CI, 0.38–0.72;
P
for interaction=0.058). Major bleeding was similar to warfarin regardless of antiplatelet use (HR, 0.93; 95% CI, 0.76–1.12 for patients who used antiplatelets; HR, 0.94; 95% CI, 0.78–1.15 for patients who did not;
P
for interaction=0.875). In the time-dependent analysis, concomitant use of a single antiplatelet seemed to increase the risk of major bleeding (HR, 1.60; 95% CI, 1.42–1.82). Dual antiplatelet seemed to increased this even more (HR, 2.31; 95% CI, 1.79–2.98). The absolute risks were lowest on dabigatran etexilate 110 mg BID in comparison with dabigatran etexilate 150 mg BID or warfarin.

Conclusions—
Concomitant antiplatelet drugs appeared to increase the risk for major bleeding in RE-LY without affecting the advantages of dabigatran over warfarin. Choosing between dabigatran etexilate 110 mg BID and dabigatran etexilate 150 mg BID requires a careful assessment of characteristics that influence the balance between benefit and harm.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00262600.
Eyes-On Training and Radiological Expertise
Authors: Beck Melissa R. , Martin Benjamin A. , Smitherman Emily , Gaschen Lorrie 
Published: December 2012

Objective: Our aim was to examine the specificity of the effects of acquiring expertise on visual working memory (VWM) and the degree to which higher levels of experience within the domain of expertise are associated with more efficient use of VWM. Background: Previous research is inconsistent on whether expertise effects are specific to the area of expertise or generalize to other tasks that also involve the same cognitive processes. It is also unclear whether more training and/or experience will lead to continued improvement on domain-relevant tasks or whether a plateau could be reached. Method: In Experiment 1, veterinary medicine students completed a one-shot visual change detection task. In Experiment 2, veterinarians completed a flicker change detection task. Both experiments involved stimuli specific to the domain of radiology and general stimuli. Results: In Experiment 1, veterinary medicine students who had completed an “eyes-on” radiological training demonstrated a domain-specific effect in which performance was better on the domain-specific stimuli than on the domain-general stimuli. In Experiment 2, veterinarians again showed a domain-specific effect, but performance was unrelated to the amount of experience veterinarians had accumulated. Conclusion: The effect of experience is domain specific and occurs during the first few years of training, after which a plateau is reached. Application: VWM training in one domain may not lead to improved performance on other VWM tasks. In acquiring expertise, eyes-on training is important initially, but continued experience may not be associated with further improvements in the efficiency of VWM.
IABP before cardiac surgery: clinical benefit compared to intraoperative implantation
Authors: Böning A , Buschbeck S , Roth P , Scheibelhut C , Bödeker RH , Brück M , Niemann B 
Published: December 2012

Background: The aim of this study was to determine whether preoperative compared to intraoperative intra-aortic balloon counterpulsation (IABP) is advantageous regarding 30-day and 2-year survival in high-risk patients (acute myocardial infarction, severely impaired left ventricular ejection fraction (LVEF), low output syndrome) undergoing coronary surgery. Methods: In the years 2004 to 2008, 156 consecutive patients undergoing coronary surgery with IABP support (119 preoperative, 37 intraoperative IABP) were observed. Applying Fisher’s exact test, as well as Wilcoxon and median tests, possible group differences were evaluated. After univariate analysis, models of logistic regression and Cox-regression were built. Results: Preoperative hemodynamic state and risk profile of the two patient groups were comparable: patients with preoperative IABP showed a similar level of urgency (21.9% vs. 18.9% emergencies), cardiogenic shock (8.4% vs. 10.8%), inotropes (8.4% vs. 8.1%), impaired LVEF (30.3% vs. 29.7%) and ventilation (5.9% vs. 5.4%) compared to patients with intraoperative IABP. Nevertheless, patients with intraoperative IABP demonstrated a significantly higher 30-day mortality rate (37.8% vs. 5.9%) and 2-year mortality rate (54.0% vs. 18.1%) compared to patients with preoperative IABP. Logistic regression revealed that patients with intraoperative IABP have a 16-times higher 30-day mortality rate after coronary surgery (OR: 16.386, 95% CI: 4.858-55.266) than patients with preoperative IABP. Two-year mortality (OR: 9.317, 95% CI: 3.430 to 25.311) and survival time were significantly better in patients with preoperative IABP therapy. Conclusion: Considering the significant benefit for patients with preoperative compared to intraoperative IABP and the absence of vascular problems after IABP insertion, the results of this study indicate a more liberal indication for IABP in high-risk patients before coronary bypass surgery.
Validation of the Instability Shoulder Index Score in a Multicenter Reliability Study in 114 Consecutive Cases
Authors: Rouleau Dominique M. , Hébert-Davies Jonah , Djahangiri Ali , Godbout Véronique , Pelet Stéphane , Balg Frédéric 
Published: December 2012

Background: Anterior shoulder stabilization surgery with the arthroscopic Bankart procedure can have a high recurrence rate in certain patients. Identifying these patients to modify outcomes has become a focal point of research. Purpose: The Instability Shoulder Index Score (ISIS) was developed to predict the success of arthroscopic Bankart repair. Scores range from 0 to 10, with higher scores predicting a higher risk of recurrence after stabilization. The interobserver reliability of the score is not known. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: This is a prospective multicenter (North America and Europe) study of patients suffering from shoulder instability and waiting for stabilization surgery. Five pairs of independent evaluators were asked to score patient instability severity with the ISIS. Patients also completed functional scores (Western Ontario Shoulder Instability Index [WOSI], Disabilities of the Arm, Shoulder and Hand–short version [QuickDASH], and Walch-Duplay test). Data on age, sex, number of dislocations, and type of surgery were collected. The test-retest method and intraclass correlation coefficient (ICC: >0.75 = good, >0.85 = very good, and >0.9 = excellent) were used for analysis. Results: A total of 114 patients with anterior shoulder instability were included, of whom 89 (78%) were men. The mean age was 28 years. The ISIS was very reliable, with an ICC of 0.933. The mean number of dislocations per patient was higher in patients who had an ISIS of ≥6 (25 vs 14; P = .05). Patients who underwent more complex arthroscopic procedures such as Hill-Sachs remplissage or open Latarjet had higher preoperative ISIS outcomes, with a mean score of 4.8 versus 3.4, respectively ( P = .002). There was no correlation between the ISIS and the quality-of-life questionnaires, with Pearson correlations all >0.05 (WOSI = 0.39; QuickDASH = 0.97; Walch-Duplay = 0.08). Conclusion: Our results show that the ISIS is reliable when used in a multicenter study with anterior traumatic instability populations. There was no correlation between the ISIS and the quality-of-life questionnaires, but surgical decisions reflected its increased use.
Increased Hip and Knee Flexion During Landing Decreases Tibiofemoral Compressive Forces in Women Who Have Undergone Anterior Cruciate Ligament Reconstruction
Authors: Tsai Liang-Ching , Powers Christopher M. 
Published: December 2012

Background: Those who have undergone anterior cruciate ligament reconstruction (ACLR) have been shown to exhibit increased muscle co-contraction, decreased knee flexion, and elevated tibiofemoral compressive forces. Elevated tibiofemoral compressive forces may be associated with the high risk of developing knee osteoarthritis in this population. Purpose: To examine whether muscle co-contraction and tibiofemoral compressive forces in women after undergoing ACLR can be reduced through the use of a landing strategy that emphasizes greater hip and knee flexion. Study Design: Controlled laboratory study. Methods: Ten female recreational athletes who had previously undergone ACLR participated in this study. Participants performed a single-legged drop-land task before and after a training session that encouraged them to use greater hip and knee flexion during landing. Peak tibiofemoral compressive forces before and after training were estimated using an electromyography (EMG)–driven knee model that incorporated joint kinematics, EMG, and subject-specific muscle volumes and patellar tendon orientation estimated from magnetic resonance imaging. A co-contraction index (CCI) was calculated to quantify the level of co-contraction between knee flexor and extensor muscles. Results: After training, peak hip and knee flexion as well as hip and knee flexion excursions increased significantly. Additionally, participants demonstrated a significant decrease after training in the areas of muscle co-contraction (CCI [mean ± SD], 0.28 ± 0.10 vs 0.18 ± 0.05; P < .001) and peak tibiofemoral compressive force (97.3 ± 8.0 vs 91.3 ± 10.2 N·kg−1; P = .044). Conclusion: Increased muscle co-contraction as well as elevated tibiofemoral compressive loads observed in individuals following ACLR can be reduced by using a landing strategy that encourages greater hip and knee flexion. Clinical Relevance: The findings of the current study provide useful information for the growth of rehabilitation and/or intervention programs aimed to decrease knee joint loading to prevent or delay the development of knee osteoarthritis in those who have undergone ACLR.
Subsequent Infections in Survivors of Sepsis
Authors: Wang Tisha , Derhovanessian Ariss , De Cruz Sharon , Belperio John A. , Deng Jane C. , Hoo Guy Soo 
Published: December 2012

Purpose: Sepsis is a devastating condition with considerable mortality. The causes of long-term mortality are poorly understood. To test the hypothesis that patients with sepsis are more susceptible to recurrent infections and death due to infectious complications, we investigated the outcomes of patients who survived sepsis, with regard to the incidence of recurrent infections and mortality. Materials and Methods: A retrospective study of the patients admitted to the intensive care unit (ICU) for sepsis from 2001 to 2002 who achieved 30-day survival (sepsis survivors [SSs], N = 78) and a control group of patients admitted to the ICU for noninfectious conditions with a similar severity of illness (N = 50) was performed. The primary end point was the number of recurrent infections in the first year posthospitalization. Results: The SSs group had higher rates of infections following hospital discharge compared to controls. Using a multivariable model, having survived sepsis was the strongest predictor of the development of subsequent infections (rate ratio [RR]: 2.83, P= .0006), the need for rehospitalization for infection in the year after the initial hospitalization (RR: 3.78, P = .0009), and postdischarge mortality (hazard ratio = 3.61, P = .003). Conclusions: Critically ill patients who survive sepsis have an increased risk of recurrent infections in the year following their septic episode that is associated with increased mortality.
A Behavioral Task Predicts Conversion to Mild Cognitive Impairment and Alzheimer’s Disease
Authors: Zola Stuart M. , Manzanares C. M. , Clopton P. , Lah J. J. , Levey A. I. 
Published: December 2012

Background/Rationale : Currently, we cannot reliably differentiate individuals at risk of cognitive decline, for example, mild cognitive impairment (MCI), Alzheimer’s disease (AD), from those individuals who are not at risk. Methods : A total of 32 participants with MCI and 60 control (CON) participants were tested on an innovative, sensitive behavioral assay, the visual paired comparison (VPC) task using infrared eye tracking. The participants were followed for 3 years after testing. Results : Scores on the VPC task predicted, up to 3 years prior to a change in clinical diagnosis, those patients with MCI who would and who would not progress to AD and CON participants who would and would not progress to MCI. Conclusions : The present findings show that the VPC task can predict impending cognitive decline. To our knowledge, this is the first behavioral task that can identify CON participants who will develop MCI or patients with MCI who will develop AD within the next few years.
Kinetic and equilibrium studies of fluoride sorption onto surfactant-modified smectites
Authors: Gamoudi S. , Frini-Srasra N. , Srasra E. 
Published: December 2012

AbstractThe use of organoclays as adsorbents in the remediation of polluted water has been the subject of many recent studies. In the present work, a Tunisian smectite modified with two cationic surfactants was used as an adsorbent to examine the adsorption kinetics, isotherms and thermodynamic parameters of fluoride ions from aqueous solution. Various pH values, initial concentrations and temperatures have been tested. Two simplified kinetic models, first-order and pseudo-second-order, were used to predict the adsorption rate constants. It was found that the adsorption kinetics of fluoride onto modified smectites at different operating conditions can best be described by the pseudo-second-order model. Adsorption isotherms and equilibrium adsorption capacities were determined by the fitting of the experimental data to well known isotherm models including those of Langmuir and Freundlich. The results showed that the Langmuir model appears to fit the adsorption better than the Freundlich adsorption model for the adsorption of fluoride ions onto modified smectites. The equilibrium constants were used to calculate thermodynamic parameters, such as the change of free energy, enthalpy and entropy. Results of this study demonstrated the effectiveness and feasibility of organoclays for the removal of fluoride ions from aqueous solution.
Reaction of bentonites with pyrite concentrate after wetting and drying cycles at 80°C: relevance to radioactive waste (Radwaste) storage
Authors: Osacky M. , Šucha V. , Miglierini M. , Madejová J. 
Published: December 2012

AbstractThe mineral stability of two bentonites was studied in the presence of pyrite concentrate to simulate the possible reactions between the bentonite barrier used in a high-level nuclear waste (HLW) repository and host rock containing up to 5 wt.% of admixed pyrite. Smectite was the only bentonite mineral affected by pyrite treatment under the experimental conditions used. Bentonites reacted differently with pyrite due to the different nature of the smectites. The distinct crystal chemistry of the smectites controlled by the composition of the parent rocks influenced the smectite surface properties (cation exchange capacity and layer charge distribution) which resulted in a different response of the bentonites to pyrite treatment. A partial transformation of the original smectites into H-smectites represented the initial stage of smectite destabilization on acid attack. Rising non-equivalent isomorphous substitution in the octahedral sheets of the smectites enhanced smectite reactivity and thus the reaction between bentonite and pyrite, causing lower stability of the bentonite containing high-charge smectite.