bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adrenomedullin Blockade Suppresses Growth of Human Hormone–Independent Prostate Tumor Xenograft in Mice
Authors: Berenguer-Daizé Caroline , Boudouresque Françoise , Bastide Cyrille , Tounsi Asma , Benyahia Zohra , Acunzo Julie , Dussault Nadège , Delfino Christine , Baeza Nathalie , Daniel Laurent , Cayol Mylène , Rossi Dominique , El Battari Assou , Bertin Denis , Mabrouk Kamel , Martin Pierre-Marie , Ouafik L'Houcine 
Published: October 2013

Abstract
Purpose: To study the role of the adrenomedullin system [adrenomedullin and its receptors (AMR), CLR, RAMP2, and RAMP3] in prostate cancer androgen-independent growth.
Experimental Design: Androgen-dependent and -independent prostate cancer models were used to investigate the role and mechanisms of adrenomedullin in prostate cancer hormone-independent growth and tumor-associated angiogenesis and lymphangiogenesis.
Results: Adrenomedullin and AMR were immunohistochemically localized in the carcinomatous epithelial compartment of prostate cancer specimens of high grade (Gleason score &gt;7), suggesting a role of the adrenomedullin system in prostate cancer growth. We used the androgen-independent Du145 cells, for which we demonstrate that adrenomedullin stimulated cell proliferation in vitro through the cAMP/CRAF/MEK/ERK pathway. The proliferation of Du145 and PC3 cells is decreased by anti-adrenomedullin antibody (αAM), supporting the fact that adrenomedullin may function as a potent autocrine/paracrine growth factor for prostate cancer androgen-independent cells. In vivo, αAM therapy inhibits the growth of Du145 androgen-independent xenografts and interestingly of LNCaP androgen-dependent xenografts only in castrated animals, suggesting strongly that adrenomedullin might play an important role in tumor regrowth following androgen ablation. Histologic examination of αAM-treated tumors showed evidence of disruption of tumor vascularity, with depletion of vascular as well as lymphatic endothelial cells and pericytes, and increased lymphatic endothelial cell apoptosis. Importantly, αAM potently blocks tumor-associated lymphangiogenesis, but does not affect established vasculature and lymphatic vessels in normal adult mice.
Conclusions: We conclude that expression of adrenomedullin upon androgen ablation in prostate cancer plays an important role in hormone-independent tumor growth and in neovascularization by supplying/amplifying signals essential for pathologic neoangiogenesis and lymphangiogenesis. Clin Cancer Res; 19(22); 6138–50. ©2013 AACR.
The Impact of Different Absolute Solar Irradiance Values on Current Climate Model Simulations
Authors: Rind David H. , Lean Judith L. , Jonas Jeffrey 
Published: October 2013

Abstract
Simulations of the preindustrial and doubled CO2 climates are made with the GISS Global Climate Middle Atmosphere Model 3 using two different estimates of the absolute solar irradiance value: a higher value measured by solar radiometers in the 1990s and a lower value measured recently by the Solar Radiation and Climate Experiment. Each of the model simulations is adjusted to achieve global energy balance; without this adjustment the difference in irradiance produces a global temperature change of 0.4°C, comparable to the cooling estimated for the Maunder Minimum. The results indicate that by altering cloud cover the model properly compensates for the different absolute solar irradiance values on a global level when simulating both preindustrial and doubled CO2 climates. On a regional level, the preindustrial climate simulations and the patterns of change with doubled CO2 concentrations are again remarkably similar, but there are some differences. Using a higher absolute solar irradiance value and the requisite cloud cover affects the model’s depictions of high-latitude surface air temperature, sea level pressure, and stratospheric ozone, as well as tropical precipitation. In the climate change experiments it leads to an underestimation of North Atlantic warming, reduced precipitation in the tropical western Pacific, and smaller total ozone growth at high northern latitudes. Although significant, these differences are typically modest compared with the magnitude of the regional changes expected for doubled greenhouse gas concentrations. Nevertheless, the model simulations demonstrate that achieving the highest possible fidelity when simulating regional climate change requires that climate models use as input the most accurate (lower) solar irradiance value.
Pacific–North American Teleconnection Controls on Precipitation Isotopes (δ18O) across the Contiguous United States and Adjacent Regions: A GCM-Based Analysis
Authors: Liu Zhongfang , Yoshmura Kei , Bowen Gabriel J. , Welker Jeffrey M. 
Published: October 2013

Abstract
The Pacific–North American (PNA) teleconnection pattern has a strong influence on North America’s winter climate, but much less is known about how the PNA pattern controls precipitation isotopes (e.g., δ18O) across the United States. In this study, an isotopically equipped atmospheric general circulation model (isoGSM) is used to investigate how divergent phases of the PNA affect precipitation δ18O values across the United States. A simulation using observational climate and isotope data over the United States is evaluated first. The simulation explains 84% of the spatial variability of winter precipitation δ18O, with an overestimation in the northern Rocky Mountains and the Great Lakes. Temporally, the simulation explains 29%–81% of the interannual variability of winter precipitation δ18O, with typically a higher explained variance in the east than the west. The modeled winter precipitation δ18O exhibits a clear northwest–southeast (NW–SE) dipolelike pattern in response to shifts in the PNA pattern, with the center of positive polarity in the northwestern United States and the Canadian prairies and the center of negative polarity over the Ohio River valley. This dipolelike spatial pattern is a result of the difference in atmospheric circulation and moisture sources associated with the PNA pattern. These results highlight the importance of the PNA-associated circulation dynamics in governing precipitation isotope patterns across the United States. This understanding improves our ability to interpret paleoclimate records of water isotope/hydrologic change across the United States with a much greater appreciation of regional traits. The robust antiphase oscillation in precipitation isotopes in response to shifting the PNA pattern provides a promising opportunity to reconstruct the past variability in the PNA pattern that may be recorded in ice cores, tree rings, lake sediments, and speleothems.
Intercondylar Roof Impingement After Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction in Patients With Knee Hyperextension
Authors: Matsubara Hirokazu , Okazaki Ken , Tashiro Yasutaka , Toyoda Kazutaka , Uemura Munenori , Hashizume Makoto , Iwamoto Yukihide 
Published: October 2013

Background: Although an anatomically placed graft in anterior cruciate ligament (ACL) reconstruction is reported to have a low risk of roof impingement, which may cause deterioration of the graft or an extension deficit, the incidence of roof impingement by these grafts has not been evaluated in hyperextensible knees. Purpose: To evaluate the incidence of roof impingement by the native ACL in hyperextensible knees and to examine the risk of roof impingement by anatomic placement of the ACL graft in hyperextensible knees. Study Design: Controlled laboratory study. Methods: Twelve patients were selected for a hyperextensible knee group (group A), defined as having hyperextension of the knee of greater than 10°. Twelve patients were recruited to a normal extension knee group (group B) with normal extension of the knee of less than 5° of hyperextension. Magnetic resonance imaging (MRI) scans of the knee positioned in 30° of flexion and full extension were acquired from all patients. The shape of the native ACL at full extension was compared between the groups. A 3-dimensional (3D) bone model was created from the acquired 2D MRI scans. A virtual anatomic double-bundle ACL reconstruction in each patient and a virtual anatomic single-bundle reconstruction in the patients in group A were performed using the 3D MRI bone models. The volume of the overlap between the graft and roof was calculated to evaluate graft impingement in each instance. Results: The MRI scans showed posterior bowing of the native ACL in the group A knees. The simulated double-bundle ACL reconstruction showed that the overlapped volume was significantly greater in patients in group A than in patients in group B ( P < .05). However, the overlap of the simulated single-bundle ACL reconstruction was significantly less than for the double-bundle ACL reconstruction ( P < .05). Conclusion: To reduce the risk of roof impingement by the graft, single-bundle ACL reconstruction with the graft placed at the center of the footprint might be the better method for patients with a hyperextensible knee than an anatomic double-bundle ACL reconstruction. Clinical Relevance: It is recommended that surgeons cautiously consider roof impingement after anatomic double-bundle ACL reconstruction in patients with a hyperextensible knee.
Digital prosumption labour on social media in the context of the capitalist regime of time
Authors: Fuchs Christian 
Published: October 2013

So-called social media such as Facebook, Twitter, YouTube, Weibo and LinkedIn are an expression of changing regimes of time in capitalist society. This paper discusses how corporate social media are related to the capitalist organization of time and the changes this organization is undergoing. It uses social theory for conceptualizing changes of society and its time regime and how these changes shape social media. These changes have been described with notions such as prosumption, consumption labour, play labour (playbour) and digital labour. The paper contextualizes digital labour on social media with the help of a model of society that distinguishes three subsystems (the economy, politics, culture) and three forms of power (economic, political, culture). In modern society, these systems are based on the logic of the accumulation of power and the acceleration of accumulation. The paper discusses the role of various dimensions of time in capitalism with the help of a model that is grounded in Karl Marx’s works. It points out the importance of the category of time for a labour theory of value and a digital labour theory of value. Social media are expressions of the changing time regimes that modern society has been undergoing, especially in relation to the blurring of leisure and labour time (play labour), production and consumption time (prosumption), new forms of absolute and relative surplus value production, the acceleration of consumption with the help of targeted online advertising and the creation of speculative, future-oriented forms of fictitious capital.
Dalfampridine improves walking speed, walking endurance, and community participation in veterans with multiple sclerosis: a longitudinal cohort study
Authors: Cameron Michelle H , Fitzpatrick Mary , Overs Shannon , Murchison Charles , Manning Jane , Whitham Ruth 
Published: October 2013

Background: In short-term trials, dalfampridine extended release (ER) improves walking in people with multiple sclerosis (MS). The tolerability and effects of dalfampridine-ER in clinical practice have not been reported. Objectives: The objective of this paper is to determine the clinical tolerability and effects of dalfampridine on walking and community participation. Methods: All patients at the Portland VA Medical Center prescribed dalfampridine-ER over one year completed the Timed 25-Foot Walk (T25FW), Multiple Sclerosis Walking Scale-12 (MSWS-12), Two-Minute Timed Walk (2MTW), and Community Integration Questionnaire (CIQ) at baseline and follow-up clinic visits. Ongoing use and measures over one year were analyzed. Results: A total of 39 patients (mean age 56.5 years, mean disease duration 19.5 years, 82% male, 38% relapsing–remitting MS, 62% progressive MS) were prescribed dalfampridine-ER. Twenty-four (62%) continued to take dalfampridine-ER. At initial follow-up, all measures improved significantly from baseline (T25FW: –2.7 s, p = 0.004; 2MTW: 41 feet (ft), p = 0.002; MSWS12: –11, p < 0.001; CIQ: 1.2, p = 0.003). At one year, walking endurance and self-perceived walking were still significantly improved (2MTW: 33 ft, p = 0.03; MSWS-12: 5.9, p = 0.007). Conclusions: Dalfampridine-ER was associated with short-term improvements in walking speed and community participation, and sustained improvements in walking endurance and self-perceived impact of MS on walking for one year. Our study supports the utility of this medication in late MS.
Role of IGF-1 pathway in lung fibroblast activation
Authors: Hung Chi F , Rohani Maryam G , Lee Sung-soon , Chen Peter , Schnapp Lynn M 
Published: October 2013

Abstract

Background
IGF-1 is elevated in pulmonary fibrosis and acute lung injury, where fibroblast activation is a prominent feature. We previously demonstrated that blockade of IGF pathway in murine model of lung fibrosis improved outcome and decreased fibrosis. We now expand that study to examine effects of IGF pathway on lung fibroblast behaviors that could contribute to fibrosis.

Methods
We first examined mice that express αSMA promoter upstream of GFP reporter treated with A12, a blocking antibody to IGF-1 receptor, after bleomycin induced lung injury. We then examined the effect of IGF-1 alone, or in combination with the pro-fibrotic cytokine TGFβ on expression of markers of myofibroblast activation in vitro, including αSMA, collagen α1, type 1, collagen α1, type III, and TGFβ expression.

Results
After bleomycin injury, we found decreased number of αSMA-GFP + cells in A12 treated mice, validated by αSMA immunofluorescent staining. We found that IGF-1, alone or in combination with TGF-β, did not affect αSMA RNA expression, promoter activity, or protein levels when fibroblasts were cultured on stiff substrate. IGF-1 stimulated Col1a1 and Col3a1 expression on stiff substrate. In contrast, IGF-1 treatment on soft substrate resulted in upregulation of αSMA gene and protein expression, as well as Col1a1 and Col3a1 transcripts. In conclusion, IGF-1 stimulates differentiation of fibroblasts into a myofibroblast phenotype in a soft matrix environment and has a modest effect on αSMA stress fiber organization in mouse lung fibroblasts.
Examination of categorical approach to symptom assessment: cross-validation of foulds’ Delusions-Symptoms-States Inventory with Korean non-patient and patient groups
Authors: Hwang Samuel Suk-Hyun , Kim Yeni , Chang Jae Seung , Yun Da Young , Kim Yong Sik , Jung Hee Yeon 
Published: October 2013

Abstract

Background
Foulds’ Delusions-Symptoms-State Inventory (DSSI) has been purported to be a reliable, systematic categorical measure to assess the patients with schizophrenia according to the degree of illness. However, further cross-validations using other clinical measures and diverse samples from other cultures have not been advanced recently. We aimed to examine the validity of the DSSI hierarchical class model using both Korean non-patient and patient (schizophrenia and depression) groups.

Method
The hypothesis of inclusive, non-reflexive relationships among the DSSI classes was tested. The power of DSSI to detect presence of symptoms was assessed via cross-validation with other clinical measures, and the differences between the clinical features among the DSSI classes were examined using the Minnesota Multiphasic Personality Inventory (MMPI).

Results
The high rate of model conformity (91.1%) across the samples and cross-validation with other criterion measures provided further support for the validity of DSSI.

Conclusions
DSSI is a reliable self-report measure that can be applied to both patient and non-patients to assess the presence and severity of psychiatric illness. Future studies that include more diverse clinical groups are necessary to lend further support for its utility in clinical practice.
Cost-effectiveness analysis of treatment with peginterferon-alfa-2a versus peginterferon-alfa-2b for patients with chronic hepatitis C under the public payer perspective in Brazil
Authors: Barros Fabio MR , Cheinquer Hugo , Tsuchiya Carolina T , Santos Eduardo AV 
Published: October 2013

Abstract

Background
Chronic hepatitis C affects approximately 170 million people worldwide, and thus being one of the main causes of chronic liver disease. About 20% of patients with chronic hepatitis C will develop cirrhosis over 20 years, and present an increased risk of developing hepatic complications. Sustained virological response (SVR) is associated with a better prognosis compared to untreated patients and treatment failures.
The objective of this analysis was to compare treatment costs and outcomes of pegylated interferon-alfa-2a versus pegylated interferon-alfa-2b, both associated with ribavirin, in the therapeutic scheme of 24 weeks and 48 week for hepatitis C genotypes 2/3 and genotype 1, respectively, under the Brazilian Public Health System (SUS) scenario.

Methods
To project disease progression, a Markov model was built based on clinical stages of chronic disease. A Delphi panel was conducted to evaluate medical resources related to each stage, followed by costing of related materials, services, procedures and pharmaceutical products. The evaluation was made from a public payer perspective. The source used for costing was government reimbursement procedures list (SAI/SIH–SUS). Drug acquisition costs were obtained from the Brazilian Official Gazette and “Banco de Preços em Saúde” (government official source). It was assumed a mean patient weight of 70 kg. Costs were reported in 2011 Brazilian Reais (US$1 ≈ $Brz1.80). A systematic review followed by a meta-analysis of the 7 identified randomized controlled trials (RCTs) which compared pegylated interferons, was conducted for obtaining relative efficacy of both drugs: for genotype 2/3, mean rate of SVR was 79.2% for peginterferon-alfa-2a and 73.8% for peginterferon-alfa-2b. For genotype 1, SVR mean rate was 42.09% versus 33.44% (peginterferon-alfa-2a and peginterferon-alfa-2b respectively). Time horizon considered was lifetime. Discount rate for costs and outcomes was 5%, according to Brazilian guidelines for Health Technology Assessment (HTA).

Results
Analysis showed that peginterferon-alfa-2a is a dominant therapy compared to peginterferon-alfa-2b for genotype 1 ($Brz 4,345 savings and 0.10 LY/0.25 QALY gains) as well for genotype 2/3 ($Brz 8,001 savings and 0.16 LY/0.39 QALY gains). Projections indicated that for each 1000 patients treated with peginterferon-alfa-2a instead of peginterferon-alfa-2b, the amount of resources saved would be of $Brz 4.3 million for genotypes 2/3 and up to $Brz 8 million for genotype 1.

Conclusion
These findings suggest that treatment with peginterferon-alfa-2a is more effective and less costly when compared to peginterferon-alfa-2b under SUS perspective in Brazil.
Multi-nutrient supplement improves hormone ratio associated with cancer risk
Authors: Bazzan Anthony J , Zabrecky George P , Newberg Andrew B 
Published: October 2013

Abstract

Background
Gynecological cancers are among the most common in women and are directly related to a variety of hormonal factors. One potential risk factor associated with developing a gynecological malignancy is the ratio of two hormone metabolites, 2-Hydroxyestrone (2-HE) and 16alpha-Hydroxyestrone (16alpha-HE). A number of botanical constituents such as indoles, flavonoids, and resveratrol have been shown to have a favorable effect on the metabolic pathways that affect this ratio. The present study was designed to evaluate if a multi-nutrient supplement containing targeted botanical constituents would affect the 2-HE/16 alpha-HE ratio in middle-aged women.

Methods
A retrospective analysis was performed on 76 female patients (mean age 54 years) who received 2-HE/16 alpha-HE ratio assessments at two separate time points. The ratio assessment was part of standard care for women who presented with risk indicators associated with a high proliferative state. All patients who completed pre and post assessments were included. Sixty-five of the patients received a multi-nutrient supplement, Lucentia Peak®, during the study period. Eleven patients chose not to take the supplement, but did receive ratio assessments at similar time points as the treatment group, allowing for between group comparisons. Paired t-tests were used to compare the changes in the 2-HE and 16alpha-HE measures as well as their ratio, both within groups and between groups.

Results
The results demonstrated a significant increase in the 2-HE/16alpha-HE ratio in the treated group (pre 0.38 to post 0.57, p<0.0001), and was significantly different (p=0.02) compared to the change in the control group (pre 0.65 to post 0.64). This change appears to be mediated primarily by an increase in the 2-HE level. Individually, 54 patients given Lucentia Peak® had increased ratios while 11 patients had a decrease. In the control group, 3 patients had an increase in their ratio and 8 patients had a decrease.

Conclusions
The results demonstrated that women receiving the Lucentia Peak® multi-nutrient supplement had significant increases in their 2-HE:16alpha-HE ratio, which appears to be mediated primarily by increasing the 2-HE levels. These results suggest further research on phytonutrients that might positively affect estrogen metabolism is warranted.
Antiviral activity of carnosic acid against respiratory syncytial virus
Authors: Shin Han-Bo , Choi Myung-Soo , Ryu Byeol , Lee Na-Rae , Kim Hye-In , Choi Hye-Eun , Chang Jun , Lee Kyung-Tae , Jang Dae Sik , Inn Kyung-Soo 
Published: October 2013

Abstract

Background
Human respiratory syncytial virus (hRSV) is a leading cause of severe lower respiratory infection and a major public health threat worldwide. To date, no vaccine or effective therapeutic agent has been developed. In a screen for potential therapeutic agents against hRSV, we discovered that an extract of Rosmarinus officinalis exerted a strong inhibitory effect against hRSV infection. Subsequent studies identified carnosic acid as a bioactive constituent responsible for anti-hRSV activity. Carnosic acid has been shown to exhibit potent antioxidant and anti-cancer activities. Anti-RSV activity of carnosic acid was further investigated in this study.

Methods
Effects of extracts from various plants and subfractions from R. officinalis on hRSV replication were determined by microneutralization assay and plaque assay. Several constituents were isolated from ethyl acetate fraction of R. officinalis and their anti-RSV activities were assessed by plaque assay as well as reverse-transcription quantitative PCR to determine the synthesis of viral RNAs.

Results
Among the tested bioactive constituents of R. officinalis, carnosic acid displayed the most potent anti-hRSV activity and was effective against both A- and B-type viruses. Carnosic acid efficiently suppressed the replication of hRSV in a concentration-dependent manner. Carnosic acid effectively suppressed viral gene expression without inducing type-I interferon production or affecting cell viability, suggesting that it may directly affect viral factors. A time course analysis showed that addition of carnosic acid 8 hours after infection still effectively blocked the expression of hRSV genes, further suggesting that carnosic acid directly inhibited the replication of hRSV.

Conclusions
The current study demonstrates that carnosic acid, a natural compound that has already been shown to be safe for human consumption, has anti-viral activity against hRSV, efficiently blocking the replication of this virus. Carnosic acid inhibited both A- and B- type hRSV, while it did not affect the replication of influenza A virus, suggesting that its antiviral activity is hRSV-specific. Collectively, this study suggests the need for further evaluation of carnosic acid as a potential treatment for hRSV.