bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher Frequencies of GARP+CTLA-4+Foxp3+ T Regulatory Cells and Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma Patients Are Associated with Impaired T-Cell Functionality
Authors: Kalathil Suresh , Lugade Amit A. , Miller Austin , Iyer Renuka , Thanavala Yasmin 
Published: February 2013

Abstract
The extent to which T-cell–mediated immune surveillance is impaired in human cancer remains a question of major importance, given its potential impact on the development of generalized treatments of advanced disease where the highest degree of heterogeneity exists. Here, we report the first global analysis of immune dysfunction in patients with advanced hepatocellular carcinoma (HCC). Using multi-parameter fluorescence-activated cell sorting analysis, we quantified the cumulative frequency of regulatory T cells (Treg), exhausted CD4+ helper T cells, and myeloid-derived suppressor cells (MDSC) to gain concurrent views on the overall level of immune dysfunction in these inoperable patients. We documented augmented numbers of Tregs, MDSC, PD-1+–exhausted T cells, and increased levels of immunosuppressive cytokines in patients with HCC, compared with normal controls, revealing a network of potential mechanisms of immune dysregulation in patients with HCC. In dampening T-cell–mediated antitumor immunity, we hypothesized that these processes may facilitate HCC progression and thwart the efficacy of immunotherapeutic interventions. In testing this hypothesis, we showed that combined regimens to deplete Tregs, MDSC, and PD-1+ T cells in patients with advanced HCC restored production of granzyme B by CD8+ T cells, reaching levels observed in normal controls and also modestly increased the number of IFN-γ producing CD4+ T cells. These clinical findings encourage efforts to restore T-cell function in patients with advanced stage disease by highlighting combined approaches to deplete endogenous suppressor cell populations that can also expand effector T-cell populations. Cancer Res; 73(8); 2435–44. ©2013 AACR.
Dynamics of Senescent Cell Formation and Retention Revealed by p14ARF Induction in the Epidermis
Authors: Tokarsky-Amiel Ronit , Azazmeh Narmen , Helman Aharon , Stein Yan , Hassan Alia , Maly Alexander , Ben-Porath Ittai 
Published: February 2013

Abstract
Cellular senescence, a state of cell-cycle arrest accompanied by dramatic morphologic and metabolic changes, is a central means by which cells respond to physiologic stress and oncogene activity. Senescence is thought to play important roles in aging and in tumor suppression, yet the dynamics by which senescent cells are formed, their effects on tissue function and their eventual fate are poorly understood. To study cellular senescence within an adult tissue, we developed transgenic mice inducibly expressing p14ARF (human ortholog of murine p19ARF), a central activator of senescence. Induction of p14ARF in the epidermis rapidly led to widespread apoptosis and cell-cycle arrest, a stage that was transient, and was followed by p53-dependent cellular senescence. The endogenous Cdkn2a products p19ARF and p16Ink4a were activated by the transgenic p14ARF through p53, revealing a senescence-promoting feed-forward loop. Commitment of cells to senescence required continued p14ARF expression, indicating that entry into this state depends on a persistent signal. However, once formed, senescent cells were retained in the epidermis, often for weeks after transgene silencing, indicating an absence of an efficient rapidly acting mechanism for their removal. Stem cells in the hair follicle bulge were largely protected from apoptosis upon p14ARF induction, but irreversibly lost their ability to proliferate and initiate follicle growth. Interestingly, induction of epidermal hyperplasia prevented the appearance of senescent cells upon p14ARF induction. Our findings provide basic insights into the dynamics of cellular senescence, a central tumor- suppressive mechanism, and reveal the potential for prolonged retention of senescent cells within tissues. Cancer Res; 73(9); 2829–39. ©2013 AACR.
Chemoprevention of Head and Neck Cancer by Simultaneous Blocking of Epidermal Growth Factor Receptor and Cyclooxygenase-2 Signaling Pathways: Preclinical and Clinical Studies
Authors: Shin Dong M. , Zhang Hongzheng , Saba Nabil F. , Chen Amy Y. , Nannapaneni Sreenivas , Amin A.R.M. Ruhul , Müller Susan , Lewis Melinda , Sica Gabriel , Kono Scott , Brandes Johann C. , Grist William J. , Moreno-Williams Rachel , Beitler Jonathan J. , Thomas Sufi M. , Chen Zhengjia , Shin Hyung Ju C. , Grandis Jennifer R. , Khuri Fadlo R. , Chen Zhuo Georgia 
Published: February 2013

Abstract
Purpose: We investigated the efficacy and underlying molecular mechanism of a novel chemopreventive strategy combining EGF receptor (EGFR) tyrosine kinase inhibitor (TKI) with cyclooxygenase-2 inhibitor (COX-2I).
Experimental Design: We examined the inhibition of tumor cell growth by combined EGFR-TKI (erlotinib) and COX-2I (celecoxib) treatment using head and neck cancer cell lines and a preventive xenograft model. We studied the antiangiogenic activity of these agents and examined the affected signaling pathways by immunoblotting analysis in tumor cell lysates and immunohistochemistry (IHC) and enzyme immunoassay (EIA) analyses on the mouse xenograft tissues and blood, respectively. Biomarkers in these signaling pathways were studied by IHC, EIA, and an antibody array analysis in samples collected from participants in a phase I chemoprevention trial of erlotinib and celecoxib.
Results: The combined treatment inhibited head and neck cancer cell growth significantly more potently than either single agent alone in cell line and xenograft models, and resulted in greater inhibition of cell-cycle progression at G1 phase than either single drug. The combined treatment modulated the EGFR and mTOR signaling pathways. A phase I chemoprevention trial of combined erlotinib and celecoxib revealed an overall pathologic response rate of 71% at time of data analysis. Analysis of tissue samples from participants consistently showed downregulation of EGFR, pERK, and pS6 levels after treatment, which correlated with clinical response.
Conclusion: Treatment with erlotinib combined with celecoxib offers an effective chemopreventive approach through inhibition of EGFR and mTOR pathways, which may serve as potential biomarkers to monitor the intervention of this combination in the clinic. Clin Cancer Res; 19(5); 1244–56. ©2013 AACR.
Caloric Restriction Reverses Obesity-Induced Mammary Gland Inflammation in Mice
Authors: Bhardwaj Priya , Du Baoheng , Zhou Xi Kathy , Sue Erika , Harbus Michael D. , Falcone Domenick J. , Giri Dilip , Hudis Clifford A. , Kopelovich Levy , Subbaramaiah Kotha , Dannenberg Andrew J. 
Published: February 2013

Abstract
Obesity is a risk factor for the development of hormone receptor–positive breast cancer in postmenopausal women. Estrogen synthesis is catalyzed by aromatase. Recently, we identified an obesity→inflammation→aromatase axis in mouse models and women. In mouse models of obesity, inflammatory foci characterized by crown-like structures (CLS) consisting of dead adipocytes encircled by macrophages were found in the mammary gland. CLS of the breast were found in most overweight and obese women. CLS were associated with adipocyte hypertrophy, activation of NF-κB, elevated levels of proinflammatory mediators and aromatase, and increased expression of the progesterone receptor (PR). Collectively, these findings provide a plausible explanation for the link between obesity, chronic inflammation, and postmenopausal breast cancer. Here, we investigated whether caloric restriction (CR) reversed the inflammatory state and related molecular changes in the mammary gland of obese mice. Obese ovariectomized C57BL/6J mice were subjected to 30% CR for 7 or 14 weeks. Findings in CR mice were compared with the results in mice fed a high-fat diet ad libitum or with control mice fed a low-fat diet. CR was associated with more than a 75% decrease in mammary CLS/cm2. Reduced histologic inflammation following CR was associated with decreased adipocyte diameter and monocyte chemoattractant protein-1 (MCP-1) levels, reduced NF-κB binding activity, and normalization of levels of proinflammatory mediators, aromatase, and PR. In summary, obesity-related inflammation of the mammary gland and elevated aromatase and PR levels were reversed with CR. Our results provide a rationale for determining whether weight loss can reverse breast inflammation associated with obesity in women. Cancer Prev Res; 6(4); 282–9. ©2013 AACR.
High-density Lipoprotein–based Therapy Reduces the Hemorrhagic Complications Associated With Tissue Plasminogen Activator Treatment in Experimental Stroke
Authors: Lapergue Bertrand , Dang Bao Quoc , Desilles Jean-Philippe , Ortiz-Munoz Guadalupe , Delbosc Sandrine , Loyau Stéphane , Louedec Liliane , Couraud Pierre-Olivier , Mazighi Mikael , Michel Jean-Baptiste , Meilhac Olivier , Amarenco Pierre 
Published: February 2013

Background and Purpose—
We have previously reported that intravenous injection of high-density lipoproteins (HDLs) was neuroprotective in an embolic stroke model. We hypothesized that HDL vasculoprotective actions on the blood–brain barrier (BBB) may decrease hemorrhagic transformation-associated with tissue plasminogen activator (tPA) administration in acute stroke.

Methods—
We used tPA alone or in combination with HDLs in vivo in 2 models of focal middle cerebral artery occlusion (MCAO) (embolic and 4-hour monofilament MCAO) and in vitro in a model of BBB. Sprague–Dawley rats were submitted to MCAO, n=12 per group. The rats were then randomly injected with tPA (10 mg/kg) or saline with or without human plasma purified-HDL (10 mg/kg). The therapeutic effects of HDL and BBB integrity were assessed blindly 24 hours later. The integrity of the BBB was also tested using an in vitro model of human cerebral endothelial cells under oxygen–glucose deprivation.

Results—

tPA-treated groups had significantly higher mortality and rate of hemorrhagic transformation at 24 hours in both MCAO models. Cotreatment with HDL significantly reduced stroke-induced mortality versus tPA alone (by 42% in filament MCAO,
P
=0.009; by 73% in embolic MCAO,
P
=0.05) and tPA-induced intracerebral parenchymal hematoma (by 92% in filament MCAO, by 100% in embolic MCAO;
P
<0.0001). This was consistent with an improved BBB integrity. In vitro, HDLs decreased oxygen–glucose deprivation–induced BBB permeability (
P
<0.05) and vascular endothelial cadherin disorganization.

Conclusions—
HDL injection decreased tPA-induced hemorrhagic transformation in rat models of MCAO. Both in vivo and in vitro results support the vasculoprotective action of HDLs on BBB under ischemic conditions.
‘Faithful Men of a Faithful God’? Masculinities in the Zimbabwe Assemblies of God Africa
Authors: Chitando Ezra ,   KudzaiBiri
Published: February 2013

Abstract
Many scholars have examined masculinities in African societies. However, these examinations cannot be generalised across Africa, given the socio-cultural, economic, political and historical factors that infringe with religious beliefs. This article offers a case study of masculinities in a specific religious context, the Zimbabwe Assemblies of God Africa (zaoga), a Pentecostal church. It utilises zaoga’s teachings on masculinities against the background of Shona religion and culture (the dominant ethnic group in Zimbabwe). The analysis specifically focuses on the role of the Jesus-figure in the discourse on masculinity in zaoga, exploring whether Jesus presents a model of ‘redemptive masculinity’ or rather reinforces hegemonic notions of masculinity. The article highlights the ambiguity of Pentecostal masculinity and offers an overall critique of the effects of masculinities upon Pentecostal faith and practice.
Reply to “Comments on ‘Searching for Information in 133 Years of California Snowfall Observations’”
Authors: Christy John R. 
Published: February 2013

Abstract
Coats raises issues regarding the utility of the snowfall metric presented by Christy in “Searching for information in 133 years of California snowfall observations,” suggesting that variance issues need more attention and that alternative metrics would be more useful than snowfall. Although discussed by Christy, the variance question is further addressed here. Regarding other metrics, it is shown that they are either inconsistently measured for long-term analysis or are actually consistent with Christy’s findings. In addition, it is demonstrated that Tahoe City, discussed by Coats, is inappropriate for examining long-term precipitation trends because of inconsistent measuring practices through time. Christy’s results remain unchanged.
Ground-Based Remote Retrievals of Cumulus Entrainment Rates
Authors: Wagner Timothy J. , Turner David D. , Berg Larry K. , Krueger Steven K. 
Published: February 2013

Abstract
While fractional entrainment rates for cumulus clouds have typically been derived from airborne observations, this limits the size and scope of available datasets. To increase the number of continental cumulus entrainment rate observations available for study, an algorithm for retrieving them from ground-based remote sensing observations has been developed. This algorithm, called the Entrainment Rate In Cumulus Algorithm (ERICA), uses the suite of instruments at the Southern Great Plains (SGP) site of the U.S. Department of Energy's Atmospheric Radiation Measurement Program (ARM) Climate Research Facility as inputs into a Gauss–Newton optimal estimation scheme, in which an assumed guess of the entrainment rate is iteratively adjusted through intercomparison of modeled cloud attributes to their observed counterparts. The forward model in this algorithm is the explicit mixing parcel model (EMPM), a cloud parcel model that treats entrainment as a series of discrete entrainment events. A quantified value for the uncertainty in the retrieved entrainment rate is also returned as part of the retrieval. Sensitivity testing and information content analysis demonstrate the robust nature of this method for retrieving accurate observations of the entrainment rate without the drawbacks of airborne sampling. Results from a test of ERICA on 3 months of shallow cumulus cloud events show significant variability of the entrainment rate of clouds in a single day and from one day to the next. The mean value of 1.06 km−1 for the entrainment rate in this dataset corresponds well with prior observations and simulations of the entrainment rate in cumulus clouds.
Improvement of Typhoon Precipitation Forecast Efficiency by Coupling SSM/I Microwave Data with Climatologic Characteristics and Precipitation
Authors: Wei Chih-Chiang 
Published: February 2013

Abstract
Prediction of flash floods in an accurate and timely fashion is one of the most important challenges in weather prediction. This study aims to address the rainfall prediction problem for quantitative precipitation forecasts over land during typhoons. To improve the efficiency of forecasting typhoon precipitation, this study develops Bayesian network (BN) and logistic regression (LR) models using three different datasets and examines their feasibility under different rain intensities. The study area is the watershed of the Tanshui River in Taiwan. The dataset includes a total of 70 typhoon events affecting the watershed from 1997 to 2008. For practicability, the three datasets used include climatologic characteristics of typhoons issued by the Central Weather Bureau (CWB), rainfall rates measured using automatic meteorological gauges in the watershed, and microwave data originated from Special Sensor Microwave Imager (SSM/I) radiometers. Five separate BN and LR models (cases), differentiated by a unique combination of input datasets, were tested, and their predicted rainfalls are compared in terms of skill scores including mean absolute error (MAE), RMSE, bias (BIA), equitable threat score (ETS), and precision (PRE). The results show that the case where all three input datasets are used is better than the other four cases. Moreover, LR can provide better predictions than BN, especially in flash rainfall situations. However, BN might be one of the most prominent approaches when considering the ease of knowledge interpretation. In contrast, LR describes associations, not causes, and does not explain the decision.
Examination of Errors in Near-Surface Temperature and Wind from WRF Numerical Simulations in Regions of Complex Terrain
Authors: Zhang Hailing , Pu Zhaoxia , Zhang Xuebo 
Published: February 2013

Abstract
The performance of an advanced research version of the Weather Research and Forecasting Model (WRF) in predicting near-surface atmospheric temperature and wind conditions under various terrain and weather regimes is examined. Verification of 2-m temperature and 10-m wind speed and direction against surface Mesonet observations is conducted. Three individual events under strong synoptic forcings (i.e., a frontal system, a low-level jet, and a persistent inversion) are first evaluated. It is found that the WRF model is able to reproduce these weather phenomena reasonably well. Forecasts of near-surface variables in flat terrain generally agree well with observations, but errors also occur, depending on the predictability of the lower-atmospheric boundary layer. In complex terrain, forecasts not only suffer from the model's inability to reproduce accurate atmospheric conditions in the lower atmosphere but also struggle with representative issues due to mismatches between the model and the actual terrain. In addition, surface forecasts at finer resolutions do not always outperform those at coarser resolutions. Increasing the vertical resolution may not help predict the near-surface variables, although it does improve the forecasts of the structure of mesoscale weather phenomena. A statistical analysis is also performed for 120 forecasts during a 1-month period to further investigate forecast error characteristics in complex terrain. Results illustrate that forecast errors in near-surface variables depend strongly on the diurnal variation in surface conditions, especially when synoptic forcing is weak. Under strong synoptic forcing, the diurnal patterns in the errors break down, while the flow-dependent errors are clearly shown.
The familial hemiplegic migraine type 1 mutation K1336E affects direct G protein-mediated regulation of neuronal P/Q-type Ca2+ channels
Authors: Garza-López Edgar , González-Ramírez Ricardo , Gandini María A , Sandoval Alejandro , Felix Ricardo 
Published: February 2013

Background Familial hemiplegic migraine type 1 (FHM-1) is an autosomal dominant form of migraine with aura characterized by recurrent migraine, hemiparesis and ataxia. FHM-1 has been linked to missense mutations in the CACNA1A gene encoding the pore-forming subunit of the neuronal voltage-gated P/Q-type Ca2+ channel (CaV2.1α1). Methods Here, we explored the effects of the FHM-1 K1336E mutation on G protein-dependent modulation of the recombinant P/Q-type channel. The mutation was introduced into the human CaV2.1α1 subunit and its functional consequences investigated after heterologous expression in HEK-293 cells using patch-clamp recordings. Results Functional analysis of the K1336E mutation revealed a reduction of Ca2+ current densities, a ∼10 mV left-shift in the current-voltage relationship, and the slowing of current inactivation kinetics. When co-expressed along with the human μ-opioid receptor, application of the agonist DAMGO inhibited whole-cell currents through both the wild-type and the mutant channels. Prepulse facilitation was also reduced by the K1336E mutation. Likewise, the kinetic analysis of the onset and decay of facilitation showed that the mutation affects the apparent dissociation and reassociation rates of the Gβγ dimer from the channel complex. Conclusions These results suggest that the extent of G-protein-mediated inhibition is significantly reduced in the K1336E mutant CaV2.1 Ca2+ channels. This alteration would contribute to render the neuronal network hyperexcitable, possibly as a consequence of reduced presynaptic inhibition, and may help to explain some aspects of the FHM-1 pathophysiology.
Underestimated phenomena: Higher cortical dysfunctions during migraine aura
Authors: Petrusic Igor , Zidverc-Trajkovic Jasna , Podgorac Ana , Sternic Nadezda 
Published: February 2013

Introduction Aura occurs in 20–30% of patients with migraine. Some descriptions of aura go far beyond the most frequent visual and sensory symptoms, suggesting the involvement of different cortical areas. The aim of this prospective study was to evaluate the frequency and types of disorders of higher cortical functions (HCF) that occur during visual and/or sensory aura. Methods We interviewed 60 patients with visual and/or sensory aura about HCF disorders of praxia, gnosia, memory, and speech, during aura. Patients were divided into two groups, with and without HCF disorders, and were compared in terms of demographic data and aura characteristics. Results From all 60 patients, 65% reported at least one HCF disorder during aura. The patients with HCF disorders had longer-lasting auras (28.51 ± 16.39 vs. 19.76 ± 11.23, p = 0.016). The most common HCF disorders were motor dysphasia (82.05%) and dysnomia (30.74%). Motor dysphasia was more often reported by patients with visual as well as sensory aura ( p = 0.002). The number of HCF disorders correlated with the aura duration ( p = 0.003). Conclusion According to our results, HCF disorders during aura occur more often than previously thought. The aura duration has some influence on the HCF disorders.
The impact of sexual activity on idiopathic headaches: An observational study
Authors: Hambach Anke , Evers Stefan , Summ Oliver , Husstedt Ingo W , Frese Achim 
Published: February 2013

Background Headache associated with sexual activity is a well-known primary headache disorder. In contrast, some case reports in the literature suggest that sexual activity during a migraine or cluster headache attack might relieve the pain in at least some patients. We performed an observational study among patients of a tertiary headache clinic. Methods A questionnaire was sent to 800 unselected migraine patients and 200 unselected cluster headache patients. We asked for experience with sexual activity during a headache attack and its impact on headache intensity. The survey was strictly and completely anonymous. Results In total, 38% of the migraine patients and 48% of the patients with cluster headache responded. In migraine, 34% of the patients had experience with sexual activity during an attack; out of these patients, 60% reported an improvement of their migraine attack (70% of them reported moderate to complete relief) and 33% reported worsening. In cluster headache, 31% of the patients had experience with sexual activity during an attack; out of these patients, 37% reported an improvement of their cluster headache attack (91% of them reported moderate to complete relief) and 50% reported worsening. Some patients, in particular male migraine patients, even used sexual activity as a therapeutic tool. Conclusions The majority of patients with migraine or cluster headache do not have sexual activity during headache attacks. Our data suggest, however, that sexual activity can lead to partial or complete relief of headache in some migraine and a few cluster headache patients.