bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Peptide Vaccine-Induced CD8 T Cells Strongly Modulate Intratumoral Macrophages Required for Tumor Regression
Authors: van der Sluis Tetje C. , Sluijter Marjolein , van Duikeren Suzanne , West Brian L. , Melief Cornelis J.M. , Arens Ramon , van der Burg Sjoerd H. , van Hall Thorbald 
Published: April 2015

AbstractAbundant macrophage infiltration of solid cancers commonly correlates with poor prognosis. Tumor-promoting functions of macrophages include angiogenesis, metastasis formation, and suppression of Th1-type immune responses. Here, we show that successful treatment of cervical carcinoma in mouse models with synthetic long peptide (SLP) vaccines induced influx of cytokine-producing CD8 T cells that strongly altered the numbers and phenotype of intratumoral macrophages. On the basis of the expression of CD11b, CD11c, F4/80, Ly6C, Ly6G, and MHC II, we identified four myeloid subpopulations that increased in numbers from 2.0-fold to 8.7-fold in regressing tumors. These changes of the intratumoral myeloid composition coincided with macrophage recruitment by chemokines, including CCL2 and CCL5, and were completely dependent on a vaccine-induced influx of tumor-specific CD8 T cells. CD4 T cells were dispensable. Incubation of tumor cells with T cell–derived IFNγ and TNFα recapitulated the chemokine profile observed in vivo, confirming the capacity of antitumor CD8 T cells to mediate macrophage infiltration of tumors. Strikingly, complete regressions of large established tumors depended on the tumor-infiltrating macrophages that were induced by this immunotherapy, because a small-molecule drug inhibitor targeting CSF-1R diminished the number of intratumoral macrophages and abrogated the complete remissions. Survival rates after therapeutic SLP vaccination deteriorated in the presence of CSF-1R blockers. Together, these results show that therapeutic peptide vaccination could induce cytokine-producing T cells with strong macrophage-skewing capacity necessary for tumor shrinkage, and suggest that the development of macrophage-polarizing, rather than macrophage-depleting, agents is warranted. Cancer Immunol Res; 3(9); 1042–51. ©2015 AACR.
Persistent High Serum Bicarbonate and the Risk of Heart Failure in Patients With Chronic Kidney Disease (CKD): A Report From the Chronic Renal Insufficiency Cohort (CRIC) Study
Authors: Dobre Mirela , Yang Wei , Pan Qiang , Appel Lawrence , Bellovich Keith , Chen Jing , Feldman Harold , Fischer Michael J. , Ham L. L. , Hostetter Thomas , Jaar Bernard G. , Kallem Radhakrishna R. , Rosas Sylvia E. , Scialla Julia J. , Wolf Myles , Rahman Mahboob ,   and the CRIC Study Investigators
Published: April 2015

Background

Serum bicarbonate varies over time in chronic kidney disease (
CKD
) patients, and this variability may portend poor cardiovascular outcomes. The aim of this study was to conduct a time‐updated longitudinal analysis to evaluate the association of serum bicarbonate with long‐term clinical outcomes: heart failure, atherosclerotic events, renal events (halving of estimated glomerular filtration rate [
eGFR
] or end‐stage renal disease), and mortality.

Methods and Results

Serum bicarbonate was measured annually, in 3586 participants with
CKD
, enrolled in the Chronic Renal Insufficiency Cohort (
CRIC
) study. Marginal structural models were created to allow for integration of all available bicarbonate measurements and proper adjustment for time‐dependent confounding. During the 6 years follow‐up, 512 participants developed congestive heart failure (26/1000 person‐years) and 749 developed renal events (37/1000 person‐years). The risk of heart failure and death was significantly higher for participants who maintained serum bicarbonate >26 mmol/L for the entire duration of follow‐up (hazard ratio [
HR
] 1.66; 95% confidence interval [
CI
], 1.23 to 2.23, and
HR
1.36, 95%
CI
1.02 to 1.82, respectively) compared with participants who kept their bicarbonate 22 to 26 mmol/L, after adjusting for demographics, co‐morbidities, medications including diuretics,
eGFR,
and proteinuria. Participants who maintained serum bicarbonate <22 mmol/L had almost a 2‐fold increased risk of renal disease progression (
HR
1.97; 95%
CI
, 1.50 to 2.57) compared with participants with bicarbonate 22 to 26 mmol/L.

Conclusion

In this large
CKD
cohort, persistent serum bicarbonate >26 mmol/L was associated with increased risk of heart failure events and mortality. Further studies are needed to determine the optimal range of serum bicarbonate in
CKD
to prevent adverse clinical outcomes.
Androgen Deprivation Therapy Reversibly Increases Endothelium‐Dependent Vasodilation in Men With Prostate Cancer
Authors: Nguyen Paul L. , Jarolim Petr , Basaria Shehzad , Zuflacht Jonah P. , Milian Jessica , Kadivar Samoneh , Graham Powell L. , Hyatt Andrew , Kantoff Philip W. , Beckman Joshua A. 
Published: April 2015

Background

Androgen deprivation therapy (
ADT
) is a standard treatment for patients with aggressive prostate cancer. Although
ADT
improves survival, it increases the risk of diabetes. Emerging evidence suggests that
ADT
increases adverse cardiovascular events as early as 3 months after initiation in patients with cardiovascular disease, but the mechanism is unknown. We hypothesized that
ADT
may impair endothelium‐dependent vasodilation due to increases in lipids and insulin resistance and may provide a link for heightened cardiovascular risk in this population.

Methods and Results

We prospectively evaluated conduit artery endothelium‐dependent and ‐independent vasodilation, lipids, and insulin resistance in 16 consecutively treated men (mean age 66±7 years; 25% with diabetes) with prostate cancer before and after 3 months of
ADT
. High‐resolution B‐mode ultrasound was used to assess flow‐mediated (endothelium‐dependent) and nitroglycerine‐mediated (endothelium‐independent) brachial artery vasodilation.
ADT
significantly increased insulin resistance, total cholesterol, HDL, and LDL. Endothelium‐dependent vasodilation was greater at 3 months than at baseline (10.8% [interquartile range: 7.7% to 14.6%] versus 8.9% [interquartile range: 4.0% to 12.6%], respectively;
P
=0.046, allometric
P
=0.037). Nitroglycerine‐mediated vasodilation did not change from baseline (
P
>0.2). The subset of participants on
ADT
for 6 months returned for reevaluation at 1 year. In this group, endothelium‐dependent vasodilation increased from baseline to 3 months and returned to baseline 6 months after ADT withdrawal (9.4% [interquartile range: 6.9% to 10.9%], 11.6% [interquartile range: 7.9% to 15.2%], and 9.0% [interquartile range: 5.1% to 12.5%], respectively;
P
=0.05).

Conclusions

In contrast to our expectation,
ADT
improved endothelium‐dependent vasodilation and its cessation returned endothelium‐dependent vasodilation to baseline. Determining the mechanism of this change requires further investigation.
Establishing Best Practices to Improve Usefulness and Usability of Web Interfaces Providing Atmospheric Data
Authors: Oakley Nina S. , Daudert Britta 
Published: April 2015

Abstract
Accessing scientific data and information through an online portal can be a frustrating task, often because of the fact that they were not built with the user’s needs in mind. The concept of making web interfaces easy to use, known as “usability,” has been thoroughly researched in the field of e-commerce but has not been explicitly addressed in the atmospheric and most other sciences. As more observation stations are installed, satellites flown, models run, and field campaigns performed, data are continuously produced. Portals on the Internet have become the favored mechanisms for sharing this information and are ever increasing in number. Portals are often created without being explicitly tested for usability with the target audience though the expenses of testing are low and the returns high. To remain competitive and relevant in the provision of atmospheric information, it is imperative that developers understand design elements of a successful portal to make their product stand out among others. This work informs the audience of the benefits and basic principles of usability that can be applied to web pages presenting atmospheric information. We will also share some of the best practices and recommendations we have formulated from the results of usability testing performed on a data provision site designed for researchers in the Southwest Climate Science Center and hosted by the Western Regional Climate Center.
Sticky Thermals: Evidence for a Dominant Balance between Buoyancy and Drag in Cloud Updrafts
Authors: Romps David M. , Charn Alexander B. 
Published: April 2015

Abstract
The vertical velocities of convective clouds are of great practical interest because of their influence on many phenomena, including severe weather and stratospheric moistening. However, the magnitudes of forces giving rise to these vertical velocities are poorly understood, and the dominant balance is in dispute. Here, an algorithm is used to extract thousands of cloud thermals from a large-eddy simulation of deep and tropical maritime convection. Using a streamfunction to define natural boundaries for these thermals, the dominant balance in the vertical momentum equation is revealed. Cloud thermals rise with a nearly constant speed determined by their buoyancy and the standard drag law with a drag coefficient of 0.6. Contrary to suggestions that cloud thermals might be slippery, with a dominant balance between buoyancy and acceleration, cloud thermals are found here to be sticky, with a dominant balance between buoyancy and drag.
Scenario Changes of Atlantic Water in the Arctic Ocean
Authors: Long Zhenxia , Perrie Will 
Published: April 2015

Abstract
The authors explore possible temperature modifications of the Atlantic Water Layer (AWL) induced by climate change, performing simulations for 1970 to 2099 with a coupled ice–ocean Arctic model (CIOM). Surface fields to drive the CIOM were provided by the Canadian Regional Climate Model (CRCM), driven by outputs from the Canadian Centre for Climate Modelling and Analysis (CCCma) Coupled Global Climate Model, version 3 (CGCM3) following the A1B climate change scenario. In the present climate, represented as 1990–2009, the CIOM can reliably reproduce the AWL compared to Polar Science Center Hydrographic Climatology (PHC) data. For the future climate, assuming the A1B climate change scenario, there is a significant increase in water volume transport into the central Arctic Ocean through Fram Strait due to the weakened atmospheric high pressure system over the western Arctic and an intensified atmospheric low pressure system over the Nordic seas. The AWL temperature tends to decrease from 0.36°C in the 2010s to 0.26°C in the 2060s. In the vertical, the warm Atlantic water core slightly expands before the 2030s, significantly shrinks after the 2050s, and essentially disappears by 2070–99, in the southern Beaufort Sea. The temperature decrease after 2030 is mainly due to the reduced heat fluxes in the Kara and Barents Seas. In the northeastern Barents and Kara Seas, the loss of sea ice increases the heat loss from the Atlantic water and reduces the water temperature near the bottom, contributing to decreased heat fluxes into the central Arctic Ocean, as well as decreased AWL temperature at central Arctic Ocean intermediate layers. In addition, the vertically integrated heat loss also plays an important role in the AWL cooling process.
Effects of Increasing Horizontal Resolution in a Convection-Permitting Model on Flood Forecasting: The 2011 Dramatic Events in Liguria, Italy
Authors: Davolio Silvio , Silvestro Francesco , Malguzzi Piero 
Published: April 2015

AbstractCoupling meteorological and hydrological models is a common and standard practice in the field of flood forecasting. In this study, a numerical weather prediction (NWP) chain based on the BOLogna Limited Area Model (BOLAM) and the MOdello LOCale in Hybrid coordinates (MOLOCH) was coupled with the operational hydrological forecasting chain of the Ligurian Hydro-Meteorological Functional Centre to simulate two major floods that occurred during autumn 2011 in northern Italy. Different atmospheric simulations were performed by varying the grid spacing (between 1.0 and 3.0 km) of the high-resolution meteorological model and the set of initial/boundary conditions driving the NWP chain. The aim was to investigate the impact of these parameters not only from a meteorological perspective, but also in terms of discharge predictions for the two flood events. The operational flood forecasting system was thus used as a tool to validate in a more pragmatic sense the quantitative precipitation forecast obtained from different configurations of the NWP system. The results showed an improvement in flood prediction when a high-resolution grid was employed for atmospheric simulations. In turn, a better description of the evolution of the precipitating convective systems was beneficial for the hydrological prediction. Although the simulations underestimated the severity of both floods, the higher-resolution model chain would have provided useful information to the decision-makers in charge of protecting citizens.
Using Microwave Satellite Data to Assess Changes in Storminess over the Pacific Ocean
Authors: Kruk Michael C. , Hilburn Kyle , Marra John J. 
Published: April 2015

Abstract
This study analyzes 25 years of Special Sensor Microwave Imager (SSM/I) retrievals of rain rate and wind speed to assess changes in storminess over the open water of the Pacific Ocean. Changes in storminess are characterized by combining trends in both the statistically derived 95th percentile exceedance frequencies of rain rate and wind speed (i.e., extremes). Storminess is computed annually and seasonally, with further partitioning done by phase of the El Niño–Southern Oscillation (ENSO) index and the Pacific decadal oscillation (PDO) index. Overall, rain-rate exceedance frequencies of 6–8 mm h−1 cover most of the western and central tropical Pacific, with higher values present around the Philippines, Japan, Mexico, and the northwest coast of Australia. Wind speed exceedance frequencies are a strong function of latitude, with values less (greater) than 12 m s−1 equatorward (poleward) of 30°N/S. Statistically significant increasing trends in rain rate were found in the western tropical Pacific near the Caroline Islands and the Solomon Islands, and in the extratropics from the Aleutian Islands down the coast along British Columbia and Washington State. Statistically significant increasing trends in wind speed are present in the equatorial central Pacific near Kiribati and the Republic of the Marshall Islands (RMI), and in the extratropics along the west coast of the United States and Canada. Thus, while extreme rain and winds are both increasing across large areas of the Pacific, these areas are modulated according to the phase of ENSO and the PDO, and their intersection takes aim at specific locations.
Effectiveness and student perceptions of high-enrolment health studies online courses
Authors: Chen Ken-Zen , Lowenthal Patrick R , Bauer Christine 
Published: April 2015

Objective: In countries such as the USA, colleges and universities are focusing on how best to serve their students in tough fiscal times and a highly competitive marketplace. Boise State University has specifically focused on providing online courses as one option to meet student needs. However, more recently, the university has begun developing high-enrolment online courses to resolve bottlenecks in enrolments, while maintaining robust, interactive and engaging learning experiences. Design: Mixed-methods case study. Setting: Three high-enrolment health studies online courses offered at a 4-year university in Boise, Idaho, USA. Method: A systemic analysis of final course evaluations, student grades and course reports from the Learning Management System were examined to investigate the effectiveness and student perceptions of high-enrolment online courses. Results: Findings provide support for the premise that offering the high-enrolment courses met enrolment demand, provided high-quality instruction and maintained student satisfaction. Conclusion: Student perceptions of high-enrolment health studies online courses designed and implemented in the manner specified here can be positive. Lesson learned and suggestions for faculty members, instructional designers and administrators are identified.
Treatment of holistic suffering in cancer: A systematic literature review
Authors: Best Megan , Aldridge Lynley , Butow Phyllis , Olver Ian , Price Melanie A , Webster Fleur 
Published: April 2015

Background: Holistic suffering is a debilitating problem for cancer patients. Although many treatments have been suggested for its alleviation, they have not been compared for effectiveness. Aim: This literature review seeks to identify what interventions are effective in treatment of holistic suffering of cancer patients. Design: A systematic review was conducted to identify and evaluate studies of interventions for holistic suffering in adult cancer patients. Search terms were generated iteratively from the literature. Data sources: MEDLINE, EMBASE, the Cochrane Library and PsycINFO databases were searched for the years 1992–2015. Included studies were peer-reviewed, English language reports of either a controlled trial or a randomised controlled trial focusing on therapies aimed at relieving suffering in adult cancer patients. Articles were excluded if focused predominantly on spiritual or existential issues or concerns not leading to suffering. Studies were graded for quality using the QualSyst quantitative checklist. Levels of evidence were ascertained by completing the National Health and Medical Research Council criteria. Results are reported according to AMSTAR guidelines. Results: The studies represented seven intervention types. Meaning-centred, hope-centred and stress-reduction interventions were found to be effective. Results of both psycho-educational and spiritual interventions in improving spiritual well-being were mixed. Supportive-expressive interventions – with the exception of forgiveness therapy – were not efficacious. There was little or no evidence for the efficacy of creative and healing arts and other assessed interventions such as animal therapy and haptotherapy. Conclusion: This systematic review found that spiritual well-being, meaning, hope and benefit finding can be positively impacted by a variety of treatment modalities.
Effects of language experience, use, and cognitive functioning on bilingual word production and comprehension
Authors: Litcofsky Kaitlyn A. , Tanner Darren , van Hell Janet G. 
Published: April 2015

Aims and objectives/purpose/research questions: Considerable research has investigated how bilinguals produce and comprehend words, focusing mainly on how bilinguals are able to select words from the appropriate language. Less research, however, has investigated whether production and comprehension involve the same underlying mechanisms. The present study explores this issue by examining whether production and comprehension, in the first language (L1) and second language (L2), are similarly influenced by factors relating to language experience, language use, and cognitive functioning. Design/methodology/approach Spanish-English bilinguals living in an English-speaking environment completed a picture naming task and a lexical decision task in their L1 and L2. In addition, participants completed the Operation Span task testing working memory and the Flanker task testing inhibitory control, and completed a language history questionnaire probing their language experience, relative proficiency, and codeswitching behavior. Data and analysis: Performance on all tasks was submitted to correlation analyses and the impact of individual difference measures on word production and comprehension was assessed via regression analyses. Findings/conclusions: Results showed that (1) production and comprehension were more closely linked in L1 than in L2; (2) production in L1 and L2 was predicted by language proficiency; and (3) comprehension in L1 and L2 was predicted by working memory. Originality: This is the first study to compare lexical processing in production and comprehension in both L1 and L2 and how these processes are influenced by language experience, use, and cognitive factors. Significance/implications: Word production and comprehension appear to be more tightly linked in L1 than L2, but seem to rely on different processing mechanisms.
The validity and reliability of the Sense of Coherence scale among Indian university students
Authors: Rajesh Gururaghavendran , Eriksson Monica , Pai Keshava , Seemanthini S , Naik Dilip G. , Rao Ashwini 
Published: April 2015

Background: The importance of salutogenesis, with the focus of what creates health rather than what causes diseases, has been highlighted for a long time. This has been operationalized by Aaron Antonovsky as the Sense of Coherence (SOC-13) scale. The aim of this study was to further examine the psychometric properties of the SOC-13 in India. Methods: The present study was carried out among second-year degree students at three randomly chosen institutions at Mangalore University. Investigators assessed the appropriateness, relevance, comprehensiveness and understandability of the scale. Further, the scale was assessed by five subject experts. The SOC-13 was then pretested by administering it to peers, individuals and a few of the study subjects. Internal consistency was assessed by Cronbach’s alpha and split-half reliability. Test-retest reliability was assessed by administering the instrument to the same study participants after two weeks. Confirmatory factor analysis employing varimax rotation was employed. Results: The SOC-13 revealed a Cronbach’s alpha value of 0.76. Split-half reliability and Guttman split-half reliability were found to be 0.71 and 0.70, respectively. Test-retest reliability was found to be 0.71 ( p < 0.01). Factor analysis revealed a three-factor solution explaining 40.53% of the variation in SOC. Conclusions: SOC-13 was found to be a reliable and valid instrument for measuring SOC in an Indian context. The present study contributes to health promotion in an Indian context, and could be useful even in other developing countries and for further research in India.
Central nervous system acute lymphoblastic leukemia: role of natural killer cells
Authors: Frishman-Levy Liron , Shemesh Avishai , Bar-Sinai Allan , Ma Chao , Ni Zhenya , Frenkel Shahar , Muench Vera , Bruckmueller Hilke , Vokuhl Christian , Debatin Klaus-Michael , Eckert Cornelia , Stanulla Martin , Schrappe Martin , Campbell Kerry S. , Loewenthal Ron , Schewe Denis M. , Hochman Jacob , Meyer Lueder H. , Kaufman Dan , Cario Gunnar , Porgador Angel , Izraeli Shai 
Published: April 2015

Key Points
Increased IL-15 expression in leukemic lymphoblasts is associated with activation of NK cells. The CNS may be an immunologic sanctuary protecting lymphoblasts from NK-cell activity.
Arginine deprivation using pegylated arginine deiminase has activity against primary acute myeloid leukemia cells in vivo
Authors: Miraki-Moud Farideh , Ghazaly Essam , Ariza-McNaughton Linda , Hodby Katharine A. , Clear Andrew , Anjos-Afonso Fernando , Liapis Konstantinos , Grantham Marianne , Sohrabi Fareeda , Cavenagh Jamie , Bomalaski John S. , Gribben John G. , Szlosarek Peter W. , Bonnet Dominique , Taussig David C. 
Published: April 2015

Key PointsMost AMLs lack ASS1, which allows synthesis of arginine, and so depend on exogenous sources. Depletion of arginine via ADI-PEG 20 reduces the burden of primary AML in vivo and in vitro.