bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic Complexity Profiling Reveals That HORMAD1 Overexpression Contributes to Homologous Recombination Deficiency in Triple-Negative Breast Cancers
Authors: Watkins Johnathan , Weekes Daniel , Shah Vandna , Gazinska Patrycja , Joshi Shalaka , Sidhu Bhavna , Gillett Cheryl , Pinder Sarah , Vanoli Fabio , Jasin Maria , Mayrhofer Markus , Isaksson Anders , Cheang Maggie C.U. , Mirza Hasan , Frankum Jessica , Lord Christopher J. , Ashworth Alan , Vinayak Shaveta , Ford James M. , Telli Melinda L. , Grigoriadis Anita , Tutt Andrew N.J. 
Published: March 2015

Abstract
Triple-negative breast cancers (TNBC) are characterized by a wide spectrum of genomic alterations, some of which might be caused by defects in DNA repair processes such as homologous recombination (HR). Despite this understanding, associating particular patterns of genomic instability with response to therapy has been challenging. Here, we show that allelic-imbalanced copy-number aberrations (AiCNA) are more prevalent in TNBCs that respond to platinum-based chemotherapy, thus providing a candidate predictive biomarker for this disease. Furthermore, we show that a high level of AiCNA is linked with elevated expression of a meiosis-associated gene, HORMAD1. Elevated HORMAD1 expression suppresses RAD51-dependent HR and drives the use of alternative forms of DNA repair, the generation of AiCNAs, as well as sensitizing cancer cells to HR-targeting therapies. Our data therefore provide a mechanistic association between HORMAD1 expression, a specific pattern of genomic instability, and an association with response to platinum-based chemotherapy in TNBC.
Significance: Previous studies have shown correlation between mutational “scars” and sensitivity to platinums extending beyond associations with BRCA1/2 mutation, but do not elucidate the mechanism. Here, a novel allele-specific copy-number characterization of genome instability identifies and functionally validates the inappropriate expression of the meiotic gene HORMAD1 as a driver of HR deficiency in TNBC, acting to induce allelic imbalance and moderate platinum and PARP inhibitor sensitivity with implications for the use of such “scars” and expression of meiotic genes as predictive biomarkers. Cancer Discov; 5(5); 488–505. ©2015 AACR.
This article is highlighted in the In This Issue feature, p. 453
Outcomes After Acute Ischemic Stroke in the United States: Does Residential ZIP Code Matter?
Authors: Agarwal Shikhar , Menon Venu , Jaber Wael A. 
Published: March 2015

Background

We sought to analyze the impact of socioeconomic status (
SES
) on in‐hospital outcomes, cost of hospitalization, and resource use after acute ischemic stroke.

Methods and Results

We used the 2003–2011 Nationwide Inpatient Sample database for this analysis. All admissions with a principal diagnosis of acute ischemic stroke were identified by using International Classification of Diseases, Ninth Revision codes.
SES
was assessed by using median household income of the residential
ZIP
code for each patient. Quartile 1 and quartile 4 reflect the lowest‐income and highest‐income
SES
quartile, respectively. During a 9‐year period, 775 905 discharges with acute ischemic stroke were analyzed. There was a progressive increase in the incidence of reperfusion on the first admission day across the
SES
quartiles (P‐trend<0.001). In addition, we observed a significant reduction in discharge to nursing facility, across the
SES
quartiles (P‐trend<0.001). Although we did not observe a significant difference in in‐hospital mortality across the
SES
quartiles in the overall cohort (P‐trend=0.22), there was a significant trend toward reduced in‐hospital mortality across the
SES
quartiles in younger patients (<75 years) (P‐trend<0.001). The mean length of stay in the lowest‐income quartile was 5.75 days, which was significantly higher compared with other
SES
quartiles. Furthermore, the mean adjusted cost of hospitalization among quartiles 2, 3, and 4, compared with quartile 1, was significantly higher by $621, $1238, and $2577, respectively. Compared with the lowest‐income quartile, there was a significantly higher use of echocardiography, invasive angiography, and operative procedures, including carotid endarterectomy, in the highest‐income quartile.

Conclusions
Patients from lower‐income quartiles had decreased reperfusion on the first admission day, compared with patients from higher‐income quartiles. The cost of hospitalization of patients from higher‐income quartiles was significantly higher than that of patients from lowest‐income quartiles, despite longer hospital stays in the latter group. This might be partially attributable to a lower use of key procedures among patients from lowest‐income quartile.
Attention and Temporal Expectations Modulate Power, Not Phase, of Ongoing Alpha Oscillations
Authors: van Diepen Rosanne M. , Cohen Michael X , Denys Damiaan , Mazaheri Ali 
Published: March 2015

Abstract
The perception of near-threshold visual stimuli has been shown to depend in part on the phase (i.e., time in the cycle) of ongoing alpha (8–13 Hz) oscillations in the visual cortex relative to the onset of that stimulus. However, it is currently unknown whether the phase of the ongoing alpha activity can be manipulated by top–down factors such as attention or expectancy. Using three variants of a cross-modal attention paradigm with constant predictable stimulus onsets, we examined if cues signaling to attend to either the visual or the auditory domain influenced the phase of alpha oscillations in the associated sensory cortices. Importantly, intermixed in all three experiments, we included trials without a target to estimate the phase at target presentation without contamination from the early evoked responses. For these blank trials, at the time of expected target and distractor onset, we examined (1) the degree of the uniformity in phase angles across trials, (2) differences in phase angle uniformity compared with a pretarget baseline, and (3) phase angle differences between visual and auditory target conditions. Across all three experiments, we found that, although the cues induced a modulation in alpha power in occipital electrodes, neither the visual condition nor the auditory cue condition induced any significant phase-locking across trials during expected target or distractor presentation. These results suggest that, although alpha power can be modulated by top–down factors such as attention and expectation, the phase of the ongoing alpha oscillation is not under such control.
Oscillatory Theta Activity during Memory Formation and Its Impact on Overnight Consolidation: A Missing Link?
Authors: Heib Dominik P. J. , Hoedlmoser Kerstin , Anderer Peter , Gruber Georg , Zeitlhofer Josef , Schabus Manuel 
Published: March 2015

Abstract
Sleep has been shown to promote memory consolidation driven by certain oscillatory patterns, such as sleep spindles. However, sleep does not consolidate all newly encoded information uniformly but rather “selects” certain memories for consolidation. It is assumed that such selection depends on salience tags attached to the new memories before sleep. However, little is known about the underlying neuronal processes reflecting presleep memory tagging. The current study sought to address the question of whether event-related changes in spectral theta power (theta ERSP) during presleep memory formation could reflect memory tagging that influences subsequent consolidation during sleep. Twenty-four participants memorized 160 word pairs before sleep; in a separate laboratory visit, they performed a nonlearning control task. Memory performance was tested twice, directly before and after 8 hr of sleep. Results indicate that participants who improved their memory performance overnight displayed stronger theta ERSP during the memory task in comparison with the control task. They also displayed stronger memory task-related increases in fast sleep spindle activity. Furthermore, presleep theta activity was directly linked to fast sleep spindle activity, indicating that processes during memory formation might indeed reflect memory tagging that influences subsequent consolidation during sleep. Interestingly, our results further indicate that the suggested relation between sleep spindles and overnight performance change is not as direct as once believed. Rather, it appears to be mediated by processes beginning during presleep memory formation. We conclude that theta ERSP during presleep memory formation reflects cortico-hippocampal interactions that lead to a better long-term accessibility by tagging memories for sleep spindle-related reprocessing.
Surrogate Population Models for Large-Scale Neural Simulations
Authors: Tripp Bryan P. 
Published: March 2015

Because different parts of the brain have rich interconnections, it is not possible to model small parts realistically in isolation. However, it is also impractical to simulate large neural systems in detail. This article outlines a new approach to multiscale modeling of neural systems that involves constructing efficient surrogate models of populations. Given a population of neuron models with correlated activity and with specific, nonrandom connections, a surrogate model is constructed in order to approximate the aggregate outputs of the population. The surrogate model requires less computation than the neural model, but it has a clear and specific relationship with the neural model. For example, approximate spike rasters for specific neurons can be derived from a simulation of the surrogate model. This article deals specifically with neural engineering framework (NEF) circuits of leaky-integrate-and-fire point neurons. Weighted sums of spikes are modeled by interpolating over latent variables in the population activity, and linear filters operate on gaussian random variables to approximate spike-related fluctuations. It is found that the surrogate models can often closely approximate network behavior with orders-of-magnitude reduction in computational demands, although there are certain systematic differences between the spiking and surrogate models. Since individual spikes are not modeled, some simulations can be performed with much longer steps sizes (e.g., 20 ms). Possible extensions to non-NEF networks and to more complex neuron models are discussed.
Spatial Patterns of Global Precipitation Change and Variability during 1901–2010
Authors: Gu Guojun , Adler Robert F. 
Published: March 2015

Abstract
This study examines global precipitation changes/variations during 1901–2010 by using the long-record GPCC land precipitation analysis, the NOAA/Cooperative Institute for Climate and Satellites (CICS) reconstructed (RECONS) precipitation analysis, and the CMIP5 outputs. In particular, spatial features of long-term precipitation changes and trends and decadal/interdecadal precipitation variations are explored by focusing on the effects of various physical mechanisms such as the anthropogenic greenhouse gas (GHG) and aerosol forcings and certain internal oscillations including the Pacific decadal variability (PDV) and Atlantic multidecadal oscillation (AMO).
Precipitation increases in the Northern Hemisphere (NH) mid- to high-latitude lands observed in GPCC can also be found in RECONS and model simulations. Over tropical/subtropical land areas, precipitation reductions generally appear in all products, but with large discrepancies on regional scales. Over ocean, consistent spatial structures of precipitation change also exist between RECONS and models. It is further found that these long-term changes/trends might be due to both anthropogenic GHG and aerosols. The aerosol effect estimated from CMIP5 historical simulations is then removed from the GPCC, RECONS, and AMIP simulations. These isolated GHG-related changes/trends have many similar spatial features when compared to the CMIP5 GHG-only simulations, especially in the zonal-mean context.
Both PDV and AMO have influence on spatial patterns of precipitation variations during the past century. In the NH middle to high latitudes, PDV and AMO have played an important role on interdecadal/multidecadal time scales. In several tropical/subtropical regions, their impacts may even become dominant for certain time spans including the recent past two decades. Therefore, these two internal mechanisms make the estimations of GHG and aerosol effects on precipitation on decadal/interdecadal time scales very challenging, especially on regional scales.
Quality Control of Antenna Alignment and Receiver Calibration Using the Sun: Adaptation to Midrange Weather Radar Observations at Low Elevation Angles
Authors: Altube Patricia , Bech Joan , Argemí Oriol , Rigo Tomeu 
Published: March 2015

AbstractA quality control method for combined online monitoring of weather radar antenna pointing biases and receiver calibration using solar signals detected by an operational radar is adapted for application to midrange radar data (80–150 km). As the original method was developed using long-range data, additional criteria based on robust statistical estimators are imposed in the sun signature detection and selection process, allowing to discard observations biased by ground clutter or precipitation and to remove very influential outliers. The validity ranges of the physical model describing the solar interferences detected by the scanning radar antenna are explicitly defined and an equation for estimation of the effective scanning width in reception is provided in a thorough theoretical derivation. The method proposed reveals its sensitivity to changes in the antenna pointing accuracy and receiver calibration when applied to operational data obtained with three C-band radars during one year. A comparative study on the goodness of fit between a three- and a five-parameter model highlights the effect on the stability and accuracy of the antenna and receiver parameters retrieved for each radar system, considering the dissimilar information content of the observations collected by each radar. The performance of the proposed methodology under the effects of the presence of ground clutter and radio local area network interferences is discussed in the results presented.
Eosinophilic Mucin Otomastoiditis and Otopolyposis
Authors: Azadarmaki Roya , Westra William , Prasad Sanjay 
Published: March 2015

Objective: The purpose of this study is to introduce and define a disease entity on a continuum of eosinophilic otitis media: eosinophilic mucin otomastoiditis and otopolyposis. Methods: A case of a 66-year-old woman with complicated chronic otitis media is reported. A literature review of the National Library of Medicine’s online database, with a focus on eosinophilic otitis media and eosinophilic mucin rhinosinusitis, was performed. Results: The authors report the case of a 66-year-old woman with a history of asthma, chronic rhinosinusitis, nasal polyposis, and chronic otitis media who presented with allergic middle ear mucin and otic polyps. Treatment involved a tympanomastoidectomy with removal of otic polyps and steroid therapy. Conclusion: Eosinophilic mucin otomastoiditis with otopolyposis is a disease entity on a continuum of eosinophilic otitis media. This disease process shares similarities with eosinophilic mucin rhinosinusitis. Otic polypectomy and steroids are suggested therapeutic measures.
Valuable Learning or “Spinning Their Wheels”? Understanding Excess Credits Earned by Community College Associate Degree Completers
Authors: Zeidenberg Matthew 
Published: March 2015

Objective: Excess credits earned by college students, over and above those required to complete their programs of study, have become increasingly a subject of interest and concern. There has been almost no research on the extent of these credits. This study focuses on all of the associate degree programs within one state’s community college system and measures the extent of excess credits within each program. Method: I created a measure of the number of excess credits earned relative to all credits earned and measured the extent to which colleges and programs vary in the levels of excess credits. Within particular academic programs, such as business, nursing, and general studies, I generated measures of the extent to which program-related and general education courses create excess credits. I examined the transcripts of some students who have earned excess credits, to see specifically what they did. Results: I take no normative position on the usefulness or harm of excess credits, but instead explore some of the factors that may generate them. Contribution: I suggest some policies that might be implemented to reduce excess credits, if desired.
Magnetic, fluorescent, and thermo-responsive poly(MMA-NIPAM-Tb(AA)3Phen)/Fe3O4 multifunctional nanospheres prepared by emulsifier-free emulsion polymerization
Authors: Gong Ying , Dai Jingwen , Li Huan , Wang Xin , Xiong Haoran , Zhang Quanyuan , Li Penghui , Yi Changfeng , Xu Zushun , Xu Haibo , Chu Paul K 
Published: March 2015

Magnetic, luminescent, and thermoresponsive multifunctional nanospheres composed of modified Fe3O4 nanoparticles as the core and rare earth complex Tb(AA)3Phen as the shell are synthesized by emulsifier-free emulsion polymerization. The core–shell spherical structure has a size between 140 and 220 nm and exhibits strong green fluorescence of the rare earth complex Tb(AA)3Phen. In the R2 relaxivity and in vivo MRI studies, the R2 relaxivity of the nanospheres is 562.56 mM–1 s–1 and enhanced T2-weighted images are observed from the nanospheres in the liver and spleen after injection as a contrast agent. The excellent superparamagnetic, thermosensitive, and fluorescent properties render the nanospheres useful in biomedical engineering and optical imaging.
Anti-Influenza Virus Activity of Propolis in Vitro and its Efficacy against Influenza Infection in Mice
Authors: Shimizu Tomomi , Hino Akane , Tsutsumi Atsuko , Park Yong Kun , Watanabe Wataru , Kurokawa Masahiko 
Published: March 2015

Background: Propolis has been used worldwide as a dietary supplement to maintain and improve human health. We examined whether ethanol extracts of Brazilian propolis exhibit antiviral activity against influenza virus in vitro and in vivo. Methods: Among 13 ethanol extracts screened in a plaque reduction assay, four showed anti-influenza virus activity. The anti-influenza efficacy of the four extracts was further examined in a murine influenza virus infection model. The mice were infected intranasally with influenza virus, and the four extracts were orally administered at 10 mg/kg three times daily for seven successive days after infection. Results: In this infection model, only one extract, AF-08, was significantly effective at 10 mg/kg in reducing the body weight loss of infected mice. The doses of 2 and 10 mg/kg were also effective in prolonging the survival times of infected mice significantly, but 0.4 mg/kg was not. The anti-influenza efficacy of AF-08 at 10 mg/kg was confirmed in a dose-dependent manner in mice. AF-08 at 10 mg/kg significantly reduced virus yields in the bronchoalveolar lavage fluids of lungs in infected mice as compared with the control. The reduction of virus yields by AF-08 at 10 mg/kg significantly corresponded to those induced by oseltamivir at 1 mg/kg twice daily from day 1 to day 4 after infection. Conclusion: The Brazilian propolis AF-08 was indicated to possess anti-influenza virus activity and to ameliorate influenza symptoms in mice. AF-08 may be a possible candidate for an anti-influenza dietary supplement for humans.
Comparison of First- and Second-Generation Fixed-Bearing Total Ankle Arthroplasty Using a Modular Intramedullary Tibial Component
Authors: Lewis John S. , Green Cynthia L. , Adams Samuel B. , Easley Mark E. , DeOrio James K. , Nunley James A. 
Published: March 2015

Background: This series reviews the clinical and radiographic outcomes of patients who underwent total ankle replacement (TAR) using first- and second-generations of a modern fixed-bearing prosthesis utilizing a modular intramedullary stem. Methods: A consecutive series of first- and second-generation primary TARs with modular intramedullary stems were identified. Clinical outcome data were collected prospectively—including visual analog scale for pain, American Orthopaedic Foot & Ankle Society hindfoot-ankle, Short Musculoskeletal Function Assessment, and Short Form–36 scores. Preoperative coronal plane deformity and correction of deformity after TAR were assessed. Complications, subsequent procedures, and failure rates were compared. A total of 193 first- and 56 second-generation patients were identified with a mean follow-up of 3.7 and 2.1 years, respectively. Results: Clinical outcome data reflected significant improvements at 1 year postoperatively, and improvements were maintained at 2-year follow-up for each group. Improvement in visual analog scale scores were significantly better in the second-generation group at 1 year postoperatively, but this was not maintained at 2 years. Mean coronal tibiotalar angles for ankles with preoperative varus or valgus deformities were significantly improved. Correction was maintained until final follow-up, with no significant differences in deformity improvement between groups. The rate of reoperation at 2 years postoperatively on the affected foot or ankle subsequent to the index ankle replacement for patients in the first-generation group (18.5%) was higher compared to the second-generation group (15.9%), but the time until reoperation was not statistically significant ( P = .376). The implant failure rate was higher in the first-generation group (6.0%) compared to the second-generation group (2.6%) at 2 years postoperatively, but the time until failure was not significantly different ( P = .295). Conclusion: Patients who underwent TAR with a first- or second-generation fixed-bearing prosthesis with an intramedullary tibial component demonstrated significant improvements in all measures of pain and function with sustained improvements in coronal plane alignment. The second-generation prosthesis demonstrated slightly better improvements at 1 year and was associated with lower reoperation and implant failure rates. Level of Evidence: Level II, comparative series.
High mobility group box 1 contributes to anti-neutrophil cytoplasmic antibody-induced neutrophils activation through receptor for advanced glycation end products (RAGE) and Toll-like receptor 4
Authors: Wang Chen , Wang Huan , Chang Dong-Yuan , Hao Jian , Zhao Ming-Hui , Chen Min 
Published: March 2015

Abstract
Introduction
High mobility group box-1 (HMGB1), a typical damage-associated molecular pattern (DAMP) protein, is associated with inflammatory conditions and tissue damage. Our recent study found that circulating HMGB1 levels could reflect the disease activity of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The current study aimed to investigate whether HMGB1 participated in ANCA-induced neutrophil activation, which is one of the most important pathogenic aspects in the development of AAV.

Methods
The various effects of HMGB1 in ANCA-induced neutrophil activation were measured. Antagonists for relevant receptors and signaling molecules were employed.

Results
ANCA antigens translocation on neutrophils primed with HMGB1 was significantly higher than non-primed neutrophils. The levels of respiratory burst and degranulation increased significantly in HMGB1-primed neutrophils activated with ANCA-positive IgG, as compared with non-primed neutrophils. Furthermore, blocking Toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE), rather than TLR2, resulted in a significant decrease in HMGB1-induced ANCA antigens translocation, respiratory burst and degranulation. Similar effects were also found when blocking MyD88 and NF-κB.

Conclusions
HMGB1 could prime neutrophils by increasing ANCA antigens translocation, and the primed neutrophils could be further induced by ANCA, resulting in the respiratory burst and degranulation. This process is TLR4- and RAGE-dependent through the MyD88/NF-κB pathway.