bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal dynamics of retinal and extraretinal signals in the FEFsem during smooth pursuit eye movements
Authors: Bakst Leah , Fleuriet Jérome , Mustari Michael J. 
Published: February 2017

Neurons in the smooth eye movement subregion of the frontal eye field (FEFsem) are known to play an important role in voluntary smooth pursuit eye movements. Underlying this function are projections to parietal and prefrontal visual association areas and subcortical structures, all known to play vital but differing roles in the execution of smooth pursuit. Additionally, the FEFsem has been shown to carry a diverse array of signals (e.g., eye velocity, acceleration, gain control). We hypothesized that distinct subpopulations of FEFsem neurons subserve these diverse functions and projections, and that the relative weights of retinal and extraretinal signals could form the basis for categorization of units. To investigate this, we used a step-ramp tracking task with a target blink to determine the relative contributions of retinal and extraretinal signals in individual FEFsem neurons throughout pursuit. We found that the contributions of retinal and extraretinal signals to neuronal activity and behavior change throughout the time course of pursuit. A clustering algorithm revealed three distinct neuronal subpopulations: cluster 1 was defined by a higher sensitivity to eye velocity, acceleration, and retinal image motion; cluster 2 had greater activity during blinks; and cluster 3 had significantly greater eye position sensitivity. We also performed a comparison with a sample of medial superior temporal neurons to assess similarities and differences between the two areas. Our results indicate the utility of simple tests such as the target blink for parsing the complex and multifaceted roles of cortical areas in behavior. NEW & NOTEWORTHY The frontal eye field (FEF) is known to play a critical role in volitional smooth pursuit, carrying a variety of signals that are distributed throughout the brain. This study used a novel application of a target blink task during step ramp tracking to determine, in combination with a clustering algorithm, the relative contributions of retinal and extraretinal signals to FEF activity and the extent to which these contributions could form the basis for a categorization of neurons.
Alteration of the microsaccadic velocity-amplitude main sequence relationship after visual transients: implications for models of saccade control
Authors: Buonocore Antimo , Chen Chih-Yang , Tian Xiaoguang , Idrees Saad , Münch Thomas A. , Hafed Ziad M. 
Published: February 2017

Microsaccades occur during gaze fixation to correct for miniscule foveal motor errors. The mechanisms governing such fine oculomotor control are still not fully understood. In this study, we explored microsaccade control by analyzing the impacts of transient visual stimuli on these movements’ kinematics. We found that such kinematics can be altered in systematic ways depending on the timing and spatial geometry of visual transients relative to the movement goals. In two male rhesus macaques, we presented peripheral or foveal visual transients during an otherwise stable period of fixation. Such transients resulted in well-known reductions in microsaccade frequency, and our goal was to investigate whether microsaccade kinematics would additionally be altered. We found that both microsaccade timing and amplitude were modulated by the visual transients, and in predictable manners by these transients’ timing and geometry. Interestingly, modulations in the peak velocity of the same movements were not proportional to the observed amplitude modulations, suggesting a violation of the well-known “main sequence” relationship between microsaccade amplitude and peak velocity. We hypothesize that visual stimulation during movement preparation affects not only the saccadic “Go” system driving eye movements but also a “Pause” system inhibiting them. If the Pause system happens to be already turned off despite the new visual input, movement kinematics can be altered by the readout of additional visually evoked spikes in the Go system coding for the flash location. Our results demonstrate precise control over individual microscopic saccades and provide testable hypotheses for mechanisms of saccade control in general. NEW & NOTEWORTHY Microsaccadic eye movements play an important role in several aspects of visual perception and cognition. However, the mechanisms for microsaccade control are still not fully understood. We found that microsaccade kinematics can be altered in a systematic manner by visual transients, revealing a previously unappreciated and exquisite level of control by the oculomotor system of even the smallest saccades. Our results suggest precise temporal interaction between visual, motor, and inhibitory signals in microsaccade control.
Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells
Authors: Ma Zhongming , Saung Wint Thu , Foskett J. Kevin 
Published: February 2017

Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na+ currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na+ and K+ channels but contributed modestly to the kinetics of action potentials.
GPS-Based Exposure to Greenness and Walkability and Accelerometry-Based Physical Activity
Authors: James Peter , Hart Jaime E. , Hipp J. Aaron , Mitchell Jonathan A. , Kerr Jacqueline , Hurvitz Philip M. , Glanz Karen , Laden Francine 
Published: February 2017

Abstract
Background: Physical inactivity is a risk factor for cancer that may be influenced by environmental factors. Indeed, dense and well-connected built environments and environments with natural vegetation may create opportunities for higher routine physical activity. However, studies have focused primarily on residential environments to define exposure and self-reported methods to estimate physical activity. This study explores the momentary association between minute-level global positioning systems (GPS)-based greenness exposure and time-matched objectively measured physical activity.
Methods: Adult women were recruited from sites across the United States. Participants wore a GPS device and accelerometer on the hip for 7 days to assess location and physical activity at minute-level epochs. GPS records were linked to 250 m resolution satellite-based vegetation data and Census Block Group-level U.S. Environmental Protection Agency (EPA) Smart Location Database walkability data. Minute-level generalized additive mixed models were conducted to test for associations between GPS measures and accelerometer count data, accounting for repeated measures within participant and allowing for deviations from linearity using splines.
Results: Among 360 adult women (mean age of 55.3 ± 10.2 years), we observed positive nonlinear relationships between physical activity and both greenness and walkability. In exploratory analyses, the relationships between environmental factors and physical activity were strongest among those who were white, had higher incomes, and who were middle-aged.
Conclusions: Our results indicate that higher levels of physical activity occurred in areas with higher greenness and higher walkability.
Impact: Findings suggest that planning and design policies should focus on these environments to optimize opportunities for physical activity. Cancer Epidemiol Biomarkers Prev; 26(4); 525–32. ©2017 AACR.
See all the articles in this CEBP Focus section, “Geospatial Approaches to Cancer Control and Population Sciences.”
Racial/Ethnic Differences in the Impact of Neighborhood Social and Built Environment on Breast Cancer Risk: The Neighborhoods and Breast Cancer Study
Authors: Conroy Shannon M. , Shariff-Marco Salma , Koo Jocelyn , Yang Juan , Keegan Theresa H.M. , Sangaramoorthy Meera , Hertz Andrew , Nelson David O. , Cockburn Myles , Satariano William A. , Yen Irene H. , Ponce Ninez A. , John Esther M. , Gomez Scarlett Lin 
Published: February 2017

Abstract
Background: Neighborhood socioeconomic status (nSES) has been found to be associated with breast cancer risk. It remains unclear whether this association applies across racial/ethnic groups independent of individual-level factors and is attributable to other neighborhood characteristics.
Methods: We examined the independent and joint associations of education and nSES with odds of breast cancer. Residential addresses were geocoded for 2,838 cases and 3,117 controls and linked to nSES and social and built environment characteristics. We estimated ORs and 95% confidence intervals (CI) using multilevel logistic regression controlling for individual-level breast cancer risk factors and assessed the extent to which nSES associations were due to neighborhood characteristics.
Results: Women living in the highest versus lowest nSES quintile had a nearly 2-fold greater odds of breast cancer, with elevated odds (adjusted ORs, 95% CI) for non-Hispanic whites (NHWs; 2.27; 1.45–3.56), African Americans (1.74; 1.07–2.83), U.S.-born Hispanics (1.82; 1.19–2.79), and foreign-born Hispanics (1.83; 1.06–3.17). Considering education and nSES jointly, ORs were increased for low education/high nSES NHWs (1.83; 1.14–2.95), high education/high nSES NHWs (1.64; 1.06–2.54), and high education/high nSES foreign-born Hispanics (2.17; 1.52–3.09) relative to their race/ethnicity/nativity-specific low education/low nSES counterparts. Adjustment for urban and mixed-land use characteristics attenuated the nSES associations for most racial/ethnic/nativity groups except NHWs.
Conclusions: Our study provides empirical evidence for a role of neighborhood environments in breast cancer risk, specifically social and built environment attributes.
Impact: Considering the role of neighborhood characteristics among diverse populations may offer insights to understand racial/ethnic disparities in breast cancer risk. Cancer Epidemiol Biomarkers Prev; 26(4); 541–52. ©2017 AACR.
Lymphotoxin-β Interacts with Methylated EGFR to Mediate Acquired Resistance to Cetuximab in Head and Neck Cancer
Authors: Hsu Dennis Shin-Shian , Hwang Wei-Lun , Yuh Chiou-Hwa , Chu Chen-Hsi , Ho Yang-Hui , Chen Pon-Bo , Lin Han-Syuan , Lin Hua-Kuo , Wu Shih-Pei , Lin Chih-Yi , Hsu Wen-Hao , Lan Hsin-Yi , Wang Hsiao-Jung , Tai Shyh-Kuan , Hung Mien-Chie , Yang Muh-Hwa 
Published: February 2017

AbstractPurpose: In head and neck squamous cell carcinoma (HNSCC), the incidence of RAS mutation, which is the major cause of cetuximab resistance, is relatively rare compared with the other types of cancers, and the mechanism mediating acquired resistance is unclear compared with the driver gene mutation–mediated de novo resistance. Here, we investigated the driver gene mutation–independent mechanism for cetuximab resistance in HNSCC.Experimental Design: We used the in vitro-selected and in vivo-selected cetuximab-resistant sublines of HNSCC cell lines for investigating the mechanism of acquired resistance to cetuximab. Zebrafish model was applied for evaluating the synergistic effect of combinatory drugs for overcoming cetuximab resistance.Results: The cetuximab-resistant HNSCC cells undergo a Snail-induced epithelial–mesenchymal transition. Mechanistically, Snail induces the expression of lymphotoxin-β (LTβ), a TNF superfamily protein that activates NF-κB, and protein arginine methyltransferase 1 (PRMT1), an arginine methyltransferase that methylates EGFR. LTβ interacts with methylated EGFR to promote its ligand-binding ability and dimerization. Furthermore, LTβ activates the NF-κB pathway through a LTβ receptor–independent mechanism. Combination of an EGFR tyrosine kinase inhibitor and a NF-κB inhibitor effectively suppressed cetuximab-resistant HNSCC and interfering with the EGFR–LTβ interaction reverses resistance.Conclusions: Our findings elucidate the mechanism of driver gene mutations–independent mechanism of acquired resistance to cetuximab in HNSCC and also provide potential strategies for combating cetuximab resistance. Clin Cancer Res; 23(15); 4388–401. ©2017 AACR.
Prospective Evaluation of Sunitinib-Induced Cardiotoxicity in Patients with Metastatic Renal Cell Carcinoma
Authors: Narayan Vivek , Keefe Stephen , Haas Naomi , Wang Le , Puzanov Igor , Putt Mary , Catino Anna , Fang James , Agarwal Neeraj , Hyman David , Smith Amanda M. , Finkelman Brian S. , Narayan Hari K. , Ewer Steven , ElAmm Chantal , Lenihan Daniel , Ky Bonnie 
Published: February 2017

Abstract
Purpose: To prospectively evaluate cardiotoxicity risk with sunitinib in metastatic renal cell carcinoma (mRCC) routine clinical practice using comprehensive echocardiography and biomarker phenotyping.
Experimental Design: In a multicenter prospective study of 90 patients with mRCC, echocardiography and biomarkers of cardiovascular injury and stress were quantified at baseline, 3.5, 15, and 33 weeks following sunitinib initiation. These “on-drug” visits corresponded to cycles 1, 3, and 6, respectively. Left ventricular (LV) dysfunction was defined as an absolute decline in LV ejection fraction (LVEF) by ≥10% to a value of &lt;50%. Conditional survival analyses predicted the risk of LV dysfunction. Linear mixed-effects models estimated changes in LVEF, high-sensitivity Troponin I (hsTnI), and B-type natriuretic peptide (BNP) over time.
Results: The predicted risk of LV dysfunction by cycle 6 was 9.7% (95% confidence interval, 3%–17%). The majority of events occurred in the first treatment cycle. This risk diminished to 5% and 2% in patients who had not experienced dysfunction by the completion of cycles 1 and 3, respectively. All evaluable patients who experienced LV dysfunction had subsequent improvement in LVEF with careful management. Six patients (6.7%) developed hsTnI elevations &gt;21.5 pg/mL, and 11 additional patients (12.2%) developed BNP elevations &gt;100 pg/mL. These elevations similarly tended to occur early and resolved over time.
Conclusions: On average, patients with mRCC receiving sunitinib exhibit modest declines in LVEF and nonsignificant changes in hsTnI and BNP. However, approximately 9.7% to 18.9% of patients develop more substantive abnormalities. These changes occur early and are largely recoverable with careful management. Clin Cancer Res; 23(14); 3601–9. ©2017 AACR.
Racial‐Ethnic Disparities in Acute Stroke Care in the Florida‐Puerto Rico Collaboration to Reduce Stroke Disparities Study
Authors: Sacco Ralph L. , Gardener Hannah , Wang Kefeng , Dong Chuanhui , Ciliberti‐Vargas Maria A. , Gutierrez Carolina M. , Asdaghi Negar , Burgin W. Scott , Carrasquillo Olveen , Garcia‐Rivera Enid J. , Nobo Ulises , Oluwole Sofia , Rose David Z. , Waters Michael F. , Zevallos Juan Carlos , Robichaux Mary , Waddy Salina P. , Romano Jose G. , Rundek Tatjana , Acosta Indrani E. , Antevy Peter , Dandapani Bhuvaneswari , Davila Angel , Diaz‐Acosta Sandra , Fenelon Kathy , Gandia Antonio , Gonzalez‐Sanchez Juan A. , Hanel Ricardo , Harris Jonathan , Hodges Wayne , Foster Dianne , Inverso Bruce , Luciano Roman Carlos , Mehta Brijesh , Mora Julia , Mueller‐Kronast Nils , Neill Terry , Nelson Joe , Rodriguez Abiezer , Rodriguez‐Colon Julio , Sand Charles , Saunders Rhoda , Walker Jeffrey , Yavagal Dileep 
Published: February 2017

Background
Racial‐ethnic disparities in acute stroke care can contribute to inequality in stroke outcomes. We examined race‐ethnic disparities in acute stroke performance metrics in a voluntary stroke registry among Florida and Puerto Rico Get With the Guidelines‐Stroke hospitals.

Methods and Results

Seventy‐five sites in the Florida Puerto Rico Stroke Registry (66 Florida and 9 Puerto Rico) recorded 58 864 ischemic stroke cases (2010–2014). Logistic regression models examined racial‐ethnic differences in acute stroke performance measures and defect‐free care (intravenous tissue plasminogen activator treatment, in‐hospital antithrombotic therapy, deep vein thrombosis prophylaxis, discharge antithrombotic therapy, appropriate anticoagulation therapy, statin use, smoking cessation counseling) and temporal trends. Among ischemic stroke cases, 63% were non‐Hispanic white (
NHW
), 18% were non‐Hispanic black (
NHB
), 14% were Hispanic living in Florida, and 6% were Hispanic living in Puerto Rico.
NHW
patients were the oldest, followed by Hispanics, and
NHB
s. Defect‐free care was greatest among
NHBs
(81%), followed by
NHWs
(79%) and Florida Hispanics (79%), then Puerto Rico Hispanics (57%) (
P
<0.0001). Puerto Rico Hispanics were less likely than Florida whites to meet any stroke care performance metric other than anticoagulation. Defect‐free care improved for all groups during 2010–2014, but the disparity in Puerto Rico persisted (2010:
NHWs
=63%,
NHBs
=65%, Florida Hispanics=59%, Puerto Rico Hispanics=31%; 2014:
NHWs
=93%,
NHBs
=94%, Florida Hispanics=94%, Puerto Rico Hispanics=63%).

Conclusions
Racial‐ethnic/geographic disparities were observed for acute stroke care performance metrics. Adoption of a quality improvement program improved stroke care from 2010 to 2014 in Puerto Rico and all Florida racial‐ethnic groups. However, stroke care quality delivered in Puerto Rico is lower than in Florida. Sustained support of evidence‐based acute stroke quality improvement programs is required to improve stroke care and minimize racial‐ethnic disparities, particularly in resource‐strained Puerto Rico.
Intravoxel Incoherent Motion Imaging in Small Vessel Disease
Authors: Zhang C. Eleana , Wong Sau May , Uiterwijk Renske , Staals Julie , Backes Walter H. , Hoff Erik I. , Schreuder Tobien , Jeukens Cécile R.L.P.N. , Jansen Jacobus F.A. , van Oostenbrugge Robert J. 
Published: February 2017

Background and Purpose—
Cerebral small vessel disease (SVD) is associated with cognitive impairment. This may be because of decreased microstructural integrity and microvascular perfusion, but data on these relationships are scarce. We determined the relationship between cognition and microvascular perfusion and microstructural integrity in SVD patients, using intravoxel incoherent motion imaging—a diffusion-weighted magnetic resonance imaging technique designed to determine microvascular perfusion and microstructural integrity simultaneously.

Methods—

Seventy-three patients with SVD and 39 controls underwent intravoxel incoherent motion imaging and neuropsychological assessment. Parenchymal diffusivity
D
(a surrogate measure of microstructural integrity) and perfusion-related measure
fD*
were calculated for the normal appearing white matter, white matter hyperintensities, and cortical gray matter. The associations between cognitive performance and
D
and
fD*
were determined.

Results—

In SVD patients, multivariable analysis showed that lower
fD*
in the normal appearing white matter and cortical gray matter was associated with lower overall cognition (
P
=0.03 and
P
=0.002, respectively), lower executive function (
P
=0.04 and
P
=0.01, respectively), and lower information-processing speed (
P
=0.04 and
P
=0.01, respectively).
D
was not associated with cognitive function. In controls, no association was found between
D
,
fD*
, and cognition.

Conclusions—
In SVD patients, lower cognitive performance is associated with lower microvascular perfusion in the normal appearing white matter and cortical gray matter. Our results support recent findings that both cortical gray matter and normal appearing white matter perfusion may play a role in the pathophysiology of cognitive dysfunction in SVD.

Clinical Trial Registration—

URL:
http://www.trialregister.nl
. Unique identifier: NTR3786.
Magnetic Resonance Imaging Plaque Hemorrhage for Risk Stratification in Carotid Artery Disease With Moderate Risk Under Current Medical Therapy
Authors: Hosseini Akram A. , Simpson Richard J. , Altaf Nishath , Bath Philip M. , MacSweeney Shane T. , Auer Dorothee P. 
Published: February 2017

Background and Purpose—
Magnetic resonance imaging (MRI)–defined carotid plaque hemorrhage (MRIPH) can predict recurrent cerebrovascular ischemic events in severe symptomatic carotid stenosis. It is less clear whether MRIPH can improve risk stratification despite optimized medical secondary prevention in those with moderate risk.

Methods—
One-hundred fifty-one symptomatic patients with 30% to 99% carotid artery stenosis (median age: 77, 60.5% men) clinically deemed to not benefit from endarterectomy were prospectively recruited to undergo MRI and clinical follow-up (mean, 22 months). The clinical carotid artery risk score could be evaluated in 88 patients. MRIPH+ve was defined as plaque intensity >150% that of adjacent muscle. Survival analyses were performed with recurrent infarction (stroke or diffusion-positive cerebral ischemia) as the main end point.

Results—

Fifty-five participants showed MRIPH+ve; 47 had low, 36 intermediate, and 5 high carotid artery risk scores. Cox regression showed MRIPH as a strong predictor of future infarction (hazard ratio, 5.2; 95% confidence interval, 1.64–16.34;
P
=0.005, corrected for degree of stenosis), also in the subgroup with 50% to 69% stenosis (hazard ratio, 4.1; 95% confidence interval, 1–16.8;
P
=0.049). The absolute risk of future infarction was 31.7% at 3 years in MRIPH+ve versus 1.8% in patients without (
P
<0.002). MRIPH increased cumulative risk difference of future infarction by 47.1% at 3 years in those with intermediate carotid artery risk score (
P
=0.004).

Conclusions—
The study confirms MRIPH to be a powerful risk marker in symptomatic carotid stenosis with added value over current risk scores. For patients undergoing current secondary prevention medication with clinically uncertain benefit from recanalization, that is, those with moderate degree stenosis and intermediate carotid artery risk scores, MRIPH offers additional risk stratification.