bluuebunny/crossref_metadata_2025 huggingface dataset:
The benefits of data linkage for firefighter injury surveillance
Authors: Widman Shannon A , LeVasseur Michael T , Tabb Loni P , Taylor Jennifer A
Published: February 2017

Background

While survey data are available for national estimates of fire events and firefighter fatalities, data on firefighter injury at the national and local levels remain incomplete and unreliable. Data linkage provides a vehicle to maximise case detection and deepen injury description for the US fire service.

Methods

By linking departmental Human Resources records, despatch data, workers' compensation and first reports of injury, researchers were able to describe reported non-fatal injuries to 3063 uniformed members of the Philadelphia Fire Department (PFD), for the period of 2005 through 2013.

Results

Among all four databases, the overall linkage rate was 56%. Among three of the four databases, the linkage rate was 88%. Because there was duplication of some variables among the datasets, we were able to deeply describe all the linked injuries in the master database. 45.5% of uniformed PFD members reported at least one injury during the study period. Strains, falls, burns and struck-by injuries were the most common causes. Burns resulted in the highest lost time claim payout, and strains accounted for the highest medical claim cost. More than 70% of injuries occurred in the first 15 years of experience.

Discussion

Data linkage provided three new benefits: (1) creation of a new variable—years of experience, (2) reduction of misclassification bias when determining cause of injury, leading to more accurate estimates of cost and (3) visualisation of injury rates when controlling for the number of fire department responses, allowing for the generation of hypotheses to investigate injury hot spots.
The efficacy of protein supplementation during recovery from muscle-damaging concurrent exercise
Authors: Eddens Lee , Browne Sarah , Stevenson Emma J. , Sanderson Brad , van Someren Ken , Howatson Glyn
Published: February 2017

This study investigated the effect of protein supplementation on recovery following muscle-damaging exercise, which was induced with a concurrent exercise design. Twenty-four well-trained male cyclists were randomised to 3 independent groups receiving 20 g protein hydrolysate, iso-caloric carbohydrate, or low-calorific placebo supplementation, per serve. Supplement serves were provided twice daily, from the onset of the muscle-damaging exercise, for a total of 4 days and in addition to a controlled diet (6 g·kg−1·day−1 carbohydrate, 1.2 g·kg−1·day−1 protein, remainder from fat). Following the concurrent exercise session at time-point 0 h, comprising a simulated high-intensity road cycling trial and 100 drop-jumps, recovery of outcome measures was assessed at 24, 48, and 72 h. The concurrent exercise protocol was deemed to have caused exercise-induced muscle damage (EIMD), owing to time effects (p < 0.001), confirming decrements in maximal voluntary contraction (peaking at 15% ± 10%) and countermovement jump performance (peaking at 8% ± 7%), along with increased muscle soreness, creatine kinase, and C-reactive protein concentrations. No group or interaction effects (p > 0.05) were observed for any of the outcome measures. The present results indicate that protein supplementation does not attenuate any of the indirect indices of EIMD imposed by concurrent exercise, when employing great rigour around the provision of a quality habitual diet and the provision of appropriate supplemental controls.
Is adherence to the Canadian 24-Hour Movement Behaviour Guidelines for Children and Youth associated with improved indicators of physical, mental, and social health?
Authors: Janssen Ian , Roberts Karen C. , Thompson Wendy
Published: February 2017

The Canadian 24-Hour Movement Guidelines for Children and Youth were released in 2016. These guidelines contained recommendations for moderate to vigorous physical activity, screen time, and sleep duration. The objectives of this study were to determine (i) if achieving the individual recommendations and combinations of the recommendations within the guidelines is associated with indicators of physical, mental, and social health within children and youth; (ii) if meeting the recommendation for a specific movement behaviour is associated with larger differences in physical, mental, and social health indicators compared with meeting the recommendations for the other specific movement behaviours; and (iii) if physical, mental, and social health indicators differ according to different combinations of the guideline recommendations achieved. To address these objectives, we studied a representative sample of over 17 000 Canadians aged 10–17 years. The findings indicated that participants achieving any given recommendation had preferable scores for the health outcomes compared with participants who did not meet the recommendations. There was a dose–response pattern between the number of recommendations achieved and the health outcomes, indicating that the health outcomes improved as more recommendations were achieved. When the number of recommendations achieved was the same, there were no differences in the health outcomes. For instance, health indicators scores were not different in the group who achieved the sleep and screen time recommendations, the group who achieved sleep and moderate to vigorous physical activity recommendations, and the group who achieved screen time and moderate to vigorous physical activity recommendations.
Computing UV–vis spectra of 1-bromo-1-propene: a comparison of model core potential and all-electron basis sets
Authors: Oakley Meagan , Klobukowski Mariusz
Published: February 2017

Vacuum ultraviolet (VUV) spectroscopy can be used to identify different isomers in complicated mixtures of many molecules. In this work, calculated VUV spectra are compared with spectra of experimental mixtures to benchmark appropriate computational methods. Because the benchmark molecule, 1-bromo-1-propene, contains a heavy atom, both all-electron and model core potential basis sets were investigated. Time-dependent density functional theory (TD-DFT) can accurately compute electronic excited states at low-energy excitations and was cross-checked at higher energies against results from the symmetry adapted cluster–configuration interaction (SAC–CI) method. TD-DFT was determined to be satisfactory at low energies; however, excitation energies can deviate by 0.5 eV at high energies. TD-DFT with both all-electron and model core potential basis sets produced satisfactory excitation energies for the lower excited states. This method is also satisfactory at predicting spectra produced experimentally, including a mixture of isomers (cis- and trans-1-bromo-1-propene), with the exception of underestimating oscillator strength.
Simulation testing the robustness of a multiregion, tag-integrated assessment model that exhibits natal homing and estimates natural mortality and reporting rate
Authors: Vincent Matthew T. , Brenden Travis O. , Bence James R.
Published: February 2017

The influence of model complexity on integrated tagging and catch-at-age analysis (ITCAAN) parameter estimation is poorly understood for populations exhibiting natal homing. We investigated ITCAAN performance under varying levels of movement, degree of similarity in population productivities, data quality, spatial complexity in parameterization, and whether natural mortality and (or) reporting rates were fixed at actual values, estimated, or misspecified. Dynamics of four populations with natal homing that intermixed during periods of harvest were simulated based on Lake Erie walleye (Sander vitreus). Our results suggest, when high-quality tagging data are available, ITCAAN models are able to simultaneously estimate movement rates, natural mortality, and tag reporting rates, though accuracy and precision of model estimates will decrease with greater model complexity and fewer tags released. Additionally, ITCAAN models may have difficulty estimating individual population abundances under certain movement rates when population productivities are vastly different. ITCAAN models that estimate natural mortality and reporting rates may perform best with similar sized populations and when data are available to assist the estimation of reporting rates.
𝜖-expansion in critical ϕ3-theory on real projective space from conformal field theory
Authors: Hasegawa Chika , Nakayama Yu
Published: February 2017

We use a compatibility between the conformal symmetry and the equations of motion to solve the one-point function in the critical [Formula: see text]-theory (a.k.a. the critical Lee–Yang model) on the [Formula: see text] dimensional real projective space to the first nontrivial order in the [Formula: see text]-expansion. It reproduces the conventional perturbation theory and agrees with the numerical conformal bootstrap result.
Quantum phase transition and Berry phase of the Dicke model in the presence of the Stark-shift
Authors: Abdel-Rady A. S. , Hassan Samia. S. A. , Osman Abdel-Nasser A. , Salah Ahmed
Published: February 2017

In this paper, we employ the energy surface method to study a system of a two-level atom Bose–Einstein condensate coupled to a high-finesse optical cavity interacting with a single-mode electromagnetic field in the presence of the Stark-shift. The energy surface, the Phase transitions and the Berry phase of the two-level atom in Dicke model are obtained. Employing the Holstein–Primakoff representation of the angular momentum Lie algebra, the coupling line separation of the normal phase and the superradiant phase which occurs in a collection of fluorescent emitters (such as atoms), between a state containing few electromagnetic excitations are studied and a mean field description of the Dicke model is presented. We notice that in the thermodynamic limit, the energy surface takes a simple form for a direct description of the phase transition. Moreover, we show that the Stark-shift parameters and the atom–atom interactions can strongly affect the phase transition point. The results in the absence of the Stark-shift agree precisely with those obtained by Li, Liu and Zhou, who studied the same model using a different method.
Phase transition and Gibbs measures of Vannimenus model on semi-infinite Cayley tree of order three
Authors: Akın Hasan
Published: February 2017

Ising model with competing nearest–neighbors (NN) and prolonged next–nearest–neighbors (NNN) interactions on a Cayley tree has long been studied, but there are still many problems untouched. This paper tackles new Gibbs measures of Ising–Vannimenus model with competing NN and prolonged NNN interactions on a Cayley tree (or Bethe lattice) of order three. By using a new approach, we describe the translation-invariant Gibbs measures (TIGMs) for the model. We show that some of the measures are extreme Gibbs distributions. In this paper, we try to determine when phase transition does occur.
Optical Flow and Prediction Residual Based Hybrid Forensic System for Inter-Frame Tampering Detection
Authors: Singh Raahat Devender , Aggarwal Naveen
Published: February 2017

In the wake of widespread proliferation of inexpensive and easy-to-use digital content editing software, digital videos have lost the idealized reputation they once held as universal, objective and infallible evidence of occurrence of events. The pliability of digital content and its innate vulnerability to unobtrusive alterations causes us to become skeptical of its validity. However, in spite of the fact that digital videos may not always present a truthful picture of reality, their usefulness in today’s world is incontrovertible. Therefore, the need to verify the integrity and authenticity of the contents of a digital video becomes paramount, especially in critical scenarios such as defense planning and legal trials where reliance on untrustworthy evidence could have grievous ramifications. Inter-frame tampering, which involves insertion/removal/replication of sets of frames into/from/within a video sequence, is among the most un-convoluted and elusive video forgeries. In this paper, we propose a potent hybrid forensic system that detects inter-frame forgeries in compressed videos. The system encompasses two forensic techniques. The first is a novel optical flow analysis based frame-insertion and removal detection procedure, where we focus on the brightness gradient component of optical flow and detect irregularities caused therein by post-production frame-tampering. The second component is a prediction residual examination based scheme that expedites detection and localization of replicated frames in video sequences. Subjective and quantitative results of comprehensive tests on an elaborate dataset under diverse experimental set-ups substantiate the effectuality and robustness of the proposed system.
Guiding SAT Solving by Formula Partitioning
Authors: Mann Zoltán Ádám , Papp Pál András
Published: February 2017

When deciding the satisfiability of a Boolean formula, one promising approach is to split the formula into two smaller independent sub-formulas. While many studies report encouraging early results with such methods, the approach is rarely used in state-of-the-art solvers. In this paper, we present a technique that uses formula partitioning to guide the solution of the SAT problem through providing initialization values for the VSIDS heuristic. Our results on a large number of benchmark instances show that the method can notably improve the performance of modern solvers, especially if the time available for solving is short. We also present some findings in the area of hypergraph partitioning, which is used as a tool for our technique.
Reviewing the Treatment of Uncertainty in Hydro-economic Modeling of the Murray–Darling Basin, Australia
Authors: Settre Claire , Connor Jeff , Wheeler Sarah Ann
Published: February 2017

Hydro-economic modeling is the combination of economic principles and hydrological modeling to achieve a more integrated representation of water resource management. In the Murray–Darling Basin (MDB), hydro-economic modeling has been widely used to analyze and inform basin-wide water policy. A growing but uneven literature base has prompted this review of MDB hydro-economic studies published over the past three decades to identify innovations and avenues for advancement. We focus particularly on the treatment of uncertainty, which is inherent in all modeling. While consideration of uncertainty is increasing in prominence, our review indicates the robust treatment of epistemic and stochastic uncertainty have not been fully integrated in the hydro-economic modeling literature. When hydro-economic modeling results are used to inform policy, treatment of uncertainty has both technical and political implications. We conclude that the methodological rigor of MDB hydro-economic modeling can be vastly improved with greater attention to quantifying, reducing and communicating uncertainties inherent in the modeling of water resources.
Behavioral Phenotyping Assays for Genetic Mouse Models of Neurodevelopmental, Neurodegenerative, and Psychiatric Disorders
Authors: Sukoff Rizzo Stacey J. , Crawley Jacqueline N.
Published: February 2017

Animal models offer heuristic research tools to understand the causes of human diseases and to identify potential treatments. With rapidly evolving genetic engineering technologies, mutations identified in a human disorder can be generated in the mouse genome. Phenotypic outcomes of the mutation are then explicated to confirm hypotheses about causes and to discover effective therapeutics. Most neurodevelopmental, neurodegenerative, and psychiatric disorders are diagnosed primarily by their prominent behavioral symptoms. Mouse behavioral assays analogous to the human symptoms have been developed to analyze the consequences of mutations and to evaluate proposed therapeutics preclinically. Here we describe the range of mouse behavioral tests available in the established behavioral neuroscience literature, along with examples of their translational applications. Concepts presented have been successfully used in other species, including flies, worms, fish, rats, pigs, and nonhuman primates. Identical strategies can be employed to test hypotheses about environmental causes and gene × environment interactions.
Antibody Repertoire Development in Swine
Authors: Butler J.E. , Wertz Nancy , Sinkora Marek
Published: February 2017

We describe the domestication of the species, explore its value to agriculture and bioscience, and compare its immunoglobulin (Ig) genes to those of other vertebrates. For encyclopedic information, we cite earlier reviews and chapters. We provide current gene maps for the heavy and light chain loci and describe their polygeny and polymorphy. B-cell and antibody repertoire development is a major focus, and we present findings that challenge several mouse-centric paradigms. We focus special attention on the role of ileal Peyer's patches, the largest secondary lymphoid tissues in newborn piglets and a feature of all artiodactyls. We believe swine fetal development and early class switch evolved to provide natural secretory IgA antibodies able to prevent translocation of bacteria from the gut while the bacterial PAMPs drive development of adaptive immunity. We discuss the value of using the isolator piglet model to address these issues.
Local vs. volume conductance activity of field potentials in the human subthalamic nucleus
Authors: Marmor Odeya , Valsky Dan , Joshua Mati , Bick Atira S , Arkadir David , Tamir Idit , Bergman Hagai , Israel Zvi , Eitan Renana
Published: February 2017

Subthalamic nucleus field potentials have attracted growing research and clinical interest over the last few decades. However, it is unclear whether subthalamic field potentials represent locally generated neuronal subthreshold activity or volume conductance of the organized neuronal activity generated in the cortex. This study aimed at understanding of the physiological origin of subthalamic field potentials and determining the most accurate method for recording them. We compared different methods of recordings in the human subthalamic nucleus: spikes (300–9,000 Hz) and field potentials (3–100 Hz) recorded by monopolar micro- and macroelectrodes, as well as by differential-bipolar macroelectrodes. The recordings were done outside and inside the subthalamic nucleus during electrophysiological navigation for deep brain stimulation procedures (150 electrode trajectories) in 41 Parkinson’s disease patients. We modeled the signal and estimated the contribution of nearby/independent vs. remote/common activity in each recording configuration and area. Monopolar micro- and macroelectrode recordings detect field potentials that are considerably affected by common (probably cortical) activity. However, bipolar macroelectrode recordings inside the subthalamic nucleus can detect locally generated potentials. These results are confirmed by high correspondence between the model predictions and actual correlation of neuronal activity recorded by electrode pairs. Differential bipolar macroelectrode subthalamic field potentials can overcome volume conductance effects and reflect locally generated neuronal activity. Bipolar macroelectrode local field potential recordings might be used as a biological marker of normal and pathological brain functions for future electrophysiological studies and navigation systems as well as for closed-loop deep brain stimulation paradigms.

NEW & NOTEWORTHY Our results integrate a new method for human subthalamic recordings with a development of an advanced mathematical model. We found that while monopolar microelectrode and macroelectrode recordings detect field potentials that are considerably affected by common (probably cortical) activity, bipolar macroelectrode recordings inside the subthalamic nucleus (STN) detect locally generated potentials that are significantly different than those recorded outside the STN. Differential bipolar subthalamic field potentials can be used in navigation and closed-loop deep brain stimulation paradigms.
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.
Central Role of Metabolism in Endothelial Cell Function and Vascular Disease
Authors: Bierhansl Laura , Conradi Lena-Christin , Treps Lucas , Dewerchin Mieke , Carmeliet Peter
Published: February 2017

The importance of endothelial cell (EC) metabolism and its regulatory role in the angiogenic behavior of ECs during vessel formation and in the function of different EC subtypes determined by different vascular beds has been recognized only in the last few years. Even more importantly, apart from a role of nitric oxide and reactive oxygen species in EC dysfunction, deregulations of EC metabolism in disease only recently received increasing attention. Although comprehensive metabolic characterization of ECs still needs further investigation, the concept of targeting EC metabolism to treat vascular disease is emerging. In this overview, we summarize EC-specific metabolic pathways, describe the current knowledge on their deregulation in vascular diseases, and give an outlook on how vascular endothelial metabolism can serve as a target to normalize deregulated endothelium.
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

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

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

Purpose: 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

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 <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 >21.5 pg/mL, and 11 additional patients (12.2%) developed BNP elevations >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.
Minocycline-Induced Hyperpigmentation in a Patient Treated with Erlotinib for Non-Small Cell Lung Adenocarcinoma
Authors: Bell Ann T. , Roman John W. , Gratrix Max L. , Brzezniak Christina E.
Published: February 2017

Introduction: While epidermal growth factor receptor (EGFR) inhibitors have improved progression-free survival in patients with non-small cell lung cancer (NSCLC), one of the most common adverse effects is papulopustular skin eruption, which is frequently severe enough to be treated with oral minocycline or doxycycline. Case: We present a case of an 87-year-old man who developed a severe papulopustular skin eruption secondary to erlotinib therapy for NSCLC. Control of the eruption with 100 mg of minocycline twice daily for 8 months eventually led to blue-gray skin hyperpigmentation. After 30 months, this side effect was recognized as minocycline drug deposition, which was confirmed with skin biopsy. Discussion: Compliance with EGFR inhibitor therapy in NSCLC is often challenging due to common side effects, most notably cutaneous skin eruptions. Treatment of cutaneous toxicities is important to preserve patient compliance with targeted cancer therapy. Use of minocycline to treat the most common cutaneous side effect (papulopustular eruption) can in turn cause blue-black skin, eye, or tooth discoloration that can nullify its benefits, resulting in suboptimal patient adherence to cancer therapy. Although this adverse effect is well known in dermatology literature as a risk when using minocycline to treat acne, rosacea, or blistering disorders, it is less well documented in oncology literature. We present this case to highlight the need for greater consideration of unique patient characteristics in selecting an oral antibiotic as a treatment modality for EGFR inhibitor skin toxicities.
Phakic Intraocular Lens Implantation: Refractive Outcome and Safety in Patients with Anterior Chamber Depth between 2.8 and 3.0 versus ≥3.0 mm
Authors: Guerra Marta G. , Silva Andreia M.M. , Marques Sara H.M. , Melo Sofia H. , Póvoa João A. , Lobo Conceição , Murta Joaquim Neto
Published: February 2017

Purpose: To compare endothelial cell (EC) variation after anterior chamber phakic intraocular lens (AC-pIOL) implantation in highly myopic patients with a preoperative anterior chamber depth (ACD) between 2.8 and 3.0 versus ≥3.0 mm. Methods: A total of 280 eyes submitted to primary AC-pIOL implantation were analyzed. Pre- and postoperative values for uncorrected distance visual acuity, corrected distance visual acuity, spherical equivalent, ACD (endothelial surface), and EC count were collected. The eyes were divided into 2 groups: group A - ACD between 2.8 and 3.0 mm; group B - ACD ≥3.0 mm. Mean global EC loss (ECL) and loss for each ACD group, according to pIOL type, were analyzed. Results: Significant improvement of the spherical equivalent (-11.38 ± 4.57 vs. -0.49 ± 0.79; p = 0.000) and a significant decrease in EC density (2,810.95 ± 343.88 vs. 2,584.09 ± 374.88 cells/mm2; p = 0.000) were noted. The mean annual ECL was -2.19 ± 3.97%. Regarding group A (n = 80), a mean annual ECL of -2.06 ± 3.88% was registered, higher for the Acrysof Cachet® subtype, while group B (n = 200) showed -2.25 ± 4.01% ECL, higher for the Verisyse® subtype. There was no significant difference between the groups (p = 0.96). Conclusions: AC-pIOL implantation significantly improves the spherical equivalent in myopic patients. The mean annual ECL after pIOL implantation was higher in the larger ACD group, but this value was not statistically significant. A 2.8-mm ACD value seems to be a safe cutoff for AC-pIOL implantation.
T-Cell Lymphoma in a Patient with Neurofibromatosis Type 1 and AIDS
Authors: de Castro Izana Junqueira , da Silva Esther Botelho Soares , dos Santos Talita Rezende , de Freitas Amanda Barroso , de Castro Inara Junqueira , Portela Alessandra Santos , de Magalhães Marilza Campos , Pires Karina Lebeis , da Silva Guilherme Almeida Rosa , de Azevedo Marcelo Costa Velho Mendes
Published: February 2017

Neurofibromatosis type 1 (NF1) and AIDS are risk factors for the development of malignant neoplasms, including hematological malignancies, such as non-Hodgkin lymphoma. NF1 is an autosomal dominant disease that primarily manifests as café-au-lait spots, dermal neurofibromas, axillary and/or inguinal ephelides or freckles, plexiform neurofibromas, Lisch nodules, and bone deformities. In this report, we present a 38-year-old female patient with NF1 from childhood and AIDS who developed peripheral T-cell lymphoma with good response to chemotherapeutic treatment.
Mammary Analogue Secretory Carcinoma Presenting as a Cervical Lymph Node Metastasis of Unknown Primary Site: A Case Report
Authors: Suzuki Kensuke , Yagi Masao , Kanda Akira , Kobayashi Yoshiki , Konishi Masaya , Miyasaka Chika , Tashiro Takashi , Iwai Hiroshi
Published: February 2017

Background: Mammary analogue secretory carcinoma (MASC) is a pathological entity arising in the salivary glands first described by Skalova et al. [Am J Surg Pathol 2010;34: 599–608]. Here, we report the ﬁrst case of MASC presenting as a cervical lymph node metastasis of unknown primary site together with a brief review of the literature. Case Report: We present a 74-year-old male with a painless lump in his left neck. Based on the fine-needle aspiration cytological findings, a possible malignant tumor was suspected. No evidence of a primary lesion was observed using imaging modalities including positron emission tomography/computed tomography. The patient underwent an ipsilateral modified radical neck dissection. Immunohistochemical staining showed that the neoplastic cells were positive for S100 protein and GATA3. A rearrangement of the ETV6 gene was noted during ﬂuorescence in situ hybridization, and the final histopathological diagnosis was MASC. Conclusion: We encountered a MASC presenting as a cervical lymph node metastasis of unknown primary site. No adjuvant therapy was administered, and no local recurrence or metastatic disease has been detected during a follow-up period of 9 months. This is the first case report of MASC presenting as a cervical lymph node metastasis of unknown primary site and suggests the new properties of MASC.
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.
Bone Marrow–Derived MicroRNA‐223 Works as an Endocrine Genetic Signal in Vascular Endothelial Cells and Participates in Vascular Injury From Kawasaki Disease
Authors: Chu Maoping , Wu Rongzhou , Qin Shanshan , Hua Wenfeng , Shan Zhen , Rong Xing , Zeng Jingjing , Hong Lanlan , Sun Yeying , Liu Ying , Li Wen , Wang Shenming , Zhang Chunxiang
Published: February 2017

Background

Kawasaki disease (
KD
) is now the most common cause of acquired cardiac disease in children due to permanent coronary artery damage with unknown etiology. The study sought to determine the role of blood micro
RNA
miR‐223 in
KD
and
KD
‐induced injuries in vascular endothelial cells (
EC
s) as well as the mechanisms involved.

Methods and Results

Micro
RNA
profiles in serum from patients with
KD
and from healthy controls were assessed by microarray analysis. We noted that multiple serum micro
RNA
s were aberrantly expressed in
KD
, among them miR‐223, which was the most upregulated abundant serum micro
RNA
. We found that bone marrow–derived blood cells (leukocytes and platelets) were able to secrete miR‐223 into serum. Vascular
EC
s had no endogenous miR‐223; however, the blood cell–secreted serum miR‐223 could enter into the vascular
EC
s in the vascular walls. The exogenous miR‐223 had strong biological effects on
EC
functions via its target genes such as
IGF
1R. Interestingly,
KD
‐induced
EC
injuries were related to increased miR‐223 because they were inhibited by miR‐223 knockdown. Finally, these observations were verified using miR‐223 knockout mice and the chimeric mice generated by transplantation of bone marrow from miR‐223 knockout mice into wild‐type mice.

Conclusions

In
KD
patients, the levels of blood cell–derived miR‐223 in
EC
s are significantly increased. The increased miR‐223 in
EC
s could work as a novel endocrine genetic signal and participate in vascular injury of
KD
. MiR‐223 may provide a novel mechanism and a new therapeutic target for vascular complication of
KD
.