bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (Ulixertinib)
Authors: Germann Ursula A. , Furey Brinley F. , Markland William , Hoover Russell R. , Aronov Alex M. , Roix Jeffrey J. , Hale Michael , Boucher Diane M. , Sorrell David A. , Martinez-Botella Gabriel , Fitzgibbon Matthew , Shapiro Paul , Wick Michael J. , Samadani Ramin , Meshaw Kathryn , Groover Anna , DeCrescenzo Gary , Namchuk Mark , Emery Caroline M. , Saha Saurabh , Welsch Dean J. 
Published: September 2017

Abstract
Aberrant activation of signaling through the RAS–RAF–MEK–ERK (MAPK) pathway is implicated in numerous cancers, making it an attractive therapeutic target. Although BRAF and MEK-targeted combination therapy has demonstrated significant benefit beyond single-agent options, the majority of patients develop resistance and disease progression after approximately 12 months. Reactivation of ERK signaling is a common driver of resistance in this setting. Here we report the discovery of BVD-523 (ulixertinib), a novel, reversible, ATP-competitive ERK1/2 inhibitor with high potency and ERK1/2 selectivity. In vitro BVD-523 treatment resulted in reduced proliferation and enhanced caspase activity in sensitive cells. Interestingly, BVD-523 inhibited phosphorylation of target substrates despite increased phosphorylation of ERK1/2. In in vivo xenograft studies, BVD-523 showed dose-dependent growth inhibition and tumor regression. BVD-523 yielded synergistic antiproliferative effects in a BRAFV600E-mutant melanoma cell line xenograft model when used in combination with BRAF inhibition. Antitumor activity was also demonstrated in in vitro and in vivo models of acquired resistance to single-agent and combination BRAF/MEK–targeted therapy. On the basis of these promising results, these studies demonstrate BVD-523 holds promise as a treatment for ERK-dependent cancers, including those whose tumors have acquired resistance to other treatments targeting upstream nodes of the MAPK pathway. Assessment of BVD-523 in clinical trials is underway (NCT01781429, NCT02296242, and NCT02608229). Mol Cancer Ther; 16(11); 2351–63. ©2017 AACR.
Hemodynamic Profile of Patients With Heart Failure and Preserved Ejection Fraction Vary by Age
Authors: Nanayakkara Shane , Haykowsky Mark , Mariani Justin , Van Empel Vanessa , Maeder Micha T. , Vizi Donna , Kaye David M. 
Published: September 2017

Background

Patients with heart failure with preserved ejection fraction (
HFpEF
) exhibit a range of cardiovascular phenotypic profiles modified by several common comorbidities. In particular, patients with HFpEF tend to be older; however, it is unclear whether the effects of cardiovascular aging per se modify the expression of
HFpEF
. We therefore sought to investigate the interaction between age and physiologic profile in patients with
HFpEF
.

Methods and Results

We assessed the hemodynamic and metabolic profile of 40 patients with
HFpEF
. Patients underwent right heart catheterization at rest and during supine cycle ergometry, and were segregated into 2 groups by the median age of the cohort. Older patients with HFpEF demonstrated reduced resting cardiac output (4.8±1.2 L/min versus 5.7±1.1 L/min). With exercise, older patients demonstrated a marked rise in arteriovenous oxygen content difference (10.8±1.8 versus 7.9±2.4 mL,
P
≤0.001), driven by enhanced oxygen extraction. There was no significant difference in peak pulmonary capillary wedge pressure (30±7 mm Hg versus 27±6,
P
=0.135), including when indexed to workload (pulmonary capillary wedge pressure/W, 0.88 mm Hg/W versus 0.92;
P
=0.83).

Conclusions

Older patients with HFpEF display a different physiological phenotype compared with younger patients, with enhanced oxygen extraction and lower increment in cardiac output to increase oxygen consumption from rest to peak supine exercise. This finding highlights the importance in considering age when considering therapeutic options in patients with
HFpEF
.
Trends in Use of Biomarker Protocols for the Evaluation of Possible Myocardial Infarction
Authors: Hachey Brian J. , Kontos Michael C. , Newby L. Kristin , Christenson Robert H. , Peacock W. Frank , Brewer Katherine C. , McCord James 
Published: September 2017

Background
Various combinations of creatine kinase‐MB, myoglobin, and cardiac troponin I or T (cTnI/cTnT) have been used to evaluate patients with suspected acute coronary syndromes. The current recommendation is to use the 99th percentile of cTnI/cTnT as the sole marker for diagnosis of acute myocardial infarction.

Methods and Results

We retrospectively analyzed cardiac marker protocols collected from 824 US hospitals undergoing Chest Pain Center Accreditation through the Society of Cardiovascular Patient Care from 2009 to 2014. Data were obtained by a self‐reported survey that addressed cardiac marker(s), sampling time periods, and cut points used for evaluation of suspected acute myocardial infarction. The combination of cTnI or cTnT with creatine kinase‐MB was the most commonly used biomarker strategy. Use of cTnI or cTnT as the sole marker increased over time (14–37%;
P
<0.0001), as did use of the 99th percentile cut point for cTnI/cTnT (30–60%;
P
<0.0001).

Conclusion
There is considerable variation in cardiac marker testing strategies used in US hospitals for evaluation of suspected acute myocardial infarction. Although increasing, 24% of hospitals used a cTn alone strategy, and only 49% used cTn at the recommended 99th percentile cut point. This has important implications for the diagnosis and treatment of patients with acute myocardial infarction.
Trends in Racial/Ethnic Disparities in Cardiovascular Health Among US Adults From 1999–2012
Authors: Pool Lindsay R. , Ning Hongyan , Lloyd‐Jones Donald M. , Allen Norrina B. 
Published: September 2017

Background

In the United States, there are persistent racial and ethnic disparities in cardiovascular disease morbidity and mortality. National efforts have focused on reducing these disparities; however, little is known about the long‐term trends in racial/ethnic disparities in cardiovascular health (
CVH
).

Methods and Results

We included 11 285 adults aged ≥20 years from the National Health and Nutrition Examination Surveys survey cycles 1999/2000 through 2011/2012.
CVH
includes 7 health factors and behaviors—diet, physical activity, smoking status, body mass index, blood pressure, blood glucose, and total cholesterol—each scored as ideal (2 points), intermediate (1 point), or poor (0 points). Overall
CVH
is a summation of these scores (range, 0–14) points. Age‐adjusted mean
CVH
scores were calculated by race/ethnicity (non‐Hispanic black, non‐Hispanic white, or Mexican American) and sex for each survey cycle. Non‐Hispanic black women had significantly lower mean
CVH
scores as compared with non‐Hispanic white women at each survey cycle (difference=0.93;
P
=0.001 in 2011/2012) and Mexican‐American women had significantly lower mean score as compared with non‐Hispanic white women at almost all survey cycles (difference=0.71;
P
=0.02 in 2011/2012). Differences between racial/ethnic groups were smaller for men and were mostly nonsignificant.

Conclusions

From 1999/2000 to 2011/2012, there were enduring disparities in
CVH
for non‐Hispanic black and Mexican‐American women as compared with non‐Hispanic white women. Disparities that were present in 1999/2000 were present in 2011/2012, though no racial/ethnic differences became more pronounced over time. These findings provide
US
nationally representative data to evaluate health factors and behaviors of particular concern regarding racial/ethnic disparities in cardiovascular health.
Kidney Disease Measures and Left Ventricular Structure and Function: The Atherosclerosis Risk in Communities Study
Authors: Matsushita Kunihiro , Kwak Lucia , Sang Yingying , Ballew Shoshana H. , Skali Hicham , Shah Amil M. , Coresh Josef , Solomon Scott 
Published: September 2017

Background
Heart failure is one of the most important complications of chronic kidney disease (CKD). However, few studies comprehensively investigated left ventricular (LV) structure and function in relation to 2 key CKD measures, estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR).

Methods and Results

Among 4175 ARIC (Atherosclerosis Risk in Communities) participants (aged 66–90 years during 2011–2013), we quantified the association of eGFR and ACR with echocardiogram parameters of LV mass, size, systolic function, and diastolic function. Adjusting for demographic variables, both CKD measures were significantly associated with most echocardiogram parameters. Additionally accounting for other potential confounders, we observed significantly higher LV mass index according to reduced eGFR (82.3 [95% confidence interval (CI), 77.6–87.0] g/m
2
for eGFR <30 mL/min per 1.73 m
2
, 80.9 [95% CI, 77.3–84.6] g/m
2
for eGFR 30–44 mL/min per 1.73 m
2
, and 80.1 [95% CI, 76.7–83.5] g/m
2
for eGFR 45–59 mL/min per 1.73 m
2
compared with 78.7 [95% CI, 75.3–82.1] g/m
2
for eGFR 75–89 mL/min per 1.73 m
2
; trend
P
<0.001). Regarding LV size and function, significant differences were observed for some parameters, particularly at eGFR <30 mL/min per 1.73 m
2
. For ACR, the associations remained significant for most parameters (eg, LV mass index, 91.5 [95% CI, 86.6–96.5] g/m
2
for ACR ≥300 mg/g and 82.9 [95% CI, 79.4–86.3] g/m
2
for ACR 30–299 mg/g compared with 77.7 [95% CI, 74.4–81.1] g/m
2
for ACR <10 mg/g [trend
P
<0.001]; left arterial volume index, 24.9 [95% CI, 22.9–26.8] and 24.7 [95% CI, 23.4–26.1] mL/m
2
compared with 23.4 [95% CI, 22.1–24.7] mL/m
2
, respectively [trend
P
=0.010]). Dichotomizing echo parameters with clinical thresholds, the stronger relationships of ACR over eGFR were further evident.

Conclusions
LV mass was related to both CKD measures, whereas LV size and function were robustly associated with albuminuria. These results have implications for pathophysiological processes behind cardiorenal syndrome and targeted cardiac assessment in patients with CKD.
Clinical Characteristics and Management of Coronary Artery Perforations: A Single‐Center 11‐Year Experience and Practical Overview
Authors: Lemmert Miguel E. , van Bommel Rutger J. , Diletti Roberto , Wilschut Jeroen M. , de Jaegere Peter P. , Zijlstra F. , Daemen Joost , Van Mieghem Nicolas M. 
Published: September 2017

Background
Coronary artery perforation (CAP) is a potentially lethal complication of percutaneous coronary intervention. We report on the incidence, clinical characteristics, and management of iatrogenic coronary perforations based on an 11‐year single‐center experience.

Methods and Results
From February 9, 2005, through November 20, 2016, 150 CAP cases were identified from our percutaneous coronary intervention database of 21 212 procedures (0.71%). Mean age of CAP patients was 66±11 years, and 62.7% were male. Treated lesion type was B2/C in 94.6%, and 31.3% were chronic total occlusions. Nonworkhorse guidewires were applied in 74.3%. CAP types were Ellis type I in 2.9%, Ellis type II in 40.4%, Ellis type III in 54.8%, and Ellis type III cavity spilling in 1.9%. CAP treatment was conservative (including prolonged balloon inflation) in 73.3%. Covered stents, coiling, and fat embolization were used in 24.0%, 0.7%, and 2.0%, respectively. Pericardiocentesis for tamponade was required for 72 patients (48.0%), of whom 28 were initially unrecognized. Twelve patients (12.7%) required emergency cardiac surgery to alleviate tamponade. Periprocedural myocardial infarction occurred in 34.0%, and in‐hospital all‐cause mortality was 8.0%. All‐cause mortality accrued to 10.7% at 30 days and 17.8% at 1 year.

Conclusions
CAP is a rare complication of percutaneous coronary intervention, but morbidity and mortality are considerable. Early recognition and adequate management are of paramount importance.
Safety Outcomes After Percutaneous Transcatheter Closure of Patent Foramen Ovale
Authors: Merkler Alexander E. , Gialdini Gino , Yaghi Shadi , Okin Peter M. , Iadecola Costantino , Navi Babak B. , Kamel Hooman 
Published: September 2017

Background and Purpose—
We sought to evaluate the real-world rate of safety outcomes after patent foramen ovale (PFO) closure in patients with ischemic stroke or transient ischemic attack (TIA).

Methods—

We performed a retrospective cohort study using administrative claims data on all hospitalizations from 2005 to 2013 in New York, California, and Florida. Using
International Classification of Diseases, Ninth Revision, Clinical Modification
codes, we identified patients who underwent percutaneous transcatheter PFO closure within 1 year of ischemic stroke or TIA. Our outcome was an adverse event occurring during the hospitalization for PFO closure, defined as in prior studies as atrial fibrillation or flutter, cardiac tamponade, pneumothorax, hemothorax, a vascular access complication, or death. Crude rates were reported with exact confidence intervals.

Results—
We identified 1887 patients who underwent PFO closure after ischemic stroke or TIA. The rate of any adverse outcome during the hospitalization for PFO closure was 7.0% (95% confidence interval [CI], 5.9%–8.2%). Rates of adverse outcomes varied by age and type of preceding cerebrovascular event. In patients >60 years of age, the rate of adverse outcomes was 10.9% (95% CI, 8.6%–13.6%) versus 4.9% (95% CI, 3.8%–6.3%) in patients ≤60 years of age. The rate of adverse outcomes was 9.9% (95% CI, 7.3%–12.5%) in patients with preceding ischemic stroke versus 5.9% (95% CI, 4.7%–7.1%) after TIA.

Conclusions—
Approximately 1 in 14 patients who underwent percutaneous transcatheter PFO closure after ischemic stroke or TIA experienced a serious periprocedural adverse outcome or death. The risk of adverse outcomes was highest in older patients and in those with preceding ischemic stroke.
Medicines education at home – A case study in Finland
Authors: Hokkanen Johanna , Elorinne Anna-Liisa , Hämeen-Anttila Katri , Keinonen Tuula 
Published: September 2017

Background: Educating children about medicines and medicine use is part of health education and is often seen as parents’ responsibility. However, to date, little research has been conducted on medicines education as provided in the home. Objective: To explore (1) parents’ attitudes towards medicines, (2) medicines education practices in the home and (3) the interaction in medicines education between the home and at school. Design: Mixed-methods case study. Setting: Pupils and their parents in one comprehensive school in Finland. Method: Before an educational intervention with Year 4 (aged 10–11 years) and Year 7 (aged 13–14 years) students, parents completed a background survey concerning their perceptions, beliefs and knowledge of medicines ( n = 250). Following the intervention, interviews with 12 mothers and 12 children, and medicine cabinet studies ( n = 10) were conducted. Quantitative data were analysed using K-mean cluster analysis to see whether respondents could be divided into different clusters based on their attitudes towards medicines. Qualitative data were analysed using theory-guided content analysis to obtain a picture of home medicines education. Results: Participants, mostly mothers, were divided into different types of medicine educators, whose attitudes towards medicines were either positive or neutral. Medicine consumption practices varied between families, but medicines were usually discussed when the child, a family member, a relative or a friend had a long-term illness; when a family member was suffering from a sickness; and while taking a medicine. In general, interaction between the home and the school was rather limited. Conclusion: The majority of mothers exhibited a strong reliance on public systems of health care. Greater interaction between schools and the home is needed in Finnish medicines education.
Influential factors in lexical richness of young heritage speakers’ family language: Iranians in New Zealand
Authors: Gharibi Khadijeh , Boers Frank 
Published: September 2017

Aims and objectives: This study investigates the extent to which young heritage speakers’ oral narratives in their first language (L1) differ from monolinguals’ narratives with regard to lexical richness (lexical diversity and lexical sophistication). It also explores which demographic factors (age, age at emigration and length of emigration) and/or socio-linguistic factors (frequency of heritage language use and parental attitudes toward heritage language maintenance) account for the differences. Data and analysis: The participants were a group of 25 young speakers of Persian as a heritage language, who were either born in or emigrated to New Zealand, and a group of 25 monolingual counterparts in Iran. Demographic information about the heritage speakers as well as information about parental attitude and practices regarding heritage language acquisition and maintenance were collected through semi-structured interviews with their parents. A film-retelling task was used to elicit the oral narratives, and these were analyzed for lexical diversity (by means of the Measure of Textual Lexical Diversity) and for lexical sophistication (by counting the incidence of low-frequency words). Findings and conclusion: As expected, the monolinguals’ narratives tended to manifest greater lexical richness than the heritage speakers’, especially according to the measure of lexical sophistication. Against expectation, frequency of heritage language use and parental attitude toward heritage language acquisition and maintenance were not found to be significant predictors of the young heritage speakers’ results. For the heritage speakers who were born in New Zealand, the results were predicted best by their age, while for those who arrived in New Zealand at a later age, the best predictors were both their age and how old they were at the time of emigration. This suggests that the demographic factors overrode the potential influence of the socio-linguistic variables examined. Originality: This study sheds light on (factors that contribute to) young heritage speakers’ L1 lexical competence, a topic that has hitherto been under-investigated. Significance and implications: A major implication of this study is showing the association of age and heritage speakers’ lexical richness. Although the statistical analyses did not show the effect of socio-linguistic variables, this finding indirectly supports the effect of parental input on heritage language proficiency in young bilinguals. Limitations: Limitations of the study include the relatively small number of participants, the use of only one task to elicit speech samples and the reliance on parents’ self-reported family language habits.
Structure Results for Semilinear Elliptic Equations with Hardy Potentials
Authors: Franca Matteo , Garrione Maurizio 
Published: September 2017

Abstract
We prove structure results for the radial solutions of the semilinear problem

Δ
⁢
u

+

λ
⁢

(

|
x
|

)

|
x
|

2

⁢
u

+

f
⁢

(

u
⁢

(
x
)

,

|
x
|

)

=
0

,

\Delta u+\frac{\lambda(|x|)}{|x|^{2}}u+f(u(x),|x|)=0,

where λ is a function and f is superlinear in the u-variable. As particular cases, we are able to deal with Matukuma potentials and with nonlinearities f having different polynomial behaviors at zero and at infinity. We give the complete picture for the subcritical, critical and supercritical cases. The technique relies on the Fowler transformation, allowing to deal with a dynamical system in

ℝ
3

{{\mathbb{R}}^{3}}

, for which elementary invariant manifold theory allows to draw the conclusions involving regular/singular and fast/slow-decay solutions.
Application of the Undifferenced GNSS Precise Positioning in Determining Coordinates in National Reference Frames
Authors: Krzan Grzegorz , Stępniak Katarzyna 
Published: September 2017

Abstract
In high-accuracy positioning using GNSS, the most common solution is still relative positioning using double-difference observations of dual-frequency measurements. An increasingly popular alternative to relative positioning are undifferenced approaches, which are designed to make full use of modern satellite systems and signals. Positions referenced to global International Terrestrial Reference Frame (ITRF2008) obtained from Precise Point Positioning (PPP) or Undifferenced (UD) network solutions have to be transformed to national (regional) reference frame, which introduces additional bases related to the transformation process. In this paper, satellite observations from two test networks using different observation time series were processed. The first test concerns the positioning accuracy from processing one year of dual-frequency GPS observations from 14 EUREF Permanent Network (EPN) stations using NAPEOS 3.3.1 software. The results were transformed into a national reference frame (PL-ETRF2000) and compared to positions from an EPN cumulative solution, which was adopted as the true coordinates. Daily observations were processed using PPP and UD multi-station solutions to determine the final accuracy resulting from satellite positioning, the transformation to national coordinate systems and Eurasian intraplate plate velocities. The second numerical test involved similar processing strategies of post-processing carried out using different observation time series (30 min., 1 hour, 2 hours, daily) and different classes of GNSS receivers. The centimeter accuracy of results presented in the national coordinate system satisfies the requirements of many surveying and engineering applications.
Analysis of Potato Consumption among Households in Odeda Local Government Area, Ogun State, Nigeria
Authors: Sanusi Muinat Mobolanle , Babatunde Damola Andrew 
Published: September 2017

Abstract
The study investigated the socio-economic factors affecting potato consumption among households in Odeda Local Government Area (LGA), Ogun State. Multistage sampling technique was used to gather information from 80 households using a structured questionnaire. Data collected were analyzed using descriptive statistics and regression model. The study showed that 67.5 % of the household-heads were male, 42.5 % were less than 30 years old, more than half (53.8 %) had income less than NG₦50,000.00 (US$322.59) monthly while 55 % and 68.8 % spend less than NG₦2,000.00 (US$12.90) on sweet and Irish potato, respectively, on a monthly basis. The linear functional form for sweet potato regression result showed that the total household income and sweet potato market price were both significant at 5 % with the coefficient of determination (R2) being 0.611 while the double-log functional form for Irish potato regression result showed that age of household-head, Irish potato market price and price of substitute (yam) were significant at 5 %, 10 % and 10 %, respectively, with coefficient of determination (R2) being 0.897; and had a positive relationship with potato consumption in the study area. Conclusively, the age of household-head, total monthly income, price of potato and price of substitute were factors that determined consumption of potato in the study area. In order to combat problems of malnutrition and to contribute to improvement in households’ welfare in Odeda LGA, efforts should be intensified in ensuring that households have access to adequate quantity of food and promotion of households’ education on the nutritional values and human nutrition with respect to age and gender are necessary.