bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anal Cancer Incidence in the United States, 1977–2011: Distinct Patterns by Histology and Behavior
Authors: Shiels Meredith S. , Kreimer Aimée R. , Coghill Anna E. , Darragh Teresa M. , Devesa Susan S. 
Published: July 2015

Abstract
Background: Although anal squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are generally combined in cancer surveillance, their etiologies likely differ. Here, we describe demographic characteristics and trends in incidence rates (IR) of anal cancer by histology (SCC, ADC) and behavior (invasive, in situ) in the United States.
Methods: With data from the Surveillance, Epidemiology, and End Results (SEER) Program, we estimated age-adjusted anal cancer IRs across behavior/histology by demographic and tumor characteristics for 2000–2011. Trends in IRs and annual percent changes during 1977–2011 were also estimated and compared with rectal cancer.
Results: Women had higher rates of SCC [rate ratio (RR), 1.45; 95% confidence interval (CI), 1.40–1.50] and lower rates of ADC (RR, 0.68; 95% CI, 0.62–0.74) and squamous carcinoma in situ (CIS; RR, 0.36; 95% CI, 0.34–0.38) than men. Blacks had lower rates of SCC (RR, 0.82; 95% CI, 0.77–0.87) and CIS (RR, 0.90; 95% CI, 0.83–0.98) than non-Hispanic whites, but higher rates of ADC (RR, 1.48; 95% CI, 1.29–1.70). Anal cancer IRs were higher in men and blacks aged &lt;40 years. During 1992–2011, SCC IRs increased 2.9%/year, ADC IRs declined nonsignificantly, and CIS IRs increased 14.2%/year. SCC and ADC IR patterns and trends were similar across anal and rectal cancers.
Conclusions: Rates of anal SCC and CIS have increased strongly over time, in contrast to rates of anal ADC, similar to trends observed for rectal SCC and ADC.
Impact: Anal SCC and ADC likely have different etiologies, but may have similar etiologies to rectal SCC and ADC, respectively. Strong increases in CIS IRs over time may reflect anal cancer screening patterns. Cancer Epidemiol Biomarkers Prev; 24(10); 1548–56. ©2015 AACR.
Intake of Meat Mutagens and Risk of Prostate Cancer in a Cohort of U.S. Health Professionals
Authors: Rohrmann Sabine , Nimptsch Katharina , Sinha Rashmi , Willett Walter C. , Giovannucci Edward L. , Platz Elizabeth A. , Wu Kana 
Published: July 2015

Abstract
Background: Evidence relating heterocyclic aromatic amines (HCA), associated with high-temperature cooking methods, to prostate cancer risk is inconsistent.
Methods: In a large U.S. cohort study, intakes of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and a meat-derived mutagenicity (MDM) index were assessed using a cooking method questionnaire administered in 1996. Until 2010, 2,770 prostate cancer cases were observed among 26,030 participants.
Results: Intake of PhIP from red meat was statistically significantly associated with total prostate cancer risk (top vs. bottom quintile HR, 1.18; 95% confidence intervals; CI, 1.03–1.35), but not other HCAs (MeIQx, 1.12; 0.98–1.27, PhIP from white meat, 1.08; 0.95–1.22, DiMeIQx, 1.09; 0.97–1.21) or MDM (1.13; 1.00–1.28). For high-grade (Gleason sum 7 with pattern 4+3 and Gleason sum 8–10, n = 483 cases) and advanced cancers (n = 281), we only observed positive associations for PhIP from red meat (top vs. bottom quintile: high grade: HR, 1.44; 95% CI, 1.04–1.98, Ptrend = 0.03; advanced: HR, 1.50; 95% CI, 0.99–2.26; Ptrend = 0.12), but associations for advanced cancers did not reach statistical significance. Observed associations remained similar after adjustment for total, unprocessed, or processed red meat intake.
Conclusion: Observed positive associations between PhIP intake from red meat and prostate cancer, particularly high-grade and possibly also advanced prostate cancer, need to be confirmed in other studies.
Impact: Results do not provide strong evidence that HCAs increase risk of prostate cancers. Cancer Epidemiol Biomarkers Prev; 24(10); 1557–63. ©2015 AACR.
Tankyrase Inhibition Blocks Wnt/β-Catenin Pathway and Reverts Resistance to PI3K and AKT Inhibitors in the Treatment of Colorectal Cancer
Authors: Arqués Oriol , Chicote Irene , Puig Isabel , Tenbaum Stephan P. , Argilés Guillem , Dienstmann Rodrigo , Fernández Natalia , Caratù Ginevra , Matito Judit , Silberschmidt Daniel , Rodon Jordi , Landolfi Stefania , Prat Aleix , Espín Eloy , Charco Ramón , Nuciforo Paolo , Vivancos Ana , Shao Wenlin , Tabernero Josep , Palmer Héctor G. 
Published: July 2015

Abstract
Purpose: Oncogenic mutations in the KRAS/PI3K/AKT pathway are one of the most frequent alterations in cancer. Although PI3K or AKT inhibitors show promising results in clinical trials, drug resistance frequently emerges. We previously revealed Wnt/β-catenin signaling hyperactivation as responsible for such resistance in colorectal cancer. Here we investigate Wnt-mediated resistance in patients treated with PI3K or AKT inhibitors in clinical trials and evaluate the efficacy of a new Wnt/tankyrase inhibitor, NVP-TNKS656, to overcome such resistance.
Experimental Design: Colorectal cancer patient-derived sphere cultures and mouse tumor xenografts were treated with NVP-TNKS656, in combination with PI3K or AKT inhibitors.We analyzed progression-free survival of patients treated with different PI3K/AKT/mTOR inhibitors in correlation with Wnt/β-catenin pathway activation, oncogenic mutations, clinicopathological traits, and gene expression patterns in 40 colorectal cancer baseline tumors.
Results: Combination with NVP-TNKS656 promoted apoptosis in PI3K or AKT inhibitor-resistant cells with high nuclear β-catenin content. High FOXO3A activity conferred sensitivity to NVP-TNKS656 treatment. Thirteen of 40 patients presented high nuclear β-catenin content and progressed earlier upon PI3K/AKT/mTOR inhibition. Nuclear β-catenin levels predicted drug response, whereas clinicopathologic traits, gene expression profiles, or frequent mutations (KRAS, TP53, or PIK3CA) did not.
Conclusions: High nuclear β-catenin content independently predicts resistance to PI3K and AKT inhibitors. Combined treatment with a Wnt/tankyrase inhibitor reduces nuclear β-catenin, reverts such resistance, and represses tumor growth. FOXO3A content and activity predicts response to Wnt/β-catenin inhibition and together with β-catenin may be predictive biomarkers of drug response providing a rationale to stratify colorectal cancer patients to be treated with PI3K/AKT/mTOR and Wnt/β-catenin inhibitors. Clin Cancer Res; 22(3); 644–56. ©2015 AACR.
Neutrophil-to-lymphocyte ratio: an inflammation marker related to cardiovascular risk in children
Authors: Gispert-Saüch Montserrat , Díaz-Roldán Ferran , Carreras-Badosa Gemma , Osiniri Inés , Planella-Colomer Montserrat , Mayol Lluís , de Zegher Francis , Ibánez Lourdes , Bassols Judit , López-Bermejo Abel , Prats-Puig Anna 
Published: July 2015

SummaryLow-grade chronic inflammation plays a pathogenic role in cardiovascular disease. An increase in the ratio of circulating neutrophils to lymphocytes (N/L ratio) may serve as a marker of cardiovascular risk in adults. It was the study objective to study whether N/L ratio associates with vascular parameters in children. Subjects were 501 prepubertal and early pubertal Caucasian children (mean age 8.0 years; mean body mass index (BMI) Z-score 0.2 ± 0.9; 266 boys and 235 girls) recruited within an ongoing population-based study. The subjects were stratified into three groups according to age. Neutrophil, lymphocyte, BMI, waist circumference, systolic blood pressure (SBP) and carotid intima-media thickness (cIMT), assessed in all children. The N/L ratio, derived from the absolute neutrophil and lymphocyte counts. In children aged < 7 years (n=190, all prepubertal), no associations were observed between N/L ratio and either anthropometric or cardiovascular parameters. In children aged 7–9 years (n=171, 1.7 % early pubertal), higher N/L ratio associated with higher BMI Z-score and waist circumference (p=0.008 to p< 0.0001). In children aged > 9 years (n=140, 29.2 % early pubertal), N/L ratio associated again with BMI Z-score and waist circumference and also positively with SBP and cIMT (all p=0.008 to p< 0.0001). These associations remained significant in linear regression models following adjustment for possible confounding variables such as age, gender, fasting triglycerides, C-reactive protein and puberty (and for SBP and cIMT, adjustment also for BMI). In conclusion, our results provide the first evidence that a higher N/L ratio is associated with a less favourable cardiovascular profile in children and delineate the development of these associations from late childhood onwards.
Novel Abetalipoproteinemia Missense Mutation Highlights the Importance of the N-Terminal β-Barrel in Microsomal Triglyceride Transfer Protein Function
Authors: Walsh Meghan T. , Iqbal Jahangir , Josekutty Joby , Soh James , Di Leo Enza , Özaydin Eda , Gündüz Mehmet , Tarugi Patrizia , Hussain M. Mahmood 
Published: July 2015

Background—
The use of microsomal triglyceride transfer protein (MTP) inhibitors is limited to severe hyperlipidemias because of associated hepatosteatosis and gastrointestinal adverse effects. Comprehensive knowledge about the structure–function of MTP might help design new molecules that avoid steatosis. Characterization of mutations in MTP causing abetalipoproteinemia has revealed that the central α-helical and C-terminal β-sheet domains are important for protein disulfide isomerase binding and lipid transfer activity. Our aim was to identify and characterize mutations in the N-terminal domain to understand its function.

Methods and Results—
We identified a novel missense mutation (D169V) in a 4-month-old Turkish male child with severe signs of abetalipoproteinemia. To study the effect of this mutation on MTP function, we created mutants via site-directed mutagenesis. Although D169V was expressed in the endoplasmic reticulum and interacted with apolipoprotein B (apoB) 17, it was unable to bind protein disulfide isomerase, transfer lipids, and support apoB secretion. Computational modeling suggested that D169 could form an internal salt bridge with K187 and K189. Mutagenesis of these lysines to leucines abolished protein disulfide isomerase heterodimerization, lipid transfer, and apoB secretion, without affecting apoB17 binding. Furthermore, mutants with preserved charges (D169E, K187R, and K189R) rescued these activities.

Conclusions—
D169V is detrimental because it disrupts an internal salt bridge leading to loss of protein disulfide isomerase binding and lipid transfer activities; however, it does not affect apoB binding. Thus, the N-terminal domain of MTP is also important for its lipid transfer activity.
Attentional Capacity Limits Gap Detection during Concurrent Sound Segregation
Authors: Leung Ada W. S. , Jolicoeur Pierre , Alain Claude 
Published: July 2015

Abstract
Detecting a brief silent interval (i.e., a gap) is more difficult when listeners perceive two concurrent sounds rather than one in a sound containing a mistuned harmonic in otherwise in-tune harmonics. This impairment in gap detection may reflect the interaction of low-level encoding or the division of attention between two sound objects, both of which could interfere with signal detection. To distinguish between these two alternatives, we compared ERPs during active and passive listening with complex harmonic tones that could include a gap, a mistuned harmonic, both features, or neither. During active listening, participants indicated whether they heard a gap irrespective of mistuning. During passive listening, participants watched a subtitled muted movie of their choice while the same sounds were presented. Gap detection was impaired when the complex sounds included a mistuned harmonic that popped out as a separate object. The ERP analysis revealed an early gap-related activity that was little affected by mistuning during the active or passive listening condition. However, during active listening, there was a marked decrease in the late positive wave that was thought to index attention and response-related processes. These results suggest that the limitation in detecting the gap is related to attentional processing, possibly divided attention induced by the concurrent sound objects, rather than deficits in preattentional sensory encoding.
Activation Patterns throughout the Word Processing Network of L1-dominant Bilinguals Reflect Language Similarity and Language Decisions
Authors: Oganian Yulia , Conrad Markus , Aryani Arash , Spalek Katharina , Heekeren Hauke R. 
Published: July 2015

Abstract
A crucial aspect of bilingual communication is the ability to identify the language of an input. Yet, the neural and cognitive basis of this ability is largely unknown. Moreover, it cannot be easily incorporated into neuronal models of bilingualism, which posit that bilinguals rely on the same neural substrates for both languages and concurrently activate them even in monolingual settings. Here we hypothesized that bilinguals can employ language-specific sublexical (bigram frequency) and lexical (orthographic neighborhood size) statistics for language recognition. Moreover, we investigated the neural networks representing language-specific statistics and hypothesized that language identity is encoded in distributed activation patterns within these networks. To this end, German–English bilinguals made speeded language decisions on visually presented pseudowords during fMRI. Language attribution followed lexical neighborhood sizes both in first (L1) and second (L2) language. RTs revealed an overall tuning to L1 bigram statistics. Neuroimaging results demonstrated tuning to L1 statistics at sublexical (occipital lobe) and phonological (temporoparietal lobe) levels, whereas neural activation in the angular gyri reflected sensitivity to lexical similarity to both languages. Analysis of distributed activation patterns reflected language attribution as early as in the ventral stream of visual processing. We conclude that in language-ambiguous contexts visual word processing is dominated by L1 statistical structure at sublexical orthographic and phonological levels, whereas lexical search is determined by the structure of both languages. Moreover, our results demonstrate that language identity modulates distributed activation patterns throughout the reading network, providing a key to language identity representations within this shared network.
Wintertime Atmospheric Response to North Atlantic Ocean Circulation Variability in a Climate Model
Authors: Frankignoul Claude , Gastineau Guillaume , Kwon Young-Oh 
Published: July 2015

Abstract
Maximum covariance analysis of a preindustrial control simulation of the NCAR Community Climate System Model, version 4 (CCSM4), shows that a barotropic signal in winter broadly resembling a negative phase of the North Atlantic Oscillation (NAO) follows an intensification of the Atlantic meridional overturning circulation (AMOC) by about 7 yr. The delay is due to the cyclonic propagation along the North Atlantic Current (NAC) and the subpolar gyre of a SST warming linked to a northward shift and intensification of the NAC, together with an increasing SST cooling linked to increasing southward advection of subpolar water along the western boundary and a southward shift of the Gulf Stream (GS). These changes result in a meridional SST dipole, which follows the AMOC intensification after 6 or 7 yr. The SST changes were initiated by the strengthening of the western subpolar gyre and by bottom torque at the crossover of the deep branches of the AMOC with the NAC on the western flank of the Mid-Atlantic Ridge and the GS near the Tail of the Grand Banks, respectively. The heat flux damping of the SST dipole shifts the region of maximum atmospheric transient eddy growth southward, leading to a negative NAO-like response. No significant atmospheric response is found to the Atlantic multidecadal oscillation (AMO), which is broadly realistic but shifted south and associated with a much weaker meridional SST gradient than the AMOC fingerprint. Nonetheless, the wintertime atmospheric response to the AMOC shows some similarity with the observed response to the AMO, suggesting that the ocean–atmosphere interactions are broadly realistic in CCSM4.
Recanalisation and ulcer recurrence rates following ultrasound-guided foam sclerotherapy
Authors: Howard Julia K , Slim Fiona JA , Wakely Margaret C , Emerson Lorraine G , Davies Colin E , Kulkarni Sachin R , Bulbulia Richard A , Whyman Mark R , Poskitt Keith R 
Published: July 2015

Objectives The aim was to assess vein recanalisation and ulcer recurrence in patients with chronic venous ulceration following ultrasound-guided foam sclerotherapy. Method Open (CEAP 6) or recently healed (CEAP 5) chronic venous leg ulcers were treated with foam sclerotherapy between July 2010 and August 2012. Venous duplex scans were performed two weeks and one and two years post treatment, recording recanalisation and reflux. One- and two-year ulcer recurrence rates were calculated using Kaplan–Meier survival analysis. Results A total of 100 legs were treated in 92 patients; 86 were CEAP 5 and 14 were CEAP 6. At two weeks complete or short segment occlusion was demonstrated in 99/100 legs. Complete follow-up was 93% at one year and 88% at two years. Complete and segmental recanalisation with new reflux was recorded in 11/93 (12%) legs and 25/93 (27%) legs, respectively (overall 36/93; 39%) at one year; and 6/88 (7%) legs and 15/88 (17%) legs, respectively (overall 21/88; 24%) at two years. Kaplan–Meier survival analysis shows 64% ulcers healed at 24 weeks and 86% at one year. Ulcer recurrence rate at one and two years was 2.3% and 5.1%. Conclusions Over one-third of superficial veins treated with foam sclerotherapy recanalised at one year and just under a quarter of superficial veins recanalised at two years. Despite this, ulcer recurrence rates were low, and recanalisation failed to predict recurrence.
Tissue Doppler indices of diastolic function in critically ill patients and association with mortality – a systematic review
Authors: Garry David , Newton Jim , Colebourn Claire 
Published: July 2015

Purpose Systolic impairment is well reported in critically ill patients but diastolic function has been relatively understudied. The objective of this review was to assess tissue Doppler indices of diastolic function in critically ill patients along with any association with mortality. Methods A systematic review of articles in English using Medline, EMBASE, CINAHL and the Cochrane database of systematic reviews. Search terms included diastolic function, diastolic dysfunction, diastolic abnormal*, diastolic heart failure, diastolic filling, ventricular relaxation, pulmonary artery occlusion pressure, left ventricular filling pressure, cardiac dysfunction, intensive care, critical care, critically ill, critical illness, sepsis and septic shock. Only studies of critically ill adult patients (excluding post-cardiac surgical patients) whose diastolic function was assessed using tissue Doppler imaging were included. Study quality was assessed using a modified version of the Newcastle–Ottawa Scale (NOS). Results Nineteen studies were included, with a total of 1365 patients. All trials were observational. There was a large heterogeneity in patient populations and the methodology of tissue Doppler assessment of diastology resulting in a descriptive analysis. Patient groups included severe sepsis or septic shock (5 studies), septic shock (5 studies), systemic inflammatory response syndrome and shock (1 study), septic shock and acute lung injury (1 study), cancer and septic shock (2 studies), general ICU patients (1 study), combined medical and surgical ICU (2 studies) and sub-arachnoid haemorrhage patients (2 studies). Seventeen studies scored 5/6 on the NOS with the remaining two scoring 4/6. Fourteen studies reported on numbers of patients diagnosed with diastolic dysfunction (500/999, mean 50%, range 20–92%). Three studies found that diastolic dysfunction was an independent predictor of mortality. Conclusions Current data shows a large range in the incidence of diastolic dysfunction in this patient population and a variable link with mortality. Future research should focus on the definition of normal values for diastolic function in critically ill patients along with the effects of ICU therapies and consensus criteria for its assessment in this patient population.
Incidental echocardiographic findings of a quadricuspid aortic valve associated with aortic regurgitation in a cat
Authors: Nakamura Takashi , Sawada Tamotsu , Takagi Mayumi 
Published: July 2015

Case summary A 10-month-old male domestic shorthair cat was brought to Kitanomori Animal Hospital for routine castration. Preoperative thoracic radiography revealed a mildly enlarged heart silhouette, and transthoracic echocardiography (ECHO) suggested a quadricuspid aortic valve associated with central aortic regurgitation (regurgitant fraction 31%). After sedation with intramuscular medetomidine and midazolam for castration, heart rate decreased from 193 to 76 beats per minute. ECHO under sedation revealed two equally small and two equally large aortic valve cusps, suggesting a type C quadricuspid aortic valve. The findings were confirmed by real-time three-dimensional ECHO. Relevance and novel information This case reveals the echocardiographic features of a feline quadricuspid aortic valve and shows that transthoracic ECHO is useful to examine aortic valve morphology in cats. It also suggests that echocardiographic screening may be beneficial for detecting congenital cardiac anomalies in apparently healthy cats.
Effects of eltrombopag on platelet count and platelet activation in Wiskott-Aldrich syndrome/X-linked thrombocytopenia
Authors: Gerrits Anja J. , Leven Emily A. , Frelinger Andrew L. , Brigstocke Sophie L. , Berny-Lang Michelle A. , Mitchell W. Beau , Revel-Vilk Shoshana , Tamary Hannah , Carmichael Sabrina L. , Barnard Marc R. , Michelson Alan D. , Bussel James B. 
Published: July 2015

Key Points
Platelet function in WAS/XLT, measured by agonist-induced surface-activated GPIIb-IIIa and P-selectin, is proportional to platelet size. Eltrombopag increased platelet counts, but did not improve platelet activation, in most WAS/XLT patients.
Design of fusion technique-based mining engine for smart business
Authors: Sato Atsushi , Huang Runhe , Yen Neil Y 
Published: July 2015

AbstractKeys to successful implementation of smart business require a wide spectrum of domain knowledge, experts, and their correlated experiences. Excluding those external factors—which can be collected by well-deployed sensors—being aware of user (or consumer) has the highest priority on the to-do-list. The more user is understood, the more user can be satisfied from an intuitive point of view, and thus, data plays a rather essential role in the scenario. However, it is never easy to achieve comprehensive understanding as the data requires further processing before its values can be extracted and used. So how the data can be properly transformed into something useful for smart business development is exactly what we pursue in this study. As a pioneer, three major tasks are focused. First, a data mining engine based on the concept of the KID model is designed and developed to be responsible for the universal collection of data and mining valuable information which is primarily from real world, cyber world, and social world. Second, we go further into the fusion process of the collected data and meaningful information extracted and interpreted by algorithms or fused algorithms in the data mining engine (e.g., the consumer purchase data shared by real-world company) and turn them into valuable knowledge about the situation of customers and business situations based on the concept of knowledge, information, and data. A three-layer analysis and mining procedure is designed to enhance the mining engine through conventional RFM (Recency, Frequency, and Monetary Value) model and a set of fusion techniques. And in the end, we make planning-based predictions for a real-world company for expansion of the business interests.