bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor Suppressor HIPK2 Regulates Malignant Growth via Phosphorylation of Notch1
Authors: Ann Eun-Jung , Kim Mi-Yeon , Yoon Ji-Hye , Ahn Ji-Seon , Jo Eun-Hye , Lee Hye-Jin , Lee Hyun-Woo , Kang Hyeok-Gu , Choi Dong Wook , Chun Kyung-Hee , Lee Ji Shin , Choi Cheol Yong , Ferrando Adolfo A. , Lee Keesook , Park Hee-Sae 
Published: June 2016

Abstract
The receptor Notch1 plays an important role in malignant progression of many cancers, but its regulation is not fully understood. In this study, we report that the kinase HIPK2 is responsible for facilitating the Fbw7-dependent proteasomal degradation of Notch1 by phosphorylating its intracellular domain (Notch1-IC) within the Cdc4 phosphodegron motif. Notch1-IC expression was higher in cancer cells than normal cells. Under genotoxic stress, Notch1-IC was phosphorylated constitutively by HIPK2 and was maintained at a low level through proteasomal degradation. HIPK2 phosphorylated the residue T2512 in Notch1-IC. Somatic mutations near this residue rendered Notch1-IC resistant to degradation, as induced either by HIPK2 overexpression or adriamycin treatment. In revealing an important mechanism of Notch1 stability, the results of this study could offer a therapeutic strategy to block Notch1-dependent progression in many types of cancer. Cancer Res; 76(16); 4728–40. ©2016 AACR.
Myc Expression Drives Aberrant Lipid Metabolism in Lung Cancer
Authors: Hall Zoe , Ament Zsuzsanna , Wilson Catherine H. , Burkhart Deborah L. , Ashmore Tom , Koulman Albert , Littlewood Trevor , Evan Gerard I. , Griffin Julian L. 
Published: June 2016

Abstract
MYC-mediated pathogenesis in lung cancer continues to attract interest for new therapeutic strategies. In this study, we describe a transgenic mouse model of KRAS-driven lung adenocarcinoma that affords reversible activation of MYC, used here as a tool for lipidomic profiling of MYC-dependent lung tumors formed in this model. Advanced mass spectrometric imaging and surface analysis techniques were used to characterize the spatial and temporal changes in lipid composition in lung tissue. We found that normal lung tissue was characterized predominantly by saturated phosphatidylcholines and phosphatidylglycerols, which are major lipid components of pulmonary surfactant. In contrast, tumor tissues displayed an increase in phosphatidylinositols and arachidonate-containing phospholipids that can serve as signaling precursors. Deactivating MYC resulted in a rapid and dramatic decrease in arachidonic acid and its eicosanoid metabolites. In tumors with high levels of MYC, we found an increase in cytosolic phospholipase A2 (cPLA2) activity with a preferential release of membrane-bound arachidonic acid, stimulating the lipoxygenase (LOX) and COX pathways also amplified by MYC at the level of gene expression. Deactivating MYC lowered cPLA2 activity along with COX2 and 5-LOX mRNA levels. Notably, inhibiting the COX/5-LOX pathways in vivo reduced tumor burden in a manner associated with reduced cell proliferation. Taken together, our results show how MYC drives the production of specific eicosanoids critical for lung cancer cell survival and proliferation, with possible implications for the use of COX and LOX pathway inhibitors for lung cancer therapy. Cancer Res; 76(16); 4608–18. ©2016 AACR.
Eritoran Suppresses Colon Cancer by Altering a Functional Balance in Toll-like Receptors That Bind Lipopolysaccharide
Authors: Kuo Wei-Ting , Lee Tsung-Chun , Yu Linda Chia-Hui 
Published: June 2016

Abstract
Colorectal carcinogenesis is affected by overexpression of the lipopolysaccharide (LPS) receptors CD14 and TLR4, which antagonize each other by affecting epithelial cell proliferation and apoptosis. Eritoran is an investigational drug for sepsis treatment that resembles the lipid A moiety of LPS and therefore acts as a TLR4 inhibitor. In the present study, we explored the potential therapeutic uses and mechanisms of action of eritoran in reducing colon cancer progression. Eritoran administration via intracolonic, intragastric, or intravenous routes significantly reduced tumor burden in a chemically induced mouse model of colorectal carcinoma. Decreased proliferation and increased apoptosis were observed in mouse tumor cells after eritoran treatment. In vitro cultures of mouse primary tumor spheroids and human cancer cell lines displayed increased cell proliferation and cell-cycle progression following LPS challenge. This effect was inhibited by eritoran and by silencing CD14 or TLR4. In contrast, apoptosis induced by eritoran was eliminated by silencing CD14 or protein kinase Cζ (PKCζ) but not TLR4. Lastly, LPS and eritoran caused hyperphosphorylation of PKCζ in a CD14-dependent and TLR4-independent manner. Blocking PKCζ activation by a Src kinase inhibitor and a PKCζ-pseudosubstrate prevented eritoran-induced apoptosis. In summary, our work offers a preclinical proof of concept for the exploration of eritoran as a clinical treatment, with a mechanistic rationale to reposition this drug to improve the management of colorectal cancer. Cancer Res; 76(16); 4684–95. ©2016 AACR.
High-Sensitive C-Reactive Protein Predicts Recurrent Stroke and Poor Functional Outcome
Authors: Li Jiejie , Zhao Xingquan , Meng Xia , Lin Jinxi , Liu Liping , Wang Chunxue , Wang Anxin , Wang Yilong , Wang Yongjun ,   on behalf of the CHANCE Investigators
Published: June 2016

Background and Purpose—
Minor stroke and transient ischemic attack are common disorders with high rate of subsequent disabling stroke. We aim to investigate the role of high-sensitive C-reactive protein (hsCRP) in predicting recurrent stroke and poor functional outcome.

Methods—
In the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial, 3044 (59%) consecutive patients from 73 (64%) prespecified centers had hsCRP levels measured. The primary outcome was any stroke within 90 days. The secondary outcome included combined vascular events and dependence or death defined as modified Rankin Scale score of 2 to 6 at 90 days and a new vascular event during 1-year follow-up. The associations of hsCRP with recurrent stroke and functional outcome were analyzed by using Cox proportional hazards and logistic regression models.

Results—

Elevated hsCRP (>3.0 mg/L) was observed in 32% of the study population. Patients with hsCRP >3 mg/L had an increased risk of recurrent stroke (adjusted hazard ratio, 1.46; 95% confidence interval, 1.08–1.98;
P
=0.039), ischemic stroke and combined vascular events, and poor functional outcome (adjusted odds ratio, 1.68; 95% confidence interval, 1.22–2.32;
P
=0.002) compared with those with hsCRP <1 mg/L within 90-day follow-up period. High hsCRP levels also independently predicted recurrent stroke during 1-year follow-up. There was no interaction of hsCRP levels with randomized antiplatelet therapy.

Conclusions—
High hsCRP levels predict recurrent stroke and poor functional outcome in acute patients with minor stroke or transient ischemic attack.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00979589.
Risk Profile of Symptomatic Lacunar Stroke Versus Nonlobar Intracerebral Hemorrhage
Authors: Morotti Andrea , Paciaroni Maurizio , Zini Andrea , Silvestrelli Giorgio , Del Zotto Elisabetta , Caso Valeria , Dell’Acqua Maria Luisa , Simone Anna Maria , Lanari Alessia , Costa Paolo , Poli Loris , De Giuli Valeria , Gamba Massimo , Ciccone Alfonso , Ritelli Marco , Di Castelnuovo Augusto , Iacoviello Licia , Colombi Marina , Agnelli Giancarlo , Grassi Mario , de Gaetano Giovanni , Padovani Alessandro , Pezzini Alessandro 
Published: June 2016

Background and Purpose—
Although lacunar stroke (LS) and deep intracerebral hemorrhage (dICH) represent acute manifestations of the same pathological process involving cerebral small vessels (small vessel disease), it remains unclear what factors predispose to one phenotype rather than the other at individual level.

Methods—
Consecutive patients with either acute symptomatic LS or dICH were prospectively enrolled as part of a multicenter Italian study. We compared the risk factor profile of the 2 subgroups using multivariable logistic regression.

Results—

During a time course of 9.5 years, 1931 subjects (1434 LS and 497 dICH; mean age, 71.3±13.3 years; males, 55.5%) qualified for the analysis. Current smoking was associated with LS (odds ratio [OR], 2.17;
P
<0.001). Conversely, dICH cases were more likely to be hypertensive (OR, 1.87;
P
<0.001), excessive alcohol consumers (OR, 1.70;
P
=0.001), and more frequently under treatment with warfarin (OR, 2.05;
P
=0.010) and statins (OR, 3.10;
P
<0.001). Hypercholesterolemia, diabetes mellitus, and antiplatelet treatment were not associated with a specific small vessel disease manifestation.

Conclusions—
The risk factor profile of dICH differs from that associated with LS. This might be used for disease risk stratification at individual level.
Spatiotemporal Snowfall Variability in the Lake Michigan Region: How is Warming Affecting Wintertime Snowfall?
Authors: Clark Craig A. , Elless Travis J. , Lyza Anthony W. , Ganesh-Babu Bharath , Koning Dana M. , Carne Alexander R. , Boney Holly A. , Sink Amanda M. , Mustered Sarah K. , Barrick Justin M. 
Published: June 2016

AbstractThis study has investigated the spatiotemporal structure and changes in Lake Michigan snowfall for the period 1950–2013. With data quality caveats acknowledged, a larger envelope of stations was included than in previous studies to explore the data using time series analysis, principal component analysis, and geographic information systems. Results indicate warming in recent decades, a near-dearth of serial correlation, midwinter dependence on teleconnection patterns, strong sensitivity of snowfall to temperature, peak snowfall variability and dependence on temperature within the lake-effect belt, an increasing fraction of seasonal snowfall occurring from December to February, and temporal behavior consistent with the previously reported trend reversal in snowfall.
ENSO Teleconnection to the Isopycnal Depth Fluctuations of the East/Japan Sea Intermediate Water in the Ulleung Basin during 1968–2002
Authors: Yun Jae-Yul , Chang Kyung-Il , Kim Kwang-Yul , Cho Yang-Ki , Park Kyung-Ae , Magaard Lorenz 
Published: June 2016

AbstractThis study first detects the decadal variability in the depths of the East/Japan Sea (EJS) Intermediate Water (ESIW) using in situ observations and relates it to strong El Niño–Southern Oscillations (ENSOs). Using multitaper cross-spectrum and cyclostationary empirical orthogonal function analysis, this study found significant coherences at the 99% confidence level and opposite phases between Niño-3 and the ESIW isopycnal depths in the Ulleung Basin (UB) at a period of 14.1 yr during 1968–2002. This suggests a teleconnection between strong ENSOs and the ESIW, the cause of which is explored. When a strong El Niño (EN) develops, the Pacific–North American pattern is intensified by the EN-related Rossby wave interfering constructively with the climatological stationary wave. The amplified wave propagates upward into the stratosphere and breaks, weakening the polar vortex. The EN-related geopotential height increases over the pole with poleward converging air and decreases over the Yakutsk Basin (YB), indicating a negative northern annular mode with the south-to-north gradient balancing the easterly anomaly that responds to vortex weakening. The converged air at the pole warms adiabatically and raises the height as it sinks. This height distribution, including the east-to-west gradient balancing the southward flow, induces the polar vortex split into two with the colder one in the YB where the EJS is closer than from the pole. The EN-related northwesterly wind directing toward the EJS is also strong. Thus, the coldest air with negative wind stress curls reaches the EJS quickly and forms more ESIW, which converges into the UB, causing the observed decadal isopycnal fluctuations.
A Meta-Analysis of the Correlates of Successful Aging in Older Adults
Authors: Kim Sin-Hyang , Park Sihyun 
Published: June 2016

Objective: Successful aging (SA) is a concept that remains without a consensus definition. The purpose of the current study was to explore the components of SA by systematically reviewing factors correlated with SA. We also compared the relative strength of the components by using the meta-analytic method. Methods: A meta-analysis was conducted to quantitatively synthesize the correlates of SA from three online databases: PubMed, CINAHL, and SCOPUS. Main Findings: The correlates were categorized into four domains: (1) avoiding disease and disability, (2) having high cognitive/mental/physical function, (3) actively engaging in life, and (4) psychologically well adapted in later life. The domain “psychologically well adapted in later life” showed the strongest association with SA, ES( r) = .482. Conclusion: The findings of this study were meaningful in terms of examining the strength of the correlations between the domains and overall SA and, further, providing evidence for building interventions for aging population.
Quality Indicators for Head and Neck Oncologic Surgery
Authors: Puram Sidharth V. , Bhattacharyya Neil 
Published: June 2016

Objectivesto determine national benchmarks for established quality indicators in head and neck cancer (HNCA) surgery, focusing on differences between academic and nonacademic institutions.Study DesignCross‐sectional analysis of national database.Subjects and MethodsHNCA surgery admissions from the 2009‐2011 Nationwide Inpatient Sample were analyzed for preoperative characteristics and postoperative outcomes. Multivariate analyses were used to identify factors influencing quality indicators after HNCA surgery. Quality metrics—including length of stay (LOS), inpatient death, return to the operating room (OR), wound infection, and transfusion—were compared for academic versus nonacademic institutions.ResultsA total of 38,379 HNCA surgery inpatient admissions (mean age, 56.5 years; 52.4% male) were analyzed (28,288 teaching vs 10,091 nonteaching). Nationally representative quality metrics for HNCA surgery were as follows: mean LOS, 4.26 ± 0.12 days; return to OR, 3.3% ± 0.2%; inpatient mortality, 0.7% ± 0.1%; wound infection rate, 0.9% ± 0.1%; wound complication rate, 4.3% ± 0.2%; and transfusion rate, 4.3% ± 0.3%. HNCA surgery patients at teaching hospitals had a greater proportion of males, radiation history, and high‐acuity procedures and greater comorbidity scores (all P <. 001). Multivariate analyses adjusting for age, sex, income, payer, prior radiation, comorbidity scores, and procedural acuity demonstrated that teaching hospitals had a slightly increased LOS (+0.30 days; P =. 009) and odds ratio for wound infection (1.54; 95% CI: 1.22‐1.94) versus nonteaching hospitals. There were no significant differences in return to OR (P =. 271), inpatient mortality (P =. 686), or transfusion rate (P =. 960).ConclusionDespite caring for substantially more complex HNCA surgery patients with greater comorbidities, teaching hospitals demonstrate only a marginally increased LOS and wound complication rate versus nonteaching hospitals, while other established quality metrics are similar.
Are Online Zenker’s Diverticulum Materials Readable and Understandable?
Authors: Balakrishnan Vini , Chandy Zachariah , Verma Sunil P. 
Published: June 2016

ObjectivePatients use a multitude of resources to learn about Zenker’s diverticulum (ZD). The objectives of this study were to assess the readability and understandability of online materials on ZD, evaluate them against the existing criteria, and investigate the relationship between readability and understandability.MethodsThe first 50 webpages from an online search for ZD were analyzed. Twenty‐one webpages had materials intended for patients and were included in the study. The patient education materials (PEMs) were analyzed using 6 readability tools. Four individuals used the Patient Education Materials Evaluation Tool (PEMAT) to assess the understandability. Fleiss κ interrater reliability analysis determined consistency among the raters. Finally, Pearson correlation coefficient analyzed the relationship between readability and understandability.ResultsThe reading grade level of the materials reviewed ranged from 10th to 16th grade while the understandability ranged from 31% to 74%. Correlation analysis demonstrated a strong negative correlation between readability and understandability (r = −0.62, P <. 05). Fleiss’ κ interrater reliability for the raters demonstrated substantial agreement between the 4 raters (κ = 0.64).ConclusionOnline PEMs pertaining to ZD are written well above the recommended reading level. Materials written at a lower reading level are more understandable. A wide range of understandability exists among materials with identical reading grade levels.Implications for PracticeHealth care providers need to create new PEMs for ZD that are available online that are both readable and understandable. The PEMAT and readability formulas can provide a framework for authors to create these materials.
Nonthyroid Metastasis to the Thyroid Gland
Authors: Russell Jonathon O. , Yan Kenneth , Burkey Brian , Scharpf Joseph 
Published: June 2016

ObjectiveNonthyroid metastases to the thyroid gland can cause morbidity, including dysphagia, dysphonia, and airway compromise. Because metastatic malignancies portend a poor prognosis, obtaining equipoise between treatment morbidity and local disease progression is paramount. We reviewed cases of nonthyroid metastases to determine treatment and prognostic recommendations.Study DesignCase series with chart review.SettingTertiary care hospital.Subjects and MethodsWe searched PubMed for reported cases between 1994 and September 2013 using search terms as follows: any combination of primary tumor locations and thyroid, as well as the terms thyroid and metastasis. Only unique cases of nonthyroid metastases were included. Combined with 17 additional tumors at our own institution, we found 818 unique nonthyroid metastases, of which 384 had management and survival data available.ResultsRenal cell carcinoma was most common, presenting in 293 (35.8%) patients, followed by lung and gastrointestinal malignancies. Patients were treated with total thyroidectomy (34.0%), subtotal thyroidectomy including lobectomy (32.6%), and no surgery (33.5%). Surgical management was associated with improved survival duration (P <. 01). Locoregional recurrence was less likely in patients treated with total versus partial thyroidectomy (4.8% vs 13%). Extent of surgical management did not have a significant effect on patient survival. Delayed presentation was associated with improved survival duration (P =. 01).ConclusionsNonthyroid metastases to the thyroid gland are unusual tumors. Surgical intervention is associated with improved survival, but expected morbidity of untreated tumors is difficult to assess. Site of origin, time to diagnosis, and surgical approach are related to survival and recurrence rates.
Diabetes mellitus is associated with adverse structural and functional cardiac remodelling in chronic heart failure with reduced ejection fraction
Authors: Walker Andrew MN , Patel Peysh A , Rajwani Adil , Groves David , Denby Christine , Kearney Lorraine , Sapsford Robert J , Witte Klaus K , Kearney Mark T , Cubbon Richard M 
Published: June 2016

Background: Diabetes mellitus is associated with an increased risk of death and hospitalisation in patients with chronic heart failure. Better understanding of potential underlying mechanisms may aid the development of diabetes mellitus–specific chronic heart failure therapeutic strategies. Methods: Prospective observational cohort study of 628 patients with chronic heart failure associated with left ventricular systolic dysfunction receiving contemporary evidence-based therapy. Indices of cardiac structure and function, along with symptoms and biochemical parameters, were compared in patients with and without diabetes mellitus at study recruitment and 1 year later. Results: Patients with diabetes mellitus (24.2%) experienced higher rates of all-cause [hazard ratio, 2.3 (95% confidence interval, 1.8–3.0)] and chronic heart failure–specific mortality and hospitalisation despite comparable pharmacological and device-based therapies. At study recruitment, patients with diabetes mellitus were more symptomatic, required greater diuretic doses and more frequently had radiologic evidence of pulmonary oedema, despite higher left ventricular ejection fraction. They also exhibited echocardiographic evidence of increased left ventricular wall thickness and pulmonary arterial pressure. Diabetes mellitus was associated with reduced indices of heart rate variability and increased heart rate turbulence. During follow-up, patients with diabetes mellitus experienced less beneficial left ventricular remodelling and greater deterioration in renal function. Conclusion: Diabetes mellitus is associated with features of adverse structural and functional cardiac remodelling in patients with chronic heart failure.
RETRACTED: The reliability estimation for the braking system of high-speed electric multiple units based on Bayes and GO method
Authors: Yang Jianwei , Zhao Chunqing , Zhu Aihua , Yao Dechen , Wu Huijie 
Published: June 2016

At the request of the Authors, the following article has been retracted. Yang, Jianwei, Zhao, Chunqing, Zhu, Aihua, Yao, Dechen and Wu, Huijie (2016) The reliability estimation for the braking system of high-speed electric multiple units based on Bayes and GO method Advances in Mechanical Engineering published 21 June 2016. doi: 10.1177/1687814016654825
Antibody-mediated immune suppression is improved when blends of anti-RBC monoclonal antibodies are used in mice
Authors: Bernardo Lidice , Amash Alaa , Marjoram Danielle , Lazarus Alan H. 
Published: June 2016

Key Points
Effective inhibition of immunization by polyclonal IgG can be recapitulated by a blend of monoclonal antibodies to different epitopes.
Time-dependent changes in mortality and transformation risk in MDS
Authors: Pfeilstöcker Michael , Tuechler Heinz , Sanz Guillermo , Schanz Julie , Garcia-Manero Guillermo , Solé Francesc , Bennett John M. , Bowen David , Fenaux Pierre , Dreyfus Francois , Kantarjian Hagop , Kuendgen Andrea , Malcovati Luca , Cazzola Mario , Cermak Jaroslav , Fonatsch Christa , Le Beau Michelle M. , Slovak Marilyn L. , Levis Alessandro , Luebbert Michael , Maciejewski Jaroslaw , Machherndl-Spandl Sigrid , Magalhaes Silvia M. M. , Miyazaki Yasushi , Sekeres Mikkael A. , Sperr Wolfgang R. , Stauder Reinhard , Tauro Sudhir , Valent Peter , Vallespi Teresa , van de Loosdrecht Arjan A. , Germing Ulrich , Haase Detlef , Greenberg Peter L. 
Published: June 2016

Key Points
Hazards regarding mortality and leukemic transformation in MDS diminish over time in higher-risk but remain stable in lower-risk patients. This change of hazard indicates time-dependent attenuation of power of basal risk scores, which is relevant for clinical decision making.