bluuebunny/crossref_metadata_2025_split huggingface dataset:
Posttranscriptional Upregulation of p53 by Reactive Oxygen Species in Chronic Lymphocytic Leukemia
Authors: Samuel Jesvin , Jayne Sandrine , Chen Yixiang , Majid Aneela , Wignall Alice , Wormull Timothy , Najeeb Hishyar , Luo Jin-Li , Jones George D.D. , Macip Salvador , Dyer Martin J.S. 
Published: September 2016

Abstract
Chronic lymphocytic leukemia (CLL) cells multiply and become more resistant to immunochemotherapy in “proliferation centers” within tissues, whereas apoptosis occurs in the periphery. Various models recapitulate these microenvironments in vitro, such as stimulation with CD154 and IL4. Using this system, we observed a 30- to 40-fold induction of wild-type p53 protein in 50 distinct human CLL specimens tested, without the induction of either cell-cycle arrest or apoptosis. In contrast, the mRNA levels for p53 did not increase, indicating that its elevation occurred posttranscriptionally. Mechanistic investigations revealed that under the conditions studied, p53 was phosphorylated on residues associated with p53 activation and increased half-life. However, p53 protein induced in this manner could transcriptionally activate only a subset of target genes. The addition of a DNA-damaging agent further upregulated p53 protein levels, which led to apoptosis. p53 induction relied on the increase in intracellular reactive oxygen species observed after CD154 and IL4 stimulation. We propose that chronic oxidative stress is a characteristic of the microenvironment in B-cell “proliferation centers” in CLL that are capable of elevating the basal expression of p53, but to levels below the threshold needed to induce arrest or apoptosis. Our findings suggest that reactivation of the full transcriptional activities of p53 in proliferating CLL cells may offer a possible therapeutic strategy. Cancer Res; 76(21); 6311–9. ©2016 AACR.
Biallelic Alteration and Dysregulation of the Hippo Pathway in Mucinous Tubular and Spindle Cell Carcinoma of the Kidney
Authors: Mehra Rohit , Vats Pankaj , Cieslik Marcin , Cao Xuhong , Su Fengyun , Shukla Sudhanshu , Udager Aaron M. , Wang Rui , Pan Jincheng , Kasaian Katayoon , Lonigro Robert , Siddiqui Javed , Premkumar Kumpati , Palapattu Ganesh , Weizer Alon , Hafez Khaled S. , Wolf J. Stuart , Sangoi Ankur R. , Trpkov Kiril , Osunkoya Adeboye O. , Zhou Ming , Giannico Giovanna , McKenney Jesse K. , Dhanasekaran Saravana M. , Chinnaiyan Arul M. 
Published: September 2016

Abstract
Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare subtype of renal cell carcinoma (RCC) with distinctive morphologic and cytogenetic features. Here, we carry out whole-exome and transcriptome sequencing of a multi-institutional cohort of MTSCC (n = 22). We demonstrate the presence of either biallelic loss of Hippo pathway tumor suppressor genes (TSG) and/or evidence of alteration of Hippo pathway genes in 85% of samples. PTPN14 (31%) and NF2 (22%) were the most commonly implicated Hippo pathway genes, whereas other genes such as SAV1 and HIPK2 were also involved in a mutually exclusive fashion. Mutations in the context of recurrent chromosomal losses amounted to biallelic alterations in these TSGs. As a readout of Hippo pathway inactivation, a majority of cases (90%) exhibited increased nuclear YAP1 protein expression. Taken together, nearly all cases of MTSCC exhibit some evidence of Hippo pathway dysregulation.
Significance: MTSCC is a rare and relatively recently described subtype of RCC. Next-generation sequencing of a multi-institutional MTSCC cohort revealed recurrent chromosomal losses and somatic mutations in the Hippo signaling pathway genes leading to potential YAP1 activation. In virtually all cases of MTSCC, there was evidence of Hippo pathway dysregulation, suggesting a common mechanistic basis for this disease. Cancer Discov; 6(11); 1258–66. ©2016 AACR.
This article is highlighted in the In This Issue feature, p. 1197
Studies of the interaction of ticagrelor with the P2Y13 receptor and with P2Y13-dependent pro-platelet formation by human megakaryocytes
Authors: Björquist Anna , Di Buduo Christian A. , Femia Eti A. , Storey Robert F. , Becker Richard C. , Balduini Alessandra , Nylander Sven , Cattaneo Marco 
Published: September 2016

SummaryTicagrelor is an antagonist of the platelet P2Y12 receptor for ADP, approved for the prevention of thromboembolic events in patients with acute coronary syndrome. Previous studies showed that ticagrelor has no significant activity versus P1 receptors for adenosine and other known P2Y receptors, with the exception of P2Y13, which was not tested. The P2Y12 antagonist cangrelor has been shown to also inhibit P2Y13 and to decrease the P2Y13-regulated capacity of megakaryocytes to produce pro-platelets. We tested whether or not ticagrelor inhibits P2Y13 signalling and function. The in vitro effects of ticagrelor, its active (TAM) and inactive (TIM) metabolites, cangrelor and the P2Y13 antagonist MRS2211 were tested in two experimental models: 1) a label-free cellular response assay in P2Y13-transfected HEK293 T-REx cells; and 2) pro-platelet formation by human megakaryocytes in culture. Ticagrelor, TAM, cangrelor and MRS2211, but not TIM, inhibited the cellular responses in P2Y13-transfected cells. In contrast, only MRS2211 and cangrelor, confirming previous results, inhibited pro-platelet formation by megakaryocytes in vitro. The platelet count of patients randomised to treatment with ticagrelor in the PLATO trial did not change during treatment and was comparable to those of patients randomised to clopidogrel. In conclusion, ticagrelor and TAM act as P2Y13 antagonists in a transfected cell system in vitro but this does not translate into any impact on pro-platelet formation in vitro or altered platelet count in patients.
ADAMTS13 deficiency promotes microthrombosis in a murine model of diet-induced liver steatosis
Authors: Geys Lotte , Bauters Dries , Roose Elien , Tersteeg Claudia , Vanhoorelbeke Karen , Hoylaerts Marc F. , Scroyen Ilse , Lijnen Roger H. 
Published: September 2016

SummaryADAMTS13 cleaves ultralarge multimeric von Willebrand Factor (VWF), thereby preventing formation of platelet-rich microthrombi. ADAMTS13 is mainly produced by hepatic stellate cells, and numerous studies have suggested a functional role of ADAMTS13 in the pathogenesis of liver diseases. The aim of our study was to investigate a potential role of ADAMTS13 in formation of hepatic microthrombi and development of non-alcoholic steatohepatitis (NASH), and furthermore to evaluate whether plasmin can compensate for the absence of ADAMTS13 in removal of thrombi. Therefore, we used a model of high-fat diet-induced steatosis in Adamts13 deficient (Adamts13−/−) and wild-type (WT) control mice. Microthrombi were more abundant in the liver of obese Adamts13−/− as compared to obese WT or to lean Adamts13−/− mice. Obese Adamts13−/− mice displayed lower platelet counts and higher prevalence of ultra-large VWF multimers. Hepatic plasmin-α2-antiplasmin complex levels were comparable for obese WT and Adamts13−/− mice and were lower for lean Adamts13−/− than WT mice, not supporting marked activation of the fibrinolytic system. High fat diet feeding, as compared to normal chow, resulted in enhanced liver triglyceride levels for both genotypes (p < 0.0001) and steatosis (p < 0.0001 for WT mice, p = 0.002 for Adamts13−/− mice) without differences between the genotypes. Expression of markers of inflammation, oxidative stress, steatosis and fibrosis was affected by diet, but not by genotype. Thus, our data confirm that obesity promotes NASH, but do not support a detrimental role of ADAMTS13 in its development. However, Adamts13 deficiency in obese mice promotes hepatic microthrombosis, whereas a compensatory role of plasmin in removal of microthrombi in the absence of ADAMTS13 could not be demonstrated.
Economic Impact of Moderate‐Vigorous Physical Activity Among Those With and Without Established Cardiovascular Disease: 2012 Medical Expenditure Panel Survey
Authors: Valero‐Elizondo Javier , Salami Joseph A. , Osondu Chukwuemeka U. , Ogunmoroti Oluseye , Arrieta Alejandro , Spatz Erica S. , Younus Adnan , Rana Jamal S. , Virani Salim S. , Blankstein Ron , Blaha Michael J. , Veledar Emir , Nasir Khurram 
Published: September 2016

Background

Physical activity (
PA
) has an established favorable impact on cardiovascular disease (
CVD
) outcomes and quality of life. In this study, we aimed to estimate the economic effect of moderate‐vigorous
PA
on medical expenditures and utilization from a nationally representative cohort with and without
CVD
.

Methods and Results

The 2012 Medical Expenditure Panel Survey data were analyzed. Our study population was limited to noninstitutionalized
US
adults ≥18 years of age. Variables of interest included
CVD
(coronary artery disease, stroke, heart failure, dysrhythmias, or peripheral artery disease) and cardiovascular modifiable risk factors (
CRF
s; hypertension, diabetes mellitus, hypercholesterolemia, smoking, and/or obesity). Two‐part econometric models were utilized to study cost data; a generalized linear model with gamma distribution and link log was used to assess expenditures per capita. The final study sample included 26 239 surveyed individuals. Overall, 47% engaged in moderate‐vigorous
PA
≥30 minutes, ≥5 days/week, translating to 111.5 million adults in the United States stratifying by
CVD
status; 32% reported moderate‐vigorous
PA
among those with
CVD
versus 49% without
CVD
. Generally, participants reporting moderate‐vigorous
PA
incurred significantly lower health care expenditures and resource utilization, displaying a step‐wise lower total annual health care expenditure as moving from
CVD
to non‐
CVD
(and each
CRF
category).

Conclusions

Moderate‐vigorous
PA
≥30 minutes, ≥5 days/week is associated with significantly lower health care spending and resource utilization among individuals with and without established
CVD
.
Mortality Risk Among Heart Failure Patients With Depression: A Nationwide Population‐Based Cohort Study
Authors: Adelborg Kasper , Schmidt Morten , Sundbøll Jens , Pedersen Lars , Videbech Poul , Bøtker Hans Erik , Egstrup Kenneth , Sørensen Henrik Toft 
Published: September 2016

Background
The prevalence of depression is 4‐ to 5‐fold higher in heart failure patients than in the general population. We examined the influence of depression on all‐cause mortality in patients with heart failure.

Methods and Results

Using Danish medical registries, this nationwide population‐based cohort study included all patients with a first‐time hospitalization for heart failure (1995–2014). All‐cause mortality risks and 19‐year mortality rate ratios were estimated based on Cox regression analysis, adjusting for age, sex, time period, comorbidity, and socioeconomic status. The analysis included 9636 patients with and 194 887 patients without a diagnosis of depression. Compared with patients without a history of depression, those with depression had higher 1‐year (36% versus 33%) and 5‐year (68% versus 63%) mortality risks. Overall, the adjusted mortality rate ratio was 1.03 (95% CI 1.01–1.06). Compared with no depression, the adjusted mortality rate ratios for mild, moderate, and severe depression, as defined by diagnostic codes, were 1.06 (95%
CI
1.00–1.13), 1.03 (95%
CI
0.99–1.08), and 1.02 (95%
CI
0.96–1.09), respectively. In a subcohort of patients, the mortality rate ratios were modified by left ventricular ejection fraction, with adjusted mortality rate ratios of 1.17 (95%
CI
, 1.05–1.31) for ≤35%, 0.98 (95%
CI
0.81–1.18) for 36% to 49%, and 0.96 (95%
CI
0.74–1.25) for ≥50%. Results were consistent after adjustment for alcohol abuse and smoking.

Conclusions
A history of depression was an adverse prognostic factor for all‐cause mortality in heart failure patients with left ventricular ejection fraction ≤35% but not for other heart failure patients.
Tracking the Indian Summer Monsoon Onset Back to the Preinstrument Period
Authors: Ordoñez Paulina , Gallego David , Ribera Pedro , Peña-Ortiz Cristina , García-Herrera Ricardo 
Published: September 2016

Abstract
The Indian summer monsoon onset is one of the most expected meteorological events of the world, affecting the lives of hundreds of millions of people. The India Meteorological Department has dated the monsoon onset since 1901, but its original methodology was considered subjective and it was updated in 2006. Unfortunately, the new method relies on OLR measurements, which impedes the construction of an objective onset series before the 1970s. An alternative approach is the use of the wind field, but the development of such an index is limited to the period covered by reanalysis products. In this paper historical wind records taken on board ships are used to develop a new onset series using only wind direction measurements, providing an objective record of the onset since the late nineteenth century. The new series captures the rapid precipitation increase associated with the onset, correlates well with previous approaches, and is robust against anomalous (bogus) onsets. A tendency for later-than-average onsets during the 1900–25 and 1970–90 periods and earlier-than-average onsets between 1940 and 1965 was found. A relatively stable relationship between ENSO and Indian monsoon onset dates was found; however, this link tends to be weaker during decades characterized by prevalent La Niña conditions. Furthermore, it was found that the link between the Pacific decadal oscillation (PDO) and the onset date is limited to the phases characterized by a shift from negative to positive PDO phases.
Construction of a 3D Mooring Array of Temperature Sensors
Authors: van Haren Hans , van Heerwaarden Johan , Bakker Roel , Laan Martin 
Published: September 2016

AbstractA small-scale 3D mooring array comprising up to 550 high-resolution temperature sensors was custom designed and constructed. The stand-alone array samples ocean temperature to depths of about 3000 m, limited by the buoyancy elements, at a rate of 1 Hz, with a precision better than 0.5 mK, a noise level better than 0.1 mK, and an endurance of 1 year. Its purpose serves quantitative studies on the development of turbulent mixing by internal wave breaking above deep-ocean topography. The 3D array consists of five parallel cables 105 m long with 3.2 mm inner diameter during the first deployment, now 5.5 mm. The cables are 4 and 5.6 m apart horizontally and are held under tension of 1000 N each using heavy buoyancy elements in a single line above. The entire array is folded into a 6-m high, 3-m-diameter structure above a 750-kg weight. It is deployed in a single overboard operation similar to that of a free-falling mooring. New here is the unfolding of the compacted array when hanging overboard and prior to release into free fall.
Raising the Bar
Authors: Seftor Neil 
Published: September 2016

Background: In 2002, the U.S. Department of Education’s Institute of Education Sciences (IES) established the What Works Clearinghouse (WWC) at the confluence of a push to improve education research quality, a shift toward evidence-based decision-making, and an expansion of systematic reviews. In addition to providing decision makers with evidence to inform their choices, a systematic review sets expectations regarding study quality and execution for research on program efficacy. In this article, we examine education research through the filter of a long running systematic review to assess research quality over time and the role of the systematic review in producing evidence. Method: Using the WWC’s database of reviewed studies, we explored the relationships between study characteristics and dispositions as well as the differences by topic area and changes over time. Conclusion: Through its design standards, the WWC has defined its requirements for a study to be considered causal evidence, which may have been one of the factors contributing to observed improvement in the quality of education research over the past 15 years. The levels and rates of studies meeting standards have been increasing over the life of the WWC. Additionally, the number and proportion of studies excluded due to ineligible design are decreasing. Thus, less research is ineligible due to design issues, and more eligible studies are meeting standards. As IES continues to conduct and fund studies designed to meet standards, and more decisions are directly tied to evidence, the body of rigorous education research may continue to grow.
Design Effectiveness Analysis of a Media Literacy Intervention to Reduce Violent Video Games Consumption Among Adolescents
Authors: Rivera Reynaldo , Santos David , Brändle Gaspar , Cárdaba Miguel Ángel M. 
Published: September 2016

Background Exposure to media violence might have detrimental effects on psychological adjustment and is associated with aggression-related attitudes and behaviors. As a result, many media literacy programs were implemented to tackle that major public health issue. However, there is little evidence about their effectiveness. Evaluating design effectiveness, particularly regarding targeting process, would prevent adverse effects and improve the evaluation of evidence-based media literacy programs. Objectives The present research examined whether or not different relational lifestyles may explain the different effects of an antiviolence intervention program. Research design Based on relational and lifestyles theory, the authors designed a randomized controlled trial and applied an analysis of variance 2 (treatment: experimental vs. control) × 4 (lifestyle classes emerged from data using latent class analysis: communicative vs. autonomous vs. meta-reflexive vs. fractured). Subjects Seven hundred and thirty-five Italian students distributed in 47 classes participated anonymously in the research (51.3% females). Measures Participants completed a lifestyle questionnaire as well as their attitudes and behavioral intentions as the dependent measures. Results The results indicated that the program was effective in changing adolescents’ attitudes toward violence. However, behavioral intentions toward consumption of violent video games were moderated by lifestyles. Those with communicative relational lifestyles showed fewer intentions to consume violent video games, while a boomerang effect was found among participants with problematic lifestyles. Conclusion Adolescents’ lifestyles played an important role in influencing the effectiveness of an intervention aimed at changing behavioral intentions toward the consumption of violent video games. For that reason, audience lifestyle segmentation analysis should be considered an essential technique for designing, evaluating, and improving media literacy programs.
Augmenting in vitro osteogenesis of a glycine–arginine–glycine–aspartic-conjugated oxidized alginate–gelatin–biphasic calcium phosphate hydrogel composite and in vivo bone biogenesis through stem cell delivery
Authors: Linh Nguyen TB , Paul Kallyanashis , Kim Boram , Lee Byong-Taek 
Published: September 2016

A functionally modified peptide-conjugated hydrogel system was fabricated with oxidized alginate/gelatin loaded with biphasic calcium phosphate to improve its biocompatibility and functionality. Sodium alginate was treated by controlled oxidation to transform the cis-diol group into an aldehyde group in a controlled manner, which was then conjugated to the amine terminus of glycine–arginine–glycine–aspartic. Oxidized alginate glycine–arginine–glycine–aspartic was then combined with gelatin-loaded biphasic calcium phosphate to form a hydrogel of composite oxidized alginate/gelatin/biphasic calcium phosphate that displayed enhanced human adipose stem cell adhesion, spreading and differentiation. 1H nuclear magnetic resonance and electron spectroscopy for chemical analysis confirmed that the glycine–arginine–glycine–aspartic was successfully grafted to the oxidized alginate. Co-delivery of glycine–arginine–glycine–aspartic and human adipose stem cell in a hydrogel matrix was studied with the results indicating that hydrogel incorporated modified with glycine–arginine–glycine–aspartic and seeded with human adipose stem cell enhanced osteogenesis in vitro and bone formation in vivo.
Nurses’ perception of ethical climate at a large academic medical center
Authors: Lemmenes Donna , Valentine Pamela , Gwizdalski Patricia , Vincent Catherine , Liao Chuanhong 
Published: September 2016

Background: Nurses are confronted daily with ethical issues while providing patient care. Hospital ethical climates can affect nurses’ job satisfaction, organizational commitment, retention, and physician collaboration. Purpose: At a metropolitan academic medical center, we examined nurses’ perceptions of the ethical climate and relationships among ethical climate factors and nurse characteristics. Design/participants: We used a descriptive correlational design and nurses ( N = 475) completed Olson’s Hospital Ethical Climate Survey. Data were analyzed using STATA. Ethical considerations: Approvals by the Nursing Research Council and Institutional Review Board were obtained; participants’ rights were protected. Results: Nurses reported an ethical climate total mean score of 3.22 ± 0.65 that varied across factors; significant differences were found for ethical climate scores by nurses’ age, race, and specialty area. Conclusion: These findings contribute to what is known about ethical climate and nurses’ characteristics and provides the foundation to develop strategies to improve the ethical climate in work settings.
Undergraduate nursing students’ ability to empathize: A qualitative study
Authors: Heggestad Anne Kari Tolo , Nortvedt Per , Christiansen Bjørg , Konow-Lund Anne-Sophie 
Published: September 2016

Background: Empathy is of great importance in nursing, as it helps us to see and meet the needs of patients and hence to care for patients in an appropriate way. Therefore, it is of great importance that nursing students and nurses develop their ability to empathize. Objective: The study aimed at gaining knowledge on what characterizes undergraduate nursing students’ ability to empathize with patients during their first practice in a nursing home. In addition, the aim of the study was to investigate what nursing students think is important with regard to upholding their ability to empathize with patients in a professional way. Research design: This research has a phenomenological and hermeneutic design, based on qualitative interviews. Participants and research context: A total of 11 undergraduate nursing students participated in interviews during or right after their first practice in a nursing home. Ethical considerations: Norwegian Social Science Data Services approved the study. Participants were informed that their participation was voluntary. The participants were also assured confidentiality, and they were informed that they could withdraw from the study at any time, without providing any reasons. Findings: What the findings show is that affective empathy is strong among undergraduate nursing students in their first practice. They think the emotions are important to be able to empathize, and they are afraid of becoming indifferent. At the same time, they are afraid that the feelings will hinder them from acting in a professional manner. Discussion: The findings are discussed in light of previous theories on empathy, and especially perspectives on empathy, emotions, and morality. Conclusion: Affective empathy seems to be strong among nursing students, and this may be of great importance to be sensitive to patients’ well-being. However, affective and cognitive empathy should be balanced if nurses will have to meet patients in a professional way.