bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using digital story telling to assess health students’ knowledge of interprofessional roles in the care of the older adult
Authors: Frost Jane , Isbel Stephen , Kellett Jane , Lawlis Tanya 
Published: October 2016

BackgroundDigital story telling (DST) is an innovative way to allow students to assess the care needs of an older adult and creates an opportunity for interdisciplinary involvement. Traditionally, a single healthcare discipline approach is used by higher education institutions for preclinical training in the care of the older adult. Interprofessional learning (IPL) is generally not integrated well into the health professional curricula of Australian Universities.AimTo explore the use of Mask-Ed as a way of eliciting students understanding of their roles in patient care and to determine readiness for IPL in a cohort of health students prior to clinical placement.MethodAn online survey of students prior to their first clinical placement was undertaken. The survey incorporated a digital story of a Mask-Ed character and the readiness for IPL scale.ResultsStudents recognised the importance of IPL. However, only 25% of students had an advanced understanding of their own roles and no student showed an advanced understanding of the other disciplines roles in the care of the older adult.ConclusionsIn this study, DST using Mask-Ed assisted with students' understanding of interprofessional roles in the care of the older adult. Our findings demonstrated that IPL is important, and this was further enhanced by the use of Mask-Ed simulation.
Can emergency medicine research benefit from adaptive design clinical trials?
Authors: Flight Laura , Julious Steven A , Goodacre Steve 
Published: October 2016

BackgroundAdaptive design clinical trials use preplanned interim analyses to determine whether studies should be stopped or modified before recruitment is complete. Emergency medicine trials are well suited to these designs as many have a short time to primary outcome relative to the length of recruitment. We hypothesised that the majority of published emergency medicine trials have the potential to use a simple adaptive trial design.MethodsWe reviewed clinical trials published in three emergency medicine journals between January 2003 and December 2013. We determined the proportion that used an adaptive design as well as the proportion that could have used a simple adaptive design based on the time to primary outcome and length of recruitment.ResultsOnly 19 of 188 trials included in the review were considered to have used an adaptive trial design. A total of 154/165 trials that were fixed in design had the potential to use an adaptive design.ConclusionsCurrently, there seems to be limited uptake in the use of adaptive trial designs in emergency medicine despite their potential benefits to save time and resources. Failing to take advantage of adaptive designs could be costly to patients and research. It is recommended that where practical and logistical considerations allow, adaptive designs should be used for all emergency medicine clinical trials.
Index Problems for Game Automata
Authors: Facchini Alessandro , Murlak Filip , Skrzypczak Michał 
Published: November 2016

For a given regular language of infinite trees, one can ask about the minimal number of priorities needed to recognize this language with a nondeterministic, alternating, or weak alternating parity automaton. These questions are known as, respectively, the nondeterministic, alternating, and weak Rabin-Mostowski index problems. Whether they can be answered effectively is a long-standing open problem, solved so far only for languages recognizable by deterministic automata (the alternating variant trivializes).
We investigate a wider class of regular languages, recognizable by so-called game automata, which can be seen as the closure of deterministic ones under complementation and composition. Game automata are known to recognize languages arbitrarily high in the alternating Rabin-Mostowski index hierarchy; that is, the alternating index problem does not trivialize anymore.
Our main contribution is that all three index problems are decidable for languages recognizable by game automata. Additionally, we show that it is decidable whether a given regular language can be recognized by a game automaton.
Tighter buffer dimensioning in AFDX networks
Authors: Benammar Nassima , Bauer Henri , Ridouard Frédéric , Richard Pascal 
Published: November 2016

The AFDX (Avionics Full DupleX Switched Ethernet) is the backbone network of most recent avionic communication systems. These systems require deterministic buffer dimensioning for certification reasons. As in such systems, static design is often preferred over dynamic allocation, a dimensioning in terms of frames rather than in terms of bits can be required.
A common approach consists in deriving the worst-case buffer size in terms of frames from the worst-case in bits. However, we show that this can lead to an overestimation of the buffer size. Thus, we propose a dedicated approach for a tighter dimensioning. Eventually, the two approaches are compared on a sample AFDX configuration.
Myocardial interstitial levels of serotonin and its major metabolite 5-hydroxyindole acetic acid during ischemia-reperfusion
Authors: Du Cheng-Kun , Zhan Dong-Yun , Akiyama Tsuyoshi , Inagaki Tadakatsu , Shishido Toshiaki , Shirai Mikiyasu , Pearson James T. 
Published: October 2016

The aim of this study was to examine the accumulation of serotonin (5-HT) and degradation of 5-HT taken up into cells in the ischemic region during myocardial ischemia-reperfusion. Using microdialysis technique in anesthetized rats, we monitored myocardial interstitial levels of 5-HT and its metabolite produced by monoamine oxidase (MAO), 5-hydroxyindole acetic acid (5-HIAA), during 30-min coronary occlusion followed by 45-min reperfusion, and investigated the effects of local administration of the MAO inhibitor pargyline and the 5-HT uptake inhibitor fluoxetine. In the vehicle group, the dialysate 5-HT concentration increased from 1.3 ± 0.2 nM at baseline to 29.6 ± 2.8 nM at 22.5–30 min of occlusion, but the dialysate 5-HIAA concentration did not change from baseline (9.9 ± 1.1 nM). Upon reperfusion, the dialysate 5-HT concentration increased further to a peak (34.2 ± 4.2 nM) at 0–7.5 min and then declined. The dialysate 5-HIAA concentration increased to 31.9 ± 5.2 nM at 7.5–15 min of reperfusion and maintained this high level until 45 min. Pargyline markedly suppressed the increase in dialysate 5-HIAA concentration after reperfusion and increased the averaged dialysate 5-HT concentration during the reperfusion period. Fluoxetine suppressed the increase in dialysate 5-HT concentration during occlusion but did not change dialysate 5-HT or 5-HIAA concentration after reperfusion. During ischemia, 5-HT secreted from ischemic tissues accumulates but 5-HT degradation by MAO is suppressed. After reperfusion, degradation of 5-HT taken up into cells is enhanced and contributes to the clearance of accumulated 5-HT. This degradation following cellular uptake is dependent on MAO activity but not the fluoxetine-sensitive uptake transporter.NEW & NOTEWORTHY By monitoring myocardial interstitial levels of 5-HT and its metabolite, 5-hydroxyindole acetic acid, we investigated 5-HT kinetics during myocardial ischemia-reperfusion. 5-HT accumulates but 5-HT degradation is suppressed during ischemia. After reperfusion, 5-HT degradation is enhanced and this degradation is dependent on monoamine oxidase activity but not fluoxetine-sensitive uptake transporter.
The Beta Subunit of Hemoglobin (HBB2/HBB) Suppresses Neuroblastoma Growth and Metastasis
Authors: Maman Shelly , Sagi-Assif Orit , Yuan Weirong , Ginat Ravit , Meshel Tsipi , Zubrilov Inna , Keisari Yona , Lu Weiyue , Lu Wuyuan , Witz Isaac P. 
Published: October 2016

Abstract
Soluble pulmonary factors have been reported to be capable of inhibiting the viability of cancer cells that metastasize to the lung, but the molecular identity was obscure. Here we report the isolation and characterization of the beta subunit of hemoglobin as a lung-derived antimetastatic factor. Peptide mapping in the beta subunit of human hemoglobin (HBB) defined a short C-terminal region (termed Metox) as responsible for activity. In tissue culture, both HBB and murine HBB2 mediated growth arrest and apoptosis of lung-metastasizing neuroblastoma cells, along with a variety of other human cancer cell lines. Metox acted similarly and its administration in human tumor xenograft models limited the development of adrenal neuroblastoma tumors as well as spontaneous lung and bone marrow metastases. Expression studies in mice indicated that HBB2 is produced by alveolar epithelial and endothelial cells and is upregulated in mice bearing undetectable metastasis. Our work suggested a novel function for HBB as a theranostic molecule: an innate antimetastasis factor with potential utility as an anticancer drug and a biomarker signaling the presence of clinically undetectable metastasis. Cancer Res; 77(1); 14–26. ©2016 AACR.
Molecular Chaperone HSP90 Is Necessary to Prevent Cellular Senescence via Lysosomal Degradation of p14ARF
Authors: Han Su Yeon , Ko Aram , Kitano Haruhisa , Choi Chel Hun , Lee Min-Sik , Seo Jinho , Fukuoka Junya , Kim Soo-Youl , Hewitt Stephen M. , Chung Joon-Yong , Song Jaewhan 
Published: October 2016

Abstract
The tumor suppressor function of p14ARF is regulated at a posttranslational level via mechanisms yet to be fully understood. Here, we report the identification of an unconventional p14ARF degradation pathway induced by the chaperone HSP90 in association with the E3 ubiquitin ligase C-terminus of HSP70-interacting protein (CHIP). The ternary complex of HSP90, CHIP, and p14ARF was required to induce the lysosomal degradation of p14ARF by an ubiquitination-independent but LAMP2A-dependent mechanism. Depletion of HSP90 or CHIP induced p14ARF-dependent senescence in human fibroblasts. Premature senescence observed in cells genetically deficient in CHIP was rescued in cells that were doubly deficient in CHIP and p14ARF. Notably, non–small cell lung cancer cells (NSCLC) positive for p14ARF were sensitive to treatment with the HSP90 inhibitor geldanamycin. Furthermore, overexpression of HSP90 and CHIP with a concomitant loss of p14ARF correlated with poor prognosis in patients with NSCLC. Our findings identify a relationship between p14ARF and its chaperones that suggest new therapeutic strategies in cancers that overexpress HSP90. Cancer Res; 77(2); 343–54. ©2016 AACR.
HER2 and EGFR Overexpression Support Metastatic Progression of Prostate Cancer to Bone
Authors: Day Kathleen C. , Hiles Guadalupe Lorenzatti , Kozminsky Molly , Dawsey Scott J. , Paul Alyssa , Broses Luke J. , Shah Rajal , Kunja Lakshmi P. , Hall Christopher , Palanisamy Nallasivam , Daignault-Newton Stephanie , El-Sawy Layla , Wilson Steven James , Chou Andrew , Ignatoski Kathleen Woods , Keller Evan , Thomas Dafydd , Nagrath Sunitha , Morgan Todd , Day Mark L. 
Published: October 2016

Abstract
Activation of the EGF receptors EGFR (ErbB1) and HER2 (ErbB2) drives the progression of multiple cancer types through complex mechanisms that are still not fully understood. In this study, we report that HER2 expression is elevated in bone metastases of prostate cancer independently of gene amplification. An examination of HER2 and NF-κB receptor (RANK) coexpression revealed increased levels of both proteins in aggressive prostate tumors and metastatic deposits. Inhibiting HER2 expression in bone tumor xenografts reduced proliferation and RANK expression while maintaining EGFR expression. In examining the role of EGFR in tumor-initiating cells (TIC), we found that EGFR expression was required for primary and secondary sphere formation of prostate cancer cells. EGFR expression was also observed in circulating tumor cells (CTC) during prostate cancer metastasis. Dual inhibition of HER2 and EGFR resulted in significant inhibition of tumor xenograft growth, further supporting the significance of these receptors in prostate cancer progression. Overall, our results indicate that EGFR promotes survival of prostate TIC and CTC that metastasize to bone, whereas HER2 supports the growth of prostate cancer cells once they are established at metastatic sites. Cancer Res; 77(1); 74–85. ©2016 AACR.
Targeting of PYK2 Synergizes with EGFR Antagonists in Basal-like TNBC and Circumvents HER3-Associated Resistance via the NEDD4–NDRG1 Axis
Authors: Verma Nandini , Müller Anna-Katharina , Kothari Charu , Panayotopoulou Effrosini , Kedan Amir , Selitrennik Michael , Mills Gordon B. , Nguyen Lan K. , Shin Sungyoung , Karn Thomas , Holtrich Uwe , Lev Sima 
Published: October 2016

Abstract
Triple-negative breast cancer (TNBC) is a highly aggressive, heterogeneous disease with poor prognosis and no effective targeted therapies. EGFR is highly expressed in basal-like TNBC and is considered as a potential therapeutic target. However, EGFR targeting exerts only marginal clinical benefits, possibly due to activation of compensatory signaling pathways, which are frequently associated with HER3 upregulation. Here we show that concomitant targeting of EGFR and the nonreceptor tyrosine kinases PYK2/FAK synergistically inhibits the proliferation of basal-like TNBC cells in vitro and attenuates tumor growth in a mouse xenograft model. Dual targeting of EGFR and PYK2/FAK inhibited complementary key growth and survival pathways mediated by AKT, S6K, STAT3, and ERK1/2 activation. PYK2 inhibition also abrogated HER3 upregulation in response to EGFR antagonists, thereby circumventing HER3-associated drug resistance. Mechanistically, PYK2 inhibition facilitated the proteasomal degradation of HER3 while inducing upregulation of NDRG1 (N-myc downstream regulated 1 gene). NDRG1 enhanced the interaction of HER3 with the ubiquitin ligase NEDD4, while PYK2, which interacts with NEDD4 and HER3, interfered with NEDD4–HER3 binding, suggesting that the PYK2–NDRG1–NEDD4 circuit has a critical role in receptor degradation, drug response, and resistance mechanism. Our studies offer a preclinical proof of concept for a strategy of cotargeting the EGFR and PYK2/FAK kinases to improve TNBC therapy. Cancer Res; 77(1); 86–99. ©2016 AACR.
KRAS/NF-κB/YY1/miR-489 Signaling Axis Controls Pancreatic Cancer Metastasis
Authors: Yuan Peng , He Xiao-Hong , Rong Ye-Fei , Cao Jing , Li Yong , Hu Yun-Ping , Liu Yingbin , Li Dangsheng , Lou Wenhui , Liu Mo-Fang 
Published: October 2016

Abstract
KRAS activation occurring in more than 90% of pancreatic ductal adenocarcinomas (PDAC) drives progression and metastasis, but the underlying mechanisms involved in these processes are still poorly understood. Here, we show how KRAS acts through inflammatory NF-κB signaling to activate the transcription factor YY1, which represses expression of the tumor suppressor gene miR-489. In PDAC cells, repression of miR-489 by KRAS signaling inhibited migration and metastasis by targeting the extracellular matrix factors ADAM9 and MMP7. miR-489 downregulation elevated levels of ADAM9 and MMP7, thereby enhancing the migration and metastasis of PDAC cells. Together, our results establish a pivotal mechanism of PDAC metastasis and suggest miR-489 as a candidate therapeutic target for their attack. Cancer Res; 77(1); 100–11. ©2016 AACR.
Adherence to the WCRF/AICR Dietary Recommendations for Cancer Prevention and Risk of Cancer in Elderly from Europe and the United States: A Meta-Analysis within the CHANCES Project
Authors: Jankovic Nicole , Geelen Anouk , Winkels Renate M. , Mwungura Blaise , Fedirko Veronika , Jenab Mazda , Illner Anne K. , Brenner Hermann , Ordóñez-Mena José M. , Kiefte de Jong Jessica C. , Franco Oscar H. , Orfanos Philippos , Trichopoulou Antonia , Boffetta Paolo , Agudo Antonio , Peeters Petra H. , Tjønneland Anne , Hallmans Göran , Bueno-de-Mesquita H. Bas , Park Yikyung , Feskens Edith J. , de Groot Lisette C. , Kampman Ellen 
Published: October 2016

AbstractBackground: It is unknown whether dietary recommendations for cancer prevention are applicable to the elderly. We analyzed WCRF/AICR recommendations in cohorts of European and U.S. adults ages 60 years and above.Methods: Individual participant data meta-analysis included 362,114 participants (43% women), from seven prospective cohort studies, free from cancer at enrollment. The WCRF/AICR diet score was based on: (i) energy-dense foods and sugary drinks, (ii) plant foods, (iii) red and processed meat, and (iv) alcoholic drinks. Cox proportional hazards regression was used to examine the association between the diet score and cancer risks. Adjusted, cohort-specific HRs were pooled using random-effects meta-analysis. Risk advancement periods (RAP) were calculated to quantify the time period by which the risk of cancer was postponed among those adhering to the recommendations.Results: After a median follow-up of 11 to 15 years across cohorts, 70,877 cancer cases were identified. Each one-point increase in the WCRF/AICR diet score [range, 0 (no) to 4 (complete adherence)] was significantly associated with a lower risk of total cancer [HR, 0.94; 95% confidence interval (CI), 0.92–0.97], cancers of the colorectum (HR, 0.84; 95% CI, 0.80–0.89) and prostate (HR, 0.94; 95% CI, 0.92–0.97), but not breast or lung. Adherence to an additional component of the WCRF/AICR diet score significantly postponed the incidence of cancer at any site by 1.6 years (RAP, −1.6; 95% CI, −4.09 to −2.16).Conclusions: Adherence to WCRF/AICR dietary recommendations is associated with lower risk of cancer among older adults.Impact: Dietary recommendations for cancer prevention are applicable to the elderly. Cancer Epidemiol Biomarkers Prev; 26(1); 136–44. ©2016 AACR.
U.S. Food and Drug Administration Approval: Cabozantinib for the Treatment of Advanced Renal Cell Carcinoma
Authors: Singh Harpreet , Brave Michael , Beaver Julia A. , Cheng Joyce , Tang Shenghui , Zahalka Eias , Palmby Todd R. , Venugopal Rajesh , Song Pengfei , Liu Qi , Liu Chao , Yu Jingyu , Chen Xiao Hong , Wang Xing , Wang Yaning , Kluetz Paul G. , Daniels Selena R. , Papadopoulos Elektra J. , Sridhara Rajeshwari , McKee Amy E. , Ibrahim Amna , Kim Geoffrey , Pazdur Richard 
Published: October 2016

Abstract
On April 25, 2016, the FDA approved cabozantinib (Cabometyx; Exelixis, Inc.) for the treatment of advanced renal cell carcinoma (RCC) in patients who have received prior antiangiogenic therapy. The approval was based on data from one randomized, open-label, multicenter study in which patients with RCC who had received prior antiangiogenic therapy were treated with either cabozantinib 60 mg orally once daily (n = 330) or everolimus 10 mg orally once daily (n = 328). The major efficacy outcome measure was progression-free survival (PFS) as assessed by a blinded independent radiology review committee in the first 375 randomized patients. A statistically significant improvement in PFS was seen, with a median PFS of 7.4 and 3.8 months in the cabozantinib and everolimus arms, respectively [hazard ratio (HR), 0.58; 95% confidence interval (CI), 0.45–0.74; P &lt; 0.0001]. At a second interim analysis, a statistically significant improvement in overall survival (OS) in the intent-to-treat population was also demonstrated, with a median OS of 21.4 and 16.5 months in the cabozantinib and everolimus arms, respectively (HR, 0.66; 95% CI, 0.53–0.83; P = 0.0003). The most common (greater than or equal to 25%) adverse reactions included diarrhea, fatigue, nausea, decreased appetite, palmar–plantar erythrodysesthesia syndrome, hypertension, vomiting, weight loss, and constipation. Clin Cancer Res; 23(2); 330–5. ©2016 AACR.
Inhibition of AKR1C3 Activation Overcomes Resistance to Abiraterone in Advanced Prostate Cancer
Authors: Liu Chengfei , Armstrong Cameron M. , Lou Wei , Lombard Alan , Evans Christopher P. , Gao Allen C. 
Published: October 2016

Abstract
Abiraterone suppresses intracrine androgen synthesis via inhibition of CYP17A1. However, clinical evidence suggests that androgen synthesis is not fully inhibited by abiraterone and the sustained androgen production may lead to disease relapse. In the present study, we identified AKR1C3, an important enzyme in the steroidogenesis pathway, as a critical mechanism driving resistance to abiraterone through increasing intracrine androgen synthesis and enhancing androgen signaling. We found that overexpression of AKR1C3 confers resistance to abiraterone while downregulation of AKR1C3 resensitizes resistant cells to abiraterone treatment. In abiraterone-resistant prostate cancer cells, AKR1C3 is overexpressed and the levels of intracrine androgens are elevated. In addition, AKR1C3 activation increases intracrine androgen synthesis and enhances androgen receptor (AR) signaling via activating AR transcriptional activity. Treatment of abiraterone-resistant cells with indomethacin, an AKR1C3 inhibitor, overcomes resistance and enhances abiraterone therapy both in vitro and in vivo by reducing the levels of intracrine androgens and diminishing AR transcriptional activity. These results demonstrate that AKR1C3 activation is a critical mechanism of resistance to abiraterone through increasing intracrine androgen synthesis and enhancing androgen signaling. Furthermore, this study provides a preclinical proof-of-principle for clinical trials investigating the combination of targeting AKR1C3 using indomethacin with abiraterone for advanced prostate cancer. Mol Cancer Ther; 16(1); 35–44. ©2016 AACR.
Severe Pulmonary Vein Stenosis Resulting From Ablation for Atrial Fibrillation
Authors: Fender Erin A. , Widmer R. Jay , Hodge David O. , Cooper George M. , Monahan Kristi H. , Peterson Laurie A. , Holmes David R. , Packer Douglas L. 
Published: October 2016

Background:
The frequency of pulmonary vein stenosis (PVS) after ablation for atrial fibrillation has decreased, but it remains a highly morbid condition. Although treatment strategies including pulmonary vein dilation and stenting have been described, the long-term impacts of these interventions are unknown. We evaluated the presentation of severe PVS, and examined the risk for restenosis after intervention using either balloon angioplasty (BA) alone or BA with stenting.

Methods:
This was a prospective, observational study of 124 patients with severe PVS evaluated between 2000 and 2014.

Results:

All 124 patients were identified as having severe PVS by computed tomography in 219 veins. One hundred two patients (82%) were symptomatic at diagnosis. The most common symptoms were dyspnea (67%), cough (45%), fatigue (45%), and decreased exercise tolerance (45%). Twenty-seven percent of patients experienced hemoptysis. Ninety-two veins were treated with BA, 86 were treated with stenting, and 41 veins were not treated. A 94% acute procedural success rate was observed and did not differ by initial management. Major procedural complications occurred in 4 of the 113 patients (3.5%) who underwent invasive assessment, and minor complications occurred in 15 patients (13.3%). Overall, 42% of veins developed restenosis including 27% of veins (n=23) treated with stenting and 57% of veins (n=52) treated with BA. The 3-year overall rate of restenosis was 37%, with 49% of BA-treated veins and 25% of stented veins developing restenosis (hazard ratio, 2.77; 95% confidence interval, 1.72–4.45;
P
<0.001). After adjustment for age, CHA2DS2-VASc score, hypertension, and the time period of the study, there was still a significant difference in the risk of restenosis for BA versus stenting (hazard ratio, 2.46; 95% confidence interval, 1.47–4.12;
P
<0.001).

Conclusions:
The diagnosis of PVS is challenging because of nonspecific symptoms and the need for dedicated pulmonary vein imaging. There is no difference in acute success by type of initial intervention; however, stenting significantly reduces the risk of subsequent pulmonary vein restenosis in comparison with BA.