bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of a risk-stratified approach to cardiac resynchronisation therapy defibrillators (high versus low) at the time of generator change
Authors: Claridge Simon , Sebag Frederic A , Fearn Steven , Behar Jonathan M , Porter Bradley , Jackson Tom , Sieniewicz Benjamin , Gould Justin , Webb Jessica , Chen Zhong , O’Neill Mark , Gill Jaswinder , Leclercq Christophe , Rinaldi Christopher A 
Published: October 2017

ObjectiveResponders to cardiac resynchronisation therapy whose device has a defibrillator component and who do not receive a therapy in the lifetime of the first generator have a very low incidence of appropriate therapy after box change. We investigated the cost implications of using a risk stratification tool at the time of generator change resulting in these patients being reimplanted with a resynchronisation pacemaker.MethodsA decision tree was created using previously published data which had demonstrated an annualised appropriate defibrillator therapy risk of 2.33%. Costs were calculated at National Health Service (NHS) national tariff rates (2016–2017). EQ-5D utility values were applied to device reimplantations, admissions and mortality data, which were then used to estimate quality-adjusted life-years (QALYs) over 5 years.ResultsAt 5 years, the incremental cost of replacing a resynchronisation defibrillator device with a second resynchronisation defibrillator versus resynchronisation pacemaker was £5045 per patient. Incremental QALY gained was 0.0165 (defibrillator vs pacemaker), resulting in an incremental cost-effectiveness ratio (ICER) of £305 712 per QALYs gained. Probabilistic sensitivity analysis resulted in an ICER of £313 612 (defibrillator vs pacemaker). For reimplantation of all patients with a defibrillator rather than a pacemaker to yield an ICER of less than £30 000 per QALY gained (current NHS cut-off for approval of treatment), the annual arrhythmic event rate would need to be 9.3%. The budget impact of selective replacement was a saving of £2 133 985 per year.ConclusionsImplanting low-risk patients with a resynchronisation defibrillator with the same device at the time of generator change is not cost-effective by current NHS criteria. Further research is required to understand the impact of these findings on individual patients at the time of generator change.
Histopathological abnormalities in the central arteries and veins of Fontan subjects
Authors: Hays Brandon S , Baker Michael , Laib Annie , Tan Wei , Udholm Sebastian , Goldstein Bryan H , Sanders Stephen P , Opotowsky Alexander R , Veldtman Gruschen R 
Published: October 2017

ObjectiveFontan circulations have obligatory venous hypertension, depressed cardiac output and abnormal arterial elastance. Ventriculovascular coupling is known to be abnormal, but the underlying mechanisms are poorly defined. We aim to describe the histopathological features of vascular remodelling encountered in the central arteries and veins in the Fontan circulation as a possible underlying pathological representation of abnormal ventriculovascular coupling.MethodsPostmortemvasculature (inferior vena cava (IVC), superior vena cava (SVC), pulmonary artery (PA), pulmonary vein (PV) and aorta) of 13 patients with a Fontan circulation (mean age 29.9 years, range 9.0–59.8 years) and 2 biventricular controls (ages 17.9 and 30.2 years) was examined.ResultsIVC and SVC: Eccentric and variable intimal fibromuscular proliferation occurred in 11 Fontan subjects. There was variable loss of medial smooth muscle bundles with reciprocal replacement with dense collagenous tissue.PA: Similar intimal fibromuscular proliferation was seen; however, these intimal changes were accompanied by medial thinning rather than expansion, medial myxoid degeneration and elastic alteration.PV: The PVs demonstrated intimal fibroproliferation and disorganisation of the muscular media.Aorta: The aortic lamina intima was thickened, with associated fibromuscular proliferation and elasticisation. There was also moderate lymphocytic inflammation in the aortic wall.ConclusionsVascular architectural remodelling is common in Fontan patients. The central veins demonstrate profound changes of eccentric intimal expansion and smooth muscle replacement with collagen. The pulmonary demonstrated abnormal intimal proliferation, and aortic remodelling was characterised by intima lamina thickening and a moderate degree of aortic wall inflammation.
Safe Kids Week: Analysis of gender bias in a national child safety campaign, 1997–2016
Authors: Bauer Michelle E E , Brussoni Mariana , Giles Audrey R , Fuselli Pamela 
Published: October 2017

Background and PurposeChild safety campaigns play an important role in disseminating injury prevention information to families. A critical discourse analysis of gender bias in child safety campaign marketing materials can offer important insights into how families are represented and the potential influence that gender bias may have on uptake of injury prevention information.MethodsOur approach was informed by poststructural feminist theory, and we used critical discourse analysis to identify discourses within the poster materials. We examined the national Safe Kids Canada Safe Kids Week campaign poster material spanning twenty years (1997-2016). Specifically, we analyzed the posters’ typeface, colour, images, and language to identify gender bias in relation to discourses surrounding parenting, safety, and societal perceptions of gender.ResultsThe findings show that there is gender bias present in the Safe Kids Week poster material. The posters represent gender as binary, mothers as primary caregivers, and showcase stereotypically masculine sporting equipment among boys and stereotypically feminine equipment among girls. Interestingly, we found that the colour and typeface of the text both challenge and perpetuate the feminization of safety.DiscussionIt is recommended that future child safety campaigns represent changing family dynamics, include representations of children with non-traditionally gendered sporting equipment, and avoid the representation of gender as binary. This analysis contributes to the discussion of the feminization of safety in injury prevention research and challenges the ways in which gender is represented in child safety campaigns.
Could the rise in mortality rates since 2015 be explained by changes in the number of delayed discharges of NHS patients?
Authors: Green Mark A , Dorling Danny , Minton Jonathan , Pickett Kate E 
Published: October 2017

Background2015 saw the largest annual spike of mortality rates in England in almost 50 years. We examine whether these changes in mortality rates are associated with an indicator of poor functioning of health and social care: delay in hospital discharges.MethodsOffice for National Statistics monthly data of death counts and mortality rates for the period August 2010–March 2016 were compared with delays in discharges from National Health Service (NHS) England data on transfers of care for acute and non-acute patients in England. Autoregressive Integrated Moving Average regression models were used in the analysis.ResultsWe estimate that each additional day an acute admission was late being discharged was associated with an increase in 0.394 deaths (95% CIs 0.220 to 0.569). For each additional acute patient delayed being discharged, we found an increase of 7.322 deaths (95% CIs 1.754 to 12.890). Findings for non-acute admissions were mixed.ConclusionThe increased prevalence of patients being delayed in discharge from hospital in 2015 was associated with increases in mortality, accounting for up to a fifth of mortality increases. Our study provides evidence that a lower quality of performance of the NHS and adult social care as a result of austerity may be having an adverse impact on population health.
Underemployment and its impacts on mental health among those with disabilities: evidence from the HILDA cohort
Authors: Milner Allison , King Tania Louise , LaMontagne Anthony D , Aitken Zoe , Petrie Dennis , Kavanagh Anne M 
Published: October 2017

BackgroundUnderemployment (defined as when a person in paid employment works for fewer hours than their desired full working capacity) is increasingly recognised as a component of employment precarity. This paper sought to investigate the effects of underemployment on the mental health of people with disabilities.MethodsUsing 14 waves of the Household, Income and Labour Dynamics in Australia survey, we used fixed-effects models to assess whether the presence of a disability modified the association between underemployment and mental health. Both disability and underemployment were assessed as time-varying factors. Measures of effect measure modification were presented on the additive scale.ResultsThe experience of underemployment was associated with a significantly greater decline in mental health when a person reported a disability (mean difference −1.38, 95% CI −2.20 to −0.57) compared with when they did not report a disability (mean difference −0.49, 95% CI −0.84 to −0.14). The combined effect of being underemployed and having a disability was nearly one point greater than the summed independent risks of having a disability and being underemployed (−0.89, 95% CI −1.75 to –0.03).ConclusionPeople with disabilities are more likely to experience underemployment and more likely to have their mental health adversely affected by it. There is a need for more research and policy attention on how to ameliorate the effects of underemployment on the mental health of persons with disabilities.
The origin and evolution of waters in the Jurassic formations of the Marginal Trough area (Poland)
Authors: Uliasz-Misiak Barbara , Winid Bogumiła 
Published: October 2017

The Permian–Mesozoic cover of the Western European Platform includes numerous aquifers containing mineralized water. An attempt has been made to determine both the genesis of water from the Jurassic formations of the Marginal Trough (tectonic unit in the Zechstein–Mesozoic structural floor, located in central Poland) and the processes to which they were subjected. The results of archival chemical analysis of waters from deep boreholes located in the Marginal Trough have been studied. Hydrogeochemical ratios of Na/Cl, Cl/Br, (SO
4
× 100)/Cl, HCO
3
/Cl and Na/(Ca + Mg), together with their variability depending on water depth, were presented and discussed.

The majority of waters from the Jurassic formations are Na–Cl waters, typical for areas isolated from hypergene zones. Their mineralization is closely related to the depths of the Jurassic formations.
The analyses of hydrochemical parameters of the Jurassic waters have shown that the vast majority of these waters are brines or chloride waters, genetically related to seawater. The diversity in mineralization and hydrochemical parameters, together with their dependence on the depth of occurrence of the analysed waters, indicate that waters from the Lower Jurassic formations originate from isolated geological structures, while the Middle and Upper Jurassic waters are/or were affected by infiltration waters.
SKP2 Activation by Thyroid Hormone Receptor β2 Bypasses Rb-Dependent Proliferation in Rb-Deficient Cells
Authors: Xu Xiaoliang L. , Li Zhengke , Liu Aihong , Fan Xianqun , Hu Dan-ning , Qi Dong-Lai , Chitty David W. , Jia Renbing , Qui Jianping , Wang Justin Q. , Sharaf Jake , Zou Jun , Weiss Rebecca , Huang Hongyan , Joseph Walter J. , Ng Lily , Rosen Richard , Shen Binghui , Reid Mark W. , Forrest Douglas , Abramson David H. , Singer Samuel , Cobrinik David , Jhanwar Suresh C. 
Published: October 2017

Abstract
Germline RB1 mutations strongly predispose humans to cone precursor–derived retinoblastomas and strongly predispose mice to pituitary tumors, yet shared cell type–specific circuitry that sensitizes these different cell types to the loss of RB1 has not been defined. Here we show that the cell type–restricted thyroid hormone receptor isoform TRβ2 sensitizes to RB1 loss in both settings by antagonizing the widely expressed and tumor-suppressive TRβ1. TRβ2 promoted expression of the E3 ubiquitin ligase SKP2, a critical factor for RB1-mutant tumors, by enabling EMI1/FBXO5–dependent inhibition of SKP2 degradation. In RB1 wild-type neuroblastoma cells, endogenous Rb or ectopic TRβ2 was required to sustain SKP2 expression as well as cell viability and proliferation. These results suggest that in certain contexts, Rb loss enables TRβ1-dependent suppression of SKP2 as a safeguard against RB1-deficient tumorigenesis. TRβ2 counteracts TRβ1, thus disrupting this safeguard and promoting development of RB1-deficient malignancies. Cancer Res; 77(24); 6838–50. ©2017 AACR.
Secretory Autophagy in Cancer-Associated Fibroblasts Promotes Head and Neck Cancer Progression and Offers a Novel Therapeutic Target
Authors: New Jacob , Arnold Levi , Ananth Megha , Alvi Sameer , Thornton Mackenzie , Werner Lauryn , Tawfik Ossama , Dai Hongying , Shnayder Yelizaveta , Kakarala Kiran , Tsue Terance T. , Girod Douglas A. , Ding Wen-Xing , Anant Shrikant , Thomas Sufi Mary 
Published: October 2017

Abstract
Despite therapeutic advancements, there has been little change in the survival of patients with head and neck squamous cell carcinoma (HNSCC). Recent results suggest that cancer-associated fibroblasts (CAF) drive progression of this disease. Here, we report that autophagy is upregulated in HNSCC-associated CAFs, where it is responsible for key pathogenic contributions in this disease. Autophagy is fundamentally involved in cell degradation, but there is emerging evidence that suggests it is also important for cellular secretion. Thus, we hypothesized that autophagy-dependent secretion of tumor-promoting factors by HNSCC-associated CAFs may explain their role in malignant development. In support of this hypothesis, we observed a reduction in CAF-facilitated HNSCC progression after blocking CAF autophagy. Studies of cell growth media conditioned after autophagy blockade revealed levels of secreted IL6, IL8, and other cytokines were modulated by autophagy. Notably, when HNSCC cells were cocultured with normal fibroblasts, they upregulated autophagy through IL6, IL8, and basic fibroblast growth factor. In a mouse xenograft model of HNSCC, pharmacologic inhibition of Vps34, a key mediator of autophagy, enhanced the antitumor efficacy of cisplatin. Our results establish an oncogenic function for secretory autophagy in HNSCC stromal cells that promotes malignant progression. Cancer Res; 77(23); 6679–91. ©2017 AACR.
Clonality, Heterogeneity, and Evolution of Synchronous Bilateral Ovarian Cancer
Authors: Yin Xia , Jing Ying , Cai Mei-Chun , Ma Pengfei , Zhang Yi , Xu Cong , Zhang Meiying , Di Wen , Zhuang Guanglei 
Published: October 2017

Abstract
Synchronous bilateral ovarian cancer (SBOC) represents a relatively frequent occurrence and clinically relevant diagnostic dilemma. Delineation of its clonal architecture, genetic heterogeneity, and evolutionary trajectories may have important implications for prognosis and management of patients with SBOC. Here, we describe the results of next-generation whole-exome or whole-genome sequencing of specimens from 12 SBOC cases and report that bilateral tumors from each individual display a comparable number of genomic abnormalities and similar mutational signatures of single-nucleotide variations. Clonality indices based on tumor-specific alterations supported monoclonal origins of SBOC. Each of the ovarian lesions was nevertheless oligoclonal, with inferred metastatic tumors harboring more subclones than their primary counterparts. The phylogenetic structure of SBOC indicated that most cancer cell dissemination occurred early, when the primary carcinoma was still relatively small (&lt;100 million cells). Accordingly, the mutation spectra and mutational signatures of somatic variants exhibited pronounced spatiotemporal differences in each patient. Overall, these findings suggest that SBOCs are clonally related and form through pelvic spread rather than independent multifocal oncogenesis. Metastatic dissemination is often an early event, with dynamic mutational processes leading to divergent evolution and intratumor and intertumor heterogeneity, ultimately contributing substantially to phenotypic plasticity and diverse clinical course in SBOC. Cancer Res; 77(23); 6551–61. ©2017 AACR.
Genetic Testing in a Population-Based Sample of Breast and Ovarian Cancer Survivors from the REACH Randomized Trial: Cost Barriers and Moderators of Counseling Mode
Authors: Steffen Laurie E. , Du Ruofei , Gammon Amanda , Mandelblatt Jeanne S. , Kohlmann Wendy K. , Lee Ji-Hyun , Buys Saundra S. , Stroup Antoinette M. , Campo Rebecca A. , Flores Kristina G. , Vicuña Belinda , Schwartz Marc D. , Kinney Anita Y. 
Published: October 2017

Abstract
Background: This study evaluates predictors of BRCA1/2 testing among breast and ovarian cancer survivors who received genetic counseling as part of a randomized trial and evaluates moderators of counseling mode on testing uptake.
Methods: Predictors of BRCA1/2 testing within one year postcounseling were evaluated using multivariable logistic regression in a population-based sample of breast and ovarian cancer survivors at increased hereditary risk randomly assigned to in-person counseling (IPC; n = 379) versus telephone counseling (TC; n = 402). Variables that moderated the association between counseling mode and testing were identified by subgroup analysis.
Results: Testing uptake was associated with higher perceived comparative mutation risk [OR = 1.32; 95% confidence interval (CI), 1.11–1.57] in the adjusted analysis. Those without cost barriers had higher testing uptake (OR = 18.73; 95% CI, 7.09–49.46). Psychologic distress and perceived comparative mutation risk moderated the effect of counseling and testing. Uptake between IPC versus TC did not differ at low levels of distress and risk, but differed at high distress (26.3% TC vs. 44.3% IPC) and high perceived comparative risk (33.9% TC vs. 50.5% IPC).
Conclusions: Cost concerns are a strong determinant of testing. Differences in testing uptake by counseling mode may depend on precounseling distress and risk perceptions.
Impact: Cost concerns may contribute to low testing in population-based samples of at-risk cancer survivors. Precounseling psychosocial characteristics should be considered when offering in-person versus telephone counseling. Cancer Epidemiol Biomarkers Prev; 26(12); 1772–80. ©2017 AACR.
A Randomized Phase II Trial of Adjuvant Galinpepimut-S, WT-1 Analogue Peptide Vaccine, After Multimodality Therapy for Patients with Malignant Pleural Mesothelioma
Authors: Zauderer Marjorie G. , Tsao Anne S. , Dao Tao , Panageas Katherine , Lai W. Victoria , Rimner Andreas , Rusch Valerie W. , Adusumilli Prasad S. , Ginsberg Michelle S. , Gomez Daniel , Rice David , Mehran Reza , Scheinberg David A. , Krug Lee M. 
Published: October 2017

Abstract
Purpose: Determine the 1-year progression-free survival (PFS) rate among patients with malignant pleural mesothelioma (MPM) receiving the WT1 peptide vaccine galinpepimut-S after multimodality therapy versus those receiving control adjuvants.
Experimental Design: This double-blind, controlled, two center phase II trial randomized MPM patients after surgery and another treatment modality to galinpepimut-S with GM-CSF and Montanide or GM-CSF and Montanide alone. An improvement in 1-year PFS from 50% to 70% was the predefined efficacy threshold, and 78 patients total were planned. The study was not powered for comparison between the two arms.
Results: Forty-one patients were randomized. Treatment-related adverse events were mild, self-limited, and not clinically significant. On the basis of a stringent prespecified futility analysis (futility = ≥10 of 20 patients on one arm experiencing progression &lt; 1 year), the control arm closed early. The treatment arm was subsequently closed because of the resultant unblinding. The PFS rate at 1 year from beginning study treatment was 33% and 45% in the control and vaccine arms, respectively. Median PFS was 7.4 months versus 10.1 months and median OS was 18.3 months versus 22.8 months in the control and vaccine arms, respectively.
Conclusions: The favorable safety profile was confirmed. PFS and OS were greater in those who received vaccine, but the trial was neither designed nor powered for comparison between the arms. On the basis of these promising results, the investigators are planning a larger randomized trial with greater statistical power to define the optimal use and benefit of galinpepimut-S in the treatment of MPM. Clin Cancer Res; 23(24); 7483–9. ©2017 AACR.
Heat Shock Protein 70 (Hsp70) Suppresses RIP1-Dependent Apoptotic and Necroptotic Cascades
Authors: Srinivasan Sharan R. , Cesa Laura C. , Li Xiaokai , Julien Olivier , Zhuang Min , Shao Hao , Chung Jooho , Maillard Ivan , Wells James A. , Duckett Colin S. , Gestwicki Jason E. 
Published: October 2017

Abstract
Hsp70 is a molecular chaperone that binds to “client” proteins and protects them from protein degradation. Hsp70 is essential for the survival of many cancer cells, but it is not yet clear which of its clients are involved. Using structurally distinct chemical inhibitors, we found that many of the well-known clients of the related chaperone, Hsp90, are not strikingly responsive to Hsp70 inhibition. Rather, Hsp70 appeared to be important for the stability of the RIP1 (RIPK1) regulators: cIAP1/2 (BIRC1 and BIRC3), XIAP, and cFLIPS/L (CFLAR). These results suggest that Hsp70 limits apoptosis and necroptosis pathways downstream of RIP1. Consistent with this model, MDA-MB-231 breast cancer cells treated with Hsp70 inhibitors underwent apoptosis, while cotreatment with z-VAD.fmk switched the cell death pathway to necroptosis. In addition, cell death in response to Hsp70 inhibitors was strongly suppressed by RIP1 knockdown or inhibitors. Thus, these data indicate that Hsp70 plays a previously unrecognized and important role in suppressing RIP1 activity.
Implications: These findings clarify the role of Hsp70 in prosurvival signaling and suggest IAPs as potential new biomarkers for Hsp70 inhibition. Mol Cancer Res; 16(1); 58–68. ©2017 AACR.