bluuebunny/crossref_metadata_2025_split huggingface dataset:
Views and experiences of using integrated care pathways (ICPs) for caring for people in the last days to hours of life: results from a cross-sectional survey of UK professionals
Authors: Collins K A , Hughes P M , Ibbotson R , Foy G , Brooks D 
Published: January 2015

ObjectivesTo determine the views and experiences of health and social care professionals on using integrated care pathways (ICPs)for caring for people in the last days to hours of life.MethodsOnline cross-sectional questionnaire survey of UK professionals working in UK primary and secondary care settings.Results1331 professionals returned completed questionnaires. Ninety-three per cent (1138/1228) of respondents used the Liverpool Care Pathway (LCP) or local variant. Eighty-eight (1089/1234) felt ICPs enabled professionals to provide better care for individuals and their families/carers. ICPs were viewed as promoting patient-centred holistic care, improving pain and symptom control, providing guidance and standards and improving communication with patients/families. Sixty-two per cent (770/1234) had no concerns regarding the use of ICPs. Areas of concern included incorrect use and implementation of the ICP, poor communication with families, junior level staff making decisions and insufficient education and support.ConclusionsThere was strong support for using ICPs for caring for people in the last days to hours of life. ICPs were viewed as supporting high-quality patient-centred holistic care. Given the recommendations of the More Care Less Pathway report, those that develop the guidance and support that replace the LCP need to incorporate the aspects of this that have resulted in the benefits seen by professionals within this survey, but also learn from the instances where ICPs have failed to prevent poor care, or worse, have contributed to it.
Physical and methylation status of human papillomavirus 16 in asymptomatic cervical infections changes with malignant transformation
Authors: Dutta Sankhadeep , Chakraborty Chandraditya , Dutta Arup Kumar , Mandal Ranajit Kumar , Roychoudhury Susanta , Basu Partha , Panda Chinmay Kumar 
Published: January 2015

AimsTo evaluate how the genetic and epigenetic profile of human papillomavirus 16 (HPV16) changes from asymptomatic cervical infections to cervical cancer (CaCx) development.MethodsHPV16 physical status, methylation of its early–late promoters and its upstream enhancer sequences were analysed in samples from asymptomatic cervical infections (n=89), pre-neoplastic lesions (low and high grade squamous intraepithelial lesions LSIL/HSIL, n=28) and primary CaCx (n=98).ResultsIn asymptomatic infection (65%, 58/89) and LSIL/HSIL (57%, 16/28) samples, the episomal form of HPV16 was predominant whereas integration of HPV16 was significantly (p=0.01) higher in CaCx (59%, 57/98). The integrated viral form was also present in asymptomatic (27%, 24/89) and LSIL/HSIL (25%, 7/28) samples. The methylation of the enhancer region was comparable (29–34%) among asymptomatic, LSIL/HSIL and CaCx samples. The episomal form exhibited relatively higher methylation of the early promoter (52%) than that of the late promoter (40%) in asymptomatic infection but the integrated form in asymptomatic carriers showed the opposite methylation pattern (early promoter (42%) vs late-promoter (54%)). A similar pattern was observed in LSIL/HSIL samples, with comparable frequencies (44%) of early and late promoter methylation of the episomal form. However, irrespective of HPV16 physical status, higher methylation of late promoter than that of early promoter was observed in CaCx samples. An inverse correlation was observed between HPV16 integration and overall methylation of the early promoter–enhancer region in CaCx (p=0.05), LSIL/HSIL (p=0.09) and asymptomatic samples (p=0.09).ConclusionsOur study indicates that integration of HPV16 along with changes in methylation pattern of early and late promoters is essential for neoplastic transformation of asymptomatic cervical infections.
Clinicopathological analysis of near-tetraploidy/tetraploidy acute myeloid leukaemia
Authors: Pang Changlee S , Pettenati Mark J , Pardee Timothy S 
Published: January 2015

AimsNear-tetraploidy/tetraploidy (NT/T) is a rare cytogenetic alteration in acute myeloid leukaemia (AML). NT/T-AML is categorised as complex cytogenetics and therefore, presumed to have an unfavourable prognosis. Our aim is to further characterise the clinical, morphological, cytogenetic and prognostic features of NT/T-AML.MethodsWe searched our cytogenetic laboratory database from 1991 to 2012 to reveal 13 cases of NT/T-AML. Each case was evaluated with regard to its demographics, morphology, immunophenotype and prognosis. Specific morphological features included blast size, irregularity of nuclear contours, cytoplasmic vacuoles, and presence and lineage of dysplasia.ResultsEleven men and two women had a median age of 68 years. Blasts were predominately large (11/13). Eight of 13 patients had AML with myelodysplasia-related changes. Sixty-nine per cent of patients achieved complete remission (CR). Median overall survival (OS) was 8.6 months. CR rate and median OS in cases with ≥5 cytogenetic abnormalities were 71% and 6 months, compared with 67% and 18.1 months in cases with <5 abnormalities.ConclusionsNT/T-AML occurs in older males, exhibits large blast size and is associated with myelodysplasia. Unlike previously reported data, our study reveals an overall better prognosis in this older population with NT/T-AML than was expected for a complex karyotype AML. Cytogenetic complexity independent of ploidy status did not greatly affect the high CR rates, but did appear to be a better estimation of prognostic risk in terms of median OS.
A novel ecological methodology for constructing ethnic-majority life tables in the absence of individual ethnicity information
Authors: Morris Melanie , Woods Laura M , Rachet Bernard 
Published: January 2015

BackgroundDeprivation-specific life tables have been in use for some time, but health outcomes are also known to vary by ethnicity over and above deprivation. The mortality experiences of ethnic groups are little studied in the UK, however, because ethnicity is not captured on death certificates.MethodsPopulation data for all Output Areas (OAs) in England and Wales were stratified by age-group, sex and ethnic proportion, and matched to the deaths counts in that OA from 2000 to 2002. We modelled the relationship between mortality, age, deprivation and ethnic proportion. We predicted mortality rates for an area that contained the maximum proportion of each ethnic group reported in any area in England and Wales, using a generalised linear model with a Poisson distribution adjusted for deprivation.ResultsAfter adjustment, Asian and White life expectancies between 1 and 80 years were very similar. Black men and women had lower life expectancies: men by 4 years and women by around 1.5 years. The Asian population had the lowest mortality of all groups over age 45 in women and over 50 in men, whereas the Black population had the highest rates throughout, except in girls under 15.ConclusionsWe adopted a novel ecological method of constructing ethnic-majority life tables, adjusted for deprivation. There is still diversity within these three broad ethnic groups, but our data show important residual differences in mortality for Black men and women. These ethnic life tables can be used to inform public health planning and correctly account for background mortality in ethnic subgroups of the population.
Dynamics of health behaviours and socioeconomic differences in mortality in the USA
Authors: Mehta Neil K , House James S , Elliott Michael R 
Published: January 2015

BackgroundTo measure the explanatory role of behavioural factors to educational and income disparities in mortality among US adults (ages 25+).MethodsData were from four waves of the American Changing Lives Study (N=3617). There were 1832 deaths between 1986 and 2011. Smoking, physical activity, alcohol and body mass index were examined.ResultsThose with 0–11 years of schooling had an 88% (95% CI 48% to 139%) increased risk of dying compared to those with 16+years of schooling. Behavioural factors explained 41% (95% CI 26% to 55%) and 50% (95% CI 30% to 70%) of this excess in models that treated behavioural factors as fixed (single point in time) and time varying (repeated), respectively. The lowest income group (bottom 20th centile) had a 209% (95% CI 172% to 256%) increased risk of dying relative to the highest income group (top 40th centile). Behavioural factors explained 24% (fixed, 95% CI 13% to 35%) and 39% (repeated, 95% CI 22% to 56%) of this difference. Analyses of deaths by causes indicated that behavioural factors were more consequential to disparities in cardiovascular mortality, explaining up to 83% of educational differences, compared to cancer and other death causes.ConclusionsBehavioural factors are one of a number of factors which explain socioeconomic mortality disparities, but their estimated explanatory role depends on a number of parameters including the socioeconomic status measure examined, the cause of death and age. In this nationally representative sample, findings based on repeated measures did not warrant a re-evaluation of earlier estimates.
Does falling testosterone with age among men underlie the increase in ischaemic heart disease
Authors: Zhao J , Schooling C M 
Published: January 2015

BackgroundObservationally, testosterone falls with age among men and ischaemic heart disease (IHD) increases with age, so testosterone is commonly assumed to protect against IHD. Here we examined whether IHD mortality rates among men increased faster with age in the USA than China, where testosterone in men remains stable throughout adulthood, and also whether the increase with age in mortality rates for IHD is faster than for other causes of death.MethodsAge-specific mortality rates from all causes, IHD, pneumonia and prostate cancer for men in the USA and China from 1991 to 1995 were obtained from the WHO, and considered in age groups because of non-linearity.ResultsThe risk of death from IHD in US men increased with age at the same rate as the risk of death from any cause. In China, the risk of death from IHD increased with age faster than the risk of death from any cause.ConclusionThe data are not consistent with the assumption that a fall in testosterone with age causes IHD.
Periprocedural complications associated with endovascular treatment of intracranial aneurysms in 1764 cases
Authors: Zheng Yongtao , Liu Yingjun , Leng Bing , Xu Feng , Tian Yanlong 
Published: January 2015

BackgroundIntracranial aneurysms are increasingly treated with endovascular treatment. Based on our observation that cerebral complications are associated with this treatment, we predict that the number of intraprocedural complications will rise as a result of this trend.MethodsBetween January 2007 and December 2013, 1739 patients underwent 1764 detachable coil embolizations to treat intracranial aneurysms (637 ruptured and 1127 unruptured). We reviewed their records and images to evaluate the periprocedural complications and related morbidity and mortality.Results61 complications occurred during coil embolization and 33 periprocedural complications occurred within 1 week. These complications were observed in 8.6% of ruptured aneurysm embolization procedures (55/637) and in 3.5% of unruptured aneurysm embolization procedures (39/1127). There were 17 (0.96%) cerebral thromboembolisms, 34 (1.93%) intraprocedural aneurysm ruptures, 8 (0.45%) coil migrations, 13 (0.74%) postprocedural aneurysmal ruptures, and 22 (1.24%) neurologic deficits or transient neurologic deficits related to embolization. 63 complications had no neurologic consequences, 3 were associated with transient neurologic morbidity, 15 resulted in persistent neurologic morbidity on discharge, and 12 resulted in death. The procedure-related neurologic morbidity and mortality rates for all 1764 procedures were 0.85% in ruptured aneurysms and 0.68% in unruptured aneurysms.ConclusionsThe periprocedural complication rate was higher in ruptured aneurysms than in unruptured aneurysms. The main causes of morbidity and mortality were thromboembolisms, intraprocedural aneurysm perforations, and postprocedural aneurysmal ruptures. While some periprocedural complications are inevitable, we can minimize the occurrence of such complications by advancing our skill and experience, thereby improving patient prognosis.
A Conversation with Susan Band Horwitz
Authors: Horwitz Susan Band , Goldman I. David 
Published: January 2015

Susan Band Horwitz is a Distinguished Professor and holds the Falkenstein Chair in Cancer Research at Albert Einstein College of Medicine in New York. She is co-chair of the Department of Molecular Pharmacology and associate director for therapeutics at the Albert Einstein Cancer Center. After graduating from Bryn Mawr College, Dr. Horwitz received her PhD in biochemistry from Brandeis University. She has had a continuing interest in natural products as a source of new drugs for the treatment of cancer. Her most seminal research contribution has been in the development of Taxol®. Dr. Horwitz and her colleagues made the discovery that Taxol had a unique mechanism of action and suggested that it was a prototype for a new class of antitumor drugs. Although Taxol was an antimitotic agent blocking cells in the metaphase stage of the cell cycle, Dr. Horwitz recognized that Taxol was blocking mitosis in a way different from that of other known agents. Her group demonstrated that the binding site for Taxol was on the β-tubulin subunit. The interaction of Taxol with the β-tubulin subunit resulted in stabilized microtubules, essentially paralyzing the cytoskeleton, thereby preventing cell division. Dr. Horwitz served as president (2002–2003) of the American Association for Cancer Research (AACR). She is a member of the National Academy of Sciences, the Institute of Medicine, the American Academy of Arts and Sciences, and the American Philosophical Society. She has received numerous honors and awards, including the C. Chester Stock Award from Memorial Sloan Kettering Cancer Center, the Warren Alpert Foundation Prize from Harvard Medical School, the Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research, the American Cancer Society's Medal of Honor, and the AACR Award for Lifetime Achievement in Cancer Research. The following interview was conducted on January 23, 2014.
Ceritinib for the Treatment of Late-Stage (Metastatic) Non–Small Cell Lung Cancer
Authors: Massarelli Erminia , Papadimitrakopoulou Vassiliki 
Published: January 2015

Abstract
Over the past decade, the non–small cell lung cancer therapeutics landscape has been dominated by the increasing focus on identification and validation of molecular targets, as well as the identification of the best candidate agents to address these targets. Among the notable successes have been the approval of erlotinib, gefitinib, and afatinib for the EGFR mutation, and more recently crizotinib for anaplastic lymphoma kinase (ALK) gene rearrangement. Despite the excellent efficacy of crizotinib, several mechanisms of resistance, including secondary mutation in the ALK gene, eventually result in disease progression, and several second-generation ALK inhibitors, notably ceritinib, have demonstrated evidence of clinical activity in this setting. This review discusses the data associated with the recent accelerated approval of ceritinib for treatment of patients with ALK-positive, metastatic lung adenocarcinoma with disease progression on or who are intolerant to crizotinib. Clin Cancer Res; 21(4); 670–4. ©2015 AACR.
Validation of the Hsp70–Bag3 Protein–Protein Interaction as a Potential Therapeutic Target in Cancer
Authors: Li Xiaokai , Colvin Teresa , Rauch Jennifer N. , Acosta-Alvear Diego , Kampmann Martin , Dunyak Bryan , Hann Byron , Aftab Blake T. , Murnane Megan , Cho Min , Walter Peter , Weissman Jonathan S. , Sherman Michael Y. , Gestwicki Jason E. 
Published: January 2015

Abstract
Hsp70 is a stress-inducible molecular chaperone that is required for cancer development at several steps. Targeting the active site of Hsp70 has proven relatively challenging, driving interest in alternative approaches. Hsp70 collaborates with the Bcl2-associated athanogene 3 (Bag3) to promote cell survival through multiple pathways, including FoxM1. Therefore, inhibitors of the Hsp70–Bag3 protein–protein interaction (PPI) may provide a noncanonical way to target this chaperone. We report that JG-98, an allosteric inhibitor of this PPI, indeed has antiproliferative activity (EC50 values between 0.3 and 4 μmol/L) across cancer cell lines from multiple origins. JG-98 destabilized FoxM1 and relieved suppression of downstream effectors, including p21 and p27. On the basis of these findings, JG-98 was evaluated in mice for pharmacokinetics, tolerability, and activity in two xenograft models. The results suggested that the Hsp70–Bag3 interaction may be a promising, new target for anticancer therapy. Mol Cancer Ther; 14(3); 642–8. ©2015 AACR.
Alternative NHEJ Pathway Components Are Therapeutic Targets in High-Risk Neuroblastoma
Authors: Newman Erika A. , Lu Fujia , Bashllari Daniela , Wang Li , Opipari Anthony W. , Castle Valerie P. 
Published: January 2015

Abstract
In neuroblastoma, MYCN genomic amplification and segmental chromosomal alterations including 1p or 11q loss of heterozygocity and/or 17q gain are associated with progression and poor clinical outcome. Segmental alterations are the strongest predictor of relapse and result from unbalanced translocations attributable to erroneous repair of chromosomal breaks. Although sequence analysis of affected genomic regions suggests that these errors arise by nonhomologous end-joining (NHEJ) of DNA double-strand breaks (DSB), abnormalities in NHEJ have not been implicated in neuroblastoma pathogenesis. On this basis, the hypothesis that an error-prone mechanism of NHEJ is critical for neuroblastoma cell survival was tested. Plasmid-based DSB repair assays demonstrated efficient NHEJ activity in human neuroblastoma cells with repair products that were error-prone relative to nontransformed cells. Neuroblastoma cells derived from tumorigenic neuroblastic phenotypes had differential DNA repair protein expression patterns compared with nontumorigenic cells. Tumorigenic neuroblastoma cells were deficient in DNA ligase IV (Lig4) and Artemis (DCLRE1C), mediators of canonical NHEJ. Conversely, enzymes required for an error-prone alternative NHEJ pathway (alt-NHEJ), DNA Ligase IIIα (Lig3), DNA Ligase I (Lig1), and PARP1 protein were upregulated. Inhibition of Lig3 and Lig1 led to DSB accumulation and cell death, linking alt-NHEJ to cell survival in neuroblastoma. Neuroblastoma cells demonstrated sensitivity to PARP1 inhibition (PARPi) that paralleled PARP1 expression. In a dataset of human neuroblastoma patient tumors, overexpression of genes encoding alt-NHEJ proteins associated with poor survival.
Implications: These findings provide an insight into DNA repair fidelity in neuroblastoma and identify components of the alt-NHEJ pathway as promising therapeutic targets. Mol Cancer Res; 13(3); 470–82. ©2015 AACR.
Aldosterone Promotes Cardiac Endothelial Cell Proliferation In Vivo
Authors: Gravez Basile , Tarjus Antoine , Pelloux Véronique , Ouvrard‐Pascaud Antoine , Delcayre Claude , Samuel Janelise , Clément Karine , Farman Nicolette , Jaisser Fréderic , Messaoudi Smail 
Published: January 2015

Background
Experimentally, aldosterone in association with NaCl induces cardiac fibrosis, oxidative stress, and inflammation through mineralocorticoid receptor activation; however, the biological processes regulated by aldosterone alone in the heart remain to be identified.

Methods and Results

Mice were treated for 7 days with aldosterone, and then cardiac transcriptome was analyzed. Aldosterone regulated 60 transcripts (51 upregulated and 9 downregulated) in the heart (fold change ≥1.5, false discovery rate <0.01). To identify the biological processes modulated by aldosterone, a gene ontology analysis was performed. The majority of aldosterone‐regulated genes were involved in cell division. The cardiac Ki‐67 index (an index of proliferation) of aldosterone‐treated mice was higher than that of nontreated mice, confirming microarray predictions. Costaining of Ki‐67 with vinculin,
CD
68, α‐smooth muscle actin,
CD
31, or caveolin 1 revealed that the cycling cells were essentially endothelial cells. Aldosterone‐induced mineralocorticoid receptor–dependent proliferation was confirmed ex vivo in human endothelial cells. Moreover, pharmacological‐specific blockade of mineralocorticoid receptor by eplerenone inhibited endothelial cell proliferation in a preclinical model of heart failure (transverse aortic constriction).

Conclusions
Aldosterone modulates cardiac gene expression and induces the proliferation of cardiac endothelial cells in vivo.
Lower Mortality Rate in Elderly Patients With Community‐Onset Pneumonia on Treatment With Aspirin
Authors: Falcone Marco , Russo Alessandro , Cangemi Roberto , Farcomeni Alessio , Calvieri Camilla , Barillà Francesco , Scarpellini Maria Gabriella , Bertazzoni Giuliano , Palange Paolo , Taliani Gloria , Venditti Mario , Violi Francesco 
Published: January 2015

Background
Pneumonia is complicated by high rate of mortality and cardiovascular events (CVEs). The potential benefit of aspirin, which lowers platelet aggregation by inhibition of thromboxane A2 production, is still unclear. The aim of the study was to assess the impact of aspirin on mortality in patients with pneumonia.

Methods and Results

Consecutive patients admitted to the University‐Hospital Policlinico Umberto I (Rome, Italy) with community‐onset pneumonia were recruited and prospectively followed up until discharge or death. The primary end point was the occurrence of death up to 30 days after admission; the secondary end point was the intrahospital incidence of nonfatal myocardial infarction and ischemic stroke. One thousand and five patients (age, 74.7±15.1 years) were included in the study: 390 were receiving aspirin (100 mg/day) at the time of hospitalization, whereas 615 patients were aspirin free. During the follow‐up, 16.2% of patients died; among these, 19 (4.9%) were aspirin users and 144 (23.4%;
P
<0.001) were aspirin nonusers. Overall, nonfatal CVEs occurred in 7% of patients, 8.3% in nonaspirin users, and 4.9% in aspirin users (odds ratio, 1.77; 95% confidence interval, 1.03 to 3.04;
P
=0.040). The Cox regression analysis showed that pneumonia severity index (
PSI
), severe sepsis, pleural effusion, and PaO
2
/FiO
2
ratio <300 negatively influenced survival, whereas aspirin therapy was associated with improved survival. Compared to patients receiving aspirin, the propensity score adjusted analysis confirmed that patients not taking aspirin had a hazard ratio of 2.07 (1.08 to 3.98;
P
=0.029) for total mortality.

Conclusions
This study shows that chronic aspirin use is associated with lower mortality rate within 30 days after hospital admission in a large cohort of patients with pneumonia.