bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seeing the forest through the trees: uncovering phenomic complexity through interactive network visualization
Authors: Warner Jeremy L , Denny Joshua C , Kreda David A , Alterovitz Gil 
Published: October 2014

Abstract
Our aim was to uncover unrecognized phenomic relationships using force-based network visualization methods, based on observed electronic medical record data.
A primary phenotype was defined from actual patient profiles in the Multiparameter Intelligent Monitoring in Intensive Care II database. Network visualizations depicting primary relationships were compared to those incorporating secondary adjacencies. Interactivity was enabled through a phenotype visualization software concept: the Phenomics Advisor.
Subendocardial infarction with cardiac arrest was demonstrated as a sample phenotype; there were 332 primarily adjacent diagnoses, with 5423 relationships. Primary network visualization suggested a treatment-related complication phenotype and several rare diagnoses; re-clustering by secondary relationships revealed an emergent cluster of smokers with the metabolic syndrome.
Network visualization reveals phenotypic patterns that may have remained occult in pairwise correlation analysis. Visualization of complex data, potentially offered as point-of-care tools on mobile devices, may allow clinicians and researchers to quickly generate hypotheses and gain deeper understanding of patient subpopulations.
Re-examining health IT policy: what will it take to derive value from our investment?
Authors: Riskin Loren , Koppel Ross , Riskin Daniel 
Published: October 2014

Abstract
Despite substantial investments in health information technology (HIT), the nation's goals of reducing cost and improving outcomes through HIT remain elusive. This period of transition, with new Office of National Coordinator for HIT leadership, upcoming Meaningful Use Stage III definitions, and increasing congressional oversight, is opportune to consider needed course corrections in HIT strategy. This article describes current problems and recommended changes in HIT policy, including approaches to usability, interoperability, and quality measurement. Recommendations refrain from interim measures, such as electronic health record adoption rates, and instead focus on measurable national value to benefit the economy, to reduce healthcare costs, and to improve clinical efficiency and care quality.
Competing with injuries: injuries prior to and during the 15th FINA World Championships 2013 (aquatics)
Authors: Mountjoy Margo , Junge Astrid , Benjamen Sarah , Boyd Kevin , Diop Mohamed , Gerrard David , van den Hoogenband Cees-Rein , Marks Saul , Martinez-Ruiz Enrique , Miller Jim , Nanousis Kyriakos , Shahpar Farhad Moradi , Veloso Jose , van Mechelen William , Verhagen Evert 
Published: October 2014

BackgroundInjury and illness surveillance is the foundation for the development of prevention strategies.ObjectiveTo examine injuries among the aquatic disciplines in the 4 weeks prior to and during the 2013 FINA World Championships.MethodsThe study was comprised of two components: (1) a retrospective athlete survey recording injuries in the 4 weeks prior to the Championships and (2) a prospective recording of injuries and illnesses by the medical teams of the participating countries and the local host medical team.ResultsOne-third of the 1116 responding athletes reported an injury/physical complaint in the 4 weeks prior to the Championships. Significantly more women (36.7%) than men (28.6%) reported injuries. Divers reported the highest rate of injury/physical complaints (55.7%). At the start of the Championships, 70% of injured respondents (n=258) were still symptomatic; however, full participation was expected by 76%. During the Championships, 186 new injuries were reported (8.3/100 registered athletes) with the highest injury incidence rate in water polo (15.3/100 registered athletes). The most common injured body part was the shoulder (21%). A total of 199 illnesses were reported during the Championships (9.0/100 registered athletes) with the most common diagnosis of illness being gastrointestinal infection. Environmental exposure (allergy, otitis and jellyfish stings) was responsible for 27% of all illnesses in open water swimming.ConclusionsInjuries pose a significant health risk for elite aquatic athletes. A prospective study would improve understanding of out-of-competition injuries. Future injury and illness surveillance at FINA World Championships is required to direct and measure the impact of prevention strategies.
Lifetime smoking habits among Norwegian men and women born between 1890 and 1994: a cohort analysis using cross-sectional data
Authors: Lund Ingeborg , Lund Karl Erik 
Published: October 2014

ObjectivesProviding lifetime smoking prevalence data and gender-specific cigarette consumption data for use in epidemiological studies of tobacco-induced cancer in Norway. Characterising smoking patterns in birth cohorts is essential for evaluating the impact of tobacco control interventions and predicting smoking-related mortality.SettingNorway.ParticipantsPreviously analysed annual surveys of smoking habits from 1954 to 1992, and individual lifetime smoking histories collected in 1965 from a sample of people born in 1893–1927, were supplemented with new annual surveys of smoking habits from 1993 to 2013. Age range 15–74 years.Primary outcome measureCurrent smoking proportions in 5-year gender-and-birth cohorts of people born between 1890 and 1994.ResultsThe proportion of smokers increased in male cohorts until the 1950s, when the highest proportion of male smokers (76–78%) was observed among those born in 1915–1934. Among women, the peak (52%) occurred 20 years later, in women born in 1940–1949. After 1970 smoking has declined in all cohorts of men and women. In the 1890–1894 cohorts, male smoking prevalence was several times higher than female, but the gap declined until no gender difference was present among those born after 1950. Gender-specific per capita consumption was even more skewed, and men have consumed over 70% of all cigarettes since 1930. The incidence of lung cancer for men peaked at around 2000, with the highest incidence rate estimated at ca. 38%. The incidence of lung cancer for women is still increasing, and estimated incidence rate for 2011 was 25.2%.ConclusionsIn an epidemiological perspective, men have had a longer and more intense exposure to cigarettes than women. The gender-specific incidence of lung cancer reflects the gender difference in consumption over time.
What do parents of children with dysphagia think about their MDT? A qualitative study
Authors: Cowpe (Jebson) Emma , Hanson Ben , Smith Christina H 
Published: October 2014

ObjectivesTo seek the experiences and perspectives of parents caring for children with dysphagia, with emphasis on their experiences of working within their child's multidisciplinary team (MDT).SettingThis research was completed in community settings, within families’ homes across the UK.Participants14 families self-selected to participate in the study. Criteria specified that participants must care for a child under the age of 18 and to decrease ambiguity the term ‘diagnosis of dysphagia’ was defined as the need for modified (thickened) fluids. Exclusion criteria: caring for an adult over the age of 18; diet and fluid modifications for reasons other than dysphagia (eg, for symptomatic treatment of gastro-oesophageal reflux disease. Participants were interviewed within their homes using a semistructured questionnaire and data was analysed using a descriptive phenomenological approach through use of thematic coding and constant comparison. Themes and relationships were inductively generated from the data.ResultsParticipants universally expressed a desire to be involved with their child's MDT; this study identified the following facilitators and barriers to collaboration: accessing services, professional knowledge and professional skillset. Participants described three means of responding to these barriers: reacting emotionally, seeking solutions and making decisions.ConclusionsThis study recorded in-depth reports of participants’ experiences of working with healthcare providers. Despite government-driven efforts towards person-centred healthcare and social care, participants shared accounts of times when this has not occurred, describing a negative impact on the well-being and quality of life of their child and family.
RAGE Expression in Tumor-Associated Macrophages Promotes Angiogenesis in Glioma
Authors: Chen Xuebo , Zhang Leying , Zhang Ian Y. , Liang Junling , Wang Huaqing , Ouyang Mao , Wu Shihua , da Fonseca Anna Carolina Carvalho , Weng Lihong , Yamamoto Yasuhiko , Yamamoto Hiroshi , Natarajan Rama , Badie Behnam 
Published: October 2014

Abstract
Interaction of RAGE (the receptor for advanced glycation endproducts) with its ligands can promote tumor progression, invasion, and angiogenesis. Although blocking RAGE signaling has been proposed as a potential anticancer strategy, functional contributions of RAGE expression in the tumor microenvironment (TME) have not been investigated in detail. Here, we evaluated the effect of genetic depletion of RAGE in TME on the growth of gliomas. In both invasive and noninvasive glioma models, animal survival was prolonged in RAGE knockout (Ager−/−) mice. However, the improvement in survival in Ager−/− mice was not due to changes in tumor growth rate but rather to a reduction in tumor-associated inflammation. Furthermore, RAGE ablation in the TME abrogated angiogenesis by downregulating the expression of proangiogenic factors, which prevented normal vessel formation, thereby generating a leaky vasculature. These alterations were most prominent in noninvasive gliomas, in which the expression of VEGF and proinflammatory cytokines were also lower in tumor-associated macrophages (TAM) in Ager−/− mice. Interestingly, reconstitution of Ager−/− TAM with wild-type microglia or macrophages normalized tumor vascularity. Our results establish that RAGE signaling in glioma-associated microglia and TAM drives angiogenesis, underscoring the complex role of RAGE and its ligands in gliomagenesis. Cancer Res; 74(24); 7285–97. ©2014 AACR.
Plasma Choline Metabolites and Colorectal Cancer Risk in the Women's Health Initiative Observational Study
Authors: Bae Sajin , Ulrich Cornelia M. , Neuhouser Marian L. , Malysheva Olga , Bailey Lynn B. , Xiao Liren , Brown Elissa C. , Cushing-Haugen Kara L. , Zheng Yingye , Cheng Ting-Yuan David , Miller Joshua W. , Green Ralph , Lane Dorothy S. , Beresford Shirley A.A. , Caudill Marie A. 
Published: October 2014

Abstract
Few studies have examined associations between plasma choline metabolites and risk of colorectal cancer. Therefore, we investigated associations between plasma biomarkers of choline metabolism [choline, betaine, dimethylglycine, and trimethylamine N-oxide (TMAO)] and colorectal cancer risk among postmenopausal women in a case–control study nested within the Women's Health Initiative Observational Study. We selected 835 matched case–control pairs, and cases were further stratified by tumor site (proximal, distal, or rectal) and stage (local/regional or metastatic). Colorectal cancer was assessed by self-report and confirmed by medical records over the mean of 5.2 years of follow-up. Baseline plasma choline metabolites were measured by LC/MS-MS. In multivariable-adjusted conditional logistic regression models, plasma choline tended to be positively associated with rectal cancer risk [OR (95% confidence interval, CI)highest vs. lowest quartile = 2.44 (0.93–6.40); P trend = 0.08], whereas plasma betaine was inversely associated with colorectal cancer overall [0.68 (0.47–0.99); P trend = 0.01] and with local/regional tumors [0.64 (0.42–0.99); P trend = 0.009]. Notably, the plasma betaine:choline ratio was inversely associated with colorectal cancer overall [0.56 (0.39–0.82); P trend = 0.004] as well as with proximal [0.66 (0.41–1.06); P trend = 0.049], rectal [0.27 (0.10–0.78); P trend = 0.02], and local/regional [0.50 (0.33–0.76); P trend = 0.001] tumors. Finally, plasma TMAO, an oxidative derivative of choline produced by intestinal bacteria, was positively associated with rectal cancer [3.38 (1.25–9.16); P trend = 0.02] and with overall colorectal cancer risk among women with lower (vs. higher) plasma vitamin B12 levels (P interaction = 0.003). Collectively, these data suggest that alterations in choline metabolism, which may arise early in disease development, may be associated with higher risk of colorectal cancer. The positive association between plasma TMAO and colorectal cancer risk is consistent with an involvement of the gut microbiome in colorectal cancer pathogenesis. Cancer Res; 74(24); 7442–52. ©2014 AACR.
Unique Molecular Landscapes in Cancer: Implications for Individualized, Curated Drug Combinations
Authors: Wheler Jennifer , Lee J. Jack , Kurzrock Razelle 
Published: October 2014

Abstract
With increasingly sophisticated technologies in molecular biology and “omic” platforms to analyze patients' tumors, more molecular diversity and complexity in cancer are being observed. Recently, we noted unique genomic profiles in a group of patients with metastatic breast cancer based on an analysis with next-generation sequencing. Among 57 consecutive patients, no two had the same molecular portfolio. Applied genomics therefore appears to represent a disruptive innovation in that it unveils a heterogeneity to metastatic cancer that may be ill-suited to canonical clinical trials and practice paradigms. Upon recognizing that patients have unique tumor landscapes, it is possible that there may be a “mismatch” between our traditional clinical trials system that selects patients based on common characteristics to evaluate a drug (drug-centric approach) and optimal treatment based on curated, individualized drug combinations for each patient (patient-centric approach). Cancer Res; 74(24); 7181–4. ©2014 AACR.
Extracellular Lumican Inhibits Pancreatic Cancer Cell Growth and Is Associated with Prolonged Survival after Surgery
Authors: Li Xinqun , Truty Mark A. , Kang Ya'an , Chopin-Laly Xavier , Zhang Ran , Roife David , Chatterjee Deyali , Lin E. , Thomas Ryan M. , Wang Huamin , Katz Matthew H. , Fleming Jason B. 
Published: October 2014

Abstract
Purpose: To evaluate the relevance between lumican expression patterns and the clinical course of patients with pancreatic ductal adenocarcinoma (PDAC), and to investigate the role of lumican in PDAC progression.
Experimental Design: One hundred thirty-one patient tumors were chosen for tissue microarray staining, and Cox regression analysis was used to test the associations between lumican expression and clinical, pathologic, and oncologic outcomes in all patients. Primary PDAC cells and recombinant human lumican protein were used to establish a working model to mimic the in vivo interactions between stromal lumican and PDAC cells. Using this model, we tested the effects of lumican on EGFR signaling via Akt and hypoxia-inducible factor-1α (HIF1α) and its subsequent influence on glucose consumption, lactate production, intracellular ATP, and apoptotic cell death.
Results: Lumican was present in the stroma surrounding PDAC cells in roughly one-half of primary tumors and the direct xenografts. Patients with stromal lumican were associated with a profound reduction in metastatic recurrence after surgery and 3-fold longer survival than patients without stromal lumican. In PDAC cells, extracellular lumican reduced EGFR expression and phosphorylation through enhanced dimerization and internalization of EGFR and the resultant inhibition of Akt kinase activity. Lumican also reduced HIF1α expression and activity via Akt. PDAC cells with enhanced HIF1α activity were resistant to lumican-induced inhibition of glucose consumption, lactate production, intracellular ATP, and apoptosis.
Conclusions: There is a positive association between stromal lumican in primary PDAC tumors and prolonged survival after tumor resection. Lumican plays a restrictive role in EGFR-expressing pancreatic cancer progression. Clin Cancer Res; 20(24); 6529–40. ©2014 AACR.
Systemic Delivery of Microencapsulated 3-Bromopyruvate for the Therapy of Pancreatic Cancer
Authors: Chapiro Julius , Sur Surojit , Savic Lynn Jeanette , Ganapathy-Kanniappan Shanmugasundaram , Reyes Juvenal , Duran Rafael , Thiruganasambandam Sivarajan Chettiar , Moats Cassandra Rae , Lin MingDe , Luo Weibo , Tran Phuoc T. , Herman Joseph M. , Semenza Gregg L. , Ewald Andrew J. , Vogelstein Bert , Geschwind Jean-François 
Published: October 2014

AbstractPurpose: This study characterized the therapeutic efficacy of a systemically administered formulation of 3-bromopyruvate (3-BrPA), microencapsulated in a complex with β-cyclodextrin (β-CD), using an orthotopic xenograft mouse model of pancreatic ductal adenocarcinoma (PDAC).Experimental Design: The presence of the β-CD–3-BrPA complex was confirmed using nuclear magnetic resonance spectroscopy. Monolayer as well as three-dimensional organotypic cell culture was used to determine the half-maximal inhibitory concentrations (IC50) of β-CD–3-BrPA, free 3-BrPA, β-CD (control), and gemcitabine in MiaPaCa-2 and Suit-2 cell lines, both in normoxia and hypoxia. Phase-contrast microscopy, bioluminescence imaging (BLI), as well as zymography and Matrigel assays were used to characterize the effects of the drug in vitro. An orthotopic lucMiaPaCa-2 xenograft tumor model was used to investigate the in vivo efficacy.Results: β-CD–3-BrPA and free 3-BrPA demonstrated an almost identical IC50 profile in both PDAC cell lines with higher sensitivity in hypoxia. Using the Matrigel invasion assay as well as zymography, 3-BrPA showed anti-invasive effects in sublethal drug concentrations. In vivo, animals treated with β-CD–3-BrPA demonstrated minimal or no tumor progression as evident by the BLI signal as opposed to animals treated with gemcitabine or the β-CD (60-fold and 140-fold signal increase, respectively). In contrast to animals treated with free 3-BrPA, no lethal toxicity was observed for β-CD–3-BrPA.Conclusion: The microencapsulation of 3-BrPA represents a promising step towards achieving the goal of systemically deliverable antiglycolytic tumor therapy. The strong anticancer effects of β-CD–3-BrPA combined with its favorable toxicity profile suggest that clinical trials, particularly in patients with PDAC, should be considered. Clin Cancer Res; 20(24); 6406–17. ©2014 AACR.
Influence of Hospitalization for Cardiovascular Versus Noncardiovascular Reasons on Subsequent Mortality in Patients With Chronic Heart Failure Across the Spectrum of Ejection Fraction
Authors: Desai Akshay S. , Claggett Brian , Pfeffer Marc A. , Bello Natalie , Finn Peter V. , Granger Christopher B. , McMurray John J.V. , Pocock Stuart , Swedberg Karl , Yusuf Salim , Solomon Scott D. 
Published: October 2014

Background—
Noncardiovascular (non-CV) comorbidities may contribute to hospitalizations in patients with heart failure (HF). We examined the incidence of mortality following hospitalization for cardiovascular (CV) versus non-CV reasons in the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program.

Methods and Results—

First hospitalizations for CV or non-CV reasons during the CHARM trial (N=7599) were related to subsequent risk of all-cause death using time-updated proportional hazards models. Over median 37.7 month follow-up, 2816 subjects (37.1%) were not hospitalized, 2893 (38.1%) were first hospitalized for CV reasons, and 1890 (24.9%) for non-CV reasons. The death rate (per 100 patient-years) among those not hospitalized was 2.8 compared with 17.8 after CV and 16.5 after non-CV hospitalization (both
P
<0.001 versus not hospitalized). Mortality at 30 days was higher after CV than non-CV hospitalization; however, among 30-day survivors of CV and non-CV hospitalization, rates of subsequent mortality were similar (14.5 versus 14.6 per 100 patient-years;
P
=0.62). Rates of CV hospitalization were higher for those with ejection fraction (EF) ≤40% than those with EF >40% (
P
<0.001), but rates of non-CV hospitalization did not vary by EF. Low EF patients had higher risk for mortality than preserved EF patients after any hospitalization, but within each EF subgroup, mortality in 30-day survivors of CV versus non-CV hospitalization was similar.

Conclusions—
Non-CV hospitalization is frequent in patients with symptomatic heart failure and associated with risk of subsequent mortality similar to CV hospitalization across the spectrum of EF. These findings may have implications for developing strategies to prevent readmissions.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00634309 (CHARM-Added), NCT00634712 (CHARM-Preserved), NCT00634400 (CHARM-Alternative).
Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation in Stented Renal Arteries
Authors: Mahfoud Felix , Tunev Stefan , Ruwart Jennifer , Schulz-Jander Daniel , Cremers Bodo , Linz Dominik , Zeller Thomas , Bhatt Deepak L. , Rocha-Singh Krishna , Böhm Michael , Melder Robert J. 
Published: October 2014

Background—
In selected patients with hypertension, renal artery (RA) stenting is used to treat significant atherosclerotic stenoses. However, blood pressure often remains uncontrolled after the procedure. Although catheter-based renal denervation (RDN) can reduce blood pressure in certain patients with resistant hypertension, there are no data on the feasibility and safety of RDN in stented RA.

Methods and Results—
We report marked blood pressure reduction after RDN in a patient with resistant hypertension who underwent previous stenting. Subsequently, radiofrequency ablation was investigated within the stented segment of porcine RA, distal to the stented segment, and in nonstented RA and compared with stent only and untreated controls. There were neither observations of thrombus nor gross or histological changes in the kidneys. After radiofrequency ablation of the nonstented RA, sympathetic nerves innervating the kidney were significantly reduced, as indicated by significant decreases in sympathetic terminal axons and reduction of norepinephrine in renal tissue. Similar denervation efficacy was found when RDN was performed distal to a renal stent. In contrast, when radiofrequency ablation was performed within the stented segment of the RA, significant sympathetic nerve ablation was not seen. Histological observation showed favorable healing in all arteries.

Conclusions—
Radiofrequency ablation of previously stented RA demonstrated that RDN provides equally safe experimental procedural outcomes in a porcine model whether the radiofrequency treatment is delivered within, adjacent, or without the stent struts being present in the RA. However, efficacious RDN is only achieved when radiofrequency ablation is delivered to the nonstented RA segment distal to the stent.