bluuebunny/crossref_metadata_2025_split huggingface dataset:
Collectives of diagnostic biomarkers identify high-risk subpopulations of hematuria patients: exploiting heterogeneity in large-scale biomarker data
Authors: Emmert-Streib Frank , Abogunrin Funso , de Matos Simoes Ricardo , Duggan Brian , Ruddock Mark W , Reid Cherith N , Roddy Owen , White Lisa , O'Kane Hugh F , O'Rourke Declan , Anderson Neil H , Nambirajan Thiagarajan , Williamson Kate E 
Published: January 2013

Abstract

Background
Ineffective risk stratification can delay diagnosis of serious disease in patients with hematuria. We applied a systems biology approach to analyze clinical, demographic and biomarker measurements (n = 29) collected from 157 hematuric patients: 80 urothelial cancer (UC) and 77 controls with confounding pathologies.

Methods
On the basis of biomarkers, we conducted agglomerative hierarchical clustering to identify patient and biomarker clusters. We then explored the relationship between the patient clusters and clinical characteristics using Chi-square analyses. We determined classification errors and areas under the receiver operating curve of Random Forest Classifiers (RFC) for patient subpopulations using the biomarker clusters to reduce the dimensionality of the data.

Results
Agglomerative clustering identified five patient clusters and seven biomarker clusters. Final diagnoses categories were non-randomly distributed across the five patient clusters. In addition, two of the patient clusters were enriched with patients with 'low cancer-risk' characteristics. The biomarkers which contributed to the diagnostic classifiers for these two patient clusters were similar. In contrast, three of the patient clusters were significantly enriched with patients harboring 'high cancer-risk" characteristics including proteinuria, aggressive pathological stage and grade, and malignant cytology. Patients in these three clusters included controls, that is, patients with other serious disease and patients with cancers other than UC. Biomarkers which contributed to the diagnostic classifiers for the largest 'high cancer- risk' cluster were different than those contributing to the classifiers for the 'low cancer-risk' clusters. Biomarkers which contributed to subpopulations that were split according to smoking status, gender and medication were different.

Conclusions
The systems biology approach applied in this study allowed the hematuric patients to cluster naturally on the basis of the heterogeneity within their biomarker data, into five distinct risk subpopulations. Our findings highlight an approach with the promise to unlock the potential of biomarkers. This will be especially valuable in the field of diagnostic bladder cancer where biomarkers are urgently required. Clinicians could interpret risk classification scores in the context of clinical parameters at the time of triage. This could reduce cystoscopies and enable priority diagnosis of aggressive diseases, leading to improved patient outcomes at reduced costs.
Changes in subcellular localization reveal interactions between human cytomegalovirus terminase subunits
Authors: Wang Jian Ben , Zhu Yali , McVoy Michael A , Parris Deborah S 
Published: January 2013

Abstract

Background
During herpesvirus replication, terminase packages viral DNA into capsids. The subunits of herpes simplex virus terminase, UL15, UL28, and UL33, assemble in the cytoplasm prior to nuclear import of the complex.

Methods
To detect similar interactions between human cytomegalovirus terminase subunits, the orthologous proteins UL89, UL56, and UL51 were expressed in HEK-293 T cells (via transfection) or insect cells (via baculovirus infection) and subcellular localizations were detected by cellular fractionation and confocal microscopy.

Results
In both cell types, UL56 and UL89 expressed alone were exclusively cytoplasmic, whereas UL51 was ~50% nuclear. Both UL89 and UL56 became ~50% nuclear when expressed together, as did UL56 when expressed with UL51. Nuclear localization of each protein was greatest when all three proteins were co-expressed.

Conclusions
These results support inclusion of UL51 as an HCMV terminase subunit and suggest that nuclear import of human cytomegalovirus terminase may involve nuclear import signals that form cooperatively upon subunit associations.
An unusual case of giant cell myocarditis missed in a Heartmate-2 left ventricle apical-wedge section: a case report and review of the literature
Authors: Anderson Kim , Carrier Michel , Romeo Philippe , Pelletier Guy B , Liszkowski Mark , Racine Normand , White Michel , Ducharme Anique 
Published: January 2013

Abstract
Herein we present a case of fulminant myocarditis in a woman previously treated for B-cell lymphoma. While the clinical context was suggestive of adriamycin-induced cardiomyopathy, the initial pathology of the Heartmate-2 apical core showed lymphocytic myocarditis. After 8 months of stability, the patient presented with progressive heart failure and recurrent ventricular arrhythmias. An endomyocardial biopsy revealed findings typical of giant cell myocarditis (GCM); poor response to immunosuppressive therapy and marked hemodynamic instability led to urgent transplantation. To our knowledge, this is the first reported case of GCM following an acute lymphocytic myocarditis and the second GCM case associated with B-cell lymphoma.
Fatty acid composition of lipids in pot marigold (Calendula officinalisL.) seed genotypes
Authors: Dulf Francisc V , Pamfil Doru , Baciu Adriana D , Pintea Adela 
Published: January 2013

Abstract

Background

Calendula officinalis L. (pot marigold) is an annual aromatic herb with yellow or golden-orange flowers, native to the Mediterranean climate areas. Their seeds contain significant amounts of oil (around 20%), of which about 60% is calendic acid. For these reasons, in Europe concentrated research efforts have been directed towards the development of pot marigold as an oilseed crop for industrial purposes.

Results
The oil content and fatty acid composition of major lipid fractions in seeds from eleven genotypes of pot marigold (Calendula officinalis L.) were determined. The lipid content of seeds varied between 13.6 and 21.7 g oil/100 g seeds. The calendic and linoleic acids were the two dominant fatty acids in total lipid (51.4 to 57.6% and 28.5 to 31.9%) and triacylglycerol (45.7 to 54.7% and 22.6 to 29.2%) fractions. Polar lipids were also characterised by higher unsaturation ratios (with the PUFAs content between 60.4 and 66.4%), while saturates (consisted mainly of palmitic and very long-chain saturated fatty acids) were found in higher amounts in sterol esters (ranging between 49.3 and 55.7% of total fatty acids).

Conclusions
All the pot marigold seed oils investigated contain high levels of calendic acid (more than 50% of total fatty acids), making them favorable for industrial use. The compositional differences between the genotypes should be considered when breeding and exploiting the pot marigold seeds for nutraceutical and pharmacological purposes.
c-Abl tyrosine kinase plays a critical role in β2 integrin-dependent neutrophil migration by regulating Vav1 activity
Authors: Tong Haibin , Zhao Bin , Shi Huifang , Ba Xueqing , Wang Xiaoguang , Jiang Yong , Zeng Xianlu 
Published: January 2013

Abstract
A central regulatory role of c-Abl kinase in controlling actin polymerization and membrane protrusion dynamics at leading edge, during β2 integrin-dependent neutrophil migration.
The recruitment and migration of neutrophils are critical for innate immunity and acute inflammatory responses. However, the mechanism that regulates the recruitment and migration of neutrophils has not been well characterized. We here reveal a novel function of c-Abl kinase in regulating neutrophil migration. Our results demonstrate that c-Abl kinase is required for neutrophil recruitment in vivo and migration in vitro, and the inhibition of c-Abl kinase activity has a significant impact on neutrophil migratory behavior. Moreover, c-Abl kinase activation depends on β2 integrin engagement, and the activated c-Abl kinase further regulates actin polymerization and membrane protrusion dynamics at the extended leading edges during neutrophil migration. In addition, we identify the Rho GEF Vav1 as a major downstream effector of c-Abl kinase. The C-terminal SH3-SH2-SH3 domain and proline-rich region of Vav1 are required for its interaction with c-Abl kinase, and c-Abl kinase probably regulates the activity of Vav1 by direct phosphorylation at Tyr-267 in the DH domain. Together, these results indicate that c-Abl kinase plays a critical role in β2 integrin-dependent neutrophil migration by regulating Vav1 activity.
Aspirin for the Prophylaxis of Venous Thromboembolic Events in Orthopedic Surgery Patients: A Comparison of the AAOS and ACCP Guidelines with Review of the Evidence
Authors: Stewart David W , Freshour Jessica E 
Published: January 2013

BACKGROUND The American Academy of Orthopaedic Surgeons (AAOS) and the American College of Chest Physicians (ACCP) have both developed evidence-based guidelines to prevent venous thromboembolism (VTE) in high-risk orthopedic surgery patients. Recent changes to these documents have brought them into agreement as to the inclusion of aspirin as an appropriate option for VTE prophylaxis in this patient population. OBJECTIVE To evaluate the appropriateness of aspirin to prevent VTE in high-risk orthopedic surgery patients. DATA SOURCES Guidelines published by the AAOS in 2011 and the ACCP in 2012 were compared regarding their recommendations on the use of aspirin for the prevention of VTE. A literature search was also conducted to identify clinical trials that evaluated the use of aspirin for the prevention of VTE in this patient population. Search terms included the MeSH terms venous thromboembolism; venous thrombosis; pulmonary embolism; aspirin; arthroplasty, replacement, knee; arthroplasty, replacement, hip; and hip fractures/surgery. STUDY SELECTION AND DATA EXTRACTION Any study that evaluated aspirin, even in combination with another method of prophylaxis (such as pneumatic compression devices), and had been published during or after 1985 was included. DATA SYNTHESIS Randomized controlled trials, meta-analyses, and other large pooled and retrospective reviews have failed to consistently arrive at similar conclusions regarding the efficacy and safety of aspirin as an option for VTE prophylaxis in patients undergoing total knee arthroplasty (TKA), total hip arthroplasty (THA), or hip fracture surgery (HFS). Disagreements in the appropriateness of surrogate markers for safety and efficacy have resulted in differing recommendations from the ACCP and AAOS. The primary argument lies in the appropriateness of deep vein thrombosis as a surrogate marker for more serious outcomes such as pulmonary emboli. CONCLUSIONS Recent changes to both the ACCP and AAOS guidelines are in agreement for those who choose to use aspirin for chemoprophylaxis of VTE. Current surgical care improvement project measures do not include aspirin as an appropriate sole option for the prevention of VTE, but in patients undergoing elective TKA or who have a contraindication to pharmacologic prophylaxis and undergo a THA or HFS, aspirin in conjunction with compression devices as part of a multimodal approach would meet these measures. Data do not support the hypothesis that aspirin is less likely to cause adverse bleeding events than more potent anticoagulants.
National Utilization Patterns of Warfarin Use in Older Patients with Atrial Fibrillation: A Population-Based Study of Medicare Part D Beneficiaries
Authors: Raji Mukaila A , Lowery Matthew , Lin Yu-Li , Kuo Yong-Fang , Baillargeon Jacques , Goodwin James S 
Published: January 2013

BACKGROUND Although warfarin therapy reduces stroke incidence in patients with atrial fibrillation (AF), the rate of warfarin use in this population remains low. In 2008, the Medicare Part D program was expanded to pay for medications for Medicare enrollees. OBJECTIVE To examine rates and predictors of warfarin use in Medicare Part D beneficiaries with AF. METHODS This population-based retrospective cohort study used claims data from 41,447 Medicare beneficiaries aged 66 and older with at least 2 AF diagnoses in 2007 and at least 1 diagnosis in 2008. All subjects had continuous Medicare Part D prescription coverage in 2008. Statistical analysis using χ2 was used to examine differences in warfarin use by patient characteristics (age, ethnicity, sex, Medicaid eligibility, comorbidities, contraindications to warfarin, and whether they visited a cardiologist or a primary care physician [PCP]), CHADS2 score (congestive heart failure, hypertension, age, diabetes, and stroke or transient ischemic attack; higher scores indicate higher risks of stroke), and geographic regions. Using hierarchical generalized linear models restricted to subjects without warfarin contraindications (n = 34,947), we examined the effect of patient characteristics and geographic regions on warfarin use. RESULTS The overall warfarin use rate was 66.8%. The warfarin use rates varied between hospital referral regions, with highest rates in the Midwestern states and lowest rates in the South. The regional variation persisted even after adjustment for patient characteristics. Multivariable analysis showed that the odds of being on warfarin decreased significantly with age and increasing comorbidity, in blacks, and among those with low income. Seeing a cardiologist (OR 1.10; 95% CI 1.05–1.16), having a PCP (OR 1.23; 95% CI 1.17–1.29), and CHADS2 score of 2 or greater (OR 1.09; 95% CI 1.01–1.17) were associated with increased odds of warfarin use. CONCLUSIONS Warfarin use rates vary by patient characteristics and region, with higher rates among residents of the Midwest and among patients seen by cardiologists and PCPs. Preventing stroke-related disability in AF requires implementation of evidence-based initiatives to increase warfarin use.
The modern miniature camera objective: an evolutionary design path from the landscape lens
Authors: Bates Rob 
Published: January 2013

Abstract
The modern miniature camera lens is the most prolific design manufactured today, yet its design form and origins are often not well understood. This paper illuminates the ancestry of the modern miniature camera lens by developing the lens form from ‘scratch.’ Starting with the Wollaston meniscus of 1812, the lens is designed progressively, employing incremental design decisions aimed at correcting limiting aberrations at each step. The result demonstrates an ancestry that is distinctly different than that of the common large-format objective lenses.
Chemical and enzymatic characterization of recombinant rabbit muscle pyruvate kinase
Authors: Boehme Christian , Bieber Frank , Linnemann Julia , Breitling Reinhard , Lorkowski Stefan , Reissmann Siegmund 
Published: January 2013

Abstract
The stepwise synthesis of thymidine triphosphate (TTP) requires a kinase for phosphorylation in the last step. Because pyruvate kinase (PK) using phosphoenolpyruvate (PEP) as substrate can regenerate adenosine triphosphate and phosphorylate thymidine diphosphate as well, we chose this enzyme for the synthesis of TTP via an enzymatic cascade reaction. The metalloenzyme PK shows pronounced promiscuity and therefore fits well to the conditions of this reaction. PK commonly used today is isolated from rabbit muscle. We cloned and expressed the respective open reading frame in Escherichia coli, purified, and characterized the His-tagged recombinant enzyme. The enzyme has an activity optimum at 37°C and in the pH range from 7.4 to 7.8. K

m
constants conformed well with the isolated native enzyme for adenosine diphosphate (ADP) to 0.37±0.02 mm and for PEP to 0.07±0.01 mm. The recombinant enzyme shows the following range in its substrate specificity: ADP>dADP>dGDP>dCDP>thymidine diphosphate (TDP). It allows the phosphorylation of TDP to TTP in high yield (up to 95%). The metal ions Mg2+ and K+ are necessary for full enzymatic activity. The addition of transition metal ions such as Mn2+, Cu2+, Co2+, and Ni2+ reduces activity. Storage of the enzyme at -20°C retains full activity.
Hypoxia, the HIF pathway and neutrophilic inflammatory responses
Authors: Thompson A.A. Roger , Binham John , Plant Tracie , Whyte Moira K.B. , Walmsley Sarah R. 
Published: January 2013

Abstract
Many inflammatory diseases are characterised by persistent and inappropriate neutrophil activation, systemic or localised hypoxia, and bacterial colonisation. Hypoxia represents an important regulator of inflammatory responses because it inhibits neutrophil apoptosis, a process central to the timely resolution of inflammation. Progress in understanding how cells respond to hypoxia has led to the identification of hypoxia-inducible transcription factors (HIFs) and their hydroxylation by the prolyl hydroxylase enzymes. There is now a significant body of data to support a critical role for this HIF pathway in regulating neutrophil function. Moreover, manipulations of specific components of this pathway have very divergent effects on myeloid cell function. In this review, we will discuss the role individual members of the HIF pathway play in regulating key neutrophil functions and the implications this has for the development of effective therapeutic strategies that selectively target inappropriate neutrophil persistence while maintaining a fully competent immune response.
nanoHUB.org: cloud-based services for nanoscale modeling, simulation, and education
Authors: Madhavan Krishna , Zentner Lynn , Farnsworth Victoria , Shivarajapura Swaroop , Zentner Michael , Denny Nathan , Klimeck Gerhard 
Published: January 2013

AbstractnanoHUB.org is arguably one of the most successful science gateways funded by the National Science Foundation (NSF). It is the cyberinfrastructure that supports the Network for Computational Nanotechnology (NCN), currently serving over 240,000 users annually in 172 countries worldwide. It features a range of resources including seminars, online courses, short courses, full-fledged tool-powered curricula, and over 260 online simulations and modeling tools. nanoHUB functions as a scientific cloud where users cannot only design and run their tools but also provide a worldwide audience access to these tools with no installation or minimal infrastructural requirements on the users’ part.
Consumer diversity interacts with prey defenses to drive ecosystem function
Authors: Rasher Douglas B. , Hoey Andrew S. , Hay Mark E. 
Published: January 2013

Prey traits linking consumer diversity to ecosystem function remain poorly understood. On tropical coral reefs, herbivores promote coral dominance by suppressing competing macroalgae, but the roles of herbivore identity and diversity, macroalgal defenses, and their interactions in affecting reef resilience and function are unclear. We studied adjacent pairs of no‐take marine reserves and fished areas on reefs in Fiji and found that protected reefs supported 7–17× greater biomass, 2–3× higher species richness of herbivorous fishes, and 3–11× more live coral cover than did fished reefs. In contrast, macroalgae were 27–61× more abundant and 3–4× more species‐rich on fished reefs. When we transplanted seven common macroalgae from fished reefs into reserves they were rapidly consumed, suggesting that rates of herbivory (ecosystem functioning) differed inside vs. outside reserves.We then video‐recorded feeding activity on the same seven macroalgae when transplanted into reserves, and assessed the functional redundancy vs. complementarity of herbivorous fishes consuming these macroalgae. Of 29 species of larger herbivorous fishes on these reefs, only four species accounted for 97% of macroalgal consumption. Two unicornfish consumed a range of brown macroalgae, a parrotfish consumed multiple red algae, and a rabbitfish consumed a green alga, with almost no diet overlap among these groups. The two most chemically rich, allelopathic algae were each consumed by a single, but different, fish species. This striking complementarity resulted from herbivore species differing in their tolerances to macroalgal chemical and structural defenses.A model of assemblage diet breadth based on our feeding observations predicted that high browser diversity would be required for effective control of macroalgae on Fijian reefs. In support of this model, we observed strong negative relationships between herbivore diversity and macroalgal abundance and diversity across the six study reefs. Our findings indicate that the total diet breadth of the herbivore community and the probability of all macroalgae being removed from reefs by herbivores increases with increasing herbivore diversity, but that a few critical species drive this relationship. Therefore, interactions between algal defenses and herbivore tolerances create an essential role for consumer diversity in the functioning and resilience of coral reefs.
Mother-Perceived Social Capital and Children’s Oral Health and Use of Dental Care in the United States
Authors: Iida Hiroko , Rozier R. Gary 
Published: January 2013

Objectives. We examined the association between mother-perceived neighborhood social capital and oral health status and dental care use in US children. Methods. We analyzed data for 67 388 children whose mothers participated in the 2007 National Survey of Children’s Health. We measured mothers’ perceived social capital with a 4-item social capital index (SCI) that captures reciprocal help, support, and trust in the neighborhood. Dependent variables were mother-perceived ratings of their child’s oral health, unmet dental care needs, and lack of a previous-year preventive dental visit. We performed bivariate and multivariable logistic regression analyses for each outcome. Results. After we controlled for potential confounders, children of mothers with high (SCI = 5–7) and lower levels (SCI ≥ 8) of social capital were 15% (P = .05) and about 40% (P ≤ .02), respectively, more likely to forgo preventive dental visits than were children of mothers with the highest social capital (SCI = 4). Mothers with the lowest SCI were 79% more likely to report unmet dental care needs for their children than were mothers with highest SCI (P = .01). Conclusions. A better understanding of social capital’s effects on children’s oral health risks may help address oral health disparities.
The Impact of Functional Health Literacy and Acculturation on the Oral Health Status of Somali Refugees Living in Massachusetts
Authors: Geltman Paul L. , Adams Jo Hunter , Cochran Jennifer , Doros Gheorghe , Rybin Denis , Henshaw Michelle , Barnes Linda L. , Paasche-Orlow Michael 
Published: January 2013

Objectives. We assessed the impact of health literacy and acculturation on oral health status of Somali refugees in Massachusetts. Methods. Between December 2009 and June 2011, we surveyed 439 adult Somalis who had lived in the United States 10 years or less. Assessments included oral examinations with decayed, missing, and filled teeth (DMFT) counts and measurement of spoken English and health literacy. We tested associations with generalized linear regression models. Results. Participants had means of 1.4 decayed, 2.8 missing, and 1.3 filled teeth. Among participants who had been in the United States 0 to 4 years, lower health literacy scores correlated with lower DMFT (rate ratio [RR] = 0.78; P = .016). Among participants who had been in the country 5 to 10 years, lower literacy scores correlated with higher DMFT (RR = 1.37; P = .012). Literacy was not significantly associated with decayed teeth. Lower literacy scores correlated marginally with lower risk of periodontal disease (odds ratio = 0.22; P = .047). Conclusions. Worsening oral health of Somali refugees over time may be linked to less access to preventive care and less utilization of beneficial oral hygiene practices.