bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adolescent knowledge and attitudes related to clinical trials
Authors: Brown Devin L , Cowdery Joan E , Jones Toni Stokes , Langford Aisha , Gammage Catherine , Jacobs Teresa L 
Published: February 2015

Background or aims Poor enrollment plagues most clinical trials. Furthermore, despite mandates to improve minority representation in clinical trial participation, little progress has been made. We investigated the knowledge and attitudes of adolescents related to clinical trials and made race/ethnicity comparisons in an attempt to identify a possible educational intervention target. Methods Students aged 13–18 years in southeast Michigan were offered participation through a class at one high school or two academic summer enrichment programs that drew from multiple high schools (73% response). Questionnaires previously validated in adults were administered. Non-Hispanic whites were compared with minorities using Wilcoxon rank-sum tests. Results Of the 82 respondents, the median age was 16 years (interquartile range: 15–17 years); 22 (28%) were white, 41 (51%) were African American, 11 (14%) were multiracial, 2 (2%) were American Indian or Alaska Native, 1 (1%) was Asian, 3 (4%) were Native Hawaiian or other Pacific Islander, and 2 respondents did not report a race (but did report Hispanic ethnicity). Nine (12%) were Hispanic. Only 27 (33%) had ever heard of a clinical trial. On a scale from 1 (most receptive) to 5 (least receptive) for learning more about a clinical trial for a relevant medical condition, the median score was 2 (interquartile range: 1–3) and for participating in a clinical trial for a relevant medical condition was 2 (interquartile range: 2–3). Overall knowledge was poor, with a median of 46% (interquartile range: 23%−62%) of knowledge answers correct. Knowledge was reduced (p = 0.0006) and attitudes were more negative (p = 0.05) in minorities than non-Hispanic whites, while minorities also endorsed more substantial barriers to trial participation (p = 0.0002). Distrust was similar between minority students and non-Hispanic whites (p = 0.15), and self-efficacy was greater in non-Hispanic whites (p = 0.05). Conclusion Educational interventions directed toward adolescents that address knowledge, attitudes, and distrust in order to improve clinical trial awareness and receptivity overall are needed and may represent a tool to address disparities in minority enrollment in clinical trials.
Clinical trial awareness: Changes over time and sociodemographic disparities
Authors: Leiter Amanda , Diefenbach Michael A , Doucette John , Oh William K , Galsky Matthew D 
Published: February 2015

Background or aims: Lack of clinical trial awareness is a known obstacle to clinical trial enrollment. We sought to define the prevalence of clinical trial awareness in the US population, determine characteristics associated with increased trial awareness, and explore potential disparities in trial awareness. Methods: We utilized data from the Health Information National Trends Survey from 2008 and 2012. Logistic regression was utilized to assess predictors of clinical trial awareness, particularly sociodemographic variables and information-seeking preferences. Trial awareness and information-seeking preferences were compared in patient subgroups and between the two time periods. Results: Clinical trial awareness increased from 68% to 74% between 2008 and 2012. In the 2012 dataset, higher education level (odds ratio: 3.52, 95% confidence interval: 2.16–5.74), higher yearly income category (odds ratio: 1.84, 95% confidence interval: 1.17–2.89), and Internet use (odds ratio: 2.13, 95% confidence interval: 1.52–3.00) were significantly associated with clinical trial awareness. Hispanic ethnicity (odds ratio: 0.41, 95% confidence interval: 0.25–0.68) was significantly associated with decreased awareness. Clinical trial awareness increased in African-American/Blacks (Δ10.6%) and Hispanics (Δ10.7%) between 2008 and 2012, as did Internet use in both subgroups (Δ14.2%, Δ18.1%, respectively). Conclusion: Overall clinical trial awareness has increased between 2008 and 2012, although a large subset of the population still lacks general awareness of clinical trials. Racial and ethnic disparities in trial awareness exist, although disparities may be decreasing among the Black population. These findings may help target educational efforts and inform approaches to increasing trial awareness.
Effectiveness of balance exercises in the acute post-operative phase following total hip and knee arthroplasty: A randomized clinical trial
Authors: Jogi Pankaj , Overend Tom J , Spaulding Sandi J , Zecevic Aleksandra , Kramer John F 
Published: February 2015

Objectives: To determine the effectiveness of balance exercises in the acute post-operative phase following total hip arthroplasty or total knee arthroplasty. Methods: Patients who had total hip arthroplasty ( n = 30) or total knee arthroplasty ( n = 33) were seen in their residence 1–2 times per week for 5 weeks. At the first post-operative home visit, patients were randomly assigned to either typical (TE, n = 33) or typical plus balance (TE + B, n = 30) exercise groups. The TE group completed seven typical surgery-specific joint range-of-motion and muscle strengthening exercises, while the TE + B group completed the typical exercises plus three balance exercises. Patients were assessed before and 5 weeks after administering the rehabilitation program using four outcome measures: (1) the Berg Balance Scale, (2) the Timed Up and Go test, (3) the Western Ontario McMaster Universities Osteoarthritis Index, and (4) the Activities-specific Balance Confidence Scale. Results: Post-intervention scores for all four outcome measures were significantly improved ( p < 0.01) over baseline scores. Patients who participated in the TE + B group demonstrated significantly greater improvement on the Berg Balance Scale and the Timed Up and Go tests ( p < 0.01). Conclusion: Balance exercises added to a typical rehabilitation program resulted in significantly greater improvements in balance and functional mobility compared to typical exercises alone.
von Willebrand factor propeptide and the phenotypic classification of von Willebrand disease
Authors: Sanders Yvonne V. , Groeneveld Dafna , Meijer Karina , Fijnvandraat Karin , Cnossen Marjon H. , van der Bom Johanna G. , Coppens M. , de Meris Joke , Laros-van Gorkom Britta A. P. , Mauser-Bunschoten Eveline P. , Leebeek Frank W. G. , Eikenboom Jeroen ,   the WiN study group
Published: February 2015

Key Points
VWFpp discriminates between type 3 VWD patients and severe type 1 VWD patients with very low VWF levels. The pathophysiological mechanisms of all types of VWD can be defined by the combined ratios of VWFpp/VWF:Ag and FVIII:C/VWF:Ag.
The diagnostic and prognostic significance of monitoring blood levels of immature neutrophils in patients with systemic inflammation
Authors: Mare Tracey Anne , Treacher David Floyd , Shankar-Hari Manu , Beale Richard , Lewis Sion Marc , Chambers David John , Brown Kenneth Alun 
Published: February 2015

Abstract
Introduction
In this cohort study, we investigated whether monitoring blood levels of immature neutrophils (myelocytes, metamyelocytes and band cells) differentiated patients with sepsis from those with the non-infectious (N-I) systemic inflammatory response syndrome (SIRS). We also ascertained if the appearance of circulating immature neutrophils was related to adverse outcome.

Methods
Blood samples were routinely taken from 136 critically ill patients within 48 hours of ICU entry and from 20 healthy control subjects. Clinical and laboratory staff were blinded to each other’s results, and patients were retrospectively characterised into those with SIRS (n = 122) and those without SIRS (n = 14). The patients with SIRS were further subdivided into categories of definite sepsis (n = 51), possible sepsis (n = 32) and N-I SIRS (n = 39). Two established criteria were used for monitoring immature white blood cells (WBCs): one where band cells >10% WBCs and the other where >10% of all forms of immature neutrophils were included but with a normal WBC count. Immature neutrophils in blood smears were identified according to nuclear morphology and cytoplasmic staining.

Results
With the first criterion, band cells were present in most patients with SIRS (mean = 66%) when compared with no SIRS (mean = 29%; P <0.01) and with healthy subjects (0%). The prevalence of band cells was higher in definite sepsis (mean = 82%) than in patients with possible sepsis (mean = 63%; P <0.05) or with N-I SIRS (mean = 39%; P <0.001), and they had a sensitivity of 84% and a specificity of 71% for the detection of definite sepsis. With the second criterion (that is, patients with normal WBC counts), we noted that immature neutrophils did not differentiate any of the patient groups from one another. Patients who died within 1 week of blood sample provision had higher levels of myelocytes and metamyelocytes (median = 9%; P <0.05) than patients who died at 2 to 4 weeks (median =0.5%).

Conclusions
Raised blood levels of band cells have diagnostic significance for sepsis, provided that measurements are not confined to patients with normal WBC counts, whereas an increased prevalence of myelocytes and metamyelocytes may have prognostic application.
Endotracheal tube biofilm translocation in the lateral Trendelenburg position
Authors: Li Bassi Gianluigi , Fernandez-Barat Laia , Saucedo Lina , Giunta Valeria , Marti Joan Daniel , Tavares Ranzani Otavio , Aguilera Xiol Eli , Rigol Montserrat , Roca Ignasi , Muñoz Laura , Luque Nestor , Esperatti Mariano , Saco Maria Adela , Ramirez Jose , Vila Jordi , Ferrer Miguel , Torres Antoni 
Published: February 2015

Abstract
Introduction
Laboratory studies demonstrated that the lateral Trendelenburg position (LTP) is superior to the semirecumbent position (SRP) in the prevention of ventilator-associated pulmonary infections. We assessed whether the LTP could also prevent pulmonary colonization and infections caused by an endotracheal tube (ETT) biofilm.

Methods
Eighteen pigs were intubated with ETTs colonized by Pseudomonas aeruginosa biofilm. Pigs were positioned in LTP and randomized to be on mechanical ventilatin (MV) up to 24 hour, 48 hour, 48 hour with acute lung injury (ALI) by oleic acid and 72 hour. Bacteriologic and microscopy studies confirmed presence of biofilm within the ETT. Upon autopsy, samples from the proximal and distal airways were excised for P.aeruginosa quantification. Ventilator-associated tracheobronchitis (VAT) was confirmed by bronchial tissue culture ≥3 log colony forming units per gram (cfu/g). In pulmonary lobes with gross findings of pneumonia, ventilator-associated pneumonia (VAP) was confirmed by lung tissue culture ≥3 log cfu/g.

Results
P.aeruginosa colonized the internal lumen of 16 out of 18 ETTs (88.89%), and a mature biofilm was consistently present. P.aeruginosa colonization did not differ among groups, and was found in 23.6% of samples from the proximal airways, and in 7.1% from the distal bronchi (P = 0.001). Animals of the 24 hour group never developed respiratory infections, whereas 20%, 60% and 25% of the animals in group 48 hour, 48 hour-ALI and 72 hour developed P.aeruginosa VAT, respectively (P = 0.327). Nevertheless, VAP never developed.

Conclusions
Our findings imply that during the course of invasive MV up to 72 hour, an ETT P.aeruginosa biofilm hastily colonizes the respiratory tract. Yet, the LTP compartmentalizes colonization and infection within the proximal airways and VAP never develops.
BitPhylogeny: a probabilistic framework for reconstructing intra-tumor phylogenies
Authors: Yuan Ke , Sakoparnig Thomas , Markowetz Florian , Beerenwinkel Niko 
Published: February 2015

AbstractCancer has long been understood as a somatic evolutionary process, but many details of tumor progression remain elusive. Here, we present , a probabilistic framework to reconstruct intra-tumor evolutionary pathways. Using a full Bayesian approach, we jointly estimate the number and composition of clones in the sample as well as the most likely tree connecting them. We validate our approach in the controlled setting of a simulation study and compare it against several competing methods. In two case studies, we demonstrate how reconstructs tumor phylogenies from methylation patterns in colon cancer and from single-cell exomes in myeloproliferative neoplasm.
An improved kilogram-scale preparation of atorvastatin calcium
Authors: Novozhilov Yuri V , Dorogov Mikhail V , Blumina Maria V , Smirnov Alexey V , Krasavin Mikhail 
Published: February 2015

Abstract

Background
If literature protocols are followed, conversion of an advanced ketal ester intermediate (available in kilogram quantities via a published Paal-Knorr synthesis) to cholesterol-lowering drug atorvastatin calcium is hampered by several process issues, particularly at the final stage where the hemi-calcium salt is obtained.

Results
We developed a high-yielding synthesis of atorvastatin calcium salt on 7 kg scale that affords >99.5% product purities by introducing the following key improvements: i. isolating the pure product of the ketal deprotection step as crystalline solid, and ii. using a convenient ethyl acetate extraction procedure to isolate the pure atorvastatin calcium at the ester hydrolysis and counter-ion exchange step.

Conclusion
The convenient and operationally simple conversion of an advanced intermediate of atorvastatin to the clinically used hemi-calcium salt form of the drug that is superior to the methods obtainable from the literature is now available to facilitate the production of atorvastatin calcium on industrial scale.
When drug discovery meets web search: Learning to Rank for ligand-based virtual screening
Authors: Zhang Wei , Ji Lijuan , Chen Yanan , Tang Kailin , Wang Haiping , Zhu Ruixin , Jia Wei , Cao Zhiwei , Liu Qi 
Published: February 2015

Abstract

Background
The rapid increase in the emergence of novel chemical substances presents a substantial demands for more sophisticated computational methodologies for drug discovery. In this study, the idea of Learning to Rank in web search was presented in drug virtual screening, which has the following unique capabilities of 1). Applicable of identifying compounds on novel targets when there is not enough training data available for these targets, and 2). Integration of heterogeneous data when compound affinities are measured in different platforms.

Results
A standard pipeline was designed to carry out Learning to Rank in virtual screening. Six Learning to Rank algorithms were investigated based on two public datasets collected from Binding Database and the newly-published Community Structure-Activity Resource benchmark dataset. The results have demonstrated that Learning to rank is an efficient computational strategy for drug virtual screening, particularly due to its novel use in cross-target virtual screening and heterogeneous data integration.

Conclusions
To the best of our knowledge, we have introduced here the first application of Learning to Rank in virtual screening. The experiment workflow and algorithm assessment designed in this study will provide a standard protocol for other similar studies. All the datasets as well as the implementations of Learning to Rank algorithms are available at http://www.tongji.edu.cn/~qiliu/lor_vs.html.
Viscosity approximation methods for asymptotically nonexpansive mapping in CAT(0) spaces
Authors: Wangkeeree Rabian , Boonkong Uraiwan , Preechasilp Pakkapon 
Published: February 2015

AbstractLet C be a nonempty, closed, and convex subset of a complete CAT(0) space X and let T be an asymptotically nonexpansive mapping of C into itself such that the set of common fixed points of T is nonempty. We introduce the iterative schemes for finding the common fixed point of an asymptotically nonexpansive mapping which is the unique solution of some variational inequalities. The strong convergence theorem of the proposed iterative schemes is established. Our result improves and generalizes several other results in the literature.
RNA-Seq analysis and annotation of a draft blueberry genome assembly identifies candidate genes involved in fruit ripening, biosynthesis of bioactive compounds, and stage-specific alternative splicing
Authors: Gupta Vikas , Estrada April D , Blakley Ivory , Reid Rob , Patel Ketan , Meyer Mason D , Andersen Stig Uggerhøj , Brown Allan F , Lila Mary Ann , Loraine Ann E 
Published: February 2015

Abstract

Background
Blueberries are a rich source of antioxidants and other beneficial compounds that can protect against disease. Identifying genes involved in synthesis of bioactive compounds could enable the breeding of berry varieties with enhanced health benefits

Results
Toward this end, we annotated a previously sequenced draft blueberry genome assembly using RNA-Seq data from five stages of berry fruit development and ripening. Genome-guided assembly of RNA-Seq read alignments combined with output from ab initio gene finders produced around 60,000 gene models, of which more than half were similar to proteins from other species, typically the grape Vitis vinifera. Comparison of gene models to the PlantCyc database of metabolic pathway enzymes identified candidate genes involved in synthesis of bioactive compounds, including bixin, an apocarotenoid with potential disease-fighting properties, and defense-related cyanogenic glycosides, which are toxic. Cyanogenic glycoside (CG) biosynthetic enzymes were highly expressed in green fruit, and a candidate CG detoxification enzyme was up-regulated during fruit ripening. Candidate genes for ethylene, anthocyanin, and 400 other biosynthetic pathways were also identified. Homology-based annotation using Blast2GO and InterPro assigned Gene Ontology terms to around 15,000 genes. RNA-Seq expression profiling showed that blueberry growth, maturation, and ripening involve dynamic gene expression changes, including coordinated up- and down-regulation of metabolic pathway enzymes and transcriptional regulators. Analysis of RNA-seq alignments identified developmentally regulated alternative splicing, promoter use, and 3′ end formation.

Conclusions
We report genome sequence, gene models, functional annotations, and RNA-Seq expression data that provide an important new resource enabling high throughput studies in blueberry.
Humic substances stimulate maize nitrogen assimilation and amino acid metabolism at physiological and molecular level
Authors: Vaccaro Silvia , Ertani Andrea , Nebbioso Antonio , Muscolo Adele , Quaggiotti Silvia , Piccolo Alessandro , Nardi Serenella 
Published: February 2015

Abstract

Background
The effects of a humic substance (HS) extracted from a volcanic soil on the nitrate assimilation pathway of Zea mays seedlings were thoroughly examined using physiological and molecular approaches. Plant growth, the amount of soluble proteins and amino acids, as well as the activities of the enzymes involved in nitrogen metabolism and Krebs cycle, were evaluated in response to different HS concentrations (0, 1 and 5 mg C L−1) supplied to maize seedlings for 48 h. To better understand the HS action, the transcript accumulation of selected genes encoding enzymes involved in nitrogen assimilation and Krebs cycle was additionally evaluated in seedlings grown for 2 weeks under nitrogen (N) sufficient condition and N deprivation.

Results
HS at low concentration (1 mg C L−1) positively influenced nitrate metabolism by increasing the content of soluble protein and amino acids synthesis. Furthermore, the activity and transcription of enzymes functioning in N assimilation and Krebs were significantly stimulated.

Conclusions
HS treatment influenced the gene expression of Zea mays plants at transcriptional level and this regulation was closely dependent on the availability of nitrate in the growth medium.
Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions
Authors: Gabay Cem , Towne Jennifer E 
Published: February 2015

Abstract
IL-36α, IL-36β, and IL-36γ are members of the IL-1 family of cytokines that signal through a common receptor composed of IL-36R and IL-1R/AcP to activate NF-κB and MAPKs, such as p38 and JNK, and promote inflammatory responses. IL-36Ra is a natural antagonist of the 3 IL-36 agonists that binds to IL-36R and inhibits binding of the agonistic ligands. These cytokines are expressed predominantly by epithelial cells and act on a number of cells, including immune cells, epithelial cells, and fibroblasts. Processing of the N terminus is required for full agonist or antagonist activity for all IL-36 members. The role of IL-36 has been demonstrated extensively in the skin, where it can act on keratinocytes and immune cells to induce a robust inflammatory response and is implicated strongly through functional and genetic evidence in the pathology of psoriatic disorders. Emerging data also suggest a role for this cytokine family in pulmonary physiology and pathology. Although much has been learned about the biochemistry of IL-36 and its role in various tissues, it is clear that we are at an early stage in our understanding of the full biology of these cytokines.
RM-493, a Melanocortin-4 Receptor (MC4R) Agonist, Increases Resting Energy Expenditure in Obese Individuals
Authors: Chen Kong Y. , Muniyappa Ranganath , Abel Brent S. , Mullins Katherine P. , Staker Pamela , Brychta Robert J. , Zhao Xiongce , Ring Michael , Psota Tricia L. , Cone Roger D. , Panaro Brandon L. , Gottesdiener Keith M. , Van der Ploeg Lex H.T. , Reitman Marc L. , Skarulis Monica C. 
Published: February 2015

Context:
Activation of the melanocortin-4 receptor (MC4R) with the synthetic agonist RM-493 decreases body weight and increases energy expenditure (EE) in nonhuman primates. The effects of MC4R agonists on EE in humans have not been examined to date.

Objective, Design, and Setting:
In a randomized, double-blind, placebo-controlled, crossover study, we examined the effects of the MC4R agonist RM-493 on resting energy expenditure (REE) in obese subjects in an inpatient setting.

Study Participants and Methods:
Twelve healthy adults (6 men and 6 women) with body mass index of 35.7 ± 2.9 kg/m2 (mean ± SD) received RM-493 (1 mg/24 h) or placebo by continuous subcutaneous infusion over 72 hours, followed immediately by crossover to the alternate treatment. All subjects received a weight-maintenance diet (50% carbohydrate, 30% fat, and 20% protein) and performed 30 minutes of standardized exercise daily. Continuous EE was measured on the third treatment day in a room calorimeter, and REE in the fasting state was defined as the mean of 2 30-minute resting periods.

Results:
RM-493 increased REE vs placebo by 6.4% (95% confidence interval, 0.68–13.02%), on average by 111 kcal/24 h (95% confidence interval, 15–207 kcal, P = .03). Total daily EE trended higher, whereas the thermic effect of a test meal and exercise EE did not differ significantly. The 23-hour nonexercise respiratory quotient was lower during RM-493 treatment (0.833 ± 0.021 vs 0.848 ± 0.022, P = .02). No adverse effect on heart rate or blood pressure was observed.

Conclusions:
Short-term administration of the MC4R agonist RM-493 increases REE and shifts substrate oxidation to fat in obese individuals.