bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design Features for Online Examination Software
Authors: Post Gerald V. , Hargis Jace 
Published: January 2012

ABSTRACTOnline education and computer‐assisted instruction (CAI) have existed for years, but few general tools exist to help instructors create and evaluate lessons. Are these tools sufficient? Specifically, what elements do instructors want to see in online testing tools? This study asked instructors from various disciplines to identify and evaluate the importance of several features that they want to see in testing tools. Along with standard elements, the respondents evaluated the importance of more advanced elements including adaptive responses and programmability, which would be used to add responsiveness and intelligence to provide more tailored questions and assistance. A latent variable analysis of the detailed model was performed and the results reveal that several advanced features not commonly available today would be useful to many instructors—particularly to handle higher level courses. Instructors teaching lower level courses tended to emphasize basic testing and simple grading features. The features were grouped into nine categories: question formats, feedback, programmability, grading, question bank, page display capabilities, platform, data analysis, and security. The results of the study examine the relative importance of the categories as well as the detail items within each category.
The Vascular‐Disrupting Agent Combretastatin Impairs Splitting and Sprouting Forms of Physiological Angiogenesis
Authors: HUSSAIN ARIF , STEIMLE MANUEL , HOPPELER HANS , BAUM OLIVER , EGGINTON STUART 
Published: January 2012

Please cite this paper as: Hussain A, Steimle M, Hoppeler H, Baum O, Egginton S. The vascular‐disrupting agent combretastatin impairs splitting and sprouting forms of physiological angiogenesis. Microcirculation 19: 296–305, 2012.AbstractObjective:  Vascular‐disrupting agents like combretastatin (CA‐4‐P), used to attenuate tumor blood flow in vivo, exert anti‐mitotic and anti‐migratory effects on endothelial cells in vitro. We tested whether anti‐vascular or anti‐angiogenic effects of CA‐4‐P are evident with physiological angiogenesis in skeletal muscle (EDL) due to sustained hyperemia (intraluminal splitting) and chronic muscle overload (abluminal sprouting).Methods:  CA‐4‐P was given i.v. (25 mg/kg on alternate days for 14 days) to mice subjected to angiogenic stimuli (prazosin or synergist extirpation). The responses of femoral artery blood flow as well as capillarity, capillary ultrastructure, and levels of Rho GTPase were measured.Results:  Blood flow was unaffected in the sprouting angiotype, but decreased in the splitting angiotype, by CA‐4‐P. In contrast, CA‐4‐P attenuated the capillarity increase in both models, associated with reduced lamellipodia and filopodia formation. Muscle overload, but not hyperemia, was accompanied by an increase in Rho GTPase with CA‐4‐P.Conclusions:  CA‐4‐P impaired the angiogenic response in both experimental models. This inhibitory effect was associated with a lower increase in femoral blood flow in splitting, whereas sprouting angiogenesis was accompanied by higher Rho activity consistent with the interruption of actin polymerization. Thus, CA‐4‐P may exert context‐dependent anti‐vascular and anti‐angiogenic effects in vivo under physiological conditions.
Cytokeratin 10‐negative nested pattern enables sure distinction of clonal seborrheic keratosis from pagetoid Bowen's disease
Authors: Böer‐Auer Almut , Jones Meriem , Lyasnichaya Olesya V. 
Published: January 2012

Background: The histopathologic pattern of clonal seborrheic keratosis (SK) is quite similar to the nested pattern of pagetoid Bowen's disease [squamous cell carcinoma in situ (SCCIS)], and differentiation between the two can be challenging, especially when only small pieces are available for interpretation.Methods: Eleven examples of clonal SK and 13 examples of pagetoid SCCIS were examined histopathologically (tabulating necrotic keratinocytes, suprabasal mitoses, infiltrate, parakeratosis housing plump nuclei, crowding of nuclei) and immunohistochemically (using Ki‐67, bcl‐2, cytokeratin 7 and cytokeratin 10). Sensitivity, specificity, p‐values (Fisher's exact test, two‐tailed) and positive/negative likelihood ratios (+LR/−LR) were calculated.Results: Significant differences were seen with regard to crowding (p = 0.0009) and mitoses (p = 0.0006); however, only complete absence of necrotic keratinocytes or of crowding appeared to be diagnostically convincing for a diagnosis of clonal SK (−LR < 0.01). Significant differences were also seen with bcl‐2 (p = 0.0005) and cytokeratin 10 antibodies (p < 0.00001). Both markers displayed a typical nested pattern in clonal SK, nests being bcl‐2‐positive and cytokeratin 10‐negative. Cytokeratin 10‐negative nests were the most convincing criterion for differentiation between clonal SK and pagetoid SCCIS (+LR > 10, −LR < 0.01).Conclusions: The most reliable marker to distinguish clonal SK from pagetoid SCCIS is cytokeratin 10 when it spares nests. Other criteria that assist in the differential diagnosis are bcl‐2 expression, absence of crowding and of mitoses.Böer‐Auer A, Jones M, Lyasnichaya OV. Cytokeratin 10‐negative nested pattern enables sure distinction of clonal seborrheic keratosis from pagetoid Bowen's disease.
High species richness in hemiboreal forests of the northern Russian Altai, southern Siberia
Authors: Chytrý Milan , Ermakov Nikolai , Danihelka Jiří , Hájek Michal , Hájková Petra , Horsák Michal , Kočí Martin , Kubešová Svatava , Lustyk Pavel , Otýpková Zdenka , Pelánková Barbora , Valachovič Milan , Zelený David 
Published: January 2012

AbstractQuestionsWe discovered forests with very high local numbers of vascular plant species in southern Siberia. Are these the most species‐rich forests of the Eurasian boreal and temperate zones, and which factors cause such high species richness?LocationAltai Mountains in southern Siberia, Altai Republic, Russia.MethodsWe sampled vegetation and measured environmental variables across the Altai Mountains in plots of 100 m2 and established series of nested plots of the size from 1 to 1000 m2 at sites with the highest species richness. We compared the richest forests with other forests of the Altai and with literature records of species‐rich vegetation types from elsewhere.ResultsThe richest forests contained 45 vascular plant species per 1 m2, 82 per 10 m2, 114 per 100 m2 and 149 per 1000 m2. They are open hemiboreal forests dominated by Pinus sylvestris, with an admixture of Betula pendula, and sparse shrub and moss layers. About 95% of their vascular plant species are in the herb layer. All species are native. These forests occur in a forest‐steppe landscape of the northern Altai, where the mean January temperature is between –12.5 and –10 °C, mean July temperature is 16–18 °C, and total annual precipitation is 560–610 mm. Soils are deep and mesic, with a pH of 6.2–6.4.ConclusionsHemiboreal forests of the northern Russian Altai are probably the most species‐rich forests in boreal and temperate Eurasia. Such a high concentration of many species in small plots probably results from the incidental combination of several factors conducive to high species richness. These factors include the rich regional flora of the Altai Mountains, stability of the environment of this region since the Pleistocene, heterogeneity of the mountainous forest‐steppe landscape with a combination of forested areas on north‐facing slopes and steppes on south‐facing ones, an open canopy that ameliorates microclimate conditions but does not exclude light‐demanding species through strong shading, a macroclimate that is not too harsh, mesic soils with near‐neutral pH, and limited competition within the herb layer.
Characterization of Nontypeable and Atypical Streptococcus pneumoniae Pediatric Isolates from 1994 to 2010
Authors: Ing Jessica , Mason Edward O. , Kaplan Sheldon L. , Lamberth Linda B. , Revell Paula A. , Luna Ruth Ann , Hulten Kristina G. 
Published: January 2012

ABSTRACT

Streptococcus pneumoniae
is a major cause of bacteremia, meningitis, pneumonia, sinusitis, and acute otitis media in children. Although optochin susceptibility, bile solubility, and Quellung testing are the standards for identifying and differentiating pneumococci, there are several reports of nontypeable pneumococci that give inconsistent results with one or more of these tests. We characterized 52 isolates previously labeled as nontypeable pneumococci. Microbiological methods included repeating the Quellung reaction using a new and expanded group of antisera, optochin susceptibility and bile solubility tests, and automated Vitek 2 identification. Molecular methods included PCR detection of
ply
and
psaA
genes, multilocus sequence typing (MLST), 16S rRNA gene sequencing, and pyrosequencing. Of the 52 isolates, 38 (73%) were optochin susceptible, were
psaA
and
ply
positive, and could be serotyped by the Quellung reaction. The remaining 14 isolates, isolated from patients with otitis media (
n
= 6), bacteremia (
n
= 6), meningitis (
n
= 1), and pneumonia (
n
= 1), underwent further analysis. Three of these 14 isolates were nontypeable due to autoagglutination but were pneumococci by all tests and represented pneumococcal sequence types previously recognized by MLST. The 11 remaining isolates were optochin resistant, and 6 of these were bile soluble. Three of 11 were both
psaA
and
ply
positive and clustered with pneumococci by MLST (2 were bile soluble); 8 lacked
psaA
(5
ply
positive, 4 bile soluble) and likely belonged to other
Streptococcus
species. In conclusion, few isolates were truly nontypeable by Quellung reaction, and MLST and the presence of
psaA
proved useful in distinguishing between atypical pneumococci and other streptococcal species.
The COMPASs Study: Community Preferences for Prostate cAncer Screening. Protocol for a quantitative preference study: Figure 1
Authors: Howard Kirsten , Salkeld Glenn P , Mann Graham J , Patel Manish I , Cunich Michelle , Pignone Michael P 
Published: January 2012

BackgroundProstate cancer screening using prostate-specific antigen (PSA) testing remains controversial. Trade-offs between the potential benefits and downsides of screening must be weighed by men deciding whether to participate in prostate cancer screening; little is known about benefit:harm trade-offs men are willing to accept.Methods/DesignThe Community Preferences for Prostate Cancer Screening (COMPASs) Study examines Australian men's preferences for prostate cancer screening using PSA testing. The aims are to (1) determine which factors influence men's decision to participate in prostate cancer screening or not and (2) determine the extent of trade-offs between benefits and harms that men are willing to accept in making these decisions. Quantitative methods will be used to assess men's preferences for PSA screening. Using data on the quantitative outcomes of PSA testing from the published literature, a discrete choice study will be designed to quantitatively assess men's preferences. A web-based survey will be conducted in approximately 1000 community respondents aged 40–69 years, stratified by family history of prostate cancer, to assess men's preferences for PSA testing. A mixed logit model will be used; model results will be expressed as parameter estimates (β) and the odds of choosing screening over no screening. Trade-offs between attributes will also be calculated.Ethics and DisseminationThe COMPASs study has been approved by the University of Sydney, Human Research Ethics committee (Protocol number 13186). The results will be published in internal reports, in peer-reviewed scientific journals as well as via conference presentations.
The utility of a novel antibody in the pathological diagnosis of pancreatic acinar cell carcinoma
Authors: Yasumoto Makiko , Hamabashiri Masato , Akiba Jun , Ogasawara Sachiko , Naito Yoshiki , Taira Tomoki , Nakayama Masamichi , Daicho Aya , Yamasaki Fumio , Shimamatsu Kazuhide , Ishida Yusuke , Kaji Ryohei , Okabe Yoshinobu , Nakashima Osamu , Ohshima Koichi , Nakashima Manabu , Sata Michio , Yano Hirohisa 
Published: January 2012

AimsAcinar cell carcinomas (ACCs) are rare tumours of the exocrine pancreas accounting for about 1–2% of all pancreatic neoplasms in adults. It is therefore difficult to come across a large number of ACC cases in a single medical institution, and only a few serial studies have been published. Since ACCs present a wide variety of morphological patterns, immunohistochemical analysis is useful. In this study, the authors established a novel monoclonal antibody 2P-1-2-1 by means of a subtractive immunisation method.MethodsImmunohistochemical staining was performed using 50 primary pancreatic tumors, including 7 ACCs, 7 neuroendocrine tumours (NETs), 5 solid-pseudopapillary neoplasms (SPNs), and 31 ductal carcinomas and organs other than the pancreas.ResultsNon-neoplastic acinar cells were stained diffusely, but epithelial cells of the pancreatic duct and the islets of Langerhans were not stained. In pancreatic tumours, all the seven ACCs were diffusely positive for the 2P-1-2-1 antibody. However, no positive staining was found in other pancreatic tumours including NETs, SPNs and ductal adenocarcinomas. The sensitivity and specificity of the 2P-1-2-1 antibody for ACCs were both 100%. In other organs studied, positive staining was observed only in the ectopic pancreas.ConclusionsIt was shown that the 2P-1-2-1 antibody specifically stained the pancreatic acinar cells and tumours of acinar cell origin, such as ACCs. Although it remains unclear at this time to which proteins the monoclonal antibody 2P-1-2-1 is directed, it is suggested to be useful for the pathological diagnosis of ACCs and for the exclusion of other pancreatic tumours.
Decreased Toll-interacting protein and peroxisome proliferator-activated receptor γ are associated with increased expression of Toll-like receptors in colon carcinogenesis
Authors: Pimentel-Nunes Pedro , Gonçalves Nádia , Boal-Carvalho Inês , Afonso Luís , Lopes Paula , Roncon-Albuquerque Roberto , Soares João-Bruno , Cardoso Elisabete , Henrique Rui , Moreira-Dias Luís , Dinis-Ribeiro Mário , Leite-Moreira Adelino F 
Published: January 2012

BackgroundAnimal data suggest that Toll-like receptors (TLR) may play an important role in colon carcinogenesis. Studies in humans to support that hypothesis are scarce.AimTo evaluate the expression of TLR2, TLR4 and TLR5, and the expression of several other related molecules, in different human colonic lesions.MethodsColon biopsy samples from normal mucosa, normal mucosa adjacent to lesion, adenoma or sporadic carcinoma were obtained from 35 consecutive patients undergoing colonoscopy. Quantification of TLR2, TLR4, TLR5, Toll-interacting protein (TOLLIP), peroxisome proliferator-activated receptor γ (PPAR-γ), nuclear factor κB, tumour necrosis factor (TNF) α, cyclooxygenase (COX) 1 and 2 mRNA was performed by real-time reverse transcription PCR. TLR2, TLR4 and TLR5 protein expression was quantified by immunohistochemistry.ResultsWhen compared with normal mucosa (1.0 arbitrary unit (AU)), adjacent normal mucosa presented higher expression of COX-2 (1.86±0.3 AU, p=0.01) and TNFα (1.44±0.18 AU, p=0.04) and lower TOLLIP expression (0.75±0.05 AU, p=0.004). Adenomas and carcinomas presented higher expression of COX-2 (1.63±0.27 and 1.38±0.14 AU, p=0.03 and p=0.05, respectively) and lower expression of TOLLIP (0.44±0.04 AU, p<0.001), with diffuse and higher TLR protein expression (p<0.001). Carcinomas also expressed higher TLR2 (2.31±0.32 AU, p=0.006) and lower PPAR-γ (0.56±0.12 AU, p=0.003). There was a trend towards decreased TOLLIP (p<0.001) and PPAR-γ (p=0.05) from normal mucosa to adenoma/carcinoma.ConclusionsPersistently positive TLR expression and lower expression of TLR inhibitors was associated with higher TLR protein levels throughout the spectrum of lesions of colon carcinogenesis. Increasing activation of these receptors by bacteria may play a crucial role in colon carcinogenesis and tumour progression.
Abundance and composition of plant biomass as potential controls for mire net ecosytem CO2exchange
Authors: Laine Anna M. , Bubier Jill , Riutta Terhi , Nilsson Mats B. , Moore Tim R. , Vasander Harri , Tuittila Eeva-Stiina 
Published: January 2012

We compared the amount and composition of different aboveground biomass (BM) fractions of four mires with their net ecosystem CO2exchange (NEE) measured by eddy covariance. We found clear differences in response of green biomass (GBM) of plant functional types (PFTs) to water table (WT), which resulted in larger spatial variation in GBM within a mire than variation between mires. GBM varied between mires from 126 ± 7 to 336 ± 16 g·m–2(mean ± SE), while within mire variation at largest was from 157 ± 17 to 488 ± 20 g·m–2(mean ± SE). GBM of dominant PFTs appeared to be better in explaining the peak growing season NEE than the total BM or GBM of a mire. The differences in photosynthetic capacity between PTFs had a major role, and thus a smaller GBM with different species composition could result in higher NEE than larger GBM. Vascular plant GBM, especially that of sedges, appeared to have a high impact on NEE. Eleven PFTs, defined here, appeared to capture well the internal variation within mires, and the differences in GBM between communities were explained by the water table response of PFTs. Our results suggest the use of photosynthesizing BM, separated into PFTs, in modelling ecosystem carbon exchange instead of using just total BM.
Functional mapping of the A2 domain from human factor VIII
Authors: Saboulard Didier , Pellequer Jean-Luc , Plantier Jean-Luc , Négrier Claude , Delcourt Marc 
Published: January 2012

SummaryCoagulation factor VIII (FVIII) is a multidomain glycoprotein in which the FVIII A2 domain is a key structural element. We aimed at identifying residues within FVIII A2 domain that are crucial for the maintenance of the cofactor function. A high number (n=206) of mutants were generated by substituting original residues with alanine. The mutants were expressed in COS-1 cells and their antigen levels and procoagulant activities were measured. The residues were classified in three categories: those with a non-detrimental alteration of their activities (activity >50 % of control FVIII; n=98), those with a moderate alteration (15 %<activity<50%; n=45) and those that were severely affected (activity<15%; n=63). The mutants sensitive to mutation were retrieved in the HAMSTeRS database with a higher percentage than those that were not affected (58.8% vs. 9.2%). The results revealed the existence of clusters of residues that are sensitive (Arg418-Phe436, Thr459-Ile475, Ser535-Gly549, Asn618-Ala635) or not (Leu398-Arg418, Pro485-Asp500, Gly506-Gly520, Pro596-Asp605) to mutations. The stretches of residues sensitive to mutations were buried within the molecule suggesting that these amino acids participate in the maintenance of the A2 domain structure. In contrast, residues resistant to mutations formed external loops without well- defined structures suggesting that these loops were not crucial for the process of factor X activation. This study provided a detailed map of the FVIII A2 domain between residues 371 and 649, identifying residues crucial for maintaining FVIII function and residues that can be mutated without jeopardising the coagulant activity.
Low Atrial Fibrillatory Rate Is Associated With Poor Outcome in Patients With Mild to Moderate Heart Failure
Authors: Platonov Pyotr G. , Cygankiewicz Iwona , Stridh Martin , Holmqvist Fredrik , Vazquez Rafael , Bayes-Genis Antoni , McNitt Scott , Zareba Wojciech , de Luna Antonio Bayes 
Published: January 2012

Background—
Atrial fibrillatory rate (AFR) is a measure of atrial remodeling caused by atrial fibrillation (AF), and its acceleration negatively affects outcome of interventions for persistent AF. However, the prognostic value of AFR in patients with congestive heart failure (CHF) has not been studied. We sought to evaluate whether AFR can predict outcome in patients with mild to moderate (New York Health Association II–III) CHF.

Methods and Results—

High-resolution 20-minute long Holter ECGs obtained from 169 CHF patients with AF at enrollment were analyzed. AFR was estimated using spatiotemporal QRST cancellation and time–frequency analysis. The patients were followed for a median of 44 months, with primary end point defined as total mortality and secondary end points as sudden death and heart failure death. Atrial signal quality was sufficient for AFR estimation in 142 patients (mean age 69±11 years, 101 male). Of those, 48 patients died during follow-up, including 18 because of CHF progression. Mean AFR was 390±60 fpm and decreased with age (
r
=−0.3,
P
<0.001). Patients with AFR ≤371 fpm (lower tertile) had 44% 3-year mortality as compared with 26% with higher AFR. Lower AFR was an independent predictor of all cause mortality (HR=1.99, 95% CI=1.09–3.63,
P
=0.025) and CHF death (HR=3.74, 95% CI=1.38–10.14,
P
=0.010) after adjustment for significant clinical covariates in multivariable Cox analysis.

Conclusions—
In CHF patients with AF, reduced AFR assessed using noninvasive approach is associated with increased risk of death because of heart failure progression, and may be considered a predictor of outcome.
A Genetic Risk Score Is Associated With Incident Cardiovascular Disease and Coronary Artery Calcium
Authors: Thanassoulis George , Peloso Gina M. , Pencina Michael J. , Hoffmann Udo , Fox Caroline S. , Cupples L. Adrienne , Levy Daniel , D'Agostino Ralph B. , Hwang Shih-Jen , O'Donnell Christopher J. 
Published: January 2012

Background—
Limited data exist regarding the use of a genetic risk score (GRS) for predicting risk of incident cardiovascular disease (CVD) in US-based samples.

Methods and Results—

By using findings from recent genome-wide association studies, we constructed GRSs composed of 13 genetic variants associated with myocardial infarction or other manifestations of coronary heart disease (CHD) and 102 genetic variants associated with CHD or its major risk factors. We also updated the 13 single-nucleotide polymorphism (SNP) GRSs with 16 SNPs recently discovered by genome-wide association studies. We estimated the association, discrimination, and risk reclassification of each GRS for incident cardiovascular events and prevalent coronary artery calcium (CAC). In analyses adjusted for age, sex, CVD risk factors, and parental history of CVD, the 13 SNP GRSs were significantly associated with incident hard CHD (hazard ratio, 1.07; 95% CI, 1.00–1.15;
P
=0.04), CVD (hazard ratio per allele, 1.05; 95% CI, 1.01–1.09;
P
=0.03), and high CAC (defined as >75
th
age- and sex-specific percentile; odds ratio per allele, 1.18; 95% CI, 1.11–1.26;
P
=3.4×10
−7
). The GRS did not improve discrimination for incident CHD or CVD but led to modest improvements in risk reclassification. However, significant improvements in discrimination and risk reclassification were observed for the prediction of high CAC. The addition of 16 newly discovered SNPs to the 13 SNP GRSs did not significantly modify these results.

Conclusions—
A GRS composed of 13 SNPs associated with coronary disease is an independent predictor of cardiovascular events and of high CAC, modestly improves risk reclassification for incident CHD, and significantly improves discrimination for high CAC. The addition of recently discovered SNPs did not significantly improve the performance of this GRS.