bluuebunny/crossref_metadata_2025_split huggingface dataset:
Burden of comorbidities among patients with atrial fibrillation
Authors: LaMori Joyce C. , Mody Samir H. , Gross Hillary J. , daCosta DiBonaventura Marco , Patel Aarti A. , Schein Jeffrey R. , Nelson Winnie W. 
Published: October 2012

Objective: This study examined comorbidity prevalence and general medication use among individuals with atrial fibrillation in the United States to convey a more comprehensive picture of their total disease burden. Methods: This was a retrospective, observational evaluation of responses to the 2009 wave of the annual Internet-based National Health and Wellness survey, which collects health data including epidemiologic data and information on medical treatment from a representative nationwide sample of adults in the United States. Responses were assessed to determine three measures of comorbidity: mean number of comorbidities, CHADS2 score reflecting stroke risk (0–6 points; low risk: 0; moderate risk: 1; high risk: ≥2), and scores on the Charlson Comorbidity Index, which is a measure of general comorbidity reflecting presence of a wide range of comorbidities. Results: Of the overall sample, 1297 participants reported having been diagnosed with atrial fibrillation. Almost all (98%) of the predominantly male (65.1%) and older (≥65 years of age, 65.7%) population with atrial fibrillation had at least one additional comorbidity, and 90% had cardiovascular comorbidities. On the Charlson Comorbidity Index, 44.9% of the respondents had scores of 1–2 and 20.5% had scores of 3 or higher. High risk for stroke, demonstrated by a CHADS2 score of at least 2, was present in 45% and moderate risk (CHADS2 score 1) in 36%. Of the respondents with atrial fibrillation, 71% reported current use of medication to manage the condition, but only 48% of individuals at high risk for stroke reported use of anticoagulation therapy. Of those who reported having common risk factors for stroke, the majority reported receiving prescription therapy for these conditions. Conclusions: The health burden carried by patients often extends far beyond atrial fibrillation. Physicians should carefully consider comorbidities and concomitant medications when managing patients with atrial fibrillation.
Biosimilars: what clinicians should know
Authors: Weise Martina , Bielsky Marie-Christine , De Smet Karen , Ehmann Falk , Ekman Niklas , Giezen Thijs J. , Gravanis Iordanis , Heim Hans-Karl , Heinonen Esa , Ho Kowid , Moreau Alexandre , Narayanan Gopalan , Kruse Nanna A. , Reichmann Gabriele , Thorpe Robin , van Aerts Leon , Vleminckx Camille , Wadhwa Meenu , Schneider Christian K. 
Published: October 2012

Abstract
Biosimilar medicinal products (biosimilars) have become a reality in the European Union and will soon be available in the United States. Despite an established legal pathway for biosimilars in the European Union since 2005 and increasing and detailed regulatory guidance on data requirements for their development and licensing, many clinicians, particularly oncologists, are reluctant to consider biosimilars as a treatment option for their patients. Major concerns voiced about biosimilars relate to their pharmaceutical quality, safety (especially immunogenicity), efficacy (particularly in extrapolated indications), and interchangeability with the originator product. In this article, the members and experts of the Working Party on Similar Biologic Medicinal Products of the European Medicines Agency (EMA) address these issues. A clear understanding of the scientific principles of the biosimilar concept and access to unbiased information on licensed biosimilars are important for physicians to make informed and appropriate treatment choices for their patients. This will become even more important with the advent of biosimilar monoclonal antibodies. The issues also highlight the need for improved communication between physicians, learned societies, and regulators.
Fcγ receptor antigen targeting potentiates cross-presentation by human blood and lymphoid tissue BDCA-3+ dendritic cells
Authors: Flinsenberg Thijs W. H. , Compeer Ewoud B. , Koning Dan , Klein Mark , Amelung Femke J. , van Baarle Debbie , Boelens Jaap Jan , Boes Marianne 
Published: October 2012

AbstractThe reactivation of human cytomegalovirus (HCMV) poses a serious health threat to immune compromised individuals. As a treatment strategy, dendritic cell (DC) vaccination trials are ongoing. Recent work suggests that BDCA-3+ (CD141+) subset DCs may be particularly effective in DC vaccination trials. BDCA-3+ DCs had however been mostly characterized for their ability to cross-present antigen from necrotic cells. We here describe our study of human BDCA-3+ DCs in elicitation of HCMV-specific CD8+ T-cell clones. We show that Fcgamma-receptor (FcγR) antigen targeting facilitates antigen cross-presentation in several DC subsets, including BDCA-3+ DCs. FcγR antigen targeting stimulates antigen uptake by BDCA-1+ rather than BDCA-3+ DCs. Conversely, BDCA-3+ DCs and not BDCA-1+ DCs show improved cross-presentation by FcγR targeting, as measured by induced release of IFNγ and TNF by antigen-specific CD8+ T cells. FcγR-facilitated cross-presentation requires antigen processing in both an acidic endosomal compartment and by the proteasome, and did not induce substantial DC maturation. FcγRII is the most abundantly expressed FcγR on both BDCA-1+ and BDCA-3+ DCs. Furthermore we show that BDCA-3+ DCs express relatively more stimulatory FcγRIIa than inhibitory FcγRIIb in comparison with BDCA-1+ DCs. These studies support the exploration of FcγR antigen targeting to BDCA-3+ DCs for human vaccination purposes.
Unwinding the von Willebrand factor strings puzzle
Authors: De Ceunynck Karen , De Meyer Simon F. , Vanhoorelbeke Karen 
Published: October 2012

Abstractvon Willebrand factor (VWF) is amongst others synthesized by endothelial cells and stored as ultra-large (UL) VWF multimers in Weibel-Palade bodies. Although UL-VWF is proteolysed by ADAMTS13 (a disintegrin-like and metalloprotease domain with thrombospondin type-1 motif, number 13) on secretion from endothelial cells, in vitro experiments in the absence of ADAMTS13 have demonstrated that a proportion of these UL-VWF multimers remain anchored to the activated endothelium. These multimers unravel, bind platelets, and wave in the direction of the flow. These so-called VWF “strings” have also been visualized in vivo, lining the lumen of activated mesenteric veins of Adamts13−/− mice. Various studies have demonstrated the extraordinary length of these VWF strings, the availability of their platelet binding and ADAMTS13 cleavage sites, and the possible nature of their endothelial attachment. VWF strings are also capable of tethering leukocytes and parasite-infected red blood cells. However, the majority of studies have been performed in the absence of ADAMTS13, a condition only experienced in thrombotic thrombocytopenic purpura. A normal functional role of VWF strings in healthy persons or in other disease pathologies remains unclear. In this review, we discuss some of the puzzling characteristics of VWF strings, and we debate whether the properties of VWF strings in the absence of ADAMTS13 might be relevant for understanding (patho)physiologic mechanisms.
Historically low mitochondrial DNA diversity in koalas (Phascolarctos cinereus)
Authors: Tsangaras Kyriakos , Ávila-Arcos María C , Ishida Yasuko , Helgen Kristofer M , Roca Alfred L , Greenwood Alex D 
Published: October 2012

Abstract

Background
The koala (Phascolarctos cinereus) is an arboreal marsupial that was historically widespread across eastern Australia until the end of the 19th century when it suffered a steep population decline. Hunting for the fur trade, habitat conversion, and disease contributed to a precipitous reduction in koala population size during the late 1800s and early 1900s. To examine the effects of these reductions in population size on koala genetic diversity, we sequenced part of the hypervariable region of mitochondrial DNA (mtDNA) in koala museum specimens collected in the 19th and 20th centuries, hypothesizing that the historical samples would exhibit greater genetic diversity.

Results
The mtDNA haplotypes present in historical museum samples were identical to haplotypes found in modern koala populations, and no novel haplotypes were detected. Rarefaction analyses suggested that the mtDNA genetic diversity present in the museum samples was similar to that of modern koalas.

Conclusions
Low mtDNA diversity may have been present in koala populations prior to recent population declines. When considering management strategies, low genetic diversity of the mtDNA hypervariable region may not indicate recent inbreeding or founder events but may reflect an older historical pattern for koalas.
Constructing a question bank based on script concordance approach as a novel assessment methodology in surgical education
Authors: Aldekhayel Salah A , ALselaim Nahar A , Magzoub Mohi Eldin , AL-Qattan Mohammad M , Al-Namlah Abdullah M , Tamim Hani , Al-Khayal Abdullah , Al-Habdan Sultan I , Zamakhshary Mohammed F 
Published: October 2012

Abstract

Background
Script Concordance Test (SCT) is a new assessment tool that reliably assesses clinical reasoning skills. Previous descriptions of developing SCT-question banks were merely subjective. This study addresses two gaps in the literature: 1) conducting the first phase of a multistep validation process of SCT in Plastic Surgery, and 2) providing an objective methodology to construct a question bank based on SCT.

Methods
After developing a test blueprint, 52 test items were written. Five validation questions were developed and a validation survey was established online. Seven reviewers were asked to answer this survey. They were recruited from two countries, Saudi Arabia and Canada, to improve the test’s external validity. Their ratings were transformed into percentages. Analysis was performed to compare reviewers’ ratings by looking at correlations, ranges, means, medians, and overall scores.

Results
Scores of reviewers’ ratings were between 76% and 95% (mean 86% ± 5). We found poor correlations between reviewers (Pearson’s: +0.38 to −0.22). Ratings of individual validation questions ranged between 0 and 4 (on a scale 1–5). Means and medians of these ranges were computed for each test item (mean: 0.8 to 2.4; median: 1 to 3). A subset of test items comprising 27 items was generated based on a set of inclusion and exclusion criteria.

Conclusion
This study proposes an objective methodology for validation of SCT-question bank. Analysis of validation survey is done from all angles, i.e., reviewers, validation questions, and test items. Finally, a subset of test items is generated based on a set of criteria.
Metabolic engineering of the purine biosynthetic pathway in Corynebacterium glutamicum results in increased intracellular pool sizes of IMP and hypoxanthine
Authors: Peifer Susanne , Barduhn Tobias , Zimmet Sarah , Volmer Dietrich A , Heinzle Elmar , Schneider Konstantin 
Published: October 2012

Abstract

Background
Purine nucleotides exhibit various functions in cellular metabolism. Besides serving as building blocks for nucleic acid synthesis, they participate in signaling pathways and energy metabolism. Further, IMP and GMP represent industrially relevant biotechnological products used as flavor enhancing additives in food industry. Therefore, this work aimed towards the accumulation of IMP applying targeted genetic engineering of Corynebacterium glutamicum.

Results
Blocking of the degrading reactions towards AMP and GMP lead to a 45-fold increased intracellular IMP pool of 22 μmol gCDW
-1. Deletion of the pgi gene encoding glucose 6-phosphate isomerase in combination with the deactivated AMP and GMP generating reactions, however, resulted in significantly decreased IMP pools (13 μmol gCDW
-1). Targeted metabolite profiling of the purine biosynthetic pathway further revealed a metabolite shift towards the formation of the corresponding nucleobase hypoxanthine (102 μmol gCDW
-1) derived from IMP degradation.

Conclusions
The purine biosynthetic pathway is strongly interconnected with various parts of the central metabolism and therefore tightly controlled. However, deleting degrading reactions from IMP to AMP and GMP significantly increased intracellular IMP levels. Due to the complexity of this pathway further degradation from IMP to the corresponding nucleobase drastically increased suggesting additional targets for future strain optimization.
Imbalance in superoxide dismutase/thioredoxin reductase activities in hypercholesterolemic subjects: relationship with low density lipoprotein oxidation
Authors: Augusti Paula Rossini , Ruviaro Amanda Roggia , Quatrin Andréia , Somacal Sabrina , Conterato Greicy Michelle Marafiga , Vicentini Juliana Tanara , Duarte Marta Medeiros Frescura , Emanuelli Tatiana 
Published: October 2012

Abstract

Background
There is a relationship among hypercholesterolemia, oxidative stress and inflammation in the atherogenesis. Thus, the objective of the present study was to assess paraoxonase (PON1), superoxide dismutase (SOD) and thioredoxin reductase (TrxR-1) activities and their relationship with lipids, oxidative stress and inflammation in subjects with different low density lipoprotein-cholesterol (LDL) levels.

Methods
Serum lipids, highly sensitive C-reactive protein (hs-CRP), lipid and protein oxidation, oxidized LDL (LDLox) and LDLox autoantibodies (LDLoxAB) levels and enzymes activities were measured in a total of 116 subjects that were divided into the following groups according to their LDL levels: low-LDL group (LDL < 100 mg/dL, n = 23), intermediate-LDL group (LDL 100–160 mg/dL, n = 50) and high-LDL group (LDL > 160 mg/dL, n = 43).

Results
The LDLox and hs-CRP levels increased in the high-LDL group (2.7- and 3.7- fold, respectively), whereas the intermediate and high-LDL groups had higher LDLoxAB (2.2- and 3.1-fold) when compared to low-LDL group (p < 0.05). Similarly, SOD activity, the atherogenic index (AI) and protein oxidation were also higher in the intermediate (1.3-, 1.3- and 1.2-fold) and high-LDL (1.6-, 2.3- and 1.6-fold) groups when compared to the low-LDL group (p < 0.05). Lipid oxidation and SOD/TrxR-1 ratio increased only in the high-LDL group (1.3- and 1.6-fold) when compared to the low-LDL group (p < 0.05). The SOD/TrxR-1 ratio was positively correlated to TBARS (r = 0.23, p < 0.05), LDLox (r = 0.18, p < 0.05), LDLoxAB (r = 0.21, p < 0.05), LDL (r = 0.19, p < 0.05) and AI (r = 0.22, p < 0.05). PON1 and TrxR-1 activities were similar among groups.

Conclusions
Some oxidative events initiate when LDL levels are clinically acceptable. Moreover, hypercholesterolemic patients have an imbalance in SOD and TrxR-1 activities that is positively associated to LDL oxidation.
The role of the 5-hydroxytryptamine pathway in reflux-induced esophageal mucosal injury in rats
Authors: Yang Lingrong , Cai Haifang , Tou Jinfa , Gu Weizhong , Shu Xiaoli , Zhang Ting , Yang Xi , Shen Zheng , Jiang Mizu 
Published: October 2012

Abstract

Background
Dysfunction of the 5-hydroxytryptamine (5-HT) signaling pathway can lead to gastrointestinal motility and secretion abnormalities and to visceral hypersensitivity. The aim of this study is to investigate the role of 5-HT in reflux-induced esophageal mucosal injury.

Methods
Fifty 8-week-old male Sprague-Dawley (SD) rats were randomly divided into a gastroesophageal reflux (GER) model group (30 rats) and a sham surgery control group (20 rats). Four weeks after surgery, the esophageal mucosa was collected for histological evaluation, 5-HT concentrations, and 5-HT selective reuptake transporter (SERT) mRNA and 5-HT4 receptor (5-HT4R) protein expressions.

Results
Twenty-seven rats in the GER model group survived, and three rats died. Histologically, in the GER model group, 20 rats had reflux esophagitis (RE group), and 7 rats had non-erosive reflux disease (NERD group). The 5-HT levels in the esophageal tissue from the RE group were significantly higher than those from the control and NERD groups. Both the RE and NERD groups showed significant increases in SERT mRNA expression of the esophageal mucosa than that of the controls, and the SERT mRNA level in the RE group was significantly higher than that in the NERD group. The 5-HT4R protein level of the esophageal mucosa in the RE group was significantly lower than that in the controls and the NERD group.

Conclusions
We conclude that a 5-HT signaling pathway disorder could be a major factor in the pathogenesis of GER and RE.
Tripled fixed point and tripled coincidence point theorems in intuitionistic fuzzy normed spaces
Authors: Abbas Mujahid , Ali Basit , Sintunavarat Wutiphol , Kumam Poom 
Published: October 2012

Abstract
The aim of this paper is to prove the existence of tripled fixed point and tripled coincidence point theorems in intuitionistic fuzzy normed spaces (IFNS). Our results generalize and extend recent coupled fixed point theorems in IFNS.

MSC:47H09, 47H10, 54H25.
Identification and characterization of naturally occurring splice variants of SAMHD1
Authors: Welbourn Sarah , Miyagi Eri , White Tommy E , Diaz-Griffero Felipe , Strebel Klaus 
Published: October 2012

Abstract

Background
Sterile Alpha Motif and HD domain-containing protein 1 (SAMHD1) is a recently identified host factor that restricts HIV-1 replication in dendritic and myeloid cells. SAMHD1 is a dNTPase that presumably reduces the cellular dNTP levels to levels too low for retroviral reverse transcription to occur. However, HIV-2 and SIV encoded Vpx counteracts the antiviral effects of SAMHD1 by targeting the protein for proteasomal degradation. SAMHD1 is encoded by a multiply spliced mRNA and consists of 16 coding exons.

Results
Here, we identified two naturally occurring splice variants lacking exons 8–9 and 14, respectively. Like wildtype SAMHD1, both splice variants localize primarily to the nucleus, interact with Vpx, and retain some sensitivity to Vpx-dependent degradation. However, the splice variants differ from full-length SAMHD1 in their metabolic stability and catalytic activity. While full-length SAMHD1 is metabolically stable in uninfected cells, both splice variants were inherently metabolically unstable and were rapidly degraded even in the absence of Vpx. Vpx strongly increased the rate of degradation of full-length SAMHD1 and further accelerated the degradation of the splice variants. However, the effect of Vpx on the splice variants was more modest due to the inherent instability of these proteins. Analysis of dNTPase activity indicates that neither splice variant is catalytically active.

Conclusions
The identification of SAMHD1 splice variants exposes a potential regulatory mechanism that could enable the cell to control its dNTPase activity on a post-transcriptional level.
DRD2 and PPP1R1B (DARPP-32) polymorphisms independently confer increased risk for autism spectrum disorders and additively predict affected status in male-only affected sib-pair families
Authors: Hettinger Joe A , Liu Xudong , Hudson Melissa L , Lee Alana , Cohen Ira L , Michaelis Ron C , Schwartz Charles E , Lewis Suzanne ME , Holden Jeanette JA 
Published: October 2012

Abstract

Background
The neurotransmitter dopamine (DA) modulates executive functions, learning, and emotional processing, all of which are impaired in individuals with autism spectrum disorders (ASDs). Our previous findings suggest a role for dopamine-related genes in families with only affected males.

Methods
We examined two additional genes which affect DA function, the DRD2 and PPP1R1B (DARPP-32) genes, in a cohort of 112 male-only affected sib-pair families. Selected polymorphisms spanning these genes were genotyped and both family-based and population-based tests were carried out for association analysis. General discriminant analysis was used to examine the gene-gene interactions in predicting autism susceptibility.

Results
There was a significantly increased frequency of the DRD2 rs1800498TT genotype (P = 0.007) in affected males compared to the comparison group, apparently due to over-transmission of the T allele (P = 0.0003). The frequency of the PPP1R1B rs1495099CC genotype in affected males was also higher than that in the comparison group (P = 0.002) due to preferential transmission of the C allele from parents to affected children (P = 0.0009). Alleles rs1800498T and rs1495099C were associated with more severe problems in social interaction (P = 0.0002 and P = 0.0016, respectively) and communication (P = 0.0004 and P = 0.0046), and increased stereotypic behaviours (P = 0.0021 and P = 0.00072). General discriminant analysis found that the DRD2 and PPP1R1B genes additively predicted ASDs (P = 0.00011; Canonical R = 0.26) and explain ~7% of the variance in our families. All findings remained significant following corrections for multiple testing.

Conclusion
Our findings support a role for the DRD2 and PPP1R1B genes in conferring risk for autism in families with only affected males and show an additive effect of these genes towards prediction of affected status in our families.
Terpenes From the Root of Salvia hypoleuca Benth
Authors: Saeidnia Soodabeh , Ghamarinia Mitra , Gohari Ahmad R , Shakeri Alireza 
Published: October 2012

Abstract

Background
The genus Salvia, with nearly 900 species, is one of the largest members of Lamiaceae family. In the Flora of Iran, the genus Salvia is represented by 58 species of which 17 species are endemic. Salvia hypoleuca Benth., is one of these species growing wildly in northern and central parts of Iran. Salvia species are well known in folk medicine and widely used for therapeutic purposes. Literature review shows that there is no report on phytochemical investigation of the roots of S. hypoleuca.

Results
The separation and purification process were carried out using various chromatographic methods. Structural elucidation was on the basis of NMR and MS data, in comparison with those reported in the literature. The isolated compounds were identified as sitosteryl oleate (1), β-sitosterol (2), stigmasterol (3), manool (4), 7α-acetoxy royleanone (5), ursolic acid (6), oleanolic acid (7), 3-epicorosolic acid (8), 3-epimaslinic acid (9) and coleonolic acid (10).

Conclusions
In the present study, three sterols, two diterpenes and five triterpenes were isolated from the ethyl acetate extract of the roots of S. hypoleuca. As the chemotaxonomic significance, some of the isolated compounds (1–7, 9) have not been previously reported from the species S. hypoleuca, while the triterpenes 8 and 10 are now documented from Salvia genus for the first time.