bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation-specific hemostatic variability in mice expressing common type 2B von Willebrand disease substitutions
Authors: Golder Mia , Pruss Cynthia M. , Hegadorn Carol , Mewburn Jeffrey , Laverty Kimberly , Sponagle Kate , Lillicrap David 
Published: April 2010

AbstractType 2B von Willebrand disease (2B VWD) results from von Willebrand factor (VWF) A1 mutations that enhance VWF-GPIbα binding. These “gain of function” mutations lead to an increased affinity of the mutant VWF for platelets and the binding of mutant high-molecular-weight VWF multimers to platelets in vivo, resulting in an increase in clearance of both platelets and VWF. Three common 2B VWD mutations (R1306W, V1316M, and R1341Q) were independently introduced into the mouse Vwf cDNA sequence and the expression vectors delivered to 8- to 10-week-old C57Bl6 VWF−/− mice, using hydrodynamic injection. The resultant phenotype was examined, and a ferric chloride–induced injury model was used to examine the thrombogenic effect of the 2B VWD variants in mice. Reconstitution of only the plasma component of VWF resulted in the generation of the 2B VWD phenotype in mice. Variable thrombocytopenia was observed in mice expressing 2B VWF, mimicking the severity seen in 2B VWD patients: mice expressing the V1316M mutation showed the most severe thrombocytopenia. Ferric chloride–induced injury to cremaster arterioles showed a marked reduction in thrombus development and platelet adhesion in the presence of circulating 2B VWF. These defects were only partially rescued by normal platelet transfusions, thus emphasizing the key role of the abnormal plasma VWF environment in 2B VWD.
HLA-mismatched unrelated donors are a viable alternate graft source for allogeneic transplantation following alemtuzumab-based reduced-intensity conditioning
Authors: Mead Adam J. , Thomson Kirsty J. , Morris Emma C. , Mohamedbhai Sajir , Denovan Shari , Orti Guillermo , Fielding Adele K. , Kottaridis Panagiotis D. , Hough Rachael , Chakraverty Ronjon , Linch David C. , Mackinnon Stephen , Peggs Karl S. 
Published: April 2010

AbstractThe impact of human leukocyte antigen (HLA) mismatch after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (RIT) using unrelated donors (UD) is unclear, and may be modulated by T-cell depletion. We therefore examined outcomes of 157 consecutive patients undergoing RIT after uniform conditioning with fludarabine, melphalan, and alemtuzumab (FMC). Donors were 10/10 HLA-matched (MUDs, n = 107) and 6 to 9/10 HLA-matched (MMUDs, n = 50), with no significant differences in baseline characteristics other than increased cytomegalovirus seropositivity in MMUDs. Rates of durable engraftment were high. Graft failure rates (persistent cytopenias with donor chimerism) were similar (8% vs 3%, P = .21), though rejection (recipient chimerism) was more frequent in MMUDs (8% vs 0%, P < .01). There were no significant differences between donors in the incidences of acute graft-versus-host disease (GVHD; 20% vs 22% grade 2-4, respectively, P = .83), chronic extensive GVHD (3-year cumulative incidence [CI] 23% vs 24%, P = .56), or treatment-related mortality (1-year CI 27% vs 27%, P = .96). Furthermore, there was no difference in 3-year overall survival (OS; 53% vs 49%, P = .44). Mismatch occurred at the antigenic level in 40 cases. The outcome in these cases did not differ significantly from the rest of the cohort. We conclude that RIT using HLA-mismatched grafts is a viable option using FMC conditioning.
Differential transcript expression between the microfilariae of the filarial nematodes, Brugia malayi and B. pahangi
Authors: Kariuki Michael M , Hearne Leonard B , Beerntsen Brenda T 
Published: April 2010

Abstract

Background

Brugia malayi and B. pahangi are two closely related nematodes that cause filariasis in humans and animals. However, B. pahangi microfilariae are able to develop in and be transmitted by the mosquito, Armigeres subalbatus, whereas most B. malayi are rapidly melanized and destroyed within the mosquito hemocoel. A cross-species microarray analysis employing the B. malayi V2 array was carried out to determine the transcriptional differences between B. malayi and B. pahangi microfilariae with similar age distribution.

Results
Following microarray data analysis, a list of preferentially expressed genes in both microfilariae species was generated with a false discovery rate estimate of 5% and a signal intensity ratio of 2 or higher in either species. A total of 308 probes were preferentially expressed in both species with 149 probes, representing 123 genes, in B. pahangi microfilariae and 159 probes, representing 107 genes, in B. malayi microfilariae. In B. pahangi, there were 76 (62%) up-regulated transcripts that coded for known proteins that mapped into the KEGG pathway compared to 61 (57%) transcripts in B. malayi microfilariae. The remaining 47 (38%) transcripts in B. pahangi and 46 (43%) transcripts in B. malayi microfilariae were comprised almost entirely of hypothetical genes of unknown function. Twenty-seven of the transcripts in B. pahangi microfilariae coded for proteins that associate with the secretory pathway compared to thirty-nine in B. malayi microfilariae. The data obtained from real-time PCR analysis of ten genes selected from the microarray list of preferentially expressed genes showed good concordance with the microarray data, indicating that the microarray data were reproducible.

Conclusion
In this study, we identified gene transcripts that were preferentially expressed in the microfilariae of B. pahangi and B. malayi, some of which coded for known immunomodulatory proteins. These comparative transcriptome data will be of interest to researchers keen on understanding the inherent differences, at the molecular level, between B. malayi and B. pahangi microfilariae especially because these microfilariae are capable of surviving in the same vertebrate host but elicit different immune response outcomes in the mosquito, Ar. subalbatus.
The analysis of oral microbial communities of wild-type and toll-like receptor 2-deficient mice using a 454 GS FLX Titanium pyrosequencer
Authors: Chun Jongsik , Kim Kap Y , Lee Jae-Hak , Choi Youngnim 
Published: April 2010

Abstract

Background
Although mice have long served as an animal model for periodontitis, information on the composition of their indigenous oral microbiota is limited. The aim of the current study was to characterize mouse oral bacterial flora by applying extensive parallel pyrosequencing using the latest model pyrosequencer, a Roche/454 Genome Sequencer FLX Titanium. In addition, the effect of Toll-like receptor (TLR) 2 deficiency on oral microbiota was evaluated.

Results
Eight oral bacterial communities of wild-type (n = 4) and TLR2 knock-out (n = 4) C57BL/6 mice were characterized by analyzing 80,046 reads of 16S rRNA genes obtained by pyrosequencing. Excluding the PCR primers, the average length of each sequencing product was 443 bp. The average species richness of the murine oral bacterial communities was estimated to be about 200, but the communities were dominated by only two main phyla and several species. Therefore, the bacterial communities were relatively simple. The bacterial composition of the murine oral microbiota was significantly different from that of humans, and the lack of TLR2 had a negligible effect on the murine oral microbiota.

Conclusion
Pyrosequencing using the Roche/454 FLX Titanium successfully characterized mouse oral bacterial communities. The relatively simple oral bacterial communities of mice were not affected by TLR2 deficiency. These findings will provide a basis for future studies on the role of periodontal pathogens in the murine model of periodontitis.
Estimation of HIV-1 incidence among five focal populations in Dehong, Yunnan: a hard hit area along a major drug trafficking route
Authors: Duan Song , Shen Sheng , Bulterys Marc , Jia Yujiang , Yang Yuecheng , Xiang Lifeng , Tian Fei , Lu Lin , Xiao Yao , Wang Minjie , Jia Manhong , Jiang Huazhou , Vermund Sten H , Jiang Yan 
Published: April 2010

Abstract

Background
Since 1989 when the first 146 HIV positives in China were identified, Dehong Prefecture had been one of the areas hardest-hit by HIV in China. The local and national governments have put substantial financial resources into tackling the HIV epidemic in Dehong from 2004. The objective of this study was to track dynamic changes in HIV-1 prevalence and incidence among five focal populations in Dehong and to assess the impact of HIV prevention and control efforts.

Methods
Consecutive cross-sectional surveys conducted in five focal populations between 2004 and 2008. Specimens seropositive for HIV were tested with the BED IgG capture enzyme immunoassay to identify recent seroconversions (median, 155 days) using normalized optical density of 0.8 and adjustments.

Results
From 2004 to 2008, estimated annual HIV incidence among injecting drug users (IDUs) decreased significantly [from 15.0% (95% CI = 11.4%-18.5%) in 2004 to 4.3% (95% CI = 2.4%-6.2%) in 2008; trend test P < 0.0001]. The incidence among other focal populations, such as HIV discordant couples (varying from 5.5% to 4.7%), female sex workers (varying from 1.4% to 1.3%), pregnant women (0.1%), and pre-marital couples (0.2 to 0.1%) remained stable. Overall, the proportion of recent HIV-1 infections was higher among females than males (P < 0.0001).

Conclusions
The HIV epidemic in Dehong continued to expand during a five-year period but at a slowing rate among IDUs, and HIV incidence remains high among IDUs and discordant couples. Intensive prevention measures should target sub-groups at highest risk to further slow the epidemic and control the migration of HIV to other areas of China, and multivariate analysis is needed to explore which measures are more effective for different populations.
Prolyl oligopeptidase is inhibited in relapsing-remitting multiple sclerosis
Authors: Tenorio-Laranga Jofre , Coret-Ferrer Francisco , Casanova-Estruch Buenaventura , Burgal María , García-Horsman J Arturo 
Published: April 2010

Abstract

Background
Multiple sclerosis (MS) is a complex, inflammatory and neurodegenerative disease of the central nervous system leading to long-term disability. Recent studies indicate a close association between inflammation and neurodegeneration in all lesions and disease stages of MS. Prolyl oligopeptidase (POP) is a proline-specific serine protease that cleaves several neuroactive peptides. This peptidase has been implicated in neurodegeneration, as well as in the modulation of the inflammatory response.

Methods
We examined plasma POP and the levels of an endogenous POP inhibitor from relapsing remitting MS patients and compared these with healthy controls, by monitoring the fluorescent changes due to standard fluorescently labelled substrate cleavage. We analysed the data in relationship to patient age and disease disability status.

Results
We observed a significant decrease in POP activity in plasma of relapsing remitting MS patients relative to healthy controls, coupled with an increase of POP endogenous inhibitor. The POP activity was also correlated with patient age and disability status. The lowered POP activity from plasma of MS patients could be rescued by reductants

Conclusions
The decrease in circulating POP activity measured in MS is reverted by reductants. This suggests that POP inactivation in MS might be a result of the oxidative conditions prevailing in the plasma of the diseased patients. Plasma levels of POP activity as well as those of their endogenous inhibitor are suggested as biomarkers of inflammation and oxidative stress in MS.
Utility of Glycated Hemoglobin in Diagnosing Type 2 Diabetes Mellitus: A Community-Based Study
Authors: Kumar Padala Ravi , Bhansali Anil , Ravikiran Muthuswamy , Bhansali Shobhit , Dutta Pinaki , Thakur J. S. , Sachdeva Naresh , Bhadada Sanjay Kumar , Walia Rama 
Published: April 2010

Abstract
Context: Although glycated hemoglobin (HbA1c) has recently been incorporated as a diagnostic test by the American Diabetes Association, its validity needs to be established in Asian Indians in a community setting.
Objective: The objective of the study was to assess the validity of HbA1c as a screening and diagnostic test in individuals with newly detected diabetes mellitus.
Design and Setting: Community based randomized cross sectional study in urban Chandigarh, a city in north India, from April 2008 to August 2009.
Subjects: Subjects included 1972 subjects aged 20 yr or older.
Intervention: Intervention included an oral glucose tolerance test and glycated hemoglobin in all the subjects.
Main Outcome Measures: Utility of HbA1c as a diagnostic method in newly detected diabetes mellitus subjects was evaluated.
Results: Using World Health Organization criteria for diagnosis of diabetes mellitus, 134 (6.7%) had newly detected diabetes mellitus, 192 (9.7%) known diabetes mellitus, 329 (16.6%) prediabetes, and 1317 (69.4%) were normal of 1972 people screened. Using only the ADA criteria, 38% people were underdiagnosed. An HbA1c level of 6.1% had an optimal sensitivity and specificity of 81% for diagnosing diabetes. A HbA1c level of 6.5% (±2 sd) and 7% (±2.7 sd) had sensitivity and specificity of 65 and 88% and 42 and 92%, respectively, with corresponding positive predictive value and negative predictive value of 75.2 and 96.5% and 90.4and 94.4%, respectively, for diagnosis of newly detected diabetes mellitus.
Conclusion: A HbA1c cut point of 6.1% has an optimal sensitivity and specificity of 81% and can be used as a screening test, and a cut point of 6.5% has optimal specificity of 88% for diagnosis of diabetes.
Vandetanib (100 mg) in Patients with Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer
Authors: Robinson Bruce G. , Paz-Ares Luis , Krebs Annetta , Vasselli James , Haddad Robert 
Published: April 2010

Abstract
Purpose: Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity. Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in patients with advanced hereditary MTC.
Patients and Methods: Eligible patients with unresectable, measurable, locally advanced, or metastatic hereditary MTC received 100 mg/d vandetanib. Upon disease progression, eligible patients could enter postprogression treatment with 300 mg/d vandetanib until a withdrawal criterion was met. The primary objective was to assess the objective response rate by response evaluation criteria in solid tumors.
Results: The study comprised 19 patients (13 males, six females; mean age 45 yr). Confirmed objective partial responses were observed in three patients, yielding an objective response rate of 16% (95% confidence interval 3.4–39.6). Stable disease lasting 24 wk or longer was reported in a further 10 patients (53%); the disease control rate was therefore 68% (95% confidence interval 43.4–87.4). Serum levels of calcitonin and carcinoembryonic antigen showed a sustained 50% or greater decrease from baseline in 16% (three of 19) and 5% (one of 19) of patients, respectively. Adverse events were predominantly grade 1 or 2 and consistent with previous vandetanib monotherapy studies.
Conclusions: Vandetanib at a once-daily dose of 100 mg has clinically relevant antitumor activity in patients with locally advanced or metastatic hereditary MTC and an overall acceptable safety profile.
Preparation of High-molecular-weight Phenolic Resins by means of a Phase-separation Reaction System
Authors: Wang Pengfei , Ogoshi Tomoki , Yamagishi Tada-Aki , Nakamoto Yoshiaki 
Published: April 2010

Abstract
High-molecular-weight o-cresol resins with narrow-molecular-weight distribution were prepared using a phase-separation reaction system. The prepared o-cresol resins included a trace of monomer, so that the molecular-weight distribution was narrow. In high molecular weight o-cresol resin, the fractions of ortho–ortho′, ortho–para′, and para–para′ methylene linkages were close to 25%, 50%, and 25%, respectively. This indicated that the reactivity of the ortho position was equal to that of the para position. It was found that the o-cresol ring was highly activated in phase separation reaction system using H2SO4/acetic acid.
Microwave-assisted One-pot Synthesis of Luminescent Organic–Inorganic Hybrids via Simultaneous Process of Sol–Gel and Suzuki–Miyaura Coupling Reactions
Authors: Kajiwara Yuichi , Nagai Atsushi , Chujo Yoshiki 
Published: April 2010

Abstract
In order to disperse luminescent compounds with low solubility or high crystallinity into silica matrices, we demonstrate here facile one-pot synthesis of organic–inorganic luminescent hybrids via simultaneous process of sol–gel reaction of 3-(chloropropyl)trimethoxysilane (CPTMS) and the Suzuki–Miyaura homocoupling of 1-pyreneboronic acid under microwave irradiation. Highly luminescent hybrid without aggregates of the pyrene dimer, which was efficiently generated in situ, was obtained by microwave irradiation due to rapid formation of silica matrices, whereas huge aggregates were observed in the hybrid prepared under conventional heating.
Color Tunable Novel Amphotropic Liquid Crystalline Acrylate End-capped with a Cholesteryl Group
Authors: Hsieh Feng-Min , Fang Hau , Liu Jui-Hsiang 
Published: April 2010

Abstract
We report a novel, monomeric, lyotropic, cholesteric liquid crystal revealing selective reflection in the visible light region and having photochromic properties in the lyotropic liquid crystal phase. Monomer (+)-cholesteryl (6-acryloyloxyhexyloxy)-4-cinnamate was synthesized. Liquid crystal phases of M1 were identified using polarized optical microscopic and X-ray diffraction methods. Reflection light spectra were analyzed using an optical fiber system.
To Wait or Not to Wait—And Who Goes First? Delay Management with Priority Decisions
Authors: Schachtebeck Michael , Schöbel Anita 
Published: April 2010

Delay management is an important issue in the daily operations of any railway company. The task is to update the planned timetable to a disposition timetable in such a way that the inconvenience for the passengers is as small as possible. The two main decisions that have to be made in this respect are the wait-depart decisions, to decide which connections should be maintained in case of delays, and the priority decisions, which determine the order in which trains are allowed to pass a specific piece of track. The latter are necessary to take the limited capacity of the track system into account. While the wait-depart decisions have been intensively studied in the literature, the priority decisions in the capacitated case have been neglected so far in delay management optimization models. In the current paper, we add the priority decisions to the integer programming formulation of the delay management problem and are hence able to deal with the capacitated case. The corresponding constraints are disjunctive constraints leading to cycles in the resulting event-activity network. Nevertheless, we are able to derive reduction techniques for the network that enable us to extend the formulation of the never-meet property from the uncapacitated delay management problem to the capacitated case. We then use our results to derive exact and heuristic solution procedures for solving the delay management problem. The results of the algorithms are evaluated both from a theoretical and a numerical point of view. The latter has been done within a case study using the railway network in the region of Harz, Germany.
Dexlansoprazole in the Treatment of Esophagitis and Gastroesophageal Reflux Disease
Authors: Abel Cheryl , Desilets Alicia R , Willett Kristine 
Published: April 2010

OBJECTIVE: To describe the pharmacology, pharmacokinetics, and efficacy of dexlansoprazole in the treatment of heartburn associated with nonerosive gastroesophageal reflux disease (GERD) and healing and maintenance of healing of all grades of erosive esophagitis (EE). DATA SOURCES: Literature searches were conducted using MEDLINE Ovid (1950-December 2009, week 4) and EMBASE (1980-2009, week 53) using the term dexlansoprazole. References from articles obtained from the search were evaluated for other relevant citations. STUDY SELECTION AND DATA EXTRACTION: All articles published in English evaluating the pharmacology, pharmacokinetics, efficacy, and adverse effect profile of dexlansoprazole were selected for inclusion. DATA SYNTHESIS: Dexlansoprazole is the newest addition to the proton pump inhibitor (PPI) class and is approved for the treatment of heartburn associated with nonerosive GERD, healing of all grades of EE, as well as maintenance of healing of EE. Dexlansoprazole has a unique dual delayed-release formulation, which releases drug at 2 points in time; the first peak occurs 1-2 hours after administration and the second occurs within 4-5 hours after administration. In Phase 3 trials conducted in adults, researchers found that dexlansoprazole increases rates of healing of EE, as well as the maintenance of healing, compared to lansoprazole. Relief of heartburn symptoms was comparable among the dexlansoprazole and lansoprazole treatment groups. Common adverse effects of dexlansoprazole are similar to those of the other PPIs, including diarrhea, abdominal pain, nausea, upper respiratory infection, vomiting, and flatulence. CONCLUSIONS: Dexlansoprazole provides another treatment option for the management of EE and symptoms of heartburn. Considering that the cost of dexlansoprazole is not favorable, further studies evaluating potential advantages over other agents are necessary to define the role of dexlansoprazole in the treatment of these conditions.