bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain microvessel cross‐presentation is a hallmark of experimental cerebral malaria
Authors: Howland Shanshan W. , Poh Chek Meng , Gun Sin Yee , Claser Carla , Malleret Benoit , Shastri Nilabh , Ginhoux Florent , Grotenbreg Gijsbert M. , Rénia Laurent 
Published: May 2013

AbstractCerebral malaria is a devastating complication of Plasmodium falciparum infection. Its pathogenesis is complex, involving both parasite‐ and immune‐mediated events. CD8+ T cells play an effector role in murine experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA (PbA) infection. We have identified a highly immunogenic CD8 epitope in glideosome‐associated protein 50 that is conserved across rodent malaria species. Epitope‐specific CD8+ T cells are induced during PbA infection, migrating to the brain just before neurological signs manifest. They are functional, cytotoxic and can damage the blood–brain barrier in vivo. Such CD8+ T cells are also found in the brain during infection with parasite strains/species that do not induce neuropathology. We demonstrate here that PbA infection causes brain microvessels to cross‐present parasite antigen, while non‐ECM‐causing parasites do not. Further, treatment with fast‐acting anti‐malarial drugs before the onset of ECM reduces parasite load and thus antigen presentation in the brain, preventing ECM death. Thus our data suggest that combined therapies targeting both the parasite and host antigen‐presenting cells may improve the outcome of CM patients.
Short‐term splenic impact of single‐strand DNA functionalized multi‐walled carbon nanotubes intraperitoneally injected in rats
Authors: Clichici Simona , Biris Alexandru Radu , Catoi Cornel , Filip Adriana , Tabaran Flaviu 
Published: May 2013

ABSTRACTIn recent years, a great deal of studies have focused on the possible toxicity of carbon nanotubes (CNT), as a result of their potential applications in the field of nanotechnologies. The investigation of spleen toxicity is part of the carbon nanotubes‐induced toxicity assessment. In this study, we investigated the possible toxic effects of CNT on the rat spleen, after intraperitoneally (i.p.) administration of a single dose [1.5 ml; 2 mg multi‐walled (MW) CNT per body weight (bw)] of multi‐walled carbon nanotubes (exterior diameter 15–25 nm, interior diameter 10–15 nm, surface 88 m2 g–1) functionalized 1:1 with single‐strand DNA (ss‐DNA‐MWCNT, 270 mg l–1). CNT functionalization with DNA determines a stable dispersion in the body fluids. For the detection of carbon nanotubes in the spleen, Raman spectroscopy, histopathologic examination, confocal microscopy and transmission electron microscopy (TEM) were performed at different time points (1, 6, 24, 48 and 144 h) after MWCNT administration. The dynamics of oxidative stress parameters (malondialdehyde, protein carbonyls and reduced glutathione), along with nitrosative stress parameters (nitric oxide, inducible NO synthase), the pro‐inflammatory cytokines [interleukin‐(IL)‐1β] and the number of cells expressing caspase 3 and proliferating cell nuclear antigen (PCNA) were assessed. Our results indicate that, after i.p. administration, MWCNT translocate progressively in the spleen, with a peak of concentration after 48 h, and determine lymphoid hyperplasia and an increase in the number of cells which undergo apoptosis, in parallel with the enhancement of the mitosis in the white pulp and with transient alterations of oxidative stress and inflammation that need further investigations for a longer period of monitoring. Copyright © 2013 John Wiley & Sons, Ltd.
Photoacoustic and photothermal detection of circulating tumor cells, bacteria and nanoparticles in cerebrospinal fluid in vivo and ex vivo
Authors: Nedosekin Dmitry A. , Juratli Mazen A. , Sarimollaoglu Mustafa , Moore Christopher L. , Rusch Nancy J. , Smeltzer Mark S. , Zharov Vladimir P. , Galanzha Ekaterina I. 
Published: May 2013

AbstractCirculating cells, bacteria, proteins, microparticles, and DNA in cerebrospinal fluid (CSF) are excellent biomarkers of many diseases, including cancer and infections. However, the sensitivity of existing methods is limited in their ability to detect rare CSF biomarkers at the treatable, early‐stage of diseases. Here, we introduce novel CSF tests based on in vivo photoacoustic flow cytometry (PAFC) and ex vivo photothermal scanning cytometry. In the CSF of tumor‐bearing mice, we molecularly detected in vivo circulating tumor cells (CTCs) before the development of breast cancer brain metastasis with 20‐times higher sensitivity than with current assays. For the first time, we demonstrated assessing three pathways (i.e., blood, lymphatic, and CSF) of CTC dissemination, tracking nanoparticles in CSF in vivo and their imaging ex vivo. In label‐free CSF samples, we counted leukocytes, erythrocytes, melanoma cells, and bacteria and imaged intracellular cytochromes, hemoglobin, melanin, and carotenoids, respectively. Taking into account the safety of PAFC, its translation for use in humans is expected to improve disease diagnosis beyond conventional detection limits. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Biocomposites reinforced by fibers or tubes as scaffolds for tissue engineering or regenerative medicine
Authors: Li Xiaoming , Yang Yu , Fan Yubo , Feng Qingling , Cui Fu‐zhai , Watari Fumio 
Published: May 2013

AbstractAs a dynamic and hierarchically organized composite, native extracellular matrix (ECM) not only supplies mechanical support, which the embedded cells need, but also regulates various cellular activities through interaction with them. On the basis of the ECM‐mimetic principle, good biocompatibility and appropriate mechanical properties are the two basic requirements that the ideal scaffolds for the tissue engineering or regenerative medicine need. Some fibers and tubes have been shown effective to reinforce scaffolds for tissue engineering or regenerative medicine. In this review, three parts, namely properties affected by the addition of fibers or tubes, scaffolds reinforced by fibers or tubes for soft tissue repair, and scaffolds reinforced by fibers or tubes for hard tissue repair are stated, which shows that tissue repair or regeneration efficacy was enhanced significantly by fiber or tube reinforcement. In addition, it indicates that these reinforcing agents can improve the biocompatibility and biodegradation of the scaffolds in most cases. However, there are still some concerns, such as the homogeneousness in structure or composition throughout the reinforced scaffolds, the adhesive strength between the matrix and the fibers or tubes, cytotoxicity of nanoscaled reinforcing agents, etc., which were also discussed in the conclusion and perspectives part. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1580–1594, 2014.
Salt‐Dependence of Homology Searching Step by RecA Nucleoprotein Filaments
Authors: Liao Song‐Mao , Wu Hung‐Yi , Li Hung‐Wen 
Published: May 2013

AbstractRecA recombinase binds onto single‐stranded DNA (ssDNA) and searches for its homologous sequence along double‐stranded DNA (dsDNA). This homologous recombination process is required for repairing double‐stranded DNA breaks. Here, we applied lateral magnetic tweezers to stretch duplex DNA molecules (Lambda DNA, 48,502 bp) in order to monitor the homology searching step by RecA nucleoprotein filaments at the single‐molecule level. From individual searching events, the diffusion coefficient of the RecA nucleoprotein filament is determined to be ∼ 0.5‐1 μm2/s. The nearly salt‐independence of the diffusion coefficients of RecA nucleoprotein filaments implies that our observed RecA searching events were mainly carried out by the one‐dimensional sliding mode.
Population Pharmacokinetic Analysis of Orally‐Administered Ruxolitinib (INCB018424 Phosphate) in Patients With Primary Myelofibrosis (PMF), Post‐Polycythemia Vera Myelofibrosis (PPV‐MF) or Post‐Essential Thrombocythemia Myelofibrosis (PET MF)
Authors: Chen Xuejun , Williams William V. , Sandor Victor , Yeleswaram Swamy 
Published: May 2013

AbstractRuxolitinib is a selective inhibitor of Janus kinase 1 and 2, which is approved to treat intermediate or high‐risk myelofibrosis. The population pharmacokinetics for ruxolitinib were characterized by a modeling dataset of 272 subjects from a Phase 2 and a Phase 3 study and validated by an external validation dataset of 142 subjects from a second Phase 3 study. The PK of ruxolitinib was adequately described by a two‐compartment disposition model with first‐order absorption and linear elimination. All model parameters were estimated with good precision. Gender and body weight were identified as covariates for oral clearance (CL/F) and volume of distribution for central compartment (Vc/F), respectively. Apparent oral clearance was 22.1 and 17.7 L/h for a typical male and female subject, respectively, with 39.1% unexplained inter‐individual variability (IIV). The typical Vc/F for a subject with a median weight of 72.9 kg was estimated to be 58.6 L, with 28% unexplained IIV. The model predictive performance was validated by visual predictive check (VPC) and the external validation dataset. This analysis suggests that effects of gender and body weight on ruxolitinib PK are not clinically significant and hence no dose adjustment is needed based on gender and weight.
Variability of Histamine Pharmacodynamic Response in Children With Allergic Rhinitis
Authors: Jones Bridgette L. , Kearns Gregory , Neville Kathleen A. , Sherwin Catherine M.T. , Spigarelli Michael M.G. , Leeder J. Steven 
Published: May 2013

AbstractHistamine iontophoresis with laser Doppler monitoring (HILD) is a robust and dynamic surrogate for histamine microvasculature response. We characterized histamine pharmacodynamics in children using HILD. HILD was performed in 54 children with allergic rhinitis. A non‐compartmental analysis and non‐linear mixed‐effects model with a linked effect PK/PD model was used to provide estimates for area under the effect curve (AUEC), maximal response over baseline (EffmaxNT), and time of EffmaxNT (Tmax). Data were placed in sub‐groups by visualization of time vs. response relationships. ANOVA and regression analyses were used for sub‐group comparisons. Three histamine response phenotypes were identified. One group demonstrated a hyper‐responsive phenotype (higher Tmax, EffmaxNt and AUEC, P < .01). AUEC and EffmaxNT were more strongly associated in this group (r2 = 0.86) than the entire cohort (r2 = 0.64). These data demonstrate a hyper‐responsive histamine phenotype via HILD. This finding is important to future pharmacologic studies of antihistamines.
Pharmacokinetic and Pharmacodynamic Interaction of Nadolol With Itraconazole, Rifampicin and Grapefruit Juice in Healthy Volunteers
Authors: Misaka Shingen , Miyazaki Nozomu , Yatabe Midori S. , Ono Tomoyuki , Shikama Yayoi , Fukushima Tetsuhito , Kimura Junko 
Published: May 2013

AbstractTo evaluate effects of itraconazole, rifampicin and grapefruit juice on pharmacokinetics and pharmacodynamics of a hydrophilic non‐selective β‐adrenoceptor blocker nadolol, we conducted an open‐label, four‐way crossover study in 10 healthy male volunteers. A single oral dose of 30 mg nadolol was administered with water (control), itraconazole (100 mg), or grapefruit juice (300 mL), or after a 6‐day pretreatment with rifampicin (450 mg/day). Plasma concentrations and urinary excretions of nadolol were measured over 48 hours after its dosing. Systolic and diastolic blood pressures and pulse rate were periodically recorded after nadolol administration as pharmacodynamic parameters. Itraconazole increased the peak plasma concentration and the area under the plasma concentration–time curve (AUC0−∞) of nadolol by 468% and 224% of control, respectively (P < .001). A slight, but not statistically significant, decrease in AUC0−∞ of nadolol was observed in rifampicin and grapefruit juice phases as compared to control. Elimination half‐life for nadolol did not differ among the four phases. During itraconazole phase, nadolol reduced pharmacodynamic parameters to a greater extent than the other phases. These results suggest that itraconazole substantially increases the oral availability of nadolol possibly by the inhibition of intestinal P‐glycoprotein, whereas grapefruit juice has little effect on nadolol pharmacokinetics.
Generation of continental rifts, basins, and swells by lithosphere instabilities
Authors: Fourel Loïc , Milelli Laura , Jaupart Claude , Limare Angela 
Published: May 2013

AbstractContinents may be affected simultaneously by rifting, uplift, volcanic activity, and basin formation in several different locations, suggesting a common driving mechanism that is intrinsic to continents. We describe a new type of convective instability at the base of the lithosphere that leads to a remarkable spatial pattern at the scale of an entire continent. We carried out fluid mechanics laboratory experiments on buoyant blocks of finite size that became unstable due to cooling from above. Dynamical behavior depends on three dimensionless numbers, a Rayleigh number for the unstable block, a buoyancy number that scales the intrinsic density contrast to the thermal one, and the aspect ratio of the block. Within the block, instability develops in two different ways in an outer annulus and in an interior region. In the outer annulus, upwellings and downwellings take the form of periodically spaced radial spokes. The interior region hosts the more familiar convective pattern of polygonal cells. In geological conditions, such instabilities should manifest themselves as linear rifts striking at a right angle to the continent‐ocean boundary and an array of domal uplifts, volcanic swells, and basins in the continental interior. Simple scaling laws for the dimensions and spacings of the convective structures are derived. For the subcontinental lithospheric mantle, these dimensions take values in the 500–1000 km range, close to geological examples. The large intrinsic buoyancy of Archean lithospheric roots prevents this type of instability, which explains why the widespread volcanic activity that currently affects Western Africa is confined to post‐Archean domains.
Comparison of comfort and image quality with two endorectal coils in MRI of the prostate
Authors: Powell Daniel K. , Kodsi Karen L. , Levin Galina , Yim Angela , Nicholson Duane , Kagen Alexander C. 
Published: May 2013

PurposeTo prospectively evaluate comfort and image quality of prostate MRI using two different endorectal (ER) coils.Materials and MethodsThirty consecutive patients were prospectively randomized to receive prostate MRI using either a prostate endocoil (PEC) or colorectal endocoil (CEC). Patients and operators were surveyed with regard to endocoil placement. Four Body MRI trained radiologists rated image quality for each examination and additional selected blinded coronal T2 weighted images.ResultsAverage patient discomfort (on a 0–10 pain scale) was greater with the PEC (5.0 for PEC and 2.7 for CEC) with a statistically significant difference (P < 0.03). Ability to identify the neurovascular bundle (NVB) was 5.8 times more likely to be rated excellent with the CEC compared with the PEC (P < 0.003). Image quality with CEC was 3.5 times more highly rated (P < 0.04). In particular, signal‐to‐noise ratio (SNR) with the CEC was 3.0 times more highly rated than with the PEC (P < 0.05).ConclusionThe smaller CEC was better tolerated by patients than the traditional PEC, and resulted in at least equivalent, and in some instances improved image quality. This may result in fewer aborted cases and lead to decreased procedural intolerance to endorectal coil MRI. J. Magn. Reson. Imaging 2014;39:419–426. © 2013 Wiley Periodicals, Inc.
Gadobutrol in the central nervous system at three doses: Results from a phase II, randomized, multicenter trial
Authors: Breuer Josy , Gutierrez Juan , Latchaw Richard , Lehr Robert , Sorensen A. Gregory 
Published: May 2013

PurposeTo investigate the efficacy and safety of three doses of gadobutrol and determine the minimum effective dose for contrast‐enhanced MRI of the central nervous system (CNS).Materials and MethodsThis was a Phase II, multicenter, double‐blind, parallel‐group controlled study in subjects referred for contrast‐enhanced MRI of the CNS. Subjects were randomized to receive gadobutrol 0.03, 0.1, or 0.3 mmol/kg body weight, and underwent unenhanced, gadobutrol‐enhanced, and comparator‐enhanced MRI scans. Three blinded readers assessed the images. Primary efficacy variables were number of lesions detected, border delineation, contrast enhancement, and internal morphology.ResultsOf the 229 randomized subjects, 173 were evaluated for efficacy. Clinically meaningful improvements in lesion border delineation, contrast enhancement, and internal morphology were observed for 0.1 mmol/kg gadobutrol. Pair‐wise comparisons of a composite score of the four primary variables showed the 0.1 mmol/kg dose to be statistically superior to the 0.03 mmol/kg dose (P = 0.003). The 0.3 mmol/kg dose showed no statistically significant difference with the 0.1 mmol/kg dose. Twenty‐two (9.8%) subjects reported at least one treatment‐emergent adverse event (TEAE). No TEAE was reported at an incidence >3.5%.ConclusionThe 0.1 mmol/kg dose of gadobutrol was effective and well tolerated for contrast‐enhanced MRI of the CNS. J. Magn. Reson. Imaging 2014;39:410–418. © 2013 Wiley Periodicals, Inc.
Whole‐body MR angiography: First experiences with the new TimCT technology with single contrast injection
Authors: Naguib Nagy N.N. , Bohrt Kevin , Nour‐Eldin Nour‐Eldin A. , Schulz Boris , Tawfik Ahmed M. , Siebenhandel Petra , Bodelle Boris , Eichler Katrin , Moritz Anton , Vogl Thomas J. , Zangos Stephan 
Published: May 2013

PurposeTo assess image quality, presence of artifacts, arterial stenosis, and interobserver agreement of Tim‐CT in assessment of the arterial system using contrast‐enhanced whole‐body‐MRA (CE‐Wb‐MRA) with a single contrast‐medium injection in patients with arteriosclerosis.Materials and MethodsThe retrospective study included 18 patients (mean age, 68 years). A total of 468 arteries were evaluated. CE‐Wb‐MRA was performed using Tim‐CT technology on a 1.5 Tesla (T) MRI after injecting a single dose of Vasovist. Evaluations were independently performed by two radiologists. The arterial system was divided into seven anatomic locations. Each radiologist assessed the image quality, degree of artifacts, and arterial stenosis in different locations.ResultsAll Wb‐MRA examinations were technically successful. Image quality: 28.42% arteries were excellent, 29.17% were good, 22.54% were satisfactory, 9.40% were poor, and 5.13% of insufficient quality. Occurrence of artifacts: 37.25% were free of artifacts, 49.44% minimal artifacts not affecting diagnosis, and 13.31% strong artifacts not permitting a diagnosis. A total of 60.00% arteries showed no stenosis, 8.76% were ≤50% stenotic, 5.17% were 51–75% stenotic, 4.38% were 76–99%, and 8.54% total occlusion. The interobserver agreement was good for supra‐aortic, pelvic, and upper and lower leg regions.ConclusionCE‐Wb‐MRA using the TimCT technology and with a single contrast injection is a feasible tool for whole‐body MRA. J. Magn. Reson. Imaging 2014;39:434–439. © 2013 Wiley Periodicals, Inc.
Endorectal MRI and MR spectroscopic imaging of prostate cancer: Developing selection criteria for MR‐guided focal therapy
Authors: Chang Stephanie T. , Westphalen Antonio C. , Jha Priyanka , Jung Adam J. , Carroll Peter R. , Kurhanewicz John , Coakley Fergus V. 
Published: May 2013

PurposeTo investigate criteria that can identify dominant treatable prostate cancer foci with high certainty at endorectal magnetic resonance imaging (MRI) and MR spectroscopic (MRS) imaging, and thus facilitate selection of patients who are radiological candidates for MR‐guided focal therapy.Materials and MethodsWe retrospectively identified 88 patients with biopsy‐proven prostate cancer who underwent endorectal MRI and MRS imaging prior to radical prostatectomy with creation of histopathological tumor maps. Two independent readers noted the largest tumor foci at MRI, if visible, and the volume of concordant abnormal tissue at MRS imaging, if present. A logistic random intercept model was used to determine the association between clinical and MR findings and correct identification of treatable (over 0.5 cm3) dominant intraprostatic tumor foci.ResultsReaders 1 and 2 identified dominant tumor foci in 50 (57%) and 58 (65%) of 88 patients; 42 (84%) and 48 (83%) of these were dominant treatable lesions at histopathology, respectively. Within the statistical model, the volume of concordant spectroscopic abnormality was the only factor that predicted correct identification of a dominant treatable lesion on T2‐weighted images (odds ratio = 1.75; 95% confidence interval = 1.08 to 2.82; P value = 0.02). In particular, all visible lesions on T2‐weighted imaging associated with at least 0.54 cm3 of concordant spectroscopic abnormality were correctly identified dominant treatable tumor foci.ConclusionPatients with dominant intraprostatic tumor foci seen on T2‐weighted MRI and associated with at least 0.54 cm3 of concordant MRS imaging abnormality may be radiological candidates for MR‐guided focal therapy. J. Magn. Reson. Imaging 2014;39:519–525. © 2013 Wiley Periodicals, Inc.
Development of a new fluorescence immunochromatography strip for detection of chloramphenicol residues in chicken muscles
Authors: Bai Zhihong , Luo Yunbo , Xu Wentao , Gao Huafang , Han Pei , Liu Tao , Wang Hui , Chen Ailiang , Huang Kunlun 
Published: May 2013

AbstractBACKGROUNDChloramphenicol (CAP), an antimicrobial drug that is widely used in animal feed, would have a negative effect on human health due to its low elimination rate and relatively high residue in animal food. It is important to develop a rapid and economic method to determine CAP in animal food to ensure that human health is not affected.RESULTSA new fluorescence immunochromatography strip was developed and established for the detection of CAP residue in chicken muscles for the first time. A CAP–bovine serum albumin conjugate, monoclonal antibody and polyclonal antibody against CAP were applied to constitute a fluorescence immunochromatography strip. The fluorescence intensity was detected by a charge‐coupled device scanner and transformed to a digital value. The CAP linearity working range was from 0.1 ng mL−1 to 20 ng mL−1 with a limit of detection of 0.1 ng mL−1 within 10 min. The performance of the strip assay was compared with a commercial ELISA kit and the correlation coefficient was 0.99, which indicated that the new strip assay had a good quantification ability for CAP.CONCLUSIONThe fluorescence immunochromatography strip was successfully applied to the detection of CAP residues in chicken samples. To our knowledge, it is the first report regarding the development of a fluorescence immunochromatography method for screening CAP in animal samples. © 2013 Society of Chemical Industry