bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics, tolerability, and preliminary efficacy of paquinimod (ABR‐215757), a new quinoline‐3‐carboxamide derivative: Studies in lupus‐prone mice and a multicenter, randomized, double‐blind, placebo‐controlled, repeat‐dose, dose‐ranging study in patients with systemic lupus erythematosus
Authors: Bengtsson Anders A. , Sturfelt Gunnar , Lood Christian , Rönnblom Lars , van Vollenhoven Ronald F. , Axelsson Bengt , Sparre Birgitta , Tuvesson Helén , Öhman Marie Wallén , Leanderson Tomas 
Published: December 2011

AbstractObjectiveTo assess the efficacy of paquinimod, a new immunomodulatory small molecule, in a murine lupus model, and to evaluate its pharmacokinetics and tolerability in systemic lupus erythematosus (SLE) patients at doses predicted to be efficacious and safe and determine the maximum tolerated dose.MethodsThe efficacy of paquinimod was studied in lupus‐prone MRL‐lpr/lpr mice and compared with that of established SLE treatments. Dose‐response data and pharmacokinetic data were used to calculate effective and safe clinical doses of paquinimod. The pharmacokinetics and tolerability of paquinimod were evaluated in a phase Ib double‐blind, placebo controlled, dose‐ranging study in which cohorts of SLE patients received daily oral treatment for 12 weeks.ResultsPaquinimod treatment resulted in disease inhibition in MRL‐lpr/lpr mice, comparable to that obtained with prednisolone and mycophenolate mofetil; prominent effects on disease manifestations and serologic markers and a steroid‐sparing effect were observed. In patients with SLE, the pharmacokinetic properties of paquinimod were linear and well suitable for once‐daily oral treatment. The majority of the adverse events (AEs) were mild or moderate, and transient. The most frequent AEs were arthralgia and myalgia, reported with the highest dose levels of paquinimod (4.5 mg/day and 6.0 mg/day). At the 4.5 mg/day dose level and higher, some AEs of severe intensity and serious adverse events were reported.ConclusionPaquinimod effectively inhibited disease and had a steroid‐sparing effect in experimental lupus. Results from preclinical models together with pharmacokinetic data were successfully translated into a safe clinical dose range, and doses of up to 3.0 mg/day were well tolerated in the SLE patients. Taken together, the promising combined data from a murine model and human SLE support the future clinical development of paquinimod.
Effect of visual–spatial ability on medical students' performance in a gross anatomy course
Authors: Lufler Rebecca S. , Zumwalt Ann C. , Romney Carla A. , Hoagland Todd M. 
Published: December 2011

AbstractThe ability to mentally manipulate objects in three dimensions is essential to the practice of many clinical medical specialties. The relationship between this type of visual–spatial ability and performance in preclinical courses such as medical gross anatomy is poorly understood. This study determined if visual–spatial ability is associated with performance on practical examinations, and if students' visual–spatial ability improves during medical gross anatomy. Three hundred and fifty‐two first‐year medical students completed the Mental Rotations Test (MRT) before the gross anatomy course and 255 at its completion in 2008 and 2009. Hypotheses were tested using logistic regression analysis and Student's t‐test. Compared with students in the lowest quartile of the MRT, students who scored in the highest quartile of the MRT were 2.2 [95% confidence interval (CI) 1.2 and 3.8] and 2.1 (95% CI 1.2 and 3.5) times more likely to score greater than 90% on practical examinations and on both practical and written examinations, respectively. MRT scores for males and females increased significantly (P < 0.0001). Measurement of students' pre‐existing visual–spatial ability is predictive of performance in medical gross anatomy, and early intervention may be useful for students with low visual–spatial ability on entry to medical school. Participation in medical gross anatomy increases students' visual–spatial ability, although the mechanism for this phenomenon is unknown. Anat Sci Educ. © 2011 American Association of Anatomists.
Noninvasive High‐Resolution Ultrasound Reveals Structural and Functional Deficits in Dimethadione‐Exposed Fetal Rat Hearts In Utero
Authors: Purssell Elizabeth , Weston Andrea D. , Thomson Jason J. , Swanson Terri A. , Brown Nigel A. , Ozolinš Terence R.S. 
Published: December 2011

BACKGROUNDWe previously showed dimethadione (DMO), the N‐demethylated metabolite of the anticonvulsant trimethadione, induces ventricular septation defects (VSD) and other heart anomalies in rat (Weston et al., 2011). Because of the relationship between cardiac structure and function, we hypothesized that DMO‐induced structural defects of the heart are associated with in utero functional deficits. To test the hypothesis, the goals were (1) define the parameters for ultrasound in the rat conceptus, and; (2) use ultrasound to identify structural and functional deficits following DMO treatment.METHODSDifferent ultrasound modes (B‐mode, M‐mode, and Pulse‐wave Doppler) using four high‐resolution ultrasound transducer heads of varying frequency (25–40 MHz) were tested on gestational day (GD) 14, 15, 16, 17, and 21. Having identified the optimal conditions, pregnant Sprague–Dawley rats were administered six 300 mg/kg doses of DMO every 12 hr beginning at 19:00hr on GD 8 to generate conceptuses with a high incidence of VSD.RESULTSThe three ultrasound modalities were used to identify VSD and several novel and rare structural heart anomalies (cardiac effusions and bifurcated septum) in live rat fetuses. DMO‐treated hearts had an array of functional deficits including a decrease in mean heart rate, ejection fraction, and cardiac output and increased incidence of bradycardia and dysrhythmia.CONCLUSIONSThe ultrasound biomicroscope is an effective tool for the real‐time characterization of the structure and function of embryo/fetal rat hearts. DMO causes significant deficits to in utero heart function for up to ten days (GD 21) following its final administration, suggesting long‐term or possible permanent changes cardiac function.
In Situ Scanning Electrochemical Microscopy (SECM) Detection of Metal Dissolution during Zinc Corrosion by Means of Mercury Sphere‐Cap Microelectrode Tips
Authors: Souto Ricardo M. , González‐García Yaiza , Battistel Dario , Daniele Salvatore 
Published: December 2011

AbstractThis work presents a scanning electrochemical microscopy (SECM)‐based in situ corrosion probing methodology that is capable of monitoring the release of zinc species in corrosion processes. It is based on the use of Hg‐coated Pt microelectrodes as SECM tips, which offer a wider negative potential range than bare platinum or other noble‐metal tips. This allows for the reduction of zinc ions at the tip to be investigated with low interference from hydrogen evolution and oxygen reduction from aqueous solutions. The processes involved in the corrosion of zinc during its immersion in chloride‐containing solutions were successfully monitored by scanning the SECM tip, set at an adequate potential, across the sample either in one direction or in the X–Y plane parallel to its surface. In this way, it was possible to detect the anodic and cathodic sites at which the dissolution of zinc and the reduction of oxygen occurred, respectively. Additionally, cyclic voltammetry (CV) or constant potential measurements were used to monitor the release of zinc species collected at the tip during an SECM scan.
Thermal Breakdown of ZnTe Nanowires
Authors: Davami Keivan , Ghassemi Hessam M. , Yassar Reza S. , Lee Jeong‐Soo , Meyyappan M. 
Published: December 2011

AbstractAs the applications for inorganic nanowires continuously grow, studies on the stability of these structures under high electrical/thermal stress conditions are needed. ZnTe nanowires are grown by the vapor‐liquid‐solid technique and their breakdown under Joule heating is studied through in situ monitoring in a transmission electron microscope (TEM). The experimental setup, consisting of a scanning tunneling microscope (STM) and a movable piezotube inside the TEM, allows the manipulation of a single nanowire. A voltage applied to the STM tip in contact with a ZnTe nanowire leads to the breakdown of the nanowire into Zn and Te particles or balls which is observed in real time. These balls grow by Ostwald ripening, rendering the surface morphology of the ZnTe nanowire progressively rough. Diffraction patterns along the stem of the wire after the partial breakdown showed substantially smaller lattice spacing compared to 0.35 nm for pristine ZnTe nanowires.
Introduction to genetic analysis workshop 17 summaries
Authors: Ziegler Andreas , Ghosh Saurabh , Dyer Thomas D. , Blangero John , MacCluer Jean , Almasy Laura 
Published: December 2011

AbstractGenetic Analysis Workshop 17 (GAW17) was held on October 13–16, 2010, in Boston, Massachusetts. The focus of GAW17 was on methods and challenges of the analysis of next‐generation sequence data using a mini‐exome data set. Two different study designs were simulated, unrelated individuals and large families, each with the same sample size. GAW17 was attended by 274 participants from 19 countries. The 166 contributions were organized into 15 discussion groups of 5–13 articles each. This supplement to Genetic Epidemiology provides further details on GAW17, and primary findings are highlighted in the individual group summary articles. In addition, the supplement includes two methodological articles (one on statistical approaches for collapsing methods and one on machine learning methods) to give an overview of the methods that many of the workshop participants used. We conclude the supplement with a discussion of critical aspects in the analysis of next‐generation sequencing data. Genet. Epidemiol. 35:S1–S4, 2011. © 2011 Wiley Periodicals, Inc.
Incorporating linkage information into a common disease/rare variant framework
Authors: Hinrichs Anthony L. , Suarez Brian K. 
Published: December 2011

AbstractRecent developments in sequencing technology have allowed the investigation of the common disease/rare variant hypothesis. In the Genetic Analysis Workshop 17 data set, we have sequence data on both unrelated individuals and eight large extended pedigrees with simulated quantitative and qualitative phenotypes. Group 11, whose focus was incorporating linkage information, considered several different ways to use the extended pedigrees to identify causal genes and variants. The first issue was the use of standard linkage or identity‐by‐descent information to identify regions containing causal rare variants. We found that rare variants of large effect segregating through pedigrees were precisely the bailiwick of linkage analysis. For a common disease, we anticipate many risk loci, so a heterogeneity linkage analysis or an analysis of a single pedigree at a time may be useful. The second issue was using pedigree data to identify individuals for sequencing. If one can identify linked regions and even carriers of risk haplotypes, the sequencing will be substantially more efficient. In fact, sequencing only 2.5% of the genome in carefully selected individuals can detect 52% of the risk variants that would be detected through whole‐exome sequencing in a large number of unrelated individuals. Finally, we found that linkage information from pedigrees can provide weights for case‐control association tests. We also found that pedigree‐based association tests have the same issues of binning variants and variant counting as those in tests of unrelated individuals. Clearly, when pedigrees are available, they can provide great assistance in the search for rare variants that influence common disorders. Genet. Epidemiol. 35:S74–S79, 2011. © 2011 Wiley Periodicals, Inc.
Association between PARP‐1 V762A polymorphism and cancer susceptibility: a meta‐analysis
Authors: Yu Hongping , Ma Hongxia , Yin Ming , Wei Qingyi 
Published: December 2011

AbstractPoly(ADP‐ribose) polymerase‐1 (PARP‐1 catalyzes poly(ADP‐ribosyl)ation to various proteins involved in many cellular processes, including DNA damage detection and repair and cell proliferation and death. PARP‐1 has been implicated in human carcinogenesis, but the association between the most‐studied PARP‐1 V762A polymorphism (rs1136410) and risk of various cancers was reported with inconclusive results. The aim of this study was to assess the association between the PARP‐1 V762A polymorphism and cancer risk. A meta‐analysis of 21 studies with 12,027 cancer patients and 14,106 cancer‐free controls was conducted to evaluate the strength of the association using odds ratio (OR) with 95% confidence interval (CI). Overall, no significant association was found between the PARP‐1 V762A polymorphism and cancer risk. In the stratified analyses, however, it was found that the variant A allele of the PARP‐1 V762A polymorphism was associated with an increased risk of cancer among Asian populations (VA + AA vs. VV: OR = 1.11, 95% CI: 1.01–1.23; Pheterogeneity = 0.210), but a decreased risk of cancer (VA + AA vs. VV: OR = 0.89, 95% CI: 0.80–1.00; Pheterogeneity = 0.004) among Caucasian populations, especially for glioma risk (OR = 0.79, 95% CI: 0.69–0.90; Pheterogeneity = 0.800). This meta‐analysis found evidence for an association of the PARP‐1 V 762A polymorphism with increased risk of cancer among Asians, but decreased risk of cancer among Caucasians, particularly of glioma. Further well‐designed studies with large sample sizes of different ethnic populations and different cancer types are warranted to confirm these findings. Genet. Epidemiol. 36 : 56–65 2012. © 2011 Wiley Periodicals, Inc.
Quantitative cartilage degeneration associated with spontaneous osteoarthritis in a guinea pig model
Authors: Fenty Matthew C. , Dodge George R. , Kassey Victor Babu , Witschey Walter R.T. , Borthakur Arijitt , Reddy Ravinder 
Published: December 2011

AbstractPurpose:To determine (i) the feasibility and intra‐ and inter‐scan reproducibility of T1ρ MRI in assessing cartilage degeneration in a guinea pig model with naturally occurring joint disease that closely mimics human osteoarthritis (OA), (ii) demonstrate the sensitivity of T1ρ MRI in assessing the age dependent cartilage degeneration in OA progression as compared to histopathological changes.Materials and Methods:Duncan‐Hartley guinea pigs were obtained at various ages and maintained under an IACUC approved protocol. The left hind stifle joint was imaged using T1ρ MRI on a 9.4 Tesla Varian horizontal 20 cm bore scanner using a custom surface coil. Reproducibility of T1ρ MRI was assessed using 4‐month‐old guinea pigs (N = 3). Three age cohorts; 3 month (N = 8), 5 month (N = 6), and 9 month (N = 5), were used to determine the age‐dependent osteoarthritic changes as measured by T1ρ MRI. Validation of age‐dependent cartilage degeneration was confirmed by histology and Safranin‐O staining.Results:T1ρ values obtained in the cartilage of the stifle joint in guinea pigs were highly reproducible with an inter‐scan mean coefficient of variation (CV) of 6.57% and a maximum intra‐scan CV of 9.29%. Mean cartilage T1ρ values in animals with late stage cartilage degeneration were 56.3–56.9 ms (5–9 month cohorts) were both significantly (P < 0.01) higher than that obtained from 3‐month‐old cohort (44 ms) demonstrating an age‐dependent variation. T1ρ was shown to be significantly greater than T2. T1ρ dispersion was observed in this animal model for the first time showing an increase of 45% between 500 Hz and 1500 Hz spin‐locking frequency. Cartilage thickness measurements were calculated from single mid‐coronal histology sections from same animals used for T1ρ MRI. Thickness calculations showed insignificant differences between 3‐ and 5‐month cohorts and was significantly decreased by 9 months of age (P < 0.01). A moderate correlation (R2 = 0.45) existed between T1ρ values and signal intensity of Safranin‐O stain.Conclusion:The data presented demonstrate that T1ρ MRI is highly reproducible in this spontaneous model of OA and may serve as a noninvasive tool to characterize joint cartilage degeneration during OA. Age‐dependent changes, verified with histological measurements of proteoglycan loss, correlated with T1ρ across different age groups. T1ρ has adequate dynamic range and is sensitive to detect and track the progression of cartilage degeneration in the guinea pig model before gross anatomical changes such as cartilage thinning has occurred. This study presents a technological advancement that would permit longitudinal studies of evaluating disease‐modifying therapies useful for treating human OA. J. Magn. Reson. Imaging 2012;35:891–898. © 2011 Wiley Periodicals, Inc.
Segmentation of carotid plaque using multicontrast 3D gradient echo MRI
Authors: Liu Wenbo , Balu Niranjan , Sun Jie , Zhao Xihai , Chen Huijun , Yuan Chun , Zhao Huilin , Xu Jianrong , Wang Guangzhi , Kerwin William S. 
Published: December 2011

AbstractPurpose:To evaluate the performance of automatic segmentation of atherosclerotic plaque components using solely multicontrast 3D gradient echo (GRE) magnetic resonance imaging (MRI).Materials and Methods:A total of 15 patients with a history of recent transient ischemic attacks or stroke underwent carotid vessel wall imaging bilaterally with a combination of 2D turbo spin echo (TSE) sequences and 3D GRE sequences. The TSE sequences included T1‐weighted, T2‐weighted, and contrast‐enhanced T1‐weighted scans. The 3D GRE sequences included time‐of‐flight (TOF), magnetization‐prepared rapid gradient echo (MP‐RAGE), and motion‐sensitized driven equilibrium prepared rapid gradient echo (MERGE) scans. From these images, the previously developed morphology‐enhanced probabilistic plaque segmentation (MEPPS) algorithm was retrained based solely on the 3D GRE sequences to segment necrotic core (NC), calcification (CA), and loose matrix (LM). Segmentation performance was assessed using a leave‐one‐out cross‐validation approach via comparing the new 3D‐MEPPS algorithm to the original MEPPS algorithm that was based on the traditional multicontrast protocol including 2D TSE and TOF sequences.Results:Twenty arteries of 15 subjects were found to exhibit significant plaques within the coverage of all imaging sequences. For these arteries, between new and original MEPPS algorithms, the areas per slice exhibited correlation coefficients of 0.86 for NC, 0.99 for CA, and 0.80 for LM; no significant area bias was observed.Conclusion:The combination of 3D imaging sequences (TOF, MP‐RAGE, and MERGE) can provide sufficient contrast to distinguish NC, CA, and LM. Automatic segmentation using 3D sequences and traditional multicontrast protocol produced highly similar results. J. Magn. Reson. Imaging 2012;35:812–819. © 2011 Wiley Periodicals, Inc.
Contribution of MRI to ultrasound in the diagnosis of fetal anomalies
Authors: Kul Sibel , Korkmaz Hatice Ayca Ata , Cansu Aysegul , Dinc Hasan , Ahmetoglu Ali , Guven Suleyman , Imamoglu Mustafa 
Published: December 2011

AbstractPurpose:To evaluate the contribution of MRI to ultrasound (US) in the diagnosis of fetal anomalies.Materials and Methods:After informed consent and institutional review board approval, concomitant US and MR imaging were performed for 184 fetuses with suspected anomalies in university hospital. Postnatal final diagnoses were obtained for 183 anomalies in 151 fetuses either by radiological examination, surgery, autopsy, or inspection. The prenatal US and MR diagnoses were compared with respect to postnatal diagnoses. Sign test was used to determine the statistical significance.Results:Both ultrasound and MR imaging correctly diagnosed 93 (50%) cases and failed in 12 (7%) cases. Ultrasound was superior in 7 (4%) cases. MR imaging was superior in 71 (39%) cases (P < 0.001). MR contributed to the prenatal diagnosis by the confirmation of the suspected US diagnosis in 13%, by demonstration of additional findings in 31% and by changing the diagnosis in 56% of the cases. The contribution rates were 55% for the central nervous system (CNS) (P < 0.001), 44% for thorax (P = 0.016), 38% for gastrointestinal system (GIS) (P = 0.031) and 29% for genitourinary system (GUS) (P = 0.003) anomalies. In facial, cardiac and extremity‐skeletal system anomalies, there was not a significant contribution of MR imaging over US.Conclusion:MR imaging can be used as an adjunct to US in the prenatal diagnosis of fetal anomalies of not only the CNS but also the non‐CNS origin especially those involving the GIS, GUS and thorax. J. Magn. Reson. Imaging 2012;35:882–890. © 2011 Wiley Periodicals, Inc.
Characterization of the regional distribution of skeletal muscle adipose tissue in type 2 diabetes using chemical shift‐based water/fat separation
Authors: Karampinos Dimitrios C. , Baum Thomas , Nardo Lorenzo , Alizai Hamza , Yu Huanzhou , Carballido‐Gamio Julio , Yap S. Paran , Shimakawa Ann , Link Thomas M. , Majumdar Sharmila 
Published: December 2011

AbstractPurpose:To show the feasibility of assessing the spatial distribution of skeletal muscle adipose tissue using chemical shift‐based water/fat separation and to characterize differences in calf intermuscular adipose tissue (IMAT) compartmentalization in patients with type 2 diabetes mellitus (T2DM) compared to healthy age‐matched controls.Materials and Methods:A chemical shift‐based water/fat separation approach using a multiecho 3D spoiled gradient echo sequence was applied in a study of 64 patients, including 35 healthy controls and 29 subjects with T2DM. Masks were defined based on manual segmentations to compute fat volume within different compartments, including regions of subcutaneous adipose tissue (SAT) and six muscular regions. IMAT was divided into two compartments representing fat within the muscular regions (intraMF) and fat between the muscular regions (interMF). Two‐sample Student's t‐tests were used to compare fat volumes between the two groups.Results:The subjects with T2DM had a lower volume of SAT compared to the healthy controls (P = 4 × 10−5). There was no statistically significant difference in the IMAT volume between the two groups. However, the intraMF volume normalized by the IMAT volume was higher in the diabetics compared to the controls (P = 0.006).Conclusion:Chemical shift‐based water/fat separation enables the quantification of fat volume within localized muscle regions, showing that the IMAT regional distribution is significantly different in T2DM compared to normal controls. J. Magn. Reson. Imaging 2012;35:899–907. © 2011 Wiley Periodicals, Inc.
Study of photorespiration in marine microalgae through the determination of glycolic acid using hydrophilic interaction liquid chromatography
Authors: Rigobello‐Masini Marilda , Penteado José C. P. , Tiba Maurício , Masini Jorge C. 
Published: December 2011

AbstractDetermination of organic acids in intracellular extracts and in the cultivation media of marine microalgae aid investigations about metabolic routes related to assimilation of atmospheric carbon by these organisms, which are known by their role in the carbon dioxide sink. The separation of these acids was investigated by hydrophilic interaction liquid chromatography (HILIC) using isocratic elution with a mobile phase composed of 70:30 v/v acetonitrile/20 mmol/L ammonium acetate buffer (pH 6.8) and detection at 220 nm. HILIC allowed the determinations of glycolic acid, the most important metabolite for the evaluation of the photorespiration process in algae, to be made with better selectivity than that achieved by reversed phase liquid chromatography, but with less detectability. The concentration of glycolic acid was determined in the cultivation media and in intracellular extracts of the algae Tetraselmis gracilis and Phaeodactylum tricornutum submitted to different conditions of aeration: (i) without forced aeration, (ii) aeration with atmospheric air, and (iii) bubbling with N2. The concentration of glycolic acid had a higher increase as the cultures were aerated with nitrogen, showing higher photorespiratory flux than that occurring in the cultures aerated with atmospheric air.