bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isothermal Microcalorimetry To Study Drugs against Schistosoma mansoni
Authors: Manneck Theresia , Braissant Olivier , Haggenmüller Yolanda , Keiser Jennifer 
Published: January 2011

ABSTRACT

Alternative antischistosomal drugs are required since praziquantel is virtually the only drug available for treatment and morbidity control of schistosomiasis. Manual microscopic reading is the current “gold standard” to assess the
in vitro
antischistosomal properties of test drugs; however, it is labor-intensive, subjective, and difficult to standardize. Hence, there is a need to develop novel tools for antischistosomal drug discovery. The
in vitro
effects of praziquantel, oxamniquine, artesunate, and mefloquine on metabolic activity and parasite motility of
Schistosoma mansoni
(newly transformed schistosomula [NTS] and 49-day-old adult worms) were studied using isothermal microcalorimetry (IMC). Results were compared to morphological readouts of viability. Results obtained for the four drugs tested with phenotypic evaluation by microscopy and IMC showed a good correlation, but IMC also identified drug effects that were not visible by microscopic evaluation, and IMC precisely determined the onset of action of the test drugs. Similar sensitivities on NTS and adult schistosomes were observed for praziquantel and mefloquine, while slight differences in the drug susceptibilities of the two developmental stages were noted with oxamniquine and artesunate. IMC is a useful tool for antischistosomal drug discovery that should be further validated. In addition, our data support the use of NTS in
in vitro
antischistosomal drug assays.
Assessment of Impact of Peptide Nucleic Acid Fluorescence In Situ Hybridization for Rapid Identification of Coagulase-Negative Staphylococci in the Absence of Antimicrobial Stewardship Intervention
Authors: Holtzman Carol , Whitney Dana , Barlam Tamar , Miller Nancy S. 
Published: January 2011

ABSTRACT

Peptide nucleic acid fluorescence
in situ
hybridization (PNA FISH) was instituted at Boston Medical Center for the rapid identification of coagulase-negative staphylococci (CoNS). Without active notification or antimicrobial stewardship intervention, a pre- and postimpact analysis showed no benefit of this assay with respect to the length of hospital stay or vancomycin use.
Three Cases of Severe Invasive Infections Caused by Campylobacter rectus and First Report of Fatal C. rectus Infection
Authors: Lam Jimmy Y. W. , Wu Alan K. L. , Ngai Dickson C. , Teng Jade L. L. , Wong Elsa S. Y. , Lau Susanna K. P. , Lee Rodney A. , Woo Patrick C. Y. 
Published: January 2011

ABSTRACT

We report the first fatal case of
Campylobacter rectus
infection due to a subdural empyema and ruptured mycotic intracranial aneurysm and two cases of limb-threatening
C. rectus
necrotizing soft tissue and bone infection and empyema thoracis that responded to amoxicillin-clavulanate and surgical debridement and drainage. All three strains were identified by 16S rRNA sequencing.
Replication ofAvocado Sunblotch Viroidin the YeastSaccharomyces cerevisiae
Authors: Delan-Forino Clémentine , Maurel Marie-Christine , Torchet Claire 
Published: January 2011

ABSTRACTViroids are the smallest known pathogenic agents. They are noncoding, single-stranded, closed-circular, “naked” RNAs, which replicate through RNA-RNA transcription. Viroids of theAvsunviroidaefamily possess a hammerhead ribozyme in their sequence, allowing self-cleavage during their replication. To date, viroids have only been detected in plant cells. Here, we investigate the replication ofAvocado sunblotch viroid(ASBVd) of theAvsunviroidaefamily in a nonconventional host, the yeastSaccharomyces cerevisiae. We demonstrate that ASBVd RNA strands of both polarities are able to self-cleave and to replicate in a unicellular eukaryote cell. We show that the viroid monomeric RNA is destabilized by the nuclear 3′ and the cytoplasmic 5′ RNA degradation pathways. For the first time, our results provide evidence that viroids can replicate in other organisms than plants and that yeast contains all of the essential cellular elements for the replication of ASBVd.
Prognostic significance and potential therapeutic target of VEGFR2 in hepatocellular carcinoma
Authors: Huang Jianfei , Zhang Xialing , Tang Qi , Zhang Feng , Li Yuhua , Feng Zhenqing , Zhu Jin 
Published: January 2011

BackgroundVascular endothelial growth factor receptor 2 (VEGFR2) has been suggested to play an important role in solid tumours. Although several reports have shown the relationship between VEGFR2 expression and hepatocellular carcinoma (HCC), the expression pattern of VEGFR2 in HCC parenchyma or stroma, as well as the relationship between VEGFR2 expression and clinicopathological characteristics in HCC, are yet to be satisfactorily defined.MethodsOne-step real-time PCR, western blotting and immunohistochemistry were used to characterise the expression of VEGFR2 in HCC using a self-made anti-VEGFR2 monoclonal antibody (A8H1).ResultsExpression of VEGFR2 in HCC cells was higher than in hepatic cells (p<0.001). Comparison of clinicopathological characteristics and immunohistochemistry by χ2test analysis showed that the high expression of VEGFR2 in HCC was related to large tumour diameter (p=0.012), poor differentiation (p=0.007), high serum α-fetoprotein (p=0.029), multifocal gross classification (p=0.007), and less than 5 years' survival (p=0.029). Kaplan–Meier survival and Cox regression analyses showed that high VEGFR2 expression (p=0.009) and stage grouping with TNM classification (p=0.004) were independent prognotic factors.ConclusionsThe efficacy of A8H1 in immunohistochemistry using HCC tissues was confirmed. There was a correlation of high VEGFR2 expression with prognostic significance in HCC. Additionally, the self-made anti-VEGFR2 monoclonal antibody could be used for future anti-HCC-targeted therapy research.
A prospective randomized single-blind trial of patient comfort following vessel closure: extravascular synthetic sealant closure provides less pain than a self-tightening suture vascular compression device
Authors: Fargen Kyle M , Hoh Brian L , Mocco J 
Published: January 2011

Background and purposeThe Mynx M5 (AccessClosure, Inc., Mountain View, California, USA), a novel vascular closure device (VCD) utilizing extravascular synthetic sealant, may effectively seal the arteriotomy while reducing the pain associated with arteriotomy closure seen with other VCDs. To date, no studies exist comparing the pain associated with deployment between differing VCDs as a primary end point.MethodsA blinded, randomized controlled trial was performed comparing the Mynx and a popular VCD that utilizes a self-tightening suture, the Angio-Seal Evolution (St Jude Medical, St Paul, Minnesota, USA). Subjects were all adult patients undergoing diagnostic cerebral angiography via femoral access. Local anesthesia and intraprocedural intravenous pain medication were standardized. Pain was assessed using a horizontal visual analog scale both before and after VCD deployment.Results64 patients were enrolled with 32 in each treatment arm. Both pain at closure and pain increase from baseline to closure were significantly higher in the Angio-Seal group (p=0.009 and 0.002, respectively). 88% of patients receiving an Angio-Seal reported closure as the most painful part of the procedure compared with only 34% of patients receiving the Mynx (p<0.001). No adverse events were detected in either treatment arm.ConclusionsIn a blinded, randomized trial comparing the Mynx with the Angio-Seal Evolution, pain with device deployment at arteriotomy closure was significantly lower with the Mynx. The reason for the large pain gradient between groups is likely due to the presence, and absence, of compression elements within the Angio-Seal and Mynx, respectively.
Activation of the Aryl Hydrocarbon Receptor AhR Promotes Retinoic Acid–Induced Differentiation of Myeloblastic Leukemia Cells by Restricting Expression of the Stem Cell Transcription Factor Oct4
Authors: Bunaciu Rodica P. , Yen Andrew 
Published: January 2011

AbstractRetinoic acid (RA) is used to treat leukemia and other cancers through its ability to promote cancer cell differentiation. Strategies to enhance the anticancer effects of RA could deepen and broaden its beneficial therapeutic applications. In this study, we describe a receptor cross-talk system that addresses this issue. RA effects are mediated by RAR/RXR receptors that we show are modified by interactions with the aryl hydrocarbon receptor (AhR), a protein functioning both as a transcription factor and a ligand-dependent adaptor in an ubiquitin ligase complex. RAR/RXR and AhR pathways cross-talk at the levels of ligand–receptor and also receptor–promoter interactions. Here, we assessed the role of AhR during RA-induced differentiation and a hypothesized convergence at Oct4, a transcription factor believed to maintain stem cell characteristics. RA upregulated AhR and downregulated Oct4 during differentiation of HL-60 promyelocytic leukemia cells. AhR overexpression in stable transfectants downregulated Oct4 and also decreased ALDH1 activity, another stem cell–associated factor, enhancing RA-induced differentiation as indicated by cell differentiation markers associated with early (CD38 and CD11b) and late (neutrophilic respiratory burst) responses. AhR overexpression also increased levels of activated Raf1, which is known to help propel RA-induced differentiation. RNA interference-mediated knockdown of Oct4 enhanced RA-induced differentiation and G0 cell-cycle arrest relative to parental cells. Consistent with the hypothesized importance of Oct4 downregulation for differentiation, parental cells rendered resistant to RA by biweekly high RA exposure displayed elevated Oct4 levels that failed to be downregulated. Together, our results suggested that therapeutic effects of RA-induced leukemia differentiation depend on AhR and its ability to downregulate the stem cell factor Oct4. Cancer Res; 71(6); 2371–80. ©2011 AACR.
MGMT Is a Molecular Determinant for Potency of the DNA-EGFR–Combi-Molecule ZRS1
Authors: Huang Ying , Rachid Zakaria , Jean-Claude Bertrand J. 
Published: January 2011

Abstract
To enhance the potency of current EGFR inhibitors, we developed a novel strategy that seeks to confer them an additional DNA damaging function, leading to the design of drugs termed combi-molecules. ZRS1 is a novel combi-molecule that contains an EGFR tyrosine kinase targeting quinazoline arm and a methyltriazene-based DNA damaging one. We examined its effect on human tumor cell lines with varied levels of EGFR and O6-methylguanine DNA methyltransferase (MGMT). ZRS1 was more potent than the clinical methylating agent temozolomide in all cell lines, regardless of their MGMT status. However, its potency was in the same range as or less than that of Iressa, an EGFR inhibitor, against MGMT-proficient cells. In the MGMT-deficient or in MGMT-proficient cells exposed to the MGMT inhibitor O6-benzylguanine, its potency was superior to that of Iressa and temozolomide or a temozolomide+Iressa combination. Cell signaling analysis in A549 (MGMT+) and A427 (MGMT−) showed that ZRS1 strongly inhibited EGFR phosphorylation and related signaling pathways. In addition, the p53 pathway was activated by DNA damage in both cell lines, but apoptosis was significantly more pronounced in A427 cells. Using MGMT shRNA to block endogenous MGMT protein expression in A549 resulted in significant sensitization to ZRS1. Furthermore, transfection of MGMT into A427 greatly decreased the potency of ZRS1. These results conclusively show that MGMT is a critical molecular determinant for the full-blown potency of the dual EGFR-DNA targeting combi-molecule. Mol Cancer Res; 9(3); 320–31. ©2011 AACR.
Left Ventricular Filling Pressure Assessment Using Left Atrial Transit Time by Cardiac Magnetic Resonance Imaging
Authors: Cao Jie J. , Wang Yi , McLaughlin Jeannette , Haag Elizabeth , Rhee Peter , Passick Michael , Toole Rena , Cheng Joshua , Berke Andrew D. , Lachman Justine , Reichek Nathaniel 
Published: January 2011

Background—
Left atrial (LA) size and function reflect left ventricular (LV) hemodynamics. In the present study, we developed a novel method to determine LA circulation transit time (LATT) by MRI and demonstrated its close association with LV filling pressure.

Methods and Results—

All subjects were prospectively recruited and underwent contrast-enhanced MR dynamic imaging. Mean LATT was determined as the time for contrast to transit through the LA during the first pass. In an invasive study group undergoing clinically indicated cardiac catheterization (n=25), LATT normalized by R-R interval (nLATT) was closely associated with LV early diastolic pressure (
r
=0.850,
P
=0.001), LV end-diastolic pressure (
r
=0.910,
P
<0.001), and mean diastolic pressure (
r
=0.912,
P
<0.001). In a larger noninvasive group (n=56), nLATT was prolonged in patients with LV systolic dysfunction (n=47) (10.1±3.0 versus 6.6±0.7 cardiac cycles in normal control subjects, n=9;
P
<0.001). Using a linear regression equation derived from the invasive group, noninvasive subjects were divided into 3 subgroups by estimated LV end-diastolic pressure: ≤10 mm Hg, 11 to 14 mm Hg, and ≥15 mm Hg. There were graded increases from low to high LV end-diastolic pressure subgroups in echocardiographic mitral medial E/e′ ratio: 9±5, 11±4, and 13±3 (
P
=0.023); in B-type natriuretic peptide (interquartile range): 44 (60) pg/mL, 87 (359) pg/mL, and 371 (926) pg/mL (
P
=0.002); and in N-terminal pro–B-type natriuretic peptide: 57 (163) pg/mL, 208 (990) pg/mL, and 931 (1726) pg/mL (
P
=0.002), demonstrating the ability of nLATT to assess hemodynamic status.

Conclusions—
nLATT by cardiac MR is a promising new parameter of LV filling pressure that may provide graded noninvasive hemodynamic assessment.
Dishabituation of Laser-evoked EEG Responses: Dissecting the Effect of Certain and Uncertain Changes in Stimulus Modality
Authors: Valentini Elia , Torta Diana M. E. , Mouraux André , Iannetti Gian Domenico 
Published: January 2011

Abstract
The repetition of nociceptive stimuli of identical modality, intensity, and location at short and constant interstimulus intervals (ISIs) determines a strong habituation of the corresponding EEG responses, without affecting the subjective perception of pain. To understand what determines this response habituation, we (i) examined the effect of introducing a change in the modality of the repeated stimulus, and (ii) dissected the relative contribution of bottom–up, stimulus-driven changes in modality and top–down, cognitive expectations of such a change, on both laser-evoked and auditory-evoked EEG responses. Multichannel EEG was recorded while participants received trains of three stimuli (S1–S2–S3, a triplet) delivered to the hand dorsum at 1-sec ISI. S3 belonged either to the same modality as S1 and S2 or to the other modality. In addition, participants were either explicitly informed or not informed of the modality of S3. We found that introducing a change in stimulus modality produced a significant dishabituation of the laser-evoked N1, N2, and P2 waves; the auditory N1 and P2 waves; and the laser- and auditory-induced event-related synchronization and desynchronization. In contrast, the lack of explicit knowledge of a possible change in the sensory modality of the stimulus (i.e., uncertainty) only increased the ascending portion of the laser-evoked and auditory-evoked P2 wave. Altogether, these results indicate that bottom–up novelty resulting from the change of stimulus modality, and not top–down cognitive expectations, plays a major role in determining the habituation of these brain responses.
Color, Context, and Cognitive Style: Variations in Color Knowledge Retrieval as a Function of Task and Subject Variables
Authors: Hsu Nina S. , Kraemer David J. M. , Oliver Robyn T. , Schlichting Margaret L. , Thompson-Schill Sharon L. 
Published: January 2011

Abstract
Neuroimaging tests of sensorimotor theories of semantic memory hinge on the extent to which similar activation patterns are observed during perception and retrieval of objects or object properties. The present study was motivated by the hypothesis that some of the seeming discrepancies across studies reflect flexibility in the systems responsible for conceptual and perceptual processing of color. Specifically, we test the hypothesis that retrieval of color knowledge can be influenced by both context (a task variable) and individual differences in cognitive style (a subject variable). In Experiment 1, we provide fMRI evidence for differential activity during color knowledge retrieval by having subjects perform a verbal task, in which context encouraged subjects to retrieve more- or less-detailed information about the colors of named common objects in a blocked experimental design. In the left fusiform, we found more activity during retrieval of more- versus less-detailed color knowledge. We also assessed preference for verbal or visual cognitive style, finding that brain activity in the left lingual gyrus significantly correlated with preference for a visual cognitive style. We replicated many of these effects in Experiment 2, in which stimuli were presented more quickly, in a random order, and in the auditory modality. This illustration of some of the factors that can influence color knowledge retrieval leads to the conclusion that tests of conceptual and perceptual overlap must consider variation in both of these processes.
Mechanism of Concentric Eyewall Replacement Cycles and Associated Intensity Change*
Authors: Zhou Xiaqiong , Wang Bin 
Published: January 2011

Abstract
To understand the mechanisms responsible for the secondary eyewall replacement cycles and associated intensity changes in intense tropical cyclones (TCs), two numerical experiments are conducted in this study with the Weather Research and Forecasting (WRF) model. In the experiments, identical initial conditions and model parameters are utilized except that the concentration of ice particles is enhanced in the sensitivity run. With enhanced ice concentrations, it is found that the secondary eyewall forms at an increased radius, the time required for eyewall replacement is extended, and the intensity fluctuation is relatively large. The enhanced concentrations of ice particles at the upper tropospheric outflow layer produces a noticeable subsidence region (moat) surrounding the primary eyewall. The presence of the moat forces the secondary eyewall to form at a relatively large radius. The axisymmetric equivalent potential temperature budget analysis reveals that the demise of the inner eyewall is primarily due to the interception of the boundary layer inflow supply of entropy by the outer convective ring, whereas the advection of low entropy air from the middle levels to the boundary inflow layers in the moat is not essential. The interception process becomes inefficient when the secondary eyewall is at a large radius; hence, the corresponding eyewall replacement is slow. After the demise of the inner eyewall, the outer eyewall has to maintain a warm core not only in the previous eye, but also in the moat. The presence of low equivalent potential temperature air in the moat results in the significant weakening of storm intensity. The results found here suggest that monitoring the features of the moat and the outer eyewall region can provide a clue for the prediction of TC intensity change associated with eyewall replacement.
High-Resolution Initialization and Simulations of Typhoon Morakot (2009)
Authors: Van Nguyen Hiep , Chen Yi-Leng 
Published: January 2011

A model self-bogus vortex is constructed by cycle runs using the Weather Research and Forecasting (WRF) model to provide high-resolution initial conditions for tropical cyclone (TC) simulations. The vortex after 1 h of model simulation is used to construct the vortex structure for the initial conditions for the next cycle run. After about 80 cycle runs, the TC structure is well adapted to the model employed and well adjusted to the given large-scale conditions. Three separate simulations using three different initial conditions including global analysis (CTRL), the bogus package from WRF (WB), and the new initialization package (NT) are performed for Typhoon Morakot (2009). The NT scheme shows advantages in generating realistic vortex features including sea level pressure, winds, a warm core, and correct TC size with the meteorological fields away from the observed TC center consistent with the global analysis. The NT scheme also shows significant improvements in TC simulations including asymmetric structure, track, intensity, strength of low-level winds, radar reflectivity, and rainfall. For other runs, such as WB and CTRL, the unbalanced initial vortex needs to adjust to the changing environment during the first 2–3 days of model simulations, which is likely to have negative impacts on the track, intensity, and rainfall forecasts in most cases. For all three different types of model initializations, the model is capable of simulating heavy orographic precipitation over southern Taiwan. However, with a better track forecast, only the NT run simulates the high-reflectivity band associated with the convergence zone between Morakot’s circulations and the southwest monsoon off the southeast coast. In addition to Morakot’s slow movement and relatively large size, Typhoons Goni and Etau were embedded within a moist monsoon gyre. The combined circulations associated with the monsoon gyre and tropical storms bring in moisture-laden flows toward the western slopes of southern Taiwan.
Non-hardware Posterior Cruciate Ligament Reconstruction Using Knot/Press-fit Technique With Periosteum-Enveloped Hamstrings Tendon Autograft
Authors: Chuang Tai-Yuan , Ho Wei-Pin , Chen Chih-Hwa , Shieh Ming-Hsin , Liau Jiann-Jong , Huang Chang-Hung 
Published: January 2011

Background: Several posterior cruciate ligament reconstruction procedures have been proposed to manage ruptures. Purpose: This study was intended to present the clinical results of non-hardware reconstruction of posterior cruciate ligament using a knot/press-fit technique with periosteum-enveloped autogenous hamstring tendons. Study Design: Case series; Level of evidence, 4. Methods: This arthroscopically assisted technique was used in 33 patients with posterior cruciate ligament ruptures. In this non-hardware technique, semitendinosus and gracilis tendons were prepared as 2 loops with knots. Each loop was enveloped in periosteum. After passing a bottleneck femoral tunnel, the grafts were fixed with a press-fit method (knotted grafts lodging in the bottleneck of the femoral tunnel). Simultaneously, the intra-articular opening of the tibial tunnel was filled with the periosteum-enveloped portion of the graft. A tie with Mersilene tape over a bone bridge for each tendon loop was used for tibial fixation. Results: The average follow-up was 35 months (range, 24-60 months). Clinical assessments included Tegner score, Lysholm knee score, International Knee Documentation Committee scores, thigh muscle assessment, and radiographic evaluation. The stress radiography results for posterior displacement changed from 13.7 ± 2.1 mm preoperatively to 4.8 ± 1.1 mm postoperatively. Average preinjury Tegner score was 5.9 (range, 3-9), decreasing to 2.9 (range, 2-5) preoperatively and increasing to 5.2 (range, 2-9) postoperatively. The Lysholm score increased from 58.5 ± 5.2 to 94.2 ± 4.1 ( P < .01). Finally, 26 patients (89.7%) were assessed as nearly normal by International Knee Documentation Committee guidelines. Conclusion: The study revealed satisfactory clinical subjective and objective results at a minimum of 2 years’ follow-up. Without using hardware, this alternative technique has the advantage of no need for removal of hardware and potentially easier magnetic resonance imaging interpretation and revision surgery.