bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interictal PET and ictal subtraction SPECT: Sensitivity in the detection of seizure foci in patients with medically intractable epilepsy
Authors: Desai Atman , Bekelis Kimon , Thadani Vijay M. , Roberts David W. , Jobst Barbara C. , Duhaime Ann‐Christine , Gilbert Karen , Darcey Terrance M. , Studholme Colin , Siegel Alan 
Published: October 2012

SummaryPurpose: Interictal positron emission tomography (PET) and ictal subtraction single photon emission computed tomography (SPECT) of the brain have been shown to be valuable tests in the presurgical evaluation of epilepsy. To determine the relative utility of these methods in the localization of seizure foci, we compared interictal PET and ictal subtraction SPECT to subdural and depth electrode recordings in patients with medically intractable epilepsy.Methods: Between 2003 and 2009, clinical information on all patients at our institution undergoing intracranial electroencephalography (EEG) monitoring was charted in a prospectively recorded database. Patients who underwent preoperative interictal PET and ictal subtraction SPECT were selected from this database. Patient characteristics and the findings on preoperative interictal PET and ictal subtraction SPECT were analyzed. Sensitivity of detection of seizure foci for each modality, as compared to intracranial EEG monitoring, was calculated.Key Findings: Fifty‐three patients underwent intracranial EEG monitoring with preoperative interictal PET and ictal subtraction SPECT scans. The average patient age was 32.7 years (median 32 years, range 1–60 years). Twenty‐seven patients had findings of reduced metabolism on interictal PET scan, whereas all 53 patients studied demonstrated a region of relative hyperperfusion on ictal subtraction SPECT suggestive of an epileptogenic zone. Intracranial EEG monitoring identified a single seizure focus in 45 patients, with 39 eventually undergoing resective surgery. Of the 45 patients in whom a seizure focus was localized, PET scan identified the same region in 25 cases (56% sensitivity) and SPECT in 39 cases (87% sensitivity). Intracranial EEG was concordant with at least one study in 41 cases (91%) and both studies in 23 cases (51%). In 16 (80%) of 20 cases where PET did not correlate with intracranial EEG, the SPECT study was concordant. Conversely, PET and intracranial EEG were concordant in two (33%) of the six cases where the SPECT did not demonstrate the seizure focus outlined by intracranial EEG. Thirty‐three patients had surgical resection and >2 years of follow‐up, and 21 of these (64%) had Engel class 1 outcome. No significant effect of imaging concordance on seizure outcome was seen.Significance: Interictal PET and ictal subtraction SPECT studies can provide important information in the preoperative evaluation of medically intractable epilepsy. Of the two studies, ictal subtraction SPECT appears to be the more sensitive. When both studies are used together, however, they can provide complementary information.
Research on Mediator Style: A Summary and Some Research Suggestions
Authors: Wall James , Kressel Kenneth 
Published: October 2012

AbstractEmpirical research on mediator style, after promising beginnings, has not kept pace with the significant and continuing interest of mediation practitioners in mediator stylistic behavior and thinking. In the hopes of closing the research‐practice gap, we consider the practical and conceptual importance of conducting research on mediator style. We then present an overview of what is known empirically about mediator stylistic behavior, with an emphasis on the research papers in this volume. Those papers address three major issues: (a) What mediators say about their stylistic preferences; (b) the degree to which mediators show stylistically flexibility; and (c) the relative impact of mediator style on the process and outcomes of mediation. We thenconsider why the empirical record on mediator style is still relatively weak, and we offer suggestions for moving forward along more vigorous research lines.
Phase IV study comparing incobotulinumtoxinA and onabotulinumtoxinA using a 1:1.5 dose‐conversion ratio for the treatment of glabellar frown lines
Authors: Prager Welf , Rappl Thomas 
Published: October 2012

SummaryBackgroundIncobotulinumtoxinA and onabotulinumtoxinA are effective treatments for glabellar frown lines, and a dose of 20 U is recommended for both preparations. However, debate continues over using the same dosages of these products, although a 1:1 dose ratio has been proven in several head‐to‐head clinical trials in neurological and esthetic indications.ObjectivesTo investigate whether a 50% higher dose of onabotulinumtoxinA was nonsuperior to incobotulinumtoxinA in the treatment of glabellar frown lines in the short and long term.Methods and materialsSubjects aged 18–65 years with symmetrical moderate‐to‐severe glabellar frown lines (score: ≥2 on a validated Merz 5‐point scale) at maximum frown were enrolled. Corrugator muscles on both sides were treated with two injections of either 4 U incobotulinumtoxinA or 6 U onabotulinumtoxinA (equivalent to 20 and 30 U, respectively, if corrugator muscles on both sides and the procerus are treated) allowing intra‐individual comparison. Glabellar frown line severity was assessed from standardized photographs every 4 weeks for 4 months and, in a subset of subjects, for up to 6 months posttreatment. The primary efficacy endpoint was the percentage of subjects with an improvement of ≥1 point on the 5‐point scale at week 4. Nonsuperiority was assessed by comparing the response rates of each product.ResultsNonsuperiority of a 50% higher dose of onabotulinumtoxinA to that of incobotulinumtoxinA was confirmed at 4 weeks, 4 months, and 6 months posttreatment.ConclusionThere is generally no reason to increase the dose of either incobotulinumtoxinA or onabotulinumtoxinA above the 20 U recommended for glabellar frown lines.
Adenylate Kinase Release as a High-Throughput-Screening-Compatible Reporter of Bacterial Lysis for Identification of Antibacterial Agents
Authors: Jacobs Anna C. , DiDone Louis , Jobson Jennielle , Sofia Madeline K. , Krysan Damian , Dunman Paul M. 
Published: October 2012

ABSTRACT

Adenylate kinase (AK) is a ubiquitous intracellular enzyme that is released into the extracellular space upon cell lysis. We have shown that AK release serves as a useful reporter of bactericidal agent activity and can be exploited for antimicrobial screening purposes. The AK assay exhibits improved sensitivity over that of growth-based assays and can detect agents that are active against bacteria in clinically relevant growth states that are difficult to screen using conventional approaches, such as small colony variants (SCV) and bacteria within established biofilms. The usefulness of the AK assay was validated by screening a library of off-patent drugs for agents that exhibit antimicrobial properties toward a variety of bacterial species, including
Escherichia coli
and all members of the “ESKAPE” pathogens (E
nterococcus faecium
, S
taphylococcus aureus
, K
lebsiella pneumoniae
, A
cinetobacter baumannii
, P
seudomonas aeruginosa
, and E
nterobacter
species). The assay detected antibiotics within the library that were expected to be active against the organism screened. Moreover, 38 drugs with no previously reported antibacterial activity elicited AK release. Four of these were acquired, and all were verified to exhibit antimicrobial activity by standard susceptibility testing. Two of these molecules were further characterized. The antihistamine, terfenadine, was active against
S. aureus
planktonic, SCV population, and biofilm-associated cells. Tamoxifen, an estrogen receptor antagonist, was active toward
E. faecium
in vitro
and also reduced
E. faecium
pathogenesis in a
Galleria mellonella
infection model. Our data demonstrate that the AK assay provides an attractive screening approach for identifying new antimicrobial agents. Further, terfenadine and tamoxifen may represent novel antimicrobial drug development scaffolds.
Thiol Peroxidase Is an Important Component of Streptococcus pneumoniae in Oxygenated Environments
Authors: Hajaj Barak , Yesilkaya Hasan , Benisty Rachel , David Maayan , Andrew Peter W. , Porat Nurith 
Published: October 2012

ABSTRACT

Streptococcus pneumoniae
is an aerotolerant Gram-positive bacterium that causes an array of diseases, including pneumonia, otitis media, and meningitis. During aerobic growth,
S. pneumoniae
produces high levels of H
2
O
2
. Since
S. pneumoniae
lacks catalase, the question of how it controls H
2
O
2
levels is of critical importance. The
psa
locus encodes an ABC Mn
2+
-permease complex (
psaBCA
) and a putative thiol peroxidase,
tpxD
. This study shows that
tpxD
encodes a functional thiol peroxidase involved in the adjustment of H
2
O
2
homeostasis in the cell. Kinetic experiments showed that recombinant TpxD removed H
2
O
2
efficiently. However,
in vivo
experiments revealed that TpxD detoxifies only a fraction of the H
2
O
2
generated by the pneumococcus. Mass spectrometry analysis demonstrated that TpxD Cys
58
undergoes selective oxidation
in vivo
, under conditions where H
2
O
2
is formed, confirming the thiol peroxidase activity. Levels of TpxD expression and synthesis
in vitro
were significantly increased in cells grown under aerobic versus anaerobic conditions. The challenge with D39 and TIGR4 with H
2
O
2
resulted in
tpxD
upregulation, while
psaBCA
expression was oppositely affected. However, the challenge of Δ
tpxD
mutants with H
2
O
2
did not affect
psaBCA
, implying that TpxD is involved in the regulation of the
psa
operon, in addition to its scavenging activity. Virulence studies demonstrated a notable difference in the survival time of mice infected intranasally with D39 compared to that of mice infected intranasally with D39Δ
tpxD
. However, when bacteria were administered directly into the blood, this difference disappeared. The findings of this study suggest that TpxD constitutes a component of the organism's fundamental strategy to fine-tune cellular processes in response to H
2
O
2
.
Dynamically dispatching speculative threads to improve sequential execution
Authors: Luo Yangchun , Zhai Antonia 
Published: October 2012

Efficiently utilizing multicore processors to improve their performance potentials demands extracting thread-level parallelism from the applications. Various novel and sophisticated execution models have been proposed to extract thread-level parallelism from sequential programs. One such execution model, Thread-Level Speculation (TLS), allows potentially dependent threads to execute speculatively in parallel.

However, TLS execution is inherently unpredictable, and consequently incorrect speculation could degrade performance for the multicore systems. Existing approaches have focused on using the compilers to select sequential program regions to apply TLS. Our research shows that even the state-of-the-art compiler makes suboptimal decisions, due to the unpredictability of TLS execution. Thus, we propose to
dynamically
optimize TLS performance.

This article describes the design, implementation, and evaluation of a runtime thread dispatching mechanism that adjusts the behaviors of speculative threads based on their efficiency. In the proposed system, speculative threads are monitored by hardware-based performance counters and their performance impact is evaluated with a novel methodology that takes into account various unique TLS characteristics. Thread dispatching policies are devised to adjust the behaviors of speculative threads accordingly.
With the help of the runtime evaluation, where and how to create speculative threads is better determined. Evaluated with all the SPEC CPU2000 benchmark programs written in C, the dynamic dispatching system outperforms the state-of-the-art compiler-based thread management techniques by 9.4% on average. Comparing to sequential execution, we achieve 1.37X performance improvement on a four-core CMP-based system.
The Metabolomic Signature of Malignant Glioma Reflects Accelerated Anabolic Metabolism
Authors: Chinnaiyan Prakash , Kensicki Elizabeth , Bloom Gregory , Prabhu Antony , Sarcar Bhaswati , Kahali Soumen , Eschrich Steven , Qu Xiaotao , Forsyth Peter , Gillies Robert 
Published: October 2012

Abstract
Although considerable progress has been made toward understanding glioblastoma biology through large-scale genetic and protein expression analyses, little is known about the underlying metabolic alterations promoting their aggressive phenotype. We conducted global metabolomic profiling on patient-derived glioma specimens and identified specific metabolic programs differentiating low- and high-grade tumors, with the metabolic signature of glioblastoma reflecting accelerated anabolic metabolism. When coupled with transcriptional profiles, we identified the metabolic phenotype of the mesenchymal subtype to consist of accumulation of the glycolytic intermediate phosphoenolpyruvate and decreased pyruvate kinase activity. Unbiased hierarchical clustering of metabolomic profiles identified three subclasses, which we term energetic, anabolic, and phospholipid catabolism with prognostic relevance. These studies represent the first global metabolomic profiling of glioma, offering a previously undescribed window into their metabolic heterogeneity, and provide the requisite framework for strategies designed to target metabolism in this rapidly fatal malignancy. Cancer Res; 72(22); 5878–88. ©2012 AACR.
Variation in Warfarin Dose Adjustment Practice Is Responsible for Differences in the Quality of Anticoagulation Control Between Centers and Countries
Authors: Van Spall Harriette G.C. , Wallentin Lars , Yusuf Salim , Eikelboom John W. , Nieuwlaat Robby , Yang Sean , Kabali Conrad , Reilly Paul A. , Ezekowitz Michael D. , Connolly Stuart J. 
Published: October 2012

Background—
The outcome of atrial fibrillation patients on warfarin partially depends on maintaining adequate time in therapeutic International Normalized Ratio range (TTR). Large differences in TTR have been reported between centers and countries. The association between warfarin dosing practice, TTR, and clinical outcomes was evaluated in Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial patients receiving warfarin.

Methods and Results—

RE-LY provided an algorithm for warfarin dosing, recommending no change for in-range, and 10% to 15% weekly dose changes for out-of-range International Normalized Ratio values. We determined whether dose adjustments were consistent with algorithm recommendations but could not verify whether providers used the algorithm. Using multilevel regression models to adjust for patient, center, and country characteristics, we assessed whether algorithm-consistent warfarin dosing could predict patient TTR and the composite outcome of stroke, systemic embolism, or major hemorrhage. We included 6022 nonvalvular atrial fibrillation patients from 912 centers in 44 countries. We found a strong association between the proportion of algorithm-consistent warfarin doses and mean country TTR (
R
2
=0.65). The degree of algorithm-consistency accounted for 87% of the between-center and 55% of the between-country TTR variation. Each 10% increase in center algorithm-consistent dosing independently predicted a 6.12% increase in TTR (95% confidence interval, 5.65–6.59) and an 8% decrease in rate of the composite clinical outcome (hazard ratio, 0.92; 95% confidence interval, 0.85–1.00).

Conclusions—
Adherence, intentional or not, to a simple warfarin dosing algorithm predicts improved TTR and accounts for considerable TTR variation between centers and countries. Systems facilitating algorithm-based warfarin dosing could optimize anticoagulation quality and improve clinical outcomes in atrial fibrillation on a global scale.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00262600.
Does the sliding dichotomy result in higher powered clinical trials for stroke and traumatic brain injury research?
Authors: Price Megan , Hertzberg Vicki , Wright David W 
Published: October 2012

Background Recent research has proposed a new method for defining a favorable outcome in traumatic brain injury and stroke research. Purpose This new method is called the sliding dichotomy, and it is suggested as a potential solution to the problem of underpowered clinical trials. Methods We present a brief simulation study and graphical comparison of the power of each method to detect varying treatment effect sizes. Results Simulations of a patient population similar to the National Acute Brain Injury Study: Hypothermia (NABISH) study indicate that the sliding dichotomy method does not result in higher power than traditional methods. Conclusions Although the sliding dichotomy may present gains in power in some cases, several aspects of the patient population need to be considered in choosing between sliding dichotomy and traditional definitions of favorable outcomes.
Development and validation of an International Prognostic Score of thrombosis in World Health Organization–essential thrombocythemia (IPSET-thrombosis)
Authors: Barbui Tiziano , Finazzi Guido , Carobbio Alessandra , Thiele Juergen , Passamonti Francesco , Rumi Elisa , Ruggeri Marco , Rodeghiero Francesco , Randi Maria Luigia , Bertozzi Irene , Gisslinger Heinz , Buxhofer-Ausch Veronika , De Stefano Valerio , Betti Silvia , Rambaldi Alessandro , Vannucchi Alessandro M. , Tefferi Ayalew 
Published: October 2012

Abstract
Accurate prediction of thrombosis in essential thrombocythemia (ET) provides the platform for prospective studies exploring preventive measures. Current risk stratification for thrombosis in ET is 2-tiered and considers low- and high-risk categories based on the respective absence or presence of either age > 60 years or history of thrombosis. In an international study of 891 patients with World Health Organization (WHO)–defined ET, we identified additional independent risk factors including cardiovascular risk factors and JAK2V617F. Accordingly, we assigned risk scores based on multivariable analysis–derived hazard ratios (HRs) to age > 60 years (HR = 1.5; 1 point), thrombosis history (HR = 1.9; 2 points), cardiovascular risk factors (HR = 1.6; 1 point), and JAK2V617F (HR = 2.0; 2 points) and subsequently devised a 3-tiered prognostic model (low-risk = < 2 points; intermediate-risk = 2 points; and high-risk = > 2 points) using a training set of 535 patients and validated the results in the remaining cohort (n = 356; internal validation set) and in an external validation set (n = 329). Considering all 3 cohorts (n = 1220), the 3-tiered new prognostic model (low-risk n = 474 vs intermediate-risk n = 471 vs high-risk n = 275), with a respective thrombosis risk of 1.03% of patients/y versus 2.35% of patients/y versus 3.56% of patients/y, outperformed the 2-tiered (low-risk 0.95% of patients/y vs high-risk 2.86% of patients/y) conventional risk stratification in predicting future vascular events.
Optimization of a direct spectrophotometric method to investigate the kinetics and inhibition of sialidases
Authors: Hayre Jasvinder Kaur , Xu Guogang , Borgianni Luisa , Taylor Garry L , Andrew Peter W , Docquier Jean-Denis , Oggioni Marco R 
Published: October 2012

Abstract

Backgrounds

Streptococcus pneumoniae expresses three distinct sialidases, NanA, NanB, and NanC, that are believed to be key virulence factors and thus, potential important drug targets. We previously reported that the three enzymes release different products from sialosides, but could share a common catalytic mechanism before the final step of product formation. However, the kinetic investigations of the three sialidases have not been systematically done thus far, due to the lack of an easy and steady measurement of sialidase reaction rate.

Results
In this work, we present further kinetic characterization of pneumococcal sialidases by using a direct spectrophotometric method with the chromogenic substrate p-nitrophenyl-N-acetylneuraminic acid (p- NP-Neu5Ac). Using our assay, the measured kinetic parameters of the three purified pneumococcal sialidase, NanA, NanB and NanC, were obtained and were in perfect agreement with the previously published data. The major advantage of this alternative method resides in the direct measurement of the released product, allowing to readily determine of initial reaction rates and record complete hydrolysis time courses.

Conclusion
We developed an accurate, fast and sensitive spectrophotometric method to investigate the kinetics of sialidase-catalyzed reactions. This fast, sensitive, inexpensive and accurate method could benefit the study of the kinetics and inhibition of sialidases in general.
Downregulation of Cyclophilin A by siRNA diminishes non-small cell lung cancer cell growth and metastasis via the regulation of matrix metallopeptidase 9
Authors: Qian Zhe , Zhao Xiaoting , Jiang Mei , Jia Wenyun , Zhang Chunyan , Wang Yue , Li Baolan , Yue Wentao 
Published: October 2012

Abstract

Background
Cyclophilin A (CypA) is a cytosolic protein possessing peptidyl-prolyl isomerase activity that was recently reported to be overexpressed in several cancers. Here, we explored the biology and molecular mechanism of CypA in non-small cell lung cancer (NSCLC).

Methods
The expression of CypA in human NSCLC cell lines was detected by real-time reverse transcription PCR. The RNA interference-mediated knockdown of CypA was established in two NSCLC cell lines (95C and A549). 239836 CypA inhibitor was also used to suppress CypA activity. Tumorigenesis was assessed based on cellular proliferation, colony formation assays, and anchorage-independent growth assays; metastasis was assessed based on wound healing and transwell assays.

Results
Suppression of CypA expression inhibited the cell growth and colony formation of A549 and 95C cells. CypA knockdown resulted in the inhibition of cell motility and invasion. Significantly, we show for the first time that CypA increased NSCLC cell invasion by regulating the activity of secreted matrix metallopeptidase 9 (MMP9). Likewise, suppression of CypA with 239836 CypA inhibitor decreased cell proliferation and MMP9 activity.

Conclusions
The suppression of CypA expression was correlated with decreased NSCLC cell tumorigenesis and metastasis.