bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of dUTPase Induces Synthetic Lethality with Thymidylate Synthase–Targeted Therapies in Non–Small Cell Lung Cancer
Authors: Wilson Peter M. , LaBonte Melissa J. , Lenz Heinz-Josef , Mack Philip C. , Ladner Robert D. 
Published: December 2011

Abstract
Chemotherapies that target thymidylate synthase (TS) continue to see considerable clinical expansion in non–small cell lung cancer (NSCLC). One drawback to TS-targeted therapies is drug resistance and subsequent treatment failure. Novel therapeutic and biomarker-driven strategies are urgently needed. The enzyme deoxyuridine triphosphate nucleotidohydrolase (dUTPase) is reported to protect tumor cells from aberrant misincorporation of uracil during TS inhibition. The goal of this study was to investigate the expression and significance of dUTPase in mediating response to TS-targeted agents in NSCLC. The expression of dUTPase in NSCLC cell lines and clinical specimens was measured by quantitative real-time reverse transcriptase PCR and immunohistochemistry. Using a validated RNA interference approach, dUTPase was effectively silenced in a panel of NSCLC cell lines and response to the fluoropyrimidine fluorodeoxyuridine (FUdR) and the antifolate pemetrexed was analyzed using growth inhibition and clonogenic assays. Apoptosis was analyzed by flow cytometry. Significant variation in the quantity and cellular expression of dUTPase was observed, including clear evidence of overexpression in NSCLC cell line models and tumor specimens at the mRNA and protein level. RNA interference–mediated silencing of dUTPase significantly sensitized NSCLC cells to growth inhibition induced by FUdR and pemetrexed. This sensitization was accompanied by a significant expansion of intracellular dUTP pools and significant decreases in NSCLC cell viability evaluated by clonogenicity and apoptotic analyses. Together, these results strongly suggest that uracil misincorporation is a potent determinant of cytotoxicity to TS inhibition in NSCLC and that inhibition of dUTPase is a mechanism-based therapeutic approach to significantly enhance the efficacy of TS-targeted chemotherapeutic agents. Mol Cancer Ther; 11(3);616–28. ©2011 AACR.
Patent Foramen Ovale Closure and Medical Treatments for Secondary Stroke Prevention
Authors: Kitsios Georgios D. , Dahabreh Issa J. , Abu Dabrh Abd Moain , Thaler David E. , Kent David M. 
Published: December 2011

Background and Purpose—
Patients discovered to have a patent foramen ovale in the setting of a cryptogenic stroke may be treated with percutaneous closure, antiplatelet therapy, or anticoagulants. A recent randomized trial (CLOSURE I) did not detect any benefit of closure over medical treatment alone; the optimal medical therapy is also unknown. We synthesized the available evidence on secondary stroke prevention in patients with patent foramen ovale and cryptogenic stroke.

Methods—
A MEDLINE search was performed for finding longitudinal studies investigating medical treatment or closure, meta-analysis of incidence rates (IR), and IR ratios of recurrent cerebrovascular events.

Results—

Fifty-two single-arm studies and 7 comparative nonrandomized studies and the CLOSURE I trial were reviewed. The summary IR of recurrent stroke was 0.36 events (95% confidence interval [CI], 0.24–0.56) per 100 person-years with closure versus 2.53 events (95% CI, 1.91–3.35) per 100 person-years with medical therapy. In comparative observational studies, closure was superior to medical therapy (IR ratio=0.19; 95% CI, 0.07–0.54). The IR for the closure arm of the CLOSURE I trial was higher than the summary estimate from observational studies; there was no significant benefit of closure over medical treatment (
P
=0.002 comparing efficacy estimates between observational studies and the trial). Observational and randomized data (9 studies) comparing medical therapies were consistent and suggested that anticoagulants are superior to antiplatelets for preventing stroke recurrence (IR ratio=0.42; 95% CI, 0.18–0.98).

Conclusions—
Although further randomized trial data are needed to precisely determine the effects of closure on stroke recurrence, the results of CLOSURE I challenge the credibility of a substantial body of observational evidence strongly favoring mechanical closure over medical therapy.
Sequential changes in neuronal activity in single neocortical neurons after spreading depression
Authors: Ghadiri Maryam Khaleghi , Kozian Martyna , Ghaffarian Nikoo , Stummer Walter , Kazemi Hadi , Speckmann Erwin-Josef , Gorji Ali 
Published: December 2011

Background: Cortical spreading depression (CSD) has an important role in migraine with aura. Prolonged neuronal depression is followed by a late excitatory synaptic plasticity after CSD. Method: Intra- and extracellular recordings were performed to investigate the effect of CSD on intracellular properties of mouse neocortical tissues in the late excitatory period. Results: During CSD, changes in the membrane potentials usually began with a relatively short hyperpolarization followed by an abrupt depolarization. These changes occurred roughly at the same time point after CSD as the beginning of the negative extracellular deflection. Forty-five minutes after CSD, neurons showed significantly smaller amplitude of afterhyperpolarization and a reduced input resistance. Depolarization and hyperpolarization of the cells by constant intracellular current injections in this period significantly changed the frequency of the action potentials. Conclusion: These data indicate higher excitability of the neocortical neurons after CSD, which can be assumed to contribute to hyperexcitability of neocortical tissues in patients suffering from migraine.
Detoxification for medication overuse headache is the primary task
Authors: Olesen Jes 
Published: December 2011

Background: Common practice in patients overusing medication is to place major emphasis on detoxification. Overview: This is based on decades of disappointing experience trying to treat patients with prophylactics despite medication overuse. Several trials have shown that, when patients are taken off medication overuse, approximately 50% of them get so much better that prophylactic drug treatment is no longer needed. There is no doubt that detoxification by one means or another is of crucial importance in the initial steps of treating patients who have a medication overuse. The methodology for detoxification may vary from country to country. Likewise, it varies whether patients are placed on prophylactic treatment simultaneously with detoxification or after a drug-free period of 2 months. Only future long-term studies can show whether one approach or the other is preferable. Conclusion: Detoxification must always be the first consideration in overusing patients, but obviously accompanied by or followed up by the necessary prophylactic or treatment.
Evidence for increased internal noise in migraineurs for contrast and shape processing
Authors: Webster Kathryn E , Dickinson J Edwin , Battista Josephine , McKendrick Allison M , Badcock David R 
Published: December 2011

Aim: Increased contrast-level dependent internal noise has been reported in migraine. This study aimed to investigate whether a general increase in internal noise impacted on other tasks thought to assess functioning in cortical area V1 and was evident in global contour coding (V4). Methods: Eleven migraineurs (six with aura) and 12 headache-free controls completed three psychophysical tasks: (i) contrast detection, (ii) discrimination of the angle of a spiral path and (iii) detection of deformation from circularity. Internal noise estimates were obtained using an N-pass method that compared responses to repeated presentations of identical stimuli. Internal noise results in inconsistent responses across different runs. Results: Migraineurs had significantly higher contrast thresholds when there was high external luminance noise. There were no other significant group differences in thresholds. Increased multiplicative noise associated with contrast processing was replicated and increased additive noise, which is independent of the visual input, was found for the global form task. Conclusions: This study provides further evidence for increased multiplicative internal noise associated with contrast processing in migraineurs. However there is no generalised increase in internal noise in V1 as noise estimates for angular discrimination were normal. Increased additive internal noise was associated with the global shape task, co-occurring with increased efficiency.
Influence of Cell Quality on Clinical Outcome After Autologous Chondrocyte Implantation
Authors: Niemeyer Philipp , Pestka Jan M. , Salzmann Gian M. , Südkamp Norbert P. , Schmal Hagen 
Published: December 2011

Background: Several factors influence clinical outcome after autologous chondrocyte implantation (ACI) for the treatment of cartilage defects of the knee joint. Hypothesis/Purpose: The aim of the present study was to investigate the influence of cell quality on clinical outcome after ACI. The hypothesis of the authors was that cell quality at the time of transplantation influences clinical outcome after ACI for cartilage defects. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 80 patients were included in the present study. Knee function was assessed before surgery as well as 6, 12, and 24 months after ACI using standard instruments (International Knee Documentation Committee [IKDC], Lysholm, and Tegner scores). Cell quality was evaluated by determination of antigen expression of CD44 expression, aggrecan, collagen type II, and cell viability. A linear regression analysis including preoperative knee function, defect size, defect location, defect origin, body mass index, patient age, and other parameters was performed to evaluate the influence of these parameters on postoperative knee function. Results: Preoperative IKDC score increased from 49.6 ± 13.8 points to 75.5 ± 14.6 points at 24 months ( P < .05). Postoperative IKDC score at 6, 12, and 24 months was significantly influenced by collagen type II expression, CD44 expression, and cell viability (all P < .05). No correlation between aggrecan and outcome was found. Quantitative influence of individual factors differed between different time points. Conclusion: Cell quality seems to be one of many factors that influences clinical outcome after ACI in patients with cartilage defects of the knee joint. It constitutes one aspect among various others affecting clinical outcome.
The Role of Axial Compressive and Quadriceps Forces in Noncontact Anterior Cruciate Ligament Injury
Authors: Wall Simon J. , Rose David M. , Sutter E. Grant , Belkoff Stephen M. , Boden Barry P. 
Published: December 2011

Background: Compressive and quadriceps forces have been associated with noncontact anterior cruciate ligament (ACL) injury. The purpose of this study was to quantify the relative importance of each load component during noncontact ACL injury. Hypothesis: We hypothesized that the introduction of a quadriceps force lowers the axial compressive force threshold to produce ACL injury. Study Design: Controlled laboratory study. Methods: Six pairs of fresh-frozen cadaveric knees, flexed to 15°, were loaded with axial compression (group A) or compression with a quadriceps force (group B) until failure. All specimens underwent axial compressive loading under displacement control with a time to peak load of 50 msec. The initial displacement of the MTS actuator was 8 mm and was increased in 2-mm increments with successive tests until catastrophic damage of the joint occurred. Failure was determined by a combination of clinical specimen examination and force-displacement data analysis and by dissection and direct visualization after failure was recognized. Differences in failure load between groups were examined using a paired t test (significance, P ≤ .05). Results: In group A, there were 2 isolated ACL injuries, 2 ACL ruptures combined with a tibial plateau fracture, and 2 isolated tibial plateau fractures. In group B, there were 5 isolated ACL ruptures and 1 tibial plateau fracture. There was a significant difference in the average failure load between groups A and B: 10 832 N (95% confidence interval [CI], 9743-11 604 N) and 6119 N (95% CI, 4335-7903 N), respectively. Conclusion: Isolated compressive forces displayed an ability to produce an ACL injury in this cadaveric model, but the addition of a quadriceps load significantly reduced the compressive force required for ACL injury. Clinical Relevance: Compressive and quadriceps forces contribute to noncontact ACL injury and should be taken into account when developing ACL injury prevention programs and rehabilitation after ACL reconstruction.
Regulation and function of the E-cadherin/catenin complex in cells of the monocyte-macrophage lineage and DCs
Authors: Van den Bossche Jan , Malissen Bernard , Mantovani Alberto , De Baetselier Patrick , Van Ginderachter Jo A. 
Published: December 2011

AbstractE-cadherin is best characterized as adherens junction protein, which through homotypic interactions contributes to the maintenance of the epithelial barrier function. In epithelial cells, the cytoplasmic tail of E-cadherin forms a dynamic complex with catenins and regulates several intracellular signal transduction pathways, including Wnt/β-catenin, PI3K/Akt, Rho GTPase, and NF-κB signaling. Recent progress uncovered a novel and critical role for this adhesion molecule in mononuclear phagocyte functions. E-cadherin regulates the maturation and migration of Langerhans cells, and its ligation prevents the induction of a tolerogenic state in bone marrow-derived dendritic cells (DCs). In this respect, the functionality of β-catenin could be instrumental in determining the balance between immunogenicity and tolerogenicity of DCs in vitro and in vivo. Fusion of alternatively activated macrophages and osteoclasts is also E-cadherin–dependent. In addition, the E-cadherin ligands CD103 and KLRG1 are expressed on DC-, T-, and NK-cell subsets and contribute to their interaction with E-cadherin–expressing DCs and macrophages. Here we discuss the regulation, function, and implications of E-cadherin expression in these central orchestrators of the immune system.
The least core in fixed-income taxation models: a brief mathematical inspection
Authors: Curt Paula , Litan Cristian M , Filip Diana Andrada 
Published: December 2011

Abstract
For models of majority voting over fixed-income taxations, we mathematically define the concept of least core. We provide a sufficient condition on the policy space such that the least core is not empty. In particular, we show that the least core is not empty for the framework of quadratic taxation, respectively piecewise linear tax schedules. For fixed-income quadratic taxation environments with no Condorcet winner, we prove that for sufficiently right-skewed income distribution functions, the least core contains only taxes with marginal-rate progressivity.
Validation of the individualised neuromuscular quality of life for the USA with comparison of the impact of muscle disease on those living in USA versus UK
Authors: Sadjadi Reza , Vincent Kelly A , Carr Alison J , Walburn Jessica , Brooks Victoria L , Pandya Shree , Kissel John T , Jackson Carlayne E , Rose Michael R ,   Muscle Study Group
Published: December 2011

Abstract

Background
The Individualised Neuromuscular Quality of Life (INQoL) questionnaire is a published muscle disease specific measure of QoL that has been validated using both qualitative and quantitative methods in a United Kingdom population of adults with muscle disease. If INQoL is to be used in other countries it needs to be linguistically and culturally validated for those countries. It may be important to understand any cultural differences in how patients rate their QoL when applying QoL measures in multi-national clinical trials.

Methods
We conducted a postal survey of QoL issues in US adults with muscle disease using an agreed translation, from UK to US English, of the same questionnaire as was used in the original construction of INQoL. This questionnaire included an opportunity for free text comments on any aspects of QoL that might not have been covered by the questionnaire. We examined the responses using both quantitative and qualitative approaches. The frequency of the responses in US versus UK populations was compared using appropriate correlation tests and Rasch analysis. A phenomenological approach was used to guide the qualitative analysis and facilitate the exploration of patients' perceptions and experiences.

Results
The US survey received 333 responses which were compared with 251 UK survey responses.
We found that INQoL domains covered all the issues raised by US subjects with no additional domains required. The experiences of those with muscle disease were remarkably similar in the US and UK but there were differences related to the impact of muscle disease on relationships and on employment which was greater for those living in the United States. The greater impact on employment was associated with a higher importance rating given to employment in the US. This may reflect the lower level of financial support for those who are unemployed, and the loss of employment related health benefits.

Conclusions
INQoL is appropriate for use in US population but there may be differences in the importance that US subject attach to certain aspects of QoL that could be the basis for further study.
If these differences are confirmed then this may have implications for the interpretation of QoL outcomes in multi-national trials.
Sex-independent neuroprotection with minocycline after experimental thromboembolic stroke
Authors: Hoda Md Nasrul , Li Weiguo , Ahmad Ajmal , Ogbi Safia , Zemskova Marina A , Johnson Maribeth H , Ergul Adviye , Hill William D , Hess David C , Sazonova Irina Y 
Published: December 2011

Abstract

Background
Minocycline provides neurovascular protection reducing acute cerebral injury. However, it is unclear whether minocycline is effective in females. We tested minocycline in both sexes and aged animals using a novel embolic stroke model in mice that closely mimics acute thromboembolic stroke in humans.

Methods
Five groups of mice were subjected to thromboembolic stroke: adult males, aged males, adult females, aged females, and adult ovariectomized females. They were treated with phosphate saline (vehicle) or minocycline (6 mg/kg) immediately after stroke onset. Behavioral outcomes, infarct volumes and cerebral blood flow were assessed. The effect of minocycline on expression and activity of MMP-9 was analyzed.

Results
The model resulted in reproducible infarct in the experimental groups. As expected, adult females were significantly more resistant to cerebral ischemic injury than males. This advantage was abolished by aging and ovariectomy. Minocycline significantly reduced the infarct volume (P < 0.0001) and also improved neurologic score (P < 0.0001) in all groups. Moreover, minocycline treatment significantly reduced mortality at 24 hours post stroke (P = 0.037) for aged mice (25% versus 54%). Stroke up-regulated MMP-9 level in the brain, and acute minocycline treatment reduced its expression in both genders (P < 0.0001).

Conclusion
In a thromboembolic stroke model minocycline is neuroprotective irrespective of mouse sex and age.
Foaminess and Viscosity Effects in Heavy Oil Flow
Authors: Alshmakhy Ahmed , Maini Brij 
Published: December 2011

Abstract
Foamy oil viscosity is a controversial topic among researchers as to what happens to the apparent oil viscosity when the dispersed gas bubbles start migrating with the oil. For conventional oils, below the true bubble point pressure, the oil viscosity increases as the gas freely evolves from the oil. For foamy oils, it has been suggested that the apparent viscosity of gas-in-oil dispersion remains relatively constant, or perhaps declines slightly, between the true bubble point and a characteristic lower pressure, called pseudo bubble point, which is the pressure at which the gas starts separating from the oil. Below this pressure, the viscosity increases, reaching the dead oil value at atmospheric pressure. However, it is a well known fact in dispersion rheology that the viscosity of dispersion is higher than the viscosity of the continuous phase. Therefore, the concept of foamy oil viscosity being lower than the oil viscosity is counterintuitive. The major difference here is the extreme viscosity of the base liquid phase for foamy oil and how this interacts with the gas phase in a porous medium. The reported results appear to be very oil specific in this area, and are also a very strong function of how rapidly pressure is depleted in a given system. It is also likely that the apparent viscosity for flow of foamy oil in porous media is not the true dispersion viscosity due to the size of dispersed bubbles being comparable to the pore sizes.
This study aims to investigate this issue by measuring the foamy oil viscosity under varied conditions. The effect of several parameters, such as shear/flow rate, foaminess and gas volume fraction on foamy oil viscosity was experimentally evaluated. A slim tube packed with sand was used to measure the apparent viscosity of gas-in-oil dispersions. The results show that the apparent viscosity of foamy oils is considerably higher than the live oil viscosity. . The results obtained also showed that the presence of an added foaming agent had only a minor impact on the apparent viscosity of foamy oil, especially at higher expansion factors. Also, at the same expansion factor, the apparent viscosity was higher at higher flow rate. Overall, the presence of a foaming agent resulted in enhanced dispersed flow of gas, as evidenced from the size of bubbles being produced and the observed pressure fluctuations
Pitfalls of Superposition When Analyzing Production Data
Authors: Moghadam S. , Mattar L. 
Published: December 2011

Abstract
Production data are usually analyzed using typecurves. Production data are typically variable rates, whereas typecurves are typically "constant rate" solutions. Therefore, "superposition" must be used to convert the multiple rates into their constant rate equivalent, before typecurves can be used to determine the flow regime.
For linear flow the kernel of the superposition function is square-root-time, for radial flow it is log-time and for boundary-dominated flow it is material-balance-time. When superposition is used, the appropriate function must be used. In practice, the dominant flow regime dictates the choice. However, the flow regimes can be determined only after typecurve matching. This creates a self-referencing procedure.
In many situations, using square-root-time superposition makes the data look like linear flow, while using log-time makes it look like radial flow, and using material-balance-time makes it look like boundary dominated flow. This is self-defeating and can easily lead to the wrong diagnosis of flow regimes. In other situations, the choice of superposition function does NOT change the shape of the data, and the diagnosis tends to be unique. Numerous variable rates are investigated in an attempt to identify when superposition is safe, or which function distorts data the least.
Superposition functions are more forgiving for the early time data, and therefore they are less likely to change the shape of the data significantly in well test analyses, whereas in production data analysis the focus is more on the late time data. Using an inappropriate superposition function can result in the wrong diagnosis of flow regimes and the wrong interpretation of production, and very critically, the wrong forecast of reserves. The choice of superposition function must be an "informed choice" by the analyst.