bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase I/II Study Combining Erlotinib and Dasatinib for Non-Small Cell Lung Cancer
Authors: Gold Kathryn A. , Lee J. Jack , Harun Nusrat , Tang Ximing , Price Justina , Kawedia Jitesh D. , Tran Hai T. , Erasmus Jeremy J. , Blumenschein George R. , William William N. , Wistuba Ignacio I. , Johnson Faye M. 
Published: August 2014

Abstract

Background.
EGFR and Src are frequently activated in non-small cell lung cancer (NSCLC). In preclinical models, combining EGFR and Src inhibition has additive synergistic effects. We conducted a phase I/II trial of the combination of Src inhibitor dasatinib with EGFR inhibitor erlotinib to determine the maximum tolerated dose (MTD), pharmacokinetic drug interactions, biomarkers, and efficacy in NSCLC.

Methods.
The phase I 3+3 dose-escalation study enrolled patients with solid tumors to determine the MTD. The phase II trial enrolled patients with advanced NSCLC who had undergone no previous treatments to determine progression-free survival (PFS) and response. Pharmacokinetic and tissue biomarker analyses were performed.

Results.
MTD was 150 mg of erlotinib and 70 mg of dasatinib daily based on 12 patients treated in the phase I portion. No responses were observed in phase I. The 35 NSCLC patients treated in phase II had an overall disease control rate of 59% at 6 weeks. Five patients (15%) had partial responses; all had activating EGFR mutations. Median PFS was 3.3 months. Epithelial-mesenchymal transition markers did not correlate with outcomes.

Conclusion.
The combination of erlotinib and dasatinib is safe and feasible in NSCLC. The results of this study do not support use of this combination in molecularly unselected NSCLC.
Mineral Trioxide Aggregate Combined With Flap Surgery for Treatment of External Root Resorption. A Long‐Term Clinical Case Report
Authors: Carnio João , Geraldeli Saulo , White Cecil 
Published: August 2014

Introduction: Defects caused by root resorption are often associated with a variety of idiopathic, external resorptions or perforations located at the mid‐third of the root surface. These defects can lead to gingival inflammation, breakdown of periodontal fibers, bone resorption, and damage to the periodontal apparatus. Treatment protocols that preclude tooth extraction are important adjuncts toward an ultimate goal of tooth/root preservation. Although a number of materials have been proposed to repair root resorption defects, only a few have been effective in the long‐term management of subgingival defects.Case Presentation: This case report presents long‐term follow‐up of a subgingival, external root resorption lesion that was successfully treated with mineral trioxide aggregate (MTA) and a coronally advanced flap. At 30 months, the results revealed gain in clinical attachment, reduction in probing depth, additional bone formation, and, ultimately, preservation of the gingival margin and esthetic appearance of the tooth.Conclusion: The use of MTA appears to be a viable and effective material to treat subgingival root resorption defects while also preserving the function and esthetics of the natural dentition.
The Liquidity Trap, Democracy and Central Bank Independence
Authors: Croitoru Lucian 
Published: August 2014

Abstract
In the wake of the financial crisis, central banks in developed countries performed unconventional operations that are fiscal in nature. On one hand, we support the view that such operations, which are not fully democratic, might lead to loss of central bank operational independence and discuss some difficulties that central banks might face when reversing quantitative easing. On the other hand, we show that, in the middle of a financial crisis, such operations are best performed by central banks. To avoid this potential conflict, the society needs to identify the best means by which the responsibility for quasi-fiscal operations implemented by the central bank is transferred to a democratic structure
The effect of resveratrol and its methylthio-derivatives on the Nrf2-ARE pathway in mouse epidermis and HaCaT keratinocytes
Authors: Krajka-Kuźniak Violetta , Szaefer Hanna , Stefański Tomasz , Sobiak Stanisław , Cichocki Michał , Baer-Dubowska Wanda 
Published: August 2014

AbstractResveratrol is the most extensively studied stilbene derivative. We previously showed that methylthiostilbenes were more effective inhibitors of CYP1A1 and 1B1 activity than resveratrol. In this study, we investigated whether resveratrol and its methylthio-substituted derivatives, i.e. 3-M-4′-MTS (S2), 3,5-DM-4′-MTS (S5) and 3,4,5-TM-4′-MTS (S7) could activate Nrf2 signaling in the mouse epidermis and in human keratinocytes. Western blot analysis showed translocation of Nrf2 from the cytosol to the nucleus in both models. All of the tested stilbenes increased GST activity, but resveratrol was the most effective inducer. Moreover, only resveratrol increased the protein level of GSTP in the mouse epidermis. GSTM was enhanced in HaCaT cells after the treatment with derivatives S2 and S5. The same effect was observed for GSTP in the case of compound S2. Resveratrol and its derivatives reduced the NQO2 protein level in HaCaT cells. Thus, it is possible that increased expression of GSTP or GSTM and GST activity was linked with NQO2 inhibition in these cells. The results of this study indicate that resveratrol and its methylthioderivatives activate Nrf2 not only in the mouse epidermis, but also in human keratinocytes. Upregulating GST isozymes might be particularly important for deactivating chemical carcinogens, such as PAH.
Independent assessment of a new pedicle probe and its ability to detect pedicle breach: a cadaveric study
Authors: Guillen Phillip T. , Knopper Ryan G. , Kroger Jared , Wycliffe Nathaniel D. , Danisa Olumide A. , Cheng Wayne K. 
Published: August 2014

Object
The authors undertook an independent, non–industry funded cadaveric study to evaluate the efficacy of a pedicle-probing device, which uses impedance measurement to warn of impending and actual pedicle screw breach.

Methods
A previously validated fresh-frozen cadaver model (saline-soaked spine) was used. Individuals at 3 levels of training (attending spine surgeon, orthopedic surgery resident, and medical student) used a cannulated pedicle-probing device to cannulate each of the levels between T-2 and S-1. Each pedicle was cannulated freehand using 2 approaches: 1) a standard trajectory through the middle of the pedicle, and 2) a medial trajectory aimed to breach the medial wall of the pedicle. A 16-slice helical CT scanner was used. The images were interpreted and analyzed by 2 orthopedic spine surgeons and a neuroradiologist.

Results
The sensitivity of the pedicle probe to detect impending breach or breach of 4 mm or less was 90.06%. The sensitivity in detecting medial wall breach was 95.8%. The positive predictive value was 87.1%. The device detected medial breach more often than lateral breach.

Conclusions
This study showed that this pedicle-probing device could reasonably be used to detect impending breach and actual breach of 4 mm or less. Medial breach was detected better than lateral breach. Use of the pedicle probe may improve patient safety.
Predictive value of C-reactive protein for the outcome after primary intracerebral hemorrhage
Authors: Löppönen Pekka , Qian Cheng , Tetri Sami , Juvela Seppo , Huhtakangas Juha , Bode Michaela K. , Hillbom Matti 
Published: August 2014

Object
Primary intracerebral hemorrhage (ICH) carries high morbidity and mortality rates. Several factors have been suggested as predicting the outcome. The value of C-reactive protein (CRP) levels in predicting a poor outcome is unclear, and findings have been contradictory. In their population-based cohort, the authors tested whether, independent of confounding factors, elevated CRP levels on admission (< 24 hours after ictus) are associated with an unfavorable outcome.

Methods
The authors identified all patients who suffered primary ICH between 1993 and 2008 among the population of Northern Ostrobothnia, Finland, and from the laboratory records they extracted the CRP values at admission. Independent predictors of an unfavorable outcome (moderate disability or worse according to the Glasgow Outcome Scale at 3 months) were tested by unconditional logistic regression in a model including all the well-established confounding factors and CRP on admission.

Results
Of 961 patients, 807 (84%) had CRP values available within 24 hours of admission, and multivariable analysis showed elevated CRP at that point to be associated with an unfavorable outcome (OR 1.41 per 10 mg/L [95% CI 1.09–1.81], p < 0.01), together with diabetes mellitus (OR 1.99 [95% CI 1.09–3.64], p < 0.05), age (1.06 per year [95% CI 1.04–1.08], p < 0.001), low Glasgow Coma Scale score (0.75 per unit [95% CI 0.67–0.84], p < 0.001), hematoma size (1.05 per ml [95% CI 1.03–1.07], p < 0.001), and the presence of an intraventricular hemorrhage (2.70 [95% CI 1.66–4.38], p < 0.001). Subcortical location predicted a favorable outcome (0.33 [95% CI 0.20–0.54], p < 0.001).

Conclusions
Elevated CRP on admission is an independent predictor of an unfavorable outcome and is only slightly associated with the clinical and radiological severity of the bleeding.
Reducing costs while maintaining quality in endovascular neurosurgical procedures
Authors: Kashlan Osama N. , Wilson Thomas J. , Chaudhary Neeraj , Gemmete Joseph J. , Stetler William R. , Dunnick N. Reed , Thompson B. Gregory , Pandey Aditya S. 
Published: August 2014

Object
As medical costs continue to rise during a time of increasing medical resource utilization, both hospitals and physicians must attempt to limit superfluous health care expenses. Neurointerventional treatment has been shown to be costly, but it is often the best treatment available for certain neuropathologies. The authors studied the effects of 3 policy changes designed to limit the costs of performing neurointerventional procedures at the University of Michigan.

Methods
The authors retrospectively analyzed the costs of performing neurointerventional procedures during the 6-month periods before and after the implementation of 3 cost-saving policies: 1) the use of an alternative, more economical contrast agent, 2) standardization of coil prices through negotiation with industry representatives to receive economies of scale, and 3) institution of a feedback method to show practitioners the costs of unused products per patient procedure. The costs during the 6-month time intervals before and after implementation were also compared with costs during the most recent 6-month time period.

Results
The policy requiring use of a more economical contrast agent led to a decrease in the cost of contrast usage of $42.79 per procedure for the first 6 months after implementation, and $137.09 per procedure for the most current 6-month period, resulting in an estimated total savings of $62,924.31 for the most recent 6-month period. The standardized coil pricing system led to savings of $159.21 per coil after the policy change, and $188.07 per coil in the most recent 6-month period. This yielded total estimated savings of $76,732.56 during the most recent 6-month period. The feedback system for unused items decreased the cost of wasted products by approximately $44.36 per procedure in the 6 months directly after the policy change and by $48.20 per procedure in the most recent 6-month period, leading to total estimated savings of $22,123.80 during the most recent 6-month period. According to extrapolation over a 1-year period, the 3 policy changes decreased costs by an estimated $323,561.34.

Conclusions
Simple cost-saving policies can lead to substantial reductions in costs of neurointerventional procedures while maintaining high levels of quality and growth of services.
Combined endoscopic third ventriculostomy and choroid plexus cauterization as primary treatment for infant hydrocephalus: a prospective North American series
Authors: Stone Scellig S. D. , Warf Benjamin C. 
Published: August 2014

Object
Combined endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) enhances the likelihood of shunt freedom over ETV alone, and thus avoidance of shunt-related morbidity, in hydrocephalic infants. To date, virtually all published reports describe experiences in Africa, thus hampering generalization to other parts of the world. Here, the authors report the first North American prospective series of this combined approach to treat hydrocephalus of various etiologies in infants.

Methods
A prospective series of 50 boys and 41 girls (mean and median ages 4.7 and 3.2 months, respectively) with hydrocephalus underwent ETV/CPC performed by the senior author at Boston Children's Hospital from August 2009 through March 2014. Success data were analyzed using the Kaplan-Meier method and Cox proportional hazards model.

Results
The 91 patients treated included those with aqueductal stenosis (23), myelomeningocele (23), posthemorrhagic hydrocephalus (25), Dandy-Walker complex (6), post-infectious hydrocephalus (6), and other conditions (8). Using Kaplan-Meier survival analysis, 57% of patients required no further hydrocephalus treatment at 1 year. Moreover, 65% remained shunt free to the limit of available follow-up (maximum roughly 4 years). A Cox proportional hazards model identified the following independent predictors of ETV/CPC failure: post-infectious etiology, age at treatment younger than 6 months, prepontine cistern scarring, and prior CSF diversion. Of patients with at least 6 months of follow-up, the overall ETV/CPC success at 6 months (59%) exceeded that predicted by the ETV Success Score (45%). Complications included 1 CSF leak and 1 transient syndrome of inappropriate antidiuretic hormone secretion, and there were no deaths.

Conclusions
ETV/CPC is an effective, safe, and durable treatment for infant hydrocephalus in a North American population, with 1-year success rates similar to those reported in Africa and equivalent to those for primary shunt placement in North America. These findings underscore the need for prospective multicenter studies of the outcomes, quality of life, and economic impact of the procedure compared with primary shunt insertion.
Use of anteroposterior view fluoroscopy for targeting percutaneous pedicle screws in cases of spinal deformity with axial rotation
Authors: Ahmad Faiz U. , Wang Michael Y. 
Published: August 2014

Object
Over the past decade percutaneous pedicle screws have become popular for the minimally invasive treatment of spinal disorders. However, until the last 5 years the presence of a significant spinal deformity was regarded as a relative contraindication for percutaneous instrumentation. Recent advances in surgical technique and intraoperative technology have made percutaneous fixation in complex spinal pathologies more commonplace. The authors report their experience using a parsimonious method for uniplanar fluoroscopic targeting of pedicles in challenging cases.

Methods
The authors performed a retrospective analysis of patients with adult spinal deformity who underwent percutaneous pedicle screw instrumentation from 2008 to 2013. Cases were included if a spiral slice postoperative CT scan was obtained. All cases had a minimum of 10° of axial rotation and typically had additional accompanying anatomical abnormalities. Screws were assessed for any pedicle violations as well as any impingement of the surrounding facet joints.

Results
A total of 410 pedicle screws were placed in 36 patients with an average 6.4 levels of instrumentation per patient. The mean age was 67 years (range 44–86 years) and there were 25 females. Of the 410 screws, 29 (7.1%) had some medial or lateral pedicle violation. Of these, 15 (3.7%) were Grade 1, 6 (1.4%) were Grade 2, and 8 (2.0%) were Grade 3 violations. Of the Grade 3 violations, 2 each were at the L-4, L-5, and S-1 levels, and 1 each was at the T-10 and L-1 levels. Two of the patients had symptoms and both underwent screw repositioning, one during the same admission and the other in a delayed fashion. Both were at the L-5 and S-1 levels with anatomically highly medialized pedicles. There were no motor deficits, and both removals were for numbness. Of the 72 screws at the proximal end of the construct, there were 6 facet violations (8.3%). Four (5.6%) of these were Grade 1, 1 (1.4%) was Grade 2, and 1 (1.4%) was Grade 3.

Conclusions
The anteroposterior fluoroscopic technique can be effectively used by spinal surgeons to cannulate the pedicles in patients with rotational deformities. The complication rate in this challenging population is acceptable and is in accordance with the existing literature. However, caution should be used at L-5 and S-1 when the pedicle is narrow and highly medialized, rendering an indistinct medial wall on anteroposterior imaging.
Incidental uptake of 18F-fluorodeoxyglucose in the prostate gland
Authors: Sadeghi R. , Giovanella L. , Treglia G. , Bertagna F. 
Published: August 2014

SummaryAim: To perform a systematic review and meta-analysis of published data on the prevalence and risk of malignancy of pros- tatic incidental uptake (PIU) detected by flu- orine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) or PET/computed tomography (PET/CT). Patients, material, methods: A comprehensive literature search of studies published up to February 2014 was performed. Pooled prevalence and malignancy risk of PIU were calculated on a per patient-based analysis including 95% confidence interval (95%CI). Furthermore, we assessed some parameters as potential predictors of malignant PIU. Results: Six studies including 47925 patients who underwent 18F-FDG PET/CT were selected. Pooled prevalence of PIU was 1.8% (95%CI: 1.3–2.3%). Overall, 444 patients with PIU were further evaluated and 121 underwent biopsy. The pooled risk of malignancy in patients with PIU further evaluated or verified by biopsy were 17% (95%CI: 12–23%) and 62% (95%CI: 54–71%), respectively. A higher mean age was observed in the group of malignant PIUs compared to benign PIUs. There was a trend towards a higher mean SUVmax in the group of malignant PIUs but without a statistically significant difference compared to benign PIUs. Peripheric site of PIU but not presence or absence of calcification was a predictor of malignancy. Conclusions: PIU is observed in about 1.8% of 18F-FDG PET/CT scans performed in male patients carrying a significant risk of malignancy. Therefore, whenever a PIU is detected further investigation is warranted to exclude malignancy, in particular when PIU is located in the peripheric site of prostate gland.
Lack of the NS5B S282T Mutation in HCV Isolates from Liver Tissue of Treatment-Naive Patients with HCV Genotype-1b Infection
Authors: Maimone Sergio , Tripodi Gianluca , Musolino Cristina , Cacciola Irene , Pollicino Teresa , Raimondo Giovanni 
Published: August 2014

Background Despite the availability of several direct-acting antivirals (DAAs) specifically inhibiting different HCV proteins, treatment of chronic HCV infection is still a challenge also because of the possible selection of resistant viral variants under DAA therapy. Indeed, only the emergence of viruses resistant to the nucleoside inhibitors of the HCV NS5B polymerase (Pol) has not yet been reported, in spite of the fact that in vitro studies have clearly shown that an S282T amino acid change in the Pol protein may confer resistance to these drugs. On the basis of a previous study showing that viral variants resistant to HCV protease inhibitors are largely present in the liver – but not in the serum – of untreated patients, we investigated the possible natural occurrence of viral populations with the S282T change in the Pol protein, analysing viral isolates from liver and serum of HCV genotype-1b treatment-naive patients. Methods HCV-1b isolates from liver specimens and serum samples of 10 chronic hepatitis C patients were analysed by cloning and sequencing. Results The S282T mutation was not found in any of the viral isolates from either liver or serum samples of all the cases, although an S282G mutation of unknown virological/clinical relevance was detected in 2/19 liver isolates from one patient. Conclusions Our study confirms that the natural selection of the S282T mutation is a rare event, thus explaining the lack of emergence and takeover of these variants under drug pressure.
The influence of weather parameters on crucifer flea beetle (Coleoptera: Chrysomelidae) capture heights
Authors: Tansey James A. , Dosdall Lloyd M. , Soroka Julie J. , Keddie B. Andrew 
Published: August 2014

AbstractThe crucifer flea beetle, Phyllotreta cruciferae (Goeze) (Coleoptera: Chrysomelidae), is the most important pest of seedling canola, Brassica napus Linnaeus (Brassicaceae), in North America, yet effects of weather on its dispersal and flight activity are not completely understood. We investigated effects of ambient temperature, relative humidity, wind speed, atmospheric pressure, barometric flux, and precipitation on capture heights of P. cruciferae over four site-years in Alberta and Saskatchewan, Canada. Capture heights increased with mean ambient temperatures for both generations of beetles, with 15°C determined as an estimated minimum temperature for flight. Although capture heights decreased with greater minimum relative humidity, and atmospheric pressure, and increased with greater mean wind speed, the contributions of these factors were determined to be minor relative to that of mean temperature. Results of the current study will contribute to more accurate predictions of the invasion of canola crops by P. cruciferae and contribute to improved integrated management of this important pest species.
Who should have a pre-discharge home assessment visit after a stroke? A qualitative study of occupational therapists' views
Authors: Whitehead Phillip , Fellows Karen , Sprigg Nikola , Walker Marion , Drummond Avril 
Published: August 2014

Introduction: The number of patients who have a pre-discharge home assessment visit following a stroke has been reported to vary nationally. The purpose of this research was to explore the factors influencing occupational therapists' decisions to complete such visits. Method: Semi-structured interviews were completed with 20 senior occupational therapists working with stroke in-patients, from a range of urban and rural locations in the United Kingdom. The interviews explored their views about those patients for whom a pre-discharge home assessment visit would and would not be required. The interviews were analysed using thematic analysis. Findings: Three themes were identified: the patient's level of physical, cognitive, or perceptual impairment and its impact on performance in activities of daily living; factors relating to the patient's home environment, including the availability of support within the home environment; and other influences on occupational therapists. The presence of a cognitive impairment was a particularly important factor. Conclusions: Occupational therapists balanced aspects from each of these themes in order to determine whether a visit was needed or not. Although the level of impairment was important, the most dependent patients were not necessarily those believed to be the most likely to need a visit.