bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Sources and Popularity of Online Drug Information: An Analysis of Top Search Engine Results and Web Page Views
Authors: Law Michael R , Mintzes Barbara , Morgan Steven G 
Published: February 2011

Background: The Internet has become a popular source of health information. However, there is little information on what drug information and which Web sites are being searched. Objective: To investigate the sources of online information about prescription drugs by assessing the most common Web sites returned in online drug searches and to assess the comparative popularity of Web pages for particular drugs. Methods: This was a cross-sectional study of search results for the most commonly dispensed drugs in the US (n = 278 active ingredients) on 4 popular search engines: Bing, Google (both US and Canada), and Yahoo. We determined the number of times a Web site appeared as the first result. A linked retrospective analysis counted Wikipedia page hits for each of these drugs In 2008 and 2009. Results: About three quarters of the first result on Google USA for both brand and generic names linked to the National Library of Medicine. In contrast, Wikipedia was the first result for approximately 80% of generic name searches on the other 3 sites. On these other sites, over two thirds of brand name searches led to industry-sponsored sites. The Wikipedia pages with the highest number of hits were mainly for opiates, benzodiazepines, antibiotics, and antidepressants. Conclusions: Wikipedia and the National Library of Medicine rank highly In online drug searches. Further, our results suggest that patients most often seek information on drugs with the potential for dependence, for stigmatized conditions, that have received media attention, and for episodic treatments. Quality improvement efforts should focus on these drugs.
Azathioprine-lnduced Fever in Sarcoidosis
Authors: McBane Sarah , Rojas Carlos 
Published: February 2011

Objective: To report a case of drug-induced fever associated with azathioprine treatment in a patient with sarcoidosis. Case Summary: A 52-year-old man with pulmonary sarcoidosis presented to the emergency department with a 1 -day history of fever (temperature 39.9 °C), chills, nausea, and vomiting. One week earlier, azathioprine 50 mg/day had been started for worsening dyspnea. The patient was admitted and evaluated for acute infectious processes. All of his home medications (hydroxychloroquine, prednisone, fluticasone/salmeterol, lovastatin, pantoprazole, Zolpidem, ibandronate, albuterol), except prednisone, were held. Results of chest X-ray, viral cultures, and urine and blood cultures revealed no source of infection. The patient's temperature returned to normal within 30 hours after discontinuation of azathioprine; rechallenge was not performed. Discussion: Fever as an adverse drug reaction is often unrecognized, particularly in medically complex patients. Azathioprine has been reported to cause drug fever in patients with inflammatory bowel disease and in those with rheumatoid arthritis; to our knowledge, there have been no previous reports documenting azathioprine-induced fever in patients with sarcoidosis. The chronological course of febrile response and defervescence is highly suggestive of drug-induced fever. Conclusions: The rapid resolution of fever after discontinuation of azathioprine suggests that it was the likely source of fever in this patient. If azathioprine is increasingly prescribed in patients with sarcoidosis, fever as an adverse reaction may become more common.
Metal nanoparticle-enhanced radiative transitions: Giving singlet oxygen emission a boost
Authors: Toftegaard Rasmus , Arnbjerg Jacob , Cong Huaiping , Agheli Hossein , Sutherland Duncan S. , Ogilby Peter R. 
Published: February 2011

The fabrication and use of metal nanoparticles to influence electronic transitions in a given molecule is of growing interest; there is much to be gained by developing and exploiting methods to enhance weak optical signals. Singlet molecular oxygen, O2(a1∆g), which is an important intermediate in many oxidation reactions, particularly in biological systems, is ideally monitored by the 1275-nm O2(a1∆g) → O2(X3Σg–) phosphorescent transition. Unfortunately, the latter is highly forbidden and, as such, often presents a severe limitation in the application of this optical probe. In this paper, we describe how this weak phosphorescent transition can be enhanced by using localized surface plasmons (LSPs) from specially engineered gold nanostructures. In an attempt to elucidate the mechanism of this process, data were recorded from samples in which we decoupled the component of the plasmon resonance that absorbs incident light from the component that scatters incident light. We find that the latter appears to be the feature of significance in the process through which singlet oxygen phosphorescence is enhanced. In this work, we also illustrate how the singlet oxygen system provides an ideal model for a general study of metal-enhanced radiative rate constants.
Upregulation of thyroid transcription factor-1 and human leukocyte antigen class I in Hashimoto's disease providing a clinical evidence for possible triggering autoimmune reaction
Authors: Huang Huibin , Li Xisheng , Lin Ling , Shi Yaxiong , Lin Xiahong , Li Liangyi , Xu Dongming 
Published: February 2011

ObjectiveAn increase in the expression of autoantigens and their presenting molecules human leukocyte antigen (HLA) class I has been demonstrated to be responsible for autoimmune diseases. Thyroid transcription factor-1 (TTF-1 or NKX2-1) synchronously upregulates both HLA class I and thyroid-specific autoantigen, which may be involved in the pathological process of autoimmune thyroiditis. In this study, the expressions and potential role of TTF-1 and HLA class I in Hashimoto's disease (HT) were examined.PatientsIn this study, 22 resection specimens clinically and histopathologically confirmed to have Hashimoto's disease and 30 normal thyroid specimens from adjacent tissues of thyroid adenoma were used.MeasurementWestern blot, real-time PCR, and immunohistochemistry were performed to assay TTF-1 and HLA class I in the thyrocytes of Hashimoto's disease as well as in the normal thyroid from adjacent tissues of thyroid adenoma.ResultsThe TTF-1 and HLA class I in Hashimoto's disease were significantly higher than those in the controls.ConclusionUpregulation of TTF-1 and HLA class I in Hashimoto's disease provide a clinical evidence for possible triggering of autoimmune reaction.
Tumor Biology and Prognostic Factors in Renal Cell Carcinoma
Authors: Finley David S. , Pantuck Allan J. , Belldegrun Arie S. 
Published: February 2011

AbstractIn the past 15 years, there has been an increased understanding of the tumor biology of renal cell carcinoma (RCC). The identification of vascular endothelial growth factor (VEGF), its related receptor (VEGFR), and the mammalian target of rapamycin as dysregulated signaling pathways in the development and progression of RCC has resulted in the rational development of pharmaceutical agents capable of specifically targeting key steps in these pathways. Clinical trials have demonstrated survival benefit with these agents, particularly in clear cell RCC patients. However, metastatic RCC will progress in all patients, resulting in a critical need to determine patient risk and optimize treatment. The goal of this article is to highlight the significant breakthroughs made in understanding the critical genetic alterations and signaling pathways underlying the pathogenesis of RCC. The discovery of prognostic factors and development of comprehensive nomograms to stratify patient risk and predictive biomarkers to facilitate individualized treatment selection and predict patient response to therapy also are reviewed.
Targeted Therapies for the Treatment of Metastatic Renal Cell Carcinoma: Clinical Evidence
Authors: Hutson Thomas E. 
Published: February 2011

Abstract
Although systemic therapy for patients with metastatic renal cell carcinoma (mRCC) was once limited to the cytokines interleukin-2 and interferon (IFN)-α, in recent years several targeted therapies have become available for first- and second-line use. These include sorafenib, sunitinib, bevacizumab (plus IFN-α), temsirolimus, everolimus, and, most recently, pazopanib. This expanded list of treatment options arose from molecular biological research that revealed aberrant signal transduction activities in RCC, enabling the identification of specific molecular targets for therapy. Molecular-targeted therapies have better efficacy and tolerability than cytokine therapy, and many are administered orally. The superior outcomes achieved with molecular-targeted agents are prompting investigators to reconsider overall survival as a primary endpoint in clinical trials, given the inherent complications of a required long duration of follow-up, a required large population, and confounding caused by crossover trial designs or effects of subsequent therapy after progression on the agent of interest. In mRCC trials, progression-free survival has become a popular primary endpoint and has served as the basis of approval for several targeted therapies. In addition to the identification of new agents, current research is focused on the evaluation of combination therapy with targeted agents. As more information regarding mechanisms of disease and drug resistance becomes available, new targets, new targeted agents, and new combinations will be studied with the goal of providing maximal efficacy with minimal toxicity. This article reviews the clinical evidence supporting the benefits of targeted agents in mRCC treatment, discusses survival endpoints used in their pivotal clinical trials, and outlines future research directions.
Treatment-Associated Adverse Event Management in the Advanced Renal Cell Carcinoma Patient Treated with Targeted Therapies
Authors: Ravaud Alain 
Published: February 2011

Abstract
Targeted therapy for advanced renal cell carcinoma (RCC) has recently expanded the available treatment options for patients with these malignancies. The rapid introduction of novel treatment options into clinical practice within a relatively short time frame has created some new challenges pertaining to adverse event (AE) management in patients with advanced RCC. Accumulating safety data from the pivotal phase III clinical trials of the anti–vascular endothelial growth factor (VEGF) antibody bevacizumab plus interferon, VEGF receptor tyrosine kinase inhibitors (sunitinib, sorafenib, and pazopanib), and mammalian target of rapamycin inhibitors (temsirolimus and everolimus) have served to characterize the toxicity profiles of these novel agents. Overall, it is evident that RCC-directed targeted therapy differs from immunotherapy and cytotoxic chemotherapy in terms of a number of unique nonhematologic AEs (some of which have not been traditionally encountered in oncology practice) and that there are distinctions within and across the various classes of agents with respect to the most prominent AEs and the risk for less common but serious complications. Although treatment-associated AEs are common, the majority of AEs reported during clinical trial experiences were grade 1 or 2 in severity and manageable with intervention in the form of supportive measures and/or dosage modification. Therefore, despite the relatively complex AE profiles of RCC-directed targeted therapy, patient education, consistent monitoring with a focus on early detection by health care providers (oncologists, general physicians, nurses), and the application of emerging AE management strategies may allow for prolonged treatment in most patients with advanced RCC.
Clinical Practice Guidelines for the Treatment of Metastatic Renal Cell Carcinoma: Today and Tomorrow
Authors: Molina Ana M. , Motzer Robert J. 
Published: February 2011

Abstract
In the U.S. and Europe, clinical practice guidelines for metastatic renal cell carcinoma have undergone several revisions as a result of the introduction of molecular-targeted therapies. Recently, the National Comprehensive Cancer Network (NCCN) and the European Association of Urology (EAU) published updated guidelines to reflect these new treatment approaches that provide greater efficacy and better tolerability than the previous standard of care, cytokine therapy with interleukin-2 or interferon-α. Recommendations are classified by line of therapy, Memorial Sloan-Kettering Cancer Center risk level for survival, and level of evidence. Although many similarities exist, levels of evidence between the NCCN and EAU guidelines have differing designations and definitions, and timing of updates varies. New research developments, such as identification of effective combinations of targeted agents, optimal regimens for sequential therapy, newly designed targeted agents, benefits in special populations, and identification of additional prognostic factors and biomarkers, will prompt continued updates and refinements of today's clinical practice guidelines, with the goal of providing physicians with the most up-to-date clinical consensus upon which to base treatment decisions. Because clinical trial populations may not represent real-life patient populations, recommendations should serve only as a guide and must be tailored to the needs of each patient.
An in vitro microbial model associated with sucrose to produce dentin caries lesions
Authors: Steiner-Oliveira Carolina , Rodrigues Lidiany , Zanin Iriana , Carvalho Carolina , Kamiya Regianne , Hara Anderson , Nobre-dos-Santos Marinês 
Published: February 2011

Abstract
The complexity of the oral environment and ethical issues have prompted the development of an in vitro bacterial model to evaluate the effect of frequency of sucrose exposure on dentin caries formation, biofilm composition, and pH changes. In the experiment, dentin specimens (n=45) were randomly divided into four groups: control (C), negative control (0S), 3S (three sucrose baths), and 6S (six sucrose baths). The specimens then were inoculated with Streptococcus mutans and treated according to the protocol described below. Dentin demineralization and lesion depth were assessed by transverse microradiography. Extracellular polysaccharides that formed in the biofilm were analyzed and counts of microorganisms in the carious dentin were measured. After a 7-day period of growth, the biofilm pH was assessed before and after sucrose baths (n=5). The addition of sucrose led to dentin caries development regardless of the number of sucrose baths performed. The number of colony forming units (cfu) from the carious dentin did not differ among the treatment groups, though the extracellular polysaccharides from both 3S and 6S differed from 0S. The pH decreased immediately after the sucrose bath but increased again after 5 min. We demonstrate here that the in vitro microbial model for the study of dentin caries formation is reproducible and able to produce dentin caries, irrespective of the frequency of sucrose exposure.
Polar constituents of Ligustrum vulgare L. and their effect on lipoxygenase activity
Authors: Mučaji Pavel , Nagy Milan , Záhradníková Anna , Holková Ivana , Bezáková Lýdia , Švajdlenka Emil , Liptaj Tibor , Prónayová Nadežda 
Published: February 2011

AbstractThe present work summarizes results of isolation and identification of polar constituents of the methanolic extract of Ligustrum vulgare L. leaves and of the evaluation of inhibiting activity of selected isolates on rat lung cytosol fraction lipoxygenase. Six different compounds were isolated from the ethylacetate and butanol portions of the methanolic extract (hydroxytyrosol and its glucoside, ligustroflavon, oleuropein, acteoside, echinacoside). The inhibitory activity of oleuropein, echinacoside and the water infusion of Ligustrum vulgare leaves tested on LOX was expressed as IC50. Kinetic parameters (K M, V max) and type of inhibition were determined. As the most effective in competitive inhibition of LOX, oleuropein was proved.
Engineering patient-specific drill templates and bioabsorbable posterior cervical plates: a feasibility study
Authors: Ryken Timothy C. , Kim John , Owen Brent D. , Christensen Gary E. , Reinhardt Joseph M. 
Published: February 2011

Object
The authors describe a method of using computer models to generate customized cervical implants. A promising yet challenging technique in cervical spine surgery involves the use of pedicle screws to assist with posterior instrumentation. Surrounding anatomical structures such as the vertebral arteries and cervical nerve roots present challenges for safe screw placement; however, the use of computer-generated templates seems to be a promising method to assist with placement. In this study, the authors explore the use of computer-generated templates and introduce their methods for creating custom, bioabsorbable posterior cervical implants.

Methods
The cervical spines (C2–T1) from 4 cadavers were scanned with volumetric CT. Using commercially available software, the authors generated volumetric models of a cervical drill template and the mold for a cervical plate spanning a desired number of vertebrae. The computer generated models of the cervical drill template and cervical plate mold were converted into physical models using a rapid prototyping machine. The biopolymer polylactic acid resin was heated to 250°C and resolidified to form thin ~ 5-mm-thick plates. The newly formed plates were reheated to 60°C and cast on the cervical mold.

Results
The resulting translucent plates were found on visual inspection to have a secure lock-and-key fit on the original cadaver spine, and the techniques used were robust and reproducible. The process described in this brief report provides the background to proceed with development and testing of these patient-absorbable templates.

Conclusions
The creation and use of patient-specific bioabsorbable posterior cervical plates in conjunction with multilevel drill templates appear promising. Additional feasibility studies are planned, and in vitro studies are required to determine the safety and efficacy of using patient-specific drill templates and converting them into bioabsorbable implants.
Thoracolumbar spine trauma classification: the Thoracolumbar Injury Classification and Severity Score system and case examples
Authors: Patel Alpesh A. , Dailey Andrew , Brodke Darrel S. , Daubs Michael , Harrop James , Whang Peter G. , Vaccaro Alexander R. , _ _ 
Published: February 2011

Object
The aim of this study was to review the Thoracolumbar Injury Classification and Severity Score (TLICS) and to demonstrate its application through a series of spine trauma cases.

Methods
The Spine Trauma Study Group collaborated to create and report the TLICS system. The TLICS system is reviewed and applied to 3 cases of thoracolumbar spine trauma.

Results
The TLICS system identifies 3 major injury characteristics to describe thoracolumbar spine injuries: injury morphology, posterior ligamentous complex integrity, and neurological status. In addition, minor injury characteristics such as injury level, confounding variables (such as ankylosing spondylitis), multiple injuries, and chest wall injuries are also identified. Each major characteristic is assigned a numerical score, weighted by severity of injury, which is then summated to yield the injury severity score. The TLICS system has demonstrated initial success and its use is increasing. Limitations of the TLICS system exist and, in some instances, have yet to be addressed. Despite these limitations, the severity score may provide a basis to judge spinal stability and the need for surgical intervention.

Conclusions
By addressing both the posterior ligamentous integrity and the patient's neurological status, the TLICS system attempts to overcome the limitations of prior thoracolumbar classification systems. The TLICS system has demonstrated both validity and reliability and has also been shown to be readily learned and incorporated into clinical practice.
Foot drop due to lumbar degenerative conditions: mechanism and prognostic factors in herniated nucleus pulposus and lumbar spinal stenosis
Authors: Iizuka Yoichi , Iizuka Haku , Tsutsumi Satoshi , Nakagawa Yumi , Nakajima Takashi , Sorimachi Yasunori , Ara Tsuyoshi , Nishinome Masahiro , Seki Takayuki , Shida Kosuke , Takagishi Kenji 
Published: February 2011

Object
The aim of this study was to analyze the mechanism and prognostic factors of foot drop caused by lumbar degenerative conditions.

Methods
The authors retrospectively reviewed the charts of 28 patients with foot drop due to a herniated nucleus pulposus (HNP) or lumbar spinal stenosis (LSS), scoring between 0 and 3 on manual muscle testing for the tibialis anterior muscles. They analyzed the mechanism of foot drop and whether the duration before the operation, preoperative tibialis anterior and extensor hallucis longus strength, age, gender, and diabetes mellitus were all found to be prognostic factors for postoperative tibialis anterior recovery. They also investigated whether the diagnosis had any influence on the prognosis.

Results
The compression of double roots and a sequestrated fragment were observed, respectively, in 9 and 13 of 16 patients with HNP. Multiple levels including the L4–5 segment were decompressed in 8 of 12 patients with LSS. Analysis did not demonstrate any prognostic factor in surgically treated HNP, but significant associations with prognosis were observed with respect to preoperative tibialis anterior (p = 0.033) and extensor hallucis longus (p = 0.020) strength in patients with LSS. In addition, the postoperative muscle recovery in patients with HNP was significantly superior to that in patients with LSS (p = 0.011).

Conclusions
Double root compression was the most common condition associated with foot drop due to HNP. The diagnosis and preoperative tibialis anterior and extensor hallucis longus strength in LSS were factors that influenced recovery following an operation.