bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chrysin activates Notch1 signaling and suppresses tumor growth of anaplastic thyroid carcinoma in vitro and in vivo
Authors: Yu Xiao‐Min , Phan TramAnh , Patel Priyesh N. , Jaskula‐Sztul Renata , Chen Herbert 
Published: September 2012

AbstractBACKGROUND:Anaplastic thyroid cancer (ATC) is a very aggressive thyroid gland malignancy with very poor prognosis. It is suspected that the Notch signaling pathway, which is not active in ATC, may have a tumor suppressor function in this neoplasm. However, it remains unknown whether activation of Notch can yield therapeutic efficacies in ATC.METHODS:The purpose of this study was to evaluate the effect of chrysin, a potential Notch inducer identified via high‐throughput screening, on ATC both in vitro and in vivo.RESULTS:Chrysin treatment of ATC cells led to a dose‐dependent inhibition of cellular growth. Protein and messenger RNA levels of Notch1 and Hes1 (hairy/enhancer of split 1), a downstream Notch1 effector, were both up‐regulated with treatment. Luciferase reporter assays incorporating the C promoter‐binding factor 1 (CBF1) binding site also confirmed the functional activity of chrysin‐induced Notch1. Oral administration of chrysin suppressed the growth of ATC xenografts by an average of 59% compared with the vehicle control group (P = .002). In addition, calculated median time to tumor progression was 11 days for control mice and 21 days for the chrysin treatment group (P = .008). Analysis of chrysin‐treated ATC tumors revealed an increase in the active intracellular domain of Notch1 protein. Activation of Notch1 in vivo was associated with the induction of cleaved Poly ADP ribose polymerase (PARP) protein, indicating that the growth inhibition was due to apoptosis.CONCLUSIONS:The novel Notch1 activator chrysin inhibits tumor growth in ATC both in vitro and in vivo. Chrysin could be a promising therapeutic candidate for ATC, and this justifies further clinical studies. Cancer 2013. © 2012 American Cancer Society.
Influence of study sponsorship on head and neck cancer randomized trial results
Authors: Sun Gordon H. , Houlton Jeffrey J. , MacEachern Mark P. , Bradford Carol R. , Hayward Rodney A. 
Published: September 2012

BackgroundThe purpose of this study was to identify associations between study sponsorship and the methodological quality and published outcomes of head and neck cancer randomized controlled trials (RCTs).MethodsWe systematically searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials for qualified RCTs, evaluating journal impact factor (IF), Jadad score (measure of study quality), and results favoring or not favoring experimental therapy.ResultsOf 118 RCTs, the most common sponsor was government (38; 32%), followed by nonprofit organizations (30; 25%) and industry (26; 22%). Industry‐supported RCTs were associated with publication in journals with higher IF compared with RCTs without industry support (p = .013). Government‐supported RCTs were associated with higher mean Jadad score (p = .026) and results favoring experimental therapy (p = .034).ConclusionsGovernment‐supported, but not industry‐supported, RCTs were significantly associated with positive study results. These findings may be confounded by broadly applied definitions of sponsorship. © 2012 Wiley Periodicals, Inc. Head Neck 35: 1515–1520, 2013
Increased presence of capillaries next to remodeling sites in adult human cancellous bone
Authors: Kristensen Helene Bjoerg , Andersen Thomas Levin , Marcussen Niels , Rolighed Lars , Delaisse Jean-Marie 
Published: September 2012

Abstract
Vascularization is a prerequisite for osteogenesis in a number of situations, including bone development, fracture healing, and cortical bone remodeling. It is unknown whether a similar link exists between cancellous bone remodeling and vascularization. Here, we show an association between remodeling sites, capillaries, proliferative cells, and putative osteoblast progenitors. Iliac crest biopsies from normal human individuals were subjected to histomorphometry and immunohistochemistry to identify the respective positions of bone remodeling sites, CD34-positive capillaries, smooth muscle actin (SMA)-positive putative osteoblast progenitors, including pericytes, Ki67-positive proliferative cells, and bone remodeling compartment (BRC) canopies. The BRC canopy is a recently described structure separating remodeling sites from the bone marrow, consisting of CD56-positive osteoblasts at an early differentiation stage. We found that bone remodeling sites were associated with a significantly increased presence of capillaries, putative osteoblast progenitors, and proliferative cells in a region within 50 µm of the bone or the canopy surface. The increases were the highest above eroded surfaces and at the level of the light-microscopically assessed contact of these three entities with the bone or canopy surfaces. Between 51 and 100 µm, their densities leveled to that found above quiescent surfaces. Electron microscopy asserted the close proximity between BRC canopies and capillaries lined by pericytes. Furthermore, the BRC canopy cells were found to express SMA. These ordered distributions support the existence of an osteogenic-vascular interface in adult human cancellous bone. The organization of this interface fits the current knowledge on the mode of action of vasculature on osteogenesis, and points to the BRC canopy as a central player in this mechanism. We propose a model where initiation of bone remodeling coincides with the induction of proximity of the vasculature to endosteal surfaces, thereby allowing capillary-BRC canopy interactions that activate marrow events, including recruitment of osteoblast progenitors to bone remodeling sites. © 2013 American Society for Bone and Mineral Research.
Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures
Authors: Patsch Janina M , Burghardt Andrew J , Yap Samuel P , Baum Thomas , Schwartz Ann V , Joseph Gabby B , Link Thomas M 
Published: September 2012

Abstract
The primary goal of this study was to assess peripheral bone microarchitecture and strength in postmenopausal women with type 2 diabetes with fragility fractures (DMFx) and to compare them with postmenopausal women with type 2 diabetics without fractures (DM). Secondary goals were to assess differences in nondiabetic postmenopausal women with fragility fractures (Fx) and nondiabetic postmenopausal women without fragility fractures (Co), and in DM and Co women. Eighty women (mean age 61.3 ± 5.7 years) were recruited into these four groups (DMFx, DM, Fx, and Co; n = 20 per group). Participants underwent dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultradistal and distal radius and tibia. In the HR-pQCT images volumetric bone mineral density and cortical and trabecular structure measures, including cortical porosity, were calculated. Bone strength was estimated using micro–finite element analysis (µFEA). Differential strength estimates were obtained with and without open cortical pores. At the ultradistal and distal tibia, DMFx had greater intracortical pore volume (+52.6%, p = 0.009; +95.4%, p = 0.020), relative porosity (+58.1%, p = 0.005; +87.9%, p = 0.011) and endocortical bone surface (+10.9%, p = 0.031; +11.5%, p = 0.019) than DM. At the distal radius DMFx had 4.7-fold greater relative porosity (p &lt; 0.0001) than DM. At the ultradistal radius, intracortical pore volume was significantly higher in DMFx than DM (+67.8%, p = 0.018). DMFx also displayed larger trabecular heterogeneity (ultradistal radius: +36.8%, p = 0.035), and lower total and cortical BMD (ultradistal tibia: −12.6%, p = 0.031; −6.8%, p = 0.011) than DM. DMFx exhibited significantly higher pore-related deficits in stiffness, failure load, and cortical load fraction at the ultradistal and distal tibia, and the distal radius than DM. Comparing nondiabetic Fx and Co, we only found a nonsignificant trend with increase in pore volume (+38.9%, p = 0.060) at the ultradistal radius. The results of our study suggest that severe deficits in cortical bone quality are responsible for fragility fractures in postmenopausal diabetic women. © 2013 American Society for Bone and Mineral Research
Characterization of Epstein–Barr virus reactivation in a modeled spaceflight system
Authors: Brinley Alaina A. , Theriot Corey A. , Nelman‐Gonzalez Mayra , Crucian Brian , Stowe Raymond P. , Barrett Alan D.T. , Pierson Duane L. 
Published: September 2012

AbstractEpstein–Barr virus (EBV) is the causative agent of mononucleosis and is also associated with several malignancies, including Burkitt's lymphoma, Hodgkin's lymphoma, and nasopharyngeal carcinoma, among others. EBV reactivates during spaceflight, with EBV shedding in saliva increasing to levels ten times those observed pre‐and post‐flight. Although stress has been shown to increase reactivation of EBV, other factors such as radiation and microgravity have been hypothesized to contribute to reactivation in space. We used a modeled spaceflight environment to evaluate the influence of radiation and microgravity on EBV reactivation. BJAB (EBV‐negative) and Raji (EBV‐positive) cell lines were assessed for viability/apoptosis, viral antigen and reactive oxygen species expression, and DNA damage and repair. EBV‐infected cells did not experience decreased viability and increased apoptosis due to modeled spaceflight, whereas an EBV‐negative cell line did, suggesting that EBV infection provided protection against apoptosis and cell death. Radiation was the major contributor to EBV ZEBRA upregulation. Combining modeled microgravity and radiation increased DNA damage and reactive oxygen species while modeled microgravity alone decreased DNA repair in Raji cells. Additionally, EBV‐infected cells had increased DNA damage compared to EBV‐negative cells. Since EBV‐infected cells do not undergo apoptosis as readily as uninfected cells, it is possible that virus‐infected cells in EBV seropositive individuals may have an increased risk to accumulate DNA damage during spaceflight. More studies are warranted to investigate this possibility. J. Cell. Biochem. 114: 616–624, 2013. © 2012 Wiley Periodicals, Inc.
Outcomes following resection of pancreatic cancer
Authors: Witkowski Elan R. , Smith Jillian K. , Tseng Jennifer F. 
Published: September 2012

AbstractPancreatic cancer is an aggressive and highly lethal malignancy. Surgical resection is a modest tool, but it provides the only potential for curative therapy and often prolongs survival. This article reviews the progress made on both local and national levels towards an era of safer pancreatic surgery, while discussing both perioperative outcomes and long‐term survival after resection. J. Surg. Oncol. 2013;107:97–103. © 2012 Wiley Periodicals, Inc.
Hearing loss resulting in malpractice litigation: What physicians need to know
Authors: Reilly Brian K. , Horn Gayle M. , Sewell Ryan K. 
Published: September 2012

AbstractObjectives/Hypothesis:To evaluate the relationship between hearing loss and malpractice litigation.Study Design:Retrospective study evaluating state and federal civil malpractice litigation pertaining to physician treatment and patient hearing loss in the United States during a 10‐year period (2001–2011).Methods:A Westlaw search of the computer database Jury Verdicts‐All for 2001–2011 was performed using the search terms “hearing loss” and “malpractice.” This database includes jury verdicts, judgments, and settlements.Results:Niney‐four cases were analyzed. There were 53 verdicts favorable for the defense (56%), 28 verdicts favorable for the plaintiff (30%), and 12 settlements. One case resulted in a mistrial. Settlements ranged from $42,500 to $12,500,000, and verdicts ranged from $0 to $8,784,000. The average payout for adult plaintiffs was less ($549,157) than the payout for minors ($1,349,121). The average payout for a surgical case was $579,098, compared to $960,048 for medical etiology of hearing loss. Otolaryngologists were the most frequently sued treating physician for hearing loss; the second most common defendant was pediatricians (eight cases). In the 13 cases in which an otolaryngologist was sued, there were nine defense verdicts and four verdicts in plaintiffs' favor. The average indemnity for an otolaryngologist was $313,230.Conclusions:Otolaryngologists are successful in most (70%) hearing loss litigation brought against them. This is true regardless of whether the allegations are of medical error or include operative procedures. Pediatric patients received more favorable jury verdicts when litigating malpractice claims than their adult counterparts, and the payouts were highest when there was alleged birth trauma and/or meningitis. Finally, the severity and degree of hearing loss sustained correlate with higher payouts. Laryngoscope, 2013
Is the Sino‐Nasal Outcome Test‐22 a suitable evaluation for septorhinoplasty?
Authors: Poirrier Anne‐Lise , Ahluwalia Suki , Goodson Alexander , Ellis Matthew , Bentley Melissa , Andrews Peter 
Published: September 2012

AbstractObjectives/Hypothesis:It is becoming increasingly important for clinicians to demonstrate the impact of their interventions. The Sino‐Nasal Outcome Test‐22 (SNOT‐22) questionnaire is a disease‐specific questionnaire involving 22 symptoms combining rhinologic issues with general health issues. We evaluated the SNOT‐22 score as a quality‐of‐life outcome measure in septorhinoplasty surgery.Study Design:Outcome research.Methods:We carried out a prospective case series in 76 patients undergoing septorhinoplasty. Their SNOT‐22 scores were compared pre‐ and postoperatively. We also recorded individual symptom scores to study the impact of surgery. To check its reliability, the SNOT‐22 score was correlated to patient‐reported symptoms on a visual analogue scale. Patients were screened for comorbid conditions. Interactions with the surgical technique and/or with the initial sinonasal disease were sought.Results:The SNOT‐22 is a reliable and responsive outcome measure in septorhinoplasty surgery. Septorhinoplasty was especially effective at addressing nasal obstruction, discharge, olfaction, related sleep disturbance, and emotional symptoms such as embarrassment or frustration. Comparison to the visual analogue scale instrument confirmed the outcome measured by the SNOT‐22.Conclusions:The SNOT‐22 could be used in routine clinical practice to highlight the impact of nasal disease in each patient and to measure the outcome and the effectiveness of the surgical intervention. Laryngoscope, 2013
The effect of topically applied antimycotic agents on inner ear vestibular and cochlear function
Authors: Perez Ronen , Nazarian Yoram , Sohmer Haim , Sichel Jean‐Yves 
Published: September 2012

AbstractObjectives/Hypothesis:To assess and compare the effect of commonly used topical antimycotic agents and their solvents on the function of the vestibular and cochlear parts of the sand rat's inner ear.Study Design:Prospective, controlled, animal study.Methods:Forty‐five fat sand rats were randomly assigned to five major groups, each receiving topical application of a different agent: saline (control), gentamicin (ototoxic control), and three antimycotic agents: nystatin, clotrimazole solution (Agisten), and bifonazole solution (Agispor). All animals underwent a right labyrinthectomy, and a polyethylene tube was inserted into the left middle ear followed by baseline recording of vestibular evoked potentials (VsEPs) and auditory nerve and brainstem responses (ABR). Subsequently, each animal received five consecutive daily applications of the specific agent into the left middle ear. Evoked potential recordings were repeated 3 and 10 days after the last application and compared to baseline. For clotrimazole and bifonazole solutions, the effect of the solvents was assessed by comparing ABR recordings at similar intervals.Results:Administration of saline did not affect VsEPs or ABR. Both could not be recorded following gentamicin application. In all three antimycotic agents, no statistically significant difference was found between VsEPs recordings before and after application. Clotrimazole and bifonazole solutions caused a significant ABR threshold elevation similar to that caused by their solvents. Nystatin caused a less significant ABR threshold elevation.Conclusions:The three commonly used topical antimycotic agents investigated here did not affect vestibular function but had a toxic effect on inner ear cochlear function. It seems the main offenders were the solvents.
Combining individual patient data and aggregate data in mixed treatment comparison meta‐analysis: Individual patient data may be beneficial if only for a subset of trials
Authors: Donegan Sarah , Williamson Paula , D'Alessandro Umberto , Garner Paul , Smith Catrin Tudur 
Published: September 2012

BackgroundIndividual patient data (IPD) meta‐analysis is the gold standard. Aggregate data (AD) and IPD can be combined using conventional pairwise meta‐analysis when IPD cannot be obtained for all relevant studies. We extend the methodology to combine IPD and AD in a mixed treatment comparison (MTC) meta‐analysis.MethodsThe proposed random‐effects MTC models combine IPD and AD for a dichotomous outcome. We study the benefits of acquiring IPD for a subset of trials when assessing the underlying consistency assumption by including treatment‐by‐covariate interactions in the model. We describe three different model specifications that make increasingly stronger assumptions regarding the interactions. We illustrate the methodology through application to real data sets to compare drugs for treating malaria by using the outcome unadjusted treatment success at day 28. We compare results from AD alone, IPD alone and all data.ResultsWhen IPD contributed (i.e. either using IPD alone or combining IPD and AD), the chains converged, and we identified statistically significant regression coefficients for the interactions. Using IPD alone, we were able to compare only three of the six treatments of interest. When models were fitted to AD, the treatment effects and regression coefficients for the interactions were far more imprecise, and the chains did not converge.ConclusionsThe models combining IPD and AD encapsulated all available evidence. When exploring interactions, it can be beneficial to obtain IPD for a subset of trials and to combine IPD with additional AD. Copyright © 2012 John Wiley & Sons, Ltd.
Modeling and optimizing energy‐efficient manual driving on high‐speed lines
Authors: Sicre Carlos , Cucala Asunción P. , Fernández Antonio , Lukaszewicz Piotr 
Published: September 2012

AbstractThis paper presents a simulation‐based model for manual driving strategies that will minimize energy consumption for high‐speed trains. Specific characteristics of both high‐speed lines (HSLs) and manual driving strategies are considered in order to obtain achievable designs that can be tested on commercial services. The proposed design model calculates a list of efficient high‐level commands to be systematically executed by the driver on an HSL along the trip. The design is based on a detailed simulation model of the train's motion (taking into account track and train characteristics and operational constraints), combined with a genetic algorithm to select the best driving. Continuous control solution by mathematical optimization is avoided, as it is not an appropriate reference for manual driving in HSL. The validation of the simulation model is focused on running resistance, tractive/braking efficiencies, and consumption of auxiliary equipment, and shows differences between real measurements and simulated results which are lower than 2% both in run time and energy consumption. Finally, a real case is presented in which the proposed model was used to design efficient driving strategies that were subsequently implemented on commercial services along the Spanish HSL Madrid–Barcelona in both directions, measuring average energy savings of 23 and 18%, respectively, when the efficient driving strategies were compared with measured standard manual driving. The future scope will be the application of this model to online recalculation of driving commands. © 2012 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
From Simple Chalcogenidotetrelate Precursors to Complex Structures and Functional Compounds
Authors: Heine Johanna , Dehnen Stefanie 
Published: September 2012

AbstractChalcogenidotetrelates show a rich and complex chemistry encompassing intricate structures and useful materials. A step‐wise coordination chemistry approach allows the sequential formation of multinary M/T/E anions (M = transition metal, T = tetrel, E = chalcogen) from simple T/E building blocks in solution. This way, a range of compounds displaying different structure types of molecular as well as extended multinary anions were obtained. To allow for even further variety, the approach can be extended to organo‐functionalized chalcogenidotetrelates. Here, the organic shell of the inorganic cages plays a decisive role in reactivity and resulting structures. The formation structures and properties of these compounds will be discussed in detail in this perspective article.
Referential Communication in Children With ADHD: Challenges in the Role of a Listener
Authors: Nilsen Elizabeth S. , Mangal Leilani , MacDonald Kristi 
Published: September 2012

Purpose
Successful communication requires that listeners accurately interpret the meaning of speakers' statements. The present work examined whether children with and without attention-deficit/hyperactivity disorder (ADHD) differ in their ability to interpret referential statements (i.e., phrases that denote objects or events) from speakers.

Method

Children (6 to 9 years old), diagnosed with ADHD (
n
= 27) and typically developing (
n
= 26), took part in an interactive task in which they were asked by an adult speaker to retrieve objects from a display case. Children interpreted the referential statements in contexts that either did or did not require perspective-taking. Children's eye movements and object choices were recorded. Parents completed questionnaires assessing their child's frequency of ADHD symptoms and pragmatic communicative abilities.

Results
Behavioral and eye movement measures revealed that children with ADHD made more interpretive errors and were less likely to consider target referents across the 2 communicative conditions. Furthermore, ADHD symptoms related to children's performance on the communicative task and to parental report of the child's pragmatic skills.

Conclusion
Children with ADHD are less accurate in their interpretations of referential statements. Such difficulties would lead to greater occurrences of miscommunication.