bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Pathways: Targeting P21-Activated Kinase 1 Signaling in Cancer—Opportunities, Challenges, and Limitations
Authors: Eswaran Jeyanthy , Li Da-Qiang , Shah Anil , Kumar Rakesh 
Published: May 2012

Abstract
The evolution of cancer cells involves deregulation of highly regulated fundamental pathways that are central to normal cellular architecture and functions. p21-activated kinase 1 (PAK1) was initially identified as a downstream effector of the GTPases Rac and Cdc42. Subsequent studies uncovered a variety of new functions for this kinase in growth factor and steroid receptor signaling, cytoskeleton remodeling, cell survival, oncogenic transformation, and gene transcription, largely through systematic discovery of its direct, physiologically relevant substrates. PAK1 is widely upregulated in several human cancers, such as hormone-dependent cancer, and is intimately linked to tumor progression and therapeutic resistance. These exciting developments combined with the kinase-independent role of PAK1-centered phenotypic signaling in cancer cells elevated PAK1 as an attractive drug target. Structural and biochemical studies revealed the precise mechanism of PAK1 activation, offering the possibility to develop PAK1-targeted cancer therapeutic approaches. In addition, emerging reports suggest the potential of PAK1 and its specific phosphorylated substrates as cancer prognostic markers. Here, we summarize recent findings about the PAK1 molecular pathways in human cancer and discuss the current status of PAK1-targeted anticancer therapies. Clin Cancer Res; 18(14); 3743–9. ©2012 AACR.
Toll-Like Receptor 4 Activation in Microvascular Endothelial Cells Triggers a Robust Inflammatory Response and Cross Talk With Mononuclear Cells via Interleukin-6
Authors: Lu Zhongyang , Li Yanchun , Jin Junfei , Zhang Xiaoming , Lopes-Virella Maria F. , Huang Yan 
Published: May 2012

Objective—
It is known that toll-like receptor 4 (TLR4) plays an important role in atherosclerosis. Because both microvascular (MIC) and macrovascular (MAC) endothelial cells (ECs) are present in atherosclerotic lesions, the present study compared TLR4-triggered inflammatory response and cross talk with mononuclear cells between MIC and MAC ECs.

Methods and Results—
ELISA, real-time polymerase chain reaction, and gene expression profiling showed that TLR4 activation by lipopolysaccharide stimulated a much higher expression of inflammatory genes including cytokines, chemokines, growth factors, and adhesion molecules in MIC ECs than MAC ECs. Furthermore, coculture studies showed that TLR4 activation in MIC ECs, but not MAC ECs, induced a cross talk with U937 mononuclear cells through MIC EC-released interleukin-6 to upregulate matrix metalloproteinase-1 expression in U937 cells. To explore molecular mechanisms underlying the different responses to TLR4 activation between MIC and MAC ECs, we showed that MIC ECs had a higher expression of TLR4 and CD14 and a higher TLR4-mediated nuclear factor-kappaB activity than MAC ECs.

Conclusion—
The present study showed that TLR4 activation triggers a more robust inflammatory response in MIC ECs than MAC ECs. Given the importance of inflammatory cytokines and matrix metalloproteinases in plaque rupture, MIC ECs may play a key role in plaque destabilization through a TLR4-dependent mechanism.
Geographic Variability of Childhood Food Allergy in the United States
Authors: Gupta Ruchi S. , Springston Elizabeth E. , Smith Bridget , Warrier Manoj R. , Pongracic Jacqueline , Holl Jane L. 
Published: May 2012

Objective The aim of this study was to describe the distribution of childhood food allergy in the United States. Methods A randomized survey was administered electronically from June 2009 to February 2010 to adults in US households with at least 1 child younger than 18 years. Data were analyzed as weighted proportions to estimate prevalence and severity of food allergy by geographic location. Multiple logistic regression models were constructed to estimate the association between geographic location and food allergy. Results Data were analyzed for 38 465 children. Increasing population density corresponded with increasing prevalence, from 6.2% in rural areas (95% confidence interval [CI] = 5.6-6.8) to 9.8% in urban centers (95% CI = 8.6-11.0). Odds of food allergy were graded, with odds in urban versus rural areas highest (odds ratio [OR] = 1.7, 95% CI = 1.5-2.0), followed by metropolitan versus rural areas (OR = 1.4, 95% CI = 1.2-1.5), and so on. Significance remained after adjusting for race/ethnicity, gender, age, household income, and latitude. Conclusions An association between urban/rural status and food allergy prevalence was observed.
Preservation of Viscoelastic Properties of Rabbit Vocal Folds after Implantation of Hyaluronic Acid‐Based Biomaterials
Authors: Choi Jeong‐Seok , Kim Nahn Ju , Klemuk Sarah , Jang Yun Ho , Park In Suh , Ahn Kyung Hyun , Lim Jae‐Yol , Kim Young‐Mo 
Published: May 2012

ObjectivesTo compare the rheological characteristics of structurally different hyaluronic acid (HA)‐based biomaterials that are presently used for phonosurgery and to investigate their influence on the viscoelastic properties of vocal folds after implantation in an in vivo rabbit model.Study DesignIn vitro and in vivo rheometric investigation.SettingExperimental laboratory, Inha and Seoul National Universities.MethodsViscoelastic shear properties of 3 HA‐based biomaterials (Rofilan, Restylane, and Reviderm) were measured with a strain‐controlled rheometer. These biomaterials were injected into the deep layers of rabbit vocal folds, and viscoelastic moduli of the injected vocal folds were determined 2 months after the injection. The vocal fold specimens were observed using a light microscope and a transmission electron microscope.ResultsAll HA‐based biomaterials showed similar levels of shear viscosity, which were slightly higher than that of human vocal folds reported in previous studies. Compared with noninjected control vocal folds, there were no significant differences in the magnitudes of both elastic shear modulus (G’) and viscous modulus (G”) of injected vocal folds among all of the materials. Light microscopic images showed that all materials were observed in the deep layers of vocal folds and electron scanning images revealed that injected HA particles were homogeneously distributed in regions of collagenous fibers.ConclusionHA‐based biomaterials could preserve the viscoelastic properties of the vocal folds, when they were injected into vocal folds in an in vivo rabbit model. However, further studies on the influence of the biomaterials on the viscoelasticity of human vocal folds in ECM surroundings are still needed.
How Good Is Google?
Authors: Pusz Max D. , Brietzke Scott E. 
Published: May 2012

ObjectiveTo assess the quality of the information a patient (parent) may encounter using a Google search for typical otolaryngology ailments.Study DesignCross‐sectional study.SettingTertiary care center.MethodsA Google keyword search was performed for 10 common otolaryngology problems including ear infection, hearing loss, tonsillitis, and so on. The top 10 search results for each were critically examined using the 16‐item (1‐5 scale) standardized DISCERN instrument. The DISCERN instrument was developed to assess the quality and comprehensiveness of patient treatment choice literature.ResultsA total of 100 Web sites were assessed. Of these, 19 (19%) were primarily advertisements for products and were excluded from DISCERN scoring. Searches for more typically chronic otolaryngic problems (eg, tinnitus, sleep apnea, etc) resulted in more biased, advertisement‐type results than those for typically acute problems (eg, ear infection, sinus infection, P =. 03). The search for “sleep apnea treatment” produced the highest scoring results (mean overall DISCERN score = 3.49, range = 1.81‐4.56), and the search for “hoarseness treatment” produced the lowest scores (mean = 2.49, range = 1.56‐3.56). Results from major comprehensive Web sites (WebMD, EMedicinehealth.com, Wikipedia, etc.) scored higher than other Web sites (mean DISCERN score = 3.46 vs 2.48, P <. 001).ConclusionThere is marked variability in the quality of Web site information for the treatment of common otolaryngologic problems. Searches on more chronic problems resulted in a higher proportion of biased advertisement Web sites. Larger, comprehensive Web sites generally provided better information but were less than perfect in presenting complete information on treatment options.
Audiovestibular Dysfunction Associated with Adoptive Cell Immunotherapy for Melanoma
Authors: Seaman Bradley J. , Guardiani Elizabeth A. , Brewer Carmen C. , Zalewski Christopher K. , King Kelly A. , Rudy Susan , Van Waes Carter , Morgan Richard A. , Dudley Mark E. , Yang James C. , Rosenberg Steven A. , Kim H. Jeffrey 
Published: May 2012

ObjectiveTo understand the audiologic and vestibular toxicities associated with adoptive cell immunotherapy (ACI) targeting pigment‐pathway antigens on melanoma and to investigate the use of intratympanic steroid injections in the treatment of these toxicities.Study DesignProspective nonrandomized study.SettingTertiary clinical research center.MethodsThirty‐two patients with progressive metastatic melanoma who failed conventional therapy underwent ACI with T cells genetically modified to target MART‐1 (n = 18) or gp100 (n = 14). All patients received serial audiometric testing. Vestibular testing was performed on patients with vestibular complaints. Patients with significant deficits received intratympanic steroid injections.ResultsOf 32 patients, 15 had no hearing change, 9 had mild hearing loss, and 8 had moderate hearing loss following treatment. Ten patients received intratympanic steroid injections for mild (n = 2) or moderate (n = 7) hearing loss or for significant imbalance (n = 1). Of those with mild hearing loss (n = 9), all but 1 recovered to pretreatment hearing levels. Four of 8 patients with moderate hearing loss recovered to baseline hearing levels, and 4 had partial recovery. All 7 patients with posttreatment vestibular complaints had demonstrable vestibular dysfunction. Three of these patients demonstrated recovery to normal vestibular function. The number of modified T cells infused for therapy correlated with the degree of audiovestibular deficit.ConclusionAdoptive cell immunotherapy targeting pigment‐pathway cell proteins, a novel therapy for melanoma, can induce hearing loss and vestibular dysfunction. The presumed mechanism of autoimmune attack on normal melanocytes in the cochlear stria vascularis and in the vestibular organs demonstrates the importance of melanocytes in normal inner ear function.
An empirical model for the carbon dioxide emissions of a diesel engine
Authors: Pennycott A , Zhang Q , Brace CJ , Burke RD , Akehurst S 
Published: May 2012

Carbon dioxide emissions from vehicles are a particular focus and challenge for automotive designers and manufacturers due to increasingly stringent engine emissions legislation. In addition to the potential environmental impacts, the rate of carbon dioxide production is strongly indicative of the efficiency and therefore fuel economy of an engine at its different operating conditions. In this paper, a neural network model is developed in order to predict the carbon dioxide production rate from a number of engine variables including engine speed, torque, temperature and parameters controlling fuel injection timing. The model structure accurately predicts the rate of carbon dioxide production and has applications in future efficiency and emissions optimisation during engine design and also in online engine control.
Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients before and after vitamin D supplementation
Authors: Pierrot-Deseilligny Charles , Rivaud-Péchoux Sophie , Clerson Pierre , de Paz Raphaël , Souberbielle Jean-Claude 
Published: May 2012

Background: Vitamin D could play a protective role in multiple sclerosis. Methods: In an observational, uncontrolled study, vitamin D3 supplementation (3010 IU/day on average) was given to 156 consecutive patients with relapsing–remitting multiple sclerosis, under first-line immunomodulatory therapy and with initial 25-OH-D serum level lower than 100 nmol/l (40 ng/ml). Relapses were determined for 29.1 ± 8.4 months during vitamin D and 29.8 ± 10.1 months before supplementation. The 25-OH-D level was measured before supplementation and several times during supplementation. The incidence rate of relapses before and during supplementation was estimated using negative binomial regression models with follow-up durations as offset terms. The incidence rate and incidence rate ratio of relapses at various 25-OH-D levels were also calculated using negative binomial regression models. Results: In 76 patients, immunomodulatory therapy preceded vitamin D supplementation (by 4.2 ± 2.7 years) and in 80 patients both treatments were started simultaneously. Under supplementation, the 25-OH-D level increased from 49 ± 22 nmol/l to 110 ± 26 nmol/l on average. Pooling data collected before and during supplementation, we found a significant strong inverse relationship between the relapse incidence rate and the 25-OH-D level ( p < 0.0001), suggesting that vitamin D did indeed influence the relapse rate. Results of univariate, bivariate and multivariate analyses were analogous: in the multivariate model adjusted for age, disease duration and previous use of immunomodulatory therapy, every 10 nmol increase in 25-OH-D level was associated with a reduction in the relapse incidence rate of 13.7%. Dividing iteratively the population made up of pooled periods into two subgroups according to the 25-OH-D levels, the relapse incidence rate ratio decreased as the 25-OH-D level increased up to 110 nmol/l, but a plateau effect was observed beyond this limit. Conclusion: Further studies are warranted for accurate quantification of the vitamin D effect.
Osteoblastic N-cadherin is not required for microenvironmental support and regulation of hematopoietic stem and progenitor cells
Authors: Bromberg Olga , Frisch Benjamin J. , Weber Jonathan M. , Porter Rebecca L. , Civitelli Roberto , Calvi Laura M. 
Published: May 2012

Abstract
Hematopoietic stem cell (HSC) regulation is highly dependent on interactions with the marrow microenvironment. Controversy exists on N-cadherin's role in support of HSCs. Specifically, it is unknown whether microenvironmental N-cadherin is required for normal marrow microarchitecture and for hematopoiesis. To determine whether osteoblastic N-cadherin is required for HSC regulation, we used a genetic murine model in which deletion of Cdh2, the gene encoding N-cadherin, has been targeted to cells of the osteoblastic lineage. Targeted deletion of N-cadherin resulted in an age-dependent bone phenotype, ultimately characterized by decreased mineralized bone, but no difference in steady-state HSC numbers or function at any time tested, and normal recovery from myeloablative injury. Intermittent parathyroid hormone (PTH) treatment is well established as anabolic to bone and to increase marrow HSCs through microenvironmental interactions. Lack of osteoblastic N-cadherin did not block the bone anabolic or the HSC effects of PTH treatment. This report demonstrates that osteoblastic N-cadherin is not required for regulation of steady-state hematopoiesis, HSC response to myeloablation, or for rapid expansion of HSCs through intermittent treatment with PTH.
Extracellular DNA traps are associated with the pathogenesis of TRALI in humans and mice
Authors: Thomas Grace M. , Carbo Carla , Curtis Brian R. , Martinod Kimberly , Mazo Irina B. , Schatzberg Daphne , Cifuni Stephen M. , Fuchs Tobias A. , von Andrian Ulrich H. , Hartwig John H. , Aster Richard H. , Wagner Denisa D. 
Published: May 2012

AbstractTransfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related death. The biologic processes contributing to TRALI are poorly understood. All blood products can cause TRALI, and no specific treatment is available. A “2-event model” has been proposed as the trigger. The first event may include surgery, trauma, or infection; the second involves the transfusion of antileukocyte antibodies or bioactive lipids within the blood product. Together, these events induce neutrophil activation in the lungs, causing endothelial damage and capillary leakage. Neutrophils, in response to pathogens or under stress, can release their chromatin coated with granule contents, thus forming neutrophil extracellular traps (NETs). Although protective against infection, these NETs are injurious to tissue. Here we show that NET biomarkers are present in TRALI patients' blood and that NETs are produced in vitro by primed human neutrophils when challenged with anti–HNA-3a antibodies previously implicated in TRALI. NETs are found in alveoli of mice experiencing antibody-mediated TRALI. DNase 1 inhalation prevents their alveolar accumulation and improves arterial oxygen saturation even when administered 90 minutes after TRALI onset. We suggest that NETs form in the lungs during TRALI, contribute to the disease process, and thus could be targeted to prevent or treat TRALI.
A perspective on the selection of unrelated donors and cord blood units for transplantation
Authors: Spellman Stephen R. , Eapen Mary , Logan Brent R. , Mueller Carlheinz , Rubinstein Pablo , Setterholm Michelle I. , Woolfrey Ann E. , Horowitz Mary M. , Confer Dennis L. , Hurley Carolyn K. 
Published: May 2012

Abstract
Selection of a suitable graft for allogeneic hematopoietic stem cell transplantation involves consideration of both donor and recipient characteristics. Of primary importance is sufficient donor-recipient HLA matching to ensure engraftment and acceptable rates of GVHD. In this Perspective, the National Marrow Donor Program and the Center for International Blood and Marrow Transplant Research provide guidelines, based on large studies correlating graft characteristics with clinical transplantation outcomes, on appropriate typing strategies and matching criteria for unrelated adult donor and cord blood graft selection.
European COPD Audit: design, organisation of work and methodology
Authors: López-Campos Jose Luis , Hartl Sylvia , Pozo-Rodriguez Francisco , Roberts C. Michael 
Published: May 2012

Clinical audit has an important role as an indicator of the clinical practice in a given community. The European Respiratory Society (ERS) chronic obstructive pulmonary disease (COPD) audit was designed as a pilot study to evaluate clinical practice variability as well as clinical and organisational factors related to outcomes for COPD hospital admissions across Europe.The study was designed as a prospective observational noninterventional cohort trial, in which 422 hospitals from 13 European countries participated. There were two databases: one for hospital’s resources and organisation and one for clinical information.The study was comprised of an initial 8-week phase during which all consecutive cases admitted to hospital due to an exacerbation of COPD were identified and information on clinical practice was gathered. During the 90-day second phase, mortality and readmissions were recorded. Patient data were anonymised and encrypted through a multi-lingual web-tool. As there is no pan-European Ethics Committee for audits, all partners accepted the general ethical rules of the ERS and ensured compliance with their own national ethical requirements.This paper describes the methodological issues encountered in organising and delivering a multi-national European audit, highlighting goals, barriers and achievements, and provides valuable information for those interested in developing clinical audits.
Evaluation of upper airway patency during Cheyne–Stokes breathing in heart failure patients
Authors: Jobin Vincent , Rigau Jordi , Beauregard Josée , Farre Ramon , Monserrat Josep , Bradley T. Douglas , Kimoff R. John 
Published: May 2012

Little is known about the changes in upper airway calibre in Cheyne–Stokes respiration (CSR) during sleep in patients with congestive heart failure. This study aimed to test the hypothesis that upper airway closure occurs during central CSR events, by assessing upper airway calibre during sleep using the forced oscillation technique (FOT).Nine males with compensated heart failure (left ventricular ejection fraction mean±sem27.9±5.1%) and predominant central CSR (apnoea/hypopnoea index 43.9±4.2 events·h−1) were studied during overnight polysomnography, which included pneumotachography, inductance plethysmography or oesophageal pressure and FOT-derived impedance signal (|Z|).Baseline |Z| values during stable breathing in stage 2 sleep were 11.0±1.3 cmH2O·s·L−1. Mean |Z| increased to 31.9±6.7 cmH2O·s·L−1during obstructive apnoeas (7% of events, n=46). Increases in |Z| consistent with upper airway narrowing (more than two-fold baseline) were common during central apnoeas (50±12% of events) occurring in the middle or end of apnoeas and occurred during some central hypopnoeas (16±10% of events), typically in the expiratory phase.These findings indicate that in heart failure patients, reductions in upper airway calibre are common during CSR apnoeas, and may also occur during central hypopnoeas.
Demasculinization of the Anopheles gambiae X chromosome
Authors: Magnusson Kalle , Lycett Gareth J , Mendes Antonio M , Lynd Amy , Papathanos Philippos-Aris , Crisanti Andrea , Windbichler Nikolai 
Published: May 2012

Abstract

Background
In a number of organisms sex-biased genes are non-randomly distributed between autosomes and the shared sex chromosome X (or Z). Studies on Anopheles gambiae have produced conflicting results regarding the underrepresentation of male-biased genes on the X chromosome and it is unclear to what extent sexual antagonism, dosage compensation or X-inactivation in the male germline, the evolutionary forces that have been suggested to affect the chromosomal distribution of sex-biased genes, are operational in Anopheles.

Results
We performed a meta-analysis of sex-biased gene expression in Anopheles gambiae which provides evidence for a general underrepresentation of male-biased genes on the X-chromosome that increased in significance with the observed degree of sex-bias. A phylogenomic comparison between Drosophila melanogaster, Aedes aegypti and Culex quinquefasciatus also indicates that the Anopheles X chromosome strongly disfavours the evolutionary conservation of male-biased expression and that novel male-biased genes are more likely to arise on autosomes. Finally, we demonstrate experimentally that transgenes situated on the Anopheles gambiae X chromosome are transcriptionally silenced in the male germline.

Conclusion
The data presented here support the hypothesis that the observed demasculinization of the Anopheles X chromosome is driven by X-chromosome inactivation in the male germline and by sexual antagonism. The demasculinization appears to be the consequence of a loss of male-biased expression, rather than a failure in the establishment or the extinction of male-biased genes.