bluuebunny/crossref_metadata_2025_split huggingface dataset:
The neuronal guidance protein netrin-1 reduces alveolar inflammation in a porcine model of acute lung injury
Authors: Mutz Christian , Mirakaj Valbona , Vagts Dierk A , Westermann Phillipp , Waibler Kristina , König Klemens , Iber Thomas , Nöldge-Schomburg Gabriele , Rosenberger Peter 
Published: November 2010

Abstract
Introduction
Acute lung injury (ALI) is an inflammatory disorder of pulmonary or extrapulmonary origin. We have previously demonstrated that netrin-1 dampens murine ALI, and in an attempt to advance this finding into future clinical practice we evaluated whether netrin-1 would reduce alveolar inflammation during porcine ALI.

Methods
This was a controlled in vivo experimental study in pigs. We induced ALI through lipoploysaccharide (LPS) infusion (50 μg/kg) for 2 hours. Following this, we exposed animals to either vehicle, intravenous netrin-1 (netrin-1 i.v.) or inhaled netrin-1 (netrin-1 inh.). Serum samples and bronchoalveolar lavage (BAL) were obtained to determine levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, interleukin-6 and interleukin-8 at baseline and 6 hours following treatment. Myeloperoxidase activity (MPO) and protein levels were determined in the BAL, and tissue samples were obtained for histological evaluation. Finally, animals were scanned with spiral CT.

Results
Following LPS infusion, animals developed acute pulmonary injury. Serum levels of TNF-α and IL-6 were significantly reduced in the netrin-1 i.v. group. BAL demonstrated significantly reduced cytokine levels 6 hours post-netrin-1 treatment (TNF-α: vehicle 633 ± 172 pg/ml, netrin-1 i.v. 84 ± 5 pg/ml, netrin-1 inh. 168 ± 74 pg/ml; both P < 0.05). MPO activity and protein content were significantly reduced in BAL samples from netrin-1-treated animals. Histological sections confirmed reduced inflammatory changes in the netrin-1-treated animals. Computed tomography corroborated reduced pulmonary damage in both netrin-1-treated groups.

Conclusions
We conclude that treatment with the endogenous anti-inflammatory protein netrin-1 reduces pulmonary inflammation during the initial stages of ALI and should be pursued as a future therapeutic option.
Cost-consequence analysis of remifentanil-based analgo-sedation vs. conventional analgesia and sedation for patients on mechanical ventilation in the Netherlands
Authors: Al Maiwenn J , Hakkaart Leona , Tan SiokSwan , Bakker Jan 
Published: November 2010

AbstractIntroductionHospitals are increasingly forced to consider the economics of technology use. We estimated the incremental cost-consequences of remifentanil-based analgo-sedation (RS) vs. conventional analgesia and sedation (CS) in patients requiring mechanical ventilation (MV) in the intensive care unit (ICU), using a modelling approach.MethodsA Markov model was developed to describe patient flow in the ICU. The hourly probabilities to move from one state to another were derived from UltiSAFE, a Dutch clinical study involving ICU patients with an expected MV-time of two to three days requiring analgesia and sedation. Study medication was either: CS (morphine or fentanyl combined with propofol, midazolam or lorazepam) or: RS (remifentanil, combined with propofol when required). Study drug costs were derived from the trial, whereas all other ICU costs were estimated separately in a Dutch micro-costing study. All costs were measured from the hospital perspective (price level of 2006). Patients were followed in the model for 28 days. We also studied the sub-population where weaning had started within 72 hours.ResultsThe average total 28-day costs were €15,626 with RS versus €17,100 with CS, meaning a difference in costs of €1474 (95% CI -2163, 5110). The average length-of-stay (LOS) in the ICU was 7.6 days in the RS group versus 8.5 days in the CS group (difference 1.0, 95% CI -0.7, 2.6), while the average MV time was 5.0 days for RS versus 6.0 days for CS. Similar differences were found in the subgroup analysis.ConclusionsCompared to CS, RS significantly decreases the overall costs in the ICU.Trial RegistrationClinicaltrials.gov NCT00158873.
Comorbidity and Mortality Results From a Randomized Prostate Cancer Screening Trial
Authors: Crawford E. David , Grubb Robert , Black Amanda , Andriole Gerald L. , Chen Ming-Hui , Izmirlian Grant , Berg Christine D. , D'Amico Anthony V. 
Published: November 2010

Purpose Estimates of prostate cancer–specific mortality (PCSM) were similar for men randomly assigned to intervention compared with usual care on the Prostate, Lung, Colorectal and Ovarian PC screening study. However, results analyzed by comorbidity strata remain unknown. Patients and Methods Between 1993 and 2001, of 76,693 men who were randomly assigned to usual care or intervention at 10 US centers, 73,378 (96%) completed a questionnaire that inquired about comorbidity and prostate-specific antigen (PSA) testing before random assignment. Fine and Gray's multivariable analysis was performed to assess whether the randomized screening arm was associated with the risk of PCSM in men with no or minimal versus at least one significant comorbidity, adjusting for age and prerandomization PSA testing. Results After 10 years of follow-up, 9,565 deaths occurred, 164 from PC. A significant decrease in the risk of PCSM (22 v 38 deaths; adjusted hazard ratio [AHR], 0.56; 95% CI, 0.33 to 0.95; P = .03) was observed in men with no or minimal comorbidity randomly assigned to intervention versus usual care, and the additional number needed to treat to prevent one PC death at 10 years was five. Among men with at least one significant comorbidity, those randomly assigned to intervention versus usual care did not have a decreased risk of PCSM (62 v 42 deaths; AHR, 1.43; 95% CI, 0.96 to 2.11; P = .08). Conclusion Selective use of PSA screening for men in good health appears to reduce the risk of PCSM with minimal overtreatment.
Strategies for Prolonged Therapy in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Fidias Panos , Novello Silvia 
Published: November 2010

Purpose A key challenge in the treatment of advanced non–small-cell lung cancer (NSCLC) is improving outcomes for patients who have achieved at least stable disease after standard first-line therapy. Although current guidelines recommend a maximum of six cycles of first-line therapy, even in responding patients, recent trials have shown benefit with maintenance therapy. Methods We reviewed the English literature for randomized controlled trials on prolonged therapy for NSCLC conducted between January 1999 and January 2010. The search was supplemented by a review of abstracts presented at the American Society of Clinical Oncology annual meetings (2004 to 2010), the World Lung Cancer Conference (2007 to 2009), and the 2009 Joint European CanCer Organisation-European Society for Medical Oncology conference. Results Several alternative strategies for prolongation of chemotherapy have been tested: these can be broadly categorized as continuation (prolongation of the first-line regimen until disease progression, unacceptable toxicity, or administration of a predefined greater number of treatment cycles), switch-maintenance (administration of an active agent immediately after completion of the initial course of chemotherapy), and continuation-maintenance (ongoing administration of a lower intensity version of the first-line chemotherapy regimen). These approaches differ from traditional second line, which is defined as treatment administered after documented clinical progression subsequent to first-line therapy. Conclusion There are no data to support continuation chemotherapy in advanced NSCLC. Switch-maintenance trials with erlotinib and pemetrexed have demonstrated an improvement in overall survival. Thus far, continuation-maintenance has shown an improvement in progression-free survival, without an overall survival advantage.
Axial Response and Bearing Capacity of Tapered Piles in Sandy Soil
Authors: Paik Kyuho , Lee Junhwan , Kim Daehong 
Published: November 2010

Abstract
14 calibration chamber tests were performed to investigate the axial responses of tapered piles in sandy soil. Three instrumented model piles with different taper angles, designed to have the same volume, were used in the tests. Results of the model pile load tests showed that the shaft load of tapered piles continuously increased with pile settlement, whereas that of cylindrical piles reached the ultimate values at a settlement equal to about 2 % of the pile diameter. The ratio of the load capacity of tapered piles to that of cylindrical piles was found to vary with both the taper angle of the piles and the soil condition of the sands. The ultimate unit shaft resistance of tapered piles was always greater than that of cylindrical piles irrespective of soil condition, whereas the ultimate unit base resistance of tapered piles was greater than that of cylindrical piles for dense sand with lateral earth pressure coefficients higher than 0.42. It was also observed that the ultimate unit shaft resistance of piles increases with increasing taper angle regardless of the relative density and stress state of the sand. However, the ultimate unit base resistance of piles increases with increasing taper angle for medium sand, but decreases for dense sand. In addition, based on the results of the model pile tests, taper factors for the ultimate unit base and shaft resistances, which can be used to estimate the base and shaft load capacities of tapered piles, were proposed.
Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors
Authors: Färkkilä Anniina , Anttonen Mikko , Pociuviene Jurate , Leminen Arto , Butzow Ralf , Heikinheimo Markku , Unkila-Kallio Leila 
Published: November 2010

ObjectiveOvarian granulosa cell tumors (GCTs) are hormonally active sex cord stromal tumors accounting for 3–5% of all ovarian cancers. These tumors are generally diagnosed at an early stage but there is a high risk of recurrence, associated with high mortality. Treatment of recurrent GCTs is difficult, and biologically targeted treatment modalities are lacking. GCTs are highly vascularized, and angiogenic factors most probably play a role in their pathology. Vascular endothelial growth factor (VEGF) is a key regulator of tumor angiogenesis, but in GCTs, the role of VEGF and its receptors VEGFR-1 (FLT1) and VEGFR-2 (KDR) remains largely unknown. Our objective is to study the expression of VEGF and its receptors in human GCTs.MethodsWe analyzed GCTs from 106 patients for the expressions of VEGF and its receptors utilizing tumor tissue microarray, tumor mRNA, and patient serum samples.ResultsWe found that VEGF and its main biologically active receptor VEGFR-2 were highly expressed in primary and recurrent GCTs, when compared with normal granulosa-lutein cells. The expression of VEGF correlated positively to tumor microvessel density and to VEGFR-2 expression at the protein (P<0.05) and mRNA (P<0.05) levels. In contrast to VEGFR-2, the expression of VEGFR-1 was weak. Tumor VEGF protein expression was not prognostic for recurrence, however, we found high levels of circulating VEGF in the serum of patients with primary GCT.ConclusionsThe results suggest an important role of VEGF and VEGFR-2 in GCT pathology and support the possibility of applying novel VEGF- or VEGFR-2-targeted treatments to patients with GCT.
Mutational Effects and Population Dynamics During Viral Adaptation Challenge Current Models
Authors: Miller Craig R , Joyce Paul , Wichman Holly A 
Published: November 2010

Abstract
Adaptation in haploid organisms has been extensively modeled but little tested. Using a microvirid bacteriophage (ID11), we conducted serial passage adaptations at two bottleneck sizes (104 and 106), followed by fitness assays and whole-genome sequencing of 631 individual isolates. Extensive genetic variation was observed including 22 beneficial, several nearly neutral, and several deleterious mutations. In the three large bottleneck lines, up to eight different haplotypes were observed in samples of 23 genomes from the final time point. The small bottleneck lines were less diverse. The small bottleneck lines appeared to operate near the transition between isolated selective sweeps and conditions of complex dynamics (e.g., clonal interference). The large bottleneck lines exhibited extensive interference and less stochasticity, with multiple beneficial mutations establishing on a variety of backgrounds. Several leapfrog events occurred. The distribution of first-step adaptive mutations differed significantly from the distribution of second-steps, and a surprisingly large number of second-step beneficial mutations were observed on a highly fit first-step background. Furthermore, few first-step mutations appeared as second-steps and second-steps had substantially smaller selection coefficients. Collectively, the results indicate that the fitness landscape falls between the extremes of smooth and fully uncorrelated, violating the assumptions of many current mutational landscape models.
Distinguishing Positive Selection From Neutral Evolution: Boosting the Performance of Summary Statistics
Authors: Lin Kao , Li Haipeng , Schlötterer Christian , Futschik Andreas 
Published: November 2010

Abstract
Summary statistics are widely used in population genetics, but they suffer from the drawback that no simple sufficient summary statistic exists, which captures all information required to distinguish different evolutionary hypotheses. Here, we apply boosting, a recent statistical method that combines simple classification rules to maximize their joint predictive performance. We show that our implementation of boosting has a high power to detect selective sweeps. Demographic events, such as bottlenecks, do not result in a large excess of false positives. A comparison to other neutrality tests shows that our boosting implementation performs well compared to other neutrality tests. Furthermore, we evaluated the relative contribution of different summary statistics to the identification of selection and found that for recent sweeps integrated haplotype homozygosity is very informative whereas older sweeps are better detected by Tajima's π. Overall, Watterson's θ was found to contribute the most information for distinguishing between bottlenecks and selection.
Differential Maintenance of DNA Sequences in Telomeric and Centromeric Heterochromatin
Authors: DeBaryshe P G , Pardue Mary-Lou 
Published: November 2010

AbstractRepeated DNA in heterochromatin presents enormous difficulties for whole-genome sequencing; hence, sequence organization in a significant portion of the genomes of multicellular organisms is relatively unknown. Two sequenced BACs now allow us to compare telomeric retrotransposon arrays from Drosophila melanogaster telomeres with an array of telomeric retrotransposons that transposed into the centromeric region of the Y chromosome &gt;13 MYA, providing a unique opportunity to compare the structural evolution of this retrotransposon in two contexts. We find that these retrotransposon arrays, both heterochromatic, are maintained quite differently, resulting in sequence organizations that apparently reflect different roles in the two chromosomal environments. The telomere array has grown only by transposition of new elements to the chromosome end; the centromeric array instead has grown by repeated amplifications of segments of the original telomere array. Many elements in the telomere have been variably 5′-truncated apparently by gradual erosion and irregular deletions of the chromosome end; however, a significant fraction (4 and possibly 5 or 6 of 15 elements examined) remain complete and capable of further retrotransposition. In contrast, each element in the centromere region has lost ≥40% of its sequence by internal, rather than terminal, deletions, and no element retains a significant part of the original coding region. Thus the centromeric array has been restructured to resemble the highly repetitive satellite sequences typical of centromeres in multicellular organisms, whereas, over a similar or longer time period, the telomere array has maintained its ability to provide retrotransposons competent to extend telomere ends.
Ingestion of Lantana camara Is Not Associated With Significant Effects in Children
Authors: Carstairs Shaun D. , Luk Joyce Y. , Tomaszewski Christian A. , Cantrell F. Lee 
Published: November 2010

OBJECTIVE:
We sought to identify characteristics of children with reported ingestion of Lantana camara.

METHODS:
We reviewed the California Poison Control System database for all reported pediatric ingestions of L camara for the years 1997–2008. Data collected included age, gender, clinical effects, duration of effects, medical interventions, and outcomes.

RESULTS:
There were a total of 641 patients; patient ages ranged from 1 to 16 years, with a mean of 2.5 years. Reported effects included vomiting (n = 30), abdominal pain (n = 8), agitation (n = 6), diarrhea (n = 6), throat/mouth irritation (n = 5), tachycardia (n = 4), drowsiness (n = 3), nausea (n = 2), and mydriasis (n = 1). There was no difference in frequency of symptoms between patients who ingested ripe (15.5% [95% confidence interval: 9.1%–21.8%]) versus unripe (6.0% [95% confidence interval: 0.9%–11.1%]) berries or between patients who ingested berries (10.5% [95% confidence interval: 7.3%–13.8%]) versus other plant parts (7.1% [95% confidence interval: 4.0%–10.3%]). Fifty-one patients (8%) were treated in a health care facility and 2 (0.3%) were admitted. No significant effects and no deaths were recorded.

CONCLUSIONS:
Ingestion of L camara (including unripe berries) was not associated with significant toxicity; patients who ingested unripe berries did not exhibit more-frequent or more-severe symptoms than did patients who ingested ripe berries or other plant parts. Most patients displayed no or minimal symptoms. Children with asymptomatic ingestions and those with mild symptoms can be treated at home.
Optimal Sequence of Implied Modalities in the Adjuvant Setting of Breast Cancer Treatment: An Update on Issues To Consider
Authors: Tsoutsou Pelagia G. , Belkacemi Yazid , Gligorov Joseph , Kuten Abraham , Boussen Hamouda , Bese Nuran , Koukourakis Michael I. ,   on behalf of the Association of Radiotherapy and Oncology in the Mediterranean area (AROME)
Published: November 2010

Abstract
The adjuvant setting of early breast cancer treatment is an evolving field where different modalities must be combined to improve outcomes; moreover, quality of life of breast cancer survivors emerges as a new important parameter to consider, thus implying a better understanding of toxicities of these modalities. We have conducted a review focusing on the latest literature of the past 3 years, trying to evaluate the existing data on the maximum acceptable delay of radiotherapy when given as sole adjuvant treatment after surgery and the optimal sequence of all these modalities with respect to each other. It becomes evident radiotherapy should be given as soon as possible and within a time frame of 6–20 weeks. Chemotherapy is given before radiotherapy and hormone therapy. However, radiotherapy should be started within 7 months after surgery in these cases. Hormone therapy with tamoxifen might be given safely concomitantly or sequentially with radiotherapy although solid data are still lacking. The concurrent administration of letrozole and radiotherapy seems to be safe, whereas data on trastuzumab can imply only that it is safe to use concurrently with radiotherapy. Randomized comparisons of hormone therapy and trastuzumab administration with radiotherapy need to be performed.
Heritability of Alveolar Bone Loss From Periodontal Disease in a Baboon Population: A Pilot Study
Authors: Miley D. Douglas , Baumgartner Mark H. , Cheverud James M. , Roseman Charles C. , Rogers Jeffrey , McLeod Dwight E. , Reyes Elio , Hildebolt Charles F. 
Published: November 2010

Background: Reports from studies of twins, disease aggregation in families, animal models for periodontal disease, and various genetic‐analysis studies have determined that genetics plays a role in the susceptibility to periodontal disease. The purpose of this pilot study is to evaluate the effect of genetics on periodontal disease by evaluating the heritability of alveolar bone loss in a captive baboon population.Methods: A collection of baboon skulls from a pedigreed colony (for which scientists and veterinarians maintain complete genealogic and veterinary records) was obtained from the Southwest National Primate Research Center, San Antonio, Texas and used in this pilot study. Measurements of alveolar bone loss were performed on 390 dry baboon skulls. A periodontal probe was used to measure alveolar bone loss. Maximum likelihood methods (designed to handle complex genealogies) were used to determine the heritability of alveolar bone loss. This software used known pedigrees in the captive baboon sample and tested the relationship between pairwise kinship and alveolar bone loss data to determine the heritability of alveolar bone loss from periodontal disease.Results: Genetic data were available for 347 of the 390 specimens. Using age and sex as covariates, genetic analysis indicated a heritability of 35% (standard error = 20%; P = 0.01). Although gender was not a significant factor in periodontal disease (P = 0.96), age was highly significantly associated with periodontal disease (P <0.0001).Conclusions: In this pilot study, analysis of alveolar bone loss measurements from captive baboons indicates that bone loss increases with age and that a portion of periodontal disease risk may be caused by genetic variance. These findings provide evidence that periodontal disease is heritable in captive baboons and indicate that a larger, more‐detailed study is warranted.
Essential Oils Compared to Chlorhexidine With Respect to Plaque and Parameters of Gingival Inflammation: A Systematic Review
Authors: Van Leeuwen M.P.C. , Slot D.E. , Van der Weijden G.A. 
Published: November 2010

Background: The purpose of this review is to systematically evaluate the effects of an essential‐oil mouthwash (EOMW) compared to a chlorhexidine mouthwash with respect to plaque and parameters of gingival inflammation.Methods: PubMed/MEDLINE and Cochrane CENTRAL databases were searched for studies up to and including September 2010 to identify appropriate articles. A comprehensive search was designed, and the articles were independently screened for eligibility by two reviewers. Articles that evaluated the effects of the EOMW compared to chlorhexidine mouthwash were included. Where appropriate, a meta‐analysis was performed, and weighted mean differences (WMDs) were calculated.Results: A total of 390 unique articles were found, of which 19 articles met the eligibility criteria. A meta‐analysis of long‐term studies (duration ≥4 weeks) showed that the chlorhexidine mouthwash provided significantly better effects regarding plaque control than EOMW (WMD: 0.19; P = 0.0009). No significant difference with respect to reduction of gingival inflammation was found between EOMW and chlorhexidine mouthwash (WMD: 0.03; P = 0.58).Conclusion: In long‐term use, the standardized formulation of EOMW appeared to be a reliable alternative to chlorhexidine mouthwash with respect to parameters of gingival inflammation.