bluuebunny/crossref_metadata_2025_split huggingface dataset:
The neuroepithelial basement membrane serves as a boundary and a substrate for neuron migration in the zebrafish hindbrain
Authors: Grant Paul K , Moens Cecilia B 
Published: March 2010

Abstract
Background
The facial branchiomotor neurons of cranial nerve VII undergo a stereotyped tangential migration in the zebrafish hindbrain that provides an ideal system for examining the complex interactions between neurons and their environment that result in directed migration. Several studies have shown the importance of the planar cell polarity pathway in facial branchiomotor neuron migration but the role of apical-basal polarity has not been determined. Here we examine the role of the PAR-aPKC complex in forming the basal structures that guide facial branchiomotor neurons on an appropriate migratory path.

Results
High resolution timelapse imaging reveals that facial branchiomotor neurons begin their migration by moving slowly ventrally and posteriorly with their centrosomes oriented medially and then, upon contact with the Laminin-containing basement membrane at the rhombomere 4-rhombomere 5 boundary, speed up and reorient their centrosomes on the anterior-posterior axis. Disruption of the PAR-aPKC complex members aPKCλ, aPKCζ, and Pard6gb results in an ectopic ventral migration in which facial branchiomotor neurons escape from the hindbrain through holes in the Laminin-containing basement membrane. Mosaic analysis reveals that the requirement for aPKC is cell-nonautonomous, indicating that it is likely required in the surrounding polarized neuroepithelium rather than in facial motor neurons themselves. Ventral facial motor neuron ectopia can be phenocopied by mutation of lamininα1, suggesting that it is defects in maintenance of the laminin-containing basement membrane that are the likely cause of ventral mismigration in aPKCλ+ζ double morphants.

Conclusions
Our results suggest that the laminin-containing ventral basement membrane, dependent on the activity of the PAR-aPKC complex in the hindbrain neuroepithelium, is both a substrate for migration and a boundary that constrains facial branchiomotor neurons to the appropriate migratory path.
Calcium deposition in osteoarthritic meniscus and meniscal cell culture
Authors: Sun Yubo , Mauerhan David R , Honeycutt Patrick R , Kneisl Jeffrey S , Norton H James , Zinchenko Natalia , Hanley Edward N , Gruber Helen E 
Published: March 2010

Abstract
Introduction
Calcium crystals exist in the knee joint fluid of up to 65% of osteoarthritis (OA) patients and the presence of these calcium crystals correlates with the radiographic evidence of hyaline cartilaginous degeneration. This study sought to examine calcium deposition in OA meniscus and to investigate OA meniscal cell-mediated calcium deposition. The hypothesis was that OA meniscal cells may play a role in pathological meniscal calcification.

Methods
Studies were approved by our human subjects Institutional Review Board. Menisci were collected during joint replacement surgeries for OA patients and during limb amputation surgeries for osteosarcoma patients. Calcium deposits in menisci were examined by alizarin red staining. Expression of genes involved in biomineralization in OA meniscal cells was examined by microarray and real-time RT-PCR. Cell-mediated calcium deposition in monolayer culture of meniscal cells was examined using an ATP-induced 45calcium deposition assay.

Results
Calcium depositions were detected in OA menisci but not in normal menisci. The expression of several genes involved in biomineralization including ENPP1 and ANKH was upregulated in OA meniscal cells. Consistently, ATP-induced calcium deposition in the monolayer culture of OA meniscal cells was much higher than that in the monolayer culture of control meniscal cells.

Conclusions
Calcium deposition is common in OA menisci. OA meniscal cells calcify more readily than normal meniscal cells. Pathological meniscal calcification, which may alter the biomechanical properties of the knee meniscus, is potentially an important contributory factor to OA.
Improved Survival of Children With Neuroblastoma Between 1979 and 2005: A Report of the Italian Neuroblastoma Registry
Authors: Haupt Riccardo , Garaventa Alberto , Gambini Claudio , Parodi Stefano , Cangemi Giuliana , Casale Fiorina , Viscardi Elisabetta , Bianchi Maurizio , Prete Arcangelo , Jenkner Alessandro , Luksch Roberto , Di Cataldo Andrea , Favre Claudio , D'Angelo Paolo , Zanazzo Giulio Andrea , Arcamone Giampaolo , Izzi Gian Carlo , Gigliotti Anna Rita , Pastore Guido , Bernardi Bruno De 
Published: March 2010

Purpose To describe treatment, clinical course, and survival of a cohort of Italian patients with neuroblastoma. Patients and Methods The study includes data from 2,216 children (age 0 to 14 years) diagnosed between 1979 and 2005. Overall survival (OS) was analyzed by clinical and biologic features at presentation and periods of diagnosis: 1979 to 1984, 1985 to 1991, 1992 to 1998, and 1999 to 2005. The relative risk of second malignant neoplasm (SMN) was assessed by the standardized incidence ratio (SIR), with the Italian population selected as referent. Results Yearly patient accrual increased over time from 58 to 102. Patients age 0 to 17 months represented 45.6% of the total population, and their incidence increased over time from 36.5% to 48.5%. The incidence of stage 1 patients increased over time from 5.8% to 23.2%. A total of 898 patients (40.5%) developed disease progression or relapse, 19 patients developed SMN, and two patients developed myelodysplasia. The cumulative risk of SMN at 20 years was 7.1%, for an SIR of 8.4 (95% CI, 5.1 to 13.2). A total of 858 patients (39%) died (779 of disease, 71 of toxicity, six of SMN, and two of tumor-unrelated surgical complications). Ten-year OS was 55.3% (95% CI, 53.0% to 57.6%) and increased over time from 34.9% to 65.0%; it was significantly better for females and patients age 0 to 17 months at diagnosis, with extra-abdominal primary, and stage 1 and 2 disease. OS improved significantly over time in stage 1 and 3 patients. In patients with stage 4 disease, the improvement occurred between the first and second time cohorts (6.7% v 23.5%), but not afterward. Conclusion The outcome of children with neuroblastoma has progressively improved. Long-term survivors bear a significant risk of SMN.
Chemotherapy and Survival Benefit in Elderly Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Davidoff Amy J. , Tang Mei , Seal Brian , Edelman Martin J. 
Published: March 2010

Purpose Platinum-doublet chemotherapy regimens have been shown to extend survival in fit patients with advanced non–small-cell lung cancer (AdvNSCLC). This study extends recent population-based analyses focusing on treatment and survival benefit from use of platinum-doublet therapy, and addressing the role of performance status (PS). Patients and Methods Patients ≥ 66 years with AdvNSCLC incident from 1997 to 2002 were identified in SEER-Medicare. Multivariate models examined tumor and patient characteristics associated with receipt of any chemotherapy and receipt of platinum-doublet compared with single-agent therapy. Nonparametric models estimated treatment effects on survival. Models controlled for patient characteristics, including a novel method to use claims-based indicators to characterize PS. Propensity score analysis adjusted for confounding. Results Of the 21,285 patients, 25.8% received first-line chemotherapy. Multivariate analyses indicate lower use of any chemotherapy and platinum-based doublet regimens with increasing age, comorbidity, and poor PS. Receipt of any chemotherapy was associated with reduction in the adjusted hazard of death (0.558; 95% CI, 0.547 to 0.569) and an increase in adjusted 1-year survival from 11.6% (95% CI, 11.1 to 12.0) to 27.0% (95% CI, 26.4 to 27.6). Platinum-doublet receipt increased adjusted 1-year survival over single agents, from 19.4% (95% CI, 18.3 to 20.4) to 30.1% (95% CI, 28.9 to 31.4). Conclusion Most elderly patients with AdvNSCLC do not receive chemotherapy, yet there are clear survival benefits, even with controls for age, comorbidity, and PS. The benefit of platinum-based doublet regimens is greater than single-agent chemotherapy. Claims-based proxy indicators of poor PS were independent predictors of treatment and merit further exploration.
Fusion Gene–Negative Alveolar Rhabdomyosarcoma Is Clinically and Molecularly Indistinguishable From Embryonal Rhabdomyosarcoma
Authors: Williamson Daniel , Missiaglia Edoardo , de Reyniès Aurélien , Pierron Gaëlle , Thuille Benedicte , Palenzuela Gilles , Thway Khin , Orbach Daniel , Laé Marick , Fréneaux Paul , Pritchard-Jones Kathy , Oberlin Odile , Shipley Janet , Delattre Olivier 
Published: March 2010

PurposeTo determine whether the clinical and molecular biologic characteristics of the alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS) subtypes have relevance independent of the presence or absence of the PAX/FOXO1 fusion gene.Patients and MethodsThe fusion gene status of 210 histopathologically reviewed, clinically annotated rhabdomyosarcoma samples was determined by reverse transcriptase polymerase chain reaction. Kaplan-Meier analysis was used to assess event-free survival and overall survival in fusion gene–negative ARMS (ARMSn; n = 39), fusion gene–positive ARMS (ARMSp; n = 94), and ERMS (n = 77). A total of 101 RMS samples were also profiled for whole-genome expression, and 128 were profiled for genomic copy number imbalances. Profiling data were analyzed by supervised and unsupervised methods to compare features related to histopathology and fusion gene status. Results were also projected by meta-analysis techniques across three separate publically available data sets.ResultsOverall and event-free survival, frequency of metastases, and distribution of site at initial presentation were not significantly different between ARMSn and ERMS. Consistent with this, analysis of gene expression signatures could not reproducibly distinguish ARMSn from ERMS whereas fusion gene–positive cases were distinct. ARMSn and ERMS frequently show whole-chromosome copy number changes, notably gain of chromosome 8 with associated high levels of expression of genes from this chromosome.ConclusionThe clinical behavior and molecular characteristics of alveolar cases without a fusion gene are indistinguishable from embryonal cases and significantly different from fusion-positive alveolar cases. This implies that fusion gene status irrespective of histology is a critical factor in risk stratification of RMS.
Phase II Study of Pegylated Arginine Deiminase for Nonresectable and Metastatic Hepatocellular Carcinoma
Authors: Glazer Evan S. , Piccirillo Mauro , Albino Vittorio , Di Giacomo Raimondo , Palaia Raffaele , Mastro Angelo A. , Beneduce Gerardo , Castello Giuseppe , De Rosa Vincenzo , Petrillo Antonella , Ascierto Paolo A. , Curley Steven A. , Izzo Francesco 
Published: March 2010

Purpose It is well known that hepatocellular carcinoma (HCC) is an arginine auxotroph due to argininosuccinate synthetase I deficiency. This study's purpose was to evaluate the effects of pegylated arginine deiminase (ADI) in terms of toxicity, tumor response, α-fetoprotein (AFP) levels, and serum arginine levels. Patients and Methods Eighty patients were randomly assigned to receive either 80 IU/m2 or 160 IU/m2 of ADI weekly for up to 6 months. Adverse events, serum arginine, AFP levels, and antibody production against ADI were measured on a regular basis. In addition, disease response and time to progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) and survival rates were evaluated. Results Four patients were excluded from the survival analysis because they developed exclusion criteria after randomization, but before first treatment. The number of patients in the two cohorts were similar (n = 37 in the low-dose cohort, n = 39 in the high-dose cohort). Mean (±SE) survival for all subjects was 15.8 months (474 days ± 39 days) from time of diagnosis of unresectable disease. Arginine levels remained below baseline for 50 days while antibodies against ADI reached a plateau at approximately the same time. There were no deaths attributed to ADI treatment. Only two patients were withdrawn for immunogenic-related adverse events. Grade 2, 3, or 4 toxicities were recorded in 92, 19, and 0 patients, respectively. Conclusion Pegylated ADI is a promising drug that capitalizes on a significant enzymatic deficiency in HCC. It is safe, well tolerated, and may benefit patients with unresectable HCC.
Patterns and Correlates of Adjuvant Radiotherapy Receipt After Lumpectomy and After Mastectomy for Breast Cancer
Authors: Jagsi Reshma , Abrahamse Paul , Morrow Monica , Hawley Sarah T. , Griggs Jennifer J. , Graff John J. , Hamilton Ann S. , Katz Steven J. 
Published: March 2010

Purpose To use patient self-report to provide more valid estimates of whether radiotherapy (RT) is underutilized than possible with registry data, as well as to evaluate for disparities and the influence of preferences and provider interactions. Methods We considered 2,260 survey respondents who had nonmetastatic breast cancer, were age 20 to 79 years, were diagnosed between July 2005 and February 2007 in Detroit and Los Angeles, and reported to Surveillance, Epidemiology and End Results (SEER) registries (72% response rate). Survey responses were merged with SEER data. We assessed rates and correlates of RT receipt among all patients with invasive cancer receiving breast-conserving surgery (BCS) and among patients undergoing mastectomy with indications for RT (ie, positive lymph nodes or T3-4 tumors). Results Among 904 patients undergoing BCS with strong indications for RT, 95.4% received RT, and 77.6% received RT among the 135 patients undergoing mastectomy with strong indications (P < .001). Among 114 patients undergoing BCS with weaker indications (ie, elderly) for RT, 80.0% received treatment, and 47.5% received RT among the 164 patients undergoing mastectomy with weaker indications (T1N1, T2N1, or T3N0 disease; P < .001). On multivariate analysis, surgery type (P < .001), indication strength (P < .001), age (P = .005), comorbidity (P < .001), income (P = .03), patient desire to avoid RT (P < .001), level of surgeon involvement in decision to have radiation (P < .001), and SEER site (P < .001) were significantly associated with likelihood of RT receipt. Conclusion RT receipt was consistently high across sociodemographic subgroups after BCS but was lower after mastectomy, even among patients with strong indications for treatment, in whom clinical benefit is similar. Surgeon involvement had a strong influence on RT receipt.
LIN28B in Constitutional Delay of Growth and Puberty
Authors: Tommiska Johanna , Wehkalampi Karoliina , Vaaralahti Kirsi , Laitinen Eeva-Maria , Raivio Taneli , Dunkel Leo 
Published: March 2010

AbstractBackground: Recently variation in LIN28B, a human ortholog of the gene-regulating processing of micro-RNAs (miRNAs) controlling the timing of major developmental events in the nematode Caenorhabtidis elegans, was reported to be associated with timing of puberty in humans. In C. elegans, a gain-of-function allele of lin-28 causes a retarded phenotype.Objective: The objective of the study was to evaluate the variation in the LIN28B gene in 145 subjects with constitutional delay of growth and puberty (CDGP).Patients and Methods: For this study, 115 males and 30 females with CDGP were included. CDGP was defined by Tanner genital or breast stage II and pubertal growth spurt taking place 2 sd later than average. The four coding exons (exons 1–4) and exon-intron boundaries, as well as the fragment of 3′ untranslated region containing miRNA recognition elements A and B, of LIN28B were PCR amplified from genomic DNA obtained from peripheral blood leukocytes of the subjects and bidirectionally sequenced.Results: No variation in the coding region of LIN28B in the 145 subjects with CDGP was found. However, 16 of 145 subjects carried a 2-nucleotide deletion immediately 5′ from miRNA recognition element A. These patients did not differ in phenotypic features as compared with noncarriers, and this variant was present in 100 controls with the same frequency.Conclusions: Our results show that mutations in the coding region or 3′ untranslated region miRNA recognition elements A and B of LIN28B do not underlie CDGP. Lack of any variation in the coding region of the gene suggests that LIN28B in developmental timing is so crucial that any changes in the conserved protein would probably be lethal.
Xenoestrogen-Induced Regulation of EZH2 and Histone Methylation via Estrogen Receptor Signaling to PI3K/AKT
Authors: Bredfeldt Tiffany G. , Greathouse K. Leigh , Safe Stephen H. , Hung Mien-Chie , Bedford Mark T. , Walker Cheryl L. 
Published: March 2010

Abstract
Although rapid, membrane-activated estrogen receptor (ER) signaling is no longer controversial, the biological function of this nongenomic signaling is not fully characterized. We found that rapid signaling from membrane-associated ER regulates the histone methyltransferase enhancer of Zeste homolog 2 (EZH2). In response to both 17β-estradiol (E2) and the xenoestrogen diethylstilbestrol, ER signaling via phosphatidylinositol 3-kinase/protein kinase B phosphorylates EZH2 at S21, reducing levels of trimethylation of lysine 27 on histone H3 in hormone-responsive cells. During windows of uterine development that are susceptible to developmental reprogramming, activation of this ER signaling pathway by diethylstilbestrol resulted in phosphorylation of EZH2 and reduced levels of trimethylation of lysine 27 on histone H3 in chromatin of the developing uterus. Furthermore, activation of nongenomic signaling reprogrammed the expression profile of estrogen-responsive genes in uterine myometrial cells, suggesting this as a potential mechanism for developmental reprogramming caused by early-life exposure to xenoestrogens. These data demonstrate that rapid ER signaling provides a direct linkage between xenoestrogen-induced nuclear hormone receptor signaling and modulation of the epigenetic machinery during tissue development.
Grammatical borrowing from Spanish/Portuguese in some native languages of Latin America
Authors: Sakel Jeanette 
Published: March 2010

Abstract
In this paper I investigate how different factors can influence the range of grammatical categories affected by language contact, drawing on a sample of ten native languages of Latin America. The languages are all in contact with the highly dominant languages Spanish and Portuguese, but they differ with respect to a range of sociolinguistic factors relating to the contact situation. I am investigating the categories affected by borrowing in the languages of the sample, relating them to these different factors. My aim is to shed light on the reasons for why some Native American languages display borrowing in a wide range of categories, whereas other appears more restricted in what is borrowed.
Don’t mess with ergatives! How the borrowing of the Spanish indefinite article affects the split-ergative system of Chamorro
Authors: Stolz Thomas 
Published: March 2010

Abstract
This paper seeks to determine in which way the introduction of the Spanish indefinite article un into the determiner system of Chamorro interferes with the inherited definiteness-based ergative split of the recipient language. It is argued that modern Chamorro employs Spanish-derived un as an indefinite article to introduce new discourse participants with relatively high topicality which are specific-referential. The employment of un in this function makes it possible to differentiate formally between two types of indefiniteness (the pre-Spanish zero article being responsible for non-specific, non-referential new discourse participants with low topicality).
Risk Factors and Estimation Tool for Death Among Extremely Premature Infants: A National Study
Authors: Bader David , Kugelman Amir , Boyko Valentina , Levitzki Orna , Lerner-Geva Liat , Riskin Arieh , Reichman Brian ,   in collaboration with the Israel Neonatal Network
Published: March 2010

OBJECTIVES:
The goals were to assess risk factors and mortality rate changes over time and to develop simple estimates of mortality rates for specific groups of infants at 23 to 26 weeks of gestation.

METHODS:
Data from the Israel national very low birth weight infant database on 3768 infants born in 1995–2006 with gestational ages (GAs) of 23 to 26 weeks were evaluated, and we developed a tool for estimating infants' mortality rates.

RESULTS:
Major factors associated with death were GA, gender-specific birth weight percentile, prenatal steroid therapy, and multiple births. There was a steady decrease in mortality rates for all GAs during the study period. In 2004–2006, mortality rates before discharge were 89%, 67%, 46%, and 26% for infants with GAs of 23, 24, 25, and 26 weeks, respectively. Estimated mortality rates were calculated as the sum of the percentages determined for each of 4 parameters, as follows: GA of 26, 25, 24, or 23 weeks, 0%, 17%, 34%, and 51%, respectively (P &lt; .001); birth weight percentile of &gt;75th, 25th to 75th, or &lt;25th, 0%, 16%, and 32%, respectively (P &lt; .001); no prenatal steroid treatment, +22% (P &lt; .001); multiple birth, +7% (P = .1). Estimated mortality rates for the 48 subgroups of infants ranged from 0% to 100% and correlated well with observed rates (intraclass correlation coefficient: 0.89).

CONCLUSION:
Mortality rates for infants born at 23 to 26 weeks of gestation could be estimated simply on the basis of GA, gender-specific birth weight quartiles, prenatal corticosteroid therapy, and multiple births.
Gastroesophageal Reflux and Asthma in Children: A Systematic Review
Authors: Thakkar Kalpesh , Boatright Renu O. , Gilger Mark A. , El-Serag Hashem B. 
Published: March 2010

CONTEXT:
The relationship between gastroesophageal reflux disease (GERD) and asthma in children has been investigated; however, the nature of the association (if any) between these 2 conditions is unclear.

OBJECTIVE:
We performed a systematic review of the literature to examine the association between GERD and asthma in children.

METHODS:
A search of the medical literature was conducted by using PubMed and Embase (1966 through December 2008). Full-length articles in English that described at least 20 subjects younger than 18 years were included if they reported the prevalence of GERD (symptoms, pH studies, endoscopy/histology) in individuals with asthma or the prevalence of asthma in individuals with GERD. We calculated pooled odds ratios from studies that examined control groups, and we pooled prevalence estimates from all studies.

RESULTS:
A total of 20 articles that described 5706 patients fulfilled the inclusion and exclusion criteria. Seventeen studies used objective methods for documenting reflux (eg, pH probe, contrast imaging, impedance, esophagogastroduodenoscopy), 2 studies relied on symptom-based questionnaires, and 1 study used diagnostic codes. Most studies (n = 19) examined the prevalence of GERD in 3726 individuals with asthma and reported highly variable estimates (19.3%–80.0%) and a pooled average of 22.8% with GERD symptoms, 62.9% of 789 patients with abnormal esophageal pH, and 34.8% of 89 patients with esophagitis. Only 5 studies included controls and enrolled 1314 case-patients with asthma and 2434 controls without asthma. The average prevalence of GERD was 22.0% in asthma cases and 4.8% in controls (pooled odds ratio: 5.6 [95% confidence interval: 4.3–6.9]).

CONCLUSIONS:
There is a possible association between GERD and asthma in pediatric patients seen with asthma in referral settings. However, because of methodologic limitations of existing studies, the paucity of population-based studies, and a lack of longitudinal studies, several aspects of this association are unclear.