bluuebunny/crossref_metadata_2025_split huggingface dataset:
T-Cell Coregulatory Molecule Expression in Urothelial Cell Carcinoma: Clinicopathologic Correlations and Association with Survival
Authors: Boorjian Stephen A. , Sheinin Yuri , Crispen Paul L. , Farmer Sara A. , Lohse Christine M. , Kuntz Susan M. , Leibovich Bradley C. , Kwon Eugene D. , Frank Igor 
Published: August 2008

AbstractPurpose: Aberrant expression of T-cell coregulatory molecules has been investigated as a mechanism by which certain cancers may evade host immune surveillance. We evaluated expression of the T-cell coregulators B7-H1, B7-H3, and PD-1 in urothelial cell carcinoma (UCC) of the bladder.Experimental Design: Immunohistochemistry for B7-H1, B7-H3, and PD-1 was done on paraffin-embedded sections from 318 consecutive patients with UCC who underwent radical cystectomy. Expression was correlated with clinicopathologic outcomes and postoperative survival.Results: B7-H3 was widely expressed in UCC, as 222 of 314 (70.7%) tumors showed positive staining. Expression of B7-H3 in UCC was significantly increased compared with adjacent, nontumor urothelium, as a median of 70% of tumor cells expressed B7-H3, compared with 20% of cells in nontumor specimens (P &lt; 0.001). The increase in B7-H3 expression was independent of tumor stage (P = 0.13). Expression of B7-H1 by UCC tumors (P &lt; 0.001) and PD-1 by tumor-infiltrating lymphocytes (P = 0.012) were significantly associated with increased pathologic stage. Patients who had received intravesical bacillus Calmette-Guerin before cystectomy tended to show increased expression of B7-H3 (P = 0.023) and PD-1 (P = 0.071) but were less likely to express B7-H1 (P = 0.027). Moreover, for the subset of patients with organ-confined disease (n = 167), B7-H1 expression independently predicted all-cause mortality after cystectomy (hazard ratio, 3.18; 95% confidence interval, 1.74-5.79; P &lt; 0.001).Conclusions: B7-H3 is highly expressed in UCC across tumor stages, whereas B7-H1 and PD-1 expression are associated with advanced disease. B7-H1 expression predicts mortality after cystectomy for patients with organ-confined tumors. These molecules may represent novel diagnostic or prognostic markers, as well as therapeutic targets, for patients with UCC.
Quantitative Analysis of the Transrenal Excretion of Circulating EBV DNA in Nasopharyngeal Carcinoma Patients
Authors: Chan K.C. Allen , Leung Sing F. , Yeung Sze W. , Chan Anthony T.C. , Lo Y.M. Dennis 
Published: August 2008

Abstract
Purpose: The existence of transrenal clearance of circulating cell-free DNA is controversial. In this study, we used NPC as a model to investigate if circulating EBV DNA can be excreted into urine and to quantify the contribution of renal excretion to the clearance of plasma EBV DNA.
Experimental Design: Quantitative analysis of urine EBV DNA was done for 74 NPC patients using real-time PCR with two different amplicon sizes. The urine concentration of EBV DNA was expressed as copies per millimole of creatinine (copies/mmol Cr) to minimize the effects of interindividual variations in hydration status.
Results: EBV DNA was detectable in the urine of 56% NPC patients using a 59-bp real-time PCR assay. The median urine EBV DNA concentrations measured by the 59- and 76-bp assays were 7,040 and 290 copies/mmol Cr, respectively. Patients with detectable urine EBV DNA had significantly higher plasma concentrations, with a positive correlation between the plasma and urine concentrations of EBV DNA. The fraction of plasma EBV DNA excreted into the urine was 0.0026% of that for creatinine.
Conclusions: We have shown that circulating EBV DNA can be excreted transrenally into urine in NPC patient and the fraction of excretion is negatively associated with the size of the DNA molecules. Because there is a positive correlation between plasma and urine EBV DNA concentration, urine EBV DNA analysis may potentially be applicable as an ultra-noninvasive test for the monitoring and prognostication of NPC patients.
Does primary myelofibrosis involve a defective stem cell niche? From concept to evidence
Authors: Lataillade Jean-Jacques , Pierre-Louis Olivier , Hasselbalch Hans Carl , Uzan Georges , Jasmin Claude , Martyré Marie-Claire , Le Bousse-Kerdilès Marie-Caroline 
Published: August 2008

AbstractPrimary myelofibrosis (PMF) is the rarest and the most severe Philadelphia-negative chronic myeloproliferative syndrome. By associating a clonal proliferation and a mobilization of hematopoietic stem cells from bone marrow to spleen with profound alterations of the stroma, PMF is a remarkable model in which deregulation of the stem cell niche is of utmost importance for the disease development. This paper reviews key data suggesting that an imbalance between endosteal and vascular niches participates in the development of clonal stem cell proliferation. Mechanisms by which bone marrow niches are altered with ensuing mobilization and homing of neoplastic hematopoietic stem cells in new or reinitialized niches in the spleen and liver are examined. Differences between signals delivered by both endosteal and vascular niches in the bone marrow and spleen of patients as well as the responsiveness of PMF stem cells to their specific signals are discussed. A proposal for integrating a potential role for the JAK2 mutation in their altered sensitivity is made. A better understanding of the cross talk between stem cells and their niche should imply new therapeutic strategies targeting not only intrinsic defects in stem cell signaling but also regulatory hematopoietic niche–derived signals and, consequently, stem cell proliferation.
Seven-year median time to progression with thalidomide for smoldering myeloma: partial response identifies subset requiring earlier salvage therapy for symptomatic disease
Authors: Barlogie Bart , van Rhee Frits , Shaughnessy John D. , Epstein Joshua , Yaccoby Shmuel , Pineda-Roman Mauricio , Hollmig Klaus , Alsayed Yazan , Hoering Antje , Szymonifka Jackie , Anaissie Elias , Petty Nathan , Kumar Naveen S. , Srivastava Geetika , Jenkins Bonnie , Crowley John , Zeldis Jerome B. 
Published: August 2008

AbstractSmoldering multiple myeloma (SMM) is usually followed expectantly without therapy. We conducted a phase 2 trial in 76 eligible patients with SMM, combining thalidomide (THAL, 200 mg/d) with monthly pamidronate. In the first 2 years, THAL dose reduction was required in 86% and drug was discontinued in 50%. Within 4 years, 63% improved, including 25% qualifying for partial response (PR); by then, 34 patients had progressed and 17 required salvage therapy. Unexpectedly, attaining PR status was associated with a shorter time to salvage therapy for disease progression (P < .001), perhaps reflecting greater drug sensitivity of more aggressive disease. Low beta-2-microglobulin levels less than 2 mg/L were independently associated with superior overall and event-free survival. Four-year survival and event-free survival estimates of 91% and 60%, respectively, together with a median postsalvage therapy survival of more than 5 years justify the conduct of a prospective randomized clinical trial to determine the clinical value of preemptive therapy in SMM. Trial registered at http://www.clinicaltrials.gov under identifier NCT00083382.
Identification and characterization of novel human tissue-specific RFX transcription factors
Authors: Aftab Syed , Semenec Lucie , Chu Jeffrey Shih-Chieh , Chen Nansheng 
Published: August 2008

Abstract

Background
Five regulatory factor X (RFX) transcription factors (TFs)–RFX1-5–have been previously characterized in the human genome, which have been demonstrated to be critical for development and are associated with an expanding list of serious human disease conditions including major histocompatibility (MHC) class II deficiency and ciliaophathies.

Results
In this study, we have identified two additional RFX genes–RFX6 and RFX7–in the current human genome sequences. Both RFX6 and RFX7 are demonstrated to be winged-helix TFs and have well conserved RFX DNA binding domains (DBDs), which are also found in winged-helix TFs RFX1-5. Phylogenetic analysis suggests that the RFX family in the human genome has undergone at least three gene duplications in evolution and the seven human RFX genes can be clearly categorized into three subgroups: (1) RFX1-3, (2) RFX4 and RFX6, and (3) RFX5 and RFX7. Our functional genomics analysis suggests that RFX6 and RFX7 have distinct expression profiles. RFX6 is expressed almost exclusively in the pancreatic islets, while RFX7 has high ubiquitous expression in nearly all tissues examined, particularly in various brain tissues.

Conclusion
The identification and further characterization of these two novel RFX genes hold promise for gaining critical insight into development and many disease conditions in mammals, potentially leading to identification of disease genes and biomarkers.
Trait correlated expression combined with expression QTL analysis reveals biological pathways and candidate genes affecting water holding capacity of muscle
Authors: Ponsuksili Siriluck , Jonas Elisabeth , Murani Eduard , Phatsara Chirawath , Srikanchai Tiranun , Walz Christina , Schwerin Manfred , Schellander Karl , Wimmers Klaus 
Published: August 2008

AbstractBackgroundLeakage of water and ions and soluble proteins from muscle cells occurs during prolonged exercise due to ischemia causing muscle damage. Alsopost mortemanoxia during conversion of muscle to meat is marked by loss of water and soluble components from the muscle cell. There is considerable variation in the water holding capacity of meat affecting economy of meat production. Water holding capacity depends on numerous genetic and environmental factors relevant to structural and biochemical muscle fibre properties a well asanteandpostslaughter metabolic processes.ResultsExpression microarray analysis of M.longissimus dorsiRNAs of 74 F2 animals of a resource population showed 1,279 transcripts with trait correlated expression to water holding capacity. Negatively correlated transcripts were enriched in functional categories and pathways like extracellular matrix receptor interaction and calcium signalling. Transcripts with positive correlation dominantly represented biochemical processes including oxidative phosphorylation, mitochondrial pathways, as well as transporter activity. A linkage analysis of abundance of trait correlated transcripts revealed 897 expression QTL (eQTL) with 104 eQTL coinciding with QTL regions for water holding capacity; 96 transcripts hadtransacting and 8 hadcisacting regulation.ConclusionThe complex relationships between biological processes taking place in live skeletal muscle and meat quality are driven on the one hand by the energy reserves and their utilisation in the muscle and on the other hand by the muscle structure itself and calcium signalling. Holistic expression profiling was integrated with QTL analysis for the trait of interest and for gene expression levels for creation of a priority list of genes out of the orchestra of genes of biological networks relevant to the liability to develop elevated drip loss.
Mutation study of Spanish patients with Hereditary Hemorrhagic Telangiectasia
Authors: Fontalba Ana , Fernandez-L Africa , García-Alegria Eva , Albiñana Virginia , Garrido-Martin Eva M , Blanco Francisco J , Zarrabeitia Roberto , Perez-Molino Alfonso , Bernabeu-Herrero Maria E , Ojeda Maria-Luisa , Fernandez-Luna Jose L , Bernabeu Carmelo , Botella Luisa M 
Published: August 2008

Abstract

Background
Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant and age-dependent vascular disorder characterised mainly by mutations in the Endoglin (ENG) or activin receptor-like kinase-1 (ALK1, ACVRL1) genes.

Methods
Here, we have identified 22 ALK1 mutations and 15 ENG mutations, many of which had not previously been reported, in independent Spanish families afflicted with HHT.

Results
We identified mutations in thirty-seven unrelated families. A detailed analysis of clinical symptoms was recorded for each patient analyzed, with a higher significant presence of pulmonary arteriovenous malformations (PAVM) in HHT1 patients over HHT2. Twenty-two mutations in ALK1 and fifteen in ENG genes were identified. Many of them, almost half, represented new mutations in ALK1 and in ENG. Missense mutations in ENG and ALK1 were localized in a tridimensional protein structure model.

Conclusion
Overall, ALK1 mutations (HHT2) were predominant over ENG mutations (HHT1) in our Spanish population, in agreement with previous data from our country and other Mediterranean countries (France, Italy), but different to Northern Europe or North America. There was a significant increase of PAVM associated with HHT1 over HHT2 in these families.
Influenza vaccination coverage rates in five European countries during season 2006/07 and trends over six consecutive seasons
Authors: Blank Patricia R , Schwenkglenks Matthias , Szucs Thomas D 
Published: August 2008

AbstractBackgroundThe objectives of the survey were to identify the level of influenza vaccination coverage in five European countries between 2001 and 2007, to understand the drivers and barriers to vaccination, to assess vaccination intentions for the winter 2007/08 as well as major encouraging factors for vaccination.MethodsBetween 2001 and 2007, representative household surveys were performed with telephone or mailed (France) interviews of individuals aged 14 and above. The questionnaire used in the UK, Germany, Italy, France and Spain was essentially the same in all seasons. The data were subsequently pooled. Four target groups were defined for the analysis: 1) persons aged 65 years and over; 2) persons working in the medical field; 3) chronically ill persons and 4) combined target group composed of individuals belonging to one or more of the previous groups 1, 2 or 3.ResultsIn 2006/07, vaccination coverage was, 25.0% in UK, 27.4% in Germany, 21.8% in Spain, 24.2% in France and 24.4% in Italy. During six influenza seasons (2001–2007), vaccination coverage showed a slight positive trend in the five countries (p ≤ 0.0001). In the elderly (≥ 65 years), across all countries, no significant trend was seen; the vaccination rate decreased non-significantly from a peak of 64.2% in season 2005/06 to 61.1% in season 2006/07. The most frequent reason for getting vaccinated was a recommendation by the family doctor or nurse (51%), and this was also perceived as the major encouraging factor for vaccination (61%). The main reason for not getting vaccinated was feeling unlikely to catch the flu (36%).ConclusionIn the UK, Germany and Spain, influenza vaccination coverage rates in season 2006/07 dropped slightly compared to the previous season. However, a trend of increasing vaccination coverage was observed from 2001/02 to 2006/07 across Europe. The family doctor is the major source of encouragement for individuals getting vaccinated. Efforts to overcome the barriers to vaccination need to be put in place to reach the WHO objective of 75% coverage in the elderly by 2010. This is a major challenge to be faced by governments, healthcare workers and healthcare organisations.
HLA-C increases HIV-1 infectivity and is associated with gp120
Authors: Matucci Andrea , Rossolillo Paola , Baroni Miriam , Siccardi Antonio G , Beretta Alberto , Zipeto Donato 
Published: August 2008

AbstractBackgroundA recently identified genetic polymorphism located in the 5' region of the HLA-C gene is associated with individual variations in HIV-1 viral load and with differences in HLA-C expression levels. HLA-C has the potential to restrict HIV-1 by presenting epitopes to cytotoxic T cells but it is also a potent inhibitor of NK cells. In addition, HLA-C molecules incorporated within the HIV-1 envelope have been shown to bind to the envelope glycoprotein gp120 and enhance viral infectivity. We investigated this last property in cell fusion assays where the expression of HLA-C was silenced by small interfering RNA sequences. Syncytia formation was analyzed by co-cultivating cell lines expressing HIV-1 gp120/gp41 from different laboratory and primary isolates with target cells expressing different HIV-1 co-receptors. Virus infectivity was analyzed using pseudoviruses. Molecular complexes generated during cell fusion (fusion complexes) were purified and analyzed for their HLA-C content.ResultsHLA-C positive cells co-expressing HIV-1 gp120/gp41 fused more rapidly and produced larger syncytia than HLA-C negative cells. Transient transfection of gp120/gp41 from different primary isolates in HLA-C positive cells resulted in a significant cell fusion increase. Fusion efficiency was reduced in HLA-C silenced cells compared to non-silenced cells when co-cultivated with different target cell lines expressing HIV-1 co-receptors. Similarly, pseudoviruses produced from HLA-C silenced cells were significantly less infectious. HLA-C was co-purified with gp120 from cells before and after fusion and was associated with the fusion complex.ConclusionVirionic HLA-C molecules associate to Env and increase the infectivity of both R5 and X4 viruses. Genetic polymorphisms associated to variations in HLA-C expression levels may therefore influence the individual viral set point not only by means of a regulation of the virus-specific immune response but also via a direct effect on the virus replicative capacity. These findings have implications for the understanding of the HIV-1 entry mechanism and of the role of Env conformational modifications induced by virion-associated host proteins.
Reliability-Based System-Level Optimization of Bridge Maintenance and Replacement Decisions
Authors: Robelin Charles-Antoine , Madanat Samer M. 
Published: August 2008

This paper addresses the problem of optimizing bridge maintenance and replacement (M&R) decisions for a heterogeneous system of facilities. The objective is to determine optimal M&R policies for each facility over a finite planning horizon based on the knowledge of the current facilities conditions and on the prediction of future conditions. The system-level problem is based on the results of an M&R optimization problem for each facility. The results of the facility-level optimization are incorporated in a reliability-based, bottom-up, system-level formulation that provides recommendations for each individual facility. We derive sufficient conditions for optimality and prove the result for the continuous case. A parametric study shows that the results obtained in the discrete-case implementation of the solution are valid approximations of the continuous case results. The computational efficiency of the system-level solution makes the formulation suitable for systems of realistic sizes.
Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcus: Comparison of Diagnosis and Treatment in the Community and at a Specialty Clinic
Authors: Gabbay Vilma , Coffey Barbara J. , Babb James S. , Meyer Laura , Wachtel Carly , Anam Seeba , Rabinovitz Beth 
Published: August 2008

OBJECTIVES. This study aimed to examine whether pediatric autoimmune neuropsychiatric disorders associated with streptococcus were appropriately diagnosed in the community and to determine subsequent rates of unwarranted use of antibiotic treatment for tics and obsessive-compulsive symptoms without the identification of an infection.METHODS. The design was a retrospective, cross-sectional, observational study of 176 children and adolescents who were evaluated in a specialty program for tics, Tourette's disorder, and related problems. Previously published diagnostic criteria were used to establish the diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus in our clinic.RESULTS. Subjects were significantly less likely to receive a diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus at the specialty clinic than in the community. In the community, subjects were significantly more likely to be treated with antibiotics or immunosuppressant medication if they received a diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus. Of the 27 subjects with a community diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus who were treated with antibiotics, 22 (82%) were treated without laboratory evidence of an infection; 2 were treated with immunomodulatory medications.CONCLUSIONS. Our results support our hypothesis that pediatric autoimmune neuropsychiatric disorders associated with streptococcus are frequently diagnosed in the community without the application of all working diagnostic criteria. This phenomenon has resulted in unwarranted use of antibiotic treatment for tics/obsessive-compulsive disorder without evidence of laboratory infection.
Preschool Child Care Participation and Obesity at the Start of Kindergarten
Authors: Maher Erin J. , Li Guanghui , Carter Louise , Johnson Donna B. 
Published: August 2008

OBJECTIVE. We examined the association between type of child care, participation in different types of child care in the year before kindergarten and the likelihood of obesity at the start of kindergarten.
METHODS. Using a nationally representative sample of 15 691 first-time kindergartners from the Early Childhood Longitudinal Study-Kindergarten Cohort, we used logistic regression to estimate the relationship between type of primary child care arrangement and children's likelihood of being obese at the start of kindergarten. Our models controlled for family and child characteristics associated with obesity and choice of child care. To examine differential effects of child care participation for groups at high risk for obesity, we tested interactions between children's ethnicity and income with primary type of child care.
RESULTS. At the start of kindergarten, 12% of the children were obese. Without controlling for other characteristics of children and families, children not in child care were significantly less likely and children in family, friend, and neighbor care were significantly more likely to be obese than children in other primary child care arrangements. White children were significantly less likely and Latino children more likely to be obese than children of other ethnic groups. After controlling for relevant child and family characteristics, children in family, friend, and neighbor care and non-Latino children in Head Start were more likely to be obese than children not in child care. For Latino children, however, participation in some types of nonparental child care had protective effects on their likelihood of being obese.
CONCLUSIONS. Primary type of child care is associated with children's obesity. For Latino children, who are at a greater risk of being obese, participation in nonparental child care seems to have a protective effect. These results suggest that child care settings may be an important site for policy intervention during a crucial developmental period. Efforts to help family, friend, and neighbor caregivers support children's physical health may be warranted.