bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and prognostic analysis of hepatitis B virus infection in diffuse large B-cell lymphoma
Authors: Wang Feng , Xu Rui-hua , Luo Hui-yan , Zhang Dong-shen , Jiang Wen-qi , Huang Hui-qiang , Sun Xiao-fei , Xia Zhong-jun , Guan Zhong-zhen 
Published: April 2008

Abstract

Background
Hepatitis B virus (HBV) infection in diffuse large B-cell lymphoma (DLBCL) patients is a common complication in China. However, the clinical relevance of HBV infection with respect to DLBCL disease stages and patient survival remains unclear. The main objective of the current study was to analyze the clinical features and to evaluate the prognostic factors of HBV infection in DLBCL patients.

Methods
In this retrospective study, DLBCL patients were divided into two groups as HBsAg-positive (n = 81) and HBsAg-negative (n = 181) patients. The HBsAg-positive patients were further divided into two subgroups based on their hepatic function during chemotherapy. Various statistical analyses were used to determine the significance of the relevant clinical parameters.

Results
Compared with the HBsAg-negative group, the HBsAg-positive DLBCL group displayed a younger median onset age (46 year vs 51), more advanced stage at grade III/IV (58% vs 42%, p = 0.016), and more frequent hepatic dysfunction before (21% vs 5.5%, p < 0.001) and during (49.4% vs 16.6%, p < 0.001) chemotherapy. Female DLBCL patients exhibited a higher frequency of HBsAg positivity (p = 0.006). However, in both groups the median overall survival (OS) duration (55.8 vs 66.8 months) and response rates (91% vs 90.4%) were similar. In the HBsAg-positive DLBCL group, the poor prognostic factors were advanced stage (p < 0.001) and hepatic dysfunction during chemotherapy (p = 0.02). The OS of HBsAg-positive patients with hepatic dysfunction during chemotherapy was significantly shorter than those without liver dysfunction (p = 0.016), and the OS rates at 3 years were 48% and 72%, respectively. The use of rituximab did not increase the rates of liver dysfunction in HBsAg-positive DLBCL patients.

Conclusion
Compared with HBsAg-negative patients, the HBsAg-positive DLBCL patients had earlier onset and more advanced stage. The disease stage and hepatic dysfunction during chemotherapy and were two significant prognostic factors in the HBsAg-positive DLBCL patients. This study suggests that prophylactic treatment of HBV may be of great importance in the cases of HBsAg-positive patients.
Androgenic dependence of exophytic tumor growth in a transgenic mouse model of bladder cancer: a role for thrombospondin-1
Authors: Johnson Aimee M , O'Connell Mary J , Miyamoto Hiroshi , Huang Jiaoti , Yao Jorge L , Messing Edward M , Reeder Jay E 
Published: April 2008

AbstractBackgroundSteroid hormones influence mitogenic signaling pathways, apoptosis, and cell cycle checkpoints, and it has long been known that incidence of bladder cancer (BC) in men is several times greater than in women, a difference that cannot be attributed to environmental or lifestyle factors alone. Castration reduces incidence of chemically-induced BC in rodents. It is unclear if this effect is due to hormonal influences on activation/deactivation of carcinogens or a direct effect on urothelial cell proliferation or other malignant processes. We examined the effect of castration on BC growth in UPII-SV40T transgenic mice, which express SV40 T antigen specifically in urothelium and reliably develop BC. Furthermore, because BC growth in UPII-SV40T mice is exophytic, we speculated BC growth was dependent on angiogenesis and angiogenesis was, in turn, androgen responsive.MethodsFlat panel detector-based cone beam computed tomography (FPDCT) was used to longitudinally measure exophytic BC growth in UPII-SV40T male mice sham-operated, castrated, or castrated and supplemented with dihydrotestosterone (DHT). Human normal bladder and BC biopsies and mouse bladder were examined quantitatively for thrombospondin-1 (TSP1) protein expression.ResultsMice castrated at 24 weeks of age had decreased BC volumes at 32 weeks compared to intact mice (p = 0.0071) and castrated mice administered DHT (p = 0.0233; one-way ANOVA, JMP 6.0.3, SAS Institute, Inc.). Bladder cancer cell lines responded to DHT treatment with increased proliferation, regardless of androgen receptor expression levels. TSP1, an anti-angiogenic factor whose expression is inhibited by androgens, had decreased expression in bladders of UPII-SV40T mice compared to wild-type. Castration increased TSP1 levels in UPII-SV40T mice compared to intact mice. TSP1 protein expression was higher in 8 of 10 human bladder biopsies of normal versus malignant tissue from the same patients.ConclusionFPDCT allows longitudinal monitoring of exophytic tumor growth in the UPII-SV40T model of BC that bypasses need for chemical carcinogens, which confound analysis of androgen effects. Androgens increase tumor cell growthin vitroandin vivoand decrease TSP1 expression, possibly explaining the therapeutic effect of castration. This effect may, in part, explain gender differences in BC incidence and implies anti-androgenic therapies may be effective in preventing and treating BC.
Clinical characterization and the mutation spectrum in Swedish adenomatous polyposis families
Authors: Kanter-Smoler Gunilla , Fritzell Kaisa , Rohlin Anna , Engwall Yvonne , Hallberg Birgitta , Bergman Annika , Meuller Johan , Grönberg Henrik , Karlsson Per , Björk Jan , Nordling Margareta 
Published: April 2008

Abstract

Background
The dominantly inherited condition familial adenomatous polyposis (FAP) is caused by germline mutations in the APC gene. Finding the causative mutations has great implications for the families. Correlating the genotypes to the phenotypes could help to improve the diagnosis and follow-up of patients.

Methods
Mutation screening of APC and the clinical characterization of 96 unrelated FAP patients from the Swedish Polyposis Registry was performed. In addition to generally used mutation screening methods, analyses of splicing-affecting mutations and investigations of the presence of low-frequency mutation alleles, indicating mosaics, have been performed, as well as quantitative real-time polymerase chain reaction to detect lowered expression of APC.

Results
Sixty-one different APC mutations in 81 of the 96 families were identified and 27 of those are novel. We have previously shown that 6 of the 96 patients carried biallelic MUTYH mutations. The 9 mutation-negative cases all display an attenuated or atypical phenotype. Probands with a genotype (codon 1250–1464) predicting a severe phenotype had a median age at diagnosis of 21.8 (range, 11–49) years compared with 34.4 (range, 14–57) years among those with mutations outside this region (P < 0.017). Dense polyposis (> 1000) occurred in 75% of the probands with a severe phenotype compared with 30% in those with mutations outside this region. The morbidity in colorectal cancer among probands was 25% at a mean age of 37.5 years and 29% at a mean age of 46.6 years.

Conclusion
Using a variety of mutation-detection techniques, we have achieved a 100% detection frequency in classical FAP. Probands with APC mutations outside codon 1250–1464, although exhibiting a less-severe phenotype, are at high risk of having a colorectal cancer at diagnosis indicating that age at diagnosis is as important as the severity of the disease for colorectal cancer morbidity.
The Greig cephalopolysyndactyly syndrome
Authors: Biesecker Leslie G 
Published: April 2008

AbstractThe Greig cephalopolysyndactyly syndrome (GCPS) is a pleiotropic, multiple congenital anomaly syndrome. It is rare, but precise estimates of incidence are difficult to determine, as ascertainment is erratic (estimated range 1–9/1,000,000). The primary findings include hypertelorism, macrocephaly with frontal bossing, and polysyndactyly. The polydactyly is most commonly preaxial of the feet and postaxial in the hands, with variable cutaneous syndactyly, but the limb findings vary significantly. Other low frequency findings include central nervous system (CNS) anomalies, hernias, and cognitive impairment.GCPS is caused by loss of function mutations in theGLI3transcription factor gene and is inherited in an autosomal dominant pattern. The disorder is allelic to the Pallister-Hall syndrome and one form of the acrocallosal syndrome.Clinical diagnosis is challenging because the findings of GCPS are relatively non-specific, and no specific and sensitive clinical have been delineated. For this reason, we have proposed a combined clinical-molecular definition for the syndrome. Apresumptivediagnosis of GCPS can be made if the patient has the classic triad of preaxial polydactyly with cutaneous syndactyly of at least one limb, hypertelorism, and macrocephaly. Patients with a phenotype consistent with GCPS (but which may not manifest all three attributes listed above) and aGLI3mutation may be diagnosed definitively with GCPS. In addition, persons with a GCPS-consistent phenotype who are related to a definitively diagnosed family member in a pattern consistent with autosomal dominant inheritance may be diagnosed definitively as well. Antenatal molecular diagnosis is technically straightforward to perform.Differential diagnoses include preaxial polydactyly type 4, the GCPS contiguous gene syndrome, acrocallosal syndrome, Gorlin syndrome, Carpenter syndrome, and Teebi syndrome.Treatment of the disorder is symptomatic, with plastic or orthopedic surgery indicated for significant limb malformations.The prognosis for typically affected patients is excellent. There may be a slight increase in the incidence of developmental delay or cognitive impairment. Patients with large deletions that includeGLI3may have a worse prognosis.The Article is a work of the United States Government. Title 17 U.S.C 5 105 provides that copyright protection is not available for any work of the United States Government in the United States. The United States hereby grants to anyone a paid-up, nonexclusive, irrevocable worldwide license to reproduce, prepare derivative works, distribute copies to the public and perform publicly and display publicly the work, and also retains the nonexclusive right to do all of the above for or on behalf of the United States.
A meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis
Authors: Smitten Allison L , Simon Teresa A , Hochberg Marc C , Suissa Samy 
Published: April 2008

Abstract
Introduction
The risk of malignancies in patients with rheumatoid arthritis (RA) has raised some concern, particularly with immunosuppressive approaches to disease management.

Methods
We conducted a systematic review of the literature and meta-analysis characterizing the associated risk of overall malignancy and four site-specific malignancies (lymphoma, lung, colorectal, and breast cancer) in patients with RA. A Medline search from 1990 to 2007 was conducted using specified search terms and predefined inclusion criteria for identification of relevant observational studies that provide estimates of relative risk of malignancy associated with RA. Study-specific estimates of the relative risk, as measured by standardized incidence ratios (SIRs) and estimated in comparison with the general population, were combined using a random effects model.

Results
A total of 21 publications were identified, of which 13 reported the SIR for overall malignancy, 14 for lymphoma, 10 for colorectal, 12 for lung, and 9 for breast cancer. Compared with the general population, the overall SIR estimates suggest that RA patients have approximately a two-fold increase in lymphoma risk (SIR 2.08, 95% confidence interval [CI] 1.80 to 2.39) and greater risk of Hodgkin than non-Hodgkin lymphoma. The risk of lung cancer was also increased with an SIR of 1.63 (95% CI 1.43 to 1.87). In contrast, a decrease in risk was observed for colorectal (SIR 0.77, 95% CI 0.65 to 0.90) and breast (SIR 0.84, 95% CI 0.79 to 0.90) cancer. The SIR for overall malignancy was 1.05 (95% CI 1.01 to 1.09).

Conclusion
Patients with RA appear to be at higher risk of lymphoma and lung cancer and potentially decreased risk for colorectal and breast cancer compared with the general population.
The influence of serum, glucose and oxygen on intervertebral disc cell growth in vitro: implications for degenerative disc disease
Authors: Johnson William EB , Stephan Simon , Roberts Sally 
Published: April 2008

Abstract
Introduction
The avascular nature of the human intervertebral disc (IVD) is thought to play a major role in disc pathophysiology by limiting nutrient supply to resident IVD cells. In the human IVD, the central IVD cells at maturity are normally chondrocytic in phenotype. However, abnormal cell phenotypes have been associated with degenerative disc diseases, including cell proliferation and cluster formation, cell death, stellate morphologies, and cell senescence. Therefore, we have examined the relative influence of possible blood-borne factors on the growth characteristics of IVD cells in vitro.

Methods
Bovine IVD cells were cultured either in monolayer to encourage cell proliferation or in alginate to induce chondrocytic differentiation. In both culture systems, cells were maintained with or without 20% serum, with or without 320 mg/dL glucose, and in atmospheric levels (~21%) of oxygen or 1% oxygen. Cell proliferation and viability, cell senescence, and collagen immunopositivity were assessed after 7 days. Statistical differences in these growth characteristics were tested using nonparametric analyses (n = 4 samples).

Results
In both culture systems, serum deprivation significantly inhibited IVD cell proliferation and increased cell positivity for senescence-associated beta-galactosidase (SA-β-gal), a marker of cell senescence. Conversely, IVD cells cultured in the presence of serum, but deprived of glucose, proliferated significantly more rapidly. In alginate cultures, this enhanced cell proliferation (through glucose deprivation) led to the formation of IVD cell clusters. Serum-deprived cells in monolayer, but not in alginate, adopted a stellate appearance. Oxygen deprivation alone had little effect on IVD cell proliferation or survival. Oxygen and glucose deprivation also had no significant effect on SA-β-gal positivity. IVD cell viability was markedly and significantly decreased in serum-deprived alginate cultures, but in all other conditions remained at or greater than approximately 95%. Glucose deprivation, but not serum or oxygen deprivation, inhibited synthesis of type I and type II collagen, both in monolayer and alginate cultures.

Conclusion
This study demonstrates that factors present in serum interact with other nutrients, notably glucose, to play a major role in regulating the behaviour of IVD cells. These findings suggest that IVD cell phenotypes seen in degenerative disc disease may arise through the cells' response to altered vascularisation and nutrient supply.
Delivering phonological and phonics training within whole‐class teaching
Authors: Shapiro Laura R. , Solity Jonathan 
Published: April 2008

Background Early, intensive phonological awareness and phonics training is widely held to be beneficial for children with poor phonological awareness. However, most studies have delivered this training separately from children's normal whole‐class reading lessons.Aims We examined whether integrating this training into whole class, mixed‐ability reading lessons could impact on children with poor phonological awareness, whilst also benefiting normally developing readers.Sample Teachers delivered the training within a broad reading programme to whole classes of children from Reception to the end of Year 1 (N = 251). A comparison group of children received standard teaching methods (N = 213).Method Children's literacy was assessed at the beginning of Reception, and then at the end of each year until 1 year post‐intervention.Results The strategy significantly impacted on reading performance for normally developing readers and those with poor phonological awareness, vastly reducing the incidence of reading difficulties from 20% in comparison schools to 5% in intervention schools.Conclusions Phonological and phonics training is highly effective for children with poor phonological awareness, even when incorporated into whole‐class teaching.
The case for polygraph testing of sex offenders
Authors: Grubin Don 
Published: April 2008

Purpose. To describe the issues associated with the post‐conviction testing of sex offenders (CST).Arguments. Post‐conviction sex offender testing (PCSOT) is used widely in sex offender treatment and supervision programmes, but it is not without controversy. Much of the criticism of PCSOT, however, arises because of confusion between it and other applications of polygraphy. It is argued that the evidence for accuracy and utility, although not definitive, is sufficient to justify the use of PCSOT. Ethical issues are also addressed.Conclusion. Whatever the pros and cons of polygraph use in other settings, PCSOT can make a valuable contribution to sex offender treatment and management.
Plasma PCSK9 Concentrations Correlate with LDL and Total Cholesterol in Diabetic Patients and Are Decreased by Fenofibrate Treatment
Authors: Lambert Gilles , Ancellin Nicolas , Charlton Francesca , Comas Daniel , Pilot Julia , Keech Anthony , Patel Sanjay , Sullivan David R , Cohn Jeffrey S , Rye Kerry-Anne , Barter Philip J 
Published: April 2008

Abstract
Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the LDL receptor (LDLr) in hepatocytes, and its expression in mouse liver has been shown to decrease with fenofibrate treatment.
Methods: We developed a sandwich ELISA using recombinant human PCSK9 protein and 2 affinity-purified polyclonal antibodies directed against human PCSK9. We measured circulating PCSK9 concentrations in 115 diabetic patients from the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study before and after fenofibrate treatment.
Results: We found that plasma PCSK9 concentrations correlate with total (r = 0.45, P = 0.006) and LDL (r = 0.54, P = 0.001) cholesterol but not with triglycerides or HDL cholesterol concentrations in that cohort. After 6 weeks of treatment with comicronized fenofibrate (200 mg/day), plasma PCSK9 concentrations decreased by 8.5% (P = 0.041 vs pretreatment). This decrease correlated with the efficacy of fenofibrate, as judged by a parallel reduction in plasma triglycerides (r = 0.31, P = 0.015) and LDL cholesterol concentrations (r = 0.27, P = 0.048).
Conclusions: We conclude that this decrease in PCSK9 explains at least in part the LDL cholesterol–lowering effects of fenofibrate. Fenofibrate might be of interest to further reduce cardiovascular risk in patients already treated with a statin.
Expanding Assay Dynamics: A Combined Competitive and Direct Assay System for the Quantification of Proteins in Multiplexed Immunoassays
Authors: Hartmann Michael , Schrenk Monika , Döttinger Anette , Nagel Sarah , Roeraade Johan , Joos Thomas O , Templin Markus F 
Published: April 2008

Abstract
Background: The concurrent detection and quantification of analytes that vary widely in concentration present a principal problem in multiplexed assay systems. Combining competitive and sandwich immunoassays permits coverage of a wide concentration range, and both highly abundant molecules and analytes present in low concentration can be quantified within the same assay.
Methods: The use of different fluorescence readout channels allows the parallel use of a competitive system and a sandwich configuration. The 2 generated assay signals are combined and used to calculate the amount of analyte. The measurement range can be adjusted by varying the competitor concentration, and an extension of the assay system’s dynamic range is possible.
Results: We implemented the method in a planar protein microarray–based autoimmune assay to detect autoantibodies against 13 autoantigens and to measure the concentration of a highly abundant protein, total human IgG, in one assay. Our results for autoantibody detection and IgG quantification agreed with results obtained with commercially available assays. The use of 2 readout channels in the protein microarray–based system reduced spot-to-spot variation and intraassay variation.
Conclusions: By combining a direct immunoassay with a competitive system, analytes present in widely varying concentrations can be quantified within a single multiplex assay. Introducing a second readout channel for analyte quantification is an effective tool for spot-to-spot normalization and helps to lower intraassay variation.
The Perfect Storm: Obesity, Adipocyte Dysfunction, and Metabolic Consequences
Authors: de Ferranti Sarah , Mozaffarian Dariush 
Published: April 2008

Abstract
Background: As the prevalence of adiposity soars in both developed and developing nations, appreciation of the close links between obesity and disease increases. The strong relationships between excess adipose tissue and poor health outcomes, including cardiovascular disease, diabetes, and cancer, mandate elucidation of the complex cellular, hormonal, and molecular pathophysiology whereby adiposity initiates and maintains adverse health effects.
Content: In this report we review adipocyte metabolism and function in the context of energy imbalance and postprandial nutrient excess, including adipocyte hypertrophy and hyperplasia, adipocyte dysfunction, and other systemic consequences. We also discuss implications for laboratory evaluation and clinical care, including the role of lifestyle modifications. Chronic energy imbalance produces adipocyte hypertrophy and hyperplasia, endoplasmic reticulum stress, and mitochondrial dysfunction. These processes lead to increased intracellular and systemic release of adipokines, free fatty acids, and inflammatory mediators that cause adipocyte dysfunction and induce adverse effects in the liver, pancreatic β-cells, and skeletal muscle as well as the heart and vascular beds. Several specialized laboratory tests can quantify these processes and predict clinical risk, but translation to the clinical setting is premature. Current and future pharmacologic interventions may target these pathways; modest changes in diet, physical activity, weight, and smoking are likely to have the greatest impact.
Summary: Adipocyte endoplasmic reticulum and mitochondrial stress, and associated changes in circulating adipokines, free fatty acids, and inflammatory mediators, are central to adverse health effects of adiposity. Future investigation should focus on these pathways and on reversing the adverse lifestyle behaviors that are the fundamental causes of adiposity.
Comparison of Diploid and Triploid Largemouth Bass Growth and Maturation through Age 1 in Puerto Rico
Authors: Neal J. Wesley , Noble Richard L. 
Published: April 2008

Abstract
Triploid largemouth bass Micropterus salmoides could be valuable both in sport fish management and in food fish production. This study compared the growth and reproductive development of diploid and triploid largemouth bass through age 1 in Lucchetti Reservoir, Puerto Rico. We produced and stocked 487 diploids and 477 triploids tagged with binary coded wire tags and recaptured these fish over 2 years. Growth rates, condition (relative weight (Wr)), and reproductive investment (gonadosomatic index (GSI)) were compared for diploid and triploid fish. Rates of mean daily growth did not differ between diploids (0.81 mm/d; SE = 0.07) and triploids (0.91 mm/d; SE = 0.09) as juveniles or overall through age 1. Diploid largemouth bass exhibited advanced reproductive development during age 1, while triploids did not. Mean GSI was higher for diploid females (mean = 1.98; SE = 0.81) than for triploid females (mean = 0.29; SE = 0.05), but male mean GSI did not significantly differ between the two groups. No difference in Wr was observed. Experimental fish in this study reached maturity in the middle of the spawning season at age 1 and therefore may not have reproduced. Additional research on triploid largemouth bass beyond age 1 is necessary to determine whether sterile triploids have growth advantages over reproductive adult diploids.