bluuebunny/crossref_metadata_2025_split huggingface dataset:
Birth Characteristics and Risk of Prostate Cancer: the Contribution of Genetic Factors
Authors: Cnattingius Sven , Lundberg Frida , Sandin Sven , Grönberg Henrik , Iliadou Anastasia 
Published: September 2009

Abstract
Background: Prostate cancer has a strong hereditary component, but it has been proposed that hormonal influences in utero may contribute to offspring risk. We investigated the associations between birth characteristics and the risk of prostate cancer in twins, and whether possible associations could be confounded by familial factors, such as shared environment and common genes.
Methods: All like-sexed male twins in the Swedish Twin Registry, born from 1926 to 1958 and alive in 1973, were eligible. Data were obtained from birth records, and 11,420 male twins with reliable birth weight data were included in the final study population. Hazard ratios with 95% confidence intervals (CI) from Cox regression models were used to estimate associations between birth characteristics and risk of prostate cancer. Paired analysis was done to account for potential confounding by familial factors.
Results: Compared with twins with a birth weight of 2,500 to 2,999 g, the hazard ratio (95% CI) for twins with a higher birth weight (≥3,000 g) corresponded to 1.22 (0.94-1.57). In analyses within twin pairs, in which both twins had a birth weight of ≥2,500 g, a 500 g increase in birth weight was associated with an increased risk of prostate cancer within dizygotic twin pairs (odds ratio, 1.41; 95% CI, 1.02-1.57), but not within monozygotic twin pairs (odds ratio, 1.06; 95% CI, 0.61-1.84).
Conclusions: High birth weight is associated with an increased risk of prostate cancer. The difference in risk within dizygotic and monozygotic twin pairs may be due to genetic factors playing an important role in this association. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2422–6)
A Novel Polymorphism rs1329149 of CYP2E1 and a Known Polymorphism rs671 of ALDH2 of Alcohol Metabolizing Enzymes Are Associated with Colorectal Cancer in a Southwestern Chinese Population
Authors: Yang Huan , Zhou Yanhong , Zhou Ziyuan , Liu Jinyi , Yuan Xiaoyan , Matsuo Ketaro , Takezaki Toshiro , Tajima Kazuo , Cao Jia 
Published: September 2009

Abstract
Background: To screen for tagging single nucleotide polymorphisms (tagSNP) in the major alcohol metabolizing enzymes: ADH1B, ALDH2, and CYP2E1, and to evaluate the association between these tagSNPs and colorectal cancer (CRC) in a southwestern Chinese population.
Methods: A hospital-based case-control study of 440 CRC patients and 800 cancer-free controls was conducted. Personal information was collected by a Semi-Quantitative Food Frequency Questionnaire. The tagSNPs were screened in the HapMap with Haploview by setting the minor allele frequency at 0.03 with the highest score of r2 form each block. Genotypes were identified by using the SNPLex System. Both crude and adjusted odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the risk of each SNP.
Results: Sixteen tagSNPs were selected, and 13 were successfully genotyped. A novel CYP2E1 locus rs1329149 and a known ALDH2 locus rs671 were found to be significantly associated with CRC risk. The adjusted OR was 1.86 (95% CI, 1.12-3.09) for the rs671 A/A genotype and 4.04 for the rs1329149 T/T genotype (95% CI, 2.44-6.70), compared with their common homozygous genotypes. Interaction was found between alcohol consumption and gene polymorphisms on CRC, the adjusted OR was 7.17 (95% CI, 2.01-25.53) for drinking habits combined with rs671 A/A or rs1329149 T/T genotype.
Conclusion: The results of this study suggest that rs671 A/A and the first reported locus rs1329149 T/T genotypes increase the susceptibility to CRC, and gene-environmental interaction between the two loci and alcohol use existed for CRC in Southwestern Chinese. Larger studies are warranted to verify our findings. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2522–7)
Saturation Density of Skin Fibroblasts as a Quantitative Screen for Human Cancer Susceptibility
Authors: Rubin Harry 
Published: September 2009

Abstract
Genomic analysis of human cancers reveals a large number of genetic changes per cell that presumably underlie development of the disease. The complexity of these changes that differ from one type of cancer to the other and from patient to patient with the same type of cancer raises questions about the feasibility of genomic analysis as an indicator of susceptibility to cancer. However, skin fibroblasts (SF) from individuals in families with heritable forms of cancer, and from cancer-bearing individuals, show correlation with a significant increase in saturation density (SD), as well as other neoplasia-related properties. Procedures are described for amplifying and quantifying differences in SD on the basis of studies of spontaneous transformation in the NIH 3T3 line of mouse fibroblasts. It is proposed that such procedures be evaluated as quantitative screens for susceptibility to cancer in the general population. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2366–72)
p21 Expression in Colon Cancer and Modifying Effects of Patient Age and Body Mass Index on Prognosis
Authors: Ogino Shuji , Nosho Katsuhiko , Shima Kaori , Baba Yoshifumi , Irahara Natsumi , Kirkner Gregory J. , Hazra Aditi , De Vivo Immaculata , Giovannucci Edward L. , Meyerhardt Jeffrey A. , Fuchs Charles S. 
Published: September 2009

Abstract
p21 (Cyclin-dependent kinase inhibitor-1A, CDKN1A or CIP1) plays a role in regulating cell cycle, and its expression is lost in most colorectal cancers. p21 Is related with energy balance status, cellular senescence, and stem cell aging. Thus, the influence of p21 loss on tumor behavior and clinical outcome may be modified by patient age and body mass index (BMI). Using 647 colon cancers in two independent prospective cohorts, p21 loss was observed in 509 (79%) tumors by immunohistochemistry. Cox proportional hazard models computed hazard ratio (HR) for death, adjusted for potential confounders, including p53, cyclin D1, KRAS, BRAF, PIK3CA, LINE-1 hypomethylation, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI). p21 Loss was independently associated with low colon cancer–specific mortality [HR, 0.58; 95% confidence interval (95% CI), 0.38-0.89; adjusted for the covariates including MSI, CIMP, and LINE-1 methylation]. The prognostic effect of p21 loss differed significantly by age at diagnosis (Pinteraction &lt; 0.0001) and BMI (Pinteraction = 0.002). The adjusted HR for cancer-specific mortality (p21 loss versus p21 expression) was 4.09 (95% CI, 1.13-14.9) among patients &lt;60 year old and 0.37 (95% CI, 0.24-0.59) among patients ≥60 year old. The adverse prognostic effect of obesity was limited to p21-expressing cases (adjusted HR, 5.85; 95% CI, 2.28-15.0; BMI, ≥30 versus &lt;30 kg/m2), but no such effect was observed among p21-lost cases. In conclusion, p21 loss in colon cancer is associated with longer survival among patients ≥60 year old, whereas it is associated with shorter survival among patients &lt;60 year old. Patient BMI also differentially influences prognosis according to p21 CDKN1A status. Our data suggest host-tumor interactions influencing tumor aggressiveness. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2513–21)
No Association between Polymorphisms in LEP, LEPR, ADIPOQ, ADIPOR1, or ADIPOR2 and Postmenopausal Breast Cancer Risk
Authors: Teras Lauren R. , Goodman Michael , Patel Alpa V. , Bouzyk Mark , Tang Weining , Diver W. Ryan , Feigelson Heather Spencer 
Published: September 2009

Abstract
There is evidence that adipokines such as leptin and adiponectin may influence breast tumor development. We conducted a nested case-control study using women in the American Cancer Society Cancer Prevention Study II to examine the association between postmenopausal breast cancer and variability in the genes encoding leptin, the leptin receptor, adiponectin, adiponectin receptor 1, and adiponectin receptor 2. Using 648 cases and 659 controls, we found no statistically significant (P &lt; 0.05) associations between breast cancer risk and any of the single nucleotide polymorphisms. Individual odds ratios ranged from 0.93 to 1.06. We found no evidence of effect modification by body mass index, adult weight gain, location of weight gain, or physical activity. Although we cannot rule out that these genes are involved in gene-gene or gene-environment interactions, our results suggest that individual single nucleotide polymorphisms in these genes do not substantially affect postmenopausal breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2553–7)
Characterization of complement factor H–related (CFHR) proteins in plasma reveals novel genetic variations of CFHR1 associated with atypical hemolytic uremic syndrome
Authors: Abarrategui-Garrido Cynthia , Martínez-Barricarte Rubén , López-Trascasa Margarita , Rodríguez de Córdoba Santiago , Sánchez-Corral Pilar 
Published: September 2009

AbstractThe factor H–related protein family (CFHR) is a group of minor plasma proteins genetically and structurally related to complement factor H (fH). Notably, deficiency of CFHR1/CFHR3 associates with protection against age-related macular degeneration and with the presence of anti-fH autoantibodies in atypical hemolytic uremic syndrome (aHUS). We have developed a proteomics strategy to analyze the CFHR proteins in plasma samples from controls, patients with aHUS, and patients with type II membranoproliferative glomerulonephritis. Here, we report on the identification of persons carrying novel deficiencies of CFHR1, CFHR3, and CFHR1/CFHR4A, resulting from point mutations in CFHR1 and CFHR3 or from a rearrangement involving CFHR1 and CFHR4. Remarkably, patients with aHUS lacking CFHR1, but not those lacking CFHR3, present anti-fH autoantibodies, suggesting that generation of these antibodies is specifically related to CFHR1 deficiency. We also report the characterization of a novel CFHR1 polymorphism, resulting from a gene conversion event between CFH and CFHR1, which strongly associates with aHUS. The risk allotype CFHR1*B, with greater sequence similarity to fH, may compete with fH, decreasing protection of cellular surfaces against complement damage. In summary, our comprehensive analyses of the CFHR proteins have improved our understanding of these proteins and provided further insights into aHUS pathogenesis.
Evaluation of pentostatin in corticosteroid-refractory chronic graft-versus-host disease in children: a Pediatric Blood and Marrow Transplant Consortium study
Authors: Jacobsohn David A. , Gilman Andrew L. , Rademaker Alfred , Browning Brittan , Grimley Michael , Lehmann Leslie , Nemecek Eneida R. , Thormann Kimberly , Schultz Kirk R. , Vogelsang Georgia B. 
Published: September 2009

Abstract
There is no standard therapy for steroid-refractory chronic graft-versus-host disease (GVHD). This problem is particularly daunting in children with chronic GVHD, whereby the effects of the disease and its treatment may impair normal growth and development. Children are also particularly vulnerable to failure and/or toxicity of therapy; for example, joint contractures or joint damage may result in life-long disability. The Pediatric Blood and Marrow Transplant Consortium performed a phase 2 trial of pentostatin for steroid-refractory chronic GVHD in 51 children (median age, 9.8 years) from 24 institutions. Overall response was 53% (95% confidence interval, 40%-64%), with a response of 59% (95% confidence interval, 42%-75%) in sclerosis. Thirteen subjects (25%) had toxicity requiring them to stop pentostatin. The drug had a significant steroid-sparing effect in those that responded. A trend was also observed toward increased survival at 3 years in responders versus nonresponders (69% vs 50%; P = .06). The intravenous administration of the drug ensures compliance in a patient group in which oral therapy is difficult to monitor. Pentostatin has activity in refractory chronic GVHD in children, and future studies, including treatment of children newly diagnosed with high-risk chronic GVHD, are warranted. The trial was registered at www.Clinicaltrials.gov as #NCT00144430.
Identification of a region required for TSC1 stability by functional analysis of TSC1missense mutations found in individuals with tuberous sclerosis complex
Authors: Mozaffari Melika , Hoogeveen-Westerveld Marianne , Kwiatkowski David , Sampson Julian , Ekong Rosemary , Povey Sue , den Dunnen Johan T , van den Ouweland Ans , Halley Dicky , Nellist Mark 
Published: September 2009

Abstract

Background
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterised by the development of hamartomas in a variety of organs and tissues. The disease is caused by mutations in either the TSC1 gene on chromosome 9q34, or the TSC2 gene on chromosome 16p13.3. The TSC1 and TSC2 gene products, TSC1 and TSC2, form a protein complex that inhibits signal transduction to the downstream effectors of the mammalian target of rapamycin (mTOR). Recently it has been shown that missense mutations to the TSC1 gene can cause TSC.

Methods
We have used in vitro biochemical assays to investigate the effects on TSC1 function of TSC1 missense variants submitted to the Leiden Open Variation Database.

Results
We identified specific substitutions between amino acids 50 and 190 in the N-terminal region of TSC1 that result in reduced steady state levels of the protein and lead to increased mTOR signalling.

Conclusion
Our results suggest that amino acid residues within the N-terminal region of TSC1 are important for TSC1 function and for maintaining the activity of the TSC1-TSC2 complex.
A global approach to the management of EMR (Electronic Medical Records) of patients with HIV/AIDS in Sub-Saharan Africa: the experience of DREAM Software
Authors: Nucita Andrea , Bernava Giuseppe M , Bartolo Michelangelo , Masi Fabio Di Pane , Giglio Pietro , Peroni Marco , Pizzimenti Giovanni , Palombi Leonardo 
Published: September 2009

Abstract

Background
The DREAM Project operates within the framework of the national health systems of several sub-Saharan African countries and aims to introduce the essential components of an integrated strategy for the prevention and treatment of HIV/AIDS. The project is intended to serve as a model for a wide-ranging scale-up in the response to the epidemic. This paper aims to show DREAM's challenges and the solutions adopted. One of the solutions is the efficient management of the clinical data regarding the treatment of the patients and epidemiological analyses.

Methods
Specific software for the management of the patients' EMR has been created within the DREAM programme in order to deal with the challenges deriving from the context in which DREAM operates. Setting up a computer infrastructure in health centres, providing a power supply, as well as managing the data and the project resources efficiently and reliably, are some of the questions that have been analysed in this study.

Results
Over the years this software has proved that it is able to respond to the need for efficient management of the clinical data and organization of the health centres. Today it is used in 10 countries in sub-Saharan Africa by thousands of professionals and by now it has reached its fourth version. The medical files of over 73,000 assisted patients are managed by this software and the data collected with it have become essential for the epidemiological research that is carried out to improve the effectiveness of the therapy.

Conclusion
Sub-Saharan Africa is the region hardest hit by HIV and AIDS in the world. However, the resources and responses adopted so far, to confront the epidemic, have at times been rather minimalist. The DREAM project has faced the battle against the epidemic by equipping itself with qualitative standards comparable to Western ones. The experience of DREAM has revealed that it is indeed possible to guarantee levels of excellence in developing countries, also in the sphere of ICT (Information and Communication Technology), thus making the intervention even more effective and contributing to bridging the digital divide.
Enhanced production of IL-17A during zymosan-induced peritonitis in obese mice
Authors: Pini Maria , Fantuzzi Giamila 
Published: September 2009

Abstract
Neutrophils from obese mice produce high levels of the pro-inflammatory cytokine IL-17A following zymosan administration; this cytokine contributes to exacerbation and delayed resolution of peritoneal inflammation in obesity.
IL-17A is a proinflammatory cytokine critical for host defense and involved in the pathogenesis of autoimmune disorders. Obesity is associated with chronic low-grade inflammation but also with a heightened acute inflammatory response. We investigated the effect of obesity on IL-17A production using the model of ZY-induced peritonitis. Compared with lean controls, administration of ZY induced a significantly exacerbated inflammatory response in obese leptin-deficient ob/ob mice and in mice with diet-induced obesity (DIO). Levels of IL-17A in the peritoneal fluid in response to ZY were elevated significantly in ob/ob and DIO mice compared with lean animals. Reconstitution of ob/ob mice with exogenous leptin did not alter production of IL-17A significantly in response to ZY. Peritoneal cells and adipose tissue obtained from ZY-injected obese mice expressed significantly higher levels of IL-17A mRNA compared with lean mice. Approximately 2% of peritoneal Ly6G+ neutrophils from ZY-injected obese mice expressed IL-17A protein, compared with 0.2% of cells obtained from lean mice. Neutralization of IL-17 in ob/ob mice inhibited neutrophil recruitment and production of neutrophil-attracting CXC chemokines and IL-6, without affecting macrophage infiltration or levels of IL-10 and the chemokine CCL2. In contrast, neutralization of IL-6 did not affect production of IL-17A or chemokines while reducing production of the acute-phase protein serum amyloid A significantly. These data demonstrate that neutrophil-derived IL-17A is increased in obese mice during acute inflammation and contributes to exacerbation of inflammatory responses.
The effects of testosterone on immune function in quail selected for divergent plasma corticosterone response
Authors: Roberts Mark L. , Buchanan Katherine L. , Evans Matthew R. , Marin Raul H. , Satterlee Daniel G. 
Published: September 2009

SUMMARYThe immunocompetence handicap hypothesis (ICHH) suggests that the male sex hormone testosterone has a dual effect; it controls the development and expression of male sexually selected signals, and it suppresses the immune system. Therefore only high quality males are able to fully express secondary sexual traits because only they can tolerate the immunosuppressive qualities of testosterone. A modified version of the ICHH suggests that testosterone causes immunosuppression indirectly by increasing the stress hormone corticosterone (CORT). Lines of Japanese quail (Coturnix japonica)selected for divergent responses in levels of plasma CORT were used to test these hypotheses. Within each CORT response line (as well as in a control stock) we manipulated levels of testosterone in castrated quail by treatment with zero (sham), low or high testosterone implants, before testing the birds'humoral immunity and phytohaemagglutinin (PHA)-induced immune response, as well as body condition. The PHA-induced response was not significantly affected by CORT selected line, testosterone treatment or their interaction. There was, however, a significant effect of CORT line on humoral immunity in that the control birds exhibited the greatest antibody production, but there was no significant effect of testosterone manipulation on humoral immunity. The males in the sham implant treatment group had significantly greater mass than the males in the high testosterone group, suggesting a negative effect of high testosterone on general body condition. We discuss these results in the context of current hypotheses in the field of sexual selection.
Acoustic behaviour of echolocating porpoises during prey capture
Authors: DeRuiter Stacy L. , Bahr Alexander , Blanchet Marie-Anne , Hansen Sabina Fobian , Kristensen Jakob Højer , Madsen Peter T. , Tyack Peter L. , Wahlberg Magnus 
Published: September 2009

SUMMARYPorpoise echolocation has been studied previously, mainly in target detection experiments using stationed animals and steel sphere targets, but little is known about the acoustic behaviour of free-swimming porpoises echolocating for prey. Here, we used small onboard sound and orientation recording tags to study the echolocation behaviour of free-swimming trained porpoises as they caught dead, freely drifting fish. We analysed porpoise echolocation behaviour leading up to and following prey capture events,including variability in echolocation in response to vision restriction, prey species, and individual porpoise tested. The porpoises produced echolocation clicks as they searched for the fish, followed by fast-repetition-rate clicks(echolocation buzzes) when acquiring prey. During buzzes, which usually began when porpoises were about 1–2 body lengths from prey, tag-recorded click levels decreased by about 10 dB, click rates increased to over 300 clicks per second, and variability in body orientation (roll) increased. Buzzes generally continued beyond the first contact with the fish, and often extended until or after the end of prey handling. This unexplained continuation of buzzes after prey capture raises questions about the function of buzzes, suggesting that in addition to providing detailed information on target location during the capture, they may serve additional purposes such as the relocation of potentially escaping prey. We conclude that porpoises display the same overall acoustic prey capture behaviour seen in larger toothed whales in the wild,albeit at a faster pace, clicking slowly during search and approach phases and buzzing during prey capture.
Metabolic function inDrosophila melanogasterin response to hypoxia and pure oxygen
Authors: Van Voorhies Wayne A. 
Published: September 2009

SUMMARYThis study examined the metabolic response of Drosophila melanogaster exposed to O2 concentrations ranging from 0 to 21% and at 100%. The metabolic rate of flies exposed to graded hypoxia remained nearly constant as O2 tensions were reduced from normoxia to ∼3 kPa. There was a rapid, approximately linear reduction in fly metabolic rate at PO2s between 3 and 0.5 kPa. The reduction in metabolic rate was especially pronounced at PO2 levels &lt;0.5 kPa, and at a PO2 of 0.1 kPa fly metabolic rate was reduced∼10-fold relative to normoxic levels. The metabolic rate of flies exposed to anoxia and then returned to normoxia recovered to pre-anoxic levels within 30 min with no apparent payment of a hypoxia-induced oxygen debt. Flies tolerated exposure to hypoxia and/or anoxia for 40 min with nearly 100%survival. Fly mortality increased rapidly after 2 h of anoxia and &gt;16 h exposure was uniformly lethal. Flies exposed to pure O2 for 24 h showed no apparent alteration of metabolic rate, even though such O2 tensions should damage respiratory enzymes critical to mitochondria function. Within a few hours the metabolic rate of flies recovering from exposure to repeated short bouts of anoxia was the same as flies exposed to a single anoxia exposure.