bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Associations of Advanced Glycation End Products and Its Soluble Receptor with Pancreatic Cancer Risk: A Case–Control Study within the Prospective EPIC Cohort
Authors: Grote Verena A. , Nieters Alexandra , Kaaks Rudolf , Tjønneland Anne , Roswall Nina , Overvad Kim , Nielsen Michael R. Skjelbo , Clavel-Chapelon Françoise , Boutron-Ruault Marie Christine , Racine Antoine , Teucher Birgit , Lukanova Annekatrin , Boeing Heiner , Drogan Dagmar , Trichopoulou Antonia , Trichopoulos Dimitrios , Lagiou Pagona , Palli Domenico , Sieri Sabina , Tumino Rosario , Vineis Paolo , Mattiello Amalia , Argüelles Suárez Marcial Vicente , Duell Eric J. , Sánchez María-José , Dorronsoro Miren , Huerta Castaño José María , Barricarte Aurelio , Jeurnink Suzanne M. , Peeters Petra H.M. , Sund Malin , Ye Weimin , Regner Sara , Lindkvist Björn , Khaw Kay-Tee , Wareham Nick , Allen Naomi E. , Crowe Francesca L. , Fedirko Veronika , Jenab Mazda , Romaguera Dora , Siddiq Afshan , Bueno-de-Mesquita H. Bas , Rohrmann Sabine 
Published: March 2012

Abstract
Background: Advanced glycation end products (AGE) and their receptors (RAGE) have been implicated in cancer development through their proinflammatory capabilities. However, prospective data on their association with cancer of specific sites, including pancreatic cancer, are limited.
Methods: Prediagnostic blood levels of the AGE product Nϵ-(carboxymethyl)lysine (CML) and the endogenous secreted receptor for AGE (esRAGE) were measured using ELISA in 454 patients with exocrine pancreatic cancer and individually matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC). Pancreatic cancer risk was estimated by calculating ORs with corresponding 95% confidence intervals (CI).
Results: Elevated CML levels tended to be associated with a reduction in pancreatic cancer risk [OR = 0.57 (95% CI, 0.32–1.01) comparing highest with lowest quintile), whereas no association was observed for esRAGE (OR = 0.98; 95% CI, 0.62–1.54). Adjustments for body mass index and smoking attenuated the inverse associations of CML with pancreatic cancer risk (OR = 0.78; 95% CI, 0.41–1.49). There was an inverse association between esRAGE and risk of pancreatic cancer for cases that were diagnosed within the first 2 years of follow-up [OR = 0.46 (95% CI, 0.22–0.96) for a doubling in concentration], whereas there was no association among those with a longer follow-up (OR = 1.11; 95% CI, 0.88–1.39; Pinteraction = 0.002).
Conclusions and Impact: Our results do not provide evidence for an association of higher CML or lower esRAGE levels with risk of pancreatic cancer. The role of AGE/RAGE in pancreatic cancer would benefit from further investigations. Cancer Epidemiol Biomarkers Prev; 21(4); 619–28. ©2012 AACR.
Aromatic DNA Adducts and Risk of Gastrointestinal Cancers: A Case–Cohort Study within the EPIC–Spain
Authors: Agudo Antonio , Peluso Marco , Munnia Armelle , Luján-Barroso Leila , Sánchez María-José , Molina-Montes Esther , Sánchez-Cantalejo Emilio , Navarro Carmen , Tormo María-José , Chirlaque María-Dolores , Barricarte Aurelio , Ardanaz Eva , Amiano Pilar , Dorronsoro Miren , Quirós J. Ramón , Piro Sara , Bonet Catalina , Sala Núria , González Carlos A. 
Published: March 2012

Abstract
Background: Colorectal (CRC) and gastric cancer (GC) are associated with meat intake and tobacco smoke, maybe because of aromatic compounds occurring in tobacco smoking and formed during cooking meat. Activated metabolites of these compounds may bind to DNA forming bulky adducts.
Methods: Forty-eight subjects diagnosed of GC and 154 of CRC during a 7-year follow-up period in the European Prospective Investigation into Cancer and Nutrition–Spain cohort were compared with a sample of 296 subjects using a case–cohort approach. Aromatic adducts to DNA from leukocytes collected at recruitment were measured by means of the 32P-postlabeling technique. The relative risk (RR) and 95% confidence interval (CI), adjusted by relevant confounders were estimated by a modified version of Cox regression.
Results: Using the log2-transformed adduct concentration, we observed a RR = 1.57 (CI: 1.25–1.97) for CRC, which means a 57% increased risk associated with doubling the level of adducts, and 47% (RR = 1.47, CI: 1.07–2.00) increase in risk of GC. The association was more marked for colon than for rectal tumors.
Conclusions: The level of aromatic adducts in the DNA is independently associated with an increased risk of gastric and CRCs. This effect could be due to aromatic compounds present in tobacco smoke or formed in meat, but they could be also due to genotoxic compounds from other sources.
Impact: Sources of aromatic compounds should be taken into account, in addition to known risk factors, in the research and prevention of tumors of the stomach, colon, and rectum. Cancer Epidemiol Biomarkers Prev; 21(4); 685–92. ©2012 AACR.
Bigger, Better, Sooner–Scaling Up for Success
Authors: Thun Michael J. , Hoover Robert N. , Hunter David J. 
Published: March 2012

Abstract
Over the last twenty years, the field of epidemiology has seen a rapidly increasing interest in, and need for, addressing low-level risks, interactions as well as main effects, and simultaneous assessment of vast numbers of biomarkers. Multiple examples over this time have shown the necessity for very large, high-quality individual studies (e.g., biobanks) or consortia of studies for these efforts to be successful. The need for this will continue to increase in the foreseeable future. It will also be important to analyze and publish aggregated data much earlier in the discovery process than typical for past efforts. Cancer Epidemiol Biomarkers Prev; 21(4); 571–5. ©2012 AACR.
Impact of polyelectrolytes and their corresponding multilayers to human primary endothelial cells
Authors: Nolte Andrea , Hossfeld Susanne , Schroeppel Birgit , Mueller Anne , Stoll Dieter , Walker Tobias , Wendel Hans Peter , Krastev Rumen 
Published: March 2012

The layer-by-layer technique, which allows simple preparation of polyelectrolyte multilayers, came into the focus of research for development of functionalized medical devices. Numerous literature exist that concentrate on the film build-up and the behaviour of cells on polyelectrolyte multilayers. However, in case of very soft polyelectrolyte multilayers, studies of the cell behaviour on these films are sometimes misleading with regard to clinical applications because cells do not die due to cytotoxicity but due to apoptosis by missing cell adhesion. It turns out that the adhesion in vitro, and thus, the viability of cells on polyelectrolyte multilayers is mostly influenced by their mechanical properties. In order to decide, which polyelectrolyte multilayers are suitable for implants, we take this problem into account by putting the substrates with soft films on top of pre-cultured human primary endothelial cells (‘reverse assay’). Hence, the present work aims giving a more complete and reliable study of typical polyelectrolyte multilayers with regard to clinical applications. In particular, coatings consisting of hyaluronic acid and chitosan as natural polymers and sulfonated polystyrene and polyallylamine hydrochlorite as synthetic polymers were studied. The adsorption of polyelectrolytes was characterized by physico-chemical methods which show regular buildup. Biological examination of the native or modified polyelectrolyte multilayers was based on their effect to cell adhesion and morphology of endothelial cells by viability assays, immunostaining and scanning electron microscopy. Using the standard method, which is typically applied in literature – seeding cells on top of films – shows that the best adhesion and thus, viability can be achieved using sulfonated polystyrene/polyallylamine hydrochlorite. However, putting the films on top of endothelial cells reveals that hyaluronic acid/chitosan may also be suitable for clinical applications: This result is especially remarkable, since hyaluronic acid and chitosan mediate per se no cytotoxic effects, whereas the individual polyelectrolytes, sulfonated polystyrene and polyallylamine hydrochlorite, and their complexes show slight cytotoxicity.
Tribological performances on porous polyphenylene sulfide self-lubricating composites with super wear resistance
Authors: Wang Huaiyuan , Wang Guiying , Zhang Shuai , Yang Shuhui , Zhu Yanji 
Published: March 2012

The porous polyphenylene sulfide (PPS) self-lubricating composites with sweating effect were designed and fabricated, and the friction and wear behavior were evaluated. Results indicated that, porous PPS self-lubricating composite modified by 1 wt.% zeolite and impregnated with lithium-base grease in the pores showed the lowest friction coefficient and wear rate, which were recorded as 0.024 and 1.79 × 10−16 m3/Nm, respectively. Compared with pure PPS under dry condition, the friction coefficient reduced by 90% and wear resistance increased by 4.67 × 104 times. The wear resistant enhanced by 3.61 times than that of PPS/30 wt.% NaCl composites, so it showed synergistic effect on improving wear resistance. By means of scanning electron microscope, it was found that the pores of porous PPS composites with 1 wt.% zeolite were uniformly distributed and grease were well embedded in these orderly pores of PPS composites. Under the effect of load and temperature, grease squeezed from micropores and nanopores can provide the excellent lubrication effect, which are the main reason for the outstanding self-lubricating and wear resistance of PPS porous composites.
Lessons from an investigation of seclusion at an older adolescent inpatient unit
Authors: Swadi Harith , Bobier Candace 
Published: March 2012

Objective: To determine the rate, indications and process for using seclusion for patients undergoing treatment at an older adolescent inpatient unit. Method: Data were gathered prospectively and retrospectively as part of a quality assurance initiative at the Christchurch Youth Inpatient Unit (YIU); paper, electronic and legal documentation were examined. Results: During the time period of the investigation, approximately 13% of individuals admitted to the unit were secluded. Psychosis, involuntary admission and Maori ethnicity were significantly associated with the use of seclusion with aggression being the most documented indication. The vast majority of seclusions occurred within the first seven days of admission and over half utilized pro re nata medication prior to seclusion. Conclusions: Opportunities exist for intensifying and focusing efforts to minimize the use of seclusion and restraint, particularly during the first week of hospitalization.
Regulation of murine normal and stress-induced erythropoiesis by Desert Hedgehog
Authors: Lau Ching-in , Outram Susan V. , Ignacio Saldaña José , Furmanski Anna L. , Dessens Johannes T. , Crompton Tessa 
Published: March 2012

AbstractThe function of Hedgehog signaling in hematopoiesis is controversial, with different experimental systems giving opposing results. Here we examined the role of Desert Hedgehog (Dhh) in the regulation of murine erythropoiesis. Dhh is one of 3 mammalian Hedgehog family proteins. Dhh is essential for testis development and Schwann cell function. We show, by analysis of Dhh-deficient mice, that Dhh negatively regulates multiple stages of erythrocyte differentiation. In Dhh-deficient bone marrow, the common myeloid progenitor (CMP) population was increased, but differentiation from CMP to granulocyte/macrophage progenitor was decreased, and the mature granulocyte population was decreased, compared with wild-type (WT). In contrast, differentiation from CMP to megakaryocyte/erythrocyte progenitor was increased, and the megakaryocyte/erythrocyte progenitor population was increased. In addition, we found that erythroblast populations were Dhh-responsive in vitro and ex vivo and that Dhh negatively regulated erythroblast differentiation. In Dhh-deficient spleen and bone marrow, BFU-Es and erythroblast populations were increased compared with WT. During recovery of hematopoiesis after irradiation, and under conditions of stress-induced erythropoiesis, erythrocyte differentiation was accelerated in both spleen and bone marrow of Dhh-deficient mice compared with WT.
The tumor suppressor p15Ink4b regulates the differentiation and maturation of conventional dendritic cells
Authors: Fares Joanna , Koller Richard , Humeniuk Rita , Wolff Linda , Bies Juraj 
Published: March 2012

Abstract
The tumor suppressor p15Ink4b is frequently inactivated by methylation in acute myeloid leukemia and premalignant myeloid disorders. Dendritic cells (DCs) as potent APCs play critical regulatory roles in antileukemic immune responses. In the present study, we investigated whether p15Ink4b can function as modulator of DC development. The expression of p15Ink4b is induced strongly during differentiation and activation of DCs, and its loss resulted in significant quantitative and qualitative impairments of conventional DC (cDC) development. Accordingly, ex vivo–generated BM-derived DCs from p15Ink4b-knockout mice express significantly decreased levels of the antigen-presenting (MHC II) and costimulatory (CD80 and CD86) molecules and have impaired immunostimulatory functions, such as antigen uptake and T-cell stimulation. Reexpression of p15Ink4b in progenitors restored these defects, and confirmed a positive role for p15Ink4b during cDC differentiation and maturation. Furthermore, we have shown herein that p15Ink4b expression increases phosphorylation of Erk1/Erk2 kinases, which leads to an elevated activity of the PU.1 transcription factor. In conclusion, our results establish p15Ink4b as an important modulator of cDC development and implicate a novel function for this tumor suppressor in the regulation of adaptive immune responses.
Asexual reproduction induces a rapid and permanent loss of sexual reproduction capacity in the rice fungal pathogen Magnaporthe oryzae: results of in vitroexperimental evolution assays
Authors: Saleh Dounia , Milazzo Joëlle , Adreit Henri , Tharreau Didier , Fournier Elisabeth 
Published: March 2012

Abstract

Background
Sexual reproduction is common in eukaryotic microorganisms, with few species reproducing exclusively asexually. However, in some organisms, such as fungi, asexual reproduction alternates with episodic sexual reproduction events. Fungi are thus appropriate organisms for studies of the reasons for the selection of sexuality or clonality and of the mechanisms underlying this selection. Magnaporthe oryzae, an Ascomycete causing blast disease on rice, reproduces mostly asexually in natura. Sexual reproduction is possible in vitro and requires (i) two strains of opposite mating types including (ii) at least one female-fertile strain (i.e. a strain able to produce perithecia, the female organs in which meiosis occurs). Female-fertile strains are found only in limited areas of Asia, in which evidence for contemporary recombination has recently been obtained. We induced the forced evolution of four Chinese female-fertile strains in vitro by the weekly transfer of asexual spores (conidia) between Petri dishes. We aimed to determine whether female fertility was rapidly lost in the absence of sexual reproduction and whether this loss was controlled genetically or epigenetically.

Results
All the strains became female-sterile after 10 to 19 rounds of selection under asexual conditions. As no single-spore isolation was carried out, the observed decrease in the production of perithecia reflected the emergence and the invasion of female-sterile mutants. The female-sterile phenotype segregated in the offspring of crosses between female-sterile evolved strains and female-fertile wild-type strains. This segregation was maintained in the second generation in backcrosses. Female-sterile evolved strains were subjected to several stresses, but none induced the restoration of female fertility. This loss of fertility was therefore probably due to genetic rather than epigenetic mechanisms. In competition experiments, female-sterile mutants produced similar numbers of viable conidia to wild-type strains, but released them more efficiently. This advantage may account for the invasion of our populations by female-sterile mutants.

Conclusions
We show for the first time that, in the absence of sexual reproduction, female-sterile mutants of M. oryzae rice strains can arise and increase in abundance in asexual generations. This change in phenotype was frequent and probably caused by mutation. These results suggest that female fertility may have been lost rapidly during the dispersion of the fungus from Asia to the rest of the world.
Functional effects of the TMEM43 Ser358Leu mutation in the pathogenesis of arrhythmogenic right ventricular cardiomyopathy
Authors: Rajkumar Revathi , Sembrat John C , McDonough Barbara , Seidman Christine E , Ahmad Ferhaan 
Published: March 2012

Abstract

Background
The Ser358Leu mutation in TMEM43, encoding an inner nuclear membrane protein, has been implicated in arrhythmogenic right ventricular cardiomyopathy (ARVC). The pathogenetic mechanisms of this mutation are poorly understood.

Methods
To determine the frequency of TMEM43 mutations as a cause of ARVC, we screened 11 ARVC families for mutations in TMEM43 and five desmosomal genes previously implicated in the disease. Functional studies were performed in COS-7 cells transfected with wildtype, mutant, and 1:2 wildtype:mutant TMEM43 to determine the effect of the Ser358Leu mutation on the stability and cellular localization of TMEM43 and other nuclear envelope and desmosomal proteins, assessed by solubility assays and immunofluorescence imaging. mRNA expression was assessed of genes potentially affected by dysfunction of the nuclear lamina.

Results
Three novel mutations in previously documented desmosomal genes, but no mutations in TMEM43, were identified. COS-7 cells transfected with mutant TMEM43 exhibited no change in desmosomal stability. Stability and nuclear membrane localization of mutant TMEM43 and of lamin B and emerin were normal. Mutant TMEM43 did not alter the expression of genes located on chromosome 13, previously implicated in nuclear envelope protein mutations leading to skeletal muscular dystrophies.

Conclusions
Mutant TMEM43 exhibits normal cellular localization and does not disrupt integrity and localization of other nuclear envelope and desmosomal proteins. The pathogenetic role of TMEM43 mutations in ARVC remains uncertain.
Response gene to complement-32 enhances metastatic phenotype by mediating transforming growth factor beta-induced epithelial-mesenchymal transition in human pancreatic cancer cell line BxPC-3
Authors: Zhu Liang , Qin Hua , Li Pei-Yuan , Xu Sheng-Nan , Pang Hui-Fang , Zhao Hui-Zhen , Li De-Min , Zhao Qiu 
Published: March 2012

AbstractBackgroundResponse gene to complement-32 (RGC-32) is comprehensively expressed in many kinds of tissues and has been reported to be expressed abnormally in different kinds of human tumors. However, the role of RGC-32 in cancer remains controversial and no reports have described the effect of RGC-32 in pancreatic cancer. The present study investigated the expression of RGC-32 in pancreatic cancer tissues and explored the role of RGC-32 in transforming growth factor-beta (TGF-β)-induced epithelial-mesenchymal transition (EMT) in human pancreatic cancer cell line BxPC-3.MethodsImmunohistochemical staining of RGC-32 and E-cadherin was performed on specimens from 42 patients with pancreatic cancer, 12 with chronic pancreatitis and 8 with normal pancreas. To evaluate the role of RGC-32 in TGF-β-induced EMT in pancreatic cancer cells, BxPC-3 cells were treated with TGF-β1, and RGC-32 siRNA silencing and gene overexpression were performed as well. The mRNA expression and protein expression of RGC-32 and EMT markers such E-cadherin and vimentin were determined by quantitative reverse transcription-PCR (qRT-PCR) and western blot respectively. Finally, migration ability of BxPC-3 cells treated with TGF-β and RGC-32 siRNA transfection was examined by transwell cell migration assay.ResultsWe found stronger expression of RGC-32 and higher abnormal expression rate of E-cadherin in pancreatic cancer tissues than those in chronic pancreatitis tissues and normal pancreatic tissues. Immunohistochemical analysis revealed that both RGC-32 positive expression and E-cadherin abnormal expression in pancreatic cancer were correlated with lymph node metastasis and TNM staging. In addition, a significant and positive correlation was found between positive expression of RGC-32 and abnormal expression of E-cadherin. Furthermore, in vitro, we found sustained TGF-β stimuli induced EMT and up-regulated RGC-32 expression in BxPC-3 cells. By means of siRNA silencing and gene overexpression, we further demonstrated that RGC-32 mediated TGF-β-induced EMT and migration in BxPC-3 cells.ConclusionsThe results above indicated that RGC-32 might be a novel metastasis promoting gene in pancreatic cancer and it enhances metastatic phenotype by mediating TGF-β-induced EMT in human pancreatic cancer cell line BxPC-3.
Utilization, Spending, and Price Trends for Benzodiazepines in the US Medicaid Program: 1991-2009
Authors: Gorevski Elizabeth , Bian Boyang , Kelton Christina ML , Martin Boone Jill E , Guo Jeff J 
Published: March 2012

Background: Although it is well-known that drug costs in the US have risen precipitously over the last 25 years, what is much less appreciated is how this rise in cost has occurred across so many seemingly distinct drug markets. Objective: To describe trends in the utilization, spending, and average per-prescription cost of benzodiazepines individually, in subgroups, and overall, in the Medicaid program. Medicaid has been the primary public payer for benzodiazepines over the past 2 decades. Methods: A retrospective, descriptive analysis was performed for the years 1991-2009 using the publicly available national Summary Files from the Medicaid State Drug Utilization Data maintained by the Centers for Medicare & Medicaid Services. Quarterly prescription counts and reimbursement amounts were calculated for all benzodiazepines reimbursed by Medicaid. Average per-prescription spending as a proxy for drug price was found by dividing reimbursement by the number of prescriptions. Results: Prescriptions for benzodiazepines among Medicaid beneficiaries increased from 8.0 million in 1991 to 17.1 million in 2009. Expenditures rose from $131.6 million to $171.1 million over the same time period. The average per-prescription price was a little over $10 in 2009. Whereas utilization of intermediate- and long-acting agents increased over time, prescriptions for short-acting drugs fell from 1.1 million to 0.3 million (1991-2009). The percentage rise in Medicaid spending on benzodiazepines since 1991 (30.0%) was less than the general rate of inflation (57.5%), as measured by the percentage change in the consumer price index over the same time period. Conclusions: Relative to the rise in the number of Medicaid beneficiaries (more than doubled over the study period), there is no evidence of an extraordinary rise in the utilization of benzodiazepines. Moreover, both nominal and real average prices of benzodiazepines have fallen, primarily because of generic entry over the last 2 decades.