bluuebunny/crossref_metadata_2025_split huggingface dataset:
JC Virus Infection in Colorectal Neoplasia That Develops after Liver Transplantation
Authors: Selgrad Michael , Koornstra Jan Jacob , Fini Lucia , Blom Marloes , Huang Rong , DeVol Edward B. , Boersma-van Ek Wytske , Dijkstra Gerard , Verdonk Robert C. , de Jong Steven , Goel Ajay , Williams Sharenda L. , Meyer Richard L. , Haagsma Elizabeth B. , Ricciardiello Luigi , Boland C. Richard 
Published: October 2008

Abstract
Purpose: Liver transplant recepients (LTRs) have an increased risk of colorectal neoplasia. The mechanism responsible for this is unknown. JCV encodes for TAg and has been implicated in colorectal carcinogenesis. We hypothesized that the use of immunosuppression in LTRs facilitates activation of JCV and is responsible for the increased risk of neoplasia.
Experimental Design: JCV TAg DNA and protein expression were determined in normal colonic epithelium (n = 15) and adenomatous polyps (n = 26) from LTRs and compared with tissue samples from control patients (normal colon, n = 21; adenomas, n = 40). Apoptosis and proliferation were determined by M30 and Ki-67 immunoreactivity, respectively.
Results: JCV TAg DNA was found in 10 of 15 (67%) of normal colonic mucosa from LTRs compared with 5 of 21 (24%) of control normal mucosa (P = 0.025). JCV TAg DNA was detected in 16 of 26 (62%) of the adenomas from LTRs and in 20 of 40 (50%) of control adenomas. JCV TAg protein was expressed in 13 of 26 (50%) adenomas from LTRs versus 2 of 40 (5%) of adenomas from controls (P &lt; 0.001). In adenomas from LTRs, the mean proliferative activity was higher compared with controls (60.3 ± 3.2% versus 42.7 ± 2.8%, P &lt; 0.001), whereas mean apoptotic indices were lower in LTRs (0.29 ± 0.08% versus 0.39 ± 0.06%, P = 0.05).
Conclusions: The presence of JCV in the colorectal mucosa and adenomas from LTRs, in concert with the use of immunosuppressive agents, suggests that JCV may undergo reactivation, and the subsequent TAg protein expression might explain the increased risk of colorectal neoplasia in LTRs.
A Phase 1 Dose-Escalation Study of Irinotecan in Combination with 17-Allylamino-17-Demethoxygeldanamycin in Patients with Solid Tumors
Authors: Tse Archie N. , Klimstra David S. , Gonen Mithat , Shah Manish , Sheikh Tahir , Sikorski Rachel , Carvajal Richard , Mui Janet , Tipian Caroll , O'Reilly Eileen , Chung Ki , Maki Robert , Lefkowitz Robert , Brown Karen , Manova-Todorova Katia , Wu Nian , Egorin Merrill J. , Kelsen David , Schwartz Gary K. 
Published: October 2008

Abstract
Purpose: Both heat shock protein 90 (Hsp90) and checkpoint kinase 1 (Chk1) have emerged as novel therapeutic targets. We conducted a phase I study of irinotecan and the Hsp90 inhibitor 17AAG, which can also down-regulate Chk1, in patients with solid tumors.
Experimental Design: During the dose escalation phase, patients received i.v. irinotecan followed by 17AAG once weekly for 2 weeks in a 21-day cycle. At the maximum tolerated dose (MTD), additional patients were enrolled to undergo pre- and post-17AAG tumor biopsies for pharmacodynamic evaluation. The pharmacokinetics of irinotecan, 17AAG, and their metabolites were characterized. Tumor p53 status as determined by immunohistochemistry was correlated with antitumor activity.
Results: Twenty-seven patients with a variety of solid tumors were enrolled. Four patients developed dose-limiting toxicity at dose level 4 (100 mg/m2 irinotecan and 375 mg/m2 17AAG) including nausea, vomiting, diarrhea, and pulmonary embolism. The pharmacokinetics of 17AAG and its metabolite were not significantly affected by the coadministration of irinotecan, and vice versa. There was no partial response, although tumor shrinkage was observed in six patients. Five of 10 patients with p53-mutant tumor had stable disease as the best response compared with 2 of 6 patients with p53-wildtype tumor (P = 0.63). Evidence for Hsp90 inhibition by 17AAG, resulting in phospho-Chk1 loss, abrogation of the G2-M cell cycle checkpoint, and cell death could be shown in tumor biopsy samples obtained at the MTD.
Conclusions: The combination of irinotecan and 17AAG can be given to patients with acceptable toxicity. The recommended phase II dose of the combination is 100 mg/m2 irinotecan and 300 mg/m2 17AAG.
Regression of Drug-Resistant Lung Cancer by the Combination of Rosiglitazone and Carboplatin
Authors: Girnun Geoffrey D. , Chen Liang , Silvaggi Jessica , Drapkin Ronny , Chirieac Lucian R. , Padera Robert F. , Upadhyay Rabi , Vafai Scott B. , Weissleder Ralph , Mahmood Umar , Naseri Elnaz , Buckley Stephanie , Li Danan , Force Jeremy , McNamara Kate , Demetri George , Spiegelman Bruce M. , Wong Kwok-Kin 
Published: October 2008

Abstract
Purpose: Current therapy for lung cancer involves multimodality therapies. However, many patients are either refractory to therapy or develop drug resistance. KRAS and epidermal growth factor receptor (EGFR) mutations represent some of the most common mutations in lung cancer, and many studies have shown the importance of these mutations in both carcinogenesis and chemoresistance. Genetically engineered murine models of mutant EGFR and KRAS have been developed that more accurately recapitulate human lung cancer. Recently, using cell-based experiments, we showed that platinum-based drugs and the antidiabetic drug rosiglitazone (PPARγ ligand) interact synergistically to reduce cancer cell and tumor growth. Here, we directly determined the efficacy of the PPARγ/carboplatin combination in these more relevant models of drug resistant non–small cell lung cancer.
Experimental Design: Tumorigenesis was induced by activation of either mutant KRAS or EGFR. Mice then received either rosiglitazone or carboplatin monotherapy, or a combination of both drugs. Change in tumor burden, pathology, and evidence of apoptosis and cell growth were assessed.
Results: Tumor burden remained unchanged or increased in the mice after monotherapy with either rosiglitazone or carboplatin. In striking contrast, we observed significant tumor shrinkage in mice treated with these drugs in combination. Immunohistochemical analyses showed that this synergy was mediated via both increased apoptosis and decreased proliferation. Importantly, this synergy between carboplatin and rosiglitazone did not increase systemic toxicity.
Conclusions: These data show that the PPARγ ligand/carboplatin combination is a new therapy worthy of clinical investigation in lung cancers, including those cancers that show primary resistance to platinum therapy or acquired resistance to targeted therapy.
Tumor-Specific Urinary Matrix Metalloproteinase Fingerprinting: Identification of High Molecular Weight Urinary Matrix Metalloproteinase Species
Authors: Roy Roopali , Louis Gwendolyn , Loughlin Kevin R. , Wiederschain Dmitri , Kilroy Susan M. , Lamb Carolyn C. , Zurakowski David , Moses Marsha A. 
Published: October 2008

Abstract
Purpose: We have previously reported that matrix metalloproteinases MMP-2, MMP-9, and the complex MMP-9/NGAL can be detected in urine of patients with a variety of cancers including prostate and bladder carcinoma. In addition, we also detected several unidentified urinary gelatinase activities with molecular weights &gt;125 kDa. The objective of the current study was to identify these high molecular weight (HMW) species, determine their potential as predictors of disease status, and ask whether a tumor-specific pattern existed based on urinary MMP analysis.
Experimental Design: Chromatography, zymography, and mass spectrometry was used to identify HMW gelatinase species of ∼140, 190, and &gt;220 kDa in urine of cancer patients. To determine whether a tumor-specific pattern of appearance existed among the MMPs detected, we analyzed the urine of 189 patients with prostate or bladder cancer and controls.
Results: The ∼140, &gt;220 kDa, and ∼190 HMW gelatinase species were identified as MMP-9/tissue inhibitor of metalloproteinase 1 complex, MMP-9 dimer, and ADAMTS-7, respectively. The frequency of detection of any MMP species was significantly higher in urine from prostate and bladder cancer groups than controls. MMP-9 dimer and MMP-9 were independent predictors for distinguishing between patients with prostate and bladder cancer (P &lt; 0.001 for each) by multivariable analysis.
Conclusions: This study is the first to identify a tumor-specific urinary MMP fingerprint that may noninvasively facilitate identification of cancer presence and type. This information may be of diagnostic and prognostic value in the detection and/or clinical monitoring of disease progression and therapeutic efficacy in patients with bladder or prostate cancer.
The Ageing Populations of Europe — Implications for Health Systems and Patients' Rights
Authors: Rynning Elisabeth 
Published: October 2008

AbstractEurope is facing a trend of demographic and social change that is likely to have a significant impact on our health systems in the coming decades. The primary concerns are related to the double challenge of population ageing and population decline. These changes will result in a shrinking workforce to handle the steadily increasing healthcare needs of the very old, who will constitute the fastest growing segment of the population. A number of strategies to meet this challenge are suggested and implemented, not least at the EU level. Adaptation of European health systems to the new situation also makes it necessary to revisit familiar medico-legal issues, in order to clarify and consolidate a number of already established patients' rights.
CMA – a comprehensive Bioconductor package for supervised classification with high dimensional data
Authors: Slawski M , Daumer M , Boulesteix A-L 
Published: October 2008

AbstractBackgroundFor the last eight years, microarray-based classification has been a major topic in statistics, bioinformatics and biomedicine research. Traditional methods often yield unsatisfactory results or may even be inapplicable in the so-called "p≫n" setting where the number of predictorspby far exceeds the number of observationsn, hence the term "ill-posed-problem". Careful model selection and evaluation satisfying accepted good-practice standards is a very complex task for statisticians without experience in this area or for scientists with limited statistical background. The multiplicity of available methods for class prediction based on high-dimensional data is an additional practical challenge for inexperienced researchers.ResultsIn this article, we introduce a new Bioconductor package called CMA (standing for "Classification forMicroArrays") for automatically performing variable selection, parameter tuning, classifier construction, and unbiased evaluation of the constructed classifiers using a large number of usual methods. Without much time and effort, users are provided with an overview of the unbiased accuracy of most top-performing classifiers. Furthermore, the standardized evaluation framework underlying CMA can also be beneficial in statistical research for comparison purposes, for instance if a new classifier has to be compared to existing approaches.ConclusionCMA is a user-friendly comprehensive package for classifier construction and evaluation implementing most usual approaches. It is freely available from the Bioconductor website athttp://bioconductor.org/packages/2.3/bioc/html/CMA.html.
p53 induces distinct epigenetic states at its direct target promoters
Authors: Vrba Lukas , Junk Damian J , Novak Petr , Futscher Bernard W 
Published: October 2008

Abstract

Background
The tumor suppressor protein p53 is a transcription factor that is mutated in many cancers. Regulation of gene expression by binding of wild-type p53 to its target sites is accompanied by changes in epigenetic marks like histone acetylation. We studied DNA binding and epigenetic changes induced by wild-type and mutant p53 in non-malignant hTERT-immortalized human mammary epithelial cells overexpressing either wild-type p53 or one of four p53 mutants (R175H, R249S, R273H and R280K) on a wild-type p53 background.

Results
Using chromatin immunoprecipitation coupled to a 13,000 human promoter microarray, we found that wild-type p53 bound 197 promoters on the microarray including known and novel p53 targets. Of these p53 targets only 20% showed a concomitant increase in histone acetylation, which was linked to increased gene expression, while 80% of targets showed no changes in histone acetylation. We did not observe any decreases in histone acetylation in genes directly bound by wild-type p53. DNA binding in samples expressing mutant p53 was reduced over 95% relative to wild-type p53 and very few changes in histone acetylation and no changes in DNA methylation were observed in mutant p53 expressing samples.

Conclusion
We conclude that wild-type p53 induces transcription of target genes by binding to DNA and differential induction of histone acetylation at target promoters. Several new wild-type p53 target genes, including DGKZ, FBXO22 and GDF9, were found. DNA binding of wild-type p53 is highly compromised if mutant p53 is present due to interaction of both p53 forms resulting in no direct effect on epigenetic marks.
Species-specific regulation of PXR/CAR/ER-target genes in the mouse and rat liver elicited by o, p'-DDT
Authors: Kiyosawa Naoki , Kwekel Joshua C , Burgoon Lyle D , Dere Edward , Williams Kurt J , Tashiro Colleen , Chittim Brock , Zacharewski Timothy R 
Published: October 2008

AbstractBackgroundDichlorodiphenyltrichloroethane (DDT) is a persistent estrogenic organochlorine pesticide that is a rodent hepatic tumor promoter, with inconclusive carcinogenicity in humans. We have previously reported thato,p'-DDT elicits primarily PXR/CAR-mediated activity, rather than ER-mediated hepatic responses, and suggested that CAR-mediated effects, as opposed to ER-mediated effects, may be more important in tumor promotion in the rat liver. To further characterize species-specific hepatic responses, gene expression analysis, with complementary histopathology and tissue level analyses were investigated in immature, ovariectomized C57BL/6 mice treated with 300 mg/kgo,p'-DDT, and compared to Sprague-Dawley rat data.ResultsRats and mice exhibited negligible histopathology with rapido,p'-DDT metabolism. Gene expression profiles were also similar, exhibiting PXR/CAR regulation with the characteristic induction ofCyp2b10andCyp3a11. However, PXR-specific target genes such asApoa4orInsig2exhibited more pronounced induction compared to CAR-specific genes in the mouse. In addition, mouseCarmRNA levels decreased, possibly contributing to the preferential activation of mouse PXR. ER-regulated genesCyp17a1andCyp7b1were also induced, suggestingo,p'-DDT also elicits ER-mediated gene expression in the mouse, while ER-mediated effects were negligible in the rat, possibly due to the inhibitory effects of CAR on ER activities. In addition,o,p'-DDT inducedGadd45a,Gadd45bandCdkn1, suggesting DNA damage may be an additional risk factor. Furthermore, elevated blood DHEA-S levels at 12 h after treatment in the mouse may also contribute to the endocrine-related effects ofo,p'-DDT.ConclusionAlthough DDT is known to cause rodent hepatic tumors, the marked species differences in PXR/CAR structure, expression patterns and ligand preference as well as significant species-specific differences in steroidogenesis, especially CYP17A1 expression and activity, confound the extrapolation of these results to humans. Nevertheless, the identification of potential modes of action as well as species-specific responses may assist in the selection and further development of more appropriate models for assessing the toxicity of DDT to humans and wildlife.
A train-the-trainer education and promotion program: chronic fatigue syndrome – a diagnostic and management challenge
Authors: Brimmer Dana J , McCleary K Kimberly , Lupton Teresa A , Faryna Katherine M , Hynes Kevin , Reeves William C 
Published: October 2008

Abstract

Background
Chronic fatigue syndrome (CFS) is a complicated illness for providers and patients. Fewer than 20% of persons with CFS have been diagnosed and treated. For providers, compounding the issue are the challenges in making a diagnosis due to the lack of a biomedical marker.

Methods
The objective of the CFS diagnosis and management curriculum was to instruct core trainers as to the evaluation, diagnosis, and management of CFS. Over a two year period, 79 primary care physicians, physician assistants, and nurse practitioners from diverse regions in the U.S. participated as core trainers in a two day Train-the-Trainer (TTT) workshop. As core trainers, the workshop participants were expected to show increases in knowledge, self-efficacy, and management skills with the primary goal of conducting secondary presentations.

Results
The optimal goal for each core trainer to present secondary training to 50 persons in the health care field was not reached. However, the combined core trainer group successfully reached 2064 primary care providers. Eighty-two percent of core trainers responded "Very good" or "Excellent" in a post-tessurvey of self-efficacy expectation and CFS diagnosis. Data from the Chicago workshops showed significant improvement on the Primary Care Opinion Survey (p < 0.01) and on the Relevance and Responsibility Factors of the CAT survey (p = 0.03 and p = 0.04, respectively). Dallas workshop data show a significant change from pre- to post-test scores on the CFS Knowledge test (p = 0.001). Qualitative and process evaluation data revealed that target audience and administrative barriers impacted secondary training feasibility.

Conclusion
Data show the workshop was successful in meeting the objectives of increasing CFS knowledge and raising perceived self-efficacy towards making a diagnosis. The CFS TTT program informed an educational provider project by shifting the format for physicians to grand rounds and continuing medical education design while retaining TTT aspects for nurse practitioners and physicians assistants. Evaluations also indicate that secondary trainings may be more readily employed and accepted if administrative barriers are addressed early in the planning phases.
Peptide P5 (residues 628–683), comprising the entire membrane proximal region of HIV-1 gp41 and its calcium-binding site, is a potent inhibitor of HIV-1 infection
Authors: Yu Huifeng , Tudor Daniela , Alfsen Annette , Labrosse Beatrice , Clavel François , Bomsel Morgane 
Published: October 2008

Abstract
The membrane proximal region (MPR) of the transmembrane subunit, gp41, of the HIV envelope glycoprotein plays a critical role in HIV-1 infection of CD4+ target cells and CD4-independent mucosal entry. It contains continuous epitopes recognized by neutralizing IgG antibodies 2F5, 4E10 and Z13, and is therefore considered to be a promising target for vaccine design. Moreover, some MPR-derived peptides, such as T20 (enfuvirtide), are in clinical use as HIV-1 inhibitors. We have shown that an extended MPR peptide, P5, harbouring the lectin-like domain of gp41 and a calcium-binding site, is implicated in the interaction of HIV with its mucosal receptor. We now investigate the potential antiviral activities of P5 and other such long MPR-derived peptides. Structural studies of gp41 MPR-derived peptides using circular dichroism showed that the peptides P5 (a.a.628–683), P1 (a.a.648–683), P5L (a.a.613–683) and P7 (a.a.613–746) displayed a well-defined α-helical structure. Peptides P5 inhibited HIV-1 envelope mediated cell-cell fusion and infection of peripheral blood mononuclear cells by both X4- and R5-tropic HIV-1 strains, whereas peptides P5 mutated in the calcium binding site or P1 lacked antiviral activity, when P5L blocked cell fusion in contrast to P7. Strikingly, P5 inhibited CD4-dependent infection by T20-resistant R5-tropic HIV-1 variants. Cell-cell fusion studies indicated that the anti-HIV-1 activity of P5, unlike T20, could not be abrogated in the presence of the N-terminal leucine zipper domain (LZ). These results suggested that P5 could serve as a potent fusion inhibitor.
Munchausen's syndrome presenting as rectal foreign body insertion: a case report
Authors: Khan Shakeeb A , Davey Christine A , Khan Shamsul A , Trigwell Peter J , Chintapatla Srinivas 
Published: October 2008

Abstract

Background
This case report shows that Munchausen's syndrome can present as rectal foreign body insertion. Although the presentation of rectal foreign bodies has frequently been described in the medical literature, the insertion of foreign bodies into the rectum for reasons other than sexual gratification has rarely been considered.

Case presentation
A 30 year old, unmarried Caucasian male presented with a history of having been sexually assaulted five days earlier in a nearby city by a group of unknown males. He reported that during the assault a glass bottle was forcibly inserted into his rectum and the bottle neck broke. On examination, there was no evidence of external injury to the patient. Further assessment lead to a diagnosis of Munchausen's syndrome. The rationale for this is explained. A description and summary of current knowledge about the condition is also provided, including appropriate treatment approaches.

Conclusion
This case report is important because assumptions regarding the motivation for insertion of foreign bodies into the rectum may lead to the diagnosis of Munchausen's syndrome being missed. This would result in the appropriate course of action, with regard to treatment, not being followed. It is suggested that clinicians consider the specific motivation for the behaviour in all cases of rectal foreign body insertion, including the possibility of factitious disorder such as Munchausen's syndrome, and avoid any assumption that it has been carried out for the purpose of sexual gratification. Early involvement of psychiatrists is recommended. Cases of Munchausen's syndrome presenting as rectal foreign body insertion may be identified and addressed more effectively using the approach described.
Research in hydraulic brake components and operational factors influencing the hysteresis losses
Authors: Tretsiak D V , Kliauzovich S V , Augsburg K , Sendler J , Ivanov V G 
Published: October 2008

Up-to-date automotive brake systems place stringent requirements upon the performance, reliability, and active safety. Such advanced systems as antilock braking systems (ABS), the electronic stability programme system, and the anti-slip control system assist a driver in ensuring driving safety under many conditions. The influence of the brake components on active safety systems is mainly determined through the hysteresis loop width. Among other negative outcomes, this parameter limits the possible frequency of cyclic braking during ABS operation. This paper presents an experimental analysis of the factors influencing the hysteresis pressure losses in a hydraulic brake system. The factors under investigations are the brake pedal stroke velocity, the gaps between the brake pads and the brake disc, and the configuration of the brake system. Experiments were carried out on the brake test equipment at the Automotive Engineering Department, Faculty for Mechanical Engineering, Technische Universität Ilmenau, Germany.