bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of full length Hepatitis C Virus particles of 1a genotype through small interference RNA
Authors: Ansar Muhammad , Ashfaq Usman Ali , shahid Imran , Sarwar Muhammad Tahir , Javed Tariq , Rehman Sidra , Hassan Sajida , Riazuddin Sheikh 
Published: May 2011

Abstract

Background
Hepatitis C virus (HCV), a member of the Flaviviridae family of viruses, is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Currently, the only treatment available consists of a combination of Pegylated interferon alpha (INF-α) and ribavirin, but only half of the patients treated show a sufficient antiviral response. Thus there is a great need for the development of new treatments for HCV infections. RNA interference (RNAi) represents a new promising approach to develop effective antiviral drugs and has been extremely effective against HCV infection.

Results
This study was design to assess or explore the silencing effect of small interference RNAs (siRNAs) against full length HCV particles of genotype 1a. In the present study six 21-bp siRNAs were designed against different regions of HCV structural genes (Core, E1 and E2). Selected siRNAs were labeled as Csi 301, Csi 29, E1si 52, E1si 192, E2si 86 and E2si 493. Our results demonstrated that siRNAs directed against HCV core gene showed 70% reduction in viral titer in HCV infected liver cells. Moreover, siRNAs against E1 and E2 envelop genes showed a dramatic reduction in HCV viral RNA, E2si 86 exhibited 93% inhibition, while E1si 192, E2si 493 and E1si 52 showed 87%, 80%, and 66% inhibition respectively. No significant inhibition was detected in cells transfected with the negative control siRNA.

Conclusion
Our results suggested that siRNAs targeted against HCV structural genes efficiently silence full length HCV particles and provide an effective therapeutic option against HCV infection.
Primary osteosarcoma of bladder diverticulum mimicking intradiverticular calculus: a case report
Authors: Grubišić Igor , Leniček Tanja , Tomas Davor , Džombeta Tihana , Trnski Davor , Tomašković Igor , Krušlin Božo 
Published: May 2011

Abstract
There is a well-documented relationship between urinary bladder diverticula and intradiverticular neoplasms. The great majorities of these tumors are urothelial carcinomas, but may also be of glandular or squamous type. Sarcomas occurring within bladder diverticula are exceptionally rare and highly malignant lesions, with only 20 well documented cases published in the literature to date (including carcinosarcomas). We report a case of osteosarcoma of the bladder diverticulum in a 68-year old man, which clinically mimicked intradiverticular calculus. To our knowledge, this is the second case described in the literature to date, and the first in English literature.

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5205089355246060.
Prospero and Pax2 combinatorially control neural cell fate decisions by modulating Ras- and Notch-dependent signaling
Authors: Charlton-Perkins Mark , Whitaker S Leigh , Fei Yueyang , Xie Baotong , Li-Kroeger David , Gebelein Brian , Cook Tiffany 
Published: May 2011

Abstract

Background
The concept of an equivalence group, a cluster of cells with equal potential to adopt the same specific fate, has served as a useful paradigm to understand neural cell type specification. In the Drosophila eye, a set of five cells, called the 'R7 equivalence group', generates a single photoreceptor neuron and four lens-secreting epithelial cells. This choice between neuronal versus non-neuronal cell fates rests on differential requirements for, and cross-talk between, Notch/Delta- and Ras/mitogen-activated protein kinase (MAPK)-dependent signaling pathways. However, many questions remain unanswered related to how downstream events of these two signaling pathways mediate distinct cell fate decisions.

Results
Here, we demonstrate that two direct downstream targets of Ras and Notch signaling, the transcription factors Prospero and dPax2, are essential regulators of neuronal versus non-neuronal cell fate decisions in the R7 equivalence group. Prospero controls high activated MAPK levels required for neuronal fate, whereas dPax2 represses Delta expression to prevent neuronal fate. Importantly, activity from both factors is required for proper cell fate decisions to occur.

Conclusions
These data demonstrate that Ras and Notch signaling are integrated during cell fate decisions within the R7 equivalence group through the combinatorial and opposing activities of Pros and dPax2. Our study provides one of the first examples of how the differential expression and synergistic roles of two independent transcription factors determine cell fate within an equivalence group. Since the integration of Ras and Notch signaling is associated with many developmental and cancer models, these findings should provide new insights into how cell specificity is achieved by ubiquitously used signaling pathways in diverse biological contexts.
Formation of VEGF isoform-specific spatial distributions governing angiogenesis: computational analysis
Authors: Vempati Prakash , Popel Aleksander S , Mac Gabhann Feilim 
Published: May 2011

AbstractBackgroundThe spatial distribution of vascular endothelial growth factor A (VEGF) is an important mediator of vascular patterning. Previous experimental studies in the mouse hindbrain and retina have suggested that VEGF alternative splicing, which controls the ability of VEGF to bind to heparan sulfate proteoglycans (HSPGs) in the extracellular matrix (ECM), plays a key role in controlling VEGF diffusion and gradients in tissues. Conversely, proteolysis notably by matrix metalloproteinases (MMPs), plays a critical role in pathological situations by releasing matrix-sequestered VEGF and modulating angiogenesis. However, computational models have predicted that HSPG binding alone does not affect VEGF localization or gradients at steady state.ResultsUsing a 3D molecular-detailed reaction-diffusion model of VEGF ligand-receptor kinetics and transport, we test alternate models of VEGF transport in the extracellular environment surrounding an endothelial sprout. We show that differences in localization between VEGF isoforms, as observed experimentally in the mouse hindbrain, as well as the ability of proteases to redistribute VEGF in pathological situations, are consistent with a model where VEGF is endogenously cleared or degraded in an isoform-specific manner. We use our predictions of the VEGF distribution to quantify a tip cell's receptor binding and gradient sensing capacity. A novel prediction is that neuropilin-1, despite functioning as a coreceptor to VEGF165-VEGFR2 binding, reduces the ability of a cell to gauge the relative steepness of the VEGF distribution. Comparing our model to available in vivo vascular patterning data suggests that vascular phenotypes are most consistently predicted at short range by the soluble fraction of the VEGF distributions, or at longer range by matrix-bound VEGF detected in a filopodia-dependent manner.ConclusionsIsoform-specific VEGF degradation provides a possible explanation for numerous examples of isoform specificity in VEGF patterning and examples of proteases relocation of VEGF upon release.
Effect of Luteinizing Hormone–Releasing Hormone Agonist on Ovarian Function After Modern Adjuvant Breast Cancer Chemotherapy: The GBG 37 ZORO Study
Authors: Gerber Bernd , von Minckwitz Gunter , Stehle Heinrich , Reimer Toralf , Felberbaum Ricardo , Maass Nikolai , Fischer Dorothea , Sommer Harald L. , Conrad Bettina , Ortmann Olaf , Fehm Tanja , Rezai Mahdi , Mehta Keyur , Loibl Sibylle 
Published: May 2011

PurposeObservational studies suggested that luteinizing hormone–releasing hormone agonists (LHRHa) might prevent premature ovarian failure resulting from adjuvant chemotherapy in premenopausal patients. We aimed to test the efficacy of ovarian function preservation with the LHRHa goserelin in patients with breast cancer.Patients and MethodsIn a prospective, randomized, open-label, controlled multicenter study, 60 patients younger than age 46 years with hormone-insensitive breast cancer were allocated to receive anthracycline/cyclophosphamide (with or without taxane) –based neoadjuvant chemotherapy with or without goserelin. The first goserelin injection was administered at least 2 weeks before the first chemotherapy cycle, continuing at 3.6 mg subcutaneously every 4 weeks until the end of the last cycle. The primary objective was the reappearance of normal ovarian function, defined as two consecutive menstrual periods within 21 to 35 days at 6 months after end of chemotherapy.ResultsFifty-three patients (88.3%) experienced temporary amenorrhea (93.3% with v 83.3% without goserelin). No significant difference was observed regarding the reappearance of menstruation at 6 months after chemotherapy (70.0% with v 56.7% without goserelin; difference of 13.3%; 95% CI, −10.85 to 37.45; P = .284). All but one evaluable patient reported regular menses at 2 years after chemotherapy. Time to restoration of menstruation was 6.8 months (95% CI, 5.2 to 8.4) with goserelin and 6.1 months (95% CI, 5.3 to 6.8) without goserelin (P = .304). Chemotherapy resulted in a decreased ovarian reserve measured by inhibin B and anti-Müllerian hormone during follow-up, supporting the other findings.ConclusionPremenopausal patients with breast cancer receiving goserelin simultaneously with modern neoadjuvant chemotherapy did not experience statistically significantly less amenorrhea 6 months after end of chemotherapy compared with those receiving chemotherapy alone.
mRNA Expression Signature of Gleason Grade Predicts Lethal Prostate Cancer
Authors: Penney Kathryn L. , Sinnott Jennifer A. , Fall Katja , Pawitan Yudi , Hoshida Yujin , Kraft Peter , Stark Jennifer R. , Fiorentino Michelangelo , Perner Sven , Finn Stephen , Calza Stefano , Flavin Richard , Freedman Matthew L. , Setlur Sunita , Sesso Howard D. , Andersson Swen-Olof , Martin Neil , Kantoff Philip W. , Johansson Jan-Erik , Adami Hans-Olov , Rubin Mark A. , Loda Massimo , Golub Todd R. , Andrén Ove , Stampfer Meir J. , Mucci Lorelei A. 
Published: May 2011

Purpose Prostate-specific antigen screening has led to enormous overtreatment of prostate cancer because of the inability to distinguish potentially lethal disease at diagnosis. We reasoned that by identifying an mRNA signature of Gleason grade, the best predictor of prognosis, we could improve prediction of lethal disease among men with moderate Gleason 7 tumors, the most common grade, and the most indeterminate in terms of prognosis. Patients and Methods Using the complementary DNA–mediated annealing, selection, extension, and ligation assay, we measured the mRNA expression of 6,100 genes in prostate tumor tissue in the Swedish Watchful Waiting cohort (n = 358) and Physicians' Health Study (PHS; n = 109). We developed an mRNA signature of Gleason grade comparing individuals with Gleason ≤ 6 to those with Gleason ≥ 8 tumors and applied the model among patients with Gleason 7 to discriminate lethal cases. Results We built a 157-gene signature using the Swedish data that predicted Gleason with low misclassification (area under the curve [AUC] = 0.91); when this signature was tested in the PHS, the discriminatory ability remained high (AUC = 0.94). In men with Gleason 7 tumors, who were excluded from the model building, the signature significantly improved the prediction of lethal disease beyond knowing whether the Gleason score was 4 + 3 or 3 + 4 (P = .006). Conclusion Our expression signature and the genes identified may improve our understanding of the de-differentiation process of prostate tumors. Additionally, the signature may have clinical applications among men with Gleason 7, by further estimating their risk of lethal prostate cancer and thereby guiding therapy decisions to improve outcomes and reduce overtreatment.
Testing Women With Endometrial Cancer to Detect Lynch Syndrome
Authors: Kwon Janice S. , Scott Jenna L. , Gilks C. Blake , Daniels Molly S. , Sun Charlotte C. , Lu Karen H. 
Published: May 2011

Purpose Women with endometrial cancer as a result of Lynch syndrome may not be identified as such by Amsterdam II criteria. We estimated the costs and benefits of different testing criteria to identify Lynch syndrome in women with endometrial cancer. Methods We developed a Markov Monte Carlo simulation model to compare six criteria for Lynch syndrome testing for women with endometrial cancer: Amsterdam II criteria; age younger than 50 years with at least one first-degree relative having a Lynch-associated cancer at any age (FDR); immunohistochemistry (IHC) triage if age younger than 50 years; IHC triage if age younger than 60 years; IHC triage at any age if 1 FDR; and IHC triage of all endometrial cancers. Net health benefit was life expectancy, and primary outcome was the incremental cost-effectiveness ratio (ICER). The model estimated the number of new colorectal cancers associated with each strategy. Results IHC triage of women with endometrial cancer having at least 1 FDR yielded a favorable ICER of $9,126 per year of life gained. This strategy would subject fewer cases to IHC but identify more mutation carriers than age thresholds of 50 or 60 years. IHC triage of all endometrial cancers could identify the most mutation carriers and prevent the most colorectal cancers but at considerable cost ($648,494 per year of life gained). Conclusion IHC triage of women with endometrial cancer at any age having at least 1 FDR with a Lynch-associated cancer is a cost-effective strategy for detecting Lynch syndrome.
Benefit/Risk Assessment for Breast Cancer Chemoprevention With Raloxifene or Tamoxifen for Women Age 50 Years or Older
Authors: Freedman Andrew N. , Yu Binbing , Gail Mitchell H. , Costantino Joseph P. , Graubard Barry I. , Vogel Victor G. , Anderson Garnet L. , McCaskill-Stevens Worta 
Published: May 2011

Purpose The Study of Tamoxifen and Raloxifene (STAR) demonstrated that raloxifene was as effective as tamoxifen in reducing the risk of invasive breast cancer (IBC) in postmenopausal women and had lower risks of thromboembolic events, endometrial cancer, and cataracts but had a nonstatistically significant higher risk of noninvasive breast cancer. There is a need to summarize the risks and benefits of these agents. Patients and Methods Baseline incidence rates of IBC and other health outcomes, absent raloxifene and tamoxifen, were estimated from breast cancer chemoprevention trials; the Surveillance, Epidemiology and End Results Program; and the Women's Health Initiative. Effects of raloxifene and tamoxifen were estimated from STAR and the Breast Cancer Prevention Trial. We assigned weights to health outcomes to calculate the net benefit from raloxifene compared with placebo and tamoxifen compared with placebo. Results Risks and benefits of treatment with raloxifene or tamoxifen depend on age, race, breast cancer risk, and history of hysterectomy. Over a 5-year period, postmenopausal women with an intact uterus had a better benefit/risk index for raloxifene than for tamoxifen. For postmenopausal women without a uterus, the benefit/risk ratio was similar. The benefits and risks of raloxifene and tamoxifen are described in tables that can help identify groups of women for whom the benefits outweigh the risks. Conclusion We developed a benefit/risk index to quantify benefits from chemoprevention with tamoxifen or raloxifene. This index can complement clinical evaluation in deciding whether to initiate chemoprevention and in comparing the benefits and risks of raloxifene versus tamoxifen.
Prospective Neurocognitive Function Over 5 Years After Allogeneic Hematopoietic Cell Transplantation for Cancer Survivors Compared With Matched Controls at 5 Years
Authors: Syrjala Karen L. , Artherholt Samantha B. , Kurland Brenda F. , Langer Shelby L. , Roth-Roemer Sari , Elrod JoAnn Broeckel , Dikmen Sureyya 
Published: May 2011

Purpose Research has documented cognitive deficits both before and after high-dose treatment followed by allogeneic hematopoietic cell transplantation (HCT), with partial recovery by 1 year. This study prospectively examined the trajectory and extent of long-term cognitive dysfunction, with a focus on 1 to 5 years after treatment. Patients and Methods Allogeneic HCT recipients completed standardized neuropsychological tests including information processing speed (Trail Making A and Digit Symbol Substitution Test), verbal memory (Hopkins Verbal Learning Test–Revised), executive function (Controlled Oral Word Association Test and Trail Making B), and motor dexterity and speed (Grooved Pegboard). Survivors (n = 92) were retested after 80 days and 1 and 5 years after transplantation. Case-matched controls (n = 66) received testing at the 5-year time point. A Global Deficit Score (GDS) summarized overall impairment. Response profiles were analyzed using linear mixed effects models. Results Survivors recovered significant cognitive function from post-transplantation (80 days) to 5 years in all tests (P < .0001) except verbal recall (P > .06). Between 1 and 5 years, verbal fluency improved (P = .0002), as did executive function (P < .01), but motor dexterity did not (P > .15), remaining below controls (P < .0001) and more than 0.5 standard deviation below population norms. In GDS, 41.5% of survivors and 19.7% of controls had mild or greater deficits (NcNemar test = 7.04, P = .007). Conclusion Although neurocognitive function improved from 1 to 5 years after HCT, deficits remained for more than 40% of survivors. Risk factors, mechanisms and rehabilitation strategies need to be identified for these residual deficits.
Cohort Study Based on the Seventh Edition of the TNM Classification for Gastric Cancer: Proposal of a New Staging System
Authors: Warneke Viktoria S. , Behrens Hans-Michael , Hartmann Jörg T. , Held Harald , Becker Thomas , Schwarz Nicolas T. , Röcken Christoph 
Published: May 2011

Purpose We investigated the effect of the new TNM classification on gastric cancer staging. Patients and Methods From hospital records, information from patients with gastric cancer, who had undergone either total or partial gastrectomy for adenocarcinomas of the stomach or esophagogastric junction, was retrieved. The pathologic TNM stage was determined according to the sixth and seventh editions of the International Union Against Cancer guidelines and was based on surgical pathologic examination. Results Five hundred fifty-four patients (338 men and 216 women; median age, 68 years) had undergone partial or complete gastrectomy for intestinal (n = 209) or diffuse (n = 249) adenocarcinoma of the esophagogastric junction and stomach. Survival data and date of death were available for all patients. Patient death correlated significantly with age at diagnosis, tumor type, histologic grade, local tumor growth (T category), number of metastatic lymph nodes, lymph node ratio, lymph node status (N category), and tumor stage. No major difference was noted between the sixth and seventh editions of the TNM classification. On the basis of survival data, we revised the stage grouping system; stage I and II tumors were confined to nonmetastatic tumors, and stage III and IV tumors were confined to metastatic tumors. The Kaplan-Meier plots of this modified stage grouping showed statistically significant differences between individual stage subgroups without crossing curves and demonstrated improved survival of patients with stage II disease. Conclusion The seventh edition of the TNM classification is associated with a stage migration in 60% of patients with esophagogastric and stomach cancer. This change did not improve the assessment of patient prognosis, and therefore, a revised staging system is proposed.
Treatment-Related Risk Factors for Transformation to Acute Myeloid Leukemia and Myelodysplastic Syndromes in Myeloproliferative Neoplasms
Authors: Björkholm Magnus , Derolf Åsa R. , Hultcrantz Malin , Kristinsson Sigurdur Y. , Ekstrand Charlotta , Goldin Lynn R. , Andreasson Björn , Birgegård Gunnar , Linder Olle , Malm Claes , Markevärn Berit , Nilsson Lars , Samuelsson Jan , Granath Fredrik , Landgren Ola 
Published: May 2011

Purpose Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have a propensity to develop acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs). Using population-based data from Sweden, we assessed the role of MPN treatment and subsequent AML/MDS risk with special focus on the leukemogenic potential of hydroxyurea (HU). Methods On the basis of a nationwide MPN cohort (N = 11,039), we conducted a nested case-control study, including 162 patients (153 and nine with subsequent AML and MDS diagnosis, respectively) and 242 matched controls. We obtained clinical and MPN treatment data for all patients. Using logistic regression, we calculated odds ratios (ORs) as measures of AML/MDS risk. Results Forty-one (25%) of 162 patients with MPNs with AML/MDS development were never exposed to alkylating agents, radioactive phosphorous (P32), or HU. Compared with patients with who were not exposed to HU, the ORs for 1 to 499 g, 500 to 999 g, more than 1,000 g of HU were 1.5 (95% CI, 0.6 to 2.4), 1.4 (95% CI, 0.6 to 3.4), and 1.3 (95% CI, 0.5 to 3.3), respectively, for AML/MDS development (not significant). Patients with MPNs who received P32 greater than 1,000 MBq and alkylators greater than 1 g had a 4.6-fold (95% CI, 2.1 to 9.8; P = .002) and 3.4-fold (95% CI, 1.1 to 10.6; P = .015) increased risk of AML/MDS, respectively. Patients receiving two or more cytoreductive treatments had a 2.9-fold (95% CI, 1.4 to 5.9) increased risk of transformation. Conclusion The risk of AML/MDS development after MPN diagnosis was significantly associated with high exposures of P32 and alkylators but not with HU treatment. Twenty-five percent of patients with MPNs who developed AML/MDS were not exposed to cytotoxic therapy, supporting a major role for nontreatment-related factors.
Perimeter of sublevel sets in infinite dimensional spaces
Authors: Caselles Vicent , Lunardi Alessandra , Miranda jr Michele , Novaga Matteo 
Published: May 2011

Abstract.
We compare the perimeter measure with the Airault–Malliavin surface measure
and we prove that all open convex subsets of abstract Wiener spaces
have finite perimeter. By an explicit counter-example, we show that in general this
is not true for compact convex domains.