bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-103/107 Promote Metastasis of Colorectal Cancer by Targeting the Metastasis Suppressors DAPK and KLF4
Authors: Chen Hsin-Yi , Lin Yu-Min , Chung Hsiang-Ching , Lang Yaw-Dong , Lin Ching-Jung , Huang John , Wang Wei-Chi , Lin Feng-Mao , Chen Zhen , Huang Hsien-Da , Shyy John Y.-J. , Liang Jin-Tung , Chen Ruey-Hwa 
Published: May 2012

Abstract
Metastasis is the major cause of poor prognosis in colorectal cancer (CRC), and increasing evidence supports the contribution of miRNAs to cancer progression. Here, we found that high expression of miR-103 and miR-107 (miR-103/107) was associated with metastasis potential of CRC cell lines and poor prognosis in patients with CRC. We showed that miR-103/107 targeted the known metastasis suppressors death-associated protein kinase (DAPK) and Krüppel-like factor 4 (KLF4) in CRC cells, resulting in increased cell motility and cell–matrix adhesion and decreased cell–cell adhesion and epithelial marker expression. miR-103/107 expression was increased in the presence of hypoxia, thereby potentiating DAPK and KLF4 downregulation and hypoxia-induced motility and invasiveness. In mouse models of CRC, miR-103/107 overexpression potentiated local invasion and liver metastasis effects, which were suppressed by reexpression of DAPK or KLF4. miR-103/107–mediated downregulation of DAPK and KLF4 also enabled the colonization of CRC cells at a metastatic site. Clinically, the signature of a miR-103/107 high, DAPK low, and KLF4 low expression profile correlated with the extent of lymph node and distant metastasis in patients with CRC and served as a prognostic marker for metastasis recurrence and poor survival. Our findings therefore indicate that miR-103/107–mediated repression of DAPK and KLF4 promotes metastasis in CRC, and this regulatory circuit may contribute in part to hypoxia-stimulated tumor metastasis. Strategies that disrupt this regulation might be developed to block CRC metastasis. Cancer Res; 72(14); 3631–41. ©2012 AACR.
Trust in Smart Systems
Authors: Verberne Frank M. F. , Ham Jaap , Midden Cees J. H. 
Published: May 2012

Objective: We examine whether trust in smart systems is generated analogously to trust in humans and whether the automation level of smart systems affects trustworthiness and acceptability of those systems. Background: Trust is an important factor when considering acceptability of automation technology. As shared goals lead to social trust, and intelligent machines tend to be treated like humans, the authors expected that shared driving goals would also lead to increased trustworthiness and acceptability of adaptive cruise control (ACC) systems. Method: In an experiment, participants ( N = 57) were presented with descriptions of three ACCs with different automation levels that were described as systems that either shared their driving goals or did not. Trustworthiness and acceptability of all the ACCs were measured. Results: ACCs sharing the driving goals of the user were more trustworthy and acceptable than were ACCs not sharing the driving goals of the user. Furthermore, ACCs that took over driving tasks while providing information were more trustworthy and acceptable than were ACCs that took over driving tasks without providing information. Trustworthiness mediated the effects of both driving goals and automation level on acceptability of ACCs. Conclusion: As when trusting other humans, trusting smart systems depends on those systems sharing the user’s goals. Furthermore, based on their description, smart systems that take over tasks are judged more trustworthy and acceptable when they also provide information. Application: For optimal acceptability of smart systems, goals of the user should be shared by the smart systems, and smart systems should provide information to their user.
An In Vivo Lapine Model for Impact-Induced Injury and Osteoarthritic Degeneration of Articular Cartilage
Authors: Alexander Peter G. , McCarron Jesse A. , Levine Matthew J. , Melvin Gary M. , Murray Patrick J. , Manner Paul A. , Tuan Rocky S. 
Published: May 2012

Objective: In this study, we applied a spring-loaded impactor to deliver traumatic forces to articular cartilage in vivo. Based on our recent finding that a 0.28-J impact induces maximal catabolic response in adult bovine articular cartilage in vitro using this device, we hypothesize that this impact will induce the formation of a focal osteoarthritic defect in vivo. Design: The femoral condyle of New Zealand White rabbits was exposed and one of the following procedures performed: 0.28 J impact, anterior cruciate ligament transection, articular surface grooving, or no joint or cartilage destruction (control). After 24 hours, 4 weeks, or 12 weeks ( n = 3 for each time point), wounds were localized with India ink, and tissue samples were collected and characterized histomorphometrically with Safranin O/Fast green staining and Hoechst 33342 nuclear staining for cell vitality. Results: The spring-loaded device delivered reproducible impacts with the following characteristics: impact area of 1.39 ± 0.11 mm2, calculated load of 326 ± 47.3 MPa, time-to-peak of 0.32 ± 0.03 ms, and an estimated maximal displacement of 25.1% ± 4.5% at the tip apex. The impact resulted in immediate cartilage fissuring and cell loss in the surface and intermediate zones, and it induced the formation of a focal lesion at 12 weeks. The degeneration was defined and appeared more slowly than after anterior cruciate ligament transection, and more pronounced and characteristic than after grooving. Conclusion: A single traumatic 0.28 J impact delivered with this spring-loaded impactor induces focal cartilage degeneration characteristic of osteoarthritis.
Mutated regions of nucleophosmin 1 elicit both CD4+ and CD8+ T-cell responses in patients with acute myeloid leukemia
Authors: Greiner Jochen , Ono Yoko , Hofmann Susanne , Schmitt Anita , Mehring Elmar , Götz Marlies , Guillaume Philippe , Döhner Konstanze , Mytilineos Joannis , Döhner Hartmut , Schmitt Michael 
Published: May 2012

Abstract
Mutations in the nucleophosmin gene (NPM1mut) are one of the most frequent molecular alterations in acute myeloid leukemia (AML), and immune responses may contribute to the favorable prognosis of AML patients with NPM1mut. In the present study, we were able to demonstrate both CD4+ and CD8+ T-cell responses against NPM1mut. Ten peptides derived from wild-type NPM1 and NPM1mut were subjected to ELISPOT analysis in 33 healthy volunteers and 27 AML patients. Tetramer assays against the most interesting epitopes were performed and Cr51-release assays were used to show the cytotoxicity of peptide-specific T cells. Moreover, HLA-DR–binding epitopes were used to test the role of CD4+ T cells in NPM1 immunogenicity. Two epitopes (epitopes #1 and #3) derived from NPM1mut induced CD8+ T-cell responses. A total of 33% of the NPM1mut AML patients showed immune responses against epitope #1 and 44% against epitope #3. Specific lysis of leukemic blasts was detected. To obtain robust immune responses against tumor cells, the activation of CD4+ T cells is crucial. Therefore, overlapping (OL) peptides were analyzed in ELISPOT assays and OL8 was able to activate both CD8+ and CD4+ T cells. The results of the present study show that NPM1mut induces specific T-cell responses of CD4+ and CD8+ T cells and therefore is a promising target for specific immunotherapies in AML.
The degree of BCR and NFAT activation predicts clinical outcomes in chronic lymphocytic leukemia
Authors: Le Roy Christine , Deglesne Pierre-Antoine , Chevallier Nathalie , Beitar Taoufik , Eclache Virginie , Quettier Maude , Boubaya Marouane , Letestu Rémi , Lévy Vincent , Ajchenbaum-Cymbalista Florence , Varin-Blank Nadine 
Published: May 2012

Abstract
B-cell antigen receptor (BCR)–mediated signaling plays a critical role in chronic lymphocytic leukemia (CLL) pathogenesis and gives an in vitro survival advantage to B cells isolated from patients with unfavorable prognostic factors. In this study, we undertook to elucidate the signaling intermediates responsible for this biologic alteration. In responding cells only, in vitro BCR engagement triggers global phosphorylation of Syk, activation of phospholipase Cγ2, and intracellular calcium mobilization, reflecting competency of BCR signaling. The calcium–calcineurin-dependent transcription factor NFAT2 is up-regulated and to some extent constitutively activated in all CLL B cells. In contrast, its DNA-binding capacity is enhanced on IgM stimulation in responding cells only. NFAT inhibition using the VIVIT peptide prevents induction of CD23 target gene and IgM-induced survival, converting responding cells to unresponsive status. At the opposite, ionomycin-induced NFAT activity allows survival of nonresponding cells. These results demonstrate that the functional heterogeneity relies on variability of protein levels establishing BCR-dependent thresholds and NFAT-dependent activation. Finally, status of the BCR-NFAT pathway for each patient reveals its relevance for CLL clinical outcome and points out to BCR-NFAT intermediates as promising functional therapeutic targets.
Workflows for microarray data processing in the Kepler environment
Authors: Stropp Thomas , McPhillips Timothy , Ludäscher Bertram , Bieda Mark 
Published: May 2012

Abstract

Background
Microarray data analysis has been the subject of extensive and ongoing pipeline development due to its complexity, the availability of several options at each analysis step, and the development of new analysis demands, including integration with new data sources. Bioinformatics pipelines are usually custom built for different applications, making them typically difficult to modify, extend and repurpose. Scientific workflow systems are intended to address these issues by providing general-purpose frameworks in which to develop and execute such pipelines. The Kepler workflow environment is a well-established system under continual development that is employed in several areas of scientific research. Kepler provides a flexible graphical interface, featuring clear display of parameter values, for design and modification of workflows. It has capabilities for developing novel computational components in the R, Python, and Java programming languages, all of which are widely used for bioinformatics algorithm development, along with capabilities for invoking external applications and using web services.

Results
We developed a series of fully functional bioinformatics pipelines addressing common tasks in microarray processing in the Kepler workflow environment. These pipelines consist of a set of tools for GFF file processing of NimbleGen chromatin immunoprecipitation on microarray (ChIP-chip) datasets and more comprehensive workflows for Affymetrix gene expression microarray bioinformatics and basic primer design for PCR experiments, which are often used to validate microarray results. Although functional in themselves, these workflows can be easily customized, extended, or repurposed to match the needs of specific projects and are designed to be a toolkit and starting point for specific applications. These workflows illustrate a workflow programming paradigm focusing on local resources (programs and data) and therefore are close to traditional shell scripting or R/BioConductor scripting approaches to pipeline design. Finally, we suggest that microarray data processing task workflows may provide a basis for future example-based comparison of different workflow systems.

Conclusions
We provide a set of tools and complete workflows for microarray data analysis in the Kepler environment, which has the advantages of offering graphical, clear display of conceptual steps and parameters and the ability to easily integrate other resources such as remote data and web services.
Reliable and rapid characterization of functional FCN2 gene variants reveals diverse geographical patterns
Authors: Ojurongbe Olusola , Ouf Eman Abou , Van Tong Hoang , Toan Nguyen L , Song Le H , Luz Paola R , Messias-Reason Iara JT , Nurjadi Dennis , Zanger Philipp , Kun Jürgen FJ , Kremsner Peter G , Velavan Thirumalaisamy P 
Published: May 2012

Abstract

Background
Ficolin-2 coded by FCN2 gene is a soluble serum protein and an innate immune recognition element of the complement system. FCN2 gene polymorphisms reveal distinct geographical patterns and are documented to alter serum ficolin levels and modulate disease susceptibility.

Methods
We employed a real-time PCR based on Fluorescence Resonance Energy Transfer (FRET) method to genotype four functional SNPs including -986 G > A (#rs3124952), -602 G > A (#rs3124953), -4A > G (#rs17514136) and +6424 G > T (#rs7851696) in the ficolin-2 (FCN2) gene. We characterized the FCN2 variants in individuals representing Brazilian (n = 176), Nigerian (n = 180), Vietnamese (n = 172) and European Caucasian ethnicity (n = 165).

Results
We observed that the genotype distribution of three functional SNP variants (−986 G > A, -602 G > A and -4A > G) differ significantly between the populations investigated (p < 0.0001). The SNP variants were highly linked to each other and revealed significant population patterns. Also the distribution of haplotypes revealed distinct geographical patterns (p < 0.0001).

Conclusions
The observed distribution of the FCN2 functional SNP variants may likely contribute to altered serum ficolin levels and this may depend on the different disease settings in world populations. To conclude, the use of FRET based real-time PCR especially for FCN2 gene will benefit a larger scientific community who extensively depend on rapid, reliable method for FCN2 genotyping.
Characterizing the spatial and temporal variation of malaria incidence in Bangladesh, 2007
Authors: Reid Heidi L , Haque Ubydul , Roy Shyamal , Islam Nazrul , Clements Archie CA 
Published: May 2012

Abstract

Background
Malaria remains a significant health problem in Bangladesh affecting 13 of 64 districts. The risk of malaria is variable across the endemic areas and throughout the year. A better understanding of the spatial and temporal patterns in malaria risk and the determinants driving the variation are crucial for the appropriate targeting of interventions under the National Malaria Control and Prevention Programme.

Methods
Numbers of Plasmodium falciparum and Plasmodium vivax malaria cases reported by month in 2007, across the 70 endemic thanas (sub-districts) in Bangladesh, were assembled from health centre surveillance reports. Bayesian Poisson regression models of incidence were constructed, with fixed effects for monthly rainfall, maximum temperature and elevation, and random effects for thanas, with a conditional autoregressive prior spatial structure.

Results
The annual incidence of reported cases was 34.0 and 9.6 cases/10,000 population for P. falciparum and P. vivax respectively and the population of the 70 malaria-endemic thanas was approximately 13.5 million in 2007. Incidence of reported cases for both types of malaria was highest in the mountainous south-east of the country (the Chittagong Hill Tracts). Models revealed statistically significant positive associations between the incidence of reported P. vivax and P. falciparum cases and rainfall and maximum temperature.

Conclusions
The risk of P. falciparum and P. vivax was spatially variable across the endemic thanas of Bangladesh and also highly seasonal, suggesting that interventions should be targeted and timed according to the risk profile of the endemic areas. Rainfall, temperature and elevation are major factors driving the spatiotemporal patterns of malaria in Bangladesh.
Struma ovarii with follicular thyroid-type carcinoma and neuroendocrine component: case report
Authors: Selvaggi Federico , Risio Domenico , Waku Mathew , Simo Daniela , Angelucci Domenico , D’Aulerio Alberto , Cotellese Roberto , Innocenti Paolo 
Published: May 2012

Abstract
Struma ovarii (SO) is a slow-growing ovarian neoplasm with thyroid tissue as its predominant component. It is an uncommon neoplasm, usually asymptomatic with an unknown risk of malignant transformation. Due to difficulties in assessing the rare biological nature and the discrepancies in the reported cases, a consensus on the appropriate treatment has not been definitively reached.
A 50-year-old female was subjected to upper gut endoscopy which showed a 30-mm mass located in the gastric antrum, suggestive of mesenchimal tumor. Incidentally, a pelvic CT scan also documented a solid mass in the right adnexa, with morphological characteristics of ovarian neoplasm. The patient underwent gastrectomy, total hysterectomy, bilateral salpingo-oophorectomy with lymph node dissection, and omentectomy. Histology documented the presence of gastric cavernous angioma, and, in the right adnexa, foci of follicular thyroid-type carcinoma arising in SO with a well-differentiated neuroendocrine component.
Here we report and discuss the clinical and morphological presentation of follicular thyroid-type carcinoma arising in SO. The neoplasm was discovered incidentally and had a favorable clinical outcome at 1-year follow-up.
Beneficial effects of non-matched allogeneic cord blood mononuclear cells upon patients with idiopathic osteoporosis
Authors: Li Jun , Zhang Li , Zhou Liang , Yu Zheng-Ping , Qi Feng , Liu Bei , Zi Su-Xia , Li Li , Li Yi , Wang San-Bin , Cui Zheng-Jiang , Pan Xing-Hua 
Published: May 2012

Abstract

Background
Immunological arguments and historical examples have shown that treatment with cord blood for non-hematopoietic activities, such as growth factor production and stimulation of angiogenesis, may not require matching or immune suppression.

Methods
To study the benefit of blood mononuclear cell therapy, 8 patients with idiopathic osteoporosis were given intermittent treatments with non-matched allogeneic cord blood mononuclear cells for 3 months. Morning fasting samples were collected for measuring urine N telopeptide of type-1 collagen, serum bone-specific alkaline phosphatase, and insulin-like growth factor 1 during one-year study.

Results
Clinical response was striking. Serum insulin-like growth factor 1 significantly increased in all patients at 3 months compared with baseline values, from 264.1 ± 107.0 to 384.4 ± 63.1 ng/mL (P = 0.002), with a tendency to return to baseline values at 12 months (312.9 ± 75.5 ng/mL, P = 0.083). In contrast, differences in serum bone-specific alkaline phosphatase and urine N telopeptide of type-1 collagen were not significant at 3 (P = 0.765, P = 0.057) or 12 months (P = 0.889, P = 0.122). A beneficial effect on bone density was observed in all patients at the lumbar spine. The mean bone mineral density calculated during therapy (0.6811 ± 0.1442 g/cm2) tended higher than baseline values (0.6239 ± 0.1362 g/cm2, P < 0), and percentage change (median) varied from 8.85% at 3 months to 7.85% at one year. All patients are now well after one year.

Conclusions
The findings indicate that for these patients with idiopathic osteoporosis, treatment with cord blood mononuclear cells led to a significant increase in insulin-like growth factor 1 levels, which favors the increase in bone mineral density.
Functional dosimetric metrics for predicting radiation-induced lung injury in non-small cell lung cancer patients treated with chemoradiotherapy
Authors: Wang Dongqing , Sun Jinbo , Zhu Jingyu , Li Xiaohong , Zhen Yanbo , Sui Songtao 
Published: May 2012

Abstract

Background
Radiation-induced lung injury (RILI) is an important dose-limiting toxicity during thoracic radiotherapy. The purpose of this study is to investigate single photon emission computed tomography (SPECT) perfusion-weighted functional dose-volume histogram (FDVH) for predicting RILI in non-small cell lung cancer (NSCLC) patients treated with definitive chemoradiotherapy.

Methods
Fifty-seven locally advanced NSCLC patients receiving chemoradiotherapy were enrolled prospectively. Patients had treatment scans and dose calculations to provide a standard dose-volume histogram (DVH). Fusion of SPECT and computed tomography scans provided perfusion-weighted FDVH and associated functional dosimetric parameters (relative volumes of functional lung receiving more than a threshold dose of 5 – 60 Gy at increments of 5 Gy [FV5 – FV60]). The predictive abilities of FDVH and DVH were calculated and compared based on the area under receiver operating characteristic (ROC) curve (AUC).

Results
The accumulative incidence of ≥ 2 grade RILI was 19.3% with a median follow-up of 12 months. Univariate analysis showed that the functional (FV5 – FV60) and standard (V5 – V40) parameters were associated with RILI (all value of p < 0.05). Close correlations between a variety of functional and standard parameters were found. By ROC curve analysis, functional metrics (AUCs were 0.784 – 0.869) provided similarly (p value 0.233 – 1.000) predictive outcome to standard metrics (AUCs were 0.695 – 0.902) in lower – median dose level parameters (FV5 – FV40). However, FDVH seemed to add some predictive value in higher dose level, the best statistical significance for comparing FV60 with V60 was 0.693 vs. 0.511 (p = 0.055).

Conclusions
Functional metrics are identified as reliable predictors for RILI, however, this observation still needs to be further verified using a larger sample size.
Neoplastic leptomeningitis presenting in a melanoma patient treated with dabrafenib (a V600EBRAF inhibitor): a case report
Authors: Simeone Ester , De Maio Eleonora , Sandomenico Fabio , Fulciniti Franco , Lastoria Secondo , Aprea Pasquale , Staibano Stefania , Montesarchio Vincenzo , Palmieri Giuseppe , Mozzillo Nicola , Ascierto Paolo A 
Published: May 2012

Abstract

Introduction
Leptomeningeal metastases are occurring at higher frequency in cancer patients. The prognosis of leptomeningeal metastases is poor and standard treatment, which includes radiotherapy and chemotherapy, is mostly ineffective. Melanoma represents one of the tumors with the highest incidence of leptomeningeal metastases. For such a disease, the BRAF inhibitors have recently been demonstrated to be effective on melanoma brain metastases harboring the V600EBRAF mutation.

Case presentation
We report a case of a 39-year-old Italian woman with advanced melanoma with brain, lung and peritoneum metastases harboring the V600EBRAF mutation. In August 2010 she was enrolled into the BRIM3 trial and after the randomization process she received dacarbazine. After two cycles, there was evidence of disease progression in her peritoneum and lung. For this reason, she was enrolled into another clinical trial with the GSK2118436 BRAF inhibitor, dabrafenib, as a second line of therapy. She had a partial response that was maintained until 13 weeks of treatment. In January 2011 she developed symptoms typical for brain metastases and received a diagnosis of leptomeningeal involvement of melanoma cells after an examination of her cerebral spinal fluid; magnetic resonance imaging was negative for meningitis or brain metastases. Analysis of her cerebral spinal fluid sample confirmed that the melanoma cells still carried the V600EBRAF mutation. After a few days, our patient went into a coma and died.

Conclusion
Starting with a clinical case, we discuss the pathogenesis of leptomeningeal metastases and whether the leptomeninges may represent a sanctuary where melanoma cells may generate resistance and/or BRAF inhibitors cannot reach an adequate concentration for significant activity. We assess whether treatment with BRAF inhibitors in melanoma patients should be interrupted as soon as disease progression appears or continued beyond progression, through the administration of additional compounds.