bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dasatinib as first-line treatment for adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia
Authors: Foà Robin , Vitale Antonella , Vignetti Marco , Meloni Giovanna , Guarini Anna , De Propris Maria Stefania , Elia Loredana , Paoloni Francesca , Fazi Paola , Cimino Giuseppe , Nobile Francesco , Ferrara Felicetto , Castagnola Carlo , Sica Simona , Leoni Pietro , Zuffa Eliana , Fozza Claudio , Luppi Mario , Candoni Anna , Iacobucci Ilaria , Soverini Simona , Mandelli Franco , Martinelli Giovanni , Baccarani Michele ,   on behalf of the GIMEMA Acute Leukemia Working Party
Published: September 2011

AbstractDasatinib is a potent BCR-ABL inhibitor effective in chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia (ALL) resistant/intolerant to imatinib. In the GIMEMA LAL1205 protocol, patients with newly diagnosed Ph+ ALL older than 18 years (with no upper age limit) received dasatinib induction therapy for 84 days combined with steroids for the first 32 days and intrathecal chemotherapy. Postremission therapy was free. Fifty-three patients were evaluable (median age, 53.6 years). All patients achieved a complete hematologic remission (CHR), 49 (92.5%) at day 22. At this time point, 10 patients achieved a BCR-ABL reduction to < 10−3. At 20 months, the overall survival was 69.2% and disease-free survival was 51.1%. A significant difference in DFS was observed between patients who showed at day 22 a decrease in BCR-ABL levels to < 10−3 compared with patients who never reached these levels during induction. In multivariate analysis, BCR-ABL levels of < 10−3 at day 85 correlated with disease-free survival. No deaths or relapses occurred during induction. Twenty-three patients relapsed after completing induction. A T315I mutation was detected in 12 of 17 relapsed cases. Treatment was well tolerated; only 4 patients discontinued therapy during the last phase of the induction when already in CHR. In adult Ph+ ALL, induction treatment with dasatinib plus steroids is associated with a CHR in virtually all patients, irrespective of age, good compliance, no deaths, and a very rapid debulking of the neoplastic clone. This trial was registered at www.clinicaltrials.gov as #NCT00391989.
Post-stroke infection: A systematic review and meta-analysis
Authors: Westendorp Willeke F , Nederkoorn Paul J , Vermeij Jan-Dirk , Dijkgraaf Marcel G , de Beek Diederik van 
Published: September 2011

AbstractBackgroundstroke is the main cause of disability in high-income countries, and ranks second as a cause of death worldwide. Patients with acute stroke are at risk for infections, but reported post-stroke infection rates vary considerably. We performed a systematic review and meta-analysis to estimate the pooled post-stroke infection rate and its effect on outcome.MethodsMEDLINE and EMBASE were searched for studies on post-stroke infection. Cohort studies and randomized clinical trials were included when post-stroke infection rate was reported. Rates of infection were pooled after assessment of heterogeneity. Associations between population- and study characteristics and infection rates were quantified. Finally, we reviewed the association between infection and outcome.Results87 studies were included involving 137817 patients. 8 studies were restricted to patients admitted on the intensive care unit (ICU). There was significant heterogeneity between studies (P < 0.001, I2= 97%). The overall pooled infection rate was 30% (24-36%); rates of pneumonia and urinary tract infection were 10% (95% confidence interval [CI] 9-10%) and 10% (95%CI 9-12%). For ICU studies, these rates were substantially higher with 45% (95% CI 38-52%), 28% (95%CI 18-38%) and 20% (95%CI 0-40%). Rates of pneumonia were higher in studies that specifically evaluated infections and in consecutive studies. Studies including older patients or more females reported higher rates of urinary tract infection. Pneumonia was significantly associated with death (odds ratio 3.62 (95%CI 2.80-4.68).ConclusionsInfection complicated acute stroke in 30% of patients. Rates of pneumonia and urinary tract infection after stroke were 10%. Pneumonia was associated with death. Our study stresses the need to prevent infections in patients with stroke.
Snail1 induces epithelial-to-mesenchymal transition and tumor initiating stem cell characteristics
Authors: Dang Hien , Ding Wei , Emerson Dow , Rountree C Bart 
Published: September 2011

Abstract

Background
Tumor initiating stem-like cells (TISCs) are a subset of neoplastic cells that possess distinct survival mechanisms and self-renewal characteristics crucial for tumor maintenance and propagation. The induction of epithelial-mesenchymal-transition (EMT) by TGFβ has been recently linked to the acquisition of TISC characteristics in breast cancer. In HCC, a TISC and EMT phenotype correlates with a worse prognosis. In this work, our aim is to elucidate the underlying mechanism by which cells acquire tumor initiating characteristics after EMT.

Methods
Gene and protein expression assays and Nanog-promoter luciferase reporter were utilized in epithelial and mesenchymal phenotype liver cancer cell lines. EMT was analyzed with migration/invasion assays. TISC characteristics were analyzed with tumor-sphere self-renewal and chemotherapy resistance assays. In vivo tumor assay was performed to investigate the role of Snail1 in tumor initiation.

Conclusion
TGFβ induced EMT in epithelial cells through the up-regulation of Snail1 in Smad-dependent signaling. Mesenchymal liver cancer post-EMT demonstrates TISC characteristics such as tumor-sphere formation but are not resistant to cytotoxic therapy. The inhibition of Snail1 in mesenchymal cells results in decreased Nanog promoter luciferase activity and loss of self-renewal characteristics in vitro. These changes confirm the direct role of Snail1 in some TISC traits. In vivo, the down-regulation of Snail1 reduced tumor growth but was not sufficient to eliminate tumor initiation. In summary, TGFβ induces EMT and TISC characteristics through Snail1 and Nanog up-regulation. In mesenchymal cells post-EMT, Snail1 directly regulates Nanog expression, and loss of Snail1 regulates tumor growth without affecting tumor initiation.
RETRACTED ARTICLE:Differential modulatory
effects of GSK-3β and HDM2 on sorafenib-induced AIF nuclear translocation (programmed
necrosis) in melanoma
Authors: Liu Qingjun , Mier James W , Panka David J 
Published: September 2011

Abstract
Background
GSK-3β phosphorylates numerous substrates that govern cell survival. It
phosphorylates p53, for example, and induces its nuclear export, HDM2-dependent
ubiquitination, and proteasomal degradation. GSK-3β can either enhance or inhibit
programmed cell death, depending on the nature of the pro-apoptotic stimulus. We
previously showed that the multikinase inhibitor sorafenib activated GSK-3β and
that this activation attenuated the cytotoxic effects of the drug in various
BRAF-mutant melanoma cell lines. In this report, we describe the results of
studies exploring the effects of GSK-3β on the cytotoxicity and antitumor activity
of sorafenib combined with the HDM2 antagonist MI-319.

Results
MI-319 alone increased p53 levels and p53-dependent gene expression in
melanoma cells but did not induce programmed cell death. Its cytotoxicity,
however, was augmented in some melanoma cell lines by the addition of sorafenib.
In responsive cell lines, the MI-319/sorafenib combination induced the
disappearance of p53 from the nucleus, the down modulation of Bcl-2 and
Bcl-xL, the translocation of p53 to the mitochondria and
that of AIF to the nuclei. These events were all GSK-3β-dependent in that they
were blocked with a GSK-3β shRNA and facilitated in otherwise unresponsive
melanoma cell lines by the introduction of a constitutively active form of the
kinase (GSK-3β-S9A). These modulatory effects of GSK-3β on the activities of the
sorafenib/MI-319 combination were the exact reverse of its effects on the
activities of sorafenib alone, which induced the down modulation of Bcl-2 and
Bcl-xL and the nuclear translocation of AIF only in cells
in which GSK-3β activity was either down modulated or constitutively low. In A375
xenografts, the antitumor effects of sorafenib and MI-319 were additive and
associated with the down modulation of Bcl-2 and Bcl-xL,
the nuclear translocation of AIF, and increased suppression of tumor
angiogenesis.

Conclusions
Our data demonstrate a complex partnership between GSK-3β and HDM2 in the
regulation of p53 function in the nucleus and mitochondria. The data suggest that
the ability of sorafenib to activate GSK-3β and alter the intracellular
distribution of p53 may be exploitable as an adjunct to agents that prevent the
HDM2-dependent degradation of p53 in the treatment of melanoma.
Phytoceramide and sphingoid bases derived from brewer's yeast Saccharomyces pastorianus activate peroxisome proliferator-activated receptors
Authors: Murakami Itsuo , Wakasa Yukari , Yamashita Shinji , Kurihara Toshio , Zama Kota , Kobayashi Naoyuki , Mizutani Yukiko , Mitsutake Susumu , Shigyo Tatsuro , Igarashi Yasuyuki 
Published: September 2011

Abstract

Background
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate lipid and glucose metabolism. PPARα is highly expressed in the liver and controls genes involved in lipid catabolism. We previously reported that synthetic sphingolipid analogs, part of which contains shorter-length fatty acid chains than natural sphingolipids, stimulated the transcriptional activities of PPARs. Sphingosine and dihydrosphingosine (DHS) are abundant sphingoid bases, and ceramide and dihydroceramide are major ceramide species in mammals. In contrast, phytosphingosine (PHS) and DHS are the main sphingoid bases in fungi. PHS and phytoceramide exist in particular tissues such as the epidermis in mammals, and involvement of ceramide species in PPARβ activation in cultured keratinocytes has been reported. The purpose of the present study is to investigate whether natural sphingolipids with C18 fatty acid and yeast-derived sphingoid bases activate PPARs as PPAR agonists.

Method
Lipids of brewer's yeast contain PHS- and DHS-based sphingolipids. To obtain the sphingoid bases, lipids were extracted from brewer's yeast and acid-hydrolyzed. The sphingoid base fraction was purified and quantified. To assess the effects of sphingolipids on PPAR activation, luciferase reporter assay was carried out. NIH/3T3 and human hepatoma (HepG2) cells were transfected with expression vectors for PPARs and retinoid × receptors, and PPAR responsive element reporter vector. When indicated, the PPAR/Gal4 chimera system was performed to enhance the credibility of experiments. Sphingolipids were added to the cells and the dual luciferase reporter assay was performed to determine the transcriptional activity of PPARs.

Results
We observed that phytoceramide increased the transcriptional activities of PPARs significantly, whereas ceramide and dihydroceramide did not change PPAR activities. Phytoceramide also increased transactivation of PPAR/Gal4 chimera receptors. Yeast-derived sphingoid base fraction, which contained PHS and DHS, or authentic PHS or DHS increased PPAR-dependent transcription. Additionally, phytoceramide stimulated PPARα activity in HepG2 hepatocytes, suggesting that phytoceramide activates genes regulated by PPARα.

Conclusions
Phytoceramide and yeast-derived sphingoid bases activate PPARs, whereas ceramide and dihydroceramide do not change the PPAR activity. The present findings suggest that phytoceramide acts as a PPAR ligand that would regulate PPAR-targeted genes.
2D DIGE analysis of maternal plasma for potential biomarkers of Down Syndrome
Authors: Heywood Wendy E , Madgett Tracey E , Wang Darrell , Wallington Amanda , Hogg Julie , Mills Kevin , Avent Neil D 
Published: September 2011

AbstractBackgroundPrenatal screening for Down Syndrome (DS) would benefit from an increased number of biomarkers to improve sensitivity and specificity. Improving sensitivity and specificity would decrease the need for potentially risky invasive diagnostic procedures.ResultsWe have performed an in depth two-dimensional difference gel electrophoresis (2D DIGE) study to identify potential biomarkers. We have used maternal plasma samples obtained from first and second trimesters from mothers carrying DS affected fetuses compared with mothers carrying normal fetuses. Plasma samples were albumin/IgG depleted and expanded pH ranges of pH 4.5 - 5.5, pH 5.3 - 6.5 and pH 6 - 9 were used for two-dimensional gel electrophoresis (2DE). We found no differentially expressed proteins in the first trimester between the two groups. Significant up-regulation of ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4, complement proteins C1s subcomponent, C4-A, C5, and C9 and kininogen 1 were detected in the second trimester in maternal plasma samples where a DS affected fetus was being carried. However, ceruloplasmin could not be confirmed as being consistently up-regulated in DS affected pregnancies by Western blotting.ConclusionsDespite the in depth 2DE approach used in this study the results underline the deficiencies of gel-based proteomics for detection of plasma biomarkers. Gel-free approaches may be more productive to increase the number of plasma biomarkers for DS for non-invasive prenatal screening and diagnosis.
Biologically-inspired data decorrelation for hyper-spectral imaging
Authors: Picon Artzai , Ghita Ovidiu , Rodriguez-Vaamonde Sergio , Iriondo Pedro Ma , Whelan Paul F 
Published: September 2011

Abstract
Hyper-spectral data allows the construction of more robust statistical models to sample the material properties than the standard tri-chromatic color representation. However, because of the large dimensionality and complexity of the hyper-spectral data, the extraction of robust features (image descriptors) is not a trivial issue. Thus, to facilitate efficient feature extraction, decorrelation techniques are commonly applied to reduce the dimensionality of the hyper-spectral data with the aim of generating compact and highly discriminative image descriptors. Current methodologies for data decorrelation such as principal component analysis (PCA), linear discriminant analysis (LDA), wavelet decomposition (WD), or band selection methods require complex and subjective training procedures and in addition the compressed spectral information is not directly related to the physical (spectral) characteristics associated with the analyzed materials. The major objective of this article is to introduce and evaluate a new data decorrelation methodology using an approach that closely emulates the human vision. The proposed data decorrelation scheme has been employed to optimally minimize the amount of redundant information contained in the highly correlated hyper-spectral bands and has been comprehensively evaluated in the context of non-ferrous material classification
Monocytes and macrophages and placental malaria infections in an area of unstable malaria transmission in eastern Sudan
Authors: Salih Magdi M , Mohammed Amal H , Mohmmed Ahmed A , Adam Gamal K , Elbashir Mustafa I , Adam Ishag 
Published: September 2011

AbstractBackgroundMaternal immunity is thought to play a major role in the increased susceptibility of pregnant women toPlasmodium falciparummalaria. Few studies exist on immunohistochemical characterization of the placental inflammatory infiltrate. The current study was conducted in Gadarif hospital in an area characterized by unstable malaria transmission in eastern Sudan.MethodNinety three placentae were investigated for malaria histological changes and immunohistochemical study for monocytes and macrophages (CD68).ResultsWhile 1(1.1%), 2(2.2%) and 20(21.5%) of the 93 placentae had acute, chronic and past malaria infections, 70(75.2%) had no malaria infections. Monocytes and macrophage (CD 68) were detected in 29 (31.2%) of these 93 placentae. Significantly higher rate of monocytes and macrophage were detected in placentae with malaria infections [11/23 (47.8%) vs. 18/70 (25.7%);P= 0.047] especially in placentae with past malaria infections. Placental malaria infections and monocytes and macrophages cells infiltration were not different between primiparae and multiparae. There was no significant difference in the birth weight between the women with placental malaria infections/monocytes and macrophages cells infiltration and those who had no placental malaria infections/cellular infiltrations.ConclusionSignificantly higher rate of monocytes and macrophage were detected in placentae with malaria infections. Neither placental malaria infections nor cellular infiltrates were associated with parity or lead to reduction of birth weight.
Anaplasmataceae and Borrelia burgdorferi sensu lato in the sand lizard Lacerta agilis and co-infection of these bacteria in hosted Ixodes ricinus ticks
Authors: Ekner Anna , Dudek Krzysztof , Sajkowska Zofia , Majláthová Viktória , Majláth Igor , Tryjanowski Piotr 
Published: September 2011

Abstract

Background

Anaplasmataceae and Borrelia burgdorferi s.l. are important tick-borne bacteria maintained in nature by transmission between ticks and vertebrate hosts. However, the potential role of lizards as hosts has not been sufficiently studied.

Results
The current study showed that 23 of 171 examined sand lizards Lacerta agilis were PCR positive for Anaplasmataceae. The nucleotide sequences of the several selected PCR products showed 100% homology with Anaplasma spp. found in Ixodes ricinus collected in Tunisia and Morocco (AY672415 - AY672420). 1.2% of lizard collar scale samples were PCR positive for B. lusitaniae. In addition, 12 of 290 examined I. ricinus were PCR positive for B. burgdorferi s.l. and 82 were PCR positive for Anaplasmatacea. The number of ticks per lizard and the number of ticks PCR positive for both microorganisms per lizard were strongly correlated. Moreover, we found a significant correlation between numbers of ticks infected with Anaplasmataceae and with B. burgdorferi s.l. living on the same lizard. However, there was no significant correlation between detection of both bacteria in the same tick.

Conclusions
To the best of our knowledge, this is the first report of Anaplasmataceae DNA and additionally the second report of B. burgdorferi s.l DNA detection in the sand lizard.
Transnationale Literatur – eine Herausforderung für die Wissenschaft: der tschechische Jude J. M. Langer
Authors: Koschmal Walter 
Published: September 2011

Abstract
Especially in Eastern Europe, literature frequently crosses borders; it has a transnational orientation. Scholarship, however, must often devise new systematic methods to analyze transnational literature. The example of the Jewish-Czech Poet J. M. Langer demonstrates this problem, in which questions such as what kind of readers do multilingual authors have and to which literary history do they belong must be addressed. It is also necessary to examine how national/European historicism has shaped scholarship, i. e. the purpose of national literary historiographies. We shall see that conjunctions of influences create a network of transna­tional intertextuality, not differences in works of literature.
Die „moderne Seele“ und ihre Topologie: Penčo Slavejkovs Slavenbilder
Authors: Kroucheva Katerina 
Published: September 2011

Abstract
These reflections on the images of the Slavs in Penčo Slavejkovs work provide a component of a more general study on modern and avant-garde concepts of ‘the nation’. Various ideas on the ‘modern soul’ and its topographical character are essential for these concepts. One of the paradoxes of the period of modernism is that the ‘soul’, – which is usually first and foremost defined as being immaterial and a-historical – can be geographically and ethnically determined. The reflections on the ‘Slavic Soul’, which play a crucial role in Slavejkovs aesthetics, are accompanied by a derogatory attitude towards other ethnicities, such as the Germanic or Latin. Nonetheless, Slavejkov is nowadays portrayed as an ironical opponent of any nationalism. The essay at hand seeks an explanation for such a characterization of Slavejkov in the key concepts of Bulgarian literary criticism, namely in the notions of “Europe” and “the Belated Nation”.
„Die Unterschiede sind nun da“: Zur sprachlichen Entwicklung in Bosnien und Herzegowina
Authors: Tolimir-Hölzl Nataša 
Published: September 2011

Abstract
Linguistically, the past two decades in Bosnia and Hercegovina were characterized by the implementation of three legal languages, “Bosnian”, “Croatian” and “Serbian”, which replaced the formerly used “Serbocroatian”. What initially looked like a merely terminological change for ideological reasons has developed into a gradually growing language change along ethnic lines, which could be measured by quantitative analysis, the methods and results of which will be presented partly in this article. Through additional qualitative analysis it became evident that these linguistic changes are not spreading equally within each linguistic group, but are only affecting the language use and speech of the majorities of certain areas. This means, that there is a great difference between the level of standardization, acceptance and actual use of the three languages in question leading to the establishment of linguistic areas rather than the planed equal trilingualism in the state.
10-year Cognition in Preterms After Random Assignment to Fatty Acid Supplementation in Infancy
Authors: Isaacs Elizabeth B. , Ross Sarah , Kennedy Kathy , Weaver Lawrence T. , Lucas Alan , Fewtrell Mary S. 
Published: September 2011

OBJECTIVE:
To test the hypothesis that long-chain polyunsaturated fatty acid (LCPUFA) supplementation in infancy would improve cognition into later childhood (after 9 years) at both general and specific levels.

METHODS:
A comprehensive cognitive battery was completed by 107 formerly preterm infants (mean age: 128 months). As infants, they had been assigned randomly to receive LCPUFA-supplemented (N = 50) or control (N = 57) formula, between birth and 9 months; the docosahexaenoic acid level (DHA) in the supplemented formulas was 0.5%. In addition to randomized comparisons, we planned supplementary analyses to examine the effects of both gender and feeding group (those receiving some maternal breast milk versus those receiving none).

RESULTS:
There were no significant differences between randomized diet groups on any cognitive measure. There was significant interaction between gender and supplementation; girls only showed beneficial effects of LCPUFAs on literacy. Significant interaction also occurred between feeding group and supplementation; increases of 0.7 SD in verbal IQ, full-scale IQ, and memory scores were found for the LCPUFA group, but only for infants who received only formula and no maternal breast milk.

CONCLUSIONS:
The results of this post–9-year cognitive follow-up study in a randomized trial of LCPUFA-supplemented formula for preterm infants suggest no overall group effects but indicate that gender-specific and diet-specific effects may exist. The data provide some evidence that LCPUFAs are a key factor in the cognitive benefits of breast milk. Caution is advised in data interpretation because of the small groups used.