bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tracking and Verification of East Atlantic Tropical Cyclone Genesis in the NCEP Global Ensemble: Case Studies during the NASA African Monsoon Multidisciplinary Analyses
Authors: Snyder Andrew D. , Pu Zhaoxia , Zhu Yuejian 
Published: May 2010

Abstract
This study evaluates the performance of the NCEP global ensemble forecast system in predicting the genesis and evolution of five named tropical cyclones and two unnamed nondeveloping tropical systems during the NASA African Monsoon Multidisciplinary Analyses (NAMMA) between August and September 2006. The overall probabilities of the ensemble forecasts of tropical cyclone genesis are verified relative to a genesis time defined to be the first designation of the tropical depression from the National Hurricane Center (NHC). Additional comparisons are also made with high-resolution deterministic forecasts from the NCEP Global Forecast System (GFS). It is found that the ensemble forecasts have high probabilities of genesis for the three strong storms that formed from African easterly waves, but failed to accurately predict the pregenesis phase of two weaker storms that formed farther west in the Atlantic Ocean. The overall accuracy for the genesis forecasts is above 50% for the ensemble forecasts initialized in the pregenesis phase. The forecast uncertainty decreases with the reduction of the forecast lead time. The probability of tropical cyclone genesis reaches nearly 90% and 100% for the ensemble forecasts initialized near and in the postgenesis phase, respectively. Significant improvements in the track forecasts are found in the ensemble forecasts initialized in the postgenesis phase, possibly because of the implementation of the NCEP storm relocation scheme, which provides an accurate initial storm position for all ensemble members. Even with coarser resolution (T126L28 for the ensemble versus T384L64 for the GFS), the overall performance of the ensemble in predicting tropical cyclone genesis is compatible with the high-resolution deterministic GFS. In addition, false alarm rates for nondeveloping waves were low in both the GFS and ensemble forecasts.
‘Feeling sad and useless’: an investigation into personal acceptance of disability and its association with depression following stroke
Authors: Townend Ellen , Tinson Deborah , Kwan Joseph , Sharpe Michael 
Published: May 2010

Objectives: To study the association of acceptance of disability with depression following stroke and its ability to predict depression at follow-up. Design: A prospective cohort mixed (quantitative and qualitative) design was used. Setting and subjects: Patients admitted to a stroke unit were consecutively recruited. Eighty-nine participated at one month and 81 were followed up nine months post stroke. Main measures: Depressive disorder was assessed using a structured clinical interview. Disability and acceptance of disability were measured using self-report scales. At one month post stroke, 60 consecutive participants also participated in open-ended interviews exploring their individual concerns about having had a stroke and their responses were analysed qualitatively. Results: One-third of participants were found to have depression (29/89; 33% at one month and 24/81; 30% at nine months). Non-acceptance of disability remained associated with depression after controlling for age, gender, original stroke severity and current disability at one month (odds ratio (OR) = 1.27, 95% confidence interval (CI) 1.09—1.47) and nine months (OR = 1.46, 95% CI 1.22—1.75). Also, non-acceptance of disability measured at one month independently predicted depression measured at nine months (OR = 1.19, 95% CI 1.05—1.35). The qualitative findings illustrated a self-reproachful element to non-acceptance of disability. Patients with depression often said that they ‘should still’ be capable and sometimes referred to themselves as ‘useless’; whereas patients who were not depressed commonly reported having accepted stroke-related disability. Conclusions: These finding suggest that personal beliefs about accepting disability are associated with and predict emotional adaptation following stroke.
Social consequences of multiple sclerosis. Part 2. Divorce and separation: a historical prospective cohort study
Authors: Pfleger CCH , Flachs EM , Koch-Henriksen Nils 
Published: May 2010

Background: There is a need for follow-up studies of the familial situation of multiple sclerosis (MS) patients. Objectives: To evaluate the probability of MS patients to remain in marriage or relationship with the same partner after onset of MS in comparison with the population. Patients and methods: All 2538 Danes with onset of MS 1980—1989, retrieved from the Danish MS-Registry, and 50,760 matched and randomly drawn control persons were included. Information on family status was retrieved from Statistics Denmark. Cox analyses were used with onset as starting point. Results: Five years after onset, the cumulative probability of remaining in the same relationship was 86% in patients vs. 89% in controls. The probabilities continued to deviate, and at 24 years, the probability was 33% in patients vs. 53% in the control persons ( p < 0.001). Among patients with young onset (< 36 years of age), those with no children had a higher risk of divorce than those having children less than 7 years (Hazard Ratio 1.51; p < 0.0001), and men had a higher risk of divorce than women (Hazard Ratio 1.33; p < 0.01). Conclusion: MS significantly affects the probability of remaining in the same relationship compared with the background population.
Some practical problems in implementing randomization
Authors: Downs Matt , Tucker Kathryn , Christ-Schmidt Heidi , Wittes Janet 
Published: May 2010

Background While often theoretically simple, implementing randomization to treatment in a masked, but confirmable, fashion can prove difficult in practice. Purpose At least three categories of problems occur in randomization: (1) bad judgment in the choice of method, (2) design and programming errors in implementing the method, and (3) human error during the conduct of the trial. This article focuses on these latter two types of errors, dealing operationally with what can go wrong after trial designers have selected the allocation method. Results We offer several case studies and corresponding recommendations for lessening the frequency of problems in allocating treatment or for mitigating the consequences of errors. Recommendations include: (1) reviewing the randomization schedule before starting a trial, (2) being especially cautious of systems that use on-demand random number generators, (3) drafting unambiguous randomization specifications, (4) performing thorough testing before entering a randomization system into production, (5) maintaining a dataset that captures the values investigators used to randomize participants, thereby allowing the process of treatment allocation to be reproduced and verified, (6) resisting the urge to correct errors that occur in individual treatment assignments, (7) preventing inadvertent unmasking to treatment assignments in kit allocations, and (8) checking a sample of study drug kits to allow detection of errors in drug packaging and labeling. Limitations Although we performed a literature search of documented randomization errors, the examples that we provide and the resultant recommendations are based largely on our own experience in industry-sponsored clinical trials. We do not know how representative our experience is or how common errors of the type we have seen occur. Conclusions Our experience underscores the importance of verifying the integrity of the treatment allocation process before and during a trial. Clinical Trials 2010; 7: 235—245. http://ctj.sagepub.com
Th17/Treg ratio in human graft-versus-host disease
Authors: Ratajczak Philippe , Janin Anne , Peffault de Latour Regis , Leboeuf Christophe , Desveaux Allison , Keyvanfar Keyvan , Robin Marie , Clave Emmanuel , Douay Corine , Quinquenel Anne , Pichereau Claire , Bertheau Philippe , Mary Jean Yves , Socié Gérard 
Published: May 2010

Abstract
Th17 cells have never been explored in human graft-versus-host disease (GVHD). We studied the correlation between the presence of Th17 cells with histologic and clinical parameters. We first analyzed a cohort of 40 patients with GVHD of the gastrointestinal tract. Tumor necrosis factor (TNF), TNF receptors, and Fas expression, and apoptotic cells, CD4+IL-17+ cells (Th17), and CD4+Foxp3+ cells (Treg) were quantified. A Th17/Treg ratio less than 1 correlated both with the clinical diagnosis (P < .001) and more than 2 pathologic grades (P < .001). A Th17/Treg ratio less than 1 also correlated with the intensity of apoptosis of epithelial cells (P = .03), Fas expression in the cellular infiltrate (P = .003), TNF, and TNF receptor expression (P < .001). We then assessed Th17/Treg ratio in 2 other independent cohorts; a second cohort of 30 patients and confirmed that Th17/Treg ratio less than 1 correlated with the pathologic grade of GI GVHD. Finally, 15 patients with skin GVHD and 11 patients with skin rash but without pathologic GVHD were studied. Results in this third cohort of patients with skin disease confirmed those found in patients with GI GVHD. These analyses in 96 patients suggest that Th17/Treg ratio could be a sensitive and specific pathologic in situ biomarker of GVHD.
Thermal stability, pH dependence and inhibition of four murine kynurenine aminotransferases
Authors: Han Qian , Cai Tao , Tagle Danilo A , Li Jianyong 
Published: May 2010

Abstract

Background
Kynurenine aminotransferase (KAT) catalyzes the transamination of kynunrenine to kynurenic acid (KYNA). KYNA is a neuroactive compound and functions as an antagonist of alpha7-nicotinic acetylcholine receptors and is the only known endogenous antagonist of N-methyl-D-aspartate receptors. Four KAT enzymes, KAT I/glutamine transaminase K/cysteine conjugate beta-lyase 1, KAT II/aminoadipate aminotransferase, KAT III/cysteine conjugate beta-lyase 2, and KAT IV/glutamic-oxaloacetic transaminase 2/mitochondrial aspartate aminotransferase, have been reported in mammalian brains. Because of the substrate overlap of the four KAT enzymes, it is difficult to assay the specific activity of each KAT in animal brains.

Results
This study concerns the functional expression and comparative characterization of KAT I, II, III, and IV from mice. At the applied test conditions, equimolar tryptophan with kynurenine significantly inhibited only mouse KAT I and IV, equimolar methionine inhibited only mouse KAT III and equimolar aspartate inhibited only mouse KAT IV. The activity of mouse KAT II was not significantly inhibited by any proteinogenic amino acids at equimolar concentrations. pH optima, temperature preferences of four KATs were also tested in this study. Midpoint temperatures of the protein melting, half life values at 65°C, and pKa values of mouse KAT I, II, III, and IV were 69.8, 65.9, 64.8 and 66.5°C; 69.7, 27.4, 3.9 and 6.5 min; pH 7.6, 5.7, 8.7 and 6.9, respectively.

Conclusion
The characteristics reported here could be used to develop specific assay methods for each of the four murine KATs. These specific assays could be used to identify which KAT is affected in mouse models for research and to develop small molecule drugs for prevention and treatment of KAT-involved human diseases.
High amino acid diversity and positive selection at a putative coral immunity gene (tachylectin-2)
Authors: Hayes Marshall L , Eytan Ron I , Hellberg Michael E 
Published: May 2010

Abstract

Background
Genes involved in immune functions, including pathogen recognition and the activation of innate defense pathways, are among the most genetically variable known, and the proteins that they encode are often characterized by high rates of amino acid substitutions, a hallmark of positive selection. The high levels of variation characteristic of immunity genes make them useful tools for conservation genetics. To date, highly variable immunity genes have yet to be found in corals, keystone organisms of the world's most diverse marine ecosystem, the coral reef. Here, we examine variation in and selection on a putative innate immunity gene from Oculina, a coral genus previously used as a model for studies of coral disease and bleaching.

Results
In a survey of 244 Oculina alleles, we find high nonsynonymous variation and a signature of positive selection, consistent with a putative role in immunity. Using computational protein structure prediction, we generate a structural model of the Oculina protein that closely matches the known structure of tachylectin-2 from the Japanese horseshoe crab (Tachypleus tridentatus), a protein with demonstrated function in microbial recognition and agglutination. We also demonstrate that at least three other genera of anthozoan cnidarians (Acropora, Montastrea and Nematostella) possess proteins structurally similar to tachylectin-2.

Conclusions
Taken together, the evidence of high amino acid diversity, positive selection and structural correspondence to the horseshoe crab tachylectin-2 suggests that this protein is 1) part of Oculina's innate immunity repertoire, and 2) evolving adaptively, possibly under selective pressure from coral-associated microorganisms. Tachylectin-2 may serve as a candidate locus to screen coral populations for their capacity to respond adaptively to future environmental change.
Griseofulvin stabilizes microtubule dynamics, activates p53 and inhibits the proliferation of MCF-7 cells synergistically with vinblastine
Authors: Rathinasamy Krishnan , Jindal Bhavya , Asthana Jayant , Singh Parminder , Balaji Petety V , Panda Dulal 
Published: May 2010

Abstract

Background
Griseofulvin, an antifungal drug, has recently been shown to inhibit proliferation of various types of cancer cells and to inhibit tumor growth in athymic mice. Due to its low toxicity, griseofulvin has drawn considerable attention for its potential use in cancer chemotherapy. This work aims to understand how griseofulvin suppresses microtubule dynamics in living cells and sought to elucidate the antimitotic and antiproliferative action of the drug.

Methods
The effects of griseofulvin on the dynamics of individual microtubules in live MCF-7 cells were measured by confocal microscopy. Immunofluorescence microscopy, western blotting and flow cytometry were used to analyze the effects of griseofulvin on spindle microtubule organization, cell cycle progression and apoptosis. Further, interactions of purified tubulin with griseofulvin were studied in vitro by spectrophotometry and spectrofluorimetry. Docking analysis was performed using autodock4 and LigandFit module of Discovery Studio 2.1.

Results
Griseofulvin strongly suppressed the dynamic instability of individual microtubules in live MCF-7 cells by reducing the rate and extent of the growing and shortening phases. At or near half-maximal proliferation inhibitory concentration, griseofulvin dampened the dynamicity of microtubules in MCF-7 cells without significantly disrupting the microtubule network. Griseofulvin-induced mitotic arrest was associated with several mitotic abnormalities like misaligned chromosomes, multipolar spindles, misegregated chromosomes resulting in cells containing fragmented nuclei. These fragmented nuclei were found to contain increased concentration of p53. Using both computational and experimental approaches, we provided evidence suggesting that griseofulvin binds to tubulin in two different sites; one site overlaps with the paclitaxel binding site while the second site is located at the αβ intra-dimer interface. In combination studies, griseofulvin and vinblastine were found to exert synergistic effects against MCF-7 cell proliferation.

Conclusions
The study provided evidence suggesting that griseofulvin shares its binding site in tubulin with paclitaxel and kinetically suppresses microtubule dynamics in a similar manner. The results revealed the antimitotic mechanism of action of griseofulvin and provided evidence suggesting that griseofulvin alone and/or in combination with vinblastine may have promising role in breast cancer chemotherapy.
A systematic review and meta-analysis of bone metabolism in prostate adenocarcinoma
Authors: Serpa Neto Ary , Tobias-Machado Marcos , Esteves Marcos AP , Senra Marília D , Wroclawski Marcelo L , Fonseca Fernando LA , dos Reis Rodolfo B , Pompeo Antônio CL , Del Giglio Auro 
Published: May 2010

Abstract

Background
Osteoporosis could be associated with the hormone therapy for metastatic prostate carcinoma (PCa) and with PCa per se. The objective of this review is to determine the incidence of bone loss and osteoporosis in patients with PCa who are or are not treated with hormone therapy (ADT).

Methods
The Medline, Embase, Cancerlit, and American Society of Clinical Oncology Abstract databases were searched for published studies on prostate cancer and bone metabolism. The outcomes assessed were: fracture, osteoporosis and osteopenia.

Results
Thirty-two articles (116,911 participants) were included in the meta-analysis. PCa patients under ADT had a higher risk of osteoporosis (RR, 1.30; p < 0.00001) and a higher risk of fractures (RR, 1.17; p < 0.00001) as compared to patients not under ADT. The total bone mineral density was lower in patients under ADT when compared with patients not under ADT (p = 0.031) but it was similar to bone mineral density found in healthy controls (p = 0.895). The time of androgen deprivation therapy correlated negatively with lumbar spine and total hip bone mineral density (Spearman's rho = -0.490 and -0.773; p = 0.028 and 0.001, respectively) and with total hip t score (Spearman's rho = -0.900; p = 0.037).

Conclusion
We found consistent evidence that the use of androgen deprivation therapy in patients with PCa reduces bone mineral density, increasing the risk of fractures in these patients.
MyD88-dependent and independent pathways of Toll-Like Receptors are engaged in biological activity of Triptolide in ligand-stimulated macrophages
Authors: Premkumar Vummidigiridhar , Dey Moul , Dorn Ruth , Raskin Ilya 
Published: May 2010

Abstract

Background
Triptolide is a diterpene triepoxide from the Chinese medicinal plant Tripterygium wilfordii Hook F., with known anti-inflammatory, immunosuppressive and anti-cancer properties.

Results
Here we report the expression profile of immune signaling genes modulated by triptolide in LPS induced mouse macrophages. In an array study triptolide treatment modulated expression of 22.5% of one hundred and ninety five immune signaling genes that included Toll-like receptors (TLRs). TLRs elicit immune responses through their coupling with intracellular adaptor molecules, MyD88 and TRIF. Although it is known that triptolide inhibits NFκB activation and other signaling pathways downstream of TLRs, involvement of TLR cascade in triptolide activity was not reported. In this study, we show that triptolide suppresses expression of proinflammatory downstream effectors induced specifically by different TLR agonists. Also, the suppressive effect of triptolide on TLR-induced NFκB activation was observed when either MyD88 or TRIF was knocked out, confirming that both MyD88 and TRIF mediated NFκB activation may be inhibited by triptolide. Within the TLR cascade triptolide downregulates TLR4 and TRIF proteins.

Conclusions
This study reveals involvement of TLR signaling in triptolide activity and further increases understanding of how triptolide activity may downregulate NFκB activation during inflammatory conditions.
Pristimerin induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation by blocking NF-κB signaling and depleting Bcr-Abl
Authors: Lu Zhongzheng , Jin Yanli , Chen Chun , Li Juan , Cao Qi , Pan Jingxuan 
Published: May 2010

Abstract
Background
Chronic myelogenous leukemia (CML) is characterized by the chimeric tyrosine kinase Bcr-Abl. Bcr-Abl-T315I is the notorious point mutation that causes resistance to imatinib and the second generation tyrosine kinase inhibitors, leading to poor prognosis. CML blasts have constitutive p65 (RelA NF-κB) transcriptional activity, and NF-κB may be a potential target for molecular therapies in CML that may also be effective against CML cells with Bcr-Abl-T315I.

Results
In this report, we discovered that pristimerin, a quinonemethide triterpenoid isolated from Celastraceae and Hippocrateaceae, inhibited growth and induced apoptosis in CML cells, including the cells harboring Bcr-Abl-T315I mutation. Additionally, pristimerin inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude mice. Pristimerin blocked the TNFα-induced IκBα phosphorylation, translocation of p65, and expression of NF-κB-regulated genes. Pristimerin inhibited two steps in NF-κB signaling: TAK1→IKK and IKK→IκBα. Pristimerin potently inhibited two pairs of CML cell lines (KBM5 versus KBM5-T315I, 32D-Bcr-Abl versus 32D-Bcr-Abl-T315I) and primary cells from a CML patient with acquired resistance to imatinib. The mRNA and protein levels of Bcr-Abl in imatinib-sensitive (KBM5) or imatinib-resistant (KBM5-T315I) CML cells were reduced after pristimerin treatment. Further, inactivation of Bcr-Abl by imatinib pretreatment did not abrogate the TNFα-induced NF-κB activation while silencing p65 by siRNA did not affect the levels of Bcr-Abl, both results together indicating that NF-κB inactivation and Bcr-Abl inhibition may be parallel independent pathways.

Conclusion
To our knowledge, this is the first report to show that pristimerin is effective in vitro and in vivo against CML cells, including those with the T315I mutation. The mechanisms may involve inhibition of NF-κB and Bcr-Abl. We concluded that pristimerin could be a lead compound for further drug development to overcome imatinib resistance in CML patients.