bluuebunny/crossref_metadata_2025_split huggingface dataset:
An HMM approach to genome-wide identification of differential histone modification sites from ChIP-seq data
Authors: Xu Han , Wei Chia-Lin , Lin Feng , Sung Wing-Kin 
Published: July 2008

Abstract
Motivation: Epigenetic modifications are one of the critical factors to regulate gene expression and genome function. Among different epigenetic modifications, the differential histone modification sites (DHMSs) are of great interest to study the dynamic nature of epigenetic and gene expression regulations among various cell types, stages or environmental responses. To capture the histone modifications at whole genome scale, ChIP-seq technology is becoming a robust and comprehensive approach. Thus the DHMSs are potentially identifiable by comparing two ChIP-seq libraries. However, little has been addressed on this issue in literature.
Results: Aiming at identifying DHMSs, we propose an approach called ChIPDiff for the genome-wide comparison of histone modification sites identified by ChIP-seq. Based on the observations of ChIP fragment counts, the proposed approach employs a hidden Markov model (HMM) to infer the states of histone modification changes at each genomic location. We evaluated the performance of ChIPDiff by comparing the H3K27me3 modification sites between mouse embryonic stem cell (ESC) and neural progenitor cell (NPC). We demonstrated that the H3K27me3 DHMSs identified by our approach are of high sensitivity, specificity and technical reproducibility. ChIPDiff was further applied to uncover the differential H3K4me3 and H3K36me3 sites between different cell states. Interesting biological discoveries were achieved from such comparison in our study.
Availability: http://cmb.gis.a-star.edu.sg/ChIPSeq/tools.htm
Contact: asflin@ntu.edu.sg; sungk@gis.a-star.edu.sg
Supplementary information: Supplementary methods and data are available at Bioinformatics online.
Efficient whole-genome association mapping using local phylogenies for unphased genotype data
Authors: Ding Zhihong , Mailund Thomas , Song Yun S. 
Published: July 2008

Abstract
Motivation: Recent advances in genotyping technology has made data acquisition for whole-genome association study cost effective, and a current active area of research is developing efficient methods to analyze such large-scale datasets. Most sophisticated association mapping methods that are currently available take phased haplotype data as input. However, phase information is not readily available from sequencing methods and inferring the phase via computational approaches is time-consuming, taking days to phase a single chromosome.
Results: In this article, we devise an efficient method for scanning unphased whole-genome data for association. Our approach combines a recently found linear-time algorithm for phasing genotypes on trees with a recently proposed tree-based method for association mapping. From unphased genotype data, our algorithm builds local phylogenies along the genome, and scores each tree according to the clustering of cases and controls. We assess the performance of our new method on both simulated and real biological datasets.
Availability The software described in this article is available at http://www.daimi.au.dk/~mailund/Blossoc and distributed under the GNU General Public License.
Contact: mailund@birc.au.dk
Postexposure Interventions to Prevent Infection With HBV, HCV, or HIV, and Tetanus in People Wounded During Bombings and Other Mass Casualty Events—United States, 2008: Recommendations of the Centers for Disease Control and Prevention and Disaster Medicine and Public Health Preparedness
Authors: Chapman Louisa E. , Sullivent Ernest E. , Grohskopf Lisa A. , Beltrami Elise M. , Perz Joseph F. , Kretsinger Katrina , Panlilio Adelisa L. , Thompson Nicola D. , Ehrenberg Richard L. , Gensheimer Kathleen F. , Duchin Jeffrey S. , Kilmarx Peter H. , Hunt Richard C. 
Published: July 2008

ABSTRACTPeople wounded during bombings or other events resulting in mass casualties or in conjunction with the resulting emergency response may be exposed to blood, body fluids, or tissue from other injured people and thus be at risk for bloodborne infections such as hepatitis B virus, hepatitis C virus, human immunodeficiency virus, or tetanus. This report adapts existing general recommendations on the use of immunization and postexposure prophylaxis for tetanus and for occupational and nonoccupational exposures to bloodborne pathogens to the specific situation of a mass casualty event. Decisions regarding the implementation of prophylaxis are complex, and drawing parallels from existing guidelines is difficult. For any prophylactic intervention to be implemented effectively, guidance must be simple, straightforward, and logistically undemanding. Critical review during development of this guidance was provided by representatives of the National Association of County and City Health Officials, the Council of State and Territorial Epidemiologists, and representatives of the acute injury care, trauma, and emergency response medical communities participating in the Centers for Disease Control and Prevention’s Terrorism Injuries: Information, Dissemination and Exchange project. The recommendations contained in this report represent the consensus of US federal public health officials and reflect the experience and input of public health officials at all levels of government and the acute injury response community. (Disaster Med Public Health Preparedness. 2008;2:150–165)
Comparative Transcriptomics of Arabidopsis Sperm Cells
Authors: Borges Filipe , Gomes Gabriela , Gardner Rui , Moreno Nuno , McCormick Sheila , Feijó José A. , Becker Jörg D. 
Published: July 2008

AbstractIn flowering plants, the two sperm cells are embedded within the cytoplasm of the growing pollen tube and as such are passively transported to the embryo sac, wherein double fertilization occurs upon their release. Understanding the mechanisms and conditions by which male gametes mature and take part in fertilization are crucial goals in the study of plant reproduction. Studies of gene expression in male gametes of maize (Zea mays) and Plumbago and in lily (Lilium longiflorum) generative cells already showed that the previously held view of transcriptionally inert male gametes was not true, but genome-wide studies were lacking. Analyses in the model plant Arabidopsis (Arabidopsis thaliana) were hindered, because no method to isolate sperm cells was available. Here, we used fluorescence-activated cell sorting to isolate sperm cells from Arabidopsis, allowing GeneChip analysis of their transcriptome at a genome-wide level. Comparative analysis of the sperm cell transcriptome with those of representative sporophytic tissues and of pollen showed that sperm has a distinct and diverse transcriptional profile. Functional classifications of genes with enriched expression in sperm cells showed that DNA repair, ubiquitin-mediated proteolysis, and cell cycle progression are overrepresented Gene Ontology categories. Moreover, analysis of the small RNA and DNA methylation pathways suggests that distinct mechanisms might be involved in regulating the epigenetic state of the paternal genome. We identified numerous candidate genes whose involvement in sperm cell development and fertilization can now be directly tested in Arabidopsis. These results provide a roadmap to decipher the role of sperm-expressed proteins.
A meta‐analysis of the utility of pre‐operative brain natriuretic peptide in predicting early and intermediate‐term mortality and major adverse cardiac events in vascular surgical patients
Authors: Rodseth R. N. , Padayachee L. , Biccard B. M. 
Published: July 2008

SummaryWe conducted a meta‐analysis of the utility of pre‐operative B‐type natriuretic peptide (BNP) and N‐terminal‐pro B‐type natriuretic peptide in predicting early (< 30 days) and intermediate (< 180 days) term mortality and major adverse cardiac events (cardiac death and nonfatal myocardial infarction) in patients following vascular surgery. A Pubmed Central and EMBASE search was conducted up to January 2008. Of 81 studies identified, seven prospective observational studies were included in the meta‐analysis representing five patient cohorts: early outcomes (504 patients) and intermediate‐term outcomes (623 patients). A B‐type natriuretic peptide or N‐terminal‐pro B‐type natriuretic peptide above the optimal discriminatory threshold determined by receiver operating characteristic curve analysis was associated with 30‐day cardiac death (OR 7.6, 95% CI 1.33–43.4, p = 0.02), nonfatal myocardial infarction (OR 6.24, 95% CI 1.82–21.4, p = 0.004) and major adverse cardiac events (OR 17.37, 95% CI 3.31–91.15, p = 0.0007), and intermediate‐term, all‐cause mortality (OR 3.1, 95% CI 1.85–5.2, p < 0.0001), nonfatal myocardial infarction (OR 2.95, 95% CI 1.17–7.46, p = 0.02) and major adverse cardiac events (OR 3.31, 95% CI 2.1–5.24, p < 0.00001). B‐type natriuretic peptide and N‐terminal‐pro B‐type natriuretic peptide are potentially useful pre‐operative prognostic tests in vascular surgical patients.
Population pharmacokinetic analysis for risperidone using highly sparse sampling measurements from the CATIE study
Authors: Feng Yan , Pollock Bruce G. , Coley Kim , Marder Stephen , Miller Del , Kirshner Margaret , Aravagiri Manickam , Schneider Lon , Bies Robert R. 
Published: July 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Risperidone metabolism is affected by blocking CYP2D6 and CYP3A4 (in CYP2D6 poor metabolizers) metabolizing enzymes.• Age affects risperidone disposition and renal function affects elimination of 9‐hydroxy‐risperidone (primary active metabolite). WHAT THIS STUDY ADDS • The detection of a systematic shift in estimated apparent clearance in the African‐American population (it is not clear if there are biological or sociological contributors), and a shift in the clearance rate of risperidone based on concomitant administration of paroxetine, manifested as a change in assignment to a different metabolizer subpopulation group that may be primarily related to CYP2D6 metabolizer status.• The study shows an age‐related decrement in 9‐hydroxy‐risperidone clearance across a wide range of ages.• Information on the nature of the pharmacokinetic variability with risperidone when used in a typical clinical patient population.• There are significant differences in the absolute values as well as the assignment to metabolizer status across race and concomitant paroxetine administration.AIMSTo characterize pharmacokinetic (PK) variability of risperidone and 9‐OH risperidone using sparse sampling and to evaluate the effect of covariates on PK parameters.METHODSPK analysis used plasma samples collected from the Clinical Antipsychotic Trials of Intervention Effectiveness. A nonlinear mixed‐effects model was developed using nonmem to describe simultaneously the risperidone and 9‐OH risperidone concentration–time profile. Covariate effects on risperidone and 9‐OH risperidone PK parameters were assessed, including age, weight, sex, smoking status, race and concomitant medications.RESULTSPK samples comprised 1236 risperidone and 1236 9‐OH risperidone concentrations from 490 subjects that were available for analysis. Ages ranged from 18 to 93 years. Population PK submodels for both risperidone and 9‐OH risperidone with first‐order absorption were selected to describe the concentration–time profile of risperidone and 9‐OH risperidone. A mixture model was incorporated with risperidone clearance (CL) separately estimated for three subpopulations [poor metabolizer (PM), extensive metabolizer (EM) and intermediate metabolizer (IM)]. Age significantly affected 9‐OH risperidone clearance. Population parameter estimates for CL in PM, IM and EM were 12.9, 36 and 65.4 l h−1 and parameter estimates for risperidone half‐life in PM, IM and EM were 25, 8.5 and 4.7 h, respectively.CONCLUSIONSA one‐compartment mixture model with first‐order absorption adequately described the risperidone and 9‐OH risperidone concentrations. Age was identified as a significant covariate on 9‐OH risperidone clearance in this study.
Early diagnostic and prognostic significance of a specific Th1/Th2 cytokine pattern in children with haemophagocytic syndrome
Authors: Tang Yongmin , Xu Xiaojun , Song Hua , Yang Shilong , Shi Shuwen , Wei Jian , Pan Binhua , Zhao Fenying , Liao Chan , Luo Chunfang 
Published: July 2008

SummaryThe haemophagocytic syndrome (HPS) is a rare but frequently fatal disorder of immune regulation caused by hypercytokinemia. Using cytometric bead array technique, the serum T‐helper cell type 1 (Th1) and 2 (Th2) cytokines including interferon‐γ (IFN‐γ), tumour necrosis factor (TNF), interleukin (IL)‐10, IL‐6, IL‐4 and IL‐2 were determined in 24 children with de novo HPS and 87 children as control. The median levels of serum IFN‐γ, IL‐10 and IL‐6 in the acute phase of HPS were 901·7, 879·0 and 63·8 pg/ml, respectively, significantly higher than those after remission, and in the healthy volunteers and patients with viral infection. IL‐4 was slightly elevated while IL‐2 and TNF were within normal range in acute phase. Patients with bacterial sepsis showed an extremely high level of IL‐6 and moderate level of IL‐10, whereas IFN‐γ was only slightly elevated. Five patients were diagnosed with HPS according to the Th1/Th2 cytokine pattern 3–13 d earlier than they fulfilled the relevant diagnostic criteria. IL‐10 level >2000 pg/ml was an unfavorable prognostic factor for HPS treatment response (P = 0·033) and outcome (P = 0·009). We conclude that the significant increase of IFN‐γ and IL‐10 and a slightly increased level of IL‐6 is an early, specific and prognostic cytokine pattern for childhood HPS.
The relationship between quality of response and clinical benefit for patients treated on the bortezomib arm of the international, randomized, phase 3 APEX trial in relapsed multiple myeloma
Authors: Niesvizky Ruben , Richardson Paul G. , Rajkumar S. Vincent , Coleman Morton , Rosiñol Laura , Sonneveld Pieter , Schuster Michael W. , Irwin David , Stadtmauer Edward A. , Facon Thierry , Harousseau Jean‐Luc , Boral Anthony L. , Esseltine Dixie‐Lee , Anderson Kenneth C. , Bladé Joan 
Published: July 2008

SummaryQuality of response is associated with prolonged overall survival (OS) in newly diagnosed multiple myeloma patients. This cohort study within the phase 3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) trial of bortezomib versus dexamethasone in relapsed myeloma assessed the relationship between quality of response to bortezomib (n = 315) and clinical benefit. Treatment‐free interval (TFI), time to alternative therapy (TTAT), time to progression (TTP) and OS were assessed in response‐evaluable patients in the bortezomib arm in cohorts defined by achievement of complete response (CR; n = 27), very good partial response (VGPR; n = 31), partial response (PR; n = 77), minimal response (MR; n = 21) or non‐response (NR, including stable and progressive disease; n = 159). CR was associated with significantly longer median TFI (24·1 vs. 6·9/6·4 months) and TTAT (27·1 vs. 13·6/14 months) versus VGPR/PR. Median TTP was similar in CR, VGPR and PR cohorts; median OS was not reached. Patients achieving MR appeared to have prolonged median TFI (3·8 vs. 2·3 months), TTAT (8·7 vs. 6·2 months), TTP (4·9 vs. 2·8 months) and OS (24·9 vs. 18·7 months) versus NR. In conclusion, bortezomib had substantial activity in relapsed myeloma patients; CR may be a surrogate marker for significant clinical benefit with bortezomib. MR appeared to be valid as a separate response category in this setting.
In vitro polydeoxyribonucleotide effects on human pre‐adipocytes
Authors: Raposio E. , Guida C. , Coradeghini R. , Scanarotti C. , Parodi A. , Baldelli I. , Fiocca R. , Santi P.L. 
Published: July 2008

Abstract.  Objectives: Adipose tissue is the most abundant and accessible source of adult stem cells. Human processed lipoaspirate contains pre‐adipocytes that possess one of the a characteristic pathways of multipotent adult stem cells and are able to differentiate in vitro into mesenchymal and also neurogenic lineages. Because stem cells have great potential for use in tissue repair and regeneration, it would be significant to be able to obtain large amounts of these cells in vitro. As demonstrated previously, purine nucleosides and nucleotides mixtures can act as mitogens for several cell types. The aim of this study was to evaluate the effects of polydeoxyribonucleotides (PDRN), at appropriate concentrations, on human pre‐adipocytes grown in a controlled medium, also using different passages, so as to investigate the relationship between the effect of this compound and cellular senescence, which is the phenomenon when normal diploid cells lose the ability to divide further. Materials and methods: Human pre‐adipocytes were obtained by liposuction. Cells from different culture passages (P6 and P16) were treated with PDRN at different experimental times. Cell number was evaluated for each sample by direct counting after trypan blue treatment. DNA assay and the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide test were also carried out in all cases. Results and Conclusions: PDRN seemed to promote proliferation of human pre‐adipocytes at both passages, but cell population growth increased in pre‐adipocyte at P16, after 9 days as compared to control. Our data suggest that PDRN could act as a pre‐adipocyte growth stimulator.
Cranially irradiated adult cancer survivors may have normal spontaneous GH secretion in the presence of discordant peak GH responses to stimulation tests (compensated GH deficiency)
Authors: Darzy Ken H. , Thorner Michael O. , Shalet Stephen M. 
Published: July 2008

Summary
Context  We have previously demonstrated that spontaneous (physiological) GH secretion was entirely normal in cranially irradiated patients who had normal individual peak GH responses to the insulin tolerance test (ITT) but reduced maximal somatotroph reserve as indicated by substantially reduced group GH responses to the GHRH + arginine stimulation test (AST). The normality of spontaneous GH secretion was attributed to a compensatory increase in hypothalamic stimulatory input within a partially damaged hypothalamic–pituitary (h–p) axis. It is unknown, however, if such compensatory stimulation can also maintain normality of GH secretion in those who fail the ITT but pass the GHRH + AST.
Study subjects and design  We studied 24‐h spontaneous GH secretion by 20‐min sampling both in the fed state (n = 11) and in the last 24 h of a 33‐h fast (n = 9) in adult cancer survivors with subnormal peak GH responses to the ITT but either normal or relatively less attenuated peak GH responses to the GHRH + AST. The study was conducted 8·3 ± 1·8 (range 2–23) years after cranial irradiation for nonpituitary brain tumours (n = 9) or leukaemia/lymphoma (n = 2) in comparison with 30 normal controls (fasting, 14).
Results  Previously published diagnostic thresholds for the ITT, GHRH + AST and spontaneous GH secretion were used to characterize GH secretion. Four of the 11 patients with impaired stimulated responses to both tests showed only minor discordancies between stimulated and spontaneous GH secretion. Two of the remaining seven patients had subnormal spontaneous GH secretion. However, spontaneous GH secretion, both individually and as a group, was entirely normal in the remaining five patients who had impaired GH responses to the ITT but normal individual responses to the GHRH + AST; in these five patients, IGF‐I standard deviation scores (SDS; –2·7 to –0·8) were significantly reduced to a moderate degree compared with normals.
Conclusions  In cranially irradiated adult cancer survivors, it cannot be assumed that failure to pass the ITT in isolation reflects severe GH deficiency (GHD). It appears that in some patients near‐maximal compensatory overdrive of the partially damaged somatotroph axis may result in near‐normal quantitative restoration of spontaneous GH secretion, thus limiting further stimulation with the ITT to the extent that impaired GH responses can be seen even before spontaneous GH secretion starts to decline in adults. However, IGF‐I status continues to provide useful information about the adequacy of the compensatory process and therefore the degree of normality of GH secretion.
Secondary deterioration of visual field during cabergoline treatment for macroprolactinoma
Authors: Raverot Gérald , Jacob Maud , Jouanneau Emmanuel , Delemer Brigitte , Vighetto Alain , Pugeat Michel , Borson‐Chazot Françoise 
Published: July 2008

SummaryObjective  During dopaminergic agonist treatment for macroprolactinoma, tumour shrinkage can be accompanied by secondary deterioration of the visual field in rare instances. The aim of the present study was to evaluate the incidence of symptomatic or asymptomatic delayed visual loss associated with chiasmal herniation during long‐term cabergoline treatment of macroprolactinomas and to report our experience of its management.Patients  The study included 28 patients (11 women and 17 men) aged 14–85 years treated for macroprolactinoma with cabergoline at our centre from 1997 to 2006.Results  Chiasmal herniation was observed at MRI in five out of the 28 cases. A systematic visual field evaluation revealed visual field worsening, during cabergoline treatment, in three out of these five patients. In two asymptomatic patients, secondary deterioration of visual field occurred 2·5 years and 4 years, respectively, after cabergoline treatment initiation. In the third case, cabergoline treatment resulted in a paradoxical worsening of an initial visual defect. In all three cases, visual fields improved after cabergoline withdrawal although chiasmal herniation persisted. Visual field remained normal in the two other patients.Conclusions  Our results suggested that chiasmal herniation associated with delayed visual field defect is not a rare feature during cabergoline treatment of macroprolactinomas. It should be assessed by systematic visual field evaluation and treated by adaptation of medical treatment.