bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and prognostic impact of allelic imbalances associated with leukemic transformation of Philadelphia chromosome–negative myeloproliferative neoplasms
Authors: Thoennissen Nils H. , Krug Utz O. , Lee Dhong Hyun Tony , Kawamata Norihiko , Iwanski Gabriela B. , Lasho Terra , Weiss Tamara , Nowak Daniel , Koren-Michowitz Maya , Kato Motohiro , Sanada Masashi , Shih Lee-Yung , Nagler Arnon , Raynaud Sophie D. , Müller-Tidow Carsten , Mesa Ruben , Haferlach Torsten , Gilliland D. Gary , Tefferi Ayalew , Ogawa Seishi , Koeffler H. Phillip 
Published: January 2010

Abstract
Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and primary myelofibrosis show an inherent tendency for transformation into leukemia (MPN-blast phase), which is hypothesized to be accompanied by acquisition of additional genomic lesions. We, therefore, examined chromosomal abnormalities by high-resolution single nucleotide polymorphism (SNP) array in 88 MPN patients, as well as 71 cases with MPN-blast phase, and correlated these findings with their clinical parameters. Frequent genomic alterations were found in MPN after leukemic transformation with up to 3-fold more genomic changes per sample compared with samples in chronic phase (P < .001). We identified commonly altered regions involved in disease progression including not only established targets (ETV6, TP53, and RUNX1) but also new candidate genes on 7q, 16q, 19p, and 21q. Moreover, trisomy 8 or amplification of 8q24 (MYC) was almost exclusively detected in JAK2V617F− cases with MPN-blast phase. Remarkably, copy number–neutral loss of heterozygosity (CNN-LOH) on either 7q or 9p including homozygous JAK2V617F was related to decreased survival after leukemic transformation (P = .01 and P = .016, respectively). Our high-density SNP-array analysis of MPN genomes in the chronic compared with leukemic stage identified novel target genes and provided prognostic insights associated with the evolution to leukemia.
Identifying autoimmune lymphoproliferative syndrome in children with Evans syndrome: a multi-institutional study
Authors: Seif Alix E. , Manno Catherine S. , Sheen Cecilia , Grupp Stephan A. , Teachey David T. 
Published: January 2010

Abstract
Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by dysregulation of the Fas apoptotic pathway. Clinical manifestations of ALPS include autoimmune cytopenias, organomegaly, and lymphadenopathy. These findings overlap with Evans syndrome (ES), defined by presence of at least 2 autoimmune cytopenias. We hypothesized a subset of patients with ES have ALPS and tested 45 children at 22 institutions, measuring peripheral blood double-negative T cells (DNTs) and Fas-mediated apoptosis. ALPS was diagnosed in 47% of patients tested. Markedly elevated DNTs (≥ 5%) were a strong predictor of ALPS (positive predictive value = 94%), whereas no patients with DNTs less than 2.5% had ALPS on apoptosis testing. Severity of cytopenias and elevated immunoglobulin levels also predicted ALPS. This is the largest published series describing children with ES and documents a high rate of ALPS among pediatric ES patients. These data suggest that children with ES should be screened for ALPS with DNTs.
Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens
Authors: Warren Edus H. , Fujii Nobuharu , Akatsuka Yoshiki , Chaney Colette N. , Mito Jeffrey K. , Loeb Keith R. , Gooley Ted A. , Brown Michele L. , Koo Kevin K. W. , Rosinski Kellie V. , Ogawa Seishi , Matsubara Aiko , Appelbaum Frederick R. , Riddell Stanley R. 
Published: January 2010

Abstract
The adoptive transfer of donor T cells that recognize recipient minor histocompatibility antigens (mHAgs) is a potential strategy for preventing or treating leukemic relapse after allogeneic hematopoietic cell transplantation (HCT). A total of 7 patients with recurrent leukemia after major histocompatibility complex (MHC)–matched allogeneic HCT were treated with infusions of donor-derived, ex vivo–expanded CD8+ cytotoxic T lymphocyte (CTL) clones specific for tissue-restricted recipient mHAgs. The safety of T-cell therapy, in vivo persistence of transferred CTLs, and disease response were assessed. Molecular characterization of the mHAgs recognized by CTL clones administered to 3 patients was performed to provide insight into the antileukemic activity and safety of T-cell therapy. Pulmonary toxicity of CTL infusion was seen in 3 patients, was severe in 1 patient, and correlated with the level of expression of the mHAg-encoding genes in lung tissue. Adoptively transferred CTLs persisted in the blood up to 21 days after infusion, and 5 patients achieved complete but transient remissions after therapy. The results of these studies illustrate the potential to selectively enhance graft-versus-leukemia activity by the adoptive transfer of mHAg-specific T-cell clones and the challenges for the broad application of this approach in allogeneic HCT. This study has been registered at http://clinicaltrials.gov as NCT00107354.
Modelling p-value distributions to improve theme-driven survival analysis of cancer transcriptome datasets
Authors: Czwan Esteban , Brors Benedikt , Kipling David 
Published: January 2010

Abstract

Background
Theme-driven cancer survival studies address whether the expression signature of genes related to a biological process can predict patient survival time. Although this should ideally be achieved by testing two separate null hypotheses, current methods treat both hypotheses as one. The first test should assess whether a geneset, independent of its composition, is associated with prognosis (frequently done with a survival test). The second test then verifies whether the theme of the geneset is relevant (usually done with an empirical test that compares the geneset of interest with random genesets). Current methods do not test this second null hypothesis because it has been assumed that the distribution of p-values for random genesets (when tested against the first null hypothesis) is uniform. Here we demonstrate that such an assumption is generally incorrect and consequently, such methods may erroneously associate the biology of a particular geneset with cancer prognosis.

Results
To assess the impact of non-uniform distributions for random genesets in such studies, an automated theme-driven method was developed. This method empirically approximates the p-value distribution of sets of unrelated genes based on a permutation approach, and tests whether predefined sets of biologically-related genes are associated with survival. The results from a comparison with a published theme-driven approach revealed non-uniform distributions, suggesting a significant problem exists with false positive rates in the original study. When applied to two public cancer datasets our technique revealed novel ontological categories with prognostic power, including significant correlations between "fatty acid metabolism" with overall survival in breast cancer, as well as "receptor mediated endocytosis", "brain development", "apical plasma membrane" and "MAPK signaling pathway" with overall survival in lung cancer.

Conclusions
Current methods of theme-driven survival studies assume uniformity of p-values for random genesets, which can lead to false conclusions. Our approach provides a method to correct for this pitfall, and provides a novel route to identifying higher-level biological themes and pathways with prognostic power in clinical microarray datasets.
Molecular and cellular evidence for biased mitotic gene conversion in hybrid scallop
Authors: Wang Shi , Zhang Lingling , Hu Jingjie , Bao Zhenmin , Liu Zhanjiang 
Published: January 2010

Abstract

Background
Concerted evolution has been believed to account for homogenization of genes within multigene families. However, the exact mechanisms involved in the homogenization have been under debate. Use of interspecific hybrid system allows detection of greater level of sequence variation, and therefore, provide advantage for tracing the sequence changes. In this work, we have used an interspecific hybrid system of scallop to study the sequence homogenization processes of rRNA genes.

Results
Through the use of a hybrid scallop system (Chlamys farreri ♀ × Argopecten irradians ♂), here we provide solid molecular and cellular evidence for homogenization of the rDNA sequences into maternal genotypes. The ITS regions of the rDNA of the two scallop species exhibit distinct sequences and thereby restriction fragment length polymorphism (RFLP) patterns, and such a difference was exploited to follow the parental ITS contributions in the F1 hybrid during early development using PCR-RFLP. The representation of the paternal ITS decreased gradually in the hybrid during the development of the hybrid, and almost diminished at the 14th day after fertilization while the representation of the maternal ITS gradually increased. Chromosomal-specific fluorescence in situ hybridization (FISH) analysis in the hybrid revealed the presence of maternal ITS sequences on the paternal ITS-bearing chromosomes, but not vice versa. Sequence analysis of the ITS region in the hybrid not only confirmed the maternally biased conversion, but also allowed the detection of six recombinant variants in the hybrid involving short recombination regions, suggesting that site-specific recombination may be involved in the maternally biased gene conversion.

Conclusion
Taken together, these molecular and cellular evidences support rapid concerted gene evolution via maternally biased gene conversion. As such a process would lead to the expression of only one parental genotype, and have the opportunities to generate recombinant intermediates; this work may also have implications in novel hybrid zone alleles and genetic imprinting, as well as in concerted gene evolution. In the course of evolution, many species may have evolved involving some levels of hybridization, intra- or interspecific, the sex-biased sequence homogenization could have led to a greater role of one sex than the other in some species.
Transcription profiles of mitochondrial genes correlate with mitochondrial DNA haplotypes in a natural population of Silene vulgaris
Authors: Elansary Hosam O , Müller Karel , Olson Matthew S , Štorchová Helena 
Published: January 2010

Abstract

Background
Although rapid changes in copy number and gene order are common within plant mitochondrial genomes, associated patterns of gene transcription are underinvestigated. Previous studies have shown that the gynodioecious plant species Silene vulgaris exhibits high mitochondrial diversity and occasional paternal inheritance of mitochondrial markers. Here we address whether variation in DNA molecular markers is correlated with variation in transcription of mitochondrial genes in S. vulgaris collected from natural populations.

Results
We analyzed RFLP variation in two mitochondrial genes, cox1 and atp1, in offspring of ten plants from a natural population of S. vulgaris in Central Europe. We also investigated transcription profiles of the atp1 and cox1 genes. Most DNA haplotypes and transcription profiles were maternally inherited; for these, transcription profiles were associated with specific mitochondrial DNA haplotypes. One individual exhibited a pattern consistent with paternal inheritance of mitochondrial DNA; this individual exhibited a transcription profile suggestive of paternal but inconsistent with maternal inheritance. We found no associations between gender and transcript profiles.

Conclusions
Specific transcription profiles of mitochondrial genes were associated with specific mitochondrial DNA haplotypes in a natural population of a gynodioecious species S. vulgaris.
Our findings suggest the potential for a causal association between rearrangements in the plant mt genome and transcription product variation.
Evidence for a "Founder Effect" among HIV-infected injection drug users (IDUs) in Pakistan
Authors: Rai Mohammad A , Nerurkar Vivek R , Khoja Suhail , Khan Saeed , Yanagihara Richard , Rehman Arish , Kazmi Shahana U , Ali Syed H 
Published: January 2010

Abstract

Background
We have previously reported a HIV-1 subtype A infection in a community of injection drug users (IDUs) in Karachi, Pakistan. We now show that this infection among the IDUs may have originated from a single source.

Methods
Phylogenetic analysis was performed of partial gag sequences, generated using PCR, from 26 HIV-positive IDU samples.

Results
Our results showed formation of a tight monophyletic group with an intra-sequence identity of < 98% indicating a "founder effect". Our data indicate that the HIV-1 epidemic in this community of IDUs may have been transmitted by an HIV positive overseas contract worker who admitted to having contact with commercial sex workers during stay abroad.

Conclusion
Specific measures need to implemented to control transmission of HIV infection in Pakistan through infected migrant workers.
Methylmercury exposure in a subsistence fishing community in Lake Chapala, Mexico: an ecological approach
Authors: Trasande Leonardo , Cortes Juanita E , Landrigan Philip J , Abercrombie Mary I , Bopp Richard F , Cifuentes Enrique 
Published: January 2010

Abstract

Background
Elevated concentrations of mercury have been documented in fish in Lake Chapala in central Mexico, an area that is home to a large subsistence fishing community. However, neither the extent of human mercury exposure nor its sources and routes have been elucidated.

Methods
Total mercury concentrations were measured in samples of fish from Lake Chapala; in sections of sediment cores from the delta of Rio Lerma, the major tributary to the lake; and in a series of suspended-particle samples collected at sites from the mouth of the Lerma to mid-Lake. A cross-sectional survey of 92 women ranging in age from 18-45 years was conducted in three communities along the Lake to investigate the relationship between fish consumption and hair mercury concentrations among women of child-bearing age.

Results
Highest concentrations of mercury in fish samples were found in carp (mean 0.87 ppm). Sediment data suggest a pattern of moderate ongoing contamination. Analyses of particles filtered from the water column showed highest concentrations of mercury near the mouth of the Lerma. In the human study, 27.2% of women had >1 ppm hair mercury. On multivariable analysis, carp consumption and consumption of fish purchased or captured from Lake Chapala were both associated with significantly higher mean hair mercury concentrations.

Conclusions
Our preliminary data indicate that, despite a moderate level of contamination in recent sediments and suspended particulate matter, carp in Lake Chapala contain mercury concentrations of concern for local fish consumers. Consumption of carp appears to contribute significantly to body burden in this population. Further studies of the consequences of prenatal exposure for child neurodevelopment are being initiated.
Different subsets of tumor infiltrating lymphocytes correlate with NPC progression in different ways
Authors: Zhang Yi-Lan , Li Jiang , Mo Hao-Yuan , Qiu Fang , Zheng Li-Min , Qian Chao-Nan , Zeng Yi-Xin 
Published: January 2010

Abstract

Background
Increasing amounts of evidence indicate that tumor infiltrating lymphocytes (TIL) are correlated with the prognosis of cancer patients. This study focuses on the association between the densities of tumor infiltrating cytotoxic T lymphocytes (CTL), activated CTL, regulatory T lymphocytes (Treg) and Th17 lymphocytes, and the prognosis and clinicopathological features of nasopharyngeal carcinoma (NPC) patients.

Results
Double immunohistochemical staining was performed in 106 biopsy specimens from newly diagnosed NPC patients. Prognostic values of infiltrating lymphocyte densities were evaluated by Kaplan-Meier analysis and Cox regression. The density of CD8+ TIL was positively correlated with lymph node metastasis, while the density of Foxp3+ TIL was negatively associated with T stage (P < 0.05). For survival evaluation, the density of Foxp3+ TIL or Foxp3+ TIL combined with GrB+ TIL together was associated with better overall survival (OS) and progression-free survival (PFS) (P < 0.01) in all patients and in the patients with late-stage diseases (Stages III and IV, P < 0.01). Meanwhile a low density of CD8+TIL or high ratio of FOXP3+TIL to CD8+TIL was correlated with better PFS in early stage patients (Stages I and II, P < 0.05). No significant association was found between IL-17+ TIL and clinicopathological characteristic or survival of NPC patients.

Conclusions
Our study identifies for the first time the tumor infiltrating Foxp3+ TIL as an independent favorable factor in the prognosis of NPC patients, especially for the patients with late-stage diseases.
Rapid chromosome territory relocation by nuclear motor activity in response to serum removal in primary human fibroblasts
Authors: Mehta Ishita S , Amira Manelle , Harvey Amanda J , Bridger Joanna M 
Published: January 2010

Abstract
Background
Radial chromosome positioning in interphase nuclei is nonrandom and can alter according to developmental, differentiation, proliferation, or disease status. However, it is not yet clear when and how chromosome repositioning is elicited.

Results
By investigating the positioning of all human chromosomes in primary fibroblasts that have left the proliferative cell cycle, we have demonstrated that in cells made quiescent by reversible growth arrest, chromosome positioning is altered considerably. We found that with the removal of serum from the culture medium, chromosome repositioning took less than 15 minutes, required energy and was inhibited by drugs affecting the polymerization of myosin and actin. We also observed that when cells became quiescent, the nuclear distribution of nuclear myosin 1β was dramatically different from that in proliferating cells. If we suppressed the expression of nuclear myosin 1β by using RNA-interference procedures, the movement of chromosomes after 15 minutes in low serum was inhibited. When high serum was restored to the serum-starved cultures, chromosome repositioning was evident only after 24 to 36 hours, and this coincided with a return to a proliferating distribution of nuclear myosin 1β.

Conclusions
These findings demonstrate that genome organization in interphase nuclei is altered considerably when cells leave the proliferative cell cycle and that repositioning of chromosomes relies on efficient functioning of an active nuclear motor complex that contains nuclear myosin 1β.
The Art of Posing Nude: Models, Moralists, and the 1893 Bal Des Quat'z-Arts
Authors: Felter-Kerley Lela 
Published: January 2010

This article examines the 1893 Bal des Quat'z-Arts as a flashpoint at which the exhibition of unclothed women became the source of aesthetic and moral debate between conservative and liberal forces, the focus of vice societies, and a target of judicial pursuit. As a collaborative effort between the saucy illustrated paper, Le courrier français, and students of the Ecole des Beaux-Arts, the ball satirized the moral hypocrisy and the materialism of bourgeois culture by employing the body of the artist's model as a site of social contestation. The presentation of models as female nudes, outside the studio in a semipublic festival, exposed the conditions under which academic art transformed working-class bodies into ideal forms and let artists actively engage in a wider social campaign testing the limits of individual freedom. The article offers a new perspective on contemporary debates about art and pornography, the New Woman, and morality at the fin de siècle.
Cet article analyse le Bal des Quat'z-Arts de 1893 en tant que moment où l'exposition des femmes déshabillées devint le point de départ d'un débat esthétique et moral entre les forces conservatrices et libérales. Le Bal attira l'attention des ligues morales et fit l'objet d'enquêtes judiciaires. Une collaboration entre une revue grivoise, Le courier français, et les étudiants de l'Ecole des Beaux-Arts, le Bal des Quat'z-Arts de 1893 se moqua de l'hypocrisie moraliste et le matérialisme de la bourgeoisie en faisant du corps du modèle un site de contestation sociale. L'exposition des modèles comme femmes nues, hors de l'atelier et dans une fête semipublique, mit en lumière les conditions dans lesquelles l'art académique a su changer des corps de la classe ouvrière en formes idéales. Sous le prétexte d'étudier « l'art pour l'art », les artistes s'embarquèrent dans une plus grande campagne pour repousser les limites de la liberté d'individuelle. La dispute qui s'ensuivit entre les moralistes et les critiques de la moralité bourgeoise devint une cause célèbre qui nous offre une nouvelle perspective sur les débats contemporains concernant l'art et la pornographie, la Nouvelle Femme et la moralité à la fin du XIXe siècle.
The Silver Foxhole: The Gis and Prostitution in Paris, 1944–1945
Authors: Roberts Mary Louise 
Published: January 2010

As the “brothel of Europe,” Paris became the favored destination of GIs on leave in 1944–45. The entry of the Americans into Paris transformed sexual commerce, leading to the downfall of the legal regulation of prostitution, ironically because the soldiers so sharply raised the demand for sexual labor. As the legal system broke down under the weight of demand, prostitution became chaotic and unprofessional, and prostitutes were left poor and unprotected. At the same time, a new culture of prostitution emerged in Paris with its own language, geography and protective customs. For the French, the prostitute came to symbolize a loss of French respectability and honor, as well as the domination of French culture by American wealth and power.
En tant que « Bordel de l'Europe », Paris est devenu la destination préférée des G.I. En permission en 1944 et 1945. L'entrée en scène des Américains a transformé le commerce sexuel à Paris, menant à l'effondrement de la réglementation juridique de la prostitution, ironiquement du à la montée en flèche de la demande des soldats pour le travail sexuel. Alors que le système juridique s'écroulait sous les exigences des soldats, la prostitution manqua totalement du professionnalisme et devint chaotique, laissant les prostituées pauvres et sans protection. En même temps, une nouvelle culture liée à la prostitution émergea à Paris avec ses propres langage, topographie des quartiers et habitudes de protection. Pour les Français, la prostituée devint un symbole de la perte de la respectabilité et de l'honneur, ainsi que de la domination de la culture française par la richesse et le pouvoir américain.