bluuebunny/crossref_metadata_2025_split huggingface dataset:
A distinctive form of immune thrombocytopenia in a phase 2 study of alemtuzumab for the treatment of relapsing-remitting multiple sclerosis
Authors: Cuker Adam , Coles Alasdair J. , Sullivan Herman , Fox Edward , Goldberg Mark , Oyuela Pedro , Purvis Annie , Beardsley Diana S. , Margolin David H. 
Published: September 2011

Abstract
In a phase 2 clinical trial of annual alemtuzumab for treatment of relapsing-remitting multiple sclerosis, 6 of 216 patients (2.8%) developed immune thrombocytopenia (ITP). Over mean follow-up of 4.5 years, the incidence rate of ITP was 6.2 (95% confidence interval, 2.3-13.3) per 1000 person-years. Median times from initial and last alemtuzumab exposure to ITP diagnosis were 24.5 and 10.5 months, respectively. Five patients developed severe thrombocytopenia. Four were symptomatic, including fatal intracranial hemorrhage in the index case. Four patients received standard first-line ITP therapy, all of whom responded to treatment within 1 week. All 5 surviving patients achieved complete remission and remained in complete remission without need for ongoing ITP therapy for a median duration of 34 months at last follow-up. A monitoring plan for the early detection of ITP, implemented after presentation of the index case, identified all 5 subsequent cases before serious hemorrhagic morbidity or mortality occurred. In conclusion, we describe a distinctive form of ITP associated with alemtuzumab treatment characterized by delayed presentation after drug exposure, responsiveness to conventional ITP therapies, and prolonged remission. Clinicians should maintain a high level of vigilance and consider routine monitoring for ITP in patients treated with this agent. This trial was registered at www.clinicaltrials.gov as #NCT00050778.
Multilocus association mapping using generalized ridge logistic regression
Authors: Liu Zhe , Shen Yuanyuan , Ott Jurg 
Published: September 2011

AbstractBackgroundIn genome-wide association studies, it is widely accepted that multilocus methods are more powerful than testing single-nucleotide polymorphisms (SNPs) one at a time. Among statistical approaches considering many predictors simultaneously, scan statistics are an effective tool for detecting susceptibility genomic regions and mapping disease genes. In this study, inspired by the idea of scan statistics, we propose a novel sliding window-based method for identifying a parsimonious subset of contiguous SNPs that best predict disease status.ResultsWithin each sliding window, we apply a forward model selection procedure using generalized ridge logistic regression for model fitness in each step. In power simulations, we compare the performance of our method with that of five other methods in current use. Averaging power over all the conditions considered, our method dominates the others. We also present two published datasets where our method is useful in causal SNP identification.ConclusionsOur method can automatically combine genetic information in local genomic regions and allow for linkage disequilibrium between SNPs. It can overcome some defects of the scan statistics approach and will be very promising in genome-wide case-control association studies.
Genome-wide analysis of WRKY gene family in Cucumis sativus
Authors: Ling Jian , Jiang Weijie , Zhang Ying , Yu Hongjun , Mao Zhenchuan , Gu Xingfang , Huang Sanwen , Xie Bingyan 
Published: September 2011

AbstractBackgroundWRKY proteins are a large family of transcriptional regulators in higher plant. They are involved in many biological processes, such as plant development, metabolism, and responses to biotic and abiotic stresses. Prior to the present study, only one full-length cucumber WRKY protein had been reported. The recent publication of the draft genome sequence of cucumber allowed us to conduct a genome-wide search for cucumber WRKY proteins, and to compare these positively identified proteins with their homologs in model plants, such asArabidopsis.ResultsWe identified a total of 55 WRKY genes in the cucumber genome. According to structural features of their encoded proteins, the cucumber WRKY (CsWRKY) genes were classified into three groups (group 1-3). Analysis of expression profiles ofCsWRKYgenes indicated that 48 WRKY genes display differential expression either in their transcript abundance or in their expression patterns under normal growth conditions, and 23 WRKY genes were differentially expressed in response to at least one abiotic stresses (cold, drought or salinity). The expression profile of stress-inducibleCsWRKYgenes were correlated with those of their putativeArabidopsis WRKY (AtWRKY)orthologs, except for the group 3 WRKY genes. Interestingly, duplicated group 3AtWRKYgenes appear to have been under positive selection pressure during evolution. In contrast, there was no evidence of recent gene duplication or positive selection pressure amongCsWRKYgroup 3 genes, which may have led to the expressional divergence of group 3 orthologs.ConclusionsFifty-five WRKY genes were identified in cucumber and the structure of their encoded proteins, their expression, and their evolution were examined. Considering that there has been extensive expansion of group 3 WRKY genes in angiosperms, the occurrence of different evolutionary events could explain the functional divergence of these genes.
Single-nucleotide resolution analysis of the transcriptome structure of Clostridium beijerinckii NCIMB 8052 using RNA-Seq
Authors: Wang Yi , Li Xiangzhen , Mao Yuejian , Blaschek Hans P 
Published: September 2011

Abstract

Background

Clostridium beijerinckii is an important solvent producing microorganism. The genome of C. beijerinckii NCIMB 8052 has recently been sequenced. Although transcriptome structure is important in order to reveal the functional and regulatory architecture of the genome, the physical structure of transcriptome for this strain, such as the operon linkages and transcript boundaries are not well understood.

Results
In this study, we conducted a single-nucleotide resolution analysis of the C. beijerinckii NCIMB 8052 transcriptome using high-throughput RNA-Seq technology. We identified the transcription start sites and operon structure throughout the genome. We confirmed the structure of important gene operons involved in metabolic pathways for acid and solvent production in C. beijerinckii 8052, including pta-ack, ptb-buk, hbd-etfA-etfB-crt (bcs) and ald-ctfA-ctfB-adc (sol) operons; we also defined important operons related to chemotaxis/motility, transcriptional regulation, stress response and fatty acids biosynthesis along with others. We discovered 20 previously non-annotated regions with significant transcriptional activities and 15 genes whose translation start codons were likely mis-annotated. As a consequence, the accuracy of existing genome annotation was significantly enhanced. Furthermore, we identified 78 putative silent genes and 177 putative housekeeping genes based on normalized transcription measurement with the sequence data. We also observed that more than 30% of pseudogenes had significant transcriptional activities during the fermentation process. Strong correlations exist between the expression values derived from RNA-Seq analysis and microarray data or qRT-PCR results.

Conclusions
Transcriptome structural profiling in this research provided important supplemental information on the accuracy of genome annotation, and revealed additional gene functions and regulation in C. beijerinckii.
Characterization of the χψ subcomplex of Pseudomonas aeruginosa DNA polymerase III
Authors: El Houry Mignan Sirine , Witte Gregor , Naue Natalie , Curth Ute 
Published: September 2011

Abstract

Background
DNA polymerase III, the main enzyme responsible for bacterial DNA replication, is composed of three sub-assemblies: the polymerase core, the β-sliding clamp, and the clamp loader. During replication, single-stranded DNA-binding protein (SSB) coats and protects single-stranded DNA (ssDNA) and also interacts with the χψ heterodimer, a sub-complex of the clamp loader. Whereas the χ subunits of Escherichia coli and Pseudomonas aeruginosa are about 40% homologous, P. aeruginosa ψ is twice as large as its E. coli counterpart, and contains additional sequences. It was shown that P. aeruginosa χψ together with SSB increases the activity of its cognate clamp loader 25-fold at low salt. The E. coli clamp loader, however, is insensitive to the addition of its cognate χψ under similar conditions. In order to find out distinguishing properties within P. aeruginosa χψ which account for this higher stimulatory effect, we characterized P. aeruginosa χψ by a detailed structural and functional comparison with its E. coli counterpart.

Results
Using small-angle X-ray scattering, analytical ultracentrifugation, and homology-based modeling, we found the N-terminus of P. aeruginosa ψ to be unstructured. Under high salt conditions, the affinity of the χψ complexes from both organisms to their cognate SSB was similar. Under low salt conditions, P. aeruginosa χψ, contrary to E. coli χψ, binds to ssDNA via the N-terminus of ψ. Whereas it is also able to bind to double-stranded DNA, the affinity is somewhat reduced.

Conclusions
The binding to DNA, otherwise never reported for any other ψ protein, enhances the affinity of P. aeruginosa χψ towards the SSB/ssDNA complex and very likely contributes to the higher stimulatory effect of P. aeruginosa χψ on the clamp loader. We also observed DNA-binding activity for P. putida χψ, making this activity most probably a characteristic of the ψ proteins from the Pseudomonadaceae.
A randomized controlled trial to investigate the influence of low dose radiotherapy on immune stimulatory effects in liver metastases of colorectal cancer
Authors: Reissfelder Christoph , Timke Carmen , Schmitz-Winnenthal Hubertus , Rahbari Nuh N , Koch Moritz , Klug Felix , Roeder Falk , Edler Lutz , Debus Jürgen , Büchler Markus W , Beckhove Philipp , Huber Peter E , Weitz Jürgen 
Published: September 2011

Abstract

Background
Insufficient migration and activation of tumor specific effector T cells in the tumor is one of the main reasons for inadequate host anti-tumor immune response. External radiation seems to induce inflammation and activate the immune response. This phase I/II clinical trial aims to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in patients with colorectal liver metastases.

Methods/Design
This is an investigator-initiated, prospective randomised, 4-armed, controlled Phase I/II trial. Patients undergoing elective hepatic resection due to colorectal cancer liver metastasis will be enrolled in the study. Patients will receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation targeted to their liver metastasis. Radiation will be applied by external beam radiotherapy using a 6 MV linear accelerator (Linac) with intensity modulated radiotherapy (IMRT) technique two days prior to surgical resection. All patients admitted to the Department of General-, Visceral-, and Transplantion Surgery, University of Heidelberg for elective hepatic resection are consecutively screened for eligibility into this trial, and written informed consent is obtained before inclusion. The primary objective is to assess the effect of active local external beam radiation dose on, tumor infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include radiogenic treatment toxicity, postoperative morbidity and mortality, local tumor control and recurrence patterns, survival and quality of life. Furthermore, frequencies of systemic tumor reactive T cells in blood and bone marrow will be correlated with clinical outcome.

Discussion
This is a randomized controlled patient blinded trial to assess the safety and efficiency of low dose radiotherapy on metastasis infiltrating T cells and thus potentially enhance the antitumor immune response.

Trial registration
ClinicalTrials.gov: NCT01191632
Service user and carer experiences of seeking help for a first episode of psychosis: a UK qualitative study
Authors: Tanskanen Sanna , Morant Nicola , Hinton Mark , Lloyd-Evans Brynmor , Crosby Michelle , Killaspy Helen , Raine Rosalind , Pilling Stephen , Johnson Sonia 
Published: September 2011

Abstract

Background
Long duration of untreated psychosis (DUP) is associated with poor outcomes and low quality of life at first contact with mental health services. However, long DUP is common. In order to inform initiatives to reduce DUP, we investigated service users' and carers' experiences of the onset of psychosis and help-seeking in two multicultural, inner London boroughs and the roles of participants' social networks in their pathways to care.

Method
In-depth interviews were conducted with service users and carers from an early intervention service in North London, purposively sampled to achieve diversity in sociodemographic characteristics and DUP and to include service users in contact with community organisations during illness onset. Interviews covered respondents' understanding of and reaction to the onset of psychosis, their help-seeking attempts and the reactions of social networks and health services. Thematic analysis of interview transcripts was conducted.

Results
Multiple barriers to prompt treatment included not attributing problems to psychosis, worries about the stigma of mental illness and service contact, not knowing where to get help and unhelpful service responses. Help was often not sought until crisis point, despite considerable prior distress. The person experiencing symptoms was often the last to recognise them as mental illness. In an urban UK setting, where involved, workers in non-health community organisations were frequently willing to assist help-seeking but often lacked skills, time or knowledge to do so.

Conclusion
Even modest periods of untreated psychosis cause distress and disruption to individuals and their families. Early intervention services should prioritise early detection. Initiatives aimed at reducing DUP may succeed not by promoting swift service response alone, but also by targeting delays in initial help-seeking. Our study suggests that strategies for doing this may include addressing the stigma associated with psychosis and community education regarding symptoms and services, targeting not only young people developing illness but also a range of people in their networks, including staff in educational and community organisations. Initiatives to enhance the effective involvement of staff in community organisations working with young people in promoting help-seeking merit research.
Factors associated with chemical burns in Zhejiang province, China: An epidemiological study
Authors: Zhang Yuan H , Han Chun M , Chen Guo X , Ye Chun J , Jiang Rui M , Liu Li P , Ni Liang F 
Published: September 2011

Abstract

Background
Work-related burns are common among occupational injuries. Zhejiang Province is an industrial area with a high incidence of chemical burns. We aimed to survey epidemiological features of chemical burns in Zhejiang province to determine associated factors and acquire data for developing a strategy to prevent and treat chemical burns.

Methods
Questionnaires were developed, reviewed and validated by experts, and sent to 25 hospitals in Zhejiang province to prospectively collect data of 492 chemical burn patients admitted during one year from Sept. 1, 2008 to Aug. 31, 2009. Questions included victims' characteristics and general condition, injury location, causes of accident, causative chemicals, total body surface area burn, concomitant injuries, employee safety training, and awareness level of protective measures. Surveys were completed for each of burn patients by burn department personnel who interviewed the hospitalized patients.

Results
In this study, 417 victims (87.61%) got chemical burn at work, of which 355 victims (74.58%) worked in private or individual enterprises. Most frequent chemicals involved were hydrofluoric acid and sulfuric acid. Main causes of chemical injury accidents were inappropriate operation of equipment or handling of chemicals and absence of or failure to use effective individual protection.

Conclusions
Most chemical burns are preventable occupational injuries that can be attributed to inappropriate operation of equipment or handling of chemicals, lack of employee awareness about appropriate action and lack of effective protective equipment and training. Emphasis on safety education and protection for workers may help protect workers and prevent chemical burns.
Laboratory demonstration of a prozone-like effect in HRP2-detecting malaria rapid diagnostic tests: implications for clinical management
Authors: Luchavez Jennifer , Baker Joanne , Alcantara Sheila , Belizario Vicente , Cheng Qin , McCarthy James S , Bell David 
Published: September 2011

Abstract

Background
Malaria rapid diagnostic tests (RDTs) are now widely used for prompt on-site diagnosis in remote endemic areas where reliable microscopy is absent. Aberrant results, whereby negative test results occur at high parasite densities, have been variously reported for over a decade and have led to questions regarding the reliability of the tests in clinical use.

Methods
In the first trial, serial dilutions of recombinant HRP2 antigen were tested on an HRP2-detectiing RDT. In a second trial, serial dilutions of culture-derived Plasmodium falciparum parasites were tested against three HRP2-detecting RDTs.

Results
A prozone-like effect occurred in RDTs at a high concentration of the target antigen, histidine-rich protein-2 (above 15,000 ng/ml), a level that corresponds to more than 312000 parasites per μL. Similar results were noted on three RDT products using dilutions of cultured parasites up to a parasite density of 25%. While reduced line intensity was observed, no false negative results occurred.

Conclusions
These results suggest that false-negative malaria RDT results will rarely occur due to a prozone-like effect in high-density infections, and other causes are more likely. However, RDT line intensity is poorly indicative of parasite density in high-density infections and RDTs should, therefore, not be considered quantitative. Immediate management of suspected severe malaria should rely on clinical assessment or microscopy. Evaluation against high concentrations of antigen should be considered in malaria RDT product development and lot-release testing, to ensure that very weak or false negative results will not occur at antigen concentrations that might be seen clinically.
Single wall carbon nanotubes enter cells by endocytosis and not membrane penetration
Authors: Yaron Peter N , Holt Brian D , Short Philip A , Lösche Mathias , Islam Mohammad F , Dahl Kris Noel 
Published: September 2011

Abstract

Background
Carbon nanotubes are increasingly being tested for use in cellular applications. Determining the mode of entry is essential to control and regulate specific interactions with cells, to understand toxicological effects of nanotubes, and to develop nanotube-based cellular technologies. We investigated cellular uptake of Pluronic copolymer-stabilized, purified ~145 nm long single wall carbon nanotubes (SWCNTs) through a series of complementary cellular, cell-mimetic, and in vitro model membrane experiments.

Results
SWCNTs localized within fluorescently labeled endosomes, and confocal Raman spectroscopy showed a dramatic reduction in SWCNT uptake into cells at 4°C compared with 37°C. These data suggest energy-dependent endocytosis, as shown previously. We also examined the possibility for non-specific physical penetration of SWCNTs through the plasma membrane. Electrochemical impedance spectroscopy and Langmuir monolayer film balance measurements showed that Pluronic-stabilized SWCNTs associated with membranes but did not possess sufficient insertion energy to penetrate through the membrane. SWCNTs associated with vesicles made from plasma membranes but did not rupture the vesicles.

Conclusions
These measurements, combined, demonstrate that Pluronic-stabilized SWCNTs only enter cells via energy-dependent endocytosis, and association of SWCNTs to membrane likely increases uptake.
Impact of childhood trauma on functionality and quality of life in HIV-infected women
Authors: Troeman Zyrhea CE , Spies Georgina , Cherner Mariana , Archibald Sarah L , Fennema-Notestine Christine , Theilmann Rebecca J , Spottiswoode Bruce , Stein Dan J , Seedat Soraya 
Published: September 2011

Abstract

Background
While there are many published studies on HIV and functional limitations, there are few in the context of early abuse and its impact on functionality and Quality of Life (QoL) in HIV.

Methods
The present study focused on HIV in the context of childhood trauma and its impact on functionality and Quality of Life (QoL) by evaluating 85 HIV-positive (48 with childhood trauma and 37 without) and 52 HIV-negative (21 with childhood trauma and 31 without) South African women infected with Clade C HIV. QoL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), the Patient's Assessment of Own Functioning Inventory (PAOFI), the Activities of Daily Living (ADL) scale and the Sheehan Disability Scale (SDS). Furthermore, participants were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Childhood Trauma Questionnaire (CTQ).

Results
Subjects had a mean age of 30.1 years. After controlling for age, level of education and CES-D scores, analysis of covariance (ANCOVA) demonstrated significant individual effects of HIV status and childhood trauma on self-reported QoL. No significant interactional effects were evident. Functional limitation was, however, negatively correlated with CD4 lymphocyte count.

Conclusions
In assessing QoL in HIV-infected women, we were able to demonstrate the impact of childhood trauma on functional limitations in HIV.
Evaluation of the new AJCC staging system for resectable hepatocellular carcinoma
Authors: Cheng Chih H , Lee Chen F , Wu Tsung H , Chan Kun M , Chou Hong S , Wu Ting J , Yu Ming C , Chen Tse C , Lee Wei C , Chen Miin F 
Published: September 2011

Abstract

Background
The aim of this study was to assess the validity of the 7th edition of the American Joint Committee on Cancer (AJCC) TNM system (TNM-7) for patients undergoing hepatectomy for hepatocellular carcinoma (HCC).

Methods
Partial hepatectomies performed for 879 patients from 1993 to 2005 were retrospectively reviewed. Clinicopathological factors, surgical outcome, overall survival (OS), and disease-free survival (DFS) were analyzed to evaluate the predictive value of the TNM-7 staging system.

Results
According to the TNM-7 system, differences in five-year survival between stages I, II, and III were statistically significant. Subgroup analysis of stage III patients revealed that the difference between stages II and IIIA was not significant (OS, p = 0.246; DFS, p = 0.105). Further stratification of stages IIIA, IIIB and IIIC also did not reveal significant differences. Cox proportional hazard models of stage III analyses identified additional clinicopathological factors affecting patient survival: lack of tumor encapsulation, aspartate aminotransferase (AST) values > 68 U/L, and blood loss > 500 mL affected DFS whereas lack of tumor encapsulation, AST values > 68 U/L, blood loss > 500 mL, and serum α-fetoprotein (AFP) values > 200 ng/mL were independent factors impairing OS. Stage III factors including tumor thrombus, satellite lesions, and tumor rupture did not appear to influence survival in the stage III subgroup.

Conclusions
In terms of 5-year survival rates, the TNM-7 system is capable of stratifying post-hepatectomy HCC patients into stages I, II, and III but is unable to stratify stage III patients into stages IIIA, IIIB and IIIC. Lack of tumor encapsulation, AST values > 68 U/L, blood loss > 500 mL, and AFP values > 200 ng/mL are independent prognostic factors affecting long-term survival.