bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Stigmatization/Discrimination on Antiretroviral Therapy Adherence among HIV-Infected Patients in a Rural Tertiary Medical Center in Nigeria
Authors: Omosanya Olusegun Emmanuel , Elegbede Olayide Toyin , Agboola Segun Matthew , Isinkaye Ayodeji Olusola , Omopariola Olusoji Adegoke 
Published: March 2013

Introduction: Stigmatization and discrimination impact negatively on interventions and act as barriers to all HIV/AIDS activities. This study assessed the relationship between stigmatization and discrimination and adherence to antiretroviral therapy (ART) among HIV-infected patients attending the Federal Medical Centre, Ido-Ekiti, Nigeria. Methods: A cross-sectional study was carried out among respondents selected by systematic random sampling. Structured, interviewer-administered questionnaires were used to collect data subsequently analyzed with SPSS 16. Results: A total of 100 respondents comprising 61 (61.0%) female participants were interviewed. A large proportion, 92.0%, had a low level of stigmatization. In all, 88 (88.0%) had a good level of antiretroviral adherence using a threshold of >95%. More people living with HIV/AIDS (PLWHAs) with low stigmatization and discrimination had good adherence to ART ( P < .001). Conclusion: The PLWHAs with low levels of stigmatization and discrimination are more likely to adhere to ART than those with high levels. Counseling services and health education on adherence should be a strong component of all PLWHA care.
Improved ex vivo expansion of adult hematopoietic stem cells by overcoming CUL4-mediated degradation of HOXB4
Authors: Lee Jennifer , Shieh Jae-Hung , Zhang Jianxuan , Liu Liren , Zhang Yue , Eom Jae Yong , Morrone Giovanni , Moore Malcolm A. S. , Zhou Pengbo 
Published: March 2013

Key Points
The CUL4 ubiquitin ligases target HOXB4 for ubiquitination and degradation. A degradation-resistant HOXB4 variant markedly enhanced ex vivo expansion of adult hematopoietic stem cells.
No increase in bleeding identified in type 1 VWD subjects with D1472H sequence variation
Authors: Flood Veronica H. , Friedman Kenneth D. , Gill Joan Cox , Haberichter Sandra L. , Christopherson Pamela A. , Branchford Brian R. , Hoffmann Raymond G. , Abshire Thomas C. , Dunn Amy L. , Di Paola Jorge A. , Hoots W. Keith , Brown Deborah L. , Leissinger Cindy , Lusher Jeanne M. , Ragni Margaret V. , Shapiro Amy D. , Montgomery Robert R. 
Published: March 2013

Key Points
D1472H sequence variation is associated with a decreased VWF:RCo/VWF:Ag ratio in type 1 VWD subjects. D1472H sequence variation is not associated with an increase in bleeding as measured by bleeding score in type 1 VWD subjects.
Clarithromycin increases linezolid exposure in multidrug-resistant tuberculosis patients
Authors: Bolhuis Mathieu S. , van Altena Richard , van Soolingen Dick , de Lange Wiel C.M. , Uges Donald R.A. , van der Werf Tjip S. , Kosterink Jos G.W. , Alffenaar Jan-Willem C. 
Published: March 2013

The use of linezolid for the treatment of multidrug-resistant tuberculosis is limited by dose- and time-dependent toxicity. Recently, we reported a case of pharmacokinetic drug–drug interaction between linezolid and clarithromycin that resulted in increased linezolid exposure. The aim of this prospective pharmacokinetic study is to quantify the effect of clarithromycin on the exposure of linezolid.Subjects were included in an open-label, single-centre, single-arm, fixed-order pharmacokinetic interaction study. All subjects received 300 mg linezolid twice daily during the entire study, consecutively co-administered with 250 mg and 500 mg clarithromycin once daily. Steady-state serum curves of linezolid and clarithromycin were analysed using validated methods, and differences between pharmacokinetic parameters were calculated.Linezolid exposure increased by a median (interquartile range) of 44% (23–102%, p=0.043) after co-administration of 500 mg clarithromycin (n=5) compared to baseline, whereas 250 mg clarithromycin had no statistically significant effect. Co-administration was well tolerated by most patients; none experienced severe adverse effects. One patient reported common toxicity criteria grade 2 gastrointestinal adverse events.In this study, we showed that clarithromycin significantly increased linezolid serum exposure after combining clarithromycin with linezolid in multidrug-resistant tuberculosis patients. The drug–drug interaction is possibly P-glycoprotein-mediated. Due to large interpatient variability, therapeutic drug monitoring is advisable to determine individual effect size.
Chronic burden of near-roadway traffic pollution in 10 European cities (APHEKOM network)
Authors: Perez Laura , Declercq Christophe , Iñiguez Carmen , Aguilera Inmaculada , Badaloni Chiara , Ballester Ferran , Bouland Catherine , Chanel Olivier , Cirarda Francisco B. , Forastiere Francesco , Forsberg Bertil , Haluza Daniela , Hedlund Britta , Cambra Koldo , Lacasaña Marina , Moshammer Hanns , Otorepec Peter , Rodríguez-Barranco Miguel , Medina Sylvia , Künzli Nino 
Published: March 2013

Recent epidemiological research suggests that near road traffic-related pollution may cause chronic disease, as well as exacerbation of related pathologies, implying that the entire “chronic disease progression” should be attributed to air pollution, no matter what the proximate cause was. We estimated the burden of childhood asthma attributable to air pollution in 10 European cities by calculating the number of cases of 1) asthma caused by near road traffic-related pollution, and 2) acute asthma events related to urban air pollution levels. We then expanded our approach to include coronary heart diseases in adults.Derivation of attributable cases required combining concentration–response function between exposures and the respective health outcome of interest (obtained from published literature), an estimate of the distribution of selected exposures in the target population, and information about the frequency of the assessed morbidities.Exposure to roads with high vehicle traffic, a proxy for near road traffic-related pollution, accounted for 14% of all asthma cases. When a causal relationship between near road traffic-related pollution and asthma is assumed, 15% of all episodes of asthma symptoms were attributable to air pollution. Without this assumption, only 2% of asthma symptoms were attributable to air pollution. Similar patterns were found for coronary heart diseases in older adults.Pollutants along busy roads are responsible for a large and preventable share of chronic disease and related acute exacerbations in European urban areas.
Ciliary dyskinesia is an early feature of respiratory syncytial virus infection
Authors: Smith Claire M. , Kulkarni Hemant , Radhakrishnan Priya , Rutman Andrew , Bankart Michael J. , Williams Gwyneth , Hirst Robert A. , Easton Andrew J. , Andrew Peter W. , O’Callaghan Chris 
Published: March 2013

Respiratory syncytial virus is a major cause of respiratory disease. There are conflicting accounts of the response of human epithelial cells to respiratory syncytial virus and a lack of data on its effect on ciliary function. Our aim was to study the early stages of respiratory syncytial virus infection of primary human basal and ciliated cultures.Using high speed videomicroscopy, we found that ciliary beat frequency was unaffected by respiratory syncytial virus infection over 72 h; however, ciliary dyskinesia significantly increased within 24 h of infection (p<0.05). Transmission electron microscopy revealed that ultrastructural abnormalities were confined to ciliated cells, including increased cilia loss and mitochondrial damage. Confocal immunofluorescence microscopy showed that respiratory syncytial virus antigen gradually spread from the cell surface to the ciliary tip of infected cells over 3 days. Interestingly, ciliated cultures secreted fewer viruses than basal (progenitor) cell cultures and produced a chemokine response focused on recruitment of neutrophils.This study highlights differences in infection models and underscores the need to explore further the role of ciliated cells in the establishment of respiratory syncytial virus infection.Increased ciliary dyskinesia combined with ciliary loss and epithelial damage is likely to result in reduced mucociliary clearance early in the infective process.
Intron retention and transcript chimerism conserved across mammals: Ly6g5b and Csnk2b-Ly6g5b as examples
Authors: Hernández-Torres Francisco , Rastrojo Alberto , Aguado Begoña 
Published: March 2013

Abstract

Background
Alternative splicing (AS) is a major mechanism for modulating gene expression of an organism, allowing the synthesis of several structurally and functionally distinct mRNAs and protein isoforms from a unique gene. Related to AS is the Transcription Induced Chimerism (TIC) or Tandem Chimerism, by which chimeric RNAs between adjacent genes can be found, increasing combinatorial complexity of the proteome. The Ly6g5b gene presents particular behaviours in its expression, involving an intron retention event and being capable to form RNA chimera transcripts with the upstream gene Csnk2b. We wanted to characterise these events more deeply in four tissues in six different mammals and analyse their protein products.

Results
While canonical Csnk2b isoform was widely expressed, Ly6g5b canonical isoform was less ubiquitous, although the Ly6g5b first intron retained transcript was present in all the tissues and species analysed. Csnk2b-Ly6g5b chimeras were present in all the samples analysed, but with restricted expression patterns. Some of these chimeric transcripts maintained correct structural domains from Csnk2b and Ly6g5b. Moreover, we found Csnk2b, Ly6g5b, and Csnk2b-Ly6g5b transcripts that present exon skipping, alternative 5' and 3' splice site and intron retention events. These would generate truncated or aberrant proteins whose role remains unknown. Some chimeric transcripts would encode CSNK2B proteins with an altered C-terminus, which could affect its biological function broadening its substrate specificity. Over-expression of human CSNK2B, LY6G5B, and CSNK2B-LY6G5B proteins, show different patterns of post-translational modifications and cell distribution.

Conclusions

Ly6g5b intron retention and Csnk2b-Ly6g5b transcript chimerism are broadly distributed in tissues of different mammals.
Xylem transcription profiles indicate potential metabolic responses for economically relevant characteristics of Eucalyptusspecies
Authors: Salazar Marcela Mendes , Nascimento Leandro Costa , Camargo Eduardo Leal Oliveira , Gonçalves Danieli Cristina , Neto Jorge Lepikson , Marques Wesley Leoricy , Teixeira Paulo José Pereira Lima , Mieczkowski Piotr , Mondego Jorge Maurício Costa , Carazzolle Marcelo Falsarella , Deckmann Ana Carolina , Pereira Gonçalo Amarante Guimarães 
Published: March 2013

Abstract

Background

Eucalyptus is one of the most important sources of industrial cellulose. Three species of this botanical group are intensively used in breeding programs: E. globulus, E. grandis and E. urophylla. E. globulus is adapted to subtropical/temperate areas and is considered a source of high-quality cellulose; E. grandis grows rapidly and is adapted to tropical/subtropical climates; and E. urophylla, though less productive, is considered a source of genes related to robustness. Wood, or secondary xylem, results from cambium vascular differentiation and is mostly composed of cellulose, lignin and hemicelluloses. In this study, the xylem transcriptomes of the three Eucalyptus species were investigated in order to provide insights on the particularities presented by each of these species.

Results
Data analysis showed that (1) most Eucalyptus genes are expressed in xylem; (2) most genes expressed in species-specific way constitutes genes with unknown functions and are interesting targets for future studies; (3) relevant differences were observed in the phenylpropanoid pathway: E. grandis xylem presents higher expression of genes involved in lignin formation whereas E. urophylla seems to deviates the pathway towards flavonoid formation; (4) stress-related genes are considerably more expressed in E. urophylla, suggesting that these genes may contribute to its robustness.

Conclusions
The comparison of these three transcriptomes indicates the molecular signatures underlying some of their distinct wood characteristics. This information may contribute to the understanding of xylogenesis, thus increasing the potential of genetic engineering approaches aiming at the improvement of Eucalyptus forest plantations productivity.
CbCTB2, an O-methyltransferase is essential for biosynthesis of the phytotoxin cercosporin and infection of sugar beet by Cercospora beticola
Authors: Staerkel Cornelia , Boenisch Marike J , Kröger Cathrin , Bormann Jörg , Schäfer Wilhelm , Stahl Dietmar 
Published: March 2013

Abstract

Background
Cercospora leaf spot disease, caused by the fungus Cercospora beticola, is the most destructive foliar disease of sugar beets (Beta vulgaris) worldwide. Cercosporin, a light-inducible toxin, is essential for necrosis of the leaf tissue and development of the typical leaf spots on sugar beet leaves.

Results
In this study we show that the O-methyltransferase gene CTB2 is essential for cercosporin production and pathogenicity in two C. beticola isolates. We established a transformation system for C. beticola protoplasts, disrupted CTB2, and transformed the Δctb2 strains as well as a wild type strain with the DsRed reporter gene. The Δctb2 strains had lost their pigmentation and toxin measurements demonstrated that the Δctb2 strains were defective in cercosporin production. Infection of sugar beets with the wild type and Δctb2 DsRed strains showed that the deletion strain was severely impaired in plant infection. Histological analysis revealed that the CTB2-deficient isolate cannot enter the leaf tissue through stomata like the wild type.

Conclusions
Taken together, these observations indicate that cercosporin has a dual function in sugar beet infection: in addition to the well-known role in tissue necrosis, the toxin is required for the early phase of sugar beet infection.
The combination of ANT2 shRNA and hNIS radioiodine gene therapy increases CTL cytotoxic activity through the phenotypic modulation of cancer cells: combination treatment with ANT2 shRNA and I-131
Authors: Choi Yun , Lee Ho Won , Lee Jaetae , Jeon Yong Hyun 
Published: March 2013

Abstract

Background
It is important to simultaneously induce strong cell death and antitumor immunity in cancer patients for successful cancer treatment. Here, we investigated the cytotoxic and phenotypic modulation effects of the combination of ANT2 shRNA and human sodium iodide symporter (hNIS) radioiodine gene therapy in vitro and in vivo and visualized the antitumor effects in an immunocompromised mouse colon cancer model.

Methods
A mouse colon cancer cell line co-expressing hNIS and the luciferase gene (CT26/hNIS-Fluc, named CT26/NF) was established. CT26/NF cells and tumor-bearing mice were treated with HBSS, scramble, ANT2 shRNA, I-131, and ANT2 shRNA + I-131. The apoptotic rates (%) and MHC class I and Fas gene expression levels were determined in treated CT26/NF cells using flow cytometry. Concurrently, the level of caspase-3 activation was determined in treated cells in vitro. For in vivo therapy, tumor-bearing mice were treated with scramble, ANT2 shRNA, I-131, and the combination therapy, and the anti-tumor effects were monitored using bioluminescence. The killing activity of cytotoxic T cells (CTLs) was measured with a lactate dehydrogenase (LDH) assay.

Results
For the in vitro experiments, the combination of ANT2 shRNA and I-131 resulted in a higher apoptotic cell death rate compared with ANT2 shRNA or I-131 alone, and the levels of MHC class I and Fas-expressing cancer cells were highest in the cells receiving combination treatment, while single treatment modestly increased the level of MHC class I and Fas gene expression. The combination of ANT2 shRNA and I-131 resulted in a higher caspase-3 activation than single treatments. Interestingly, in vivo combination treatment led to increased gene expression of MHC class I and Fas than the respective mono-therapies; furthermore, bioluminescence showed increased antitumor effects after combination treatment than monotherapies. The LDH assay revealed that the CTL killing activity against CT26/NF cells was most effective after combination therapy.

Conclusions
Increased cell death and phenotypic modulation of cancer cells in vitro and in vivo were achieved simultaneously after combination therapy with ANT2 shRNA and I-131, and this combination therapy induced remarkable antitumor outcomes through improvements in CTL immunity against CT26/NF. Our results suggest that combination therapy can be used as a new therapeutic strategy for cancer patients who show resistance to single therapy such as radiation or immunotherapy.
Derepression of Cancer/Testis Antigens in cancer is associated with distinct patterns of DNA Hypomethylation
Authors: Kim Robert , Kulkarni Prakash , Hannenhalli Sridhar 
Published: March 2013

Abstract

Background
The Cancer/Testis Antigens (CTAs) are a heterogeneous group of proteins whose expression is typically restricted to the testis. However, they are aberrantly expressed in most cancers that have been examined to date. Broadly speaking, the CTAs can be divided into two groups: the CTX antigens that are encoded by the X-linked genes and the non-X CT antigens that are encoded by the autosomes. Unlike the non-X CTAs, the CTX antigens form clusters of closely related gene families and their expression is frequently associated with advanced disease with poorer prognosis. Regardless however, the mechanism(s) underlying their selective derepression and stage-specific expression in cancer remain poorly understood, although promoter DNA demethylation is believed to be the major driver.

Methods
Here, we report a systematic analysis of DNA methylation profiling data from various tissue types to elucidate the mechanism underlying the derepression of the CTAs in cancer. We analyzed the methylation profiles of 501 samples including sperm, several cancer types, and their corresponding normal somatic tissue types.

Results
We found strong evidence for specific DNA hypomethylation of CTA promoters in the testis and cancer cells but not in their normal somatic counterparts. We also found that hypomethylation was clustered on the genome into domains that coincided with nuclear lamina-associated domains (LADs) and that these regions appeared to be insulated by CTCF sites. Interestingly, we did not observe any significant differences in the hypomethylation pattern between the CTAs without CpG islands and the CTAs with CpG islands in the proximal promoter.

Conclusion
Our results corroborate that widespread DNA hypomethylation appears to be the driver in the derepression of CTA expression in cancer and furthermore, demonstrate that these hypomethylated domains are associated with the nuclear lamina-associated domains (LADS). Taken together, our results suggest that wide-spread methylation changes in cancer are linked to derepression of germ-line-specific genes that is orchestrated by the three dimensional organization of the cancer genome.
Psychometric behaviour of the strengths and difficulties questionnaire (SDQ) in the Spanish national health survey 2006
Authors: Gómez-Beneyto Manuel , Nolasco Andreu , Moncho Joaquín , Pereyra-Zamora Pamela , Tamayo-Fonseca Nayara , Munarriz Mikel , Salazar José , Tabarés-Seisdedos Rafael , Girón Manuel 
Published: March 2013

Abstract

Background
The Strengths and Difficulties Questionnaire (SDQ) is a tool to measure the risk for mental disorders in children. The aim of this study is to describe the diagnostic efficiency and internal structure of the SDQ in the sample of children studied in the Spanish National Health Survey 2006.

Methods
A representative sample of 6,773 children aged 4 to 15 years was studied. The data were obtained using the Minors Questionnaire in the Spanish National Health Survey 2006. The ROC curve was constructed and calculations made of the area under the curve, sensitivity, specificity and the Youden J indices. The factorial structure was studied using models of exploratory factorial analysis (EFA) and confirmatory factorial analysis (CFA).

Results
The prevalence of behavioural disorders varied between 0.47% and 1.18% according to the requisites of the diagnostic definition. The area under the ROC curve varied from 0.84 to 0.91 according to the diagnosis. Factor models were cross-validated by means of two different random subsamples for EFA and CFA. An EFA suggested a three correlated factor model. CFA confirmed this model. A five-factor model according to EFA and the theoretical five-factor model described in the bibliography were also confirmed. The reliabilities of the factors of the different models were acceptable (>0.70, except for one factor with reliability 0.62).

Conclusions
The diagnostic behaviour of the SDQ in the Spanish population is within the working limits described in other countries. According to the results obtained in this study, the diagnostic efficiency of the questionnaire is adequate to identify probable cases of psychiatric disorders in low prevalence populations. Regarding the factorial structure we found that both the five and the three factor models fit the data with acceptable goodness of fit indexes, the latter including an externalization and internalization dimension and perhaps a meaningful positive social dimension.
Accordingly, we recommend studying whether these differences depend on sociocultural factors or are, in fact, due to methodological questions.
Compliance, persistence, costs and quality of life in young patients treated with antipsychotic drugs: results from the COMETA study
Authors: Cortesi Paolo A , Mencacci Claudio , Luigi Ferrannini , Pirfo Elvezio , Berto Patrizia , Sturkenboom Miriam CJM , Lopes Fabiana L , Giustra Maria G , Mantovani Lorenzo G , Scalone Luciana 
Published: March 2013

Abstract

Background
Little data is available on the real-world socio-economic burden and outcomes in schizophrenia. This study aimed to assess persistence, compliance, costs and Health-Related Quality-of-Life (HRQoL) in young patients undergoing antipsychotic treatment according to clinical practice.

Methods
A naturalistic, longitudinal, multicentre cohort study was conducted: we involved 637 patients aged 18–40 years, with schizophrenia or schizophreniform disorder diagnosed ≤10 years before, enrolled in 86 Italian Mental Health Centres and followed-up for 1 year. Comparisons were conducted between naïve (i.e., patients visiting the centre for the first time and starting a new treatment regimen) and non naïve patients.

Results
At enrolment, 84% of patients were taking atypical drugs, 3.7% typical, 10% a combination of the two classes, and 2% were untreated. During follow-up, 23% of patients switched at least once to a different class of treatment, a combination or no treatment. The mean Drug-Attitude-Inventory score was 43.4, with 94.3% of the patients considered compliant by the clinicians. On average, medical costs at baseline were 390.93€/patient-month, mostly for drug treatment (29.5%), psychotherapy (29.2%), and hospitalizations (27.1%). Patients and caregivers lost 3.5 days/patient-month of productivity. During follow-up, attitude toward treatment remained fairly similar, medical costs were generally stable, while productivity, clinical statusand HRQoL significantly improved. While no significantly different overall direct costs trends were found between naïve and non naïve patients, naïve patients showed generally a significant mean higher improvement of clinical outcomes, HRQoL and indirect costs, compared to the others.

Conclusions
Our results suggest how tailoring the treatment strategy according to the complex and specific patient needs make it possible to achieve benefits and to allocate more efficiently resources. This study can also provide information on the most relevant items to be considered when conducting cost-effectiveness studies comparing specific alternatives for the treatment of target patients.