bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential MicroRNA Expression in Experimental Cerebral and Noncerebral Malaria
Authors: El-Assaad Fatima , Hempel Casper , Combes Valéry , Mitchell Andrew J. , Ball Helen J. , Kurtzhals Jørgen A. L. , Hunt Nicholas H. , Mathys Jean-Marie , Grau Georges E. R. 
Published: March 2011

ABSTRACTMicroRNAs (miRNAs) are posttranscriptional regulatory molecules that have been implicated in the regulation of immune responses, but their role in the immune response toPlasmodiuminfection is unknown. We studied the expression of selected miRNAs following infection of CBA mice withPlasmodium bergheiANKA (PbA), which causes cerebral malaria (CM), orPlasmodium bergheiK173 (PbK), which causes severe malaria but without cerebral complications, termed non-CM. The differential expression profiles of selected miRNAs (let-7i, miR-27a, miR-150, miR-126, miR-210, and miR-155) were analyzed in mouse brain and heart tissue by quantitative reverse transcription-PCR (qRT-PCR). We identified three miRNAs that were differentially expressed in the brain of PbA-infected CBA mice: let7i, miR-27a, and miR-150. In contrast, no miRNA changes were detected in the heart, an organ with no known pathology during acute malaria. To investigate the involvement of let-7i, miR-27a, and miR-150 in CM-resistant mice, we assessed the expression levels in gamma interferon knockout (IFN-γ−/−) mice on a C57BL/6 genetic background. The expression of let-7i, miR-27a, and miR-150 was unchanged in both wild-type (WT) and IFN-γ−/−mice following infection. Overexpression of these three miRNAs during PbA, but not PbK, infection in WT mice may be critical for the triggering of the neurological syndrome via regulation of their potential downstream targets. Our data suggest that in the CBA mouse at least, miRNA may have a regulatory role in the pathogenesis of severe malaria.
SpyA, a C3-Like ADP-Ribosyltransferase, Contributes to Virulence in a Mouse Subcutaneous Model of Streptococcus pyogenes Infection
Authors: Hoff Jessica S. , DeWald Mark , Moseley Steve L. , Collins Carleen M. , Voyich Jovanka M. 
Published: March 2011

ABSTRACTStreptococcus pyogenesis an important human pathogen with an expansive repertoire of verified and putative virulence factors. Here we demonstrate that a mutant deficient in the production of the streptococcal ADP-ribosyltransferase SpyA generates lesions of reduced size in a subcutaneous mouse infection model. At early stages of infection, when the difference in lesion size is first established, inflamed tissue isolated from lesions of mice infected withspyAmutant bacteria has higher levels of mRNA encoding the chemokines CXCL1 and CCL2 than does tissue isolated from mice infected with wild-type bacteria. In addition, at these early times, the mRNA levels for the gene encoding the intermediate filament vimentin are higher in the mutant-infected tissue. As wound resolution progresses, mRNA levels of the gene encoding matrix metallopeptidase 2 are lower in mutant-infected tissue. Furthermore, we demonstrate that thespyAmutant is internalized more efficiently than wild-type bacteria by HeLa cells. We conclude that SpyA contributes to streptococcal pathogenesis in the mouse subcutaneous infection model. Our observations suggest that the presence of SpyA delays wound healing in this model.
Lcl of Legionella pneumophila Is an Immunogenic GAG Binding Adhesin That Promotes Interactions with Lung Epithelial Cells and Plays a Crucial Role in Biofilm Formation
Authors: Duncan Carla , Prashar Akriti , So Jannice , Tang Patrick , Low Donald E. , Terebiznik Mauricio , Guyard Cyril 
Published: March 2011

ABSTRACTLegionellosis is mostly caused byLegionella pneumophilaand is defined by a severe respiratory illness with a case fatality rate ranging from 5 to 80%.In vitroandin vivo, interactions ofL. pneumophilawith lung epithelial cells are mediated by the sulfated glycosaminoglycans (GAGs) of the host extracellular matrix. In this study, we have identified severalLegionellaheparin binding proteins. We have shown that one of these proteins, designated Lcl, is a polymorphic adhesin ofL. pneumophilathat is produced during legionellosis. Homologues of Lcl are ubiquitous inL. pneumophilaserogroups but are undetected in otherLegionellaspecies. Recombinant Lcl binds to GAGs, and a Δlpg2644mutant demonstrated reduced binding to GAGs and human lung epithelial cells. Importantly, we showed that the Δlpg2644strain is dramatically impaired in biofilm formation. These data delineate the role of Lcl in the GAG binding properties ofL. pneumophilaand provide molecular evidence regarding its role inL. pneumophilaadherence and biofilm formation.
CD4+T Cells Mediate the Protective Effect of the Recombinant Asp f3-Based Anti-Aspergillosis Vaccine
Authors: Diaz-Arevalo Diana , Bagramyan Karine , Hong Teresa B. , Ito James I. , Kalkum Markus 
Published: March 2011

ABSTRACTThe mortality and morbidity caused by invasive aspergillosis present a major obstacle to the successful treatment of blood cancers with hematopoietic cell transplants. Patients who receive hematopoietic cell transplants are usually immunosuppressed for extended periods, and infection with the ubiquitous moldAspergillus fumigatusis responsible for most cases of aspergillosis. Previously, we demonstrated that vaccination with recombinant forms of theA. fumigatusprotein Asp f3 protected cortisone acetate-immunosuppressed mice from experimentally induced pulmonary aspergillosis. Here, we investigated the vaccine's protective mechanism and evaluated in particular the roles of antibodies and T cells. After vaccination, Asp f3-specific preinfection IgG titers did not significantly differ between surviving and nonsurviving mice, and passive transfer of anti-Asp f3 antibodies did not protect immunosuppressed recipients from aspergillosis. We experimentally confirmed Asp f3's predicted peroxisomal localization inA. fumigatushyphae. We found that fungal Asp f3 is inaccessible to antibodies, unless both cell walls and membranes have been permeabilized. Antibody-induced depletion of CD4+T cells reduced the survival of recombinant Asp f3 (rAsp f3)-vaccinated mice to nonimmune levels, and transplantation of purified CD4+T cells from rAsp f3-vaccinated mice into nonimmunized recipients transferred antifungal protection. In addition, residues 60 to 79 and 75 to 94 of Asp f3 contain epitopes that induce proliferation of T cells from vaccinated survivors. Vaccine-primed CD4+T cells are not expected to clear the fungal pathogen directly; however, they may locally activate immunosuppressed phagocytes that elicit the antifungal effect.
Methodological Issues in Evaluating Auricular Acupuncture Therapy for Problems Arising from the Use of Drugs and Alcohol
Authors: Cowan David 
Published: March 2011

Auricular acupuncture is an accessible, non-confrontational therapy that appears to be effective when used in drug and alcohol treatment facilities, hospitals and prisons in the UK, Europe and the USA. Despite being popular, research evidence on its effectiveness is lacking, and as a result services are underfunded and risk being withdrawn. There are methodological problems in researching auricular acupuncture. In these days of evidence-based medicine, most studies in this area are explanatory randomised controlled trials, which is limited in capturing the complete benefits of the intervention. Furthermore, there is lack of consensus over definitions of the concept of ‘addiction’ and whether or not this should be perceived as a ‘disease’ that can be ‘cured’ by an intervention such as auricular acupuncture. Basic concepts such as these need to inform development of outcome measures, which should include retention of clients in treatment as an indicator of success. It is argued here that the best approach will integrate research on physical effects with research on subjective experience of those with drug and alcohol problems. The challenge is to design large scale, high quality, pragmatic randomised controlled trials to assess the effectiveness of auricular acupuncture over the longer term in settings that mimic the delivery of treatment in practice and are informed by acupuncture's own diagnostic traditions, using a combination of objective, quantitative methods and subjective, qualitative methods.
Inter-endoscopist agreement in diagnosis of Barrett's oesophagus
Authors: Doherty Glen A , Cheriyan Danny G , Leyden Jan E , O'Dowd John F , Murray Frank E , Patchett Stephen E 
Published: March 2011

ObjectiveTo assess how interpretation of abnormalities at the oesophago-gastric junction (OGJ) when making a diagnosis of Barrett's oesophagus (BO) varies between endoscopists and to examine the impact of the endoscopy experience on these decisions.Design/settingMembers of the Irish Society of Gastroenterology who regularly perform gastroscopy were invited to participate in a web based image assessment study.InterventionsQuestions were posed to ascertain level of endoscopy experience, and participants were asked to indicate the presence or absence of BO in 12 endoscopic images of the OGJ.Outcome measuresPrimary outcome was overall level of agreement in responses and relationship to endoscopy experience.ResultsThe responses of 65 clinicians regularly performing gastroscopy were analysed. In 3/12 images, showing typical long segment BO, there was a strong consensus on the endoscopic diagnosis (>95% agreement). However, agreement was fair to poor (κ for multiple raters, 0.31) on the presence or absence of short BO segments at endoscopy. Minimal differences were observed between experienced endoscopists (individuals with >10 years' endoscopy experience) and less experienced counterparts in the threshold for BO diagnosis. Inter-endoscopist agreement overall was not significantly better within the more experienced group.ConclusionThe study demonstrates low interobserver agreement in endoscopic diagnosis of (short segment) BO, even among experienced endoscopists. Given the costs associated with endoscopic surveillance of BO, prompt efforts to promote consensus diagnosis and improve agreement are required as an important quality improvement measure in this area.
Observed use of tethers in forward-facing child restraint systems
Authors: Jermakian Jessica S , Wells JoAnn K 
Published: March 2011

BackgroundUse of top tethers with forward-facing child restraints is a simple way for parents to keep their children safer when travelling in passenger vehicles, but tether use remains low.ObjectivesTo obtain an updated estimate of top tether use.MethodsData on forward-facing child restraints were collected through an observational survey in the Washington DC metropolitan area during July–August 2010. The study sample included all forward-facing restraints that were installed in parked passenger vehicles and visible such that tether use could be observed. For each restraint, certified child passenger safety technicians collected information on the vehicle, seat row, restraint position, and tether.ResultsA total of 1321 cars, minivans, pickups, and sport utility vehicles, with a total of 1543 forward-facing child restraints, were observed. Tethers were used with 43.0% of all forward-facing child restraints. Tether use was similar (42.7–45.4%) among cars, minivans, and sport utility vehicles but lower (17.2%) for pickups. Tether use was higher (47.5%) for 2001 and newer vehicles, but dropped to 43.0% when only taut installations were considered.ConclusionsDespite LATCH education campaigns and the increased availability of tether anchors, observed tether use was less than 50%. Tether use was even lower in older vehicles, yet many children continue to travel in these vehicles. If tether anchors are unavailable, parents should be encouraged to retrofit vehicle seating positions. Because many child restraints are still installed with vehicle seat belts, efforts to educate parents on the importance of tether use regardless of installation method may be warranted.
The reference interval of thyroid-stimulating hormone in Hong Kong Chinese
Authors: Chan Angel O K , Iu Y P , Shek C C 
Published: March 2011

AimThe upper reference limit of thyroid-stimulating hormone (TSH) is critical for defining patients with subclinical hypothyroidism, a condition which carries a higher risk of progression to overt hypothyroidism and adverse cardiovascular events. Yet, there is a lack of consensus on its absolute value, and data in non-pregnant adult Chinese are lacking.MethodsApparently healthy and drug-free local adult Chinese were recruited by completing health questionnaires. Their serum samples were tested for TSH, free thyroxine (FT4), thyroglobulin antibody and thyroid peroxidase antibody levels. After excluding subjects with thyroid antibodies, the TSH level was log-transformed, and the reference limits were defined as mean±1.96SD. The 2.5th and 97.5th percentiles of FT4 were also calculated.ResultsSerum samples from 212 subjects were used in this study. 51 subjects were seropositive to thyroglobulin antibody, 31 were seropositive to thyroid peroxidase antibody, and 27 were seropositive to both. The reference intervals after excluding subjects seropositive to thyroid antibodies were: TSH: 0.68–3.70 mIU/l; FT4: 13.5–21.3 pmol/l (male) and 12.6–19.7 pmol/l (female). Including subjects with thyroid antibodies only minimally changed the reference intervals of these hormones.ConclusionThe authors have set up the reference interval of TSH for the local population, and their findings also suggest that the importance of excluding subjects with thyroid antibodies in the reference population should not be overemphasised. Moreover, the international authorities should consider recommending percentile-equivalent action limits instead of an absolute cut-off on TSH for categorisation of different types of thyroid dysfunction.
Risk factors for chlamydial infection in chlamydia contacts: a questionnaire-based study
Authors: Schembri Gabriel , Schober Paul 
Published: March 2011

Background and methodologyTreatment of individuals with chlamydial infection and their sexual partners is an important aspect of reproductive health care. Partners of infected individuals are currently offered ‘epidemiological treatment’, which means that they are offered antibiotic treatment at their first visit without waiting for the result of their chlamydia test. We carried out a study to identify the risk factors for chlamydial infection in partners of infected individuals. Individuals attending a genitourinary clinic as chlamydia contacts were identified and asked to complete a questionnaire about their relationship with the index case and their prior sexual history. The result of their chlamydia test was then analysed against those variables.ResultsA total of 115 chlamydia contacts were analysed in this study; 60 (52%) were found to be positive for chlamydial infection. In a multivariate analysis, young age, more than one episode of sexual intercourse with the infected partner and a greater total number of sexual partners were associated with a positive chlamydia result. A prediction model for chlamydial infection using these risk factors had a discriminatory ability quantified by an area under the curve (AUC) of 0.76 (95% CI 0.66–0.85).Discussion and conclusionsThe risk factors identified can be used when discussing epidemiological treatment with individuals who attend sexual health services as chlamydia contacts, or to target clinic resources to a higher-risk group. Larger studies will be necessary to assess the benefits and risks of changing to a policy of offering epidemiologic treatment to ‘high-risk’ contacts only, identified using a predictive model such as the one described here.
Women in Cairo, Egypt and their risk factors for unmet contraceptive need: a community-based study
Authors: Kotb Mohammed Mahmoud , Bakr Iman , Ismail Nanees A , Arafa Naglaa , El-Gewaily Mohamed 
Published: March 2011

Background and methodologyAlthough modern family planning methods are readily available in Egypt at low cost, a considerable proportion of women still have an unmet contraceptive need. The aim of this study was to detect the risk factors of unmet contraceptive need among married women in the childbearing period in an underprivileged area in Cairo with high population density. A survey of 2340 women in the Marg district of Eastern Cairo was conducted by means of home interviews. For every woman identified as having an unmet contraceptive need (n=174), the next two women identified with met contraceptive need were selected as controls (n=348).ResultsThe prevalence of unmet need was 7.4%. Risk factors identified were: belief that contraception is religiously prohibited (OR 2.08, 95% CI 1.06–4.09); poor interspousal communication about the desired number of children (OR 2.59, 95% CI 1.40–4.79); husband opposition to contraceptive use (OR 2.96, 95% CI 1.47–5.97); a previous history of unwanted pregnancy (OR 2.98, 95% CI 1.73–5.14); and experiencing side effects from previous contraceptive use (OR 5.69, 95% CI 3.46–9.37).ConclusionsThe authors propose training physicians to identify and counsel women who experience contraceptive side effects and/or a previous unwanted pregnancy, as well as the transmission of clear media messages on the religious acceptability of contraceptive use.
Assessment of feline blood for transfusion purposes in the Dublin area of Ireland
Authors: Juvet F. , Brennan S. , Mooney C. T. 
Published: March 2011

The prevalence of A, B and AB blood types and of feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) infection was determined in cats in Ireland, in order to determine risk factors for blood taken for transfusion purposes. EDTA blood samples were available from 137 non‐pedigree cats and 39 pedigree cats (91 females and 85 males, aged four months to 15.0 years) in the Dublin area of Ireland. Of the 176 EDTA blood samples obtained, 112 (from 92 healthy cats and 20 sick cats) were tested for the presence of both FIV antibodies and FeLV antigens. Blood typing was performed using an immunochromatographic cartridge (CHROM; Alvedia). Testing for FIV and FeLV was performed by ELISA (SNAP FIV/FeLV Combo Test; Idexx Laboratories). Of the 39 pedigree cats, the majority (38 [97.4 per cent]) was type A, and only one (2.6 per cent) was type B. Of the 137 non‐pedigree cats, the majority (116 [84.7 per cent]) was type A, 20 (14.6 per cent) were type B, and one (0.7 per cent) was type AB. Of the 92 healthy cats tested, the prevalence of FIV and FeLV positivity was 4.35 and 1.09 per cent, respectively. None of the 20 sick cats tested was FIV‐positive; two (10 per cent) of the 20 sick cats were FeLV‐positive.
USING RULE STRUCTURE TO EVALUATE THE COMPLETENESS OF RULE-BASED SYSTEM TESTING: A CASE STUDY
Authors: MEDDERS STEPHEN C. , ALLEN EDWARD B. , LUKE EDWARD A. 
Published: March 2011

Rule-based systems are typically tested using a set of inputs which will produce known outputs. However, one does not know how thoroughly the software has been exercised. Traditional test-coverage metrics do not account for the dynamic data-driven flow of control in rule-based systems. Our literature review found that there has been little prior work on coverage metrics for rule-based systems. This paper proposes test-coverage metrics for rule-based systems derived from metrics defined by prior work, and presents an industrial scale case study. We conducted a case study to evaluate the practicality and usefulness of the proposed metrics. The case study applied the metrics to a system for computational fluid-dynamics models based on a rule-based application framework. These models were tested using a regression-test suite. The data-flow structure built by the application framework, along with the regression-test suite, provided case-study data. The test suite was evaluated against three kinds of coverage. The measurements indicated that complete coverage was not achieved, even at the lowest level definition. Lists of rules not covered provided insight into how to improve the test suite. The case study illustrated that structural coverage measures can be utilized to measure the completeness of rule-based system testing.
Matters of design, part II
Authors: Hong Jason 
Published: March 2011

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Jason Hong discusses how Apple creates well-designed products and what the human-computer interaction community can learn from its methods.
Metformin Induces Both Caspase-Dependent and Poly(ADP-ribose) Polymerase-Dependent Cell Death in Breast Cancer Cells
Authors: Zhuang Yongxian , Miskimins W. Keith 
Published: March 2011

Abstract
There is substantial evidence that metformin, a drug used to treat type 2 diabetics, is potentially useful as a therapeutic agent for cancer. However, a better understanding of the molecular mechanisms through which metformin promotes cell-cycle arrest and cell death of cancer cells is necessary. It will also be important to understand how the response of tumor cells differs from normal cells and why some tumor cells are resistant to the effects of metformin. We have found that exposure to metformin induces cell death in all but one line, MDA-MB-231, in a panel of breast cancer cell lines. MCF10A nontransformed breast epithelial cells were resistant to the cytotoxic effects of metformin, even after extended exposure to the drug. In sensitive lines, cell death was mediated by both apoptosis and a caspase-independent mechanism. The caspase-independent pathway involves activation of poly(ADP-ribose) polymerase (PARP) and correlates with enhanced synthesis of PARP and nuclear translocation of apoptosis-inducing factor (AIF), which plays an important role in mediating cell death. Metformin-induced, PARP-dependent cell death is associated with a striking enlargement of mitochondria. Mitochondrial enlargement was observed in all sensitive breast cancer cell lines but not in nontransformed cells or resistant MDA-MB-231. Mitochondrial enlargement was prevented by inhibiting PARP activity or expression. A caspase inhibitor blocked metformin-induced apoptosis but did not affect PARP-dependent cell death or mitochondrial enlargement. Thus, metformin has cytotoxic effects on breast cancer cells through 2 independent pathways. These findings will be pertinent to efforts directed at using metformin or related compounds for cancer therapy. Mol Cancer Res; 9(5); 603–15. ©2011 AACR.