bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of GAMA, a Plasmodium falciparum Merozoite Micronemal Protein, as a Novel Blood-Stage Vaccine Candidate Antigen
Authors: Arumugam Thangavelu U. , Takeo Satoru , Yamasaki Tsutomu , Thonkukiatkul Amporn , Miura Kazutoyo , Otsuki Hitoshi , Zhou Hong , Long Carole A. , Sattabongkot Jetsumon , Thompson Jennifer , Wilson Danny W. , Beeson James G. , Healer Julie , Crabb Brendan S. , Cowman Alan F. , Torii Motomi , Tsuboi Takafumi 
Published: September 2011

ABSTRACT

One of the solutions for reducing the global mortality and morbidity due to malaria is multivalent vaccines comprising antigens of several life cycle stages of the malarial parasite. Hence, there is a need for supplementing the current set of malaria vaccine candidate antigens. Here, we aimed to characterize glycosylphosphatidylinositol (GPI)-anchored micronemal antigen (GAMA) encoded by the PF08_0008 gene in
Plasmodium falciparum
. Antibodies were raised against recombinant GAMA synthesized by using a wheat germ cell-free system. Immunoelectron microscopy demonstrated for the first time that GAMA is a microneme protein of the merozoite. Erythrocyte binding assays revealed that GAMA possesses an erythrocyte binding epitope in the C-terminal region and it binds a nonsialylated protein receptor on human erythrocytes. Growth inhibition assays revealed that anti-GAMA antibodies can inhibit
P. falciparum
invasion in a dose-dependent manner and GAMA plays a role in the sialic acid (SA)-independent invasion pathway. Anti-GAMA antibodies in combination with anti-erythrocyte binding antigen 175 exhibited a significantly higher level of invasion inhibition, supporting the rationale that targeting of both SA-dependent and SA-independent ligands/pathways is better than targeting either of them alone. Human sera collected from areas of malaria endemicity in Mali and Thailand recognized GAMA. Since GAMA in
P. falciparum
is refractory to gene knockout attempts, it is essential to parasite invasion. Overall, our study indicates that GAMA is a novel blood-stage vaccine candidate antigen.
Conserved Mutations in the Pneumococcal Bacteriocin Transporter Gene,
blpA
, Result in a Complex Population Consisting of Producers and Cheaters
Authors: Son Matthew R. , Shchepetov Mikhail , Adrian Peter V. , Madhi Shabir A. , de Gouveia Linda , von Gottberg Anne , Klugman Keith P. , Weiser Jeffrey N. , Dawid Suzanne 
Published: September 2011

ABSTRACT

All fully sequenced strains of
Streptococcus pneumoniae
possess a version of the
blp
locus, which is responsible for bacteriocin production and immunity. Activation of the
blp
locus is stimulated by accumulation of the peptide pheromone, BlpC, following its secretion by the ABC transporter, BlpA. The
blp
locus is characterized by significant diversity in
blpC
type and in the region of the locus containing putative bacteriocin and immunity genes. In addition, the
blpA
gene can represent a single large open reading frame or be divided into several smaller fragments due to the presence of frameshift mutations. In this study, we use a collection of strains with
blp
-dependent inhibition and immunity to define the genetic changes that bring about phenotypic differences in bacteriocin production or immunity. We demonstrate that alterations in
blpA
,
blpC
, and bacteriocin/immunity content likely play an important role in competitive interactions between pneumococcal strains. Importantly, strains with a highly conserved frameshift mutation in
blpA
are unable to secrete bacteriocins or BlpC, but retain the ability to respond to exogenous peptide pheromone produced by cocolonizing strains, stimulating
blp
-mediated immunity. These “cheater” strains can only coexist with bacteriocin-producing strains that secrete their cognate BlpC and share the same immunity proteins. The variable outcome of these interactions helps to explain the heterogeneity of the
blp
pheromone, bacteriocin, and immunity protein content.

IMPORTANCE
Streptococcus pneumoniae
resides in a polymicrobial environment and competes for limited resources by the elaboration of small antimicrobial peptides called bacteriocins. A conserved cluster of genes in the
S. pneumoniae
genome is involved in the production of bacteriocins and their associated protective immunity proteins through secretion of a signaling pheromone. In this study, we show that a significant number of strains have lost the ability to secrete bacteriocins and signaling pheromones due to a specific mutation in a dedicated transporter protein. Because the regulatory and immunity portion of the locus is retained, these “cheater” strains can survive in the face of invasion from a bacteriocin-producing strain without the cost of bacteriocin secretion. The outcome of such interactions depends on each strain’s repertoire of pheromone, immunity protein, and bacteriocin genes, such that intrastrain competition drives the diversity in bacteriocin, immunity protein, and pheromone content.
Passive smoking and chronic obstructive pulmonary disease: cross-sectional analysis of data from the Health Survey for England
Authors: Jordan Rachel E , Cheng Kar Keung , Miller Martin R , Adab Peymané 
Published: September 2011

ObjectivesThere is increasing evidence that passive smoking is associated with chronic respiratory diseases, but its association with chronic obstructive pulmonary disease (COPD) requires more study. In this cross-sectional analysis of data from 3 years of the Health Survey for England, the association between passive smoking exposure and risk of COPD is evaluated.DesignCross-sectional analysis of the 1995, 1996 and 2001 Health Surveys for England including participants of white ethnicity, aged 40+ years with valid lung function data. COPD was defined using the lower limit of normal spirometric criteria for airflow obstruction. Standardised questions elicited self-reported information on demography, smoking history, ethnicity, occupation, asthma and respiratory symptoms (dyspnoea, chronic cough, chronic phlegm, wheeze). Passive smoking was measured by self-report of hours of exposure to cigarette smoke per week.ResultsIncreasing passive smoke exposure was independently associated with increased risk of COPD, with adjusted OR 1.05 (95% CI 0.93 to 1.18) for 1–19 h and OR 1.18 (95% CI 1.01 to 1.39) for 20 or more hours of exposure per week. Similar patterns (although attenuated and non-significant) were observed among never smokers. More marked dose–response relationships were observed between passive smoking exposure and respiratory symptoms, but the most marked effects were on the development of clinically significant COPD (airflow obstruction plus symptoms), where the risk among never smokers was doubled (OR 1.98 (95% CI 1.03 to 3.79)) if exposure exceeded 20 h/week.ConclusionThis analysis adds weight to the evidence suggesting an association between passive smoking exposure and COPD.
Open versus closed IV infusion systems: a state based model to predict risk of catheter associated blood stream infections
Authors: Graves Nicholas , Barnett Adrian G , Rosenthal Victor D 
Published: September 2011

ObjectivesTo quantify the change in risk of central line associated blood stream infection (CLABSI) following the introduction of a closed infusion container in intensive care units (ICUs) in two Latin American cities.DesignA state-space model was used to describe the flow of admissions through the ICU. This approach correctly treats infection as a time-dependent covariate.ResultsA closed system reduced the risk of CLABSI. The hazard ratios for the closed versus open container were between 0.15 and 0.31 (p values<0.001), indicating a clinically significant reduction in the risk of admissions having a CLABSI. A simulation study showed that a closed system reduced the number of infections, costs and deaths.ConclusionsThe data reveal costs are saved and health benefits gained from fewer cases of CLABSI after adoption of a closed infusion system. Information is required on the costs of implementing the closed system widely in these settings.
Development of a primary care physician task list to evaluate clinic visit workflow: Table 1
Authors: Wetterneck Tosha B , Lapin Jamie A , Krueger Daniel J , Holman G Talley , Beasley John W , Karsh Ben-Tzion 
Published: September 2011

BackgroundInterventions designed to improve the delivery of primary care, including Patient-Centered Medical Homes and electronic health records, require an understanding of clinical workflow to be successfully implemented. However, there is a lack of tools to describe and study primary care physician workflow. We developed a comprehensive list of primary care physician tasks that occur during a face-to-face patient visit.MethodsA validated list of tasks performed by primary care physicians during patient clinic visits was developed from a secondary data analysis of observation data from two studies evaluating primary care workflow. Thirty primary care physicians participated from a convenience sample of 17 internal medicine and family medicine clinics in Wisconsin and Iowa across rural and urban settings and community and academic settings.ResultsThe final task list has 12 major tasks, 189 subtasks, and 191 total tasks. The major tasks are: Enter Room, Gather Information from Patient, Review Patient Information, Document Patient Information, Perform, Recommend / Discuss Treatment Options, Look Up, Order, Communicate, Print / Give Patient (advice, instructions), Appointment Wrap-up, and Leave Room. Additional subcodes note use of paper or EHR and the presence of a caregiver or medical student.ConclusionsThe task list presented here is a tool that will help clinics study their workflows so they can plan for changes that will take place because of EHR implementation and/or transformation to a patient centered medical home.
Tandem mass spectrometry findings at autopsy for detection of metabolic disease in infant deaths: postmortem changes and confounding factors
Authors: Pryce J W , Weber M A , Heales S , Malone M , Sebire N J 
Published: September 2011

AimTandem mass spectrometry (MS/MS) is a recommended investigation for sudden unexpected death in infancy (SUDI), but there are limited data regarding yield and potential influencing factors. This study investigates postmortem acylcarnitine profiles in a large cohort of infant deaths from a single centre, including those with metabolic disease.MethodsAcylcarnitine results obtained by MS/MS from routine blood/bile spot samples during the standard autopsy investigation were identified from infant deaths over a 14-year period. Results were categorised as normal or abnormal according to the clinical report by a specialist paediatric biochemist. Possible interdependent variables were assessed, multiple linear regression models were constructed and residual comparison was undertaken.Results397 blood and 268 bile MS/MS results were identified from infant cases, including 255 matched blood–bile pairs. There was significant association between blood acylcarnitine findings and postmortem interval (PMI), body mass index and liver weight. A probable cause of death was identified in 40% of sudden death cases, including 18 (2%) with a definite or highly likely cause of death as underlying metabolic disease; this represented 12 (12%) unexpected deaths in the first week of life and six (<1%) aged 7–365 days. Fatty acid oxidation disorders identified included very long chain acyl-CoA dehydrogenase deficiency, medium chain acyl-CoA dehydrogenase deficiency and carnitine transporter defects.ConclusionPostmortem blood and bile acylcarnitine profiles are influenced by several variables, and PMI can influence MS/MS acylcarnitine results. Metabolic disease may present as SUDI and may be identified from postmortem samples.
Autoantibodies to Mesothelin in Infertility
Authors: Luborsky Judith L. , Yu Yi , Edassery Seby L. , Jaffar Jade , Yip Yuan Yee , Liu Pu , Hellstrom Karl Eric , Hellstrom Ingegerd 
Published: September 2011

Abstract
Background: According to extensive epidemiologic data, infertility is associated with increased ovarian cancer risk. Previous studies showed that both women with infertility and those with ovarian cancer have autoantibodies to ovarian antigens. The objective was to determine if women with infertility have antibodies to mesothelin, a well-characterized ovarian cancer antigen.
Methods: Sera were obtained from women with infertility (n = 109), ovarian cancer (n = 28), benign ovarian tumors or cysts (n = 24), and from healthy women (n = 152). Infertility included those with a risk for ovarian cancer; endometriosis (n = 23), ovulatory dysfunction (n = 17), premature ovarian failure (POF; n = 25) and unexplained infertility (n = 44). Sera were assayed for mesothelin antibodies and for circulating mesothelin antigen by immunoassay and compared with assay control sera (n = 16) to determine a positive result.
Results: Mesothelin antibodies were significantly more frequent in women with prematurely reduced ovarian function including ovulatory dysfunction (59%), ovarian failure (44%) and unexplained infertility (25%) compared with controls. In contrast, women with endometriosis, who also have a high risk for ovarian cancer, did not have mesothelin antibodies. Serum levels of mesothelin were rarely elevated in women with infertility but were high in most patients with ovarian cancer.
Conclusions and Impact: We show for the first time that antibodies to mesothelin, a well-characterized ovarian cancer antigen, occur in some women with epidemiologic risk for ovarian cancer. The results suggest it may be possible to identify which women with infertility have ovarian cancer risk. Cancer Epidemiol Biomarkers Prev; 20(9); 1970–8. ©2011 AACR.
Evaluation of Multiplexed Cytokine and Inflammation Marker Measurements: a Methodologic Study
Authors: Chaturvedi Anil K. , Kemp Troy J. , Pfeiffer Ruth M. , Biancotto Angelique , Williams Marcus , Munuo Stella , Purdue Mark P. , Hsing Ann W. , Pinto Ligia , McCoy J. Philip , Hildesheim Allan 
Published: September 2011

AbstractBackground: Chronic inflammation is etiologically related to several cancers. We evaluated the performance [ability to detect concentrations above the assay's lower limit of detection, coefficients of variation (CV), and intraclass correlation coefficients (ICC)] of 116 inflammation, immune, and metabolic markers across two Luminex bead–based commercial kits and three specimen types.Methods: From 100 cancer-free participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Trial, serum, heparin plasma, and EDTA plasma samples were utilized. We measured levels of 67 and 97 markers using Bio-Rad and Millipore kits, respectively. Reproducibility was assessed using 40 blinded duplicates (20 within-batches and 20 across-batches) for each specimen type.Results: A majority of markers were detectable in more than 25% of individuals on all specimen types/kits. Of the 67 Bio-Rad markers, 51, 52, and 47 markers in serum, heparin plasma, and EDTA plasma, respectively, had across-batch CVs of less than 20%. Likewise, of 97 Millipore markers, 75, 69, and 78 markers in serum, heparin plasma, and EDTA plasma, respectively, had across-batch CVs of less than 20%. When results were combined across specimen types, 45 Bio-Rad and 71 Millipore markers had acceptable performance (&gt;25% detectability on all three specimen types and across-batch CVs &lt;20% on at least two of three specimen types). Median concentrations and ICCs differed to a small extent across specimen types and to a large extent between Bio-Rad and Millipore.Conclusions: Inflammation and immune markers can be measured reliably in serum and plasma samples using multiplexed Luminex-based methods.Impact: Multiplexed assays can be utilized for epidemiologic investigations into the role of inflammation in cancer etiology. Cancer Epidemiol Biomarkers Prev; 20(9); 1902–11. ©2011 AACR.
Self-sample HPV Tests As an Intervention for Nonattendees of Cervical Cancer Screening in Finland: a Randomized Trial
Authors: Virtanen Anni , Nieminen Pekka , Luostarinen Tapio , Anttila Ahti 
Published: September 2011

AbstractBackground: Attendance in screening is an important determinant of cervical cancer. Previous experience on high-risk human papillomavirus (hrHPV) DNA testing on patient-obtained samples suggests a good effect among nonattendees of screening. We assessed the effects of self-sampling on attendance in the Finnish screening program.Methods: Nonattendees after the primary invitation in one municipality (Espoo) were randomized to receive either a self-sampling kit (2,397 women) or an extra invitation (6,302 women). One fourth (1,315 women) of reminder letter arm nonattendees also received a self-sampling kit as a third intervention. Main outcomes were increases in screening attendance and coverage.Results: The adjusted relative risk for participation by self-sampling as a second intervention in comparison to a reminder letter arm was 1.21 (95% CI: 1.13–1.30). Total attendance increased from 65% to 76% by self-sampling and from 65% to 74% with a reminder letter. Combining the interventions (reminder letter and then self-sampling) increased total attendance from 63% to 78%. One fifth of the participants in all three groups increased screening coverage (previous Pap smear ≥5 years ago or never). Self-obtained samples were more often HPV positive than provider-obtained ones (participants after primary invitation and reminder letter), 12% to 13% versus 7%.Conclusions: Self-sampling is a feasible option in enhancing the attendance at organized screening, particularly as an addition to a reminder letter.Impact: If self-sampling is used as a third intervention after two written invitations, the overall attendance in Finland could most likely reach the desired 80% to 85%. Cancer Epidemiol Biomarkers Prev; 20(9); 1960–9. ©2011 AACR.
Estrogen Levels in Nipple Aspirate Fluid and Serum during a Randomized Soy Trial
Authors: Maskarinec Gertraud , Ollberding Nicholas J. , Conroy Shannon M. , Morimoto Yukiko , Pagano Ian S. , Franke Adrian A. , Gentzschein Elisabet , Stanczyk Frank Z. 
Published: September 2011

AbstractBackground: On the basis of hypothesized protective effect, we examined the effect of soy foods on estrogens in nipple aspirate fluid (NAF) and serum, possible indicators of breast cancer risk.Methods: In a crossover design, we randomized 96 women who produced 10 μL or more NAF to a high- or low-soy diet for 6 months. During the high-soy diet, participants consumed 2 soy servings of soy milk, tofu, or soy nuts (∼50 mg of isoflavones per day); during the low-soy diet, they maintained their usual diet. Six NAF samples were obtained using a FirstCyte aspirator. Estradiol (E2) and estrone sulfate (E1S) were assessed in NAF and estrone (E1) in serum only, using highly sensitive radioimmunoassays. Mixed-effects regression models accounting for repeated measures and left-censoring limits were applied.Results: Mean E2 and E1S were lower during the high-soy than the low-soy diet (113 vs. 313 pg/mL and 46 vs. 68 ng/mL, respectively) without reaching significance (P = 0.07); the interaction between group and diet was not significant. There was no effect of the soy treatment on serum levels of E2 (P = 0.76), E1 (P = 0.86), or E1S (P = 0.56). Within individuals, NAF and serum levels of E2 (rs = 0.37; P &lt; 0.001) but not of E1S (rs = 0.004; P = 0.97) were correlated. E2 and E1S in NAF and serum were strongly associated (rs = 0.78 and rs = 0.48; P &lt; 0.001).Conclusion: Soy foods in amounts consumed by Asians did not significantly modify estrogen levels in NAF and serum.Impact: The trend toward lower estrogen levels in NAF during the high-soy diet counters concerns about adverse effects of soy foods on breast cancer risk. Cancer Epidemiol Biomarkers Prev; 20(9); 1815–21. ©2011 AACR.
Serum Selenium, Genetic Variation in Selenoenzymes, and Risk of Colorectal Cancer: Primary Analysis from the Women's Health Initiative Observational Study and Meta-analysis
Authors: Takata Yumie , Kristal Alan R. , King Irena B. , Song Xiaoling , Diamond Alan M. , Foster Charles B. , Hutter Carolyn M. , Hsu Li , Duggan David J. , Langer Robert D. , Petrovitch Helen , Shikany James M. , Vaughan Thomas L. , Lampe Johanna W. , Prentice Ross L. , Peters Ulrike 
Published: September 2011

Abstract
Background: Selenium may prevent colorectal cancer. However, several previous studies are small and few investigated the association between selenium and colorectal cancer among women whose selenium metabolism may differ from men. Furthermore, genetic variants in selenoenzymes may be associated with colorectal cancer risk.
Methods: This nested case–control study investigated whether serum selenium concentration and genetic variants in five selenoenzymes (glutathione peroxidase 1–4 and selenoprotein P) were associated with colorectal cancer risk in 804 colorectal cancer cases and 805 matched controls from the Women's Health Initiative (WHI) Observational Study. A meta-analysis was conducted to compare the WHI result with previous studies including 12 observational studies and two clinical trials on selenium.
Results: Within the WHI, selenium concentrations were relatively high (mean = 135.6 μg/L) and were not associated with colorectal cancer risk (Ptrend = 0.10); the adjusted OR comparing the fifth with first quintile was 1.26 (95% CI, 0.91–1.73). Moreover, genetic variants in selenoenzymes were not significantly associated with colorectal cancer risk. Consistent with the finding in WHI, our meta-analysis showed no association between selenium and colorectal tumor risk in women (OR = 0.97; 95% CI, 0.79–1.18) comparing the highest quantile with the lowest); however, in men, there was a significant inverse association (OR = 0.68; 95% CI, 0.57–0.82) (P = 0.01).
Conclusion: Consistent with previous studies, we observed no protective effect of selenium on colorectal cancer among women.
Impact: Our analyses suggest that a population with relatively high selenium concentrations, especially women, would not benefit from increasing selenium intake. Cancer Epidemiol Biomarkers Prev; 20(9); 1822–30. ©2011 AACR.
Circulating Soluble CD30 and Future Risk of Lymphoma; Evidence from Two Prospective Studies in the General Population
Authors: Vermeulen Roel , Hosnijeh Fatemeh Saberi , Portengen Lützen , Krogh Vittorio , Palli Domenico , Panico Salvatore , Tumino Rosario , Sacredote Carlotta , Purdue Mark , Lan Qing , Rothman Nathaniel , Vineis Paolo 
Published: September 2011

Abstract
Background: Elevated circulating soluble CD30 (sCD30) has been previously associated with AIDS-related non-Hodgkin lymphoma (NHL) risk. This finding was recently extended to the general population where elevated levels of sCD30 were reported in prediagnostic serum among subjects that developed NHL later in life.
Methods: We carried out a replication study within the Italian European Prospective Investigation into Cancer and Nutrition cohort. Plasma sCD30 concentration was measured by ELISA in prospectively collected blood of 35 B-cell lymphoma cases and 36 matched controls.
Results: We observed significantly increased relative risks for lymphoma with increasing sCD30 levels [OR (95% CI) for second and third tertiles vs. first tertile: 5.5 (1.5–20.2), 4.0 (1.1–13.9), respectively]. In addition, spline analyses showed that the dose–response curve of sCD30 and lymphoma risk was monotonic and quite similar to the risks reported in the previous study.
Conclusion: This replication study adds to the evidence that sCD30 is related to future lymphoma risk in a concentration-dependent manner in the general population.
Impact: The results of this study strengthen the observation that chronic sustained B-cell activation plays an important role in lymphomagenesis. Cancer Epidemiol Biomarkers Prev; 20(9); 1925–7. ©2011 AACR.