bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of the Maxim and Sedia Limiting Antigen Avidity assays for population-level HIV incidence surveillance
Authors: Sempa Joseph B. , Welte Alex , Busch Michael P. , Hall Jake , Hampton Dylan , Keating Sheila M. , Facente Shelley N. , Marson Kara , Parkin Neil , Pilcher Christopher D. , Murphy Gary , Grebe Eduard ,   on behalf of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA)
Published: March 2019

AbstractBackgroundTwo manufacturers, Maxim Biomedical and Sedia Biosciences Corporation, supply US CDC-approved versions of the HIV-1 Limiting Antigen Avidity EIA (LAg assay) for detecting ‘recent’ HIV infection in cross-sectional incidence estimation. This study assesses and compares the performance of the Maxim and Sedia LAg assays for incidence surveillance.MethodsWe ran both assays on a panel of 2,500 well-characterized HIV-1-infected specimens, most with estimated dates of (detectable) infection. We analysed concordance of assay results, assessed reproducibility using repeat testing and estimated the critical performance characteristics of a test for recent infection—mean duration of recent infection (MDRI) and false-recent rate (FRR)—for a range of normalized optical density (ODn) recency discrimination thresholds, alone and in combination with viral load thresholds. We further defined three hypothetical surveillance scenarios and evaluated overall performance for incidence surveillance, defined as the precision of incidence estimates, by estimating context-specific performance characteristics.ResultsThe Maxim assay produced lower ODn values than the Sedia assay on average, largely as a result of higher calibrator readings (mean calibrator OD of 0.749 vs. 0.643). Correlation of non-normalized OD readings was greater (R2 = 0.938) than those of ODn readings (R2 = 0.908), and the slope was closer to unity (1.054 vs. 0.899). Reproducibility of repeat testing of three blinded control specimens (25 replicates each) was slightly better for the Maxim assay (CV 8.9% to 14.8% vs. 13.2% to 15.0%). The MDRI of a Maxim-based algorithm at the ‘standard’ recency discrimination threshold in combination with viral load (ODn ≤1.5 & VL >1,000) was 201 days (95% CI: 180,223) and for Sedia was 171 days (95% CI: 152,191). Commensurately, the Maxim algorithm had a higher FRR in treatment-naive subjects (1.7% vs. 1.1%). We observed statistically significant differences in MDRI using the ODn alone (≤1.5) and in combination with viral load (>1,000). Under three fully-specified hypothetical surveillance scenarios (comparable to South Africa, Kenya and a concentrated epidemic), recent infection testing algorithms based on the two assays produced similar precision of incidence estimates.ConclusionsDifferences in ODn measurements between the Maxim and Sedia LAg assays on the same specimens largely resulted from differences in the reactivity of calibrators supplied by the manufacturers. Performance for surveillance purposes was extremely similar, although different ODn thresholds were optimal and different values of MDRI and FRR were appropriate for use in survey planning and incidence estimation.
Making Pastoralists Count: Geospatial Methods for the Health Surveillance of Nomadic Populations
Authors: Wild Hannah , Glowacki Luke , Maples Stace , Mejía-Guevara Iván , Krystosik Amy , Bonds Matthew H. , Hiruy Abiy , Desiree LaBeaud A. , Barry Michele 
Published: March 2019

AbstractNomadic pastoralists are among the world’s hardest-to-reach and least-served populations. Pastoralist communities are difficult to capture in household surveys due to factors including their high degree of mobility over remote terrain, fluid domestic arrangements, and cultural barriers. Most surveys utilize census-based sampling frames which do not accurately capture the demographic and health parameters of nomadic populations. As a result, pastoralists are “invisible” in population data such as the Demographic and Health Surveys (DHS). By combining remote sensing and geospatial analysis, we developed a sampling strategy designed to capture the current distribution of nomadic populations.We then implemented this sampling frame to survey a population of mobile pastoralists in southwest Ethiopia, focusing on maternal and child health (MCH) indicators. Using standardized instruments from DHS questionnaires, we draw comparisons with regional and national data finding disparities with DHS data in core MCH indicators including vaccination coverage, skilled birth attendance, and nutritional status. Our field validation demonstrates that this method is a logistically feasible alternative to conventional sampling frames and may be used at the population level. Geospatial sampling methods provide cost-affordable and logistically feasible strategies for sampling mobile populations, a crucial first step towards reaching these groups with health services.
Evolution of Phototransduction Genes in Lepidoptera
Authors: Macias-Muñoz Aide , Rangel Olguin Aline G. , Briscoe Adriana D. 
Published: March 2019

AbstractVision is underpinned by phototransduction, a signaling cascade that converts light energy into an electrical signal. Among insects, phototransduction is best understood inDrosophila melanogaster.A survey of phototransduction genes in four insect genomes found gains and losses betweenD. melanogasterand other insects; this study did not include lepidopterans. Diurnal butterflies and nocturnal moths occupy different light environments and have distinct eye morphologies, which might impact the expression of their phototransduction genes. Here, we used transcriptomics and phylogenetics to identify phototransduction genes that vary betweenD. melanogasterand Lepidoptera, and between moths and butterflies. Most phototransduction genes were conserved betweenD. melanogasterand Lepidoptera, with some exceptions. We found two lepidopteran opsins lacking aD. melanogasterortholog, and using antibodies found that one, a candidate retinochrome which we name unclassified opsin (UnRh), is expressed in the crystaline cone cells and the pigment cells of the butterflyHeliconius melpomene. We also found differences between Lepidoptera andD. melanogasterphototransduction in diacylglycerol regulation where a lepidopteran paralog, DAGβ, may be taking on a role in vision. Lastly, butterflies express similar amounts oftrpandtrplchannel mRNAs, while moths express approximately 50x lesstrp. Since TRP/TRPL channels allow Ca2+and Na+influx this might explain why moths appear to express lessCalxandNckx30CNa+/Ca2+channel mRNAs. Our findings suggest that while many single-copyD. melanogasterphototransduction genes are conserved in lepidopterans, phototransduction gene expression differences exist between moths and butterflies that may be linked to their visual light environment.
Deep Learning with Multimodal Representation for Pancancer Prognosis Prediction
Authors: Cheerla Anika , Gevaert Olivier 
Published: March 2019

AbstractEstimating the future course of cancer is invaluable to physicians; however, current clinical methods fail to effectively use the vast amount of multimodal data that is available for cancer patients.To tackle this problem, we constructed a deep neural network based model to predict the survival of patients for 20 different cancer types using gene expressions, microRNA data, clinical data and histopathology whole slide images (WSIs). We developed an unsupervised encoder to compress these four data modalities into a single feature vector for each patient, handling missing data through a resilient, multimodal dropout method. Encoding methods were tailored to each data type - using deep highway networks to extract features from genomic and clinical data, and convolutional neural networks extract features from pathology images. We then used these feature encodings trained on pancancer data to predict pancancer and single cancer survival data, achieving a C-index of 0.784 overall.This work shows that it is possible to build a pancancer model for prognosis that also predicts prognosis in single cancer sites. Furthermore, our model handles multiple data modalities, efficiently analyzes WSIs, and summarizes patient details flexibly into an unsupervised, informative profile. We thus present a powerful automated tool to accurately determine prognosis, a key step towards personalized treatment for cancer patients.
Effectiveness and selectivity of a heroin conjugate vaccine to attenuate heroin, 6-acetylmorphine, and morphine antinociception in rats: Comparison with naltrexone
Authors: Schwienteck Kathryn L. , Blake Steven , Bremer Paul T. , Poklis Justin L. , Townsend E. Andrew , Negus S. Stevens , Banks Matthew L. 
Published: March 2019

AbstractBackgroundOne emerging strategy to address the opioid crisis includes opioid-targeted immunopharmacotherapies. This study compared effectiveness of a heroin-tetanus toxoid (TT) conjugate vaccine to antagonize heroin, 6-acetylmorphine (6-AM), morphine, and fentanyl antinociception in rats.MethodsAdult male and female Sprague Dawley rats received three doses of active or control vaccine at weeks 0, 2, and 4. Vaccine pharmacological selectivity was assessed by comparing opioid dose-effect curves in 50°C warm-water tail-withdrawal procedure before and after active or control heroin-TT vaccine. Route of administration [subcutaneous (SC) vs. intravenous [IV)] was also examined as a determinant of vaccine effectiveness. Continuous naltrexone treatment (0.0032-0.032 mg/kg/h) effects on heroin, 6-AM, and morphine antinociceptive potency was also determined as a benchmark for minimal vaccine effectiveness.ResultsThe heroin-TT vaccine decreased potency of SC heroin (5-fold), IV heroin (3-fold), and IV 6-AM (3-fold) for several weeks without affecting IV morphine or SC and IV fentanyl potency. The control vaccine did not alter potency of any opioid. Naltrexone dose-dependently decreased antinociceptive potency of SC heroin, and treatment with 0.01 mg/kg/h naltrexone produced similar, approximate 8-fold decreases in potencies of SC and IV heroin, IV 6-AM, and IV morphine. The combination of naltrexone and active vaccine was more effective than naltrexone alone to antagonize SC heroin but not IV heroin.ConclusionsThe heroin-TT vaccine formulation examined is less effective, but more selective, than chronic naltrexone to attenuate heroin antinociception in rats. Furthermore, these results provide an empirical framework for future preclinical opioid vaccine research to benchmark effectiveness against naltrexone.
Constructing a Draft Map of the Cannabis Proteome
Authors: Jenkins Conor , Orsburn Ben 
Published: March 2019

AbstractRecently we have seen a relaxing on the historic restrictions on the use and subsequent research on the cannabis plants, generally classified as Cannabis sativa and Cannabis indica. What research has been performed to date has centered on chemical analysis of plant flower products, namely cannabinoids and various terpenes that directly contribute to phenotypic characteristics of the female flowers. In addition, we have seen many groups recently completing genetic profiles of various plants of commercial value. To date, no comprehensive attempt has been made to profile the proteomes of these plants. In this study we present our initial findings consisting of the identification of 17,269 unique proteins identified from Cannabis plant materials, as well as 6,110 post-translational modifications identified on these proteins. The results presented demonstrate the first steps toward constructing a complete draft map of the Cannabis proteome.
Depiction of secondary metabolites and antifungal activity of Bacillus velezensis DTU001
Authors: Devi Sagarika , Kiesewalter Heiko T. , Kovács Renátó , Frisvad Jens Christian , Weber Tilmann , Larsen Thomas Ostenfeld , Kovács Ákos T. , Ding Ling 
Published: March 2019

ABSTRACTFor a safe and sustainable environment, effective microbes as biocontrol agents are in high demand. We have isolated a new Bacillus velezensis strain DTU001, investigated its antifungal spectrum, sequenced its genome, and uncovered the production of lipopeptides in HPLC-HRMS analysis. To test the antifungal efficacy, extracts of B. velezensis DTU001 was tested against a range of twenty human or plant pathogenic fungi. We demonstrate that inhibitory potential of B. velezensis DTU001 against selected fungi is superior in comparison to single lipopeptide, either iturin or fengycin. The isolate showed analogous biofilm formation to other closely related Bacilli. To further support the biocontrol properties of the isolate, coculture with Candida albicans demonstrated that B. velezensis DTU001 exhibited excellent antiproliferation effect against C. albicans. In summary, the described isolate is a potential antifungal agent with a broad antifungal spectrum that might assist our aims to avoid hazardous pathogenic fungi and provide alternative to toxicity caused by chemicals.
Recent global changes have decoupled species richness from specialization patterns in North American birds
Authors: Mimet Anne , Buitenwerf Robert , Sandel Brody , Svenning Jens-Christian , Normand Signe 
Published: March 2019

AbstractAimTheory suggests that increasing productivity and climate stability toward the tropics can explain the latitudinal richness gradient by favouring specialization. A positive relationship between species richness and specialization should thus emerge as a fundamental biogeographic pattern. However, land use and climate change disproportionally increase the local extirpation risk for specialists, potentially impacting this pattern. Here, we empirically quantify the richness-specialization prediction and test how 50 years of climate and land use change has affected the richness-specialization relationship.LocationUSATime period1966-2015Major taxa studiedBirdsMethodsWe used the North American breeding bird survey to quantify bird community richness and specialization to habitat and climate. We assess i) temporal change in the slope of the richness-specialization relationship, using a Generalized Mixed Model; ii) temporal change in spatial covariation of richness and specialization as driven by local environmental conditions, using Generalized Additive Models; and iii) land use, climate and topographic drivers of the spatio-temporal changes in the relationship, using a multivariate method.ResultsWe found evidence for a positive richness-specialization relationship in bird communities. However, the slope of the relationship declined strongly over time. Richness spatially covaried with specialization following a unimodal pattern. The peak of the unimodal pattern shifted toward less specialized communities over time. These temporal changes were associated with precipitation change, decreasing temperature stability and land use.Main conclusionsRecent climate and land use changes induced two antagonist types of community responses. In human-dominated areas, the decoupling of richness and specialization drove a general biotic homogenization trend. In human-preserved areas under increasing climate harshness, specialization increased while richness decreased in a “specialization” trend. Our results offer new support for specialization as a key driver of macroecological diversity patterns, and show that global changes are erasing this fundamental macroecological pattern.BiosketchAnne Mimet is a postdoctoral researcher interested in the understanding of human impacts on biodiversity through land use and climate changes, at various spatio-temporal scales. She is interested in embracing the complexity of socio-ecological systems, and in the understanding of biodiversity trends in a human-dominated world in the context of the general theories of ecology.
Cannabis-associated symptom profiles in patients with first episode psychosis and population controls
Authors: Quattrone Diego , Ferraro Laura , Tripoli Giada , Cascia Erika La , Quigley Harriet ,   EU-GEI group, Gayer-Anderson Charlotte , Jones Peter B. , Kirkbride James B. , Barbera Daniele La , Tarricone Ilaria , Lynskey Michael T. , Freeman Tom P. , Sham Pak C. , Cardno Alaistar , Vassos Evangelos , van Os Jim , Morgan Craig , Reininghaus Ulrich , Lewis Cathryn M. , Murray Robin M. , Di Forti Marta 
Published: March 2019

AbstractObjectiveThe evidence is mixed on whether cannabis use is associated with a particular symptomatology in first episode psychosis (FEP) patients.The authors set out to investigate a) patterns of association between cannabis use and transdiagnostic symptom dimensions; b) whether the extent of use of cannabis contributes to the variation in clinical and subclinical symptom profiles.MethodThe authors analysed data from 901 patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Item response modelling was used to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use was evaluated using linear mixed effects models analyses.ResultsIn patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high potency cannabis having the highest score (B=0.35; 95%CI 0.14 to 0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B=-0.27; 95%CI −0.42 to −0.12).In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use.Neither patients nor controls presented differences in the depressive dimension related to cannabis use.ConclusionsThe extent of use of cannabis explains part of the heterogeneous distribution of positive and negative symptoms of FEP patients.
Prenatal thyroid hormone exposure increases growth but not oxidative stress in a wild passerine species
Authors: Sarraude Tom , Hsu Bin-Yan , Groothuis Ton G.G. , Ruuskanen Suvi 
Published: March 2019

AbstractHormones transferred from mothers to their offspring are thought to be a maternal tool for mothers to prepare their progeny for expected environmental conditions, thus increasing fitness. Thyroid hormones (THs) are crucial across vertebrates for embryonic and post-natal development and metabolism. Nevertheless, the studies that investigated the consequences of maternal hormones have mostly focused on steroid hormones and ignored maternally-derived thyroid hormones. In this study, we experimentally elevated yolk thyroid hormones in a wild population of a migratory passerine, the European Pied flycatcherFicedula hypoleuca. We injected eggs with a mixture of T4and T3within the natural range of the species to assess its effects on hatching success, nestling survival, growth and oxidative status (antioxidant enzyme activity, lipid peroxidation and oxidative balance). We found no effects of yolk THs on egg hatchability or nestling survival. Yolk THs increased nestling growth during the second week post hatching, but this potentially beneficial effect did not incur any costs in terms of oxidative stress. The results should stimulate more research on thyroid hormone mediated maternal effects, further studies into the underlying mechanistic pathways for these effects and how they translate into adulthood and fitness.Summary statementThyroid hormones have been overlooked in the context of hormone-mediated maternal effects. We found that yolk thyroid hormones in a wild bird species increase growth without incurring oxidative stress.
HSC70 regulates cold-induced caspase-1 hyperactivation by an autoinflammation-causing mutant of cytoplasmic immune receptor NLRC4
Authors: Raghawan Akhouri Kishore , Ramaswamy Rajashree , Radha Vegesna , Swarup Ghanshyam 
Published: March 2019

AbstractNLRC4 is an innate immune receptor, which upon detection of certain pathogens or internal distress signal, initiates caspase-1 mediated inflammatory response. A gain-of-function mutation, H443P in NLRC4, causes familial cold autoinflammatory syndrome (FCAS) characterized by cold-induced hyperactivation of caspase-1 and inflammation. Here, we show that heat shock cognate protein 70 (HSC70) complexes with NLRC4 and negatively regulates caspase-1 activation by NLRC4-H443P. Compared to NLRC4, the structurally altered NLRC4-H443P shows enhanced interaction with HSC70. Knockdown of HSC70 or inhibition of its ATPase activity enhances caspase-1 activation by NLRC4-H443P. Exposure to subnormal temperature resulted in reduced interaction of NLRC4-H443P with HSC70, and an increase in its ability to form ASC-specks and activate caspase-1. By demonstrating that HSC70 differentially interacts with NLRC4-H443P mutant in a temperature-dependent manner to regulate caspase-1 activation, we provide a mechanism for cold-induced inflammation seen in FCAS patients with NLRC4-H443P mutation.
Interplay of primary bovine lymphocytes and Mycobacterium avium subsp. paratuberculosis shows distinctly different proteome changes and immune pathways in host-pathogen interaction
Authors: Kleinwort Kristina J.H. , Hauck Stefanie M. , Degroote Roxane L. , Scholz Armin M. , Hölzel Christina , Märtlbauer Erwin P. , Deeg Cornelia A. 
Published: March 2019

AbstractMycobacterium avium subsp. paratuberculosis (MAP) is a pathogen causing paratuberculosis in cattle and small ruminants. During the long asymptomatic subclinical stage, high numbers of MAP are excreted and can be transmitted to food, where they survive many of the standard techniques of food decontamination. If these MAP are harmful to the consumers is currently under debate. In general, there is a lack of information regarding interaction of the hosts immune system with MAP.In this study, we tested the interaction of peripheral blood lymphocytes (PBL) from cattle with MAP in their exoproteomes/secretomes. Because in other mycobacterial infections, the immune phenotype correlates with susceptibility, we additionally tested the interaction of MAP with recently detected immune deviant cows.In PBL, different biological pathways were enhanced in response to MAP dependent on the immune phenotype of the host. PBL of control cows activated members of cell activation and chemotaxis of leukocytes pathway as well as IL-12 mediated signaling. In contrast, in ID cows CNOT1 was detected as highly abundant protein, pointing to a different immune response, which could be favorable for MAP. Additionally, MAP reacted different to the hosts. Their exoproteomes differed in either GroEL1 or DnaK abundance, depending on the interacting immune response.These findings point to an interdependent, tightly regulated response of MAP and the immune system.