bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Single Intramuscular Dose of a Plant-Made Virus-Like Particle Vaccine Elicits a Balanced Humoral and Cellular Response and Protects Young and Aged Mice from Influenza H1N1 Virus Challenge despite a Modest/Absent Humoral Response
Authors: Hodgins Breanna , Yam Karen K. , Winter Kaitlin , Pillet Stephane , Landry Nathalie , Ward Brian J. 
Published: October 2017

ABSTRACT
Virus-like-particle (VLP) influenza vaccines can be given intramuscularly (i.m.) or intranasally (i.n.) and may have advantages over split-virion formulations in the elderly. We tested a plant-made VLP vaccine candidate bearing the viral hemagglutinin (HA) delivered either i.m. or i.n. in young and aged mice. Young adult (5- to 8-week-old) and aged (16- to 20-month-old) female BALB/c mice received a single 3-μg dose based on the HA (A/California/07/2009 H1N1) content of a plant-made H1-VLP (i.m. or i.n.) split-virion vaccine (i.m.) or were left naive. After vaccination, humoral and splenocyte responses were assessed, and some mice were challenged. Both VLP and split vaccines given i.m. protected 100% of the young animals, but the VLP group lost the least weight and had stronger humoral and cellular responses. Compared to split-vaccine recipients, aged animals vaccinated i.m. with VLP were more likely to survive challenge (80% versus 60%). The lung viral load postchallenge was lowest in the VLP i.m. groups. Mice vaccinated with VLP i.n. had little detectable immune response, but survival was significantly increased. In both age groups, i.m. administration of the H1-VLP vaccine elicited more balanced humoral and cellular responses and provided better protection from homologous challenge than the split-virion vaccine.
Rapid Nanopore Sequencing of Plasmids and Resistance Gene Detection in Clinical Isolates
Authors: Lemon Jamie K. , Khil Pavel P. , Frank Karen M. , Dekker John P. 
Published: October 2017

ABSTRACT

Recent advances in nanopore sequencing technology have led to a substantial increase in throughput and sequence quality. Together, these improvements may permit real-time benchtop genomic sequencing and antimicrobial resistance gene detection in clinical isolates. In this study, we evaluated workflows and turnaround times for a benchtop long-read sequencing approach in the clinical microbiology laboratory using the Oxford Nanopore Technologies MinION sequencer. We performed genomic and plasmid sequencing of three clinical isolates with both MinION and Illumina MiSeq, using different library preparation methods (2D and rapid 1D) with the goal of antimicrobial resistance gene detection. We specifically evaluated the advantages of using plasmid DNA for sequencing and the value of supplementing MinION sequences with MiSeq reads for increasing assembly accuracy. Resequencing of three plasmids in a reference
Klebsiella pneumoniae
isolate demonstrated ∼99% accuracy of draft MinION-only assembly and >99.9% accuracy of assembly polished with MiSeq reads. Plasmid DNA sequencing of previously uncharacterized clinical extended-spectrum β-lactamase (ESBL)-producing
Escherichia coli
and
K. pneumoniae
isolates using MinION allowed successful identification of antimicrobial resistance genes in the draft assembly corresponding to all classes of observed plasmid-based phenotypic resistance. Importantly, use of plasmid DNA enabled lower depth sequencing, and assemblies sufficient for full antimicrobial resistance gene annotation were obtained with as few as 2,000 to 5,000 reads, which could be acquired in 20 min of sequencing. With a MinION-only workflow that balances accuracy against turnaround time, full annotation of plasmid resistance gene content could be obtained in under 6 h from a subcultured isolate, less time than traditional phenotypic susceptibility testing.
Characterization of the African Swine Fever Virus Decapping Enzyme during Infection
Authors: Quintas Ana , Pérez-Núñez Daniel , Sánchez Elena G. , Nogal Maria L. , Hentze Matthias W. , Castelló Alfredo , Revilla Yolanda 
Published: October 2017

ABSTRACT

African swine fever virus (ASFV) infection is characterized by a progressive decrease in cellular protein synthesis with a concomitant increase in viral protein synthesis, though the mechanism by which the virus achieves this is still unknown. Decrease of cellular mRNA is observed during ASFV infection, suggesting that inhibition of cellular proteins is due to an active mRNA degradation process. ASFV carries a gene (Ba71V D250R/Malawi g5R) that encodes a decapping protein (ASFV-DP) that has a Nudix hydrolase motif and decapping activity
in vitro
. Here, we show that ASFV-DP was expressed from early times and accumulated throughout the infection with a subcellular localization typical of the endoplasmic reticulum, colocalizing with the cap structure and interacting with the ribosomal protein L23a. ASFV-DP was capable of interaction with poly(A) RNA in cultured cells, primarily mediated by the N-terminal region of the protein. ASFV-DP also interacted with viral and cellular RNAs in the context of infection, and its overexpression in infected cells resulted in decreased levels of both types of transcripts. This study points to ASFV-DP as a viral decapping enzyme involved in both the degradation of cellular mRNA and the regulation of viral transcripts.

IMPORTANCE
Virulent ASFV strains cause a highly infectious and lethal disease in domestic pigs for which there is no vaccine. Since 2007, an outbreak in the Caucasus region has spread to Russia, jeopardizing the European pig population and making it essential to deepen knowledge about the virus. Here, we demonstrate that ASFV-DP is a novel RNA-binding protein implicated in the regulation of mRNA metabolism during infection, making it a good target for vaccine development.
HIV-Exposed Infants Vaccinated with an MF59/Recombinant gp120 Vaccine Have Higher-Magnitude Anti-V1V2 IgG Responses than Adults Immunized with the Same Vaccine
Authors: McGuire Erin P. , Fong Youyi , Toote Christopher , Cunningham Coleen K. , McFarland Elizabeth J. , Borkowsky William , Barnett Susan , Itell Hannah L. , Kumar Amit , Gray Glenda , McElrath M. Julianna , Tomaras Georgia D. , Permar Sallie R. , Fouda Genevieve G. 
Published: October 2017

ABSTRACTIn the RV144 vaccine trial, IgG responses against the HIV envelope variable loops 1 and 2 (V1V2) were associated with decreased HIV acquisition risk. We previously reported that infants immunized with an MF59-adjuvanted rgp120 vaccine developed higher-magnitude anti-V1V2 IgG responses than adult RV144 vaccinees. To determine whether the robust antibody response in infants is due to differences in vaccine regimens or to inherent differences between the adult and infant immune systems, we compared Env-specific IgG responses in adults and infants immunized with the same MF59- and alum-adjuvanted HIV envelope vaccines. At peak immunogenicity, the magnitudes of the gp120- and V1V2-specific IgG responses were comparable between adults and infants immunized with the alum/MNrgp120 vaccine (gp120 median fluorescence intensities [FIs] in infants = 7,118 and in adults = 11,510,P= 0.070; V1V2 median MFIs of 512 [infants] and 804 [adults],P= 0.50), whereas infants immunized with the MF59/SF-2 rgp120 vaccine had higher-magnitude antibody levels than adults (gp120 median FIs of 15,509 [infants] and 2,290 [adults],P< 0.001; V1V2 median FIs of 23,926 [infants] and 1,538 [adults];P< 0.001). Six months after peak immunogenicity, infants maintained higher levels Env-specific IgG than adults. Anti-V1V2 IgG3 antibodies that were associated with decreased HIV-1 risk in RV144 vaccinees were present in 43% of MF59/rgp120-vaccinated infants but only in 12% of the vaccinated adults (P= 0.0018). Finally, in contrast to the rare vaccine-elicited Env-specific IgA in infants, rgp120 vaccine-elicited Env-specific IgA was frequently detected in adults. Our results suggest that vaccine adjuvants differently modulate gp120-specific antibody responses in adults and infants and that infants can robustly respond to HIV Env immunization.IMPORTANCEMore than 150,000 pediatric HIV infections occur yearly, despite the availability of antiretroviral prophylaxis. A pediatric HIV vaccine could reduce the number of these ongoing infant infections and also prime for long-term immunity prior to sexual debut. We previously reported that immunization of infants with an MF59-adjuvanted recombinant gp120 vaccine induced higher-magnitude, potentially protective anti-V1V2 IgG responses than in adult vaccinees receiving the moderately effective RV144 vaccine. In the present study, we demonstrate that the robust response observed in infants is not due to differences in vaccine regimen or vaccine dose between adults and infants. Our results suggest that HIV vaccine adjuvants may differentially modulate immune responses in adults and infants, highlighting the need to conduct vaccine trials in pediatric populations.
Quiescence Promotes Latent HIV Infection and Resistance to Reactivation from Latency with Histone Deacetylase Inhibitors
Authors: Painter Mark M. , Zaikos Thomas D. , Collins Kathleen L. 
Published: October 2017

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) establishes transcriptionally silent latent infections in resting memory T cells and hematopoietic stem and progenitor cells (HSPCs), which allows the virus to persist in infected individuals despite antiretroviral therapy. Developing
in vitro
models of HIV-1 latency that recapitulate the characteristics of latently infected cells
in vivo
is crucial to identifying and developing effective latency-reversing therapies. HSPCs exist in a quiescent state
in vivo
, and quiescence is correlated with latent infections in T cells. However, current models for culturing HSPCs and for infecting T cells
in vitro
require that the cells be maintained in an actively proliferating state. Here we describe a novel culture system in which primary human HSPCs cultured under hypothermic conditions are maintained in a quiescent state. We show that these quiescent HSPCs are susceptible to predominantly latent infection with HIV-1, while actively proliferating and differentiating HSPCs obtain predominantly active infections. Furthermore, we demonstrate that the most primitive quiescent HSPCs are more resistant to spontaneous reactivation from latency than more differentiated HSPCs and that quiescent HSPCs are resistant to reactivation by histone deacetylase inhibitors or P-TEFb activation but are susceptible to reactivation by protein kinase C (PKC) agonists. We also demonstrate that inhibition of HSP90, a known regulator of HIV transcription, recapitulates the quiescence and latency phenotypes of hypothermia, suggesting that hypothermia and HSP90 inhibition may regulate these processes by similar mechanisms. In summary, these studies describe a novel model for studying HIV-1 latency in human primary cells maintained in a quiescent state.

IMPORTANCE
Human immunodeficiency virus type 1 (HIV-1) establishes a persistent infection for which there remains no feasible cure. Current approaches are unable to clear the virus despite decades of therapy due to the existence of latent reservoirs of integrated HIV-1, which can reactivate and contribute to viral rebound following treatment interruption. Previous clinical attempts to reactivate the latent reservoirs in an individual so that they can be eliminated by the immune response or viral cytopathic effect have failed, indicating the need for a better understanding of the processes regulating HIV-1 latency. Here we characterize a novel
in vitro
model of HIV-1 latency in primary hematopoietic stem and progenitor cells isolated from human cord blood that may better recapitulate the behavior of latently infected cells
in vivo
. This model can be used to study mechanisms regulating latency and potential therapeutic approaches to reactivate latent infections in quiescent cells.
Stochastic Community Assembly: Does It Matter in Microbial Ecology?
Authors: Zhou Jizhong , Ning Daliang 
Published: October 2017

SUMMARYUnderstanding the mechanisms controlling community diversity, functions, succession, and biogeography is a central, but poorly understood, topic in ecology, particularly in microbial ecology. Although stochastic processes are believed to play nonnegligible roles in shaping community structure, their importance relative to deterministic processes is hotly debated. The importance of ecological stochasticity in shaping microbial community structure is far less appreciated. Some of the main reasons for such heavy debates are the difficulty in defining stochasticity and the diverse methods used for delineating stochasticity. Here, we provide a critical review and synthesis of data from the most recent studies on stochastic community assembly in microbial ecology. We then describe both stochastic and deterministic components embedded in various ecological processes, including selection, dispersal, diversification, and drift. We also describe different approaches for inferring stochasticity from observational diversity patterns and highlight experimental approaches for delineating ecological stochasticity in microbial communities. In addition, we highlight research challenges, gaps, and future directions for microbial community assembly research.
Diurnal cortisol and mental well-being in middle and older age: evidence from four cohort studies
Authors: Stafford Mai , Ben-Shlomo Yoav , Cooper Cyrus , Gale Catharine , Gardner Michael P , Geoffroy Marie-Claude , Power Chris , Kuh Diana , Cooper Rachel 
Published: October 2017

ObjectivesWe conducted an individual participant meta-analysis to test the hypothesis that cortisol patterns indicative of dysregulated hypothalamic–pituitary–adrenal axis functioning would be prospectively associated with poorer well-being at follow-up.SettingFour large UK-based cohort studies.ParticipantsThose providing valid salivary or serum cortisol samples (n=7515 for morning cortisol; n=1612 for cortisol awakening response) at baseline (age 44–82) and well-being data on the Warwick Edinburgh Mental Wellbeing Scale at follow-up (0–8 years) were included.ResultsWell-being was not associated with morning cortisol, diurnal slope or awakening response though a borderline association with evening cortisol was found. Adjusting for sex and follow-up time, each 1 SD increase in evening cortisol was associated with a −0.47 (95% CI −1.00 to 0.05) point lower well-being. This was attenuated by adjustment for body mass index, smoking and socioeconomic position. Between-study heterogeneity was low.ConclusionsThis study does not support the hypothesis that diurnal cortisol is prospectively associated with well-being up to 8 years later. However, replication in prospective studies with cortisol samples over multiple days is required.
Randomised controlled pilot trial of an exercise plus behaviour change intervention in people with multiple sclerosis: the Step it Up study
Authors: Hayes Sara , Uszynski Marcin Kacper , Motl Robert W , Gallagher Stephen , Larkin Aidan , Newell John , Scarrott Carl , Coote Susan 
Published: October 2017

ObjectiveTo investigate feasibility of multiple sclerosis (MS) exercise guidelines for inactive people with MS (PwMS) and to examine preliminary efficacy for walking. To investigate effect of augmenting that intervention with education based on social cognitive theory (SCT).DesignPilot multicentre, double-blind, randomised, parallel, controlled trial.SettingCommunity-delivered programme.ParticipantsSixty-five physically inactive PwMS walked independently, scored 0–3 on the Patient Determined Disease Steps Scale, had no MS relapse or change in MS medication in 12 weeks.Interventions10-week exercise plus SCT education (SCT) compared with exercise plus attention control education (CON).Outcome measuresSix-Minute Walk Test (6MWT), Timed Up and Go (TUG) test and Multiple Sclerosis Walking Scale-12 (MSWS-12).Results174 expressed interest, 92 were eligible and 65 enrolled (SCT, n=32; CON, n=33). The intervention was feasible and delivered as intended. 68% of SCT group and 50% of control group met the exercise guidelines after intervention. Using linear mixed effects models, intention-to-treat basis, there was insufficient evidence for difference between the groups over the trial (6MWT, p=0.30; TUG, p=0.4; MSWS-12, p=0.8). Using secondary analysis of a cohort with data for≥3 assessments (SCT, n=21; CON, n=20), there was significant treatment effect favouring the intervention group (p=0.04) with mean effect for 6MWT 39.0 m (95% CI 2.26 to 75.73) at 12 weeks and 40.0 m (95% CI 2.3 to 77.8) at 36 weeks. Both groups improved significantly in 6MWT following 10-week intervention (SCT, mean ∆=83.02, SD=60.1, p≤0.01; CON, mean ∆=56.92, SD=73.5, p≤0.01), TUG (SCT, ∆=−0.70, SD=1.25, p≤0.01; CON, ∆=−0.54, SD=0.95, p≤0.01) and MSWS-12 (SCT, ∆=−8.03, SD=16.18, p=0.02; CON, ∆=−0.86, SD=18.74, p=0.81).ConclusionsA 10-week exercise programme based on the MS exercise guidelines for improving walking in previously inactive PwMS was feasible. There is marginal evidence of a treatment effect in favour of the exercise plus SCT intervention at 12 and 36 weeks.Trial registration numberNCT02301442; Results.
Assessment of potential predictors of calretinin and mesothelin to improve the diagnostic performance to detect malignant mesothelioma: results from a population-based cohort study
Authors: Casjens Swaantje , Weber Daniel G , Johnen Georg , Raiko Irina , Taeger Dirk , Meinig Carmen , Moebus Susanne , Jöckel Karl-Heinz , Brüning Thomas , Pesch Beate 
Published: October 2017

ObjectivesMesothelin and calretinin are blood-based markers for malignant mesothelioma. The objective of this study was to analyse the markers in plasma samples from cancer-free men and to identify factors influencing their concentrations to minimise false-positive test results when using these markers for the early detection of malignant mesothelioma.SettingThe present analyses used data and archived blood samples of the population-based Heinz Nixdorf Recall Study among elderly people collected from 2011 to 2014.ParticipantsA total of 569 men (median age 70 years) without a malignant disease at the time of blood sampling were selected for these analyses.Primary and secondary outcomeMesothelin and calretinin concentration in plasma samples.ResultsWe observed 24 mesothelin concentrations ≥1.5 nM (specificity 95.8%, 95% CI 93.8% to 97.2%) and 34 calretinin concentrations ≥1.0 ng/mL (specificity 94.0%, 95% CI 91.7% to 95.7%). Only five men had both markers above these cut-offs. Renal dysfunction and hypertension were major predictors of elevated mesothelin in addition to age. Regarding calretinin, the effect of renal dysfunction was slightly weaker and hypertension was not associated with increased concentrations. However, a diagnosis of cancer after blood collection and bronchial asthma were associated with positive calretinin results.ConclusionsThe combined determination of mesothelin and calretinin results in only few false-positive marker tests. Both markers are mainly influenced by renal dysfunction. The determination of cystatin C concentrations may be informative when interpreting the test results.
A county-level cross-sectional analysis of positive deviance to assess multiple population health outcomes in Indiana
Authors: Hendryx Michael , Guerra-Reyes Lucia , Holland Benjamin D , McGinnis Michael Dean , Meanwell Emily , Middlestadt Susan E , Yoder Karen M 
Published: October 2017

ObjectiveTo test a positive deviance method to identify counties that are performing better than statistical expectations on a set of population health indicators.DesignQuantitative, cross-sectional county-level secondary analysis of risk variables and outcomes in Indiana. Data are analysed using multiple linear regression to identify counties performing better or worse than expected given traditional risk indicators, with a focus on ‘positive deviants’ or counties performing better than expected.ParticipantsCounties in Indiana (n=92) constitute the unit of analysis.Main outcome measuresPer cent adult obesity, per cent fair/poor health, low birth weight per cent, per cent with diabetes, years of potential life lost, colorectal cancer incidence rate and circulatory disease mortality rate.ResultsCounty performance that outperforms expectations is for the most part outcome specific. But there are a few counties that performed particularly well across most measures.ConclusionsThe positive deviance approach provides a means for state and local public health departments to identify places that show better health outcomes despite demographic, social, economic or behavioural disadvantage. These places may serve as case studies or models for subsequent investigations to uncover best practices in the face of adversity and generalise effective approaches to other areas.
Preparing the prescription: a review of the aim and measurement of social referral programmes
Authors: Rempel Emily S , Wilson Emma N , Durrant Hannah , Barnett Julie 
Published: October 2017

ObjectiveOur aim is to review, and qualitatively evaluate, the aims and measures of social referral programmes. Our first objective is to identify the aims of social referral initiatives. Our second objective is to identify the measures used to evaluate whether the aims of social referral were met.DesignLiterature review.BackgroundSocial referral programmes, also called social prescribing and emergency case referral, link primary and secondary healthcare with community services, often under the guise of decreasing health system costs.MethodFollowing the PRISMA guidelines, we undertook a literature review to address that aim. We searched in five academic online databases and in one online non-academic search engine, including both academic and grey literature, for articles referring to ‘social prescribing’ or ‘community referral’.ResultsWe identified 41 relevant articles and reports. After extracting the aims, measures and type of study, we found that most social referral programmes aimed to address a wide variety of system and individual health problems. This included cost savings, resource reallocation and improved mental, physical and social well-being. Across the 41 studies and reports, there were 154 different kinds of measures or methods of evaluation identified. Of these, the most commonly used individual measure was the Warwick-Edinburgh Mental Well-being Scale, used in nine studies and reports.ConclusionsThese inconsistencies in aims and measures used pose serious problems when social prescribing and other referral programmes are often advertised as a solution to health services-budgeting constraints, as well as a range of chronic mental and physical health conditions. We recommend researchers and local community organisers alike to critically evaluate for whom, where and why their social referral programmes ‘work’.