A systems analysis was conducted to determine the potential molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical trial of the radiation-attenuated whole sporozoite PfSPZ Vaccine in African infants. Innate immune activation and myeloid signatures at pre-vaccination baseline correlated with protection from Pf parasitemia in placebo controls. These same signatures were associated with susceptibility to parasitemia among infants who received the highest and most protective PfSPZ Vaccine dose. Machine learning identified spliceosome, proteosome, and resting dendritic cell signatures as pre-vaccination features predictive of protection after highest-dose PfSPZ vaccination, whereas baseline CSP-specific IgG predicted non-protection. Pre-vaccination innate inflammatory and myeloid signatures were associated with higher sporozoite-specific IgG Ab response but undetectable PfSPZ-specific CD8+ T-cell responses post-vaccination. Consistent with these human data, innate stimulation in vivo conferred protection against infection by sporozoite injection in malaria-naïve mice while diminishing the CD8+ T-cell response to radiation-attenuated sporozoites. These data suggest a dichotomous role of innate stimulation for malaria protection and induction of protective immunity of whole-sporozoite malaria vaccines. The uncoupling of vaccine-induced protective immunity achieved by Abs from more protective CD8+ T cell responses suggest that PfSPZ Vaccine efficacy in malaria-endemic settings may be constrained by opposing antigen presentation pathways.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.

BACKGROUND: Antenatal care provides unique opportunities to assess severe acute respiratory syndrome coronavirus 2 seroprevalence and antibody response duration after natural infection detected during pregnancy; transplacental antibody transfer may inform peripartum and neonatal protection. We estimated seroprevalence and durability of antibodies from natural infection (anti-nucleocapsid immunoglobulin G) among pregnant people, and evaluated transplacental transfer efficiency. OBJECTIVE AND DESIGN: We conducted a cross-sectional study to measure severe acute respiratory syndrome coronavirus 2 seroprevalence, and a prospective cohort study to longitudinally measure anti-nucleocapsid immunoglobulin G responses and transplacental transfer of maternally derived anti-nucleocapsid antibodies. METHODS: We screened pregnant people for the seroprevalence study between 9 December 2020 and 19 June 2021 for anti-nucleocapsid immunoglobulin G in Seattle, Washington. We enrolled anti-nucleocapsid immunoglobulin G positive people from the seroprevalence study or identified through medical records with positive reverse transcription polymerase chain reaction or antigen positive results in a prospective cohort between 9 December 2020 and 9 August 2022. RESULTS: In the cross-sectional study (N = 1284), 5% (N = 65) tested severe acute respiratory syndrome coronavirus 2 anti-nucleocapsid immunoglobulin G positive, including 39 (60%) without prior positive reverse transcription polymerase chain reaction results and 42 (65%) without symptoms. In the prospective cohort study (N = 107 total; N = 65 from the seroprevalence study), 86 (N = 80%) had anti-nucleocapsid immunoglobulin G positive results during pregnancy. Among 63 participants with delivery samples and prior anti-nucleocapsid positive results, 29 (46%) were anti-nucleocapsid immunoglobulin G negative by delivery. Of 34 remaining anti-nucleocapsid immunoglobulin G positive at delivery with paired cord blood, 19 (56%) had efficient transplacental anti-nucleocapsid immunoglobulin G antibody transfer. Median time from first anti-nucleocapsid immunoglobulin G positive to below positive antibody threshold was 19 weeks and did not differ by prior positive reverse transcription polymerase chain reaction status. CONCLUSIONS: Maternally derived severe acute respiratory syndrome coronavirus 2 antibodies to natural infection may wane before delivery. Vaccines are recommended for pregnant persons to reduce severe illness and confer protection to infants.

OBJECTIVES: Despite clinical relevance, commercially available molecular tools for accurate β-lactamase detection are limited. In this study, we evaluated the performance of the ARM-D® β-lactamase Kit, a commercially available multiplex PCR assay designed to detect nine β-lactamase genes, including the five major plasmid-mediated carbapenemases, ESBL, or AmpC genes circulating in the United States. METHODS: A diverse collection of 113 Gram-negative isolates, including 42 with multiple β-lactamases was selected from the U.S. Centers for Disease Control and Prevention (CDC) & Food and Drug Administration (FDA) Antibiotic Resistance Isolate Bank, to represent the most frequently detected bacterial species carrying plasmid-mediated β-lactam resistance genes. RESULTS: Results were compared with whole genome sequence data. Of 164 β-lactamase gene targets with 49 unique variants, all were detected correctly without any cross-reactivity. The sensitivity and specificity were 100% (164/164) and 99.9% (852/853), respectively. CONCLUSION: The ARM-D® β-lactamase Kit detected a wide range of β-lactamase genotypes at a low upfront cost. The Streck assay represents a suitable, comprehensive tool for the detection of key β-lactamase resistance genes of public health concern in the United States.

Importance: Antenatal care provides unique opportunities to assess SARS-CoV-2 seroprevalence and antibody response duration after natural infection detected during pregnancy; transplacental antibody transfer may inform peripartum and neonatal protection. Objective(s): Estimate seroprevalence and durability of antibodies from natural infection (anti-nucleocapsid (anti-N) IgG) among pregnant people, and evaluate transplacental transfer efficiency. Design(s): Seroprevalence study: cross-sectional SARS-CoV-2 antibody screening among pregnant people December 9, 2020-June 19, 2021. Cohort study: Pregnant people screened anti-N IgG+ by Abbott Architect chemiluminescent immunoassay in seroprevalence study or identified through medical records with RT-PCR+ or antigen positive results enrolled in a prospective cohort December 9, 2020-June 30, 2022 to longitudinally measure anti-N IgG responses. We collected cord blood and assessed transplacental transfer of maternally-derived anti-N antibodies. Setting(s): Three hospitals and 14 affiliated clinics providing antenatal and delivery care, Seattle, Washington metropolitan area. Participant(s): Seroprevalence study: pregnant people were screened for SAR-CoV-2 anti-N IgG during routine care. Cohort study: Pregnant people with evidence of prior SARS-CoV-2 infection (screened anti-N IgG+ from seroprevalence study or identified with a RT-PCR+ or antigen positive result from medical records) were enrolled in a cohort study to longitudinally measure anti-N IgG responses. Exposure(s) (for observational studies): COVID-19 diagnosis, symptoms, and disease severity. Main Outcome(s) and Measure(s): Presence and durability of SARS-CoV-2 anti-N IgG, transplacental transfer of maternally-derived anti-N IgG. Result(s): Of 1289 pregnant people screened in the seroprevalence study, 5% (65) tested SARS-CoV-2 anti-N IgG+, including 39 (60%) without prior RT-PCR+ or antigen positive results and 53 (82%) without symptoms. Among 89 participants enrolled in the cohort study, 73 (82%) had anti-N IgG+ results during pregnancy. Among 49 participants with delivery samples 33 (67%) were anti-N IgG negative by delivery. Of 24 remaining anti-N IgG+ at delivery with paired cord blood samples, 12 (50%) had efficient transplacental anti-N IgG antibody transfer. Median time from first anti-N IgG to below positive antibody threshold was 17 weeks and did not differ by prior RT-PCR+ or antigen positive status. Conclusions and Relevance: Maternally-derived SARS-CoV-2 antibodies to natural infection may wane before delivery. Vaccines are recommended for pregnant persons to reduce severe illness and confer protection to infants. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

OBJECTIVE: To identify characteristics associated with bullying involvement in pediatric ADHD. METHODS: Data from the 2016 to 2017 National Survey of Children's Health for children aged 6 to 17 years with ADHD were evaluated to assess the association between parent-reported bullying victimization or perpetration and the following potential predictors: demographic characteristics, family factors, school factors, and child conditions/behaviors. RESULTS: Among children with ADHD, 46.9% were bullying victims and 16.2% were perpetrators. Factors associated with victimization included having family financial strain, developmental delay or intellectual disability, friendship difficulties, and school reports about problems. Factors linked to perpetration included being male, receiving government assistance, lack of school engagement, school reports about problems, and having difficulties with friendships, staying calm, and arguing. CONCLUSIONS: Children with ADHD frequently were bullying victims and sometimes bullying perpetrators. Factors related to family financial strain, developmental disabilities, emotional regulation, peer relationships, and school functioning may help to identify risk for bullying and opportunities for anti-bullying interventions.

BACKGROUND: Although 10000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality. METHODS: In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged 18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose-response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inverse-variance weighted random effects models. FINDINGS: We identified 15 studies, of which seven were published and eight were unpublished, with study start dates between 1999 and 2018. The total sample included 47471 adults, among whom there were 3013 deaths (101 per 1000 participant-years) over a median follow-up of 71 years ([IQR 43-99]; total sum of follow-up across studies was 297837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3, and 10901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 060 (95% CI 051-071) for quartile 2, 055 (049-062) for quartile 3, and 047 (039-057) for quartile 4. Restricted cubic splines showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of steps per day until 6000-8000 steps per day and among adults younger than 60 years until 8000-10000 steps per day. Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping rates and mortality was attenuated but remained significant for a peak of 30 min (HR 067 [95% CI 056-083]) and a peak of 60 min (067 [050-090]), but not significant for time (min per day) spent walking at 40 steps per min or faster (112 [096-132]) and 100 steps per min or faster (086 [058-128]). INTERPRETATION: Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health promotion of physical activity. FUNDING: US Centers for Disease Control and Prevention.

Co-infections with sexually transmittable pathogens are common and more likely in women with disturbed vaginal bacteriome. Among those pathogens, the protozoan parasite Trichomonas vaginalis (TV) is most common after accounting for the highly persistent DNA viruses human papillomavirus (HPV) and genital herpes. The parasitic infection often concurs with the dysbiotic syndrome diagnosed as bacterial vaginosis (BV) and both are associated with risks of superimposed viral infections. Yet, the mechanisms of microbial synergisms in evading host immunity remain elusive. We present clinical and experimental evidence for a new role of galectins, glycan-sensing family of proteins, in mixed infections. We assessed participants of the HIV Epidemiology Research Study (HERS) at each of their incident TV visits (223 case visits) matched to controls who remained TV-negative throughout the study. Matching criteria included age, race, BV (by Nugent score), HIV status, hysterectomy, and contraceptive use. Non-matched variables included BV status at 6 months before the matched visit, and variables examined at baseline, within 6 months of and/or at the matched visit e.g. HSV-2, HPV, and relevant laboratory and socio-demographic parameters. Conditional logistic regression models using generalized estimating equations calculated odds ratios (OR) for incident TV occurrence with each log(10) unit higher cervicovaginal concentration of galectins and cytokines. Incident TV was associated with higher levels of galectin-1, galectin-9, IL-1β and chemokines (ORs 1.53 to 2.91, p <0.001). Galectin-9, IL-1β and chemokines were up and galectin-3 down in TV cases with BV or intermediate Nugent versus normal Nugent scores (p <0.001). Galectin-9, IL-1β and chemokines were up in TV-HIV and down in TV-HPV co-infections. In-vitro, TV synergized with its endosymbiont Trichomonasvirus (TVV) and BV bacteria to upregulate galectin-1, galectin-9, and inflammatory cytokines. The BV-bacterium Prevotella bivia alone and together with TV downregulated galectin-3 and synergistically upregulated galectin-1, galectin-9 and IL-1β, mirroring the clinical findings of mixed TV-BV infections. P. bivia also downregulated TVV+TV-induced anti-viral response e.g. IP-10 and RANTES, providing a mechanism for conducing viral persistence in TV-BV co-infections. Collectively, the experimental and clinical data suggest that galectin-mediated immunity may be dysregulated and exploited by viral-protozoan-bacterial synergisms exacerbating inflammatory complications from dysbiosis and sexually transmitted infections.

In August of 2018, the United States Food and Drug Administration (FDA) announced a Class I recall associated with a methicillin-resistant Staphylococcus aureus (MRSA) Safety Alert.

BACKGROUND: Hepatitis B virus (HBV) infection is highly endemic in most low income countries including Cambodia. This nationwide serosurvey was conducted to assess the impact of hepatitis B vaccination and to determine whether Cambodia met the WHO regional 2017 target of hepatitis B surface antigen (HBsAg) seroprevalence less than 1% in five-year-old children. METHODS: A cross-sectional multi-stage cluster survey was conducted among children born during 2010-2012 and their mothers in Cambodia. HBsAg prevalence was estimated by rapid point-of-care testing, and demographic data, including vaccination history, was collected. Vaccine coverage in children and the prevalence of HBsAg among children and mothers was calculated taking into account the complex survey design. Factors associated with children's failure to receive timely (within 24h) vaccination were analysed by multivariate logistic analysis. FINDINGS: A total of 2,520 children 5-7years old and 2,028 mothers were recruited. In total, 78.4% of children received hepatitis B vaccination birth-dose (HepB-BD); of these, 58.7% were administered</=24h. Birth at home or "other" location were independent risk factors for children's failure to receive timely HepB-BD. Overall HBsAg seroprevalence was 4.39% (95%CI: 3.53%-5.45%) among mothers and 0.56% (95%CI: 0.32%-0.98%) among children. The prevalence among children without hepatitis B vaccination was 4.62% (95%CI: 1.31%-14.97%). Among children with a HBsAg-positive mother, prevalence was 10.11% (95%CI: 5.41%-18.11%). INTERPRETATION: Having achieved the 2017 target of less than 1% HBsAg prevalence among 5years old children, Cambodia can now focus on eliminating mother-to-child transmission of HBV. Moreover, the high HBsAg prevalence among mothers suggests that routine screening with proper linkage to care and treatment is needed. Strengthening measures to improve vaccination coverage further and eliminate mother-to-child transmission by coordinated programming with other services offering additional HBV interventions will help move towards the global goal of hepatitis B elimination by 2030. FUNDING: As per sources of funding.

We conducted a serologic survey of 2,430 serum samples collected during 1997-2012 for various studies to determine the prevalence of the hemorrhagic fever virus Ebola virus (EBOV) in equatorial Africa. We screened serum samples for neutralizing antibodies by using a pseudotype microneutralization assay and a newly developed luciferase immunoprecipitation system assay. Specimens seroreactive for EBOV were confirmed by using an ELISA. Our results suggest a serologic prevalence of 2%-3.5% in the Republic of the Congo and the Democratic Republic of the Congo, which have reported outbreaks of infection with EBOV. In addition we detected a seroprevalence of 1.3% in southern Cameroon, which indicated a low risk for exposure in this region.

Size and shape distributions of gold nanorod samples are critical to their physico-chemical properties, especially their longitudinal surface plasmon resonance. This interlaboratory comparison study developed methods for measuring and evaluating size and shape distributions for gold nanorod samples using transmission electron microscopy (TEM) images. The objective was to determine whether two different samples, which had different performance attributes in their application, were different with respect to their size and/or shape descriptor distributions. Touching particles in the captured images were identified using a ruggedness shape descriptor. Nanorods could be distinguished from nanocubes using an elongational shape descriptor. A non-parametric statistical test showed that cumulative distributions of an elongational shape descriptor, that is, the aspect ratio, were statistically different between the two samples for all laboratories. While the scale parameters of size and shape distributions were similar for both samples, the width parameters of size and shape distributions were statistically different. This protocol fulfills an important need for a standardized approach to measure gold nanorod size and shape distributions for applications in which quantitative measurements and comparisons are important. Furthermore, the validated protocol workflow can be automated, thus providing consistent and rapid measurements of nanorod size and shape distributions for researchers, regulatory agencies, and industry.

The primary crystallite size of titania powder relates to its properties in a number of applications. Transmission electron microscopy was used in this interlaboratory comparison (ILC) to measure primary crystallite size and shape distributions for a commercial aggregated titania powder. Data of four size descriptors and two shape descriptors were evaluated across nine laboratories. Data repeatability and reproducibility was evaluated by analysis of variance. One-third of the laboratory pairs had similar size descriptor data, but 83% of the pairs had similar aspect ratio data. Scale descriptor distributions were generally unimodal and were well-described by lognormal reference models. Shape descriptor distributions were multi-modal but data visualization plots demonstrated that the Weibull distribution was preferred to the normal distribution. For the equivalent circular diameter size descriptor, measurement uncertainties of the lognormal distribution scale and width parameters were 9.5% and 22%, respectively. For the aspect ratio shape descriptor, the measurement uncertainties of the Weibull distribution scale and width parameters were 7.0% and 26%, respectively. Both measurement uncertainty estimates and data visualizations should be used to analyze size and shape distributions of particles on the nanoscale.

The present study compared the airborne fungi collection performance of a two-stage cyclone sampler (active method) to the performance of the Personal Aeroallergen Sampler (passive method) using quantitative polymerase chain reaction (qPCR) assays. Indoor air concentrations of the common fungal species Alternaria alternata, Cladosporium cladosporioides, Epicoccum nigrum, and Penicillium chrysogenum were considered. Good correlations between the two sampling methods for the fungi A. alternata, C. cladosporioides, and E. nigrum were observed and the mean effective passive sampling rates (+/-std. dev.) for these species were 0.032 (+/-0.006), 0.058 (+/-0.006), and 0.066 (+/-0.044) l min-1, respectively. Gravitational settling was the dominant collection mechanism for A. alternata and E. nigrum. The root mean square precisions for the passive sampler measurements were also comparable to those of the active sampler (49-73% and 50-102%, respectively). The passive sampler did not allow for the collection of P. chrysogenum, likely due to the insufficient gravitational settling velocity of the fungal particle with its aerodynamic diameter of less than 5 micrometers. The passive sampler, in conjunction with growth-independent qPCR detection methodologies, can be utilized in future exposure assessment studies to deepen our understanding of how individuals are affected by inhalation of airborne fungal pathogens and allergens, especially for those with an aerodynamic diameter greater than 5 micrometers.

This work investigated exposures to nanoparticles and nanofibers during solid core drilling of two types of advanced carbon nanotube (CNT)-hybrid composites: (1) reinforced plastic hybrid laminates (alumina fibers and CNT); and (2) graphite-epoxy composites (carbon fibers and CNT). Mutliple real-time instruments were used to characterize the size distribution (5.6 nm to 20 μm), number and mass concentration, particle-bound polyaromatic hydrocarbons (b-PAHs), and surface area of airborne particles at the source and breathing zone. Time-integrated samples included grids for electron microscopy characterization of particle morphology and size resolved (2 nm to 20 μm) samples forthe quantification of metals. Several new important findings herein include generation of airborne clusters of CNTs not seen during saw-cutting of similar composites, fewer nanofibers and respirable fibers released, similarly high exposures to nanoparticles with less dependence on the composite thickness, and ultrafine (< 5 nm) aerosol originating from thermal degradation of the composite material.