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Abstract Background Understanding the level of exposure to Lassa virus (LASV) in at-risk communities allows for the administration of effective preventive interventions to mitigate epidemics of Lassa fever. We assessed the seroprevalence of LASV antibodies in rural and semiurban communities of two cosmopolitan cities in Nigeria with poorly understood Lassa epidemiology. Methods A cross-sectional study was conducted in ten communities located in the Abuja Municipal Area Council (AMAC), Abuja, and Ikorodu Local Government Area (LGA), Lagos, from February 2nd to July 5th, 2022. Serum samples collected from participants were analyzed for IgG and IgM antibodies using a ReLASV® Pan-Lassa NP IgG/IgM enzyme-linked immunosorbent assay (ELISA) kit. A questionnaire administered to participants collected self-reported sociodemographic and LASV exposure information. Seroprevalence of LASV IgG/IgM was estimated overall, and by study site. Univariate and multivariate log-binomial models estimated unadjusted and adjusted prevalence ratios (aPRs) and 95% confidence intervals (CI) for site-specific risk factors for LASV seropositivity. Grouped Least Absolute Shrinkage and Selection Operator (LASSO) was used for variable selection for multivariate analysis. Results A total of 628 participants with serum samples were included in the study. Most participants were female (434, 69%), married (459, 73%), and had a median age of 38 years (interquartile range 28–50). The overall seroprevalence was 27% (171/628), with a prevalence of 33% (126/376) in Abuja and 18% (45/252) in Lagos. Based on site-specific grouped LASSO selection, enrollment in the dry season (vs. wet; aPR, 95% CI: 1.73, 1.33–2.24), reported inconsistent washing of fruits and vegetables (aPR, 95% CI: 1.45, 1.10–1.92), and a positive malaria rapid test (aPR, 95% CI: 1.48, 1.09-2.00) were independently associated with LASV seropositivity in Abuja, whereas, only a self-reported history of rhinorrhea (PR, 95% CI: 2.21, 1.31–3.72) was independently associated with Lassa seropositivity in Lagos. Conclusions The LASV seroprevalence was comparable to that in other areas in Nigeria. Our findings corroborate those from other studies on the importance of limiting human exposure to rodents and focusing on behavioral factors such as poor hygiene practices to reduce exposure to LASV.

In plants, plasmodesmata establish cytoplasmic continuity between cells to allow for communication and resource exchange across the cell wall. While plant pathogens use plasmodesmata as a pathway for both molecular and physical invasion, the benefits of molecular invasion (cell-to-cell movement of pathogen effectors) are poorly understood. To establish a methodology for identification and characterization of the cell-to-cell mobility of effectors, we performed a quantitative live imaging-based screen of candidate effectors of the fungal pathogen Colletotrichum higginsianum. We predicted C. higginsianum effectors by their expression profiles, the presence of a secretion signal, and their predicted and in planta localization when fused to green fluorescent protein. We assayed for cell-to-cell mobility of nucleocytosolic effectors and identified 14 that are cell-to-cell mobile. We identified that three of these effectors are “hypermobile,” showing cell-to-cell mobility greater than expected for a protein of that size. To explore the mechanism of hypermobility, we chose two hypermobile effectors and measured their impact on plasmodesmata function and found that even though they show no direct association with plasmodesmata, each increases the transport capacity of plasmodesmata. Thus, our methods for quantitative analysis of cell-to-cell mobility of candidate microbe-derived effectors, or any suite of host proteins, can identify cell-to-cell hypermobility and offer greater understanding of how proteins affect plasmodesmal function and intercellular connectivity. [Graphic: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Abstract Intravenous remdesivir (RDV) is US Food and Drug Administration–approved for hospitalized and nonhospitalized individuals with coronavirus disease 2019. RDV undergoes intracellular metabolic activation to form the active triphosphate, GS‐443902, and other metabolites. Alternative administration routes, including localized pulmonary delivery, can lower systemic exposure and maximize exposure at the site of action. This study evaluated the pharmacokinetics (PK) and safety of inhaled RDV in healthy adults. This phase Ia, randomized, placebo‐controlled study evaluated inhaled RDV in healthy participants randomized 4:1 to receive RDV or placebo as single doses (4 cohorts) or multiple once‐daily doses (3 cohorts). Doses in cohorts 1–6 were administered as an aerosolized solution for inhalation through a sealed facemask; doses in cohort 7 were administered as an aerosolized solution for inhalation through a mouthpiece. Safety was assessed throughout the study. Seventy‐two participants were enrolled (inhaled RDV, n = 58 and placebo, n = 14). Following single RDV doses, RDV, GS‐704277, and GS‐441524 plasma PK parameters indicated dose‐proportional increases in area under the concentration‐time curve (AUC) extrapolated to infinite time, AUC from time zero to last quantifiable concentration, and maximum observed concentration. Analyte plasma concentrations after multiple RDV doses were consistent with those for single‐dose RDV. Analyte plasma exposures were lower when RDV was administered with a mouthpiece versus a sealed facemask. The most common adverse events included nausea, dizziness, and cough. Single‐ and multiple‐dose inhaled RDV exhibited linear and dose‐proportional plasma PK. Administration of RDV via inhalation was generally safe and well‐tolerated.

Abstract PF614, a trypsin‐activated abuse protection oxycodone prodrug designed to reduce recreational drug abuse, was compared to OxyContin for safety and pharmacokinetics (PKs) of plasma oxycodone following oral administration. This study was a two‐part design including a multi‐ascending dose (part A) and a bioequivalence (BE) study (part B) in healthy volunteers. In part A, 24 subjects were randomized 3:1 to receive PF614 (50, 100, or 200 mg, n = 6/cohort) or OxyContin (20, 40, or 80 mg; n = 2/cohort) in ascending cohorts, delivered every 12 h for a total of nine doses. In part B, 60 subjects randomized in a four‐way crossover to evaluate BE, received PF614 100 mg and OxyContin 40 mg in fasted and fed (high‐fat diet) states. All subjects were naltrexone blocked prior to first study drug administration to protect against opioid‐related adverse effects; repeat doses were provided on days 1–5. In part A, PF614 was well‐tolerated following twice daily doses of up to 200 mg for 5 days. Plasma oxycodone maximal plasma concentration and area under the concentration time curve increased linearly with increasing doses. Part B showed that plasma oxycodone BE was achieved following 100 mg PF614 or 40 mg OxyContin under both fasted and fed conditions. Additionally, PF614 provided similar oxycodone exposures following both fasted and fed states. This study confirms findings from our single‐ascending dose study, showing that PF614 100 mg releases oxycodone with a PK profile comparable to 40 mg OxyContin under both fasted and fed conditions and with a similar safety profile under naltrexone‐blocked conditions.

IntroductionWe describe herein a large-scale, multidisciplinary course-based undergraduate research experience program (CRE) developed at Lawrence Technological University (LTU). In our program, all students enrolled in CRE classes participate in authentic research experiences within the framework of the curriculum, eliminating self-selection processes and other barriers to traditional extracurricular research experiences.MethodsSince 2014, we have designed and implemented more than 40 CRE courses in our College of Arts and Sciences involving more than 30 instructors from computer science, mathematics, physics, biology, chemistry, English composition, literature, philosophy, media communication, nursing, and psychology.ResultsAssessment survey data indicates that students who participate in CRE courses have an enhanced attitude towards research and discovery, as well as increased self-efficacy. This intervention is particularly relevant for non-traditional students, such as students who commute and/or have significant work or childcare commitments, who often experience limited access to research activities.DiscussionHerein we highlight the importance of a systemic institutional change that has made this intervention sustainable and likely to outlast the external funding phase. Systemic change can emerge from a combination of conditions, including: (1) developing a critical mass of CRE courses by providing instructors with both incentives and training; (2) developing general principles on which instructors can base their CRE activities; (3) securing and maintaining institutional support to promote policy changes towards a more inclusive institution; and (4) diversifying the range of the intervention, both in terms of initiatives and disciplines involved.

Abstract Background Very premature birth (gestational age between 28 and 31 + 6 weeks) is associated with increased risk of cognitive delay and attention deficit disorder, which have been linked to anomalies in the development of executive functions (EFs) and their precursors. In particular, very preterm (VP) infants display anomalies in controlling attention and gathering task-relevant information. Early interventions that support attention control may be pivotal in providing a secure base for VP children’s later attainments. The Attention Control Training (ACT) is a cognitive training intervention that targets infants’ abilities to select visual information according to varying task demands but had not been tested in VP infants. We conducted a feasibility study to test the processes we intend to use in a trial delivering the ACT to VP infants. Methods and design We tested recruitment and retention of VP infants and their families in a randomised trial, as well as acceptability and completion of baseline and outcome measures. To evaluate these aims, we used descriptive quantitative statistics and qualitative methods to analyse feedback from infants’ caregivers. We also investigated the quality of eye-tracking data collected and indicators of infants’ engagement in the training, using descriptive statistics. Results Twelve VP infants were recruited, and 10 (83%) completed the study. Participants’ parents had high education attainment. The rate of completion of baseline and outcome measures was optimal. VP infants demonstrated engagement in the training, completing on average 84 min of training over three visits, and displaying improved performance during this training. Eye-tracking data quality was moderate, but this did not interfere with infants’ engagement in the training. Discussion The results suggest the ACT can be delivered to VP infants. However, challenges remain in recruitment of numerous and diverse samples. We discuss strategies to overcome these challenges informed by results of this study. Trial registration Registered Registration ID: NCT03896490 . Retrospectively registered at Clinical Trials Protocol Registration and Results System ( clinicaltrials.gov ).

Abstract Background Children born preterm may display cognitive, learning, and behaviour difficulties as they grow up. In particular, very premature birth (gestation age between 28 and less than 32 weeks) may put infants at increased risk of intellectual deficits and attention deficit disorder. Evidence suggests that the basis of these problems may lie in difficulties in the development of executive functions. One of the earliest executive functions to emerge around 1 year of age is the ability to control attention. An eye-tracking-based cognitive training programme to support this emerging ability, the Attention Control Training (ACT), has been developed and tested with typically developing infants. The aim of this study is to investigate the feasibility of using the ACT with healthy very preterm (VP) infants when they are 12 months of age (corrected age). The ACT has the potential to address the need for supporting emerging cognitive abilities of VP infants with an early intervention, which may capitalise on infants’ neural plasticity. Methods/design The feasibility study is designed to investigate whether it is possible to recruit and retain VP infants and their families in a randomised trial that compares attention and social attention of trained infants against those that are exposed to a control procedure. Feasibility issues include the referral/recruitment pathway, attendance, and engagement with testing and training sessions, completion of tasks, retention in the study, acceptability of outcome measures, quality of data collected (particularly, eye-tracking data). The results of the study will inform the development of a larger randomised trial. Discussion Several lines of evidence emphasise the need to support emerging cognitive and learning abilities of preterm infants using early interventions. However, early interventions with preterm infants, and particularly very preterm ones, face difficulties in recruiting and retaining participants. These problems are also augmented by the health vulnerability of this population. This feasibility study will provide the basis for informing the implementation of an early cognitive intervention for very preterm infants. Trial registration Registered Registration ID: NCT03896490 . Retrospectively registered at Clinical Trials Protocol Registration and Results System (clinicaltrials.gov).

BackgroundVery preterm (VP) infants (born 28 to MethodsWe tested the feasibility of a randomised trial where VP infants took part in a computerised cognitive procedure to train attention control. Ten healthy VP infants aged approximately 12 months (corrected age) and randomly allocated with 1:1 ratio to the training (interactive computerised presentations) or an active control procedure completed the study. Before and after the training programme, participating infants completed a battery of screen-based attention tests, naturalistic attention and communication tasks, and temperament assessments. In a previous study we analysed the data concerning feasibility (e.g. recruitment and retention). In the paper presented here we considered the infants' performance and used Bayesian regression in order to provide credible treatment estimates considering the data collected.ResultsEstimates indicate moderate treatment effects in visual memory: compared to controls, trained infants displayed improvements equivalent to 0.59 SD units. Trained infants also improved in their abilities to attend to less salient stimuli presentations by 0.82 SD units, compared to controls. However, results did not indicate relevant gains in attention habituation or disengagement. We also reported moderate improvements in focused attention during naturalistic tasks, and in directing other people's attention to shared objects.DiscussionThe results warrant further investigation concerning the effectiveness of training attention control in VP infants, extending this line of research beyond our small and homogeneous sample of healthy VP infants. This study also emphasises the utility of Bayesian approaches in estimating potentially relevant effects in small samples or exploratory studies. The scope for further research on early attention control training is discussed in light of studies indicating VP children's susceptibility to positive environmental inputs.Trial registrationRegistration ID: NCT03896490. Retrospectively registered at Clinical Trials Protocol Registration and Results System (clinicaltrials.gov).

Statistical machine learning algorithms have been widely used to analyse industrial data for batch process monitoring and control. In this study, we aimed to take a two-step approach to systematically reduce data dimensionality and to design soft-sensors for product quality prediction. The approach first employs partial least squares to screen the entire dataset and identify critical time regions and operational variables, then adopts multiway partial least squares to construct soft-sensors within the reduced space to estimate final product quality. Innovations of this approach include the ease of data visualisation and ability to identify major operational activities within the factory. To highlight efficiency and practical benefits, an industrial personal care product manufacturing process was presented as an example and two soft-sensors were successfully developed for product end viscosity estimation. Furthermore, the accuracy, reliability, and data efficiency of the soft-sensors were thoroughly discussed. This paper, therefore, demonstrates the industrial potential of the proposed approach.

The importance of honey for medicinal purposes is well documented in some of the world’s oldest literature. Honey is well known and studied for its antimicrobial properties. The medicinal properties in honey originate from the floral source used by bees. Manuka honey is a dark monofloral honey rich in phenolic content, and currently it is gaining much attention for its antimicrobial activity. Researchers have found that honey is effective against a wide range of pathogens. The antibacterial potency of Manuka honey was found to be related to the Unique Manuka Factor (UMF) rating, which is correlated with the methylglyoxal and total phenols content. It is reported that different types of Manuka honey have differing effects and Gram-negative bacteria are more resistant than Gram-positive bacteria. Bacterial resistance to honey as antimicrobial agent has yet to be identified, possibly due to the presence of a complex mixture of methylglyoxal and other components. Honey is also reported to alter a bacterium’s shape and size through septal ring alteration, which affects cell morphology and growth. Research has shown that Manuka honey of different UMF values has medicinal properties of interest and it can be beneficial when used as a combination treatment with other antimicrobial agents.

In light of the rapid spread of coronavirus disease 2019 (COVID-19) across the United States, the Centers for Disease Control and Prevention (CDC) and hospitals nationwide have developed new protocols to address infection control as well as the care of critical patients. Airway management has been particularly difficult; the challenge of quickly establishing an airway in patients must be balanced by the risk of aerosolizing respiratory secretions and putting the provider at risk of infection. Significant attention has been given to developing protocols for the emergency department and critical care units, but little guidance regarding establishing airway and respiratory support for patients in the prehospital setting has been made available. While some of the recommendations can be extrapolated from hospital guidelines, other factors such as environment and available resources make these protocols unfeasible. Through review of current literature the authors established recommendations regarding airway management and the provision of respiratory support to patients developing respiratory failure related to COVID-19.

An amendment to this paper has been published and can be accessed via the original article.

Linear Shaped Charges (LSCs) have been assumed to function in the same manner as Conical Shaped Charges (CSCs) in the published literature that describes a metallic jet process for penetration. However, based on the facts that the LSC liner is composed of flat surfaces instead of the curved cone shaped liner of a CSC and the LSC detonation propagation is perpendicular to the penetrator projection direction, the approach to investigate the penetrator formation process of LSCs should be examined from a different perspective. Because there are fundamental differences between CSCs and LSCs in the formation of a jet, the cutting performances would be under different regimes. As a preliminary investigation, in this paper, we report a numerical observation of the LSC jetting properties using AUTODYN®.

Visual search is a complex task that involves many neural pathways to identify relevant areas of interest within a scene. Humans remain a critical component in visual search tasks, as they can effectively perceive anomalies within complex scenes. However, this task can be challenging, particularly under time pressure. In order to improve visual search training and performance, an objective, process-based measure is needed. Eye tracking technology can be used to drive real-time parsing of EEG recordings, providing an indication of the analysis process. In the current study, eye fixations were used to generate ERPs during a visual search task. Clear differences were observed following performance, suggesting that neurophysiological signatures could be developed to prevent errors in visual search tasks.