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In this registered report, we propose to stress-test existing models for predicting the ideology-prejudice association, which varies in size and direction across target groups. Previous models of this relationship use the perceived ideology, status, and choice in group membership of target groups to predict the ideology-prejudice association across target groups. These analyses show that models using only the perceived ideology of the target group are more accurate and parsimonious in predicting the ideology-prejudice association than models using perceived status, choice, and all of the characteristics in a single model. Here, we stress-test the original models by testing the models' predictive utility with new measures of explicit prejudice, a comparative operationalization of prejudice, the Implicit Association Test, and additional target groups. In Study 1, we propose to directly test the previous models using an absolute measure of prejudice that closely resembles the measure used in the original study. This will tell us if the models replicate with distinct, yet conceptually similar measures of prejudice. In Study 2, we propose to develop new ideology-prejudice models for a comparative operationalization of prejudice using both explicit measures and the Implicit Association Test. We will then test these new models using data from the Ideology 2.0 project collected by Project Implicit. We do not have full access to this data yet, but upon acceptance of our Stage 1 registered report, we will gain access to the complete dataset. Currently, we have access to an exploratory subset of the data that we use to demonstrate the feasibility of the study, but its limited number of target groups prevents conclusions from being made.

BackgroundPatients experience emotional distress and hold cardiac misconceptions following ST-elevation myocardial infarction. These issues informed the co-production of Cardiac Brief Intervention with patients and clinicians. The current study will establish a knowledge base for the feasibility of delivering this intervention to patients following ST-elevation myocardial infarction, with a preliminary exploration of impact on associated outcomes (ClinicalTrials.gov: NCT05848674).MethodsA pilot randomised controlled trial incorporating a mixed-methods design will be conducted. Patients with ST-elevation myocardial infarction (number = 40) will be recruited from coronary care units at two hospital centres in Northern Ireland, with participants randomised (1:1) to the intervention or control group. Cardiac Brief Intervention constitutes a nurse-led, short (20 minutes) emotional and educational support discussion with a patient, with a leaflet that serves as a memory-aid. It will be delivered to the intervention group prior to discharge from a coronary care unit. The control group will receive standard care information. Data will be collected at baseline, post-intervention, 4 weeks from diagnosis, and 14 weeks from diagnosis. Feasibility measurements and process evaluation (quantitative and qualitative) will assess the viability of the research design and intervention delivery. Cardiac rehabilitation attendance data will be collected, and participants will complete questionnaires related to associated outcomes. Quantitative data will be reported with descriptive statistics and qualitative data will be analysed using framework analysis, with data integrated to achieve triangulation of findings.DiscussionEducational and emotional difficulties following ST-elevation myocardial infarction may impede patient outcomes and cardiac rehabilitation participation. These issues informed the co-production of Cardiac Brief Intervention with patients and clinicians. This study will evaluate the feasibility of delivering Cardiac Brief Intervention to patients. These results will inform large-scale definitive testing of the intervention, which may lead to adoption in clinical practice to improve cardiac rehabilitation uptake and patient outcomes.

Financial toxicity is common in individuals with COVID-19 and Long COVID. However, the extent of financial toxicity experienced, in comparison to other common comorbidities, is uncertain. Contributing factors exacerbating financial challenges in Long COVID are also unclear. These knowledge gaps are addressed via a cross-sectional analysis utilizing data from the 2022 National Health Interview Survey (NHIS), a representative sample drawn from the United States. COVID-19 cases were identified through self-reported positive testing or physician diagnoses. Long COVID was defined as experiencing COVID-19-related symptoms for more than three months. Comorbidity was assessed based on self-reported diagnoses of ten doctor-diagnosed conditions (Yes/No). Financial toxicity was defined as having difficulty paying medical bills, cost-related medication nonadherence, delaying healthcare due to cost, and/or not obtained healthcare due to cost. A total of 27,492 NHIS 2022 respondents were included in our analysis, representing 253 million U.S. adults. In multivariable logistic regression models, adults with Long COVID (excluding respondents with COVID-19 but not Long COVID), showed increased financial toxicity compared to those with other comorbidities, such as epilepsy (OR [95% CI]: 1.69 [1.22, 2.33]), dementia (1.51 [1.01, 2.25]), cancer (1.43 [1.19, 1.71]) or respiratory/cardiovascular conditions (1.18 [1.00, 1.40]/1.23 [1.02, 1.47]). Long COVID-related financial toxicity was associated with female sex, age

An individual's likelihood of developing non-communicable diseases is often influenced by the types, intensities and duration of exposures at work. Job exposure matrices provide exposure estimates associated with different occupations. However, due to their time-consuming expert curation process, job exposure matrices currently cover only a subset of possible workplace exposures and may not be regularly updated. Scientific literature articles describing exposure studies provide important supporting evidence for developing and updating job exposure matrices, since they report on exposures in a variety of occupational scenarios. However, the constant growth of scientific literature is increasing the challenges of efficiently identifying relevant articles and important content within them. Natural language processing methods emulate the human process of reading and understanding texts, but in a fraction of the time. Such methods can increase the efficiency of both finding relevant documents and pinpointing specific information within them, which could streamline the process of developing and updating job exposure matrices. Named entity recognition is a fundamental natural language processing method for language understanding, which automatically identifies mentions of domain-specific concepts (named entities) in documents, e.g., exposures, occupations and job tasks. State-of-the-art machine learning models typically use evidence from an annotated corpus, i.e., a set of documents in which named entities are manually marked up (annotated) by experts, to learn how to detect named entities automatically in new documents. We have developed a novel annotated corpus of scientific articles to support machine learning based named entity recognition relevant to occupational substance exposures. Through incremental refinements to the annotation process, we demonstrate that expert annotators can attain high levels of agreement, and that the corpus can be used to train high-performance named entity recognition models. The corpus thus constitutes an important foundation for the wider development of natural language processing tools to support the study of occupational exposures.

The global fight against the COVID-19 pandemic has underscored the critical importance of widespread vaccination to mitigate the impact of the virus on public health. The current study aimed to investigate which social influences might be most important for predicting attitudes towards COVID-19 vaccination and vaccine uptake among young students in the UK. We focused on the cultural evolution and social transmission aspects, i.e., parent-to-child versus peer-to-peer, of attitudes and vaccine uptake during the COVID-19 pandemic. A sample of 192 UK students (aged 18 to 35 years old) filled in an online survey including measures for attitudes towards COVID-19 vaccination and vaccine uptake and/or intention, age, and gender. Participants were also asked about their mother's, father's, and best friend's attitudes towards COVID-19 vaccination and vaccine uptake. Finally, they provided a subjective measure of the quality relationship with their parents. Overall, our results suggest that both parents and very close friends are important agents in understanding the students' attitudes towards COVID-19 vaccination and vaccine uptake. More specifically, our findings suggest the mother's vaccine uptake as the most salient predictor of students' attitudes towards COVID-19 vaccination and vaccine uptake, particularly when the students report having a positive relationship with their parents. In cases where students' experience negative relationship with their parents, the best friend's vaccine uptake may supersede the mother's influence. Despite these nuances, a general trend emerges from our data suggesting that vaccine uptake could be primarily guided by vertical transmission (i.e., parent to child). Our results have the potential to influence public health strategies, communication campaigns, and targeted interventions to enhance vaccination uptake. Identifying key social predictors can enable policymakers and health authorities to tailor vaccination promotion efforts towards mothers' and peers' vaccine uptake to increase overall positive attitudes and vaccine uptake among young people.

[This corrects the article DOI: 10.1371/journal.pone.0258979.].

Overcoming the TB epidemic requires moving past expanding the coverage of healthcare services and looking to improve the quality of TB services. During COVID-19, the suboptimal state of TB services has further deteriorated, and little is known about how these services have fared after the pandemic. The study aims to assess the quality TB diagnostic services in primary health care (PHC) clinics in the eThekwini district, South Africa. Twenty-one clinics with the lowest and highest headcounts from each region of eThekwini were purposively selected. An audit tool adapted from the United States Agency for International Development (USAID) and the national TB guidelines was used to collect data on six different audit components. To assess quality, a 3-point scale was used where clinics could get a rating of either excellent, moderate, or poor performance. Descriptive statistics were employed to summarize and analyze clinic scores in Stata v15.1. Additionally, associations between clinic scores and clinic characteristics were investigated using Pearson's pairwise correlation coefficient and a linear regression model, where p < 0.05 was the measure of statistical significance. The audit found that the quality of diagnostic services in eThekwini was moderate. The gaps that required addressing were the lack of TB training among staff, adherence to infection prevention and control practices, and contact screening. Without feasible solutions, these will hinder current TB management strategies and slow progress toward ending the TB epidemic.

Chemical information has become increasingly ubiquitous and has outstripped the pace of analysis and interpretation. We have developed an R package, uafR, that automates a grueling retrieval process for gas -chromatography coupled mass spectrometry (GC -MS) data and allows anyone interested in chemical comparisons to quickly perform advanced structural similarity matches. Our streamlined cheminformatics workflows allow anyone with basic experience in R to pull out component areas for tentative compound identifications using the best published understanding of molecules across samples (pubchem.gov). Interpretations can now be done at a fraction of the time, cost, and effort it would typically take using a standard chemical ecology data analysis pipeline. The package was tested in two experimental contexts: (1) A dataset of purified internal standards, which showed our algorithms correctly identified the known compounds with R2 values ranging from 0.827-0.999 along concentrations ranging from 1 × 10-5 to 1 × 103 ng/μl, (2) A large, previously published dataset, where the number and types of compounds identified were comparable (or identical) to those identified with the traditional manual peak annotation process, and NMDS analysis of the compounds produced the same pattern of significance as in the original study. Both the speed and accuracy of GC -MS data processing are drastically improved with uafR because it allows users to fluidly interact with their experiment following tentative library identifications [i.e. after the m/z spectra have been matched against an installed chemical fragmentation database (e.g. NIST)]. Use of uafR will allow larger datasets to be collected and systematically interpreted quickly. Furthermore, the functions of uafR could allow backlogs of previously collected and annotated data to be processed by new personnel or students as they are being trained. This is critical as we enter the era of exposomics, metabolomics, volatilomes, and landscape level, high-throughput chemotyping. This package was developed to advance collective understanding of chemical data and is applicable to any research that benefits from GC -MS analysis. It can be downloaded for free along with sample datasets from Github at github.org/castratton/uafR or installed directly from R or RStudio using the developer tools: 'devtools::install_github("castratton/uafR")'.

IntroductionMaternal disorders are the third leading cause of sepsis globally, accounting for 5.7 million (12%) cases in 2017. There are increasing concerns about the emergence of antimicrobial resistance (AMR) in bacteria commonly causing maternal sepsis. Our aim is to describe the protocol for a clinical and microbiology laboratory study to understand risk factors for and the bacterial etiology of maternal sepsis in a tertiary Obstetrics and Gynaecology Hospital.MethodsThis case-control study aims to recruit 100 cases and 200 controls at Tu Du Hospital in Ho Chi Minh City, Vietnam, which had approximately 55,000 births in 2022. Women aged ≥ 18 years and ≥ 28 weeks gestation having a singleton birth will be eligible for inclusion as cases or controls, unless they have an uncomplicated localised or chronic infection, or an infection with SARS-CoV-2. Cases will include pregnant or recently pregnant women with sepsis recognised between the onset of labour and/or time of delivery/cessation of pregnancy for up to 42 days post-partum. Sepsis will be defined as suspected or confirmed infection with an obstetrically modified Sequential Organ Failure Assessment score of ≥ 2, treatment with intravenous antimicrobials and requested cultures of any bodily fluid. Controls will be matched by age, location, parity, mode of delivery and gestational age. Primary and secondary outcomes are risk factors associated with the development of maternal sepsis, the frequency of adverse outcomes due to maternal sepsis, bacterial etiology and AMR profiles of cases and controls.DiscussionThis study will improve understanding of the epidemiology and clinical implications of maternal sepsis management including the presence of AMR in women giving birth in Vietnam. It will help us to determine whether women in this setting are receiving optimal care and to identify opportunities for improvement.

Geochemical proxies of sea surface temperature (SST) and seawater pH (pHsw) in scleractinian coral skeletons are valuable tools for reconstructing tropical climate variability. However, most coral skeletal SST and pHsw proxies are univariate methods that are limited in their capacity to circumvent non-climate-related variability. Here we present a novel multivariate method for reconstructing SST and pHsw from the geochemistry of coral skeletons. Our Scleractinian Multivariate Isotope and Trace Element (SMITE) method optimizes reconstruction skill by leveraging the covariance across an array of coral elemental and isotopic data with SST and pHsw. First, using a synthetic proxy experiment, we find that SMITE SST reconstruction statistics (correlation, accuracy, and precision) are insensitive to noise and variable calibration period lengths relative to Sr/Ca. While SMITE pHsw reconstruction statistics remain relative to δ11B throughout the same synthetic experiment, the magnitude of the long-term trend in pHsw is progressively lost under conditions of moderate-to-high analytical uncertainty. Next, we apply the SMITE method to an array of seven coral-based geochemical variables (B/Ca, δ11B, Li/Ca, Mg/Ca, Sr/Ca, U/Ca & Li/Mg) measured from two Bermudan Porites astreoides corals. Despite a

[This corrects the article DOI: 10.1371/journal.pone.0256815.].

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is associated with high mortality rates. Despite antibiotic therapy, persistent bacteremia is challenging to treat. Combination therapy with ceftaroline has emerged as a potential treatment option; however, the optimal duration and clinical implications after bacteremia clearance are unknown.MethodsThis retrospective cohort study examined patients with high-grade or persistent MRSA bacteremia who were treated with ceftaroline combination therapy at the University of New Mexico Hospital between January 2014 and June 2021. Patients were categorized into short- (ResultsA total of 32 patients were included in this study. The most common sources of bacteremia were bone/joint and endovascular (28.1%, 9/32 each). The median duration of combination therapy after clearance was seven days (IQR 2.8, 11). Patients in the long-duration group had a lower Charlson comorbidity index (1.0 vs 5.5, p = 0.017) than those in the short-duration group. After adjusting for confounders, there was no significant difference in the 30-day all-cause mortality between the groups (AOR 0.17, 95% CI 0.007-1.85, p = 0.18). No association was found between combination therapy duration and recurrence (OR 2.53, 95% CI 0.19-inf, p = 0.24) or adverse drug events (OR 3.46, 95% CI 0.39-74.86, p = 0.31). After controlling for total hospital length of stay, there was no significant difference in the post-bacteremia clearance length of stay between the two groups (p = 0.37).ConclusionsProlonging ceftaroline combination therapy after bacteremia clearance did not significantly improve outcomes in patients with persistent or high-grade MRSA bacteremia. The limitations of this study warrant cautious interpretation of its results. Larger studies are needed to determine the optimal duration and role of combination therapy for this difficult-to-treat infection.

Social network analysis can support quality improvement in care homes but traditional approaches to social network analysis are not always feasible in care homes. Recalling contacts and movements in a home is difficult for residents and staff and documentary and other sources of individual contacts can be unreliable. Bluetooth enabled wearable devices are a potential means of generating reliable, trustworthy, social network data in care home communities. In this paper, we explore the empirical, theoretical and real-world potential and difficulties in using Bluetooth enabled wearables with residents and staff in care homes for quality improvement. We demonstrate, for the first time, that a relatively simple system built around the Internet of Things, Bluetooth enabled wearables for residents and staff and passive location devices (the CONTACT intervention) can capture social networks and data in homes, enabling social network analysis, measures, statistics and visualisations. Unexpected variations in social network measures and patterns are surfaced, alongside "uncomfortable" information concerning staff time spent with residents. We show how technology might also help identify those most in need of social contact in a home. The possibilities of technology-enabled social network analysis must be balanced against the implementation-related challenges associated with introducing innovations in complex social systems such as care homes. Behavioural challenges notwithstanding, we argue that armed with social network information, care home staff could better tailor, plan and evaluate the effects of quality improvement with the sub-communities that make up a care home community.

IntroductionConsidering the usefulness of mobile health (mHealth) technologies in healthcare delivery in low- and middle-income countries, including Ghana; there is a need to explore healthcare professionals' perspectives on the availability and use of mHealth for disease screening and treatment of patients' conditions. The study's main aim is to explore healthcare professionals' perspectives regarding the availability and use of mHealth applications for disease screening and management at point-of-care in Ghana's Ashanti Region.Materials and methodsWe conducted in-depth interviews with healthcare professionals who use mHealth applications daily between July and September 2020. A purposive sampling strategy was employed to select healthcare professionals who have been using mobile health application tools to support healthcare delivery. The researchers conducted 14 in-depth interviews with healthcare professionals on the availability and use of mHealth applications to support disease diagnosis and treatment of patients' conditions. Data were transcribed, coded, arranged, and analyzed to determine categories and themes.ResultsThe study results demonstrated that healthcare workers had positive perceptions towards mHealth applications. Healthcare professionals identified significant challenges concerning mHealth applications: the high cost of data; lack of education or limited awareness; poor mobile networks; unstable internet connectivity; erratic power supply; and unavailability of logistics. Healthcare professionals identified the following prerequisite strategies to strengthen the use and scale-up of mHealth applications: stable internet connectivity; creating awareness; supplying logistics; reducing the cost of data; and developing local mobile apps.ConclusionsThe study results revealed the availability of mHealth applications at the individual level for disease screening and treatment support of patients' conditions. The study also showed several significant challenges facing mHealth applications which need to be addressed to guarantee the successful implementation and scaling-up of mHealth activities at all levels of healthcare delivery. Hence, future research should incorporate healthcare professionals' perspectives to completely understand mHealth implementation and scaling-up challenges and measures to inform policy regulations.

Hippocampal interneurons are a very diverse population of cells. Using single-cell quantitative PCR to analyze rat CA1 hippocampal interneurons, we quantified neuronal nicotinic acetylcholine receptor (nAChR) mRNA subunit expression and detailed possible nAChR subtype combinations for the α2, α3, α4, α5, α7, β2, β3, and β4 subunits. We also compared the expression detected in the stratum oriens and the stratum radiatum hippocampal layers. We show that the majority of interneurons in the CA1 of the rat hippocampus contain detectable levels of nAChR subunit mRNA. Our results highlight the complexity of the CA1 nAChR population. Interestingly, the α3 nAChR subunit is one of the highest expressed subunit mRNAs in this population, while the α4 is one of the least likely subunits to be detected in CA1 interneurons. The β2 nAChR subunit is the highest expressed beta subunit mRNA in these cells. In addition, Pearson's correlation coefficient values are calculated to identify significant differences between the nAChR subunit combinations expressed in the CA1 stratum oriens and the stratum radiatum. Statistical analysis also indicates that there are likely over 100 different nAChR subunit mRNA combinations expressed in rat CA1 interneurons. These results provide a valid avenue for identifying nAChR subtype targets that may be effective hippocampus-specific pharmacological targets.

RiSE study aims to evaluate a race-based stress-reduction intervention as an effective strategy to improve coping and decrease stress-related symptoms, inflammatory burden, and modify DNA methylation of stress response-related genes in older AA women. This article will describe genomic analytic methods to be utilized in this longitudinal, randomized clinical trial of older adult AA women in Chicago and NYC that examines the effect of the RiSE intervention on DNAm pre- and post-intervention, and its overall influence on inflammatory burden. Salivary DNAm will be measured at baseline and 6 months following the intervention, using the Oragene-DNA kit. Measures of perceived stress, depressive symptoms, fatigue, sleep, inflammatory burden, and coping strategies will be assessed at 4 time points including at baseline, 4 weeks, 8 weeks, and 6 months. Genomic data analysis will include the use of pre-processed and quality-controlled methylation data expressed as beta (β) values. Association analyses will be performed to detect differentially methylated sites on the targeted candidate genes between the intervention and non-intervention groups using the Δβ (changes in methylation) with adjustment for age, health behaviors, early life adversity, hybridization batch, and top principal components of the probes as covariates. To account for multiple testing, we will use FDR adjustment with a corrected p-value of

Urban agriculture is increasingly valued as a strategy for improving quality of life in cities, but urban growers face challenges and often lack coordinated support from governments and the agricultural industry. We surveyed urban growers through an online survey, primarily in the Northeastern United States, to develop a profile of growers and associated organizations, assess the current state of urban agriculture, and determine how universities could help meet their needs. A total of 394 respondents completed the survey and most urban growers were white (non-Hispanic) and younger than 45 years old. Women and men were in almost equal proportion. Urban growers were well-educated, but most did not receive a degree in agriculture. Urban agriculture in our study area was dominated by relatively small non-profit organizations and home and community gardens were the most common types of organizations. Urban agricultural organizations want to improve environmental sustainability and socio-cultural conditions through food access and security, regardless of their tax status. Urban growers face diverse barriers and challenges and the most ubiquitous barriers and challenges reported by respondents were related to availability of land and long-term access in urban areas. Many respondents received low revenue or were operating at a net loss even though they reported diverse income streams. Respondents need a wide range of training, including in traditional agricultural topics as well as financial management and business trainings. Universities can play a key role in promoting urban agriculture by offering training and research. Workforce development is a large priority among universities, so urban growers should regularly be consulted, and the results shared with career and workforce development professionals and researchers in urban areas to identify training and research that meets the needs of stakeholders.

BackgroundInequalities exist in uptake of bowel cancer screening in England with low uptake in areas with high deprivation and amongst certain ethnic and religious groups. Individuals from these groups are more likely to receive a late diagnosis of bowel cancer. Uptake in Muslim communities, for example, has been shown to be lower than in the general population. Culturally adapted interventions are needed to address these inequalities. This feasibility study aims to assess the acceptability and accessibility of an educational faith-placed bowel cancer screening intervention in the East of England, alongside its impact on bowel screening uptake. It was developed by the British Islamic Medical Association in partnership with community stakeholders and professionals.MethodsEthical approval was granted on the 27 October 2021, REC reference number 21/EE/0231. A two-group non-randomised feasibility mixed methods study will be conducted, using surveys, focus groups and semi-structured interviews. Participants eligible for bowel screening will be recruited through local mosques and community venues. We aim to recruit 100 participants to the intervention group and 150 to the comparison group (not receiving the intervention). Intervention group participants will complete a survey at baseline, post-intervention and at six-month follow up. Comparison group participants will complete a survey at baseline and at six-month follow up. Outcomes will include: intention to take up screening; actual screening uptake; knowledge, attitudes, barriers and facilitators towards screening. Regional screening hub records will be used to ascertain actual screening uptake at six-month follow-up. Quantitative survey data will be summarised using descriptive statistics (e.g., proportion), and exploratory univariate analysis will be undertaken (e.g., chi-squared test). Two focus group interviews will be conducted with intervention group participants (with up to 16 participants). Semi-structured interviews will be conducted with 10 clinicians delivering the intervention to explore the acceptability of the intervention, training, and delivery. All qualitative data will be subject to a general inductive analysis.DiscussionThe findings will inform how faith-placed interventions can be implemented to increase uptake of bowel cancer screening, and potentially other health promotion programmes, to address health inequalities in ethnically diverse communities in England.

This study aimed to better understand the vulnerability of children in their first year of school, aged between 5 years 5 months and 6 years 6 months, based on five health and development domains. Identification of subgroups of children within these domains can lead to more targeted policies to reduce these vulnerabilities. The focus of this study was to determine clusters of geographical regions with high and low proportions of vulnerable children in Queensland, Australia. This was achieved by carrying out a K-means analysis on data from the Australian Early Development Census and the Australian Bureau of Statistics. The clusters were then compared with respect to their geographic locations and risk factor profiles. The results are made publicly available via an interactive dashboard application developed in R Shiny.

ObjectiveThe gastrointestinal microbiome in preterm infants exhibits significant influence on optimal outcomes-with dysbiosis shown to substantially increase the risk of the life-threatening necrotizing enterocolitis. Iron is a vital nutrient especially during the perinatal window of rapid hemoglobin production, tissue growth, and foundational neurodevelopment. However, excess colonic iron exhibits potent oxidation capacity and alters the gut microbiome-potentially facilitating the proliferation of pathological bacterial strains. Breastfed preterm infants routinely receive iron supplementation starting 14 days after delivery and are highly vulnerable to morbidities associated with gastrointestinal dysbiosis. Therefore, we set out to determine if routine iron supplementation alters the preterm gut microbiome.MethodsAfter IRB approval, we collected stool specimens from 14 infants born ResultsWe observed no significant differences in either phyla or key genera relative abundance between pre- and post-iron timepoints. We observed notable shifts in infant microbiome composition based on season of delivery.ConclusionThough no obvious indication of iron-induced dysbiosis was observed in this unique study in the setting of prematurity, further investigation in a larger sample is warranted to fully understand iron's impact on the gastrointestinal milieu.

Amyotrophic lateral sclerosis (ALS) has been linked to overactivity of the protein kinase RNA-like ER kinase (PERK) branch of the unfolded protein response (UPR) pathway, both in ALS patients and mouse models. However, attempts to pharmacologically modulate PERK for therapeutic benefit have yielded inconsistent and often conflicting results. This study sought to address these discrepancies by comprehensively evaluating three commonly used, CNS-penetrant, PERK modulators (GSK2606414, salubrinal, and Sephin1) in the same experimental models, with the goal of assessing the viability of targeting the PERK pathway as a therapeutic strategy for ALS. To achieve this goal, a tunicamycin-challenge assay was developed using wild-type mice to monitor changes in liver UPR gene expression in response to PERK pathway modulation. Subsequently, multiple dosing regimens of each PERK modulator were tested in standardized, well-powered, gender-matched, and litter-matched survival efficacy studies using the SOD1G93A mouse model of ALS. The alpha-2-adrenergic receptor agonist clonidine was also tested to elucidate the results obtained from the Sephin1, and of the previously reported guanabenz studies, by comparing the effects of presence or absence of α-2 agonism. The results revealed that targeting PERK may not be an ideal approach for ALS treatment. Inhibiting PERK with GSK2606414 or activating it with salubrinal did not confer therapeutic benefits. While Sephin1 showed some promising therapeutic effects, it appears that these outcomes were mediated through PERK-independent mechanisms. Clonidine also produced some favorable therapeutic effects, which were unexpected and not linked to the UPR. In conclusion, this study highlights the challenges of pharmacologically targeting PERK for therapeutic purposes in the SOD1G93A mouse model and suggests that exploring other targets within, and outside, the UPR may be more promising avenues for ALS treatment.

Calcium/calmodulin-dependent protein kinase II (CaMKII) is a complex multifunctional kinase that is highly expressed in central nervous tissues and plays a key regulatory role in the calcium signaling pathway. Despite over 30 years of recombinant expression and characterization studies, CaMKII continues to be investigated for its impact on signaling cooperativity and its ability to bind multiple substrates through its multimeric hub domain. Here we compare and optimize protocols for the generation of full-length wild-type human calcium/calmodulin-dependent protein kinase II alpha (CaMKIIα). Side-by-side comparison of expression and purification in both insect and bacterial systems shows that the insect expression method provides superior yields of the desired autoinhibited CaMKIIα holoenzymes. Utilizing baculovirus insect expression system tools, our results demonstrate a high yield method to produce homogenous, monodisperse CaMKII in its autoinhibited state suitable for biophysical analysis. Advantages and disadvantages of these two expression systems (baculovirus insect cell versus Escherichia coli expression) are discussed, as well as purification optimizations to maximize the enrichment of full-length CaMKII.

Research on the transfer of skill from the circumstances in which it was learned to partially or completely novel tasks or situations is a foundational topic in the study of learning, memory, education, and expertise. A long history of transfer research has led to the conclusion that skill learning is generally domain specific. One important transfer problem occurs when a domain of expertise undergoes a fundamental shift, as when experts must adapt to changes in technology, rules, or professional practice. Here we examine skill maintenance in StarCraft 2, a video game of skills which undergoes frequent changes due to updates and includes a variety of gameplay options. Of particular interest are two competing predictions about how transfer will interact with expertise in this domain. The first approach emphasizes perceived similarity of the domains and predicts that skilled individuals will exhibit more favourable transfer than novices as these people will know enough to avoid processes, methods, and strategies which no longer apply after a domain change. The second emphasizes maximal adaptation to task constraints and predicts that experts will suffer the most during a domain change because of the loss of exploitable affordances. Neither approach did a good job explaining behaviour after the major game update called 'StarCraft 2: Heart of the Swarm,' perhaps because transfer was generally strong across all players. However, when examining transfer in the context of larger changes to gameplay, transfer seemed slightly better in more experienced players. The theoretical implications of this apparent interaction effect, and of the apparent resilience of more experienced StarCraft 2 players to transfer costs, are discussed.

Yeast-derived products have become more of an interest in the poultry industry as of late because of their use in modulating the gastrointestinal tract (GIT) microbiome to both improve production parameters and prevent infection. This study aimed to evaluate the effects of various yeast-derived products on Salmonella enterica inoculation in un in vitro rooster cecal incubations and associated effects on the cecal microbiome. Cecal contents were obtained from 53-wk old White Leghorn H & N Nick Chick roosters (n = 3) fed a wheat-based, commercial-type basal diet. Cecal contents were diluted 1:3000 in anaerobic dilution solution (ADS) in an anaerobic chamber, with 20 mL aliquoted to each serum bottle. There were three controls (n = 3): basal diet only, diluted cecal contents only, and basal diet and diluted cecal contents; and five treatments containing the basal diet and diluted cecal contents (n = 3): Citristim® (ADM), ImmunoWall® (ICC), Maxi-Gen Plus® (CBS Bio Platforms), Hilyses® (ICC), and Original XPC® (Diamond V). All treatments were applied at a rate of 2.5 kg/tonne or less. All groups were inoculated with a nalidixic acid-resistant strain of Salmonella Enteritidis at 10^7 CFU/mL and incubated at 37 deg C. Samples were collected at 0, 24, and 48 h for S. Enteritidis enumeration and 16S rDNA microbial sequencing. Salmonella data were log-transformed and analyzed in a two-way ANOVA with means separated using Tukey's HSD (P≤0.05). Genomic DNA was extracted, and resulting libraries were prepared and sequenced using an Illumina MiSeq. Sequencing data were analyzed in QIIME2 (2021.4) with diversity metrics (alpha and beta), and an analysis of the composition of microbiomes (ANCOM) was performed. Main effects were considered significant at P≤0.05, with pairwise differences considered significant at Q≤0.05. There was an interaction of treatment and time on the enumeration of Salmonella where treatments of Citristim, Immunowall, Hilyses, and XPC reduced Salmonella by 1 log CFU/mL compared to the controls. At 48 h, each yeast product treatment reduced Salmonella by 3 log CFU/mL compared to the controls. There was no main effect of treatment on the alpha diversity metrics, richness, or evenness (P > 0.05). Treatment affected the beta diversity, abundance, and phylogenetic differences, but there were no pairwise differences (P>0.05, Q>0.05). Using ANCOM at the genus level, the taxa Synergistes, Alloprevotella, Sutterella, and Megasphaera abundance were significantly different (W = 154,147,145,140, respectively). These results demonstrate the potential of these yeast-derived products to reduce foodborne pathogens, such as Salmonella Enteriditis, in vitro, without negatively disrupting the cecal microbiome.

Status threat (i.e., concern that one's dominant social group will be undermined by outsiders) is a significant factor in current United States politics. While demographic factors such as race (e.g., Whiteness) and political affiliation (e.g., conservatism) tend to be associated with heightened levels of status threat, its psychological facets have yet to be fully characterized. Informed by a "paranoid" model of American politics, we explored a suite of possible psychological and demographic associates of perceived status threat, including race/ethnicity, political conservatism, analytic thinking, magical ideation, subclinical paranoia, and conspiracy mentality. In a small, quota sample drawn from the United States (N = 300), we found that conspiracy mentality, subclinical paranoia, conservatism, and age were each positively (and uniquely) associated with status threat. In addition to replicating past work linking conservatism to status threat, this study identifies subclinical paranoia and conspiracy mentality as novel psychological associates of status threat. These findings pave the way for future research regarding how and why status threat concerns may become exaggerated in certain individuals, possibly to the detriment of personal and societal wellbeing.

BackgroundTo fully leverage the potential of the early care and education (ECE) setting for childhood obesity prevention, initiatives must not intervene solely at the organizational level, but rather they should also address the health needs of the ECE workers. Workers suffer disproportionately high rates of obesity, and have reported low confidence in modeling and promoting healthy eating and activity behaviors. However, information regarding the effectiveness of improving ECE workers' health behaviors or whether such improvements elicit meaningful change in the ECE environment and/or the children in their care is limited.MethodThe proposed study will integrate a staff wellness intervention into a nationally recognized, ECE obesity prevention initiative (Go NAPSACC). Go NAPSACC+ Staff Wellness program will be assessed using a clustered randomized controlled trial including 84 ECE centers, 168 workers, and 672 2-5-year-old children. Centers will be randomly assigned to 1) standard "Go NAPSACC" or 2) Go NAPSACC+ Staff Wellness. Outcome measures will assess impact on dietary intake and PA behaviors of 2-5-year-old children at 6 months (primary aim) and 12 months. Secondarily, we will compare the impact of the intervention on centers' implementation of healthy weight practices and the effect on ECE workers' diet quality and PA at 6- and 12 months.DiscussionThis trial expects to increase our understanding of how ECE worker's personal health behaviors impact the health behaviors of the children in their care and the ECE environment.Trial registrationClinicalTrials.gov: NCT05656807, registered on 19 December 2022. Protocol version 1.0, 22 March 2023.

Pathogen surveillance for great ape health monitoring has typically been performed on non-invasive samples, primarily feces, in wild apes and blood in sanctuary-housed apes. However, many important primate pathogens, including known zoonoses, are shed in saliva and transmitted via oral fluids. Using metagenomic methods, we identified viruses in saliva samples from 46 wild-born, sanctuary-housed chimpanzees at two African sanctuaries in Republic of Congo and Uganda. In total, we identified 20 viruses. All but one, an unclassified CRESS DNA virus, are classified in five families: Circoviridae, Herpesviridae, Papillomaviridae, Picobirnaviridae, and Retroviridae. Overall, viral prevalence ranged from 4.2% to 87.5%. Many of these viruses are ubiquitous in primates and known to replicate in the oral cavity (simian foamy viruses, Retroviridae; a cytomegalovirus and lymphocryptovirus; Herpesviridae; and alpha and gamma papillomaviruses, Papillomaviridae). None of the viruses identified have been shown to cause disease in chimpanzees or, to our knowledge, in humans. These data suggest that the risk of zoonotic viral disease from chimpanzee oral fluids in sanctuaries may be lower than commonly assumed.

BackgroundInfective endocarditis (IE) has increased in rural states such as West Virginia (WV) with high injection drug use. IE is medically managed with antimicrobial treatment alone or combined with surgical treatment. This study aimed to characterize the predictors associated with surgical treatment and rates of inpatient mortality and readmission among IE patients in WV's rural centers.MethodsThis retrospective review of electronic health records includes all adults hospitalized for IE at major rural tertiary cardiovascular centers in WV during 2014-2018. Descriptive statistics were presented on demographics, history of injection drug use, clinical characteristics, and hospital utilization by surgery status, and multivariable logistic regression examined the association of surgery with key predictor variables, generating odds ratios (OR).ResultsOf the 780 patients with IE, 38% had surgery, with a 26-fold increase in patients undergoing surgery between 2014-2018. Comparing surgery and non-surgery patients revealed significant differences. Surgery patients were significantly younger (median age 35.6 vs. 40.5 years; pConclusionThis study characterizes the predictors associated with surgical treatment and rates of inpatient mortality and readmission among IE patients across rural WV. The decision to perform cardiac surgery on IE patients is complex. Results with increased injection drug use-associated IE emphasize the importance of comprehensive care by a multidisciplinary team for optimal management of patients with IE.

IntroductionInfections of the central nervous system are a considerable basis of mortality in people living with HIV, with progression to cryptococcal meningitis documented at around 15% of HIV-associated mortality globally, with nearly three-quarters occurring in the sub-Saharan Africa. Discoveries from previous studies prelude to the mortality of cryptococcal antigen positive, which persisted to be elevated than in cryptococcal antigen negative persons. One feasible interpretation of this could be due to undiagnosed cryptococcus. Laboratory investigations identify cryptococcal disease prior to cryptococcal meningitis progression. Point-of-care testing has high sensitivity and specificity as seen with the cryptococcal antigen lateral flow assay screening to expedite treatment. The aim of the study is to map and translate evidence on cryptococcal antigen infection among HIV-infected persons in sub-Saharan Africa.MethodologyThe proposed scoping review will be conducted using guidelines proposed by Arksey and O'Malley methodological framework and Levac et al. advanced method. It will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Scoping Reviews. A comprehensive literature search of studies published from the first relevant publication to 2022 will be conducted on multiple electronic databases. Additional sources (grey literature) will also be searched. The search strategy will be generated and implemented by the principal investigator with assistance from a subject specialist, and an information specialist. Two reviewers will screen eligible studies. The screening will be guided by an inclusion and exclusion criteria. The mixed methods appraisal tool version 2018 will be used to appraise the quality of the empirical studies.DiscussionThe proposed scoping review will map and translate evidence on cryptococcal antigen infection among HIV-infected persons in sub-Saharan Africa. Synthesising and sharing recent evidence in this area has potential to help guide future research and interventions aimed at improving the management of cryptococcal antigen infection among HIV-infected persons in sub-Saharan Africa and other high HIV- burdened settings.

To our knowledge, this is the first epidemiologic study to examine the association between physical activity (PA) and cancer using data from the American College Health Association-National College Health Assessment (ACHA-NCHA). The goal of the study was to understand the dose-response relation between PA and cancer, as well as the associations between meeting US PA guidelines and overall cancer risk in US college students. The ACHA-NCHA provided self-reported information on demographic characteristics, PA, body mass index, smoking status, and overall cancer during 2019-2022 (n = 293,682; 0.08% cancer cases). To illustrate the dose-response relationship, a restricted cubic spline logistic regression analysis was used to evaluate the association of overall cancer with moderate-to-vigorous PA (MVPA) on a continuous basis. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals for the associations between meeting the three U.S. PA guidelines and overall cancer risk. The cubic spline observed that MVPA was inversely associated with the odds of overall cancer risk after adjusting for covariates; a one hour/week increase in moderate and vigorous PA was associated with a 1% and 5% reduced overall cancer risk, respectively. Multivariable-adjusted logistic regression analyses showed that meeting the US guidelines for aerobic PA for adults (≥150 minutes/week of moderate aerobic PA or ≥75 minutes of vigorous PA) (OR: 0.85), for PA for adults (≥2 days of muscle strengthening activity in addition to aerobic MVPA) (OR: 0.90), and for highly active adults (≥2 days of muscle strengthening activity and ≥300 minutes/week of aerobic moderate PA or 150 minutes/week of vigorous PA) (OR: 0.89) were statistically significant and inversely associated with cancer risk. MVPA, especially meeting US guidelines, may be inversely associated with overall cancer among college students in the US. To reduce cancer risks, multilevel interventions to promote US physical activity guidelines among college students are warranted.

Marine fjords along the northern Labrador coast of Arctic Canada are influenced by freshwater, nutrients, and sediment inputs from ice fields and rivers. These ecosystems, further shaped by both Atlantic and Arctic water masses, are important habitats for fishes, marine mammals, seabirds, and marine invertebrates and are vital to the Labrador Inuit who have long depended on these areas for sustenance. Despite their ecological and socio-cultural importance, these marine ecosystems remain largely understudied. Here we conducted the first quantitative underwater scuba surveys, down to 12 m, of the nearshore marine ecology of Nachvak Fjord, which is surrounded by Torngat Mountains National Park located in Nunatsiavut, the Indigenous lands claim region of northeastern Canada. Our goal was to provide the Nunatsiavut Government with a baseline of the composition and environmental influences on the subtidal community in this isolated region as they work towards the creation of an Indigenous-led National Marine Conservation Area that includes Nachvak Fjord. We identified four major benthic habitat types: (1) boulders (2) rocks with sediment, (3) sediment with rocks, and (4) unconsolidated sediments, including sand, gravel, and cobble. Biogenic cover (e.g., kelp, coralline algae, and sediment) explained much of the variability in megabenthic invertebrate community structure. The kelp species Alaria esculenta, Saccharina latissima, and Laminaria solidungula dominated the boulder habitat outside of the fjord covering 35%, 13%, and 11% of the sea floor, respectively. In contrast, the middle and inner portions of the fjord were devoid of kelp and dominated by encrusting coralline algae. More diverse megabenthic invertebrate assemblages were detected within the fjord compared to the periphery. Fish assemblages were depauperate overall with the shorthorn sculpin, Myoxocephalus scorpius, and the Greenland cod, Gadus ogac, dominating total fish biomass contributing 64% and 30%, respectively. Understanding the composition and environmental influences within this fjord ecosystem not only contributes towards the protection of this ecological and culturally important region but serves as a baseline in a rapidly changing climatic region.

BackgroundWomen are less likely to receive left ventricular assist devices and are more likely to experience poor outcomes. However, how gender impacts LVAD decision-making regarding LVAD implantation and the effects of that decision remains unknown.MethodsWe performed a sub-group analysis from the stepped-wedge DECIDE-LVAD trial, which tested a decision-support intervention for patients considering LVAD therapy.ResultsExcluding 9 patients who withdrew from assessments, of the 239 patients analyzed, 203 (85%) were men and 36 (15%) were women. More men received LVADs (70%) than women (61%) and more men were alive at 6 months compared to women, both among those who received LVADs (87% vs 82%) and those who did not (74% vs 50%) (p = 0.002). Compared to men, women were more likely to have decision regret, depressive symptoms and perceived stress at baseline but not at follow-up. At 6-month follow-up, men experience improvements in decisional conflict, acceptance of illness, struggle with illness, and perceived stress-none of those improvements were noted amongst women. Compared to men who received LVADs, women receiving LVADs had worse decision regret and depressive symptoms at baseline and worse acceptance of illness and perceived stress at six months. Men who received LVADs experienced improvement in decisional conflict and perceived stress, while women did not experience these improvements. Both men and women who received LVADs experienced improvement in depressive symptoms. Quality of life as assessed by EuroQol visual analog scale improved for both men and women who received LVADs but not for those who did not receive LVADs; no gender differences in quality of life were noted.ConclusionWomen require greater decisional support at time of decision to undergo LVAD implantation and subsequently might benefit from more intensive psychosocial support.

The majority of people who contract COVID-19 experience a short period of symptomatic infection. However, symptoms persist for months or years following initial exposure to the virus in some cases. This has been described as long COVID. Little is known about the lived experience of this condition, as it has only recently emerged. This study aimed to explore the experiences of mental health, quality of life, and coping among people living with long COVID. A sample of 47 adults with lived experience participated in web-based focus groups. Separate focus groups were held for 24 individuals with pre-existing mental health conditions and 23 individuals without pre-existing mental health conditions. Data were analyzed using a codebook thematic analysis approach. Five themes were identified as integral to the long COVID experience: The Emotional Landscape of Long COVID, New Limits to Daily Functioning, Grief and Loss of Former Identity, Long COVID-related Stigmatization, and Learning to Cope with Persisting Symptoms. These findings illustrate the immense impact of long COVID on mental health and quality of life. Minimal differences were found between those with and those without pre-existing mental health conditions, as both groups were substantially impacted by the condition. Attention to the perspectives of people with lived experience of long COVID is necessary to inform future directions for research and clinical practice.

BackgroundMedical students have high levels of stress, which is associated with higher incidents of burnout, depression, and suicide compared to age-matched peers. Mindfulness practices have been shown to reduce stress among medical students.PurposeThe purpose of this systematic review and meta-analysis was to examine if mindfulness interventions have an overall effect on stress outcomes in the high-stress population of medical students globally, particularly given the wide variety of interventions. Any intervention designed to promote mindfulness was included.MethodsA comprehensive literature search was completed to include multiple databases, ancestry, and hand-searching and 35 studies were included. Standardized mean difference effect sizes (ES) were synthesized across studies using a random-effects model for changes in stress levels in medical students ≥ 18. Moderator analyses were performed to explore variations in effects by participant and intervention characteristics.ResultsMindfulness interventions significantly improved stress among medical students in both the two-arm studies (d = 0.370, k = 19, n = 2,199, 95% CI 0.239-0.501, p < .001) and one-arm pre-post studies (d = 0.291, k = 30, n = 18 (two cohorts from Dyrbye et al), 95% CI 0.127-0.455, p = 0.001). Moderator analyses found trends in less hours and less required practice resulted in better improvement in stress.ConclusionsThis study further confirms that despite a wide variety of mindfulness interventions for medical students around the world, they produce an overall small-to-moderate effect on stress reduction. Future research looking at the most effective protocols for high-stress medical students would be beneficial.

Refined handling improves laboratory mouse welfare and research outcomes when compared to traditional tail handling, yet implementation does not seem to be widespread. Refined handling includes picking up a mouse using a tunnel or cupped hands. The aim of this study was to determine the current prevalence of and beliefs towards refined handling using the theory of planned behavior. It was predicted that refined handling prevalence is low compared to traditional handling methods, and its implementation is determined by individual and institutional beliefs. Research personnel were recruited via online convenience sampling through email listservs and social media. A total of 261 participants in diverse roles (e.g. veterinarians, managers, caretakers, researchers, etc.) responded primarily from the USA (79%) and academic institutions (61%) Participants were surveyed about their current use, knowledge, and beliefs about refined handling. Quantitative data were analyzed via descriptive statistics and generalised regression. Qualitative data were analyzed by theme. Research personnel reported low levels of refined handling implementation, with only 10% of participants using it exclusively and a median estimate of only 10% of institutional mice being handled with refined methods. Individually, participants had positive attitudes, neutral norms, and positive control beliefs about refined handling. Participants' intention to provide refined handling in the future was strongly associated with their attitudes, norms, and control beliefs (p

BackgroundAccess to drug resistant testing for tuberculosis (TB) remains a challenge in high burden countries. Recently, the World Health Organization approved the use of several moderate complexity automated nucleic acid amplification tests (MC-NAAT) that have performance profiles suitable for placement in a range of TB laboratory tiers to improve drug susceptibility tests (DST) coverage.MethodsWe conducted cost analysis of two MC-NAATs with different testing throughput: Lower Throughput (LT, < 24 tests per run) and Higher Throughput (HT, upto 90+ tests per run) for placement in a hypothetical laboratory in a resource limited setting. We used per-test cost as the main indicator to assess 1) drivers of cost by resource types and 2) optimized levels of annual testing volumes for the respective MC-NAATs.ResultsThe base-case per test cost of $18.52 (range: $13.79 - $40.70) for LT test and $15.37 (range: $9.61 - $37.40) for HT test. Per test cost estimates were most sensitive to the number of testing days per week, followed by equipment costs and TB-specific workloads. In general, HT NAATs were cheaper at all testing volume levels, but at lower testing volumes (less than 2,000 per year) LT tests can be cheaper if the durability of the testing system is markedly better and/or procured equipment costs are lower than that of HT NAAT.ConclusionAssuming equivalent performance and infrastructural needs, placement strategies for MC-NAATs need to be prioritized by laboratory system's operational factors, testing demands, and costs.

Access to point-of-care (POC) diagnostics in resource-limited settings, where laboratory-based diagnostics are limited, depends on efficient supply chain management (SCM). This study evaluated the SCM for SARS-CoV-2 POC diagnostic services in resource-limited settings to determine the effect of SCM on accessibility to SARS-CoV-2 POC tests and to identify barriers and enablers of accessibility to SARS-CoV-2 diagnostic services in Mopani District, Limpopo Province, South Africa. We purposively assessed 47 clinics providing POC diagnostic services between June and September 2022. One participant per clinic completed an audit tool developed by the authors with guidance from the World Health Organization and the Management Sciences for Health guidelines. The audit tool evaluated the following SCM parameters: selection, quantification, storage, procurement, quality assurance, distribution, redistribution, inventory management, and human resource capacity. Percentage rating scores between 90–100% indicated that the facility was compliant with SCM guidelines, while rating scores < 90% indicated non-compliance. The clinic audit scores were summarized and compared across clinics and sub-districts. Clinics had compliance scores ranging from 60.5% to 89.2%. Compliance scores were the highest for procurement, redistribution, and quality assurance (all 100%), followed by storage (mean = 95.2%, 95% CI: 90.7–99.7), quantification (mean = 89.4%, 95% CI: 80.2–98.5), and selection (mean = 87.5%, 95% CI: 87.5%–87.5%). Compliance scores were the lowest for inventory management (mean = 53.2%, 95% CI: 47.9%–58.5%), distribution (mean = 48.6%, 95% CI: 44.6%–52.7%), and human resource capacity (mean = 50.6%, 95% CI: 43.3%–58.0%). A significant correlation was found between compliance score and clinic headcount (r = 0.4, p = 0.008), and compliance score and ideal clinic score (r = 0.4, p = 0.0003). Overall, the 47 clinics audited did not comply with international SCM guidelines. Of the nine SCM parameters evaluated, only procurement, redistribution, and quality assurance did not need improvement. All parameters are key in ensuring full functionality of SCM systems and equitable access to SARS-CoV-2 POC diagnostics in resource limited settings.

During the COVID-19 pandemic, many residents of high-income countries (HICs) were eligible for COVID-19 vaccine boosters, while many residents of lower-income countries (LICs) had not yet received a first dose. HICs made some efforts to contribute to COVID-19 vaccination efforts in LICs, but these efforts were limited in scale. A new literature discusses the normative importance of an international redistribution of vaccines. Our analysis contributes an empirical perspective on the willingness of citizens in a HIC to contribute to such efforts (which we term international vaccine solidarity). We analyse the levels and predictors of international vaccine solidarity. We surveyed a representative sample of German adults (n = 2019) who participated in a two-wave YouGov online survey (w1: Sep 13-21, 2021 and w2: Oct 4-13, 2021). International vaccine solidarity is measured by asking respondents preferences for sharing vaccine supplies internationally versus using that supply as boosters for the domestic population. We examine a set of pre-registered hypotheses. Almost half of the respondents in our sample (48%) prioritize giving doses to citizens in less developed countries. A third of respondents (33%) prefer to use available doses as boosters domestically, and a fifth of respondents (19%) did not report a preference. In line with our hypotheses, respondents higher in cosmopolitanism and empathy, and those who support domestic redistribution exhibit more support for international dose-sharing. Older respondents (who might be more at risk) do not consistently show less support for vaccine solidarity. These results help us to get a better understanding of the way citizens' form preferences about a mechanism that redistributes medical supplies internationally during a global crisis.

Swallowing impairment is a major complication of radiation treatment for oropharyngeal cancers. Developing targeted therapies that improve swallowing outcomes relies on an understanding of the mechanisms that influence motor function after radiation treatment. The purpose of this study was to determine whether there is a correlation between radiation induced changes in tongue movement and structural changes in irradiated submental muscles, as well as assess other possible causes for dysfunction. We hypothesized that a clinically relevant total radiation dose to the submental muscles would result in: a) quantifiable changes in tongue strength and displacement during drinking two months post treatment; and b) a profibrotic response and/or fiber type transition in the irradiated tissue. Sprague-Dawley adult male rats received radiation to the submental muscles at total dose-volumes known to provoke dysphagia in humans. A clinical linear accelerator administered 8 fractions of 8Gy for a total of 64Gy. Comparisons were made to sham-treated rats that received anesthesia only. Swallowing function was assessed using videofluoroscopy and tongue strength was analyzed via force lickometer. TGFβ1 expression was analyzed via ELISA. The amount of total collagen was analyzed by picrosirius red staining. Immunofluorescence was used to assess fiber type composition and size. Significant changes in licking function during drinking were observed at two months post treatment, including a slower lick rate and reduced tongue protrusion during licking. In the mylohyoid muscle, significant increases in TGFβ1 protein expression were found post radiation. Significant increases in the percentage of collagen content were observed in the irradiated geniohyoid muscle. No changes in fiber type expression were observed. Results indicate a profibrotic transition within the irradiated swallowing muscles that contributes to tongue dysfunction post-radiation treatment.

The continuous dissemination of coronavirus disease of 2019 (COVID-19) literature can inform decision-makers and the public. Since the widespread use of COVID-19 vaccines, more systematic reviews have summarized the effectiveness and reported adverse events associated with vaccination. Previous systematic and scoping reviews on COVID-19 summarized various aspects surrounding COVID-19, however, a scoping review is needed to summarize the characteristics of COVID-19 vaccines and associated adverse events reported in systematic reviews and meta-analyses to provide comprehensive evidence for informed medical decision-making. We will conduct a scoping review concerning COVID-19 vaccines and adverse events from vaccines. We will search from December 2019 to present in Epistemonikos, Campbell Library, CINAHL (Ovid), MEDLINE (Ovid), Scopus, CENTRAL (Ovid), Web of Science, WHO COVID-19 database, Joanna Briggs Institute of Excellence, and COVID-19 Evidence Reviews resource. We will include systematic reviews, meta-analyses, or both of randomized controlled trials and observational studies and exclude individual randomized controlled trials and observational studies. Abstracts and full-texts will be screened prior to selection. Investigators will independently use a calibrated quantitative and qualitative data extraction sheet and rate the quality of articles with AMSTAR, resolving disagreements to aim for good agreement (≥80%). An updated scoping review of the characteristics and safety of COVID-19 vaccines would highlight the accuracy of the evidence to inform decision-making concerning COVID-19 vaccination.

BackgroundLesotho is one of the 30 countries with the highest tuberculosis incidence rates in the world, estimated at 650 per 100,000 population. Tuberculosis case detection is extremely low, particularly with the rapid spread of COVID-19, dropping from an estimated 51% in 2020 to 33% in 2021. The aim of this study is to understand the barriers to tuberculosis diagnosis and treatment completion.MethodsWe used a convergent mixed methods study design. We collected data on the number of clients reporting symptoms upon tuberculosis screening, their sputum test results, the number of clients diagnosed, and the number of clients who started treatment from one district hospital and one health center in Berea district, Lesotho. We conducted in-depth interviews and focus group discussions with 53 health workers and patients. We used a content analysis approach to analyze qualitative data and integrated quantitative and qualitative findings in a joint display.FindingsDuring March-August, 2019, 218 clients at the hospital and 292 clients at the health center reported tuberculosis symptoms. The full diagnostic testing process was completed for 66% of clients at the hospital and 68% at the health center. Among clients who initiated tuberculosis treatment, 68% (61/90) at the hospital and 74% (32/43) at the health center completed treatment. The main barriers to testing and treatment completion were challenges at sample collection, lack of decentralized diagnostic services, and socioeconomic factors such as food insecurity and high patient movement to search for jobs.ConclusionsTuberculosis diagnosis could be improved through the effective decentralization of laboratory services at the health facility level, and treatment completion could be improved by providing food and other forms of social support to patients.

ObjectiveDiverticular disease (DD) is one of the most prevalent conditions encountered by gastroenterologists, affecting ~50% of Americans before the age of 60. Our aim was to identify genetic risk variants and clinical phenotypes associated with DD, leveraging multiple electronic health record (EHR) data sources of 91,166 multi-ancestry participants with a Natural Language Processing (NLP) technique.Materials and methodsWe developed a NLP-enriched phenotyping algorithm that incorporated colonoscopy or abdominal imaging reports to identify patients with diverticulosis and diverticulitis from multicenter EHRs. We performed genome-wide association studies (GWAS) of DD in European, African and multi-ancestry participants, followed by phenome-wide association studies (PheWAS) of the risk variants to identify their potential comorbid/pleiotropic effects in clinical phenotypes.ResultsOur developed algorithm showed a significant improvement in patient classification performance for DD analysis (algorithm PPVs ≥ 0.94), with up to a 3.5 fold increase in terms of the number of identified patients than the traditional method. Ancestry-stratified analyses of diverticulosis and diverticulitis of the identified subjects replicated the well-established associations between ARHGAP15 loci with DD, showing overall intensified GWAS signals in diverticulitis patients compared to diverticulosis patients. Our PheWAS analyses identified significant associations between the DD GWAS variants and circulatory system, genitourinary, and neoplastic EHR phenotypes.DiscussionAs the first multi-ancestry GWAS-PheWAS study, we showcased that heterogenous EHR data can be mapped through an integrative analytical pipeline and reveal significant genotype-phenotype associations with clinical interpretation.ConclusionA systematic framework to process unstructured EHR data with NLP could advance a deep and scalable phenotyping for better patient identification and facilitate etiological investigation of a disease with multilayered data.

Protein Tyrosine Phosphatase receptor type D (PTPRD) is a member of the protein tyrosine phosphatase family that mediates cell adhesion and synaptic specification. Genetic studies have linked Ptprd to several neuropsychiatric phenotypes, including Restless Leg Syndrome (RLS), opioid abuse disorder, and antipsychotic-induced weight gain. Genome-wide association studies (GWAS) of either pediatric obsessive-compulsive traits, or Obsessive-Compulsive Disorder (OCD), have identified loci near PTPRD as genome-wide significant, or strongly suggestive for this trait. We assessed Ptprd wild-type (WT), heterozygous (HT), and knockout (KO) mice for behavioral dimensions that are altered in OCD, including anxiety and exploration (open field test, dig test), perseverative behavior (splash-induced grooming, spatial d), sensorimotor gating (prepulse inhibition), and home cage goal-directed behavior (nest building). No effect of genotype was observed in any measure of the open field test, dig test, or splash test. However, Ptprd KO mice of both sexes showed impairments in nest building behavior. Finally, female, but not male, Ptprd KO mice showed deficits in prepulse inhibition, an operational measure of sensorimotor gating that is reduced in female, but not male, OCD patients. Our results indicate that constitutive lack of Ptprd may contribute to the development of certain domains that are altered OCD, including goal-directed behavior, and reduced sensorimotor gating specifically in females.