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BACKGROUND: Cauda equina syndrome (CES) is a lumbosacral surgical emergency that has been associated with chiropractic spinal manipulation (CSM) in case reports. However, identifying if there is a potential causal effect is complicated by the heightened incidence of CES among those with low back pain (LBP). The study hypothesis was that there would be no increase in the risk of CES in adults with LBP following CSM compared to a propensity-matched cohort following physical therapy (PT) evaluation without spinal manipulation over a three-month follow-up period. METHODS: A query of a United States network (TriNetX, Inc.) was conducted, searching health records of more than 107 million patients attending academic health centers, yielding data ranging from 20 years prior to the search date (July 30, 2023). Patients aged 18 or older with LBP were included, excluding those with pre-existing CES, incontinence, or serious pathology that may cause CES. Patients were divided into two cohorts: (1) LBP patients receiving CSM or (2) LBP patients receiving PT evaluation without spinal manipulation. Propensity score matching controlled for confounding variables associated with CES. RESULTS: 67,220 patients per cohort (mean age 51 years) remained after propensity matching. CES incidence was 0.07% (95% confidence intervals [CI]: 0.05-0.09%) in the CSM cohort compared to 0.11% (95% CI: 0.09-0.14%) in the PT evaluation cohort, yielding a risk ratio and 95% CI of 0.60 (0.42-0.86; p = .0052). Both cohorts showed a higher rate of CES during the first two weeks of follow-up. CONCLUSIONS: These findings suggest that CSM is not a risk factor for CES. Considering prior epidemiologic evidence, patients with LBP may have an elevated risk of CES independent of treatment. These findings warrant further corroboration. In the meantime, clinicians should be vigilant to identify LBP patients with CES and promptly refer them for surgical evaluation.

IntroductionThe incidence of varicella in Canada has decreased by almost 99% since vaccination was introduced. However, variation in the timing and eligibility of vaccination programs across the country has resulted in some cohorts being under-vaccinated and therefore potentially susceptible to infection.MethodsWe used nationally representative specimens from the Biobank of Statistics Canada's Canadian Health Measures Survey (CHMS) as well as residual specimens from Ontario collected between 2009-2014 to estimate population immunity across age-groups and geography, and identify any groups at increased risk of varicella infection.ResultsThe weighted proportion of specimens with antibody levels above the threshold of protection was 93.6% (95% CI: 92.4, 95.0). Protection was lowest among those aged 3-5 years (54.3%; 95% CI: 47.3, 61.4), but increased with age. Individuals born outside Canada had more than twice the odds of varicella susceptibility than those born in Canada (aOR: 2.7; 95% CI: 1.4, 5.0; p = 0.004). There were no differences by sex or geography within Canada, and there were no statistically significant differences when Ontario CHMS sera were compared to Ontario residual sera, apart from in participants aged 12-19 year age-group, for whom the CHMS estimate (91.2%; 95% CI: 86.7, 95.7) was significantly higher (p = 0.03) than that from residual specimens (85.9%, 95% CI: 81.1, 90.8).DiscussionVaricella immunity in Canada is changing. Children appear to have low population immunity, placing them at greater risk of infection and at increased risk of severe disease as they age. Our results underscore the importance of performing periodic serosurveys to monitor further population immunity changes as the proportion of vaccine-eligible birth-cohorts increases, and to continually assess the risk of outbreaks.

In this article we study the social dynamic of temporal partitioning congestion games (TPGs), in which participants must coordinate an optimal time-partitioning for using a limited resource. The challenge in TPGs lies in determining whether users can optimally self-organize their usage patterns. Reaching an optimal solution may be undermined, however, by a collectively destructive meta-reasoning pattern, trapping users in a socially vicious oscillatory behavior. TPGs constitute a dilemma for both human and animal communities. We developed a model capturing the dynamics of these games and ran simulations to assess its behavior, based on a 2×2 framework that distinguishes between the players' knowledge of other players' choices and whether they use a learning mechanism. We found that the only way in which an oscillatory dynamic can be thwarted is by adding learning, which leads to weak convergence in the no-information condition and to strong convergence in the with-information condition. We corroborated the validity of our model using real data from a study of bats' behaviour in an environment of water scarcity. We conclude by examining the merits of a complexity-based, agent-based modelling approach over a game-theoretic one, contending that it offers superior insights into the temporal dynamics of TPGs. We also briefly discuss the policy implications of our findings.

THIS ARTICLE USES WORDS OR LANGUAGE THAT IS CONSIDERED PROFANE, VULGAR, OR OFFENSIVE BY SOME READERS. Hate speech detection in online social networks is a multidimensional problem, dependent on language and cultural factors. Most supervised learning resources for this task, such as labeled datasets and Natural Language Processing (NLP) tools, have been specifically tailored for English. However, a large portion of web users around the world speak different languages, creating an important need for efficient multilingual hate speech detection approaches. In particular, such approaches should be able to leverage the limited cross-lingual resources currently existing in their learning process. The cross-lingual transfer in this task has been difficult to achieve successfully. Therefore, we propose a simple yet effective method to approach this problem. To our knowledge, ours is the first attempt to create a multilingual embedding model specific to this problem. We validate the effectiveness of our approach by performing an extensive comparative evaluation against several well-known general-purpose language models that, unlike ours, have been trained on massive amounts of data. We focus on a zero-shot cross-lingual evaluation scenario in which we classify hate speech in one language without having access to any labeled data. Despite its simplicity, our embeddings outperform more complex models for most experimental settings we tested. In addition, we provide further evidence of the effectiveness of our approach through an ad hoc qualitative exploratory analysis, which captures how hate speech is displayed in different languages. This analysis allows us to find new cross-lingual relations between words in the hate-speech domain. Overall, our findings indicate common patterns in how hate speech is expressed across languages and that our proposed model can capture such relationships significantly.

Influenza viruses constitute a major threat to human health globally. The viral surface glycoprotein hemagglutinin (HA) is the immunodominant antigen, contains the site for binding to the cellular receptor (RBS), and it is the major target of neutralizing antibody responses post-infection. We developed llama-derived single chain antibody fragments (VHHs) specific for type A influenza virus. Four VHHs were identified and further characterized. VHH D81 bound residues in the proximity of the C-terminal region of HA1 of H1 and H5 subtypes, and showed weak neutralizing activity, whereas VHH B33 bound residues in the proximity of the N-terminal region of the HA's stem domain (HA2) of H1, H5, and H9 subtypes, and showed no neutralizing activity. Of most relevance, VHHs E13 and G41 recognized highly conserved conformational epitopes on the H1 HA's globular domain (HA1) and showed high virus neutralizing activity (ranging between 0.94 to 0.01μM), when tested against several human H1N1 isolates. Additionally, E13 displayed abrogated virus replication of a panel of H1N1 strains spanning over 80 years of antigenic drift and isolated from human, avian, and swine origin. Interestingly, E13 conferred protection in vivo at a dose as low as 0.05 mg/kg. Mice treated with E13 intranasally resulted in undetectable virus challenge loads in the lungs at day 4 post-challenge. The transfer of sterilizing pan-H1 immunity, by a dose in the range of micrograms given intranasally, is of major significance for a monomeric VHH and supports the further development of E13 as an immunotherapeutic agent for the mitigation of influenza infections.

Heart Failure (HF) continues to be a complex public health issue with increasing world population prevalence. Although overall mortality has decreased for HF and hypertrophic cardiomyopathy (HCM), a precursor for HF, their prevalence continues to increase annually. Because the etiology of HF and HCM is heterogeneous, it has been difficult to identify novel therapies to combat these diseases. Isoproterenol (ISP), a non-selective β-adrenoreceptor agonist, is commonly used to induce cardiotoxicity and cause acute and chronic HCM and HF in mice. However, the variability in dose and duration of ISP treatment used in studies has made it difficult to determine the optimal combination of ISP dose and delivery method to develop a reliable ISP-induced mouse model for disease. Here we examined cardiac effects induced by ISP via subcutaneous (SQ) and SQ-minipump (SMP) infusions across 3 doses (2, 4, and 10mg/kg/day) over 2 weeks to determine whether SQ and SMP ISP delivery induced comparable disease severity in C57BL/6J mice. To assess disease, we measured body and heart weight, surface electrocardiogram (ECG), and echocardiography recordings. We found all 3 ISP doses comparably increase heart weight, but these increases are more pronounced when ISP was administered via SMP. We also found that the combination of ISP treatment and delivery method induces contrasting heart rate, RR interval, and R and S amplitudes that may place SMP treated mice at higher risk for sustained disease burden. Mice treated via SMP also had increased heart wall thickness and LV Mass, but mice treated via SQ showed greater increase in gene markers for hypertrophy and fibrosis. Overall, these data suggest that at 2 weeks, mice treated with 2, 4, or 10mg/kg/day ISP via SQ and SMP routes cause similar pathological heart phenotypes but highlight the importance of drug delivery method to induce differing disease pathways.

[This corrects the article DOI: 10.1371/journal.pone.0275275.].

Breast cancer remains a critical global concern, underscoring the urgent need for early detection and accurate diagnosis to improve survival rates among women. Recent developments in deep learning have shown promising potential for computer-aided detection (CAD) systems to address this challenge. In this study, a novel segmentation method based on deep learning is designed to detect tumors in breast ultrasound images. Our proposed approach combines two powerful attention mechanisms: the novel Positional Convolutional Block Attention Module (PCBAM) and Shifted Window Attention (SWA), integrated into a Residual U-Net model. The PCBAM enhances the Convolutional Block Attention Module (CBAM) by incorporating the Positional Attention Module (PAM), thereby improving the contextual information captured by CBAM and enhancing the model's ability to capture spatial relationships within local features. Additionally, we employ SWA within the bottleneck layer of the Residual U-Net to further enhance the model's performance. To evaluate our approach, we perform experiments using two widely used datasets of breast ultrasound images and the obtained results demonstrate its capability in accurately detecting tumors. Our approach achieves state-of-the-art performance with dice score of 74.23% and 78.58% on BUSI and UDIAT datasets, respectively in segmenting the breast tumor region, showcasing its potential to help with precise tumor detection. By leveraging the power of deep learning and integrating innovative attention mechanisms, our study contributes to the ongoing efforts to improve breast cancer detection and ultimately enhance women's survival rates. The source code of our work can be found here: https://github.com/AyushRoy2001/DAUNet.

BackgroundPerinatal mortality remains a global challenge. This challenge may be worsened by the negative effects of the COVID-19 pandemic on maternal and child health.ObjectivesExamine the impact of the COVID-19 pandemic on perinatal care and outcomes in the Tamale Teaching Hospital in northern Ghana.MethodsA hospital-based retrospective study was conducted in the Tamale Teaching Hospital. We compared antenatal care attendance, total deliveries, cesarean sections, and perinatal mortality before the COVID-19 pandemic (March 1, 2019 to February 28, 2020) and during the COVID-19 pandemic (March 1, 2020 to February 28, 2021). Interrupted time series analyses was performed to evaluate the impact of the COVID-19 pandemic on perinatal care and outcomes at TTH.ResultsA total number of 35,350 antenatal visits and 16,786 deliveries were registered at TTH from March 2019 to February 2021. Antenatal care, early neonatal death, and emergency cesarean section showed a rapid decline after the onset of the pandemic, with a progressive recovery over the following months. The total number of deliveries and fresh stillbirths showed a step change with a marked decrease during the pandemic, while the macerated stillbirths showed a pulse change, a temporary marked decrease with a quick recovery over time.ConclusionThe COVID-19 pandemic had a negative impact on perinatal care and outcomes in our facility. Pregnancy monitoring through antenatal care should be encouraged and continued even as countries tackle the pandemic.

Carpal tunnel syndrome (CTS) occurs more often among individuals with diabetes. The aim of this retrospective observational registry study was to examine whether individuals with diabetes and CTS are treated surgically to the same extent as individuals with CTS but without diabetes. Data on CTS diagnosis and surgery were collected from the Skåne Healthcare Register (SHR). A total of 35,105 individuals (age ≥ 18 years) diagnosed with CTS from 2004-2019 were included. Data were matched to the Swedish National Diabetes Register (NDR. Cox regression models were used to calculate the risk of the use of surgical treatment. Of the 35,105 included individuals with a CTS diagnosis, 17,662 (50%) were treated surgically, and 4,966 (14%) had diabetes. A higher number of individuals with diabetes were treated surgically (2,935/4,966, 59%) than individuals without diabetes (14,727/30,139, 49%). In the Cox regression model, diabetes remained a significant risk factor for surgical treatment (PR 1.14 (95% CI 1.11-1.17)). Individuals with type 1 diabetes were more frequently treated surgically (490/757, 65%) than individuals with type 2 diabetes (2,445/4,209, 58%). There was no difference between the sexes and their treatment. The duration of diabetes was also a risk factor for surgical treatment in diabetes type 2, but high HbA1c levels were not. Individuals with diabetes are more likely to be treated surgically for CTS than individuals without diabetes. Individuals with type 1 diabetes are more likely to be treated surgically for CTS than individuals with type 2 diabetes.

ObjectivesThe aim of the study was to describe the facilitators, barriers to and level of uptake of COVID-19 vaccines among healthcare workers in primary healthcare facilities in an urban setting in Uganda.Materials and methodsWe conducted a cross-sectional study among HCWs in private and public health facilities in Entebbe municipality between July 2021 and August 2021. Data was collected using a structured questionnaire that was shared, via an online link, to consented participants. Uptake of the vaccines among healthcare workers was analysed as proportions, and logistic regression was used to analyse barriers and facilitators to uptake of COVID-19 vaccines.ResultsThe study enrolled 360 participants, with 61.7% (n = 222) females. A total of 236 (65.6%) healthcare workers had received at least one dose of COVID-19 vaccine, with higher uptake among females 64% (n = 151). Age above 40 years (OR 2.16), working in a government healthcare facility (OR 3.12), participating in COVID-19 vaccine related activities (OR 4.62), and having tested for SARS-COV-2 (OR 3.05) increased the odds of having been vaccinated. Working in small roadside clinics reduced the odds of being vaccinated by almost 70%, while HCWs in government health services were 3.1 times more likely to have been vaccinated. History of having cared for a COVID-19 patient and having a positive SARS-COV-2 test result did not influence the uptake of the vaccines in the study population.ConclusionVaccine uptake among HCWs was close to the World Health Organisation (WHO) recommended uptake of 70% by mid-2022.

Psoriasis has been related to metabolic dysfunction-associated fatty liver disease and, liver fibrosis. This study aimed to evaluate the prevalence of liver fibrosis in psoriasis and identify predictors for fibrosis. This is a cross-sectional study conducted from December 2012 to June 2016 assessing psoriasis and psoriatic arthritis patients attended at four centers in Mexico City. Data regarding history of the skin disease, previous and current medication, and previously diagnosed liver disease was collected. Liver fibrosis was assessed with four different non-invasive methods (FIB4, APRI, NAFLD score and elastography). We compared data based on the presence of fibrosis. Adjusted-logistic regression models were performed to estimate OR and 95% CI. A total of 160 patients were included. The prevalence of significant fibrosis using elastography was 25% (n = 40), and 7.5% (n = 12) for advanced fibrosis. Patients with fibrosis had higher prevalence of obesity (60% vs 30.8%, P = 0.04), type 2 diabetes (40% vs 27.5%, P = 0.003), gamma-glutamyl transpeptidase levels (70.8±84.4 vs. 40.1±39.2, P = 0.002), and lower platelets (210.7±58.9 vs. 242.8±49.7, P = 0.0009). Multivariate analysis showed that body mass index (OR1.11, 95%CI 1.02-1.21), type 2 diabetes (OR 3.44, 95%CI 1.2-9.88), and gamma-glutamyl transpeptidase (OR 1.01, 95%CI1-1.02) were associated with the presence of fibrosis. The use of methotrexate was not associated. Patients with psoriasis are at higher risk of fibrosis. Metabolic dysfunction, rather than solely the use of hepatotoxic drugs, likely plays a major role; it may be beneficial to consider elastography regardless of the treatment used. Metabolic factors should be assessed, and lifestyle modification should be encouraged.

BackgroundAccurate and fast measurement of physical activity is important for surveillance. Even though many physical activity questionnaires (PAQ) are currently used in research, it is unclear which of them is the most reliable, valid, and easy to use. This systematic review aimed to identify existing brief PAQs, describe and compare their measurement properties, and assess their level of readability.MethodsWe performed a systematic review based on the PRISMA statement. Literature searches were conducted in six scientific databases. Articles were included if they evaluated validity and/or reliability of brief (i.e., with a maximum of three questions) physical activity or exercise questionnaires intended for healthy adults. Due to the heterogeneity of studies, data were summarized narratively. The level of readability was calculated according to the Flesch-Kincaid formula.ResultsIn total, 35 articles published in English or Spanish were included, evaluating 32 distinct brief PAQs. The studies indicated moderate to good levels of reliability for the PAQs. However, the majority of results showed weak validity when validated against device-based measurements and demonstrated weak to moderate validity when validated against other PAQs. Most of the assessed PAQs met the criterion of being "short," allowing respondents to complete them in less than one minute either by themselves or with an interviewer. However, only 17 questionnaires had a readability level that indicates that the PAQ is easy to understand for the majority of the population.ConclusionsThis review identified a variety of brief PAQs, but most of them were evaluated in only a single study. Validity and reliability of short and long questionnaires are found to be at a comparable level, short PAQs can be recommended for use in surveillance systems. However, the methods used to assess measurement properties varied widely across studies, limiting the comparability between different PAQs and making it challenging to identify a single tool as the most suitable. None of the evaluated brief PAQs allowed for the measurement of whether a person fulfills current WHO physical activity guidelines. Future development or adaptation of PAQs should prioritize readability as an important factor to enhance their usability.

IntroductionTuberculosis remains one of the top ten causes of mortality globally. Children accounted for 12% of all TB cases and 18% of all TB deaths in 2022. Paediatric TB is difficult to diagnose with conventional laboratory tests, and chest radiographs remain crucial. However, in low-and middle-income countries with high TB burden, the capacity for radiological diagnosis of paediatric TB is rarely documented and data on the associated radiation exposure limited.MethodsA multicentre, mixed-methods study is proposed in three countries, Mozambique, South Africa and Spain. At the national level, official registry databases will be utilised to retrospectively compile an inventory of licensed imaging resources (mainly X-ray and Computed Tomography (CT) scan equipment) for the year 2021. At the selected health facility level, three descriptive cross-sectional standardised surveys will be conducted to assess radiology capacity, radiological imaging diagnostic use for paediatric TB diagnosis, and radiation protection optimization: a site survey, a clinician-targeted survey, and a radiology staff-targeted survey, respectively. At the patient level, potential dose optimisation will be assessed for children under 16 years of age who were diagnosed and treated for TB in selected sites in each country. For this component, a retrospective analysis of dosimetry will be performed on TB and radiology data routinely collected at the respective sites. National inventory data will be presented as the number of units per million people by modality, region and country. Descriptive analyses will be conducted on survey data, including the demographic, clinical and programmatic characteristics of children treated for TB who had imaging examinations (chest X-ray (CXR) and/or CT scan). Dose exposure analysis will be performed by children's age, gender and disease spectrum.DiscussionAs far as we know, this is the first multicentre and multi-national study to compare radiological capacity, radiation protection optimization and practices between high and low TB burden settings in the context of childhood TB management. The planned comparative analyses will inform policy-makers of existing radiological capacity and deficiencies, allowing better resource prioritisation. It will inform clinicians and radiologists on best practices and means to optimise the use of radiological technology in paediatric TB management.

ObjectiveTo study the white matter connections between anterior cingulate cortex, anterior insula and amygdala as key regions of the frontal-limbic network that have been related to meditation.DesignTwenty experienced practitioners of Sahaja Yoga Meditation and twenty nonmeditators matched on age, gender and education level, were scanned using Diffusion Weighted Imaging, using a 3T scanner, and their white matter connectivity was compared using diffusion tensor imaging analyses.ResultsThere were five white matter fiber paths in which meditators showed a larger number of tracts, two of them connecting the same area in both hemispheres: the left and right amygdalae and the left and right anterior insula; and the other three connecting left anterior cingulate with the right anterior insula, the right amygdala and the left amygdala. On the other hand, non-meditators showed larger number of tracts in two paths connecting the left anterior insula with the left amygdala, and the left anterior insula with the left anterior cingulate.ConclusionsThe study shows that long-term practice of Sahaja Yoga Meditation is associated with larger white matter tracts strengthening interhemispheric connections between limbic regions and connections between cingulo-amygdalar and cingulo-insular brain regions related to top-down attentional and emotional processes as well as between top-down control functions that could potentially be related to the witness state perceived through the state of mental silence promoted with this meditation. On the other hand, reduced connectivity strength in left anterior insula in the meditation group could be associated to reduced emotional processing affecting top-down processes.

Many proteins in higher eukaryotes, especially those with crucial functions, have multiple isoforms with redundant roles providing protection against potential functional deficiencies in one isoform. However, these isoforms can also have some unique roles. Protein kinase B, also known as Akt, is one such protein that has three isoforms encoded on different genes. Due to high sequence similarity and the general lack of specific reagents, most studies on Akt generalize their findings and do not distinguish between the isoforms. Using an established chemical genetic strategy and a set of known Akt substrates, this work explores substrate specificity of Akt isoforms under steady state conditions in two commonly used cell lines. This strategy can be applied to study any Akt isoform-specific substrates of interest in any cell line of choice as long as the cell line can be transfected.

BackgroundCauda equina syndrome (CES) is a lumbosacral surgical emergency that has been associated with chiropractic spinal manipulation (CSM) in case reports. However, identifying if there is a potential causal effect is complicated by the heightened incidence of CES among those with low back pain (LBP). The study hypothesis was that there would be no increase in the risk of CES in adults with LBP following CSM compared to a propensity-matched cohort following physical therapy (PT) evaluation without spinal manipulation over a three-month follow-up period.MethodsA query of a United States network (TriNetX, Inc.) was conducted, searching health records of more than 107 million patients attending academic health centers, yielding data ranging from 20 years prior to the search date (July 30, 2023). Patients aged 18 or older with LBP were included, excluding those with pre-existing CES, incontinence, or serious pathology that may cause CES. Patients were divided into two cohorts: (1) LBP patients receiving CSM or (2) LBP patients receiving PT evaluation without spinal manipulation. Propensity score matching controlled for confounding variables associated with CES.Results67,220 patients per cohort (mean age 51 years) remained after propensity matching. CES incidence was 0.07% (95% confidence intervals [CI]: 0.05-0.09%) in the CSM cohort compared to 0.11% (95% CI: 0.09-0.14%) in the PT evaluation cohort, yielding a risk ratio and 95% CI of 0.60 (0.42-0.86; p = .0052). Both cohorts showed a higher rate of CES during the first two weeks of follow-up.ConclusionsThese findings suggest that CSM is not a risk factor for CES. Considering prior epidemiologic evidence, patients with LBP may have an elevated risk of CES independent of treatment. These findings warrant further corroboration. In the meantime, clinicians should be vigilant to identify LBP patients with CES and promptly refer them for surgical evaluation.

A growing body of research demonstrates the potential of mindfulness to reduce employee stress. However, with work increasingly migrating from the physical to the digital workplace, evidence is lacking on how mindfulness might help employees live healthy digital working lives. In addition, employees' confidence when using the digital workplace is seen as important for productivity but may also play a role in reducing well-being impacts from digital working. Using the Job-Demands Resources model as a theoretical foundation, 142 workers were surveyed regarding their levels of trait mindfulness and digital workplace confidence, along with their experiences of the dark side effects (stress, overload, anxiety, Fear of Missing Out and addiction) and well-being outcomes (burnout and health). 14 workers were also interviewed to provide qualitative insights on these constructs. Results from regression analyses indicated that more digitally confident workers were less likely to experience digital workplace anxiety, while those with higher mindfulness were better protected against all of the dark side of digital working effects. Interview data indicated ways in which digital mindfulness helps protect well-being, as well as how digital workplace confidence enables healthier digital habits.

The Keen model is designed to represent an economy as a dynamic system governed by the interactions between private debt, wage share, and employment rate. When certain conditions are met, the model can lead to a debt spiral, which accurately mimics the impact of a financial crisis on an economy. This manuscript presents a recipe for breaking this spiral by expressing Keen's model as an affine nonlinear system that can be modified through policy interventions. We begin by considering critical initial conditions that resemble a financial crisis to achieve this goal. We then locate a desired point within the system's vector field that leads to a desirable equilibrium and design a path towards it. This path is later followed using one-step-ahead optimal control. We illustrate our approach by presenting simulated control scenarios.

Wildlife trafficking creates favorable scenarios for intra- and inter-specific interactions that can lead to parasite spread and disease emergence. Among the fauna affected by this activity, primates are relevant due to their potential to acquire and share zoonoses - infections caused by parasites that can spread between humans and other animals. Though it is known that most primate parasites can affect multiple hosts and that many are zoonotic, comparative studies across different contexts for animal-human interactions are scarce. We conducted a multi-parasite screening targeting the detection of zoonotic infections in wild-caught monkeys in nine Peruvian cities across three contexts: captivity (zoos and rescue centers, n = 187); pet (households, n = 69); and trade (trafficked or recently confiscated, n = 132). We detected 32 parasite taxa including mycobacteria, simian foamyvirus, bacteria, helminths, and protozoa. Monkeys in the trade context had the highest prevalence of hemoparasites (including Plasmodium malariae/brasilianum, Trypanosoma cruzi, and microfilaria) and enteric helminths and protozoa were less common in pet monkeys. However, parasite communities showed overall low variation between the three contexts. Parasite richness (PR) was best explained by host genus and the city where the animal was sampled. Squirrel (genus Saimiri) and wooly (genus Lagothrix) monkeys had the highest PR, which was ~2.2 times the PR found in tufted capuchins (genus Sapajus) and tamarins (genus Saguinus/Leontocebus) in a multivariable model adjusted for context, sex, and age. Our findings illustrate that the threats of wildlife trafficking to One Health encompass exposure to multiple zoonotic parasites well-known to cause disease in humans, monkeys, and other species. We demonstrate these threats continue beyond the markets where wildlife is initially sold; monkeys trafficked for the pet market remain a reservoir for and contribute to the translocation of zoonotic parasites to households and other captive facilities where contact with humans is frequent. Our results have practical applications for the healthcare of rescued monkeys and call for urgent action against wildlife trafficking and ownership of monkeys as pets.

Understanding the influence of emotions on social interactions is important for a global understanding of the dynamics of human behavior. In this study, we investigated the interplay between emotions, spontaneous approach or avoidance tendencies, and the regulation of interpersonal distance. Fifty-seven healthy adults participated in a three-part experiment involving exposure to approaching or withdrawing emotional faces (neutral, happy, sad, fearful, disgusted, angry). The sequence began with an initial computerized stop-distance task, followed by a postural task in which participants' approach or avoidance tendencies were quantified via center of pressure (CoP-Y) displacements on a force platform, and concluded with a final computerized stop-distance task. Our findings revealed a gradient in postural responses, with the most forward CoP-Y displacements for neutral and happy faces, indicative of approach tendencies. These were followed by lesser forward displacements for sad and fearful faces, and most pronounced backward displacements for disgusted and angry faces, indicating avoidance. Furthermore, we observed modulations in participants' preferred interpersonal distance based on emotional cues, with neutral and happy faces associated with shorter distances, and disgusted and angry faces linked to larger distances. Despite these similar results, no direct correlation was found between CoP-Y and preferred interpersonal distance, underscoring a dissociation between spontaneous and voluntary social behaviors. These results contribute to a better understanding of how emotional expressions shape social interactions and underscore the importance of considering emotional cues, postural action tendencies, and interpersonal distance in facilitating successful social interactions.

Greyhounds metabolize cytochrome P450 (CYP) 2B11 substrates more slowly than other dog breeds. However, CYP2B11 gene variants associated with decreased CYP2B11 expression do not fully explain reduced CYP2B11 activity in this breed. P450 oxidoreductase (POR) is an essential redox partner for all CYPs. POR protein variants can enhance or repress CYP enzyme function in a CYP isoform and substrate dependent manner. The study objectives were to identify POR protein variants in greyhounds and determine their effect on coexpressed CYP2B11 and CYP2D15 enzyme function. Gene sequencing identified two missense variants (Glu315Gln and Asp570Glu) forming four alleles, POR-H1 (reference), POR-H2 (570Glu), POR-H3 (315Gln, 570Glu) and POR-H4 (315Gln). Out of 68 dog breeds surveyed, POR-H2 was widely distributed across multiple breeds, while POR-H3 was largely restricted to greyhounds and Scottish deerhounds (35% allele frequencies), and POR-H4 was rare. Three-dimensional protein structure modelling indicated significant effects of Glu315Gln (but not Asp570Glu) on protein flexibility through loss of a salt bridge between Glu315 and Arg519. Recombinant POR-H1 (reference) and each POR variant (H2-H4) were expressed alone or with CYP2B11 or CYP2D15 in insect cells. No substantial effects on POR protein expression or enzyme activity (cytochrome c reduction) were observed for any POR variant (versus POR-H1) when expressed alone or with CYP2B11 or CYP2D15. Furthermore, there were no effects on CYP2B11 or CYP2D15 protein expression, or on CYP2D15 enzyme kinetics by any POR variant (versus POR-H1). However, Vmax values for 7-benzyloxyresorufin, propofol and bupropion oxidation by CYP2B11 were significantly reduced by coexpression with POR-H3 (by 34-37%) and POR-H4 (by 65-72%) compared with POR-H1. Km values were unaffected. Our results indicate that the Glu315Gln mutation (common to POR-H3 and POR-H4) reduces CYP2B11 enzyme function without affecting at least one other major canine hepatic P450 (CYP2D15). Additional in vivo studies are warranted to confirm these findings.

ObjectiveTo examine the effects of the COVID-19 pandemic among Latino communities, with an emphasis on understanding barriers and facilitators to vaccine intention prior to the development of the vaccine.MethodsQualitative data were collected between April and June 2020 from 3 focus groups with Latino adults (n = 21) and interviews with administrators of community-based organizations serving Latino communities (n = 12) in urban (Los Angeles) and rural (Fresno) California, supplemented by Community Advisory Board input in May 2021to elucidate the findings. Data were analyzed with deductive content analysis.ResultsWe have identified four main themes that are barriers to vaccinating against COVID-19: 1) concerns about accessing appropriate healthcare services, 2) financial issues and 3) immigration matters, as well as 4) misinformation.ConclusionsFindings illustrate the pervasive role of addressable social determinants of health in the intention of rural and urban Latino communities in being vaccinated, which is a pressing public health issue. Policy implications: Findings provide evidence for a systemic shift to prioritize equitable access to COVID-19 vaccines to Latino communities.

Bacteriophages exhibit a vast spectrum of relatedness and there is increasing evidence of close genomic relationships independent of host genus. The variability in phage similarity at the nucleotide, amino acid, and gene content levels confounds attempts at quantifying phage relatedness, especially as more novel phages are isolated. This study describes three highly similar novel Arthrobacter globiformis phages-Powerpuff, Lego, and YesChef-which were assigned to Cluster AZ using a nucleotide-based clustering parameter. Phages in Cluster AZ, Microbacterium Cluster EH, and the former Microbacterium singleton Zeta1847 exhibited low nucleotide similarity. However, their gene content similarity was in excess of the recently adopted Microbacterium clustering parameter, which ultimately resulted in the reassignment of Zeta1847 to Cluster EH. This finding further highlights the importance of using multiple metrics to capture phage relatedness. Additionally, Clusters AZ and EH phages encode a shared integrase indicative of a lysogenic life cycle. In the first experimental verification of a Cluster AZ phage's life cycle, we show that phage Powerpuff is a true temperate phage. It forms stable lysogens that exhibit immunity to superinfection by related phages, despite lacking identifiable repressors typically required for lysogenic maintenance and superinfection immunity. The ability of phage Powerpuff to undergo and maintain lysogeny suggests that other closely related phages may be temperate as well. Our findings provide additional evidence of significant shared phage genomic content spanning multiple actinobacterial host genera and demonstrate the continued need for verification and characterization of life cycles in newly isolated phages.

Host-associated microbiomes can play important roles in the ecology and evolution of their insect hosts, but bacterial diversity in many insect groups remains poorly understood. Here we examine the relationship between host environment, host traits, and microbial diversity in three species in the ground beetle family (Coleoptera: Carabidae), a group of roughly 40,000 species that synthesize a wide diversity of defensive compounds. This study used 16S amplicon sequencing to profile three species that are phylogenetically distantly related, trophically distinct, and whose defensive chemical secretions differ: Anisodactylus similis LeConte, 1851, Pterostichus serripes (LeConte, 1875), and Brachinus elongatulus Chaudoir, 1876. Wild-caught beetles were compared to individuals maintained in the lab for two weeks on carnivorous, herbivorous, or starvation diets (n = 3 beetles for each species-diet combination). Metagenomic samples from two highly active tissue types-guts, and pygidial gland secretory cells (which produce defensive compounds)-were processed and sequenced separately from those of the remaining body. Bacterial composition and diversity of these ground beetles were largely resilient to controlled changes to host diet. Different tissues within the same beetle harbor unique microbial communities, and secretory cells in particular were remarkably similar across species. We also found that these three carabid species have patterns of microbial diversity similar to those previously found in carabid beetles. These results provide a baseline for future studies of the role of microbes in the diversification of carabids.

Using Twitter to implement public health awareness campaigns is on the rise, but campaign monitoring and evaluation are largely dependent on basic Twitter Analytics. To establish the potential of social network theory-based metrics in better understanding public health campaigns, we analyzed real-time user interactions on Twitter during the 2020 World Breastfeeding Week (WBW) as an exemplar case. Social network analysis (SNA), including community and influencer identification, as well as topic modeling were used to compare the activity of n = 29,958 campaign participants and n = 10,694 reference users from the six-months pre-campaign period. Users formed more inter-connected relationships during the campaign, retweeting and mentioning each other 46,161 times compared to 10,662 times in the prior six months. Campaign participants formed identifiable communities that were not only based on their geolocation, but also based on interests and professional background. While influencers who dominated the WBW conversations were disproportionally members of the scientific community, the campaign did mobilize influencers from the general public who seemed to play a "bridging" role between the public and the scientific community. Users communicated about the campaign beyond its original themes to also discuss breastfeeding within the context of social and racial inequities. Applying SNA allowed understanding of the breastfeeding campaign's messaging and engagement dynamics across communities and influencers. Moving forward, WBW could benefit from improving targeting to enhance geographic coverage and user interactions. As this exemplar case indicates, social network theory and analysis can be used to inform other public health campaigns with data on user interactions that go beyond traditional metrics.

A major challenge in HIV vaccine development is the identification of immunogens able to elicit broadly neutralizing antibodies (bNAbs). While remarkable progress has been made in the isolation and characterization of bNAbs, the epitopes they recognize appear to be poorly immunogenic. Thus, none of the candidate vaccines developed to date has induced satisfactory levels of neutralizing antibodies to the HIV envelope protein (Env). One approach to the problem of poor immunogenicity is to build vaccines based on envelope (env) genes retrieved from rare individuals termed elite neutralizers (ENs) who at one time possessed specific sequences that stimulated the formation of bNAbs. Env proteins selected from these individuals could possess uncommon, yet to be defined, structural features that enhance the immunogenicity of epitopes recognized by bNAbs. Here we describe the recovery of envs from an EN that developed unusually broad and potent bNAbs. As longitudinal specimens were not available, we combined plasma and provirus sequences acquired from a single time-point to infer a phylogenetic tree. Combining ancestral reconstruction data with virus neutralization data allowed us to sift through the myriad of virus quasi-species that evolved in this individual to identify envelope sequences from the nodes that appeared to define the transition from neutralization sensitive envs to the neutralization resistant envs that occur in EN plasma. Synthetic genes from these nodes were functional in infectivity assays and sensitive to neutralization by bNAbs, and may provide a novel source of immunogens for HIV vaccine development.

Boutwell, Nedelec, Winegard, Shackelford, Beaver, Vaughn, Barnes, & Wright (2017) published an article in this journal that interprets data from the Add Health dataset as showing that only one-quarter of individuals in the United States experience discrimination. In Study 1, we attempted to replicate Boutwell et al.s findings using a more direct measure of discrimination. Using data from the Pew Research Center, we examined a large sample of American respondents (N = 3,716) and explored the prevalence of discrimination experiences among various racial groups. Our findings stand in contrast to Boutwell et al.s estimates, revealing that between 50% and 75% of Black, Hispanic, and Asian respondents (depending on the group and analytic approach) reported discriminatory treatment. In Study 2, we explored whether question framing affected how participants responded to Boutwells question about experiencing less respect and courtesy. Regardless of question framing, non-White participants reported more experiences than White participants. Further, there was an interaction of participant race and question framing such that when participants were asked about experiences of less respect or courtesy broadly, there were no differences between non-White participants and White participants, but when they were asked about experiences that were specifically race-based, non-White participants reported more experiences than White participants. The current research provides a counterweight to the claim that discrimination is not a prevalent feature of the lives of minority groups and the serious implications this claim poses for research and public policy.

ObjectivesTo propose a novel framework for COVID-19 vaccine allocation based on three components of Vulnerability, Vaccination, and Values (3Vs).MethodsA combination of geospatial data analysis and artificial intelligence methods for evaluating vulnerability factors at the local level and allocate vaccines according to a dynamic mechanism for updating vulnerability and vaccine uptake.ResultsA novel approach is introduced including (I) Vulnerability data collection (including country-specific data on demographic, socioeconomic, epidemiological, healthcare, and environmental factors), (II) Vaccination prioritization through estimation of a unique Vulnerability Index composed of a range of factors selected and weighed through an Artificial Intelligence (AI-enabled) expert elicitation survey and scientific literature screening, and (III) Values consideration by identification of the most effective GIS-assisted allocation of vaccines at the local level, considering context-specific constraints and objectives.ConclusionsWe showcase the performance of the 3Vs strategy by comparing it to the actual vaccination rollout in Kenya. We show that under the current strategy, socially vulnerable individuals comprise only 45% of all vaccinated people in Kenya while if the 3Vs strategy was implemented, this group would be the first to receive vaccines.

Milk production in the Andean highlands is variable over space and time. This variability is related to fluctuating environmental factors such as rainfall season which directly influence the availability of livestock feeding resources. The main aim of this study was to develop a time-series model to forecast milk production in a mountainous geographical area by analysing the dynamics of milk records thorough the year. The study was carried out in the Andean highlands, using time-series models of monthly milk records collected routinely from dairy cows maintained in a controlled experimental farm over a 9-year period (2008-2016). Several statistical forecasting models were compared. The Mean Absolute Error (MAE), Root Mean Square Error (RMSE), and Mean Absolute Percent Error (MAPE) were used as selection criteria to compare models. A relation between monthly milk records and the season of the year was modelled using seasonal autoregressive integrated moving average (SARIMA) methods to explore temporal redundancy (trends and periodicity). According to white noise residual test (Q = 13.951 and p = 0.052), Akaike Information Criterion and MAE, MAPE, and RMSE values, the SARIMA (1, 0, 0) x (2, 0, 0)12 time-series model resulted slightly better forecasting model compared to others. In conclusion, time-series models were promising, simple and useful tools for producing reasonably reliable forecasts of milk production thorough the year in the Andean highlands. The forecasting potential of the different models were similar and they could be used indistinctly to forecast the milk production seasonal fluctuations. However, the SARIMA model performed the best good predictive capacity minimizing the prediction interval error. Thus, a useful effective strategy has been developed by using time-series models to monitor milk production and alleviate production drops due to seasonal factors in the Andean highlands.

[This corrects the article DOI: 10.1371/journal.pone.0290721.].

Class Demospongiae is the largest in the phylum Porifera (Sponges) and encompasses nearly 8,000 accepted species in three subclasses: Keratosa, Verongimorpha, and Heteroscleromorpha. Subclass Heteroscleromorpha contains ∼90% of demosponge species and is subdivided into 17 orders. The higher level classification of demosponges underwent major revision as the result of nearly three decades of molecular studies. However, because most of the previous molecular work only utilized partial data from a small number of nuclear and mitochondrial (mt) genes, this classification scheme needs to be tested by larger datasets. Here we compiled a mt dataset for 136 demosponge species-including 64 complete or nearly complete and six partial mt-genome sequences determined or assembled for this study-and used it to test phylogenetic relationships among Demospongiae in general and Heteroscleromorpha in particular. We also investigated the phylogenetic position of Myceliospongia araneosa, a highly unusual demosponge without spicules and spongin fibers, currently classified as Demospongiae incertae sedis, for which molecular data were not available. Our results support the previously inferred sister-group relationship between Heteroscleromorpha and Keratosa + Verongimorpha and suggest five main clades within Heteroscleromorpha: Clade C0 composed of order Haplosclerida; Clade C1 composed of Scopalinida, Sphaerocladina, and Spongillida; Clade C2 composed of Axinellida, Biemnida, Bubarida; Clade C3 composed of Tetractinellida; and Clade C4 composed of Agelasida, Clionaida, Desmacellida, Merliida, Suberitida, Poecilosclerida, Polymastiida, and Tethyida. The inferred relationships among these clades were (C0(C1(C2(C3+C4)))). Analysis of molecular data from M. araneosa placed it in the C3 clade as a sister taxon to the highly skeletonized tetractinellids Microscleroderma sp. and Leiodermatium sp. Molecular clock analysis dated divergences among the major clades in Heteroscleromorpha from the Cambrian to the Early Silurian, the origins of most heteroscleromorph orders in the middle Paleozoic, and the most basal splits within these orders around the Paleozoic to Mesozoic transition. Overall, the results of this study are mostly congruent with the accepted classification of Heteroscleromorpha, but add temporal perspective and new resolution to phylogenetic relationships within this subclass.

BackgroundChildren with familial dysautonomia (FD) are smaller and grow more slowly than the general population. It is unknown whether this abnormal growth is due to comorbidities that patients with FD live with, or if it is a direct effect of the disease-causing homozygous ELP-1 mutations. Here, we created growth curves for weight, height, and body mass index (BMI) in male and female children with FD to monitor the nutritional status of patients with FD.MethodsWe used the New York University (NYU) FD Registry which includes data from 680 individuals with FD who were followed longitudinally since birth. We generated sex-specific FD growth charts for three age ranges (birth to 36 months, 2 to 20 years, and 2 to 40 years) and compared them to the general population. We generated Kaplan-Meier curves to test the hypothesis that FD patients with low BMI had shorter survival than the rest of the cohort.ResultsGrowth charts generated from 591 individuals with FD show that these patients grow more slowly, reach less height, and gain less weight than the general population. The impact of FD on height was more pronounced in girls than in boys. However, both groups showed markedly low weights, which resulted in low BMI. Low weight, but not height, is already evident at birth. In a subpopulation of FD patients, we found that treatment with growth hormone or spinal fusion surgery helped patients achieve the expected growth characteristic of FD patients, but these treatments did not lead FD patients to achieve the growth pattern of the general population. Contrary to our hypothesis, low BMI had no impact on patient survival.ConclusionsPediatric patients with FD have lower height, weight, and BMI compared to the general pediatric population, but this does not appear to affect survival. Growth curves specific to the FD population are an important tool to monitor growth and nutritional status in pediatric patients with FD when the general population growth curves are of limited use.

IntroductionPrevious reviews on active learning in dental education have not comprehensibly summarized the research activity on this topic as they have largely focused on specific active learning strategies. This scoping review aimed to map the breadth and depth of the research activity on active learning strategies in undergraduate classroom dental education.MethodsThe review was guided by Arksey & O'Malley's multi-step framework and followed the PRISMA Extension Scoping Reviews guidelines. MEDLINE, ERIC, EMBASE, and Scopus databases were searched from January 2005 to October 2022. Peer-reviewed, primary research articles published in English were selected. Reference lists of relevant studies were verified to improve the search. Two trained researchers independently screened titles, abstracts, and full-texts articles for eligibility and extracted the relevant data.ResultsIn total, 93 studies were included in the review. All studies performed outcome evaluations, including reaction evaluation alone (n = 32; 34.4%), learning evaluation alone (n = 19; 20.4%), and reaction and learning evaluations combined (n = 42; 45.1%). Most studies used quantitative approaches (n = 85; 91.3%), performed post-intervention evaluations (n = 70; 75.3%), and measured student satisfaction (n = 73; 78.5%) and knowledge acquisition (n = 61; 65.6%) using direct and indirect (self-report) measures. Only 4 studies (4.3%) reported faculty data in addition to student data. Flipped learning, group discussion, problem-based learning, and team-based learning were the active learning strategies most frequently evaluated (≥6 studies). Overall, most studies found that active learning improved satisfaction and knowledge acquisition and was superior to traditional lectures based on direct and indirect outcome measures.ConclusionActive learning has the potential to enhance student learning in undergraduate classroom dental education; however, robust process and outcome evaluation designs are needed to demonstrate its effectiveness in this educational context. Further research is warranted to evaluate the impact of active learning strategies on skill development and behavioral change in order to support the competency-based approach in dental education.