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Osteoarthritis (OA) is the commonest musculoskeletal disease worldwide, with an increasing prevalence due to aging. It causes joint pain and disability, decreased quality of life, and a huge burden on healthcare services for society. However, the current main diagnostic methods are not suitable for early diagnosing patients of OA. The use of machine learning (ML) in OA diagnosis has increased dramatically in the past few years. Hence, in this review article, we describe the research progress in the application of ML in the early diagnosis of OA, discuss the current trends and limitations of ML approaches, and propose future research priorities to apply the tools in the field of OA. Accurate ML-based predictive models with imaging techniques that are sensitive to early changes in OA ahead of the emergence of clinical features are expected to address the current dilemma. The diagnostic ability of the fusion model that combines multidimensional information makes patient-specific early diagnosis and prognosis estimation of OA possible in the future.

IntroductionEarly detection of depression is a cost-effective way to prevent adverse outcomes on brain physiology, cognition, and health. Here we propose that loneliness and social adaptation are key factors that can anticipate depressive symptoms.MethodsWe analyzed data from two separate samples to evaluate the associations between loneliness, social adaptation, depressive symptoms, and their neural correlates.ResultsFor both samples, hierarchical regression models on self-reported data showed that loneliness and social adaptation have negative and positive effects on depressive symptoms. Moreover, social adaptation reduces the impact of loneliness on depressive symptoms. Structural connectivity analysis showed that depressive symptoms, loneliness, and social adaptation share a common neural substrate. Furthermore, functional connectivity analysis demonstrated that only social adaptation was associated with connectivity in parietal areas.DiscussionAltogether, our results suggest that loneliness is a strong risk factor for depressive symptoms while social adaptation acts as a buffer against the ill effects of loneliness. At the neuroanatomical level, loneliness and depression may affect the integrity of white matter structures known to be associated to emotion dysregulation and cognitive impairment. On the other hand, socio-adaptive processes may protect against the harmful effects of loneliness and depression. Structural and functional correlates of social adaptation could indicate a protective role through long and short-term effects, respectively. These findings may aid approaches to preserve brain health via social participation and adaptive social behavior.

Purpose: Timely diagnosis of eye diseases is paramount to obtaining the best treatment outcomes. OCT and OCT angiography (OCTA) have several advantages that lend themselves to early detection of ocular pathology; furthermore, the techniques produce large, feature-rich data volumes. However, the full clinical potential of both OCT and OCTA is stymied when complex data acquired using the techniques must be manually processed. Here, we propose an automated diagnostic framework based on structural OCT and OCTA data volumes that could substantially support the clinical application of these technologies. Design: Cross sectional study. Participants: Five hundred twenty-six OCT and OCTA volumes were scanned from the eyes of 91 healthy participants, 161 patients with diabetic retinopathy (DR), 95 patients with age-related macular degeneration (AMD), and 108 patients with glaucoma. Methods: The diagnosis framework was constructed based on semisequential 3-dimensional (3D) convolutional neural networks. The trained framework classifies combined structural OCT and OCTA scans as normal, DR, AMD, or glaucoma. Fivefold cross-validation was performed, with 60% of the data reserved for training, 20% for validation, and 20% for testing. The training, validation, and test data sets were independent, with no shared patients. For scans diagnosed as DR, AMD, or glaucoma, 3D class activation maps were generated to highlight subregions that were considered important by the framework for automated diagnosis. Main Outcome Measures: The area under the curve (AUC) of the receiver operating characteristic curve and quadratic-weighted kappa were used to quantify the diagnostic performance of the framework. Results: For the diagnosis of DR, the framework achieved an AUC of 0.95 ± 0.01. For the diagnosis of AMD, the framework achieved an AUC of 0.98 ± 0.01. For the diagnosis of glaucoma, the framework achieved an AUC of 0.91 ± 0.02. Conclusions: Deep learning frameworks can provide reliable, sensitive, interpretable, and fully automated diagnosis of eye diseases. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Choline is an essential nutrient that is necessary for both fetal development and maintenance of neural function, while its effect on female ovarian development is largely unexplored. Our previous study demonstrated that choline supplementation promotes ovarian follicular development and ovulation, although its underlying mechanism was unclear. To uncover the potential regulation pathway, eighteen female Yorkshire × Landrace gilts were fed with either standard commercial diet (Control group, n = 9) or choline supplemented diet (Choline group, additional 500 mg/kg of control diet, n = 9) from day 90 of age to day 186. At day 186, feces samples were analyzed for effects on the gut microbiome using 16S ribosomal RNA gene V3–V4 region sequencing with Illumina MiSeq, serum samples were analyzed for trimethylamine (TMA) and trimethylamine-N-oxide (TMAO) using HILIC method, and jejunum tissues were analyzed for immune related gene expression using qRT-PCR. Our results show that choline supplementation did not alter the circulating level of TMA and TMAO (P > 0.05), but rather increased gut microbiome alpha diversity (P < 0.05). Beta diversity analysis results showed that the choline diet mainly increased the abundance of Firmicutes, Proteobacteria, and Actinobacteria, but decreased the abundance of Bacteroidetes, Spirochaetes, and Euryarchaeota at the phyla level. Meta-genomic analysis revealed that choline supplementation activated pathways in the gut microbiota associated with steroid hormone biosynthesis and degradation of infertility-causing environmental pollutants (bisphenol, xylene, and dioxins). To further verify the effect of choline on intestinal activity, a porcine intestine cell line (IPEC-J2) was treated with serial concentrations of choline chloride in vitro. Our data demonstrated that choline promoted the proliferation of IPEC-J2 while inhibiting the apoptotic activity. qRT-PCR results showed that choline significantly increased the expression level of Bcl2 in both IPEC-J2 cells and jejunum tissues. The expression of IL-22, a cytokine that has been shown to impact ovarian function, was increased by choline treatment in vitro. Our findings reveal the beneficial effect of choline supplementation on enhancing the gut microbiome composition and intestinal epithelial activity, and offer insights into how these changes may have contributed to the ovarian development-promoting effect we reported in our previous study.

This article describes a dataset of high-resolution visible-spectrum images of safflower (Carthamus tinctorius L.) plants obtained from a LemnaTec Scanalyser automated phenomics platform along with the associated image analysis output and manually acquired biomass data. This series contains 1832 images of 200 diverse safflower genotypes, acquired at the Plant Phenomics Victoria, Horsham, Victoria, Australia. Two Prosilica GT RGB (red-green-blue) cameras were used to generate 6576 × 4384 pixel portable network graphic (PNG) images. Safflower genotypes were either subjected to a salt treatment (250 mM NaCl) or grown as a control (0 mM NaCl) and imaged daily from 15 to 36 days after sowing. Each snapshot consists of four images collected at a point in time; one of which is taken from above (top-view) and the remainder from the side at either 0°, 120° or 240°. The dataset also includes analysis output quantifying traits and describing phenotypes, as well as manually collected biomass and leaf ion content data. The usage of the dataset is already demonstrated in Thoday-Kennedy et al. (2021) [1]. This dataset describes the early growth differences of diverse safflower genotypes and identified genotypes tolerant or susceptible to salinity stress. This dataset provides detailed image analysis parameters for phenotyping a large population of safflower that can be used for the training of image-based trait identification pipelines for a wide range of crop species.

BackgroundCognitive flexibility (CF) enables individuals to readily shift from one concept or mode of practice/thoughts to another in response to changes in the environment and feedback, making CF vital to optimise success in obtaining goals. However, how CF relates to other executive functions (e.g., working memory, response inhibition), mental abilities (e.g., creativity, literacy, numeracy, intelligence, structure learning), and social factors (e.g., multilingualism, tolerance of uncertainty, perceived social support, social decision-making) is less well understood. The current study aims to (1) establish the construct validity of CF in relation to other executive function skills and intelligence, and (2) elucidate specific relationships between CF, structure learning, creativity, career decision making and planning, and other life skills.MethodsThis study will recruit up to 400 healthy Singaporean young adults (age 18-30) to complete a wide range of cognitive tasks and social questionnaires/tasks. The richness of the task/questionnaire battery and within-participant administration enables us to use computational modelling and structural equation modelling to examine connections between the latent constructs of interest.Significance and impactThe current study is the first systematic investigation into the construct validity of CF and its interrelationship with other important cognitive skills such as learning and creativity, within an Asian context. The study will further explore the concept of CF as a non-unitary construct, a novel theoretical proposition in the field. The inclusion of a structure learning paradigm is intended to inform future development of a novel intervention paradigm to enhance CF. Finally, the results of the study will be useful for informing classroom pedagogy and the design of lifelong learning policies and curricula, as part of the wider remit of the Cambridge-NTU Centre for Lifelong Learning and Individualised Cognition (CLIC).

IntroductionChronic Pelvic Pain (CPP) is a complex, multifaceted condition that affects both women and men. There is limited literature on the cost utilization the healthcare system and CPP patients incur. The purpose of this analysis is to characterize the overall healthcare utilization, cost burden, and quality-of-life restrictions experienced by CPP patients using data from an outpatient pelvic rehabilitation practice.MethodsHealthcare utilization data was gathered by systematically reviewing and analyzing data from new patient visit progress notes stored in the clinic's electronic health records (EHR). We obtained in-network costs by using the FAIR Health Consumer online database. Overall costs were then calculated as the utilization times the per-unit costs from the FAIR database. Additionally, data on patients' visual analogue scale (VAS), absenteeism, presenteeism emergency room visits, usage of common pain medications, use of diagnostics, and participation in common treatment modalities was gathered.ResultsData from 607 patients was used. The overall cost burden per patient for all surgeries combined was $15,750 for in-network services. The cost burden for diagnostics was $5,264.22 and treatments was $8,937 per patient for in-network treatments.ConclusionChronic Pelvic Pain was found to have a large cost burden of $29,951 for in-network services which includes treatments, diagnostics, and surgeries. This analysis sets the stage for future investigations involving data on costs of medications that patients have tried prior to presenting to us and costs associated with work hours lost.

Objective To determine the association of quantitative infrapatellar fat pad (IPFP) signal intensity alteration with knee osteoarthritis (OA) progression.Method This study was performed based on the Foundation for the National Institutes of Health OA Biomarkers Consortium study, a nested case–control study consisting of 600 participants. The IPFP signal intensity alterations were quantitatively measured at baseline, 12 months and 24 months. The associations of baseline and time-integrated values over 12 and 24 months of IPFP signal intensity measures with knee OA progression over 48 months were evaluated with adjustment for baseline confounders.Results The baseline level of clustering effect of high signal intensity (Clustering factor (H)) was predictive of clinically relevant progression (both radiographic and pain progression) (OR 1.22). The time-integrated values of all IPFP signal intensity measures, except for mean value of IPFP signal intensity (Mean (IPFP)) over 24 months (ORs ranging from 1.23 to 1.39) as well was all except for Mean (IPFP) and mean value of IPFP high signal intensity (Mean (H)) over 12 months (ORs ranging from 1.20 to 1.31), were positively associated with clinically relevant progression. When the associations of quantitative IPFP signal intensity measures with radiographic and pain progression were examined separately, more IPFP signal intensity measures with stronger effect sizes were associated with radiographic progression compared with pain progression.Conclusion The associations of short-term alteration in quantitative IPFP signal intensity measures with long-term knee OA progression suggest that these measures might serve as efficacy of intervention biomarkers of knee OA.

IntroductionTraditionally, empathy has been studied from two main perspectives: the theory-theory approach and the simulation theory approach. These theories claim that social emotions are fundamentally constituted by mind states in the brain. In contrast, classical phenomenology and recent research based on the enactive theories consider empathy as the basic process of contacting others’ emotional experiences through direct bodily perception and sensation.ObjectiveThis study aims to enrich the knowledge of the empathic experience of pain using an experimental phenomenological method.Materials and methodsImplementing an experimental paradigm used in affective neuroscience, we exposed 28 healthy adults to a video of sportspersons suffering physical accidents while practicing extreme sports. Immediately after watching the video, each participant underwent a phenomenological interview to gather data on embodied, multi-layered dimensions (bodily sensations, emotions, and motivations) and temporal aspects of empathic experience. We also performed quantitative analyses of the phenomenological categories.ResultsExperiential access to the other person’s painful experience involves four main themes. Bodily resonance: participants felt a multiplicity of bodily, affective, and kinesthetic sensations in coordination with the sportsperson’s bodily actions. Attentional focus: some participants centered their attention more on their own personal discomfort and sensations of rejection, while others on the pain and suffering experienced by the sportspersons. Kinesthetic motivation: some participants experienced the feeling in their bodies to avoid or escape from watching the video, while others experienced the need to help the sportspersons avoid suffering any injury while practicing extreme sports. The temporality of experience: participants witnessed temporal fluctuations in their experiences, bringing intensity changes in their bodily resonance, attentional focus, and kinesthetic motivation. Finally, two experiential structures were found: one structure is self-centered empathic experience, characterized by bodily resonance, attentional focus centered on the participant’s own experience of seeing the sportsperson suffering, and self-protective kinesthetic motivation; the other structure is other-centered empathic experience, characterized by bodily resonance, attentional focus centered on the sportsperson, and prosocial kinesthetic motivation to help them.DiscussionWe show how phenomenological data may contribute to comprehending empathy for pain in social neuroscience. In addition, we address the phenomenological aspect of the enactive approach to the three dimensions of an embodiment of human consciousness, especially the intersubjective dimension. Also, based on our results, we suggest an extension of the enactive theory of non-interactive social experience.

Abstract Tall fescue (Festuca arundinacea) is an important cool‐season perennial forage grass that forms mutualistic symbioses with fungal endophytes. Physiological, biochemical and transcriptional comparisons were made between two tall fescue genotypes with contrasting drought tolerance (tolerant, T400, and sensitive, S279), either with or without endophyte (Epichloë coenophiala). Drought stress was applied by withholding watering until plants reached mild, moderate and severe stresses. Physiological characterization showed that T400 had narrower, thicker leaves, and lower leaf conductance under well‐watered conditions, compared to S279. After severe drought and recovery, endophytic T400 had greater shoot and root biomass than other plant types. Under drought, leaf osmotic pressure increased much more in T400 than S279, consistent with accumulation of metabolites/osmolytes, especially proline. Gene Ontology enrichment analysis indicated that T400 had more active organic acid metabolism than S279 under drought, and implicated the role of endophyte in stimulating protein metabolism in both genotypes. Overall T400 and S279 responded to endophyte differently in aspects of physiology, gene transcription and metabolites, indicating plant genotype‐specific reactions to endophyte infection.

IntroductionUnintentional falls are a leading cause of injury-related hospital visits among Canadians, especially seniors. While certain meteorological conditions are suspected risk factors for fall-related injuries, few studies have quantified these associations across a wider range of age groups and with population-based datasets. MethodsWe applied a time-stratified case-crossover study design to characterize associations of highly-spatially-resolved meteorological factors and emergency department (ED) visits for falls, in Ontario, among those aged 5 years and older during the winter months (November to March) between 2011 and 2015. Conditional logistic models were used to estimate the odds ratios (ORs) and their 95% confidence intervals (CIs) for these visits in relation to daily snowfall accumulation, including single-day lags of up to one week before the visit, and daily mean temperature on the day of the visit. Analyses were stratified by age and sex. ResultsWe identified 761 853 fall-related ED visits. The odds for these visits was increased for most days up to a week after a snowfall of 0.2 cm or greater (OR = 1.05–1.08) compared to days with no snowfall. This association was strongest among adults aged 30 to 64 years (OR = 1.16–1.19). The OR for fall-related ED visits on cold days (less than −9.4 °C) was reduced by 0.05 relative to days with an average daily temperature of 3.0 °C or higher (OR = 0.95; 95% CI: 0.94, 0.96), and this pattern was evident across all ages. There were no substantive differences in the strength of this association by sex. ConclusionSnowfall and warmer winter temperatures were associated with an increased risk of fall-related ED visits during Ontario winters. These findings are relevant for developing falls prevention strategies and ensuring timely treatment.

IntroductionLes chutes accidentelles sont l’une des principales causes de visites à l’hôpital liées à des blessures chez les Canadiens, en particulier chez les personnes âgées. Bien qu’on soupçonne certaines conditions météorologiques d’être des facteurs de risque des blessures liées aux chutes, peu d’études ont quantifié ces associations auprès d’un large éventail de groupes d’âge et en utilisant des bases de données populationnelles. MéthodologieNous avons appliqué une méthode d’étude de type cas-croisé stratifié en fonction du temps pour caractériser les associations entre les facteurs météorologiques à haute résolution spatiale et les visites aux services d’urgence en raison de chutes en Ontario, chez les personnes âgées de cinq ans et plus, pendant les mois d’hiver (novembre à mars) pour 2011 à 2015. Des modèles logistiques conditionnels ont été utilisés pour estimer les rapports de cotes (RC) avec intervalles de confiance (IC) à 95 % associés à ces visites en fonction de l’accumulation quotidienne de neige (intégrant les écarts variant entre une journée et une semaine avant la visite) et de la température quotidienne moyenne le jour de la visite. Les analyses ont été stratifiées par âge et par sexe. RésultatsNous avons recensé 761 853 visites aux services d’urgence liées à une chute. La probabilité de survenue de ces visites augmente pour la plupart des jours jusqu’à une semaine après une chute de neige de 0,2 cm ou plus (RC = 1,05 à 1,08) par rapport aux jours sans chute de neige. Cette association s’est révélée la plus forte chez les adultes de 30 à 64 ans (RC = 1,16 à 1,19). Le RC des visites aux services d’urgence liées à une chute lors de journées froides (moins de −9,4°C) a été réduit de 0,05 par rapport aux jours où la température quotidienne moyenne était de 3,0°C ou plus (RC = 0,95; IC à 95 % : 0,94 à 0,96), et cette tendance était valide pour tous les âges. Aucune différence notable dans la force de cette association selon le sexe n’a été relevée. ConclusionLes chutes de neige et les températures hivernales plus chaudes sont associées à un risque accru de visites aux services d’urgence liées à une chute pendant les hivers ontariens. Ces conclusions peuvent servir à élaborer les stratégies de prévention des chutes et à s’assurer d’un traitement rapide.

Abstract Background The novel anti-malarial cipargamin (KAE609) has potent, rapid activity against Plasmodium falciparum. Transient asymptomatic liver function test elevations were previously observed in cipargamin-treated subjects in two trials: one in malaria patients in Asia and one in volunteers with experimentally induced malaria. In this study, the hepatic safety of cipargamin given as single doses of 10 to 150 mg and 10 to 50 mg once daily for 3 days was assessed. Efficacy results, frequency of treatment-emerging mutations in the atp4 gene and pharmacokinetics have been published elsewhere. Further, the R561H mutation in the k13 gene, which confers artemisinin-resistance, was associated with delayed parasite clearance following treatment with artemether–lumefantrine in Rwanda in this study. This was also the first study with cipargamin to be conducted in patients in sub-Saharan Africa. Methods This was a Phase II, multicentre, randomized, open-label, dose-escalation trial in adults with uncomplicated falciparum malaria in five sub-Saharan countries, using artemether–lumefantrine as control. The primary endpoint was ≥ 2 Common Terminology Criteria for Adverse Events (CTCAE) Grade increase from baseline in alanine aminotransferase (ALT) or aspartate transaminase (AST) during the 4-week trial. Results Overall, 2/135 patients treated with cipargamin had ≥ 2 CTCAE Grade increases from baseline in ALT or AST compared to 2/51 artemether–lumefantrine patients, with no significant difference between any cipargamin treatment group and the control group. Cipargamin exposure was comparable to or higher than those in previous studies. Hepatic adverse events and general safety and tolerability were similar for all cipargamin doses and artemether–lumefantrine. Cipargamin was well tolerated with no safety concerns. Conclusions This active-controlled, dose escalation study was a detailed assessment of the hepatic safety of cipargamin, across a wide range of doses, in patients with uncomplicated falciparum malaria. Comparison with previous cipargamin trials requires caution as no clear conclusion can be drawn as to whether hepatic safety and potential immunity to malaria would differ with ethnicity, patient age and or geography. Previous concerns regarding hepatic safety may have been confounded by factors including malaria itself, whether natural or experimental infection, and should not limit the further development of cipargamin. Trial registration ClinicalTrials.gov number: NCT03334747 (7 Nov 2017), other study ID CKAE609A2202

Tracking of nanoparticle dynamics in solution often require labelling. Here, the authors use a high-finesse microcavity and simultaneously measure dispersive frequency shifts of three transverse modes, demonstrating 3D tracking of unlabelled single nanospheres, and quantitatively determine their physical properties.

While the concept of charisma is widely used in the social sciences, its embodied nature is less thoroughly explored and theorised. This paper revisits the key embodied characteristics of Weber's sociology of charisma and re-interprets these using Shilling's (2005, 2013) umbrella notions of the body as a source and location of and means for society as a way of analysing the idea of the charismatic body as a force for social change. It then draws on a range of embodied concepts to illuminate how charisma is significant channel of infra and inter-corporeal affective interaction between “leaders” and their followers. In particular, Freund's (2009) social synaesthesia and bio-agency, Massumi's (2002) perspective of affect and the moving body, Thrift's (2010) charismatic celebrity, allure and glamour, Mellor and Shilling's (1997) sensual solidarities, and Seyfert's (2012) conception of affectif. To develop and illustrate this perspective of the charismatically affective body in action, the life of film star and martial artist Bruce Lee (1940–1973) is utilised.

Abstract Background Accurately predicting impending death is essential for clinicians to clarify goals of care. We aimed to develop diagnostic models to predict death ≤3 days in cancer patients. Methods In this multicenter cohort study, we consecutively enrolled advanced cancer patients admitted to 23 inpatient hospices in 2017. Fifteen clinical signs related to impending death were documented daily from the day when the Palliative Performance Scale (PPS) declined to ≤20–14 days later. We conducted recursive partitioning analysis using the entire data set and performed cross‐validation to develop the model (prediction of 3‐day impending death‐decision tree [P3did‐DT]). Then, we summed the number of systems (nervous/cardiovascular/respiratory/musculoskeletal), where any sign was present to underpin P3did score (range = 0–4). Results Data following PPS ≤20 were obtained from 1396 of 1896 inpatients (74%). The mean age was 73 ± 12 years, and 399 (29%) had gastrointestinal tract cancer. The P3did‐DT was based on three variables and had four terminal leaves: urine output (u/o) ≤200 ml/day and decreased response to verbal stimuli, u/o ≤200 ml/day and no decreased response to verbal stimuli, u/o >200 ml/day and Richmond Agitation‐Sedation Scale (RASS) ≤−2, and u/o >200 ml/day and RASS ≥−1. The 3‐day mortality rates were 80.3%, 53.3%, 39.9%, and 20.6%, respectively (accuracy = 68.3%). In addition, 79.6%, 62.9%, 47.2%, 32.8%, and 17.4% of patients with P3did scores of 4, 3, 2, 1, and 0, respectively, died ≤3 days. Conclusion We successfully developed diagnostic models for death ≤3 days. These may further help clinicians predict impending death and help patients/families prepare for their final days.

Abstract Previously, we reported a collagenase-based, animal product-free protocol for cultivated oral mucosal epithelial cell sheets for transplantation (COMET). Here, we reported the long-term outcomes of first 2 clinical cases. A 27-year-old man suffered from thermal burn, which resulted in symblepharon of lower fornix OD. COMET was performed, and the cornea remained clear with few peripheral NV and no more symblepharon 34 months postoperatively. Another 42-year-old man suffered from severe alkaline burn OD. He underwent COMET, followed by corneal transplantation half a year later. A biopsy taken two years after COMET showed stratified epithelium positive for keratin 4, 13, and 3 in the suprabasal layer. Staining for p63 and p75NTR was both positive in the basal layer. The graft remained clear up to post-OP 4 years. Our study confirmed the long-term survival of the transplanted OMECs, suggesting that collagenase-based spheroidal suspension culture is a promising technique for COMET. Trial registration ClinicalTrials.gov, ClinicalTrials.gov ID: NCT03943797 Registered 9 May 2019-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03943797 .

Abstract Introduction Malaria accounts for more than one-tenth of sub-Saharan Africa’s 2.8 million annual childhood deaths, and remains a leading cause of post-neonatal child mortality in Uganda. Despite increased community-based treatment in Uganda, children continue to die because services fail to reach those most at risk. This study explores the influence of two key equity factors, socioeconomic position and rurality, on whether children with fever in eastern Uganda receive timely access to appropriate treatment for suspected malaria. Methods This was a cross-sectional study in which data were collected from 1094 caregivers of children aged 6–59 months on: illness and care-seeking during the previous two weeks, treatment received, and treatment dosing schedule. Additional data on rurality and household socioeconomic position were extracted from the Iganga-Mayuge Health and Demographic Surveillance Site (HDSS) database. A child was considered to have received prompt and appropriate care for symptoms of malaria if they received the recommended drug in the recommended dosing schedule on the day of symptom onset or the next day. Unadjusted and adjusted logistic regression models were developed to explore associations of the two equity factors with the outcome. The STROBE checklist for observational studies guided reporting. Results Seventy-four percent of children had symptoms of illness in the preceding two weeks, of which fever was the most common. Children from rural households were statistically more likely to receive prompt and appropriate treatment with artemisinin-combination therapy than their semi-urban counterparts (OR 2.32, CI 1.17–4.59, p = 0.016). This association remained significant following application of an adjusted regression model that included the age of the child, caregiver relationship, and household wealth index (OR 2.4, p = 0.036). Wealth index in its own right did not exert a significant effect for children with reported fever (OR for wealthiest quintile = 1.02, CI 0.48–2.15, p = 0.958). Conclusions The findings from this study help to identify the role and importance of two key equity determinants on care seeking and treatment receipt for fever in children. Whilst results should be interpreted within the limitations of data and context, further studies have the potential to assist policy makers to target inequitable social and spatial variations in health outcomes as a key strategy in ending preventable child morbidity and mortality.

Abstract Background Numerous Ebola virus outbreaks have occurred in Equatorial Africa over the past decades. Besides human fatalities, gorillas and chimpanzees have also succumbed to the fatal virus. The 2004 outbreak at the Odzala-Kokoua National Park (Republic of Congo) alone caused a severe decline in the resident western lowland gorilla (Gorilla gorilla gorilla) population, with a 95% mortality rate. Here, we explore the immediate genetic impact of the Ebola outbreak in the western lowland gorilla population. Results Associations with survivorship were evaluated by utilizing DNA obtained from fecal samples from 16 gorilla individuals declared missing after the outbreak (non-survivors) and 15 individuals observed before and after the epidemic (survivors). We used a target enrichment approach to capture the sequences of 123 genes previously associated with immunology and Ebola virus resistance and additionally analyzed the gut microbiome which could influence the survival after an infection. Our results indicate no changes in the population genetic diversity before and after the Ebola outbreak, and no significant differences in microbial community composition between survivors and non-survivors. However, and despite the low power for an association analysis, we do detect six nominally significant missense mutations in four genes that might be candidate variants associated with an increased chance of survival. Conclusion This study offers the first insight to the genetics of a wild great ape population before and after an Ebola outbreak using target capture experiments from fecal samples, and presents a list of candidate loci that may have facilitated their survival.

The fungal family Serendipitaceae encompasses root-associated lineages with endophytic, ericoid, orchid, and ectomycorrhizal lifestyles. Switchgrass is an important bioenergy crop for cellulosic ethanol production owing to high biomass production on marginal soils otherwise unfit for food crop cultivation. The aim of this study was to investigate the host plant responses to Serendipita spp. colonization by characterizing the switchgrass root transcriptome during different stages of symbiosis in vitro. For this, we included a native switchgrass strain, Serendipita bescii, and a related strain, S. vermifera, isolated from Australian orchids. Serendipita colonization progresses from thin hyphae that grow between root cells to, finally, the production of large, bulbous hyphae that fill root cells during the later stages of colonization. We report that switchgrass seems to perceive both fungi prior to physical contact, leading to the activation of chemical and structural defense responses and putative host disease resistance genes. Subsequently, the host defense system appears to be quenched and carbohydrate metabolism adjusted, potentially to accommodate the fungal symbiont. In addition, prior to contact, switchgrass exhibited significant increases in root hair density and root surface area. Furthermore, genes involved in phytohormone metabolism such as gibberellin, jasmonic acid, and salicylic acid were activated during different stages of colonization. Both fungal strains induced plant gene expression in a similar manner, indicating a conserved plant response to members of this fungal order. Understanding plant responsiveness to Serendipita spp. will inform our efforts to integrate them into forages and row crops for optimal plant–microbe functioning, thus facilitating low-input, sustainable agricultural practices.[Graphic: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Unhealthy diets are a critical global concern while dietary measure methods are time consuming and expensive. There is limited evidence that phone-based interventions can improve nutrition data collection and dietary quality, especially for adolescents in developing countries. We developed an artificial-intelligence-based phone application called Food Recognition Assistance and Nudging Insights (FRANI) to address these problems. FRANI can recognize foods in images, track food consumption, display statistics and use gamified nudges to give positive feedback on healthy food choice. This study protocol describes the design of new pilot studies aimed at measuring the feasibility (acceptability, adherence, and usability) of FRANI and its effects on the quality of food choice of adolescents in Ghana and Vietnam. In each country, 36 adolescents (12–18 years) will be randomly allocated into two groups: The intervention group with the full version of FRANI and the control group with the functionality limited to image recognition and dietary assessment. Participants in both groups will have their food choices tracked for four weeks. The control groups will then switch to the full version of FRANI and both groups will be tracked for a further 2 weeks to assess acceptability, adherence, and usability. Analysis of outcomes will be by intent to treat and differences in outcomes between intervention and control group will use Poisson and odds ratio regression models, accounting for repeated measures at individual levels. If deemed feasible, acceptable and usable, FRANI will address gaps in the literature and advance the nutrition field by potentially improving the quality of food choices of adolescent girls in developing countries. This pilot study will also provide insights on the design of a large randomized controlled trial. The functioning and dissemination of FRANI can be an important step towards highly scalable nutrition data collection and healthier food choices for a population at risk of malnutrition.The study protocol and the methods and materials were approved by the Institutional Review Board (IRB) of the IFPRI on April 29th, 2020 (registration number #00007490), the Thai Nguyen National Hospital on April 14th, 2020 (protocol code 274/ĐĐĐ-BVTWTN) and the University of Ghana on August 10th, 2020 (Federalwide Assurance FWA 00001824; NMIMR-IRB CPN 078–19/20). The study protocol was registered in the International Standard Randomized Controlled Trial Number (ISRCTN 10681553; https://doi.org/10.1186/ISRCTN10681553) on November 12, 2021.

Primary metaphors are focal points for the present-day global advertising industry (Ortiz, 2010, 2011; Pérez-Hernández, 2013a, 2013b, 2014, 2019; Pérez-Sobrino, 2017). Nevertheless, there is little research on how they operate in relation to the nature of different products/services. This paper aims to provide (1) insights into the pervasiveness and functioning of primary metaphors in printed advertisements; and (2) a thorough analysis on their productivity in relation to the nature (material vs. immaterial) of the target product. The analysis of a corpus of 300 printed ads reveals that primary metaphors largely outnumber resemblance metaphors in the advertisements under scrutiny. It provides a detailed inventory of the source and target domains involved, and a description of the interaction patterns between primary metaphors and the product/service. The analysis of the data unveils a higher frequency of occurrence of primary metaphor mappings in relation to tangible products and elucidates reasons for this attested trend.

Purpose: To report the distinct pattern of retinal perfusion loss captured on optical coherence tomographic angiography (OCTA) in a case of compressive optic neuropathy associated with pituitary adenoma. Observations: A 51-year-old male had bitemporal hemianopia caused by a pituitary adenoma that compressed the optic chiasm. OCTA scans in both eyes showed peripapillary nerve fiber layer plexus defects in the nasal hemispheres and papillomacular corridors. On macular scans, the ganglion cell layer plexus showed papillomacular defects. The perfusion defects corresponded with thinning on structural OCT measurement and loss of sensitivity on visual field tests. Conclusions and importance: Chiasm compression produces a characteristic pattern of perfusion loss that can be recognized OCTA. This knowledge may be useful in the diagnosis and classification of optic neuropathies.

Brief motivational intervention (BMI) and personalized feedback intervention (PFI) are individual-focused brief alcohol intervention approaches that have been proven efficacious for reducing alcohol use among college students and young adults. Although the efficacy of these two intervention approaches has been well established, little is known about the factors that may modify their effects on alcohol outcomes. In particular, high school drinking may be a risk factor for continued and heightened use of alcohol in college, and thus may influence the outcomes of BMI and PFI. The purpose of this study was to investigate whether high school drinking was associated with different intervention outcomes among students who received PFI compared to those who received BMI. We conducted moderation analyses examining 348 mandated students (60.1% male; 73.3% White; and 61.5% first-year student) who were randomly assigned to either a BMI or a PFI and whose alcohol consumption was assessed at 4-month and 15-month follow-ups. Results from marginalized zero-inflated Poisson models showed that high school drinking moderated the effects of PFI and BMI at the 4-month follow-up but not at the 15-month follow-up. Specifically, students who reported no drinking in their senior year of high school consumed a 49% higher mean number of drinks after receiving BMI than PFI at the 4-month follow-up. The results suggest that alcohol consumption in high school may be informative when screening and allocating students to appropriate alcohol interventions to meet their different needs.

Introduction: International guidelines recommend hospital care for patients with severe Coronavirus disease (COVID-19), but fragile health care systems struggle to cope with high number of admissions, placing patients at risk of receiving substandard care. We describe an outpatient ambulatory surveillance and treatment strategy (OPAT) for health care workers (HCWs) with severe COVID-19 during low hospital bed availability periods in Mexico City. Methods: In this observational, descriptive, retrospective study, we included HCWs with severe disease for whom there were no hospital beds available at the time of evaluation. We provided daily assessments by infectious disease specialists, daily ambulatory steroid, oral thromboprophylaxis and domiciliary low-dose oxygen. We recorded the number of patients who recovered, were hospitalized or died on follow-up. Results: From 18 March 2020 to 16 July 2021, 1739 HCWs attended our service. A total of 540 were diagnosed with COVID-19. Seventy-four had severe COVID-19 and needed hospitalization. Immediate hospitalization was not possible in 56 patients who were sent to the OPAT and included in our study. Twenty-four patients subsequently required hospitalization and 32 recovered as outpatients. Conclusions: We describe a feasible and safe outpatient management strategy for HCWs with severe COVID-19 in a low-resource setting.

Purpose: Stereotactic radiosurgery (SRS) is a highly effective therapy for newly diagnosed brain metastases. Prophylactic antiepileptic drugs are no longer routinely used in current SRS practice, owing to a perceived low overall frequency of new-onset seizures and potential side effects of medications. It is nonetheless desirable to prevent unwanted side effects following SRS. Risk factors for new-onset seizures after SRS have not been well established. As such, we aimed to characterize variables associated with increased seizure risk. Methods and Materials: Patients treated with SRS for newly diagnosed brain metastases between 2013 and 2016 were retrospectively reviewed at a single institution. Data on baseline demographics, radiation parameters, and clinical courses were collected. Results: The cohort consisted of 305 patients treated with SRS without prior seizure history. Median age and baseline Karnofsky Performance Scale score were 64 years (interquartile range, 55-70) and 80 (interquartile range, 80-90), respectively. Twenty-six (8.5%) patients developed new-onset seizures within 3 months of SRS. There was no association between new-onset seizures and median baseline Karnofsky Performance Scale score, prior resection, or prior whole brain radiation therapy. There were significant differences in the combined total irradiated volume (12.5 vs 3.7 cm3, P < .001), maximum single lesion volume (8.8 vs 2.8 cm3, P = .003), lesion diameter (3.2 vs 2.0 cm, P = .003), and number of lesions treated (3 vs 1, P = .018) between patients with and without new-onset seizures, respectively. On multivariate logistic regression, total irradiated volume (odds ratio, 1.09 for every 1-cm1 increase in total volume; confidence interval, 1.02-1.17; P = .016) and pre-SRS neurologic symptoms (odds ratio, 3.08; 95% confidence interval, 1.19-7.99; P = .020) were both significantly correlated with odds of seizures following SRS. Conclusions: Our data suggest that larger total treatment volume and the presence of focal neurologic deficits at presentation are associated with new-onset seizures within 3 months of SRS. High-risk patients undergoing SRS may benefit from counseling or prophylactic antiseizure therapy.

Despite all advances in the treatment of neoplasms and substantial increases in fiveyear survival rates, most patients still die due to their diseases. Late diagnosis in some circumstances and resistance mechanisms throughout treatment still cause most patients to require palliative care integrated with cancer treatment, since diagnosis. Most palliative care interventions can and should be carried out by the oncologist, with reference to the multidisciplinary team specialized in palliative care in the most critical moments of clinical evolution. It is important that the oncologist develops their skills in this scenario and knows how to recognize the moment of referral. The following text outlines the basic skills that are expected of oncologists, such as recognition of the prognosis, identification and correct assessment of symptoms, definition of the time to stop antineoplastic therapy, how to communicate these aspects to patients and family, how to involve psychosocial and spiritual issues and, finally, how to stay within the limits established by modern bioethics. This work consists of brief recommendations for oncologists working in Brazil.

Abstract The climate scenarios that form the basis for current climate risk assessments have no assigned probabilities, and this impedes the analysis of future climate risks. This paper proposes an approach to estimate the probability of carbon dioxide (CO2) concentration scenarios used in key climate change modeling experiments. It computes the CO2 emissions compatible with the concentrations prescribed by Coupled Model Intercomparison Project Phase 5 (CMIP5) and CMIP6 experiments. The distribution of these compatible cumulative emissions is interpreted as the likelihood of future emissions given a concentration pathway. Using Bayesian analysis, the probability of each pathway can be estimated from a probabilistic sample of future emissions. The approach is demonstrated with five probabilistic CO2 emission simulation ensembles from four Integrated Assessment Models (IAM), leading to independent estimates of the likelihood of the CO2 concentration of Representative Concentration Pathways (RCP) and Shared Socioeconomic Pathways (SSP). Results suggest that SSP5‐8.5 is unlikely for the second half of the 21st century, but offer no clear consensus on which of the remaining scenarios is most likely. Estimates of likelihoods of CO2 concentrations associated with RCP and SSP scenarios are affected by sampling errors, differences in emission sources simulated by the IAMs, and a lack of a common experimental framework for IAM simulations. These shortcomings, along with a small IAM ensemble size, limit the applicability of the results presented here. Novel joint IAM and the Earth System Model experiments are needed to deliver actionable probabilistic climate risk assessments.

As aquaculture production continues to grow, producers are looking for more sustainable methods to promote growth and increase fish health and survival. Butyrate is a short-chain fatty acid (SCFA) with considerable benefits to gut health, and in recent years, butyrate has been commonly used as an alternative to antimicrobials in livestock production. In this study, we aimed to assess the protective effects of sodium butyrate (NaB) on larval zebrafish subjected to a lethal Pseudomonas aeruginosa lipopolysaccharide (LPS) endotoxin challenge and to elucidate potential protective mechanisms of action. Larval zebrafish were pre-treated with 0, 3000, or 6000 μM NaB for 24 h at 72 h post-fertilization (hpf), then immune challenged for 24 h with 60 μg/mL of LPS at 96 hpf. Our results demonstrate that larval zebrafish pre-treated with 6000 μM of NaB prior to lethal LPS challenge experienced significantly increased survival by 40%, and this same level of NaB significantly down-regulated the expression of pro-inflammatory Tumor Necrosis Factor α (TNF-alpha). Findings from this study are consistent with the beneficial effects of NaB on other vertebrate species and support the potential use of NaB in aquaculture.

There have been sustained efforts toward using naturalistic methods in developmental science to measure infant behaviors in the real world from an egocentric perspective because statistical regularities in the environment can shape and be shaped by the developing infant. However, there is no user-friendly and unobtrusive technology to densely and reliably sample life in the wild. To address this gap, we present the design, implementation and validation of the EgoActive platform, which addresses limitations of existing wearable technologies for developmental research. EgoActive records the active infants’ egocentric perspective of the world via a miniature wireless head-mounted camera concurrently with their physiological responses to this input via a lightweight, wireless ECG/acceleration sensor. We also provide software tools to facilitate data analyses. Our validation studies showed that the cameras and body sensors performed well. Families also reported that the platform was comfortable, easy to use and operate, and did not interfere with daily activities. The synchronized multimodal data from the EgoActive platform can help tease apart complex processes that are important for child development to further our understanding of areas ranging from executive function to emotion processing and social learning.

Background: Infections are the most common complications among hospitalized severe burn patients. However, limited literature reports early effective predictors of bloodstream infections (BSI) among burn patients. This study aimed to identify cost-effective biomarkers and valuable clinical scoring systems in the emergency department (ED) for the prediction of subsequent BSI in mass burn casualties. Methods: In 2015, a flammable cornstarch-based powder explosion resulted in 499 burn casualties in Taiwan. A total of 35 patients were admitted at Taipei Veterans General Hospital. These severe burn patients (median total body surface area [TBSA] 54%) were young and previously healthy. We assessed the potential of various parameters to predict subsequent BSI, including initial laboratory tests performed at the ED, TBSA, and multiple scoring systems. Results: Fourteen patients (40.0%) had subsequent BSI. The most common causative pathogen was the Acinetobacter baumannii (Ab) group, mostly carbapenem resistant and associated with a poor outcome. The area under the receiver operating characteristic curve revealed that the revised Baux score, TBSA, and initial white blood cell count had excellent discrimination ability in predicting subsequent BSI (0.898, 0.889, and 0.821, respectively). The rate of subsequent BSI differed significantly at the cut-off points of revised Baux score >76, TBSA >55%, and WBC count >16,200/mm3. Conclusion: The initial WBC count at the ED, TBSA, and revised Baux score were good and cost-effective biomarkers for predicting subsequent BSI after burn injuries.

The present work investigates the Zr-containing precipitate evolution and its effect on the mechanical properties of a Cu–Cr–Zr alloy after solution treatment at 1253 K for 2 h and aging at 763 K for 0–6 h. The results show that the precipitation sequence of the Zr-containing precipitates in the Cu–Cr–Zr alloy is supersaturated solid solution→Zr-rich atomic clusters→Cu5Zr phase. Zr atoms first segregate at the {111} crystal plane of the copper and form coherent Zr-rich atomic clusters during the aging process, which are composed of Zr-rich atoms monolayers and exhibit plate-shaped. Some of the Zr-rich atomic clusters is transformed into the more stable phase of Cu5Zr phase as the aging time increases, the habit plane of which is the {111}Cu crystal plane. The contribution of Zr-rich atomic clusters and Cu5Zr precipitates to the yield strength of the alloy is calculated by coherency strengthening and Orowan strengthening, respectively. The total yield strength is very close to the experimentally measured strength.

Abstract Background It is estimated that 1–13% of cases of bronchiectasis in adults globally are attributable to primary ciliary dyskinesia (PCD) but many adult patients with bronchiectasis have not been investigated for PCD. PCD is a disorder caused by mutations in genes required for motile cilium structure or function, resulting in impaired mucociliary clearance. Symptoms appear in infancy but diagnosis is often late or missed, often due to the lack of a “gold standard” diagnostic tool and non-specific symptoms. Mutations in > 50 genes account for around 70% of cases, with additional genes, and non-coding, synonymous, missense changes or structural variants (SVs) in known genes presumed to account for the missing heritability. Methods UK patients with no identified genetic confirmation for the cause of their PCD or bronchiectasis were eligible for whole genome sequencing (WGS) in the Genomics England Ltd 100,000 Genomes Project. 21 PCD probands and 52 non-cystic fibrosis (CF) bronchiectasis probands were recruited in Wessex Genome Medicine Centre (GMC). We carried out analysis of single nucleotide variants (SNVs) and SVs in all families recruited in Wessex GMC. Results 16/21 probands in the PCD cohort received confirmed (n = 9), probable (n = 4) or possible (n = 3) diagnosis from WGS, although 13/16 of these could have been picked up by current standard of care gene panel testing. In the other cases, SVs were identified which were missed by panel testing. We identified variants in novel PCD candidate genes (IFT140 and PLK4) in 2 probands in the PCD cohort. 3/52 probands in the non-CF bronchiectasis cohort received a confirmed (n = 2) or possible (n = 1) diagnosis of PCD. We identified variants in novel PCD candidate genes (CFAP53 and CEP164) in 2 further probands in the non-CF bronchiectasis cohort. Conclusions Genetic testing is an important component of diagnosing PCD, especially in cases of atypical disease history. WGS is effective in cases where prior gene panel testing has found no variants or only heterozygous variants. In these cases it may detect SVs and is a powerful tool for novel gene discovery.

Kostrzewski et al. introduce an in vitro microphysiological model of non-alcoholic steatohepatitis (NASH), consisting of co-cultured primary human liver cells. The authors characterised the transcriptomic, inflammatory and fibrotic phenotype of the model and show that major features of NASH can be recapitulated and therapeutic interventions mimicked.

Integrating river system and economy-wide models in a dynamic, iterative, bidirectional fashion allows assessing some economic impacts of interventions in river systems. Here the authors use this framework to compare water resources management strategies for the Nile in a quest for efficient use of the river’s limited and stressed water resources.

The article deals with the Subcarpathian Ruthenia in the Czechoslovak Constitution of 1920 and its rights, as well as with some aspects of the preparation of the Constitution. The attention is also paid to the tasks of the Constitutional Court and the search for adequate representatives of the Subcarpathian Ruthenia therein.

Abstract Background Buruli ulcer disease (BUD) is a necrotic skin neglected tropical disease (NTD) that has both a mental and physical health impact on affected individuals. Although there is increasing evidence suggesting a strong association between neglected tropical diseases (NTDs) and mental illness, there is a relative lack of information on BUD’s impact on the mental health and quality of life (QoL) of affected individuals in Ghana. This study is to assess the impact of BUD on mental health and quality of life of patients with active and past BUD infection, and their caregivers. Methods We conducted a case control study in 3 BUD endemic districts in Ghana between August and November 2019. Face-to-face structured questionnaire-based interviews were conducted on BUD patients with active and past infection, as well as caregivers of BUD patients using WHO Quality of Life scale, WHO Disability Assessment Schedule, Self-Reporting Questionnaire, Buruli Ulcer Functional Limitation Score and Hospital Anxiety and Depression Scale data tools. Descriptive statistics were used to summarize the characteristics of the study participants. Participant groups were compared using student t test and chi-square (χ 2) or Fisher’s exact tests. Mean quality of life scores are reported with their respective 95% confidence intervals. Data was analysed using STATA statistical software. Results Our results show that BUD patients with active and past infection, along with their caregivers, face significant levels of distress and mental health sequelae compared to controls. Depression (P = 0.003) was more common in participants with active (27%) and past BU infection (17%), compared to controls (0%). Anxiety was found in 42% (11/26) and 20% (6/29) of participants with active and past BUD infection compared to 14% (5/36) of controls. Quality of life was also significantly diminished in active BUD infection, compared to controls. In the physical health domain, mean QoL scores were 54 ± 11.1 and 56 ± 11.0 (95% CI: 49.5‒58.5 and 52.2‒59.7) respectively for participants with active infection and controls. Similarly in the psychological domain, scores were lower for active infection than controls [57.1 ± 15.2 (95% CI: 50.9‒63.2) vs 64.7 ± 11.6 (95% CI: 60.8‒68.6)]. Participants with past infection had high QoL scores in both physical [61.3 ± 13.5 (95% CI: 56.1‒66.5)] and psychological health domains [68.4 ± 14.6 (95% CI: 62.7‒74.0)]. Conclusions BUD is associated with significant mental health distress and reduced quality of life in affected persons and their caregivers in Ghana. There is a need for integration of psychosocial interventions in the management of the disease. Graphic abstract

The increased attention given to health, food security, and biodiversity conservation in recent years should bring together conventional scientists and indigenous people to share their knowledge systems for better results. This work aims to assess how grasshoppers are perceived by the local people in southern Cameroon, particularly in terms of food, health, and landscape conservation. Villagers were interviewed individually using a rapid rural assessment method in the form of a semi-structured survey. Nearly all people (99%) declared that they are able to identify local grasshoppers, generally through the color of the insect (80%). Crop fields were the most often cited landscape (16%) in terms of abundance of grasshoppers, with forest being less mentioned (8%). In general, villagers claimed that grasshopper abundance increased with forest degradation. Grasshoppers were found during all seasons of the year but noted to be more abundant during the long dry seasons. People found grasshoppers both useful and harmful, the most harmful reported being Zonocerus variegatus, an important crop pest. Cassava is the most attacked crop with 75–100% losses. Industrial crops, such as cocoa, coffee, and bananas, were not cited as being damaged by grasshoppers. The most effective conventional method cited for the control of pest grasshoppers is the use of pesticides (53%) with, in most cases (27%), a 75–100% efficiency. The traditional method of spreading ash was also often cited (19%), with an estimated efficiency of 25–75%. Biological methods were neither cited nor used by the villagers. Most of them (87%) declared that they eat grasshoppers; some sold these insects in the market (58%) and some used them to treat diseases (11%).