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A mixed-methods study was used to determine if an online, mastery-based learning resource was successful in improving content knowledge and retention of critical elements and developmental stages of 16 fundamental movement skills (FMS); a secondary purpose was to determine participant perceptions of their experience with the online resource. Participants (N = 323; motor development (MD) = 94; movement education (ME) = 124; elementary physical education (EPE) = 105) were Teacher Candidates (TCs) in a Physical Education Teacher Education (PETE) Program. Pre- and post-survey data, and pre-, post-, and retention test scores were used to evaluate the program's effectiveness. Paired samples t-tests indicated higher post-test scores for MD ([delta]37.23, p < 0.001, d = 2.32) and ME ([delta]32.12, p < 0.001, d = 1.72). Results from a one-way ANOVA indicated significant improvement and retention of test scores over time, F(3, 331) = 27.761, p < 0.001, [eta-squared] = 0.963. Perceptions of PETE TCs reported positive reactions to the use of the online modules to improve their ability to analyze FMS. Based on these findings, the authors propose that implementing an online, mastery-based resource to analyze FMS may be a positive learning experience for TCs and could lead to long-term content knowledge acquisition of critical elements of FMS.

Estimation of damage in plants is a key issue for crop protection. Currently, experts in the field manually assess the plots. This is a time-consuming task that can be automated thanks to the latest technology in computer vision (CV). The use of image-based systems and recently deep learning-based systems have provided good results in several agricultural applications. These image-based applications outperform expert evaluation in controlled environments, and now they are being progressively included in non-controlled field applications.A novel solution based on deep learning techniques in combination with image processing methods is proposed to tackle the estimate of plant damage in the field. The proposed solution is a two-stage algorithm. In a first stage, the single plants in the plots are detected by an object detection YOLO based model. Then a regression model is applied to estimate the damage of each individual plant. The solution has been developed and validated in oilseed rape plants to estimate the damage caused by flea beetle.The crop detection model achieves a mean precision average of 91% with a mAP@0.50 of 0.99 and a mAP@0.95 of 0.91 for oilseed rape specifically. The regression model to estimate up to 60% of damage degree in single plants achieves a MAE of 7.11, and R2 of 0.46 in comparison with manual evaluations done plant by plant by experts. Models are deployed in a docker, and with a REST API communication protocol they can be inferred directly for images acquired in the field from a mobile device.

Abstract Honey bees are commonly co-exposed to pesticides during crop pollination, including the fungicide captan and neonicotinoid insecticide thiamethoxam. We assessed the impact of exposure to these two pesticides individually and in combination, at a range of field-realistic doses. In laboratory assays, mortality of larvae treated with captan was 80–90% greater than controls, dose-independent, and similar to mortality from the lowest dose of thiamethoxam. There was evidence of synergism (i.e., a non-additive response) from captan-thiamethoxam co-exposure at the highest dose of thiamethoxam, but not at lower doses. In the field, we exposed whole colonies to the lowest doses used in the laboratory. Exposure to captan and thiamethoxam individually and in combination resulted in minimal impacts on population growth or colony mortality, and there was no evidence of synergism or antagonism. These results suggest captan and thiamethoxam are each acutely toxic to immature honey bees, but whole colonies can potentially compensate for detrimental effects, at least at the low doses used in our field trial, or that methodological differences of the field experiment impacted results (e.g., dilution of treatments with natural pollen). If compensation occurred, further work is needed to assess how it occurred, potentially via increased queen egg laying, and whether short-term compensation leads to long-term costs. Further work is also needed for other crop pollinators that lack the social detoxification capabilities of honey bee colonies and may be less resilient to pesticides.

Abstract Pediatric central nervous system tumors remain challenging to diagnose. Imaging approaches do not provide sufficient detail to discriminate between different tumor types, while the histopathological examination of tumor tissue shows high inter-observer variability. Recent studies have demonstrated the accurate classification of central nervous system tumors based on the DNA methylation profile of a tumor biopsy. However, a brain biopsy holds significant risk of bleeding and damaging the surrounding tissues. Liquid biopsy approaches analyzing circulating tumor DNA show high potential as an alternative and less invasive tool to study the DNA methylation pattern of tumors. Here, we explore the potential of classifying pediatric brain tumors based on methylation profiling of the circulating cell-free DNA (cfDNA) in cerebrospinal fluid (CSF). For this proof-of-concept study, we collected cerebrospinal fluid samples from 19 pediatric brain cancer patients via a ventricular drain placed for reasons of increased intracranial pressure. Analyses on the cfDNA showed high variability of cfDNA quantities across patients ranging from levels below the limit of quantification to 40 ng cfDNA per milliliter of CSF. Classification based on methylation profiling of cfDNA from CSF was correct for 7 out of 20 samples in our cohort. Accurate results were mostly observed in samples of high quality, more specifically those with limited high molecular weight DNA contamination. Interestingly, we show that centrifugation of the CSF prior to processing increases the fraction of fragmented cfDNA to high molecular weight DNA. In addition, classification was mostly correct for samples with high tumoral cfDNA fraction as estimated by computational deconvolution (> 40%). In summary, analysis of cfDNA in the CSF shows potential as a tool for diagnosing pediatric nervous system tumors especially in patients with high levels of tumoral cfDNA in the CSF. Further optimization of the collection procedure, experimental workflow and bioinformatic approach is required to also allow classification for patients with low tumoral fractions in the CSF.

Abstract Bioresorbable electrochemical sensors remain mostly unexplored despite their ability to provide continuous in situ measurements of critical biomarkers. The primary challenge arises from the direct exposure of the electrodes’ thin metal films to biofluids, which poses difficulties in ensuring both proper operational lifetimes and sensing performance. Molybdenum (Mo) presents itself as a promising biometal due to its uniquely gradual dissolution in biofluids, facilitated by the formation of a slower‐dissolving MoOx surface layer. Consequently, carefully engineered MoOx films can endow transient electrochemical sensors with unparalleled stability during extended operational lifetimes. Herein an unprecedented sensor architecture achieved via the unique pairing of sputtered Mo and MoOx thin films, probed as a pH and dissolved oxygen sensor is reported. Compared to a bare Mo electrode, a bilayer Mo+MoOx electrode subjected to post‐deposition annealing (400 °C, 60 min, N2 environment) displayed a largely improved stability (>24 h) in solution and demonstrated predictable functionality during ongoing film dissolution at 37 °C. Collectively, this work establishes a pioneering strategy for the fabrication of reliable and clinically relevant implantable electrochemical sensors.

Abstract Despite limited supporting evidence, the practice of thickening breast milk or infant formula with commercially available thickening agents is prevalent. This study explored the viscosity‐enhancing impact of carob bean gum (CBG) and sodium carboxymethylcellulose (NaCMC) when added to infant formula at various concentrations and for different thickening durations. The findings indicate that thickening leads to an exponential increase in milk viscosity, from 25% of the recommended dosage onward. This suggests that minor adjustments in dosage can significantly impact formula thickness, underscoring the importance of accurately dosing and preparing infant milk. The considerable variability in viscosity also emphasizes the need for thoughtful selection of teat size, considering the energy expenditure of the sucking infant. When using 50% of the recommended CBG dose or 25% of NaCMC, the resulting viscosity matches that of a commercially available casein‐based formula containing CBG for anti‐regurgitation. In the case of CBG, a viscosity plateau is only reached after 30 min. Therefore, educating parents on the correct handling and preparation steps for CBG‐thickened infant milk is crucial, including a 30‐min waiting period to achieve the intended thickening effect.

Abstract Background Lack of Cytomegalovirus (CMV) knowledge among healthcare professionals has been proven to be the main threat to pregnant women's awareness, preventing them from reducing the risk of infection. The aims of this study were to assess the knowledge and practices of French-speaking Swiss perinatal professionals in terms of CMV prevention, as well as the sociodemographic-professional factors that influence them. Methods This observational study used a cross-sectional design to collect data-via an anonymous electronic questionnaire in French distributed to gynecologists-obstetricians, general practitioners and midwives via various channels: e-mails and social networks of partner centers, professional associations, and conferences. The 41-item questionnaire collected data on sociodemographic and professional characteristics, general CMV knowledge, national recommendation knowledge and prevention practices. Univariable and multivariable analyses were performed. Results A total of 110 gynecologist-obstetricians, 5 general practitioners and 226 midwives participated in the study. While more than 80% of practitioners were familiar with protective hygiene measures, significant gaps were highlighted concerning the transmission routes, as well as the signs of short- and long-term congenital CMV infection. Regarding practice, 63.3% of participants provided information on CMV to their patients, mainly during the first antenatal visit. Among those who did not, lack of knowledge and forgetfulness were the two main reasons cited. Concerning systematic screening, 45.7% of participants offered it to their patients, and 37.3% only offered it to “at risk” groups. The existence of national guidelines on CMV was known by 62.0% of participants. Multivariable analysis revealed that working as a gynecologist-obstetrician was independently associated with higher score of preventive practices, while performing ultrasound or preconception consultations was independently associated with a higher score of general CMV knowledge, and working in a university hospital was independently associated with a higher score of Swiss recommendation knowledge. A level of training higher than the basic medical or midwifery diploma and participation in fetal medicine symposia both promote a higher score of CMV knowledge and prevention practices in line with current recommendations. Conclusion This study confirms the significant gaps in CMV knowledge among French-speaking Swiss caregivers along with the heterogeneity of their prevention practices. To raise awareness among pregnant women and reduce the burden of congenital CMV infections, improving professional knowledge through access to specific training and standardizing practices should be a national priority.

BackgroundGenome-wide studies of gene-environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer.MethodsAnalyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs.ResultsAssuming a 1 × 10-5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability

BackgroundLow-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.MethodsWe evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.ResultsIn European ancestry samples, 14 genes were significantly associated (q

Although agricultural intensification has generally increased crop yields, it also resulted in a range of environmental issues. These include increased erosion rates and declined soil organic carbon (SOC) stocks. In order to improve our understanding on how erosion impacts the overall SOC storage capacity of croplands, this study analyses the 3D distribution of SOC as a function of water and tillage erosion in a conventionally ploughed field in the Belgian silt loam region. We present a novel methodological framework to integrate the output of an advanced erosion model as a co-variate within a Digital Soil Mapping (DSM) approach with the objective to create detailed SOC maps. More precisely, we combined (i) the Water and Tillage Erosion Model and Sediment Delivery Model (WaTEM/SEDEM), simulating spatial patterns of soil erosion and sediment deposition due to water and tillage erosions, with (ii) a SOC sampling campaign, resulting in a SOC spatial distribution model that considers both types of erosion. The results show that, as compared to plateaus, SOC stocks are nearly half as large along eroding slopes (i.e. convex slope positions affected by tillage erosion and steep slopes affected by water erosion). Yet, they are up to twice as large in areas characterized by sediment deposition (i.e. concave positions due to tillage erosion and foot slope positions due to water erosion). Our results further show that tillage erosion has a significant influence on the SOC stocks in the top 0.7 m and in particular on the top 0.4 m. The influence of water erosion is less strong but mostly significant along the entire depth profile. Overall, this work demonstrates the relevance of considering different erosion processes when aiming to predict spatial patterns of SOC. Considering the top 1 m and a WaTEM/SEDEM application at a resolution of 10 m our 3D SOC modelling approach obtained a coefficient of determination (R2) of 0.62, a relative root mean square error (RRMSE) of 30.5 % and a relative mean absolute error (RMAE) of 26.0 %. While future work may likely lead to further improvements e.g. a more detailed SOC sampling network along the foot slopes and thalwegs in order to obtain a more spatially detailed prediction of the area characterized by depositions due to water erosion, we demonstrate the great potential of existing erosion and deposition models in doing so.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Despite new treatments, the HCC rate remains important, making it necessary to develop novel therapeutic strategies. Photodynamic therapy (PDT) using a Rose-Bengal (RB) photosensitizer (RB-PDT) could be a promising approach for liver tumor treatment. However, the lack of standardization in preclinical research and the diversity of illumination parameters used make comparison difficult across studies. This work presents and characterizes a novel illumination device based on one green light-emitting diode (CELL-LED-550/3) dedicated to an in vitro RB-PDT. The device was demonstrated to deliver a low average irradiance of 0.62 mW/cm2 over the 96 wells of a multi-well plate. Thermal characterization showed that illumination does not cause cell heating and can be performed inside an incubator, allowing a more rigorous assessment of cell viability after PDT. An in vitro cytotoxic study of the RB-PDT on an HCC cell line (HepG2) demonstrated that RB-PDT induces a significant decrease in cell viability: almost all the cells died after a light dose irradiation of 0.3 J/cm2 using 75 µM of RB (

Abstract Background Genome-wide studies of gene–environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene–environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 × 10–5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability

Abstract Non-native pests, climate change, and their interactions are likely to alter relationships between trees and tree-associated organisms with consequences for forest health. To understand and predict such changes, factors structuring tree-associated communities need to be determined. Here, we analysed the data consisting of records of insects and fungi collected from dormant twigs from 155 tree species at 51 botanical gardens or arboreta in 32 countries. Generalized dissimilarity models revealed similar relative importance of studied climatic, host-related and geographic factors on differences in tree-associated communities. Mean annual temperature, phylogenetic distance between hosts and geographic distance between locations were the major drivers of dissimilarities. The increasing importance of high temperatures on differences in studied communities indicate that climate change could affect tree-associated organisms directly and indirectly through host range shifts. Insect and fungal communities were more similar between closely related vs. distant hosts suggesting that host range shifts may facilitate the emergence of new pests. Moreover, dissimilarities among tree-associated communities increased with geographic distance indicating that human-mediated transport may serve as a pathway of the introductions of new pests. The results of this study highlight the need to limit the establishment of tree pests and increase the resilience of forest ecosystems to changes in climate.

BackgroundSurgical site infections (SSI) are a significant concern following traumatic brain injury (TBI) surgery and often stem from the skin's microbiota near the surgical site, allowing bacteria to penetrate deeper layers and potentially causing severe infections in the cranial cavity. This study investigated the relationship between scalp skin microbiota composition and the risk of SSI after TBI surgery in sub-Saharan Africa (SSA).MethodsThis was a prospective cohort study, enrolling patients scheduled for TBI surgery. Sterile skin swabs were taken from the surrounding normal skin of the head and stored for analysis at -80°Celcius. Patients were monitored postoperatively for up to three months to detect any occurrences of SSI. 16S rRNA sequencing was used to analyze the skin microbiota composition, identifying different taxonomic microorganisms at the genus level. The analysis compared two groups: those who developed SSI and those who did not.ResultsA total of 57 patients were included, mostly male (89.5%) with a mean age of 26.5 years, predominantly from urban areas in Uganda and victims of assault. Graphical visualization and metagenomic metrics analysis revealed differences in composition, richness, and evenness of skin microbiota within samples (α) or within the community (β), and showed specific taxa (phylum and genera) associated with either the group of SSI or the No SSI.ConclusionsMetagenomic sequencing analysis uncovered several baseline findings and trends regarding the skin microbiome's relationship with SSI risk. There is an association between scalp microbiota composition (abundancy and diversity) and SSI occurrence following TBI surgery in SSA. We hypothesize under reserve that the scalp microbiota dysbiosis could potentially be an independent predictor of the occurrence of SSI; we advocate for further studies with larger cohorts.

The parasite Leishmania donovani is one of the species causing visceral leishmaniasis in humans, a deadly infection claiming up to 40,000 lives each year. The current drugs for leishmaniasis treatment have severe drawbacks and there is an urgent need to find new anti-leishmanial compounds. However, the search for drug candidates is complicated by the intracellular lifestyle of Leishmania. Here, we investigate the use of human induced pluripotent stem cell (iPS)-derived macrophages (iMACs) as host cells for L. donovani. iMACs obtained through embryoid body differentiation were infected with L. donovani promastigotes, and high-content imaging techniques were used to optimize the iMACs seeding density and multiplicity of infection, allowing us to reach infection rates up to 70% five days after infection. IC50 values obtained for miltefosine and amphotericin B using the infected iMACs or mouse peritoneal macrophages as host cells were comparable and in agreement with the literature, showing the potential of iMACs as an infection model for drug screening.

Plasmacytoid dendritic cells (pDC) are the major producer of type 1 IFN in response to TLR7 agonists. Aberrant TLR7 activation and type 1 IFN expression by pDCs are linked to the pathogenesis of certain types of autoimmune diseases, including systemic lupus erythematosus (SLE). This study investigated the underlying mechanisms for TLR7-mediated cytokine expression by pDCs using a late endosome trafficking inhibitor, EGA (4-bromobenzaldehyde N-(2,6-dimethylphenyl) semicarbazone). We found that EGA treatment decreased IFNα expression by pDCs stimulated with imiquimod (R837), single-stranded RNA40, and influenza virus. EGA also decreased TNFα expression and secretion by R837-stimulated pDCs. Mechanistically, EGA treatment decreased phosphorylation of IKKα/β, STAT1, and p38, and prolonged degradation of IκBα. Furthermore, EGA treatment decreased the colocalization of 3F, a substituted adenine TLR7 agonist, with LAMP1+ compartments in pDCs. EGA was also capable of diminishing IFNα expression by SLE pDCs treated with R837 or live PR8/A/34 influenza viruses. Therefore, we concluded that trafficking of TLR7 agonists to LAMP1+ compartments is important for IFNα expression by pDCs. Data from this study support additional examinations of the potential benefits of EGA in treating type 1 IFN-associated inflammatory diseases in the future.

Objectives Despite treatment, one-third of patients with lupus nephritis (LN) show a decline in renal function. Prognostic markers of poor outcome as well as novel therapeutic targets are therefore highly sought. We showed that p16INK4a, a marker of cellular senescence, is observed in baseline kidney biopsies from patients with LN, and is associated with renal disease. Here, we set out to assess for whether these findings are recapitulated in the B6.NZMSle1/Sle2/Sle3 (B6.Sle1.2.3) mouse model of spontaneous lupus.Methods We evaluated the occurrence and time of onset of p16Ink4a staining by immunohistochemistry on kidney sections, and tested for its association with multiple renal and systemic disease parameters, fibrosis and CD8+ T cell infiltration, in two cohorts of B6.Sle1.2.3 mice.Results The presence of p16Ink4a-positive cells in kidney was significantly associated with increased urine albumin/creatinine ratio, histopathological scores, CD8+ T cell infiltration and fibrosis, in both B6.Sle1.2.3 cohorts. In contrast, p16Ink4a staining was not associated with systemic disease parameters. A time course showed that systemic disease parameters as well as glomerular IgG deposits appeared in B6.Sle1.2.3 mice by 4 months of age; the appearance of p16Ink4a-positive cells occurred later, by 8 months of age, overlapping with renal disease.Conclusion We report, for the first time, the presence of p16Ink4a-positive cells, a marker of cellular senescence, in the B6.Sle1.2.3 kidney, and their association with renal disease severity. This provides a preclinical model in which to test for the role of cellular senescence in the pathogenesis of LN, as a potential kidney-intrinsic disease mechanism.

ABSTRACTBackground: Sexual assault (SA) can induce a negative impact on victims’ mental health. Specialised SA services generally offer medical care and a forensic examination to SA victims. However, there is a large variation in how these services provide mental health support.Objective: This study aims to assess mental health problems of SA victims attending the Belgian Sexual Assault Care Centres (SACCs) and identify predictors for victims’ use of support from in-house psychologists.Method: Health records of victims ≥ 16 years who presented within one week post-SA to one of the three Belgian SACCs between 25 October 2017 and 31 October 2019 were reviewed. An AIC-based stepwise backward binary logistic regression was used to analyse the association between victim, assault, service use and mental health characteristics and follow-up by a SACC-psychologist.Results: Of the 555 victims, more than half had a history of mental health problems. Of those assessed, over 70% showed symptoms of posttraumatic stress disorder (PTSD), depression and/or anxiety disorder. One in two victims consulted a SACC-psychologist. Victims with a mental health history (OR 1.46, p = .04), victims accompanied by a support person during acute care (OR 1.51, p = .04), and victims who were assaulted by an acquaintance in comparison to those assaulted by a stranger (OR 1.60, p = .039) were more likely to attend their appointment with the SACC-psychologist.Conclusion: The study reaffirms the high mental health burden among victims attending specialised SA services, stressing the need to provide effective mental health interventions at these services and improve their longer-term use by victims. Prescheduling of appointments with an in-house psychologist in combination with phone reminders may improve the uptake of such services. Health care providers must be vigilant about potential barriers faced by victims without a mental health history or social support in attending appointments with mental health professionals.