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The setup of a flexible and cost-effective 96-SNP assignment panel to be used in Pekin duck (Anas platyrhynchos), Muscovy duck (Cairina moschata) and their mule duck hybrid, is presented. SNP were selected on the available 600K array in ducks. This SNP array is made of two libraries (one for the Muscovy duck, the other for the common duck which encompasses the Pekin duck), the intersection of which, after a preliminary elimination on the primer length, contained only 399 SNP that were considered a starting point to obtain a final list. A first step was to obtain a list of 192 SNP, based on technical properties, using a reference set of 600K genotypes from commercial lines. In a second step, to obtain the final 96 markers, a subset of the previous reference set was combined with genotypes from 133 Pekin and 127 Muscovy, which were the parents of the experimental populations to assign. Assignment rates were 99%, 96% and 88% in the mule, Pekin and Muscovy populations respectively. The lower-than-expected assignment rate in the Muscovy population was due to the absence of 16 parental samples. Availability of an effective and affordable assignment panel was deemed necessary after switching from a system where breeders are housed in individual cages to a system where females are housed and inseminated in groups. In the latter case, a factorial mating design replaced the hierarchical design, common in poultry. This new design impacted the population structure, creating more sire x dam combinations, offering possibilities for a better estimation of non-additive genetic effects, which could prove relevant in the foie gras sector. Finally, a list of 135 markers resulted from this study that could be used to build an efficient 96 SNP panel for any local or commercial population.

PurposeModels to study metastatic disease in rare cancers are needed to advance preclinical therapeutics and to gain insight into disease biology. Osteosarcoma is a rare cancer with a complex genomic landscape in which outcomes for patients with metastatic disease are poor. As osteosarcoma genomes are highly heterogeneous, multiple models are needed to fully elucidate key aspects of disease biology and to recapitulate clinically relevant phenotypes.Experimental designMatched patient samples, patient-derived xenografts (PDX), and PDX-derived cell lines were comprehensively evaluated using whole-genome sequencing and RNA sequencing. The in vivo metastatic phenotype of the PDX-derived cell lines was characterized in both an intravenous and an orthotopic murine model. As a proof-of-concept study, we tested the preclinical effectiveness of a cyclin-dependent kinase inhibitor on the growth of metastatic tumors in an orthotopic amputation model.ResultsPDXs and PDX-derived cell lines largely maintained the expression profiles of the patient from which they were derived despite the emergence of whole-genome duplication in a subset of cell lines. The cell lines were heterogeneous in their metastatic capacity, and heterogeneous tissue tropism was observed in both intravenous and orthotopic models. Single-agent dinaciclib was effective at dramatically reducing the metastatic burden.ConclusionsThe variation in metastasis predilection sites between osteosarcoma PDX-derived cell lines demonstrates their ability to recapitulate the spectrum of the disease observed in patients. We describe here a panel of new osteosarcoma PDX-derived cell lines that we believe will be of wide use to the osteosarcoma research community.

This publication explains the importance of breastmilk to the infant gut microbiome. First, the gut microbiome is defined, then the source of infant microbes is introduced, and finally the role of breastfeeding in infant gut microbiome and infant health. It is intended for a general audience of all educational backgrounds.

BackgroundYoung children may be exposed to pesticides in child care centers, but little is known about determinants of pesticide contamination in these environments.ObjectiveCharacterize pesticide contamination in early care and education (ECE) centers and identify predictors of pesticide concentrations and loading in dust collected from classroom carpets.MethodsCarpet dust samples were collected from 51 licensed child care centers in Northern California and analyzed for 14 structural and agricultural pesticides. Program characteristics were collected through administration of director interviews and observational surveys, including an integrated pest management (IPM) inspection. Pesticide use information for the prior year was obtained from the California Department of Pesticide Regulation to characterize structural applications and nearby agricultural pesticide use.ResultsThe most frequently detected pesticides were cis-permethrin (98%), trans-permethrin (98%), bifenthrin (94%), fipronil (94%), and chlorpyrifos (88%). Higher bifenthrin levels were correlated with agricultural applications within 3 kilometers, and higher fipronil levels were correlated with professional pesticide applications in the prior year. In multivariable models, higher IPM Checklist scores were associated with lower loading of chlorpyrifos and permethrin. Placement of the sampled area carpet was also a predictor of chlorpyrifos loading. The strongest predictor of higher pesticide loading for the most frequently detected pesticides was location in California's San Joaquin Valley.SignificanceOur findings contribute to the growing understanding that pesticides are ubiquitous in children's environments. Pesticide levels in carpet dust were associated with some factors that ECE directors may have control over, such as IPM practices, and others that are beyond their control, such as geographic location. IPM is an important tool that has the potential to reduce pesticide exposures in ECE environments, even for pesticides no longer in use.ImpactOne million children in California under six years old attend child care programs where they may spend up to 40 h per week. Children are uniquely vulnerable to environmental contaminants; however early care settings are under researched in environmental health studies. Little is known about predictors of pesticide levels found in environmental samples from child care facilities. This study aims to identify behavioral and environmental determinants of pesticide contamination in California child care centers. Findings can empower child care providers and consumers and inform decision makers to reduce children's exposures to pesticides and promote lifelong health.

Summary: Background: It is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID. Methods: Non-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo. Findings: Participants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53–0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID. Interpretation: Amubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID. Funding: National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.

The mule duck accounts for over 90% of French foie gras production, a sector where feed represents two-thirds of production costs. This study focuses on analysing the feeding behaviours of the mule duck and its parental populations (Pekin and Muscovy) using automated feeders. To assess feed efficiency, feed conversion ratio and residual feed intake were analysed, along with six traits derived at the daily and meal levels. Genetic parameters were estimated separately in purebred populations, as well as with a joint crossbred model that estimated the parental contributions to the hybrid crossbred performances. In relation to higher feed intakes and much−reduced feeding times (P 0.41 ± 0.20) for fatty liver weight. Altogether, improving liver traits and feed efficiency in the hybrid through selection in the parental populations could be enhanced by considering feeding traits recorded with electronic feeders, provided that adverse correlations are properly accounted for in a multitrait index.

Hepatic stellate cells (HSC) are the source of extracellular matrix (ECM) whose overproduction leads to fibrosis, a condition that impairs liver functions in chronic liver diseases. Understanding the dynamics of HSCs will provide insights needed to develop new therapeutic approaches. Few models of hepatic fibrosis have been proposed, and none of them include the heterogeneity of HSC phenotypes recently highlighted by single-cell RNA sequencing analyses. Here, we developed rule-based models to study HSC dynamics during fibrosis progression and reversion. We used the Kappa graph rewriting language, for which we used tokens and counters to overcome temporal explosion. HSCs are modeled as agents that present seven physiological cellular states and that interact with (TGFβ1) molecules which regulate HSC activation and the secretion of type I collagen, the main component of the ECM. Simulation studies revealed the critical role of the HSC inactivation process during fibrosis progression and reversion. While inactivation allows elimination of activated HSCs during reversion steps, reactivation loops of inactivated HSCs (iHSCs) are required to sustain fibrosis. Furthermore, we demonstrated the model's sensitivity to (TGFβ1) parameters, suggesting its adaptability to a variety of pathophysiological conditions for which levels of (TGFβ1) production associated with the inflammatory response differ. Using new experimental data from a mouse model of CCl4-induced liver fibrosis, we validated the predicted ECM dynamics. Our model also predicts the accumulation of iHSCs during chronic liver disease. By analyzing RNA sequencing data from patients with non-alcoholic steatohepatitis (NASH) associated with liver fibrosis, we confirmed this accumulation, identifying iHSCs as novel markers of fibrosis progression. Overall, our study provides the first model of HSC dynamics in chronic liver disease that can be used to explore the regulatory role of iHSCs in liver homeostasis. Moreover, our model can also be generalized to fibroblasts during repair and fibrosis in other tissues.

Wearing of face coverings serves two purposes: reducing the concentration of ambient particles inhaled and reducing the emission of respiratory particles generated by the wearer. The efficiency of different face coverings depends on the material, design, and fit. Face coverings such as N95 respirators, when worn properly, are highly efficient at filtering ambient particles during inhalation. Some N95 respirators, as well as other face covering types, include a one-way valve to allow easier exhalation while still maintaining a high efficiency of filtration of inhaled ambient particles. The extent to which these valves decrease the efficiency of filtration of emitted respiratory particles is, however, not well established. Here, we show that different valved N95s exhibit highly variable filtration efficiencies for exhaled respiratory particles. As such, valved N95s may not provide reliable source control of respired particles and their use should be discouraged in situations in which such source control is needed.

Small genes (40,000 small-gene families in ∼2.3 million phage genome contigs. We find that small genes in phage genomes are approximately 3-fold more prevalent than in host prokaryotic genomes. Our approach enriches for small genes that are translated in microbiomes, suggesting the small genes identified are coding. More than 9,000 families encode potentially secreted or transmembrane proteins, more than 5,000 families encode predicted anti-CRISPR proteins, and more than 500 families encode predicted antimicrobial proteins. By combining homology and genomic-neighborhood analyses, we reveal substantial novelty and diversity within phage biology, including small phage genes found in multiple host phyla, small genes encoding proteins that play essential roles in host infection, and small genes that share genomic neighborhoods and whose encoded proteins may share related functions.

IntroductionYoung children may be exposed to pesticides used in child care centers and their family homes. We examined pesticide use and environmental and behavioral factors potentially associated with child exposures in these settings.MethodPreschool-age children (n = 125) wore silicone wristbands to assess pesticide exposures in their child care centers and home environments. Information about environmental and behavioral exposure determinants was collected using parent surveys, child care director interviews, and observations.ResultsCommonly detected pesticides were bifenthrin, chlorpyrifos, cypermethrin, fipronil, and cis- and trans-permethrin. Pesticide chemical storage onsite, cracks in the walls, using doormats, observed pests, or evidence of pests were associated with child exposures. Exposures were higher in counties with higher agricultural or commercial pesticide use or when children lived in homes near agricultural fields.DiscussionYoung children are being exposed to harmful pesticides, and interventions are needed to lower their risk of health problems later in life.

Each year, wildfires ravage the western U.S. and change the lives of millions of inhabitants. Situated in southern California, coastal Santa Barbara has witnessed devastating wildfires in the past decade, with nearly all ignitions started by humans. Therefore, estimating the risk imposed by unplanned ignitions in this fire-prone region will further increase resilience toward wildfires. Currently, a fire-risk map does not exist in this region. The main objective of this study is to provide a spatial analysis of regions at high risk of fast wildfire spread, particularly in the first two hours, considering varying scenarios of ignition locations and atmospheric conditions. To achieve this goal, multiple wildfire simulations were conducted using the FARSITE fire spread model with three ignition modeling methods and three wind scenarios. The first ignition method considers ignitions randomly distributed in 500 m buffers around previously observed ignition sites. Since these ignitions are mainly clustered around roads and trails, the second method considers a 50 m buffer around this built infrastructure, with ignition points randomly sampled from within this buffer. The third method assumes a Euclidean distance decay of ignition probability around roads and trails up to 1000 m, where the probability of selection linearly decreases further from the transportation paths. The ignition modeling methods were then employed in wildfire simulations with varying wind scenarios representing the climatological wind pattern and strong, downslope wind events. A large number of modeled ignitions were located near the major-exit highway running north–south (HWY 154), resulting in more simulated wildfires burning in that region. This could impact evacuation route planning and resource allocation under climatological wind conditions. The simulated fire areas were smaller, and the wildfires did not spread far from the ignition locations. In contrast, wildfires ignited during strong, northerly winds quickly spread into the wildland–urban interface (WUI) toward suburban and urban areas.