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It's a time of change at Lakewood Elementary. Arthur and Buster are going into 4th grade (and will do anything to get the cool new teacher, MC-voiced by special guest B.J. Novak). Meanwhile, D.W. and Bud prepare to enter kindergarten and Muffy and Francine contemplate how spending the summer away from each other will affect their friendship. Educational Objective: Arthur and friends learn to embrace the future, while appreciating the past.

When a powerful hurricane hits Elwood City, everyone's affected. Ladonna's dad is called up by the Army Corps of Engineers. Muffy relocates to a shelter, while Arthur struggles to reunite lost pets and owners. And Brain seeks the help of a therapist -- voiced by special guest Idina Menzel --to help him manage his anxiety. Educational Objective: Arthur and friends realize the importance of family, friendship, and the support and compassion of others in times of crisis.

There's a new kid in town: Ladonna Compson, the Louisiana native with the gift of gab. Ladonna charms Arthur and friends with her amazing \"true\" stories. But are her stories really fact ... or fiction?

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for selenium. Systematic reviews of the literature were conducted to identify evidence regarding excess selenium intake and clinical effects and potential biomarkers of effect, risk of chronic diseases and impaired neuropsychological development in humans. Alopecia, as an early observable feature and a well‐established adverse effect of excess selenium exposure, is selected as the critical endpoint on which to base a UL for selenium. A lowest‐observed‐adverse‐effect‐level (LOAEL) of 330 μg/day is identified from a large randomised controlled trial in humans (the Selenium and Vitamin E Cancer Prevention Trial (SELECT)), to which an uncertainty factor of 1.3 is applied. A UL of 255 μg/day is established for adult men and women (including pregnant and lactating women). ULs for children are derived from the UL for adults using allometric scaling (body weight0.75). Based on available intake data, adult consumers are unlikely to exceed the UL, except for regular users of food supplements containing high daily doses of selenium or regular consumers of Brazil nuts. No risk has been reported with the current levels of selenium intake in European countries from food (excluding food supplements) in toddlers and children, and selenium intake arising from the natural content of foods does not raise reasons for concern. Selenium‐containing supplements in toddlers and children should be used with caution, based on individual needs.

Germplasm collections hold valuable allelic diversity for crop improvement and genetic mapping of complex traits. To gain access to the genetic diversity within the USDA National Small Grain Collection (NSGC), we developed the Barley Recombinant Inbred Diverse Germplasm Population (BRIDG6), a six-row spring barley multiparent population (MPP) with 88 cultivated accessions crossed to a common parent (Rasmusson). The parents were randomly selected from a core subset of the NSGC that represents the genetic diversity of landrace and breeding accessions. In total, we generated 6160 F5 recombinant inbred lines (RILs), with an average of 69 and a range of 37–168 RILs per family, that were genotyped with 7773 SNPs, with an average of 3889 SNPs segregating per family. We detected 23 quantitative trait loci (QTL) associated with flowering time with five QTL found coincident with previously described flowering time genes. A major QTL was detected near the flowering time gene, HvPpd-H1 which affects photoperiod. Haplotype-based analysis of HvPpd-H1 identified private alleles to families of Asian origin conferring both positive and negative effects, providing the first observation of flowering time-related alleles private to Asian accessions. We evaluated several subsampling strategies to determine the effect of sample size on the power of QTL detection, and found that, for flowering time in barley, a sample size >50 families or 3000 individuals results in the highest power for QTL detection. This MPP will be useful for uncovering large and small effect QTL for traits of interest, and identifying and utilizing valuable alleles from the NSGC for barley improvement.

Background This systematic review aims to explore the prevalence of the impact of the COVID-19, MERS, and SARS pandemics on the mental health of pregnant women. Methods All COVID-19, SARS and MERS studies that evaluated the mental health of pregnant women with/without gynaecological conditions that were reported in English between December 2000 – July 2021 were included. The search criteria were developed based upon the research question using PubMed, Science Direct, Ovid PsycINFO and EMBASE databases. A wide search criterion was used to ensure the inclusion of all pregnant women with existing gynaecological conditions. The Newcastle-Ottawa-Scale was used to assess the risk of bias for all included studies. Random effects model with restricted maximum-likelihood estimation method was applied for the meta-analysis and I-square statistic was used to evaluate heterogeneity across studies. The pooled prevalence rates of symptoms of anxiety, depression, PTSD, stress, and sleep disorders with 95% confidence interval (CI) were computed. Results This systematic review identified 217 studies which included 638,889 pregnant women or women who had just given birth. There were no studies reporting the mental health impact due to MERS and SARS. Results showed that women who were pregnant or had just given birth displayed various symptoms of poor mental health including those relating to depression (24.9%), anxiety (32.8%), stress (29.44%), Post Traumatic Stress Disorder (PTSD) (27.93%), and sleep disorders (24.38%) during the COVID-19 pandemic. Discussion It is important to note that studies included in this review used a range of outcome measures which does not allow for direct comparisons between findings. Most studies reported self-reported measure of symptoms without clinical diagnoses so conclusions can be made for symptom prevalence rather than of mental illness. The importance of managing mental health during pregnancy and after-delivery improves the quality of life and wellbeing of mothers hence developing an evidence-based approached as part of pandemic preparedness would improve mental health during challenging times. Other The work presented in this manuscript was not funded by any specific grants . A study protocol was developed and published in PROSPERO (CRD42021235356) to explore several key objectives.

Epidermal growth factor receptor (EGFR) signalling is activated by ligand-induced receptor dimerization. Notably, ligand binding also induces EGFR oligomerization, but the structures and functions of the oligomers are poorly understood. Here, we use fluorophore localization imaging with photobleaching to probe the structure of EGFR oligomers. We find that at physiological epidermal growth factor (EGF) concentrations, EGFR assembles into oligomers, as indicated by pairwise distances of receptor-bound fluorophore-conjugated EGF ligands. The pairwise ligand distances correspond well with the predictions of our structural model of the oligomers constructed from molecular dynamics simulations. The model suggests that oligomerization is mediated extracellularly by unoccupied ligand-binding sites and that oligomerization organizes kinase-active dimers in ways optimal for auto-phosphorylation in trans between neighbouring dimers. We argue that ligand-induced oligomerization is essential to the regulation of EGFR signalling. Epidermal growth factor receptors have been shown to oligomerise upon binding to their cognate ligands. Here, the authors use biochemical, biophysical and cell biology techniques to analyse the structures of these oligomers, and argue that these formations are required for signalling.

An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry and modes of action are desperately needed worldwide to tackle the public health menace posed by antimicrobial resistance. Here, our consortium presents a strategic blueprint to substantially improve our ability to discover and develop new antibiotics. We propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding, aiming to bridge the gap between academic, industrial and political stakeholders, and to unite interdisciplinary expertise in order to efficiently fuel the translational pipeline for the benefit of future generations. Antimicrobial resistance is an increasing threat to public health and encouraging the development of new antimicrobials is one of the most important ways to address the problem. This Roadmap article aims to bring together industrial, academic and political partners, and proposes both short-term and long-term solutions to this challenge.

Patients can be immunocompromised from a diverse range of disease and treatment factors, including malignancies, autoimmune disorders and their treatments, and organ and stem-cell transplantation. Infections are a leading cause of morbidity and mortality in immunocompromised patients, and the disease treatment landscape is continually evolving. Despite being a critical but preventable and curable adverse event, the reporting of infection events in randomised trials lacks sufficient detail while inconsistency of categorisation and definition of infections in observational and registry studies limits comparability and future pooling of data. A core reporting dataset consisting of category, site, severity, organism, and endpoints was developed as a minimum standard for reporting of infection events in immunocompromised patients across study types. Further additional information is recommended depending on study type. The standardised reporting of infectious events and attributable complications in immunocompromised patients will improve diagnostic, treatment, and prevention approaches and facilitate future research in this patient group.

Clinical development of monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is challenging due to rapid changes in the variant landscape. This study identified a threshold model for neutralising antibody (nAb) titres associated with clinically relevant protection against symptomatic COVID-19 for vulnerable populations. Using efficacy data from the phase 3 PROVENT pre-exposure prophylaxis trial of tixagevimab–cilgavimab (NCT04625725), individual nAb ID 50 titres were predicted by dividing serum mAb concentration by prevalence-adjusted tixagevimab–cilgavimab potency (from in vitro IC 50 values combined with viral surveillance data) and related to efficacy with a Cox model. The Threshold of Protection (ToP) Cox model was externally validated using data from the phase 3 SUPERNOVA trial (NCT05648110), which assessed sipavibart efficacy against symptomatic COVID-19 in immunocompromised participants. The PROVENT ToP model estimated the variant-specific observed efficacies from SUPERNOVA for 3 and 6 months post any dose with Lin’s concordance of 0.86 and 0.75, respectively. This approach integrates predicted nAb ID 50 titres against multiple SARS-CoV-2 variants into a ToP model that can be applied across different variants and could serve as a surrogate endpoint in immunobridging studies to expedite clinical evaluation and regulatory approval for mAbs targeting SARS-CoV-2. Neutralising antibody levels are an important correlate of protection for pre-exposure prophylaxis against COVID-19, but it can be difficult to account for immune evasion of emerging virus variants. Here the authors present a variant-adjusted threshold of protection model, developed and validated with data from two clinical trials, which can be used to infer efficacy against any SARS-CoV-2 variant.