Baloxavir marboxil is an antiviral drug that targets the endonuclease activity of the influenza virus polymerase acidic (PA) protein. PA I38T/M/F substitutions reduce its antiviral efficacy. To understand the effects of the 19 possible amino acid (AA) substitutions at PA 38 on influenza A(H1N1)pdm09 polymerase activity and inhibition by baloxavir acid, the active metabolite of baloxavir marboxil. Influenza A(H1N1)pdm09 viral polymerase complexes containing all 19 I38X AA substitutions were reconstituted in HEK293T cells in a mini-replicon assay. Polymerase complex activity and baloxavir inhibitory activity were measured in the presence or absence of 50 nM baloxavir acid. Only three substitutions (R, K, P) reduced polymerase activity to <79% of I38-WT. Selleck LTGO-33 When compared with the prototypical baloxavir marboxil resistance marker T38, 5 substitutions conferred 10%-35% reductions in baloxavir acid inhibitory activity (M, L, F, Y, C) and 11 substitutions conferred >50% reductions (R, K, S, N, G, W, A, Q, E, D, H), while two substitutions (V, P) maintained baloxavir acid inhibitory activity. Most PA 38 substitutions permit a functional replication complex retaining some drug resistance in the mini-replicon assay. This study provides a targeted approach for virus rescue and analysis of novel baloxavir marboxil reduced-susceptibility markers, supports the consideration of a broader range of these markers during antiviral surveillance and adds to the growing knowledge of baloxavir marboxil resistance profiles.Most PA 38 substitutions permit a functional replication complex retaining some drug resistance in the mini-replicon assay. This study provides a targeted approach for virus rescue and analysis of novel baloxavir marboxil reduced-susceptibility markers, supports the consideration of a broader range of these markers during antiviral surveillance and adds to the growing knowledge of baloxavir marboxil resistance profiles.Despite the established benefits of regular physical activity in cardiovascular disease prevention, coronary events in the context of atherosclerotic coronary artery disease have been found to be the most common cause of exercise-related sudden death. A paradoxical development of an increased coronary calcification burden is likely to be associated with endurance training even in the absence of any of the traditional cardiovascular risk factors. In this case report, we present a 50-year old, male, long-distance runner with excessive, subclinical myocardial ischemia.Successful hematopoietic progenitor cell (HPC) transplant therapy is improved by mobilizing HPCs from the bone marrow niche in donors. Notch receptor-ligand interactions are known to retain HPCs in the bone marrow, and neutralizing antibodies against Notch ligands, JAG1 or DLL4, or NOTCH2 receptor potentiates HPC mobilization. Notch-ligand interactions are dependent on posttranslational modification of Notch receptors with O-fucose and are modulated by Fringe-mediated extension of O-fucose moieties. We previously reported that O-fucosylglycans on Notch are required for Notch receptor-ligand engagement controlling hematopoietic stem cell quiescence and retention in the marrow niche. Here we generated recombinant fragments of NOTCH1 or NOTCH2 extracellular domain carrying the core ligand binding regions (EGF11-13) either as unmodified forms or as O-fucosylglycan-modified forms. We found that the addition of O-fucose monosaccharide or the Fringe-extended forms of O-fucose to EGF11-13 showed substantial increases in binding to DLL4. Further, the O-fucose and Fringe-extended NOTCH1 EGF11-13 protein displayed much stronger binding to DLL4 than the NOTCH2 counterpart. When assessed in an in vitro 3D osteoblastic niche model, we showed that the Fringe-extended NOTCH1 EGF11-13 fragment effectively released lodged HPC cells with a higher potency than the NOTCH2 blocking antibody. We concluded that O-fucose and Fringe-modified NOTCH1 EGF11-13 protein can be utilized as effective decoys for stem cell niche localized ligands to potentiate HPC egress and improve HPC collection for hematopoietic cell therapy. Female athletes/performing artists can present with low energy availability (LEA) either through unintentional (e.g., inadvertent undereating) or intentional methods (e.g., eating disorder [ED]). While LEA and ED risk have been examined independently, little research has examined these simultaneously. Awareness of LEA with or without ED risk may provide clinicians with innovative prevention and intervention strategies. To examine LEA with or without ED risk (e.g., eating attitudes, pathogenic behaviors) in female collegiate athletes/performing artists. Cross-sectional and descriptive. Free-living in sport-specific settings. Collegiate female athletes/performing artist (n=121; age 19.8±2.0 years; height 168.9±7.7 cm; weight 63.6±9.26 kg) in equestrian (n=28), volleyball (n=12), softball (n=17), beach volleyball (n=18), ballet (n=26) and soccer (n=20) participated in this study. Anthropometric measurements (height, weight, body composition), resting metabolic rate, energy intake, total daily energy for LEA with ED risk, thus warranting education, identification, prevention, and intervention strategies relative to fueling for performance.Our results suggest a large proportion of collegiate female athletes/performing artists are at risk for LEA with ED risk, thus warranting education, identification, prevention, and intervention strategies relative to fueling for performance.Adequate supervision is critical to maintain the performance of health workers who provide essential maternal and child health services in low-resource areas. Supportive supervision emphasizing problem-solving, skill development and mentorship has been shown to improve the motivation and effectiveness of health workers, especially at the community level, but it is not always routinely provided. Previous studies have assessed the uptake of supportive supervision among volunteer health workers and paid health centre staff, but less is known about the supervision experiences of paid community-based staff, such as community health nurses (CHNs) in Ghana. This mixed-methods study explores the frequency and content of CHN supervision in five districts in the Greater Accra and Volta regions of Ghana. We analysed quantitative data from 197 satisfaction surveys and qualitative data from 29 in-depth interviews (IDIs) and four focus group discussions (FGDs) with CHNs. While the majority of CHNs received supervision at least monthly, they reported that supervision was primarily focused on meeting clinical targets (48%) rather than on handling specific cases or patients (23%).