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ABSTRACT: Studies have described a highly convergent plan toward the synthesis of leiodolide A (1), a potent cytotoxic sponge metabolite. The enantiocontrolled preparation of aldehyde 6 is achieved with the application of several advances of methodology for the synthesis of substituted 1,3-oxazoles. Efforts have examined the halogen dance reaction, the selectivity of Stille cross coupling reactions of 4-bromo-1,3-oxazoles, and nucleophilic displacement of the 2-phenylsulfonyl substitu-ent with organolithium reagents as preparatively useful reactions. These techniques have facilitated the efficient synthesis of 6 from the starting bromide 12, alkenylstannane 16 and the primary nonracemic alcohol 25. 

ABSTRACT: A convergent route toward the synthesis of leiodolide A (1) is described. Our studies explore reactions of the indium chloride-induced transmetallation of allylic stannane 32 for nucleophilic addition with nonracemic aldehyde 15. The stereoselective formation of the all-syn stereotriad was rationalized by in situ isomerization to produce the Z-allylindium reagent for subsequent anti-Felkin addition. The inversion of C17 stereochemistry led to an effective -allyl Stille cross cou-pling utilizing Z-alkenylstannane 11b. The Horner–Wadsworth–Emmons reaction provides macrolactone 37 which exhibits discrepancies as compared to reported NMR data for purported leiodolide A. 

Abstract The large-scale universal structure comprises strands of dark matter and galaxies with large underdense volumes known as voids. We measure the fraction of the line of sight that intersects voids for active galactic nuclei (AGN) detected by Fermi Large Area Telescope (LAT) and quasars from the Sloan Digital Sky Survey (SDSS). This “voidiness” fraction is a rudimentary proxy for the density along the line of sight to the galaxies. The voidiness of SDSS-observed quasars (QSOs) is distinctly different from randomly distributed source populations, with a medianp-value of 4.6 × 10⁻⁵and ≪1 × 10⁻⁷, when compared with 500 simulated populations with randomly simulated locations but matching redshifts in the 0.1 ≤z< 0.4 and 0.4 ≤z< 0.7 intervals, respectively. A similar comparison of the voidiness for LAT-detected AGN shows medianp-values greater than 0.05 in each redshift interval. When comparing the SDSS QSO population to the LAT-detected AGN, we mitigate potential bias from a relationship between redshift and voidiness by comparing the LAT-detected AGN to a “redshift-matched” set of SDSS QSOs. The LAT-detected AGN between a redshift of 0.4 and 0.7 show higher voidiness compared to the redshift-matched SDSS QSO populations, with a medianp-value of 2.3 × 10⁻⁵(a 4.1σdeviation). No deviation is found when comparing the same populations between redshifts of 0.1 and 0.4 (p> 0.05). We do not study possible causes of this voidiness difference. It might relate to propagation effects from lower magnetic or radiative background fields within voids or to an environment more favorable for gamma-ray production for AGN near voids. 

Abstract The production and consumption of food is one of the main drivers of environmental change globally. Meanwhile, many populations remain malnourished due to insufficient or unhealthy diets. Increasingly, dietary shifts are proposed as a means to address both environmental and health concerns. We have a limited understanding of how dietary shifts could alter where food is produced and consumed and how these changes would affect the distribution of environmental pressures both globally and across different groups of people. Here we combine new food flow data linking producing to consuming country with environmental pressures to estimate how a global shift to each of four diets (Indian, EAT-Lancet, Mediterranean, and mean Food Based Dietary Guidelines (FBDGs)) could affect environmental pressures at the global, country income group, and country level. Globally, cumulative pressures decrease under the Indian, EAT-Lancet, and Mediterranean scenarios and increase under FBDGs. On average, low income countries increase their cumulative consumption and production pressures while high income countries decrease their consumption pressures, and typically decrease their production pressures. Increases in low income countries are likely due to the nutritional inadequacy of current diets and the corresponding increases in consumption quantities with a shift to our diet scenarios. Despite these increases, we believe that three out four of our simulated dietary shifts can be seen as a net benefit by decreasing global pressures while low income countries increase pressures to adequately feed their populations. Additionally, considering principles of fairness applied, some nations are more responsible for causing historical environmental pressures and should shoulder more of the change. To facilitate more equitable shifts in global diets, resources, capacity, and knowledge sharing of sustainable agricultural practices are critical to minimize the increases in pressures that low income countries would incur to adequately feed their populations. 

Background:The Glycemia Risk Index (GRI) was developed in adults with diabetes and is a validated metric of quality of glycemia. Little is known about the relationship between GRI and type 1 diabetes (T1D) self-management habits, a validated assessment of youths’ engagement in habits associated with glycemic outcomes. Method:We retrospectively examined the relationship between GRI and T1D self-management habits in youth with T1D who received care from a Midwest pediatric diabetes clinic network. The GRI was calculated using seven days of continuous glucose monitor (CGM) data, and T1D self-management habits were assessed ±seven days from the GRI score. A mixed-effects Poisson regression model was used to evaluate the total number of habits youth engaged in with GRI, glycated hemoglobin A1c (HbA1c), age, race, ethnicity, and insurance type as fixed effects and participant ID as a random effect to account for multiple clinic visits per individual. Results:The cohort included 1182 youth aged 2.5 to 18.0 years (mean = 13.8, SD = 3.5) comprising 50.8% male, 84.6% non-Hispanic White, and 64.8% commercial insurance users across a total of 6029 clinic visits. Glycemia Risk Index scores decreased as total number of habits performed increased, suggesting youth who performed more self-management habits achieved a higher quality of glycemia. Conclusions:In youth using CGMs, GRI may serve as an easily obtainable metric to help identify youth with above target glycemia, and engagement/disengagement in the T1D self-management habits may inform clinicians with suitable interventions for improving glycemic outcomes. 

Background:The glycemia risk index (GRI) is a composite metric developed and used to estimate quality of glycemia in adults with diabetes who use continuous glucose monitor (CGM) devices. In a cohort of youth with type 1 diabetes (T1D), we examined the utility of the GRI for evaluating quality of glycemia between clinic visits by analyzing correlations between the GRI and longitudinal glycated hemoglobin A1c (HbA1c) measures. Method:Using electronic health records and CGM data, we conducted a retrospective cohort study to analyze the relationship between the GRI and longitudinal HbA1c measures in youth (T1D duration ≥1 year; ≥50% CGM wear time) receiving care from a Midwest pediatric diabetes clinic network (March 2016 to May 2022). Furthermore, we analyzed correlations between HbA1c and the GRI high and low components, which reflect time spent with high/very high and low/very low glucose, respectively. Results:In this cohort of 719 youth (aged = 2.5-18.0 years [median = 13.4; interquartile range [IQR] = 5.2]; 50.5% male; 83.7% non-Hispanic White; 68.0% commercial insurance), baseline GRI scores positively correlated with HbA1c measures at baseline and 3, 6, 9, and 12 months later (r = 0.68, 0.65, 0.60, 0.57, and 0.52, respectively). At all time points, strong positive correlations existed between HbA1c and time spent in hyperglycemia. Substantially weaker, negative correlations existed between HbA1c and time spent in hypoglycemia. Conclusions:In youth with T1D, the GRI may be useful for evaluating quality of glycemia between scheduled clinic visits. Additional CGM-derived metrics are needed to quantify risk for hypoglycemia in this population. 

Methodology is described for synthesis of C6 derivatives of raloxifene, a prescribed drug for the treatment and prevention of osteoporosis. Studies explore the incorporation of electron-withdrawing substituents at C6 of the benzothiophene core. Effi-cient processes are also examined to introduce hydrogen bond donor and acceptor functionality. Raloxifene derivatives are evaluated with in vitro testing to determine estrogen receptor (ER) binding affinity and gene expression in MC3T3 cells.