Novel Antibacterial Compounds and Methods of Making and Using Same

The invention provides novel antibacterial diamide compounds, pharmaceutical compositions comprising the compounds and methods for treating or preventing an infection in a subject using the compounds

DNA methylation profiling to predict recurrence risk in meningioma: development and validation of a nomogram to optimize clinical management

Abstract Background Variability in standard-of-care classifications precludes accurate predictions of early tumor recurrence for individual patients with meningioma, limiting the appropriate selection of patients who would benefit from adjuvant radiotherapy to delay recurrence. We aimed to develop an individualized prediction model of early recurrence risk combining clinical and molecular factors in meningioma. Methods DNA methylation profiles of clinically annotated tumor samples across multiple institutions were used to develop a methylome model of 5-year recurrence-free survival (RFS). Subsequently, a 5-year meningioma recurrence score was generated using a nomogram that integrated the methylome model with established prognostic clinical factors. Performance of both models was evaluated and compared with standard-of-care models using multiple independent cohorts. Results The methylome-based predictor of 5-year RFS performed favorably compared with a grade-based predictor when tested using the 3 validation cohorts (ΔAUC = 0.10, 95% CI: 0.03–0.018) and was independently associated with RFS after adjusting for histopathologic grade, extent of resection, and burden of copy number alterations (hazard ratio 3.6, 95% CI: 1.8–7.2, P &lt; 0.001). A nomogram combining the methylome predictor with clinical factors demonstrated greater discrimination than a nomogram using clinical factors alone in 2 independent validation cohorts (ΔAUC = 0.25, 95% CI: 0.22–0.27) and resulted in 2 groups with distinct recurrence patterns (hazard ratio 7.7, 95% CI: 5.3–11.1, P &lt; 0.001) with clinical implications. Conclusions The models developed and validated in this study provide important prognostic information not captured by previously established clinical and molecular factors which could be used to individualize decisions regarding postoperative therapeutic interventions, in particular whether to treat patients with adjuvant radiotherapy versus observation alone. </jats:sec

A Diamond in the Desert: Bringing Major League Baseball to Las Vegas

In this 90-minute documentary, we will explore the past, present, and future of Las Vegas as a Major League Baseball city. With the success of the Vegas Golden Knights as well as the Las Vegas Raiders, it is likely that future professional sports franchises will soon call Las Vegas their home. While it is likely that Las Vegas will be home to many different sporting teams in the future, the prospect of an MLB franchise calling Las Vegas their home exhibits the most challenges. What lies ahead for Las Vegas as a baseball town requires an investigation of the past. In a town once deemed unsuitable for professional sports because of sports betting, a culture of minor league teams and university athletics was the only home-town team dynamic available for residents to call their own. Now that Las Vegas has become America’s newest sporting destination, we look to the future to determine what steps and policy decisions need to be made to make Las Vegas an attractive location for MLB expansion. This documentary will consist of a mixture of historical footage from all of Las Vegas’s previous and current baseball endeavors as well as interviews with historians, experts, and baseball fans alike. The goal of this documentary is to inform about Vegas’ rich history of baseball involvement and provide evidence for why Las Vegas needs MLB and why MLB needs Las Vegas

An Improved Protocol for the Synthesis and Purification of Yariv Reagents

Yariv reagents are widely used tools to study plant proteoglycans known as the Arabinogalactan proteins (AGPs). Despite widespread use of the Yariv reagent in the study of AGPs and several reports of synthetic protocols, there remains a lack of a simple procedure to obtain pure Yariv reagents. We report our optimized protocols to address the purification issues faced upon synthesis of Yariv reagents. Additionally, we report challenges that make characterization difficult such as peak broadening in NMR due to Yariv-water interactions. We also show ways of processing Yariv reagents to overcome the characterization issues caused by peak broadening

The Chirality of Yariv Reagent Aggregates Correlates with AGP–binding Ability

Yariv reagents are glycosylated triphenylazo dyes, some of which bind to the polysaccharide component of arabinogalactan proteins (AGPs), proteoglycans found in plant cell walls. However, the exact reason for the selectivity in the presence/absence of AGP binding ability among Yarivs remains unknown. The Yariv reagents are known to form supramolecular aggregates in solution. We use circular dichroism to show that the Yariv reagent aggregates possess helical chirality, and the AGP binding ability of the Yariv reagents is correlated to its helical chirality

Comparative effectiveness of glatiramer acetate and interferon beta formulations in relapsing-remitting multiple sclerosis

Background: The results of head-to-head comparisons of injectable immunomodulators (interferon β, glatiramer acetate) have been inconclusive and a comprehensive analysis of their effectiveness is needed. Objective: We aimed to compare, in a real-world setting, relapse and disability outcomes among patients with multiple sclerosis (MS) treated with injectable immunomodulators. Methods: Pairwise analysis of the international MSBase registry data was conducted using propensity-score matching. The four injectable immunomodulators were compared in six head-to-head analyses of relapse and disability outcomes using paired mixed models or frailty proportional hazards models adjusted for magnetic resonance imaging variables. Sensitivity and power analyses were conducted. Results: Of the 3326 included patients, 345–1199 patients per therapy were matched (median pairwise-censored follow-up was 3.7 years). Propensity matching eliminated >95% of the identified indication bias. Slightly lower relapse incidence was found among patients treated with glatiramer acetate or subcutaneous interferon β-1a relative to intramuscular interferon β-1a and interferon β-1b (p≤0.001). No differences in 12-month confirmed progression of disability were observed. Conclusion: Small but statistically significant differences in relapse outcomes exist among the injectable immunomodulators. MSBase is sufficiently powered to identify these differences and reflects practice in tertiary MS centres. While the present study controlled indication, selection and attrition bias, centre-dependent variance in data quality was likely

Loss of H3K27me3 in meningiomas

BackgroundThere is a critical need for objective and reliable biomarkers of outcome in meningiomas beyond WHO classification. Loss of H3K27me3 has been reported as a prognostically unfavorable alteration in meningiomas. We sought to independently evaluate the reproducibility and prognostic value of H3K27me3 loss by immunohistochemistry (IHC) in a multicenter study.MethodsIHC staining for H3K27me3 and analyses of whole slides from 181 meningiomas across three centers was performed. Staining was analyzed by dichotomization into loss and retained immunoreactivity, and using a 3-tiered scoring system in 151 cases with clear staining. Associations of grouping with outcome were performed using Kaplan-Meier survival estimates.ResultsA total of 21 of 151 tumors (13.9%) demonstrated complete loss of H3K27me3 staining in tumor with retained endothelial staining. Overall, loss of H3K27me3 portended a worse outcome with shorter times to recurrence in our cohort, particularly for WHO grade 2 tumors which were enriched in our study. There were no differences in recurrence-free survival (RFS) for WHO grade 3 patients with retained vs loss of H3K27me3. Scoring by a 3-tiered system did not add further insights into the prognostic value of this H3K27me3 loss. Overall, loss of H3K27me3 was not independently associated with RFS after controlling for WHO grade, extent of resection, sex, age, and recurrence status of tumor on multivariable Cox regression analysis.ConclusionsLoss of H3K27me3 identifies a subset of WHO grade 2 and possibly WHO grade 1 meningiomas with increased recurrence risk. Pooled analyses of a larger cohort of samples with standardized reporting of clinical definitions and staining patterns are warranted