A Fluorinated Sialic Acid Vaccine Lead Against Meningitis B and C.

Inspired by the specificity of α-(2,9)-sialyl epitopes in bacterial capsular polysaccharides (CPS), a doubly fluorinated disaccharide has been validated as a vaccine lead against Neisseria meningitidis serogroups C and/or B. Emulating the importance of fluorine in drug discovery, this molecular editing approach serves a multitude of purposes, which range from controlling α-selective chemical sialylation to mitigating competing elimination. Conjugation of the disialoside with two carrier proteins (CRM197 and PorA) enabled a semisynthetic vaccine to be generated; this was then investigated in six groups of six mice. The individual levels of antibodies formed were compared and classified as highly glycan-specific and protective. All glycoconjugates induced a stable and long-term IgG response and binding to the native CPS epitope was achieved. The generated antibodies were protective against MenC and/or MenB; this was validated in vitro by SBA and OPKA assays. By merging the fluorinated glycan epitope of MenC with an outer cell membrane protein of MenB, a bivalent vaccine against both serogroups was created. It is envisaged that validation of this synthetic, fluorinated disialoside bioisostere as a potent antigen will open new therapeutic avenues.

Using a Flipped Classroom and Role-Play to Introduce Nursing Students to LGBTQIA+ Patient Care.

ABSTRACT: This project used a flipped classroom method to introduce prelicensure baccalaureate nursing students to the concept of sexual orientation and gender identity and increase student knowledge and comfort in the care of these individuals. Teaching-learning strategies included self-instruction via video and classroom activities of group discussion and role-play. The educational activity used a pre- and posttest design to evaluate learning outcomes. After implementation, students reported a greater understanding of the needs of lesbian, gay, bisexual, transgender, queer/questioning, intersex, and asexual (LGBTQIA+) patients. The results suggest that even a short introduction to the LGBTQIA+ patient's needs could increase nursing students' knowledge.

Fluorinated carbohydrates for 18F-positron emission tomography (PET).

Carbohydrate diversity is foundational in the molecular literacy that regulates cellular function and communication. Consequently, delineating and leveraging this structure-function interplay continues to be a core research objective in the development of candidates for biomedical diagnostics. A totemic example is the ubiquity of 2-deoxy-2-[18F]-fluoro-D-glucose (2-[18F]-FDG) as a radiotracer for positron emission tomography (PET), in which metabolic trapping is harnessed. Building on this clinical success, more complex sugars with unique selectivities are gaining momentum in molecular recognition and personalised medicine: this reflects the opportunities that carbohydrate-specific targeting affords in a broader sense. In this Tutorial Review, key milestones in the development of 2-[18F]-FDG and related glycan-based radiotracers for PET are described, with their diagnostic functions, to assist in navigating this rapidly expanding field of interdisciplinary research.

Barriers and facilitators to cancer clinical trial enrollment and participation among rural populations: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to identify barriers and facilitators related to cancer clinical trial enrollment and participation among rural populations. INTRODUCTION: Advancing the effectiveness of cancer treatment and increasing early detection of cancer relies on enrollment and participation of individuals in cancer clinical trials. Lack of enrollment and participation in trials is a concern, and there is evidence that individuals living in rural areas are unlikely to participate in such trials. Information on barriers to, and facilitators of, enrollment and participation in cancer clinical trials is needed for the development of evidence-based interventions to increase the enrollment and participation of rural populations. INCLUSION CRITERIA: The review will consider studies on adults aged 18 years or older living in rural areas. Studies that report on barriers and facilitators to enrollment and participation in cancer clinical trials, including both cancer therapeutic and cancer early detection trials, will be included in the review. The review will consider quantitative, qualitative, and text and opinion papers for inclusion. METHODS: The search strategy will aim to locate published primary studies, reviews, and opinion papers, the latter including those by professional oncology organizations. The databases to be searched include MEDLINE, CINAHL, Embase, Web of Science, and Cochrane Library. Gray literature databases will also be searched. Two independent reviewers will retrieve full-text studies and extract data. The results will be presented in diagrammatic format with a narrative summary.

Geographic Variation in Obesity at the State Level in the All of Us Research Program.

INTRODUCTION: National obesity prevention strategies may benefit from precision health approaches involving diverse participants in population health studies. We used cohort data from the National Institutes of Health All of Us Research Program (All of Us) Researcher Workbench to estimate population-level obesity prevalence. METHODS: To estimate state-level obesity prevalence we used data from physical measurements made during All of Us enrollment visits and data from participant electronic health records (EHRs) where available. Prevalence estimates were calculated and mapped by state for 2 categories of body mass index (BMI) (kg/m2): obesity (BMI >30) and severe obesity (BMI >35). We calculated and mapped prevalence by state, excluding states with fewer than 100 All of Us participants. RESULTS: Data on height and weight were available for 244,504 All of Us participants from 33 states, and corresponding EHR data were available for 88,840 of these participants. The median and IQR of BMI taken from physical measurements data was 28.4 (24.4- 33.7) and 28.5 (24.5-33.6) from EHR data, where available. Overall obesity prevalence based on physical measurements data was 41.5% (95% CI, 41.3%-41.7%); prevalence of severe obesity was 20.7% (95% CI, 20.6-20.9), with large geographic variations observed across states. Prevalence estimates from states with greater numbers of All of Us participants were more similar to national population-based estimates than states with fewer participants. CONCLUSION: All of Us participants had a high prevalence of obesity, with state-level geographic variation mirroring national trends. The diversity among All of Us participants may support future investigations on obesity prevention and treatment in diverse populations.

Randomized, Ascending Dose, Phase 2 Study of KHK4083, an Anti-OX40 Monoclonal Antibody, in Moderately Active Ulcerative Colitis.

Background: OX40 (CD134) plays a role in the maintenance of late T-cell proliferation and survival. KHK4083 is a monoclonal antibody directed against OX40. We aimed to assess the safety and preliminary efficacy of KHK4083 in patients with moderately active ulcerative colitis (UC). Methods: In this multicenter, double-blind, parallel-group, phase 2 study, patients with moderately active UC patients were randomized to ascending doses of intravenous KHK4083 (1, 3, or 10 mg/kg) or placebo every 2 weeks for 12 weeks. The primary endpoint was safety. The primary efficacy end point was the change from baseline in mean modified Mayo endoscopy subscore at week 12. Treatment with KHK4083 or placebo was continued every 4 weeks for up to 52 weeks in responders. Results: Long-term treatment with KHK4083 was well tolerated, with treatment-related adverse events being predominantly transient mild-to-moderate infusion-related reactions. Exploratory analysis of biopsy samples showed the virtually complete elimination of OX40+ cells in colon mucosa after 12 weeks of KHK4083 treatment. There were no significant differences between any of the randomized KHK4083 dose groups and placebo for the mean change in Mayo endoscopy subscore from baseline to week 12. Conclusions: KHK4083 can be safely administered intravenously at doses up to 10 mg/kg every 2 or 4 weeks for up to 52 weeks. Proof of pharmacodynamic action was confirmed by depletion of the elevated levels of the OX40+ cells associated with UC at all tested doses. Clinical response and mucosal healing (endoscopic improvement) in this population was not correlated with ablation of OX40+ T cells.

Corrigendum to: Randomized, Ascending Dose, Phase 2 Study of KHK4083, an Anti-OX40 Monoclonal Antibody, in Moderately Active Ulcerative Colitis.

[This corrects the article DOI: 10.1093/crocol/otaa049.].

Optimism and cardiovascular health among African Americans in the Jackson Heart Study.

Little research has examined associations of positive psychosocial factors with the American Heart Association Life's Simple 7™ (LS7) among African Americans. This study examined the associations between positive optimistic orientation and LS7 among African Americans. Using exam 1 data (2000-2004) from the Jackson Heart Study, we examined cross-sectional associations of optimism (in tertiles) with LS7 components [smoking, physical activity, diet, body mass index, blood pressure, cholesterol, glucose] and a composite LS7 score (classified as poor, intermediate, ideal) among 4734 African Americans free of cardiovascular disease. Multivariable prevalence regression was used to estimate prevalence ratios (PR, 95% confidence interval-CI) of intermediate and ideal (vs. poor) individual LS7 components and composite LS7 score by optimism levels, adjusting for demographics, socioeconomic status, and depressive symptoms. For LS7 components with low prevalence, we estimated odds ratios. A greater percentage of participants with high vs. low optimism were younger, female, high SES, and not depressed. After full covariate adjustment, the prevalence ratio of ideal (vs. poor) composite LS7 score was 1.24 for participants who reported high (vs. low) optimism (95% CI 1.09-1.42) at exam 1. Higher levels of optimism were also associated with greater prevalence of ideal (vs. poor) physical activity and smoking. Promoting positive optimistic orientation may be an important step toward increasing the likelihood of achieving optimal cardiovascular health among African Americans.

Aspirin Treatment Effect and Association with PIK3CA Mutation in Breast Cancer: A Biomarker Analysis.

BACKGROUND: Studies suggest regular aspirin use decreases breast cancer (BRCA) risk, with high doses exerting an "anti-cancer" effect. Despite reports suggesting aspirin's protective role in BRCA, no findings on aspirin dose association(s) with treatment outcomes have been reported, nor have any molecular subtype associations by which aspirin influences outcomes been elucidated. To interrogate aspirin's effect and determine which populations may benefit from its use, we retrospectively explored data from 1227 patients with BRCA. In this population, 32 used high-dose aspirin (325 mg), 121 used low-dose aspirin (81 mg), and 1074 used no aspirin before and/or after diagnosis. PATIENTS AND METHODS: Several association tests were performed to examine the correlations of clinical variables and PIK3CA mutations from 45 patients with BRCA who used 81 mg of aspirin daily. Kaplan-Meyer survival curves and the log-rank test were utilized to compare survival outcome differences for aspirin dose, usage history, and PIK3CA mutation status. Cox proportional hazards models were used to compute the multivariate hazard ratio (HR) for death. RESULTS: Patients who regularly used high-dose aspirin (325 mg) had better survival outcomes than those who used low-dose aspirin (81 mg) (HR, 0.094; 95% confidence interval [CI], 0.014-0.62; P = .014). Patients who used aspirin post-diagnosis only achieved significant benefits in overall survival (HR, 0.082; 95% CI, 0.023-0.3; P = 1.39E-04). Also, a subgroup of patients in the low-dose, long-term aspirin group with a PIK3CA mutation showed a small beneficial effect (HR, 0.37; 95% CI, 0.04-3.25; P = .37). CONCLUSION: High-dose aspirin after diagnosis may confer BRCA treatment benefits. Future studies should assess the comprehensive mechanism of aspirin for the PIK3CA mutant subgroup in a large study.

Association of psychosocial factors with leukocyte telomere length among African Americans in the Jackson Heart Study.

Leukocyte telomere length (LTL) is a biomarker of cellular aging. African Americans report more stress than other groups; however, the association of psychosocial stressors with biological aging among African Americans remains unclear. The current study evaluated the association of psychosocial factors (negative affect and stressors) with LTL in a large sample of African American men and women (n = 2,516) from the Jackson Heart Study. Using multivariable linear regression, we examined the sex-specific associations of psychosocial factors (cynical distrust, anger in and out, depressive symptoms, negative affect summary scores, global stress, weekly stress, major life events, and stress summary scores) with LTL. Model 1 adjusted for demographics and education. Model 2 adjusted for model 1, smoking, alcohol intake, physical activity, diabetes, hypertension, and high-sensitivity C-reactive protein. Among women, high (vs. low) cynical distrust was associated with shorter mean LTL in model 1 (b = -0.12; p = 0.039). Additionally, high (vs. low) anger out and expressed negative affect summary scores were associated with shorter LTL among women after full adjustment (b = -0.13; p = 0.011; b = -0.12, p = 0.031, respectively). High levels of cynical distrust, anger out, and negative affect summary scores may be risk factors for shorter LTL, particularly among African-American women.