Citations

Abstract Neurofilament light chain, a putative measure of neuronal damage, is measurable in blood and CSF and is predictive of cognitive function in individuals with Alzheimer’s disease. There has been limited prior work linking neurofilament light and functional connectivity, and no prior work has investigated neurofilament light associations with functional connectivity in autosomal dominant Alzheimer’s disease. Here, we assessed relationships between blood neurofilament light, cognition, and functional connectivity in a cross-sectional sample of 106 autosomal dominant Alzheimer’s disease mutation carriers and 76 non-carriers. We employed an innovative network-level enrichment analysis approach to assess connectome-wide associations with neurofilament light. Neurofilament light was positively correlated with deterioration of functional connectivity within the default mode network and negatively correlated with connectivity between default mode network and executive control networks, including the cingulo-opercular, salience, and dorsal attention networks. Further, reduced connectivity within the default mode network and between the default mode network and executive control networks was associated with reduced cognitive function. Hierarchical regression analysis revealed that neurofilament levels and functional connectivity within the default mode network and between the default mode network and the dorsal attention network explained significant variance in cognitive composite scores when controlling for age, sex, and education. A mediation analysis demonstrated that functional connectivity within the default mode network and between the default mode network and dorsal attention network partially mediated the relationship between blood neurofilament light levels and cognitive function. Our novel results indicate that blood estimates of neurofilament levels correspond to direct measurements of brain dysfunction, shedding new light on the underlying biological processes of Alzheimer’s disease. Further, we demonstrate how variation within key brain systems can partially mediate the negative effects of heightened total serum neurofilament levels, suggesting potential regions for targeted interventions. Finally, our results lend further evidence that low-cost and minimally invasive blood measurements of neurofilament may be a useful marker of brain functional connectivity and cognitive decline in Alzheimer’s disease.

Abstract Background: Globally, Black men suffer the greatest prostate cancer (CaP) burden. Blacks are diagnosed more at advanced stages of CaP, greater morbidity and mortality and poorer survivorship outcomes. Blacks are exposed to adverse, discriminatory societal determinants. How these determinants impact the CaP disparities, in particular survivorship and health related quality of life inequities are understudied. Studies examining patient-reported outcomes of Black CaP survivors reveal heightened negative HRQOL sequelae, and depression, family, work and living situation instability due to cancer treatment and societal determinants of health (SDOH). SDOH is used mostly in Public Health to predict population health risk and outcomes, but rarely integrated into HRQOL research and practice. This project is novel by incorporating SDOH into the assessment and relief of HRQOL threats. Despite the Black CaP disparities in survivorship, there remains unacceptable lack of focus and prioritization to provide comprehensive relief. Methods: In response to this noticeable scientific gap, our requisite multidisciplinary investigatory team including Survivor-Advocate Investigators joins forces to achieve the study goal. We are employing community engaged research practice to create a CaP survivorship care plan (SCP) template targeted to Blacks. Our SCP will provide a comprehensive best-practice roadmap to document medical information with treatment history and status, along with relevant resources and health advisories to provide relief for unfavorable sequalae due to cancer and its treatments as well as improve quality of life for CaP survivors. We are building upon the Science of Survivorship, and Contextual Socioecological and the Behavioral Precision Medicine Models with full survivor-advocate partnership to create the SCP. This project to develop a SCP template employs an informative consensus panel to inform the initial SCP. Results: Based on advocate-survivor input and guidance, the SCP will include resources and tools focused on SDOH, treatment adherence, treatment side effects and symptom relief, co-occurring chronic conditions, cardio-protective strategies, and physical, emotional and social wellbeing towards improving in patient outcomes and HRQOL in Black CaP survivors. Data from the Engagement Core and Survivor-Advocate Community Advisory Board, and the preliminary SCP CaP for Black men will be presented at the meeting. Conclusion: Our Consortium builds upon the work of the multidisciplinary PIs, and provide team science approach with robust scientific methods to better understand and address the HRQOL needs of Black CaP survivors. Importantly, this research will make available a patient-centered SCP for CaP survivors, focused on Black men. The iCCaRE Consortium will use this SCP_CaP to inform the development of Artificial Intelligence interventions addressing medical, follow-up care, surveillance, social and emotional support, SDOH and health advisories that will be deployed on popular mobile platforms for greater reach and on-demand use. Citation Format: Kimlin T. Ashing, Folakemi T. Odedina, Cassandra N. Moore, Che Ngufor, Getachew A. Dagne, Fornati Bedell, Diana Londoño, John McCall, Arnold Merriweather, JoAnne S. Oliver, Rotimi Rotimi Oladapo. The iCCARE Consortium for Prostate Cancer in Black men: Creating a survivorship care plan for Black prostate cancer survivors [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A033.

Abstract Since the proposition of the pro‐invasive activity of proteolytic enzymes over 70 years ago, several roles for proteases in cancer progression have been established. About half of the 473 active human proteases are expressed in the prostate and many of the most well‐characterized members of this enzyme family are regulated by androgens, hormones essential for development of prostate cancer. Most notably, several kallikrein‐related peptidases, including KLK3 (prostate‐specific antigen, PSA), the most well‐known prostate cancer marker, and type II transmembrane serine proteases, such as TMPRSS2 and matriptase, have been extensively studied and found to promote prostate cancer progression. Recent findings also suggest a critical role for proteases in the development of advanced and aggressive castration‐resistant prostate cancer (CRPC). Perhaps the most intriguing evidence for this role comes from studies showing that the protease‐activated transmembrane proteins, Notch and CDCP1, are associated with the development of CRPC. Here, we review the roles of proteases in prostate cancer, with a special focus on their regulation by androgens.

OBJECTIVE Bioresorbable flow diverters (BRFDs) could significantly improve the performance of next-generation flow diverter technology. In the current work, magnesium and iron alloy BRFDs were prototyped and compared in terms of porosity/pore density, radial strength, flow diversion functionality, and resorption kinetics to offer insights into selecting the best available bioresorbable metal candidate for the BRFD application. METHODS BRFDs were constructed with braided wires made from alloys of magnesium (MgBRFD) or iron (FeBRFD). Pore density and crush resistance force were measured using established methods. BRFDs were deployed in silicone aneurysm models attached to flow loops to investigate flow diversion functionality and resorption kinetics in a simulated physiological environment. RESULTS The FeBRFD exhibited higher pore density (9.9 vs 4.3 pores/mm2) and crush resistance force (0.69 ± 0.05 vs 0.53 ± 0.05 N/cm, p = 0.0765, n = 3 per group) than the MgBRFD, although both crush resistances were within the range previously reported for FDA-approved flow diverters. The FeBRFD demonstrated greater flow diversion functionality than the MgBRFD, with significantly higher values of established flow diversion metrics (mean transit time 159.6 ± 11.9 vs 110.9 ± 1.6, p = 0.015; inverse washout slope 192.5 ± 9.0 vs 116.5 ± 1.5, p = 0.001; n = 3 per group; both metrics expressed as a percentage of the control condition). Last, the FeBRFD was able to maintain its braided structure for > 12 weeks, whereas the MgBRFD was almost completely resorbed after 5 weeks. CONCLUSIONS The results of this study demonstrated the ability to manufacture BRFDs with magnesium and iron alloys. The data suggest that the iron alloy is the superior material candidate for the BRFD application due to its higher mechanical strength and lower resorption rate relative to the magnesium alloy.

Abstract Objective To determine COVID-19 vaccine-related adverse events (AEs) in the seven-day post-vaccination period in patients with SLE vs autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HC). Methods Data were captured through the COVID-19 Vaccination in Autoimmune Diseases (COVAD) questionnaire (March–December 2021). Multivariable regression models accounted for age, gender, ethnicity, vaccine type and background treatment. Results Among 9462 complete respondents, 583 (6.2%) were SLE patients (mean age: 40.1 years; 94.5% females; 40.5% Asian; 42.9% Pfizer-recipients). Minor AEs were reported by 83.0% of SLE patients, major by 2.6%, hospitalization by 0.2%. AE and hospitalization frequencies were similar between patients with active and inactive SLE. Rashes were more frequent in SLE patients vs HC (OR; 95% CI: 1.2; 1.0, 1.5), chills less frequent in SLE vs AIRDs (0.6; 0.4, 0.8) and nrAIDs (0.5; 0.3, 0.8), and fatigue less frequent in SLE vs nrAIDs (0.6; 0.4, 0.9). Pfizer-recipients reported higher overall AE (2.2; 1.1, 4.2) and injection site pain (2.9; 1.6, 5.0) frequencies than recipients of other vaccines, Oxford/AstraZeneca-recipients more body ache, fever, chills (OR: 2.5, 3.0), Moderna-recipients more body ache, fever, chills, rashes (OR: 2.6, 4.3). Hospitalization frequencies were similar across vaccine types. AE frequencies were similar across treatment groups, although chills were less frequent in antimalarial users vs non-users (0.5; 0.3, 0.9). Conclusion While COVID-19 vaccination-related AEs were reported by four-fifths of SLE patients, those were mostly minor and comparable to AEs reported by healthy individuals, providing reassurance regarding COVID-19 vaccination safety in SLE.