H&E and MALDI-MSI images of N-glycans of full tissue samples

Segmentation Analysis of tissues according to N-glycan analysis

Table of all detected ECM peptides following LCMS analysis

Annotated LCMS spectra for COL1A1;COL1A2

PCA graphs from collagenase digestion

MALDI Images from EndoF3 digestion

IntroductionThe aim of this study was to determine if specific anatomical changes were present in patients with recurrent headaches including patients with chronic migraines, chronic tension-type headaches, and daily persistent headaches. A retrospective study of 200 patients was performed to evaluate the potential of measuring the amount of nasal blood pool activity (nasal congestion) as a predictive marker for recurrent headaches.MethodsA cohort analysis was performed involving patients who had been referred to the Nuclear Medicine Clinic over a 3-year period for whole-body blood pool scans. The scans were evaluated by region of interest (ROI) analysis of nasal and heart max pixel count ratios (NHMRs) to determine an association between nasal blood pooling activity and recurrent headaches at the time of the initial scan and in follow-up evaluations over a period of 3–6 years.ResultsSignificantly greater NHMRs were observed in 122 patients with chronic headaches at the time of referral for their initial whole-body blood pool scan when compared with those patients without recurrent headaches (p = 0.004; OR 10.5; 95% CI 2.22–56.7). An additional 15 patients, for a total of 137, developed recurrent headaches following their initial scan and before their follow-up evaluation. NHMRs were also significantly increased in the additional patients when compared to those without recurrent headaches (p = 0.004; OR 12.3; 95% CI 2.34–75.5).ConclusionPatients with recurrent headaches have significantly increased nasal activity as observed on 99mTc-MDP whole-body blood pool scans, supporting the hypothesis that nasal lymphatic dysfunction plays a role in the etiology of recurrent headaches. This research highlights a novel diagnostic use of the whole-body blood pool scan for the assessment of nasal turbinate vasodilation as well as a possible new target for the treatment of recurrent headaches.

Trajectories following a diagnosis of mild cognitive impairment (MCI) are varied and may fluctuate over time. Among diverse ethnic and racial groups, social factors, medical comorbidities, and biases in assessment procedures may contribute to greater heterogeneity in the MCI diagnostic category and affect its prognostic significance for dementia. The study goal was to evaluate the frequency and variables associated with MCI transitions among non-Hispanic White (NHW) and Latinx older adults. Multistate Markov models characterized transitions across diagnostic states (cognitively unimpaired (CU), MCI, dementia) over ten years. Variables associated with transitions were assessed using hazard ratios (HR) and 95% confidence intervals (CIs). The study included 413 participants (58% female, mean age 72 ± 8, 52% Latinx ethnicity). Following an MCI diagnosis, the likelihood of converting to dementia versus reverting to CU were equally probable. Older age, NHW ethnicity, APOE ε4, diabetes, lower BMI, and higher neuropsychiatric symptoms associated with elevated risk for dementia conversion, whereas younger age and lower neuropsychiatric symptoms associated with CU reversion. Above other factors, higher baseline serum glial fibrillary acidic protein (HR = 1.762 (95% CI: 1.367-2.271)) and neurofilament light (HR = 1.467 (95% CI: 1.152-1.69)) associated with increased dementia risk. Trajectories following an MCI diagnosis were highly variable with lower dementia conversion rates among Latinx relative to NHW adults, highlighting the need for strong diverse representation in research to capture the range of exposures shaping risk and resilience for cognitive decline. Well-validated blood-based biomarkers are likely to be instrumental for further improving personalized dementia risk predictions.

MALDI Images from EndoF3 digestion with 5 TMAs

Collagenase-digested peptide LCMS list

Objectives/Goals: Translational researchers often struggle to navigate a complex constellation of institutional resources spanning the IRB to bioinformatics units. We had two aims 1) Systematically map all institution-wide research support units and 2) leverage this database within a generative AI virtual concierge tailored to local investigator queries and needs. Methods/Study Population: This study leveraged mixed methods approach. First, we conducted needs assessments of local study teams to identify barriers to translation, revealing that research resources are often unknown to study teams. Second, we identified all investigators, institutional units, and offices offering such resources that we call research support units (RSUs). RSUs were surveyed, collecting contact information (leadership, website, physical location), services provided, type of research supported, and performance metrics. Third, the resource database was integrated into a large language model (LLM, e.g., ChatGPT4o) using a retrieval augmented generation (RAG) system within an R Shiny application called virtual concierge. Queries and responses are recorded for quality improvement. Results/Anticipated Results: Needs assessment focus groups consisted of clinical and basic science investigators, study team members (e.g., clinical research assistants), core directors, and administrators (n = 26). Six sessions were conducted in Spring 2024. A major resultant theme was difficulty finding RSUs “by trial and error” and lacking a “clear defined pathway” for accessing RSUs. This prompted a survey-based environmental scan to identify institutional research resources. There were 122 diverse RSUs ranging from the IRB, to grant writing, to single cell sequencing. Each research unit offered a median of 6 service types, totaling 410 service types overall. The resultant Virtual Concierge meaningfully responds to investigator resource queries with appropriate contact and access information. Usability testing is underway. Discussion/Significance of Impact: Linking researchers with translational resources requires mutual understanding, timely communication, and coordination across teams. We systematically filled these information gaps between investigators and institutional resources. Our Virtual Concierge AI bot can help researchers navigate resources through the translational process.

BackgroundSexually transmitted infections (STIs) continue to cause morbidity among women in resource-constrained settings, where asymptomatic infections are often overlooked due to syndromic management protocols. We investigated correlates of asymptomatic STIs among women in the Dominican Republic (DR).MethodsWe analyzed data collected from cisgender women in DR between 2015 and 2019. Classified groups included pregnant youth (PY), people with HIV (PWH), residents of bateyes (RB), and sex workers (SW). Nucleic acid amplification or rapid plasma reagin tests detected STIs (Chlamydia/Gonorrhoeae/Syphilis/Trichomonas). Asymptomatic comprised no self-reported vaginal discharge, dysuria, groin lymphadenopathy, and genital/anal pain/ulcers. Logistic regressions identified sociodemographic, clinical, and behavioral correlates.ResultsAmong 833 asymptomatic women (median age 29, IQR 19-37), 35% were PY, 27% PWH, 11% RB, and 27% SW. STI prevalence was 24%: most (61%) had Chlamydia and few (≤25%) had Gonorrhoea, Syphilis, or Trichomonas. Asymptomatic STI correlates included age ≤24 (Adjusted Odds Ratio [aOR] = 2.32, [1.65-3.28]), early (≤14) sexual debut (aOR = 1.56, [1.11-2.18]), greater mobility (aOR = 1.41, [1.01-1.97]), lack of regular doctor (aOR = 1.42, [1.01-1.99]), and drug use in last 6 months (aOR = 1.88, [1.07-3.26]).ConclusionsCorrelates of asymptomatic STIs-age, sexual debut, mobility, healthcare access, and drug use-should inform targeted screening and prevention efforts where diagnostic testing is not widely available.

Liver biopsy is the gold standard for quantifying steatosis and fibrosis. It is unclear how noninvasive tests (NITs) accurately correlate to liver biopsy. The aim of this study was to characterize patients with metabolic-associated steatotic liver disease who underwent liver biopsy in South Texas and had at least 1 contemporaneous NIT result available to determine the accuracy of NITs as compared to liver biopsy in accurately staging fibrosis and steatosis. The study included 460 patients with liver biopsy and at least 1 NIT. Data captured was based on standard of care and was non-interventional in nature. Performance characteristics of the NITs were analyzed based on the degree of fibrosis defined by liver biopsy. The majority of patients were female (66.4%), middle-aged (51 years), and Hispanic/Latino (73.3%). In patients with F3/F4 fibrosis, FibroScan accurately identified only 45.9% with advanced fibrosis. Even when using society recommended results from fibrosis-4 combined with FibroScan, concordance with liver biopsy was only reported in 68.9% of patients. Patients with biopsy-defined advanced steatosis (S3) were identified as having advanced steatosis by FibroScan controlled attenuation parameter score in 89.7% of patients; however, controlled attenuation parameter score overly predicted advanced steatosis in 81.4% with biopsy-defined S1/S2 steatosis. NITs should be used as first line to assess steatosis and fibrosis; however, the optimal combination of these tests has not been elucidated and properly compared to liver biopsy to assess true diagnostic accuracy. Until the optimal set of NITs are found, any diagnostic or clinical inconsistencies should be resolved with liver biopsy to avoid staging errors, particularly underestimating fibrosis in those with advanced disease.

A growing number of compounds are reported to extend lifespan, but it remains unclear whether they reduce mortality across the entire life course or only at specific ages. This uncertainty persists because the commonly used log-rank test cannot detect age-specific effects. Here, we introduce a new analytical method that addresses this limitation by revealing when, how long, and to what extent interventions alter mortality risk. Applied to survival data from 42 compounds tested in mice by the National Institute on Aging Interventions Testing Program, it identified 22 that reduced mortality at certain ages, more than detected by the log-rank test, while 15 increased mortality at certain ages. Most compounds were effective only within restricted age ranges; just 8 reduced mortality late in life, when burdens of aging are greatest. Compared to conventional methods, this approach uncovers more beneficial and harmful effects, offers deeper insight into timing and mechanism, and can guide development of future anti-aging therapies.

Aging is the primary risk factor for frailty, sarcopenia, and functional decline, as well as cancer, cardiovascular and neurodegenerative diseases. Gaining insight into the biological mechanisms of aging could lead to interventions that broadly reduce age-related morbidity and mortality. To identify interventions that extend lifespan and delay aging, the National Institute on Aging launched the Interventions Testing Program (ITP) in 2004. This multi-site effort uses genetically heterogeneous UM-HET3 mice to evaluate the effects of candidate compounds. Over the past two decades, the ITP has tested 54 agents in more than 30, 000 mice. This is the first comprehensive review of the program's results, with particular emphasis on a striking pattern of sex-specific responses. By presenting the full scope of the findings, readers can better understand the overall impact of the program and easily access detailed information on specific drugs of interest. Notably, most compounds that extended lifespan were effective primarily or exclusively in male mice. Dosage and age of treatment onset influenced efficacy and were also sexually dimorphic. These sex differences suggest that mechanisms of aging are sexually dimorphic and highlight the importance of recognizing biological sex as a modifier of treatment efficacy. Investigating the basis for these differences should enable more targeted and effective geroprotective strategies for both sexes.

Analysis of collagen/ECM profile of NED vs. MET cohort from data obtained by LC-MS/MS. A, Pie chart representations of abundance (peak intensity and number of peptides identified via LC-MS/MS) of all detected protein species within the MET cohort. B, Pie chart representations of abundance of all detected protein species within the NED cohort.

AbstractBackgroundLatinos/Hispanics are at higher risk for developing gastric cancer (GC) compared with non‐Hispanic whites, and social determinants of health (SDoH) are thought to contribute.Aims/Materials and MethodsThis study addressed SDoH and their interactions contributing to disparities in the testing and treatment of Helicobacter pylori (HP) infection and diagnosis of GC and its known precursors, among Latinos/Hispanics relative to non‐Latinos at two affiliated but independent health systems in San Antonio, Texas, using a mixed methods approach.ResultsSecondary data abstraction and analysis showed that GCs represented 2.6% (n = 600) of our population. Men and older individuals were at higher GC risk. Individuals with military insurance were 2.7 times as likely to be diagnosed as private insurance. Latinos/Hispanics had significantly (24%) higher GC risk than Whites. Poverty and lack of insurance contributed to GC risk among the minorities classified as other (Asians, Native Americans, Multiracial; all p < 0.01). All SDoH were associated with H. pylori infection (p < 0.001). Qualitative analysis of patient and provider interviews showed providers reporting insurance as a major care barrier; patients reported appointment delays, and lack of clinic staff. Providers universally agreed treatment of H. pylori was necessary, but disagreed on its prevalence. Patients did not report discussing H. pylori or its cancer risk with providers.Discussion/ConclusionThese data indicate the importance of considering SDoH in diagnosis and treatment of GC and its precursors, and educating providers and patients on H. pylori risks for GC.