eScholarship@UMassChan
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Publication Open Access UMCCTS Newsletter, June 2026(UMass Chan Medical School, 2026-06-01)This is the June 2026 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.Publication Metadata only Peritraumatic C-reactive protein levels predict pain outcomes following traumatic stress exposure in a sex-dependent manner(2026-05-28)Chronic pain following traumatic stress exposure (TSE) is common. Increasing evidence suggests inflammatory and immune mechanisms are activated following TSE, play a role in the transition from acute to chronic pain, and may differ by sex. In this study, we tested the hypothesis that elevated levels of the inflammatory marker C-reactive protein (CRP) would be associated with acute and chronic pain in a sex-specific manner. We utilized blood-plasma samples and pain questionnaire data from men (n=116) and women (n=269) enrolled in AURORA, a multi-site emergency department (ED)-based longitudinal study of TSE survivors. CRP levels were measured by ELISA using plasma samples collected in the ED ('peritraumatic CRP') and six-months following TSE. Multivariate models were used to assess the relationship between CRP and pain. Men and women reported similar acute pain levels in the ED; however, pain resolved more rapidly in men over time. Peritraumatic CRP was not associated with acute pain severity in either men or women. However, six-month CRP levels were positively associated with six-month pain severity in both men (r=0.19, p=0.089, non-significant) and women (r=0.21, p=0.0015). In men only, higher peritraumatic CRP predicted lower chronic pain severity (β=-0.36, p=0.024) whereas no association was observed in women (β=0.04, p=0.628). Among men with elevated peritraumatic CRP, decreases in CRP over time were associated with decreases in pain over time (r=-0.38, p=0.0197). These findings suggest sex-specific relationships between CRP and chronic pain following TSE and highlight inflammation as a potential mechanism contributing to differential pain recovery trajectories in men and women. PERSPECTIVE: Longitudinal CRP levels following traumatic stress exposure showed sex-dependent associations with chronic pain outcomes. Unexpectedly, higher early CRP predicted lower chronic pain severity in men, suggesting inflammatory responses may differentially influence pain recovery trajectories in men and women.Publication Open Access Microbiome functional gene pathways are indicative of cognitive performance in older adults at risk for Alzheimer's disease(2026-05-24)Disturbances in the gut microbiome are increasingly correlated with neurodegenerative disorders, including Alzheimer's disease. Multiple lines of emerging evidence are consistent with the microbiome's involvement in disease pathology in AD by triggering or potentiating systemic and neuroinflammation, thereby influencing disease pathology through the "microbiota-gut-brain axis." Currently, the copathologies contributing to cognitive decline and symptomatic progression in AD remain unknown and understudied. Changes in the gut microbiome composition may offer clues to potential systemic physiologic and neuropathologic changes that contribute to cognitive decline. Here, we recruited a cohort of 260 older adults (aged 60 y or older) living in the community and followed them over time, tracking objective measures of cognition, clinical information, and gut microbiome samples. Subjects were classified as healthy controls, exhibiting mild cognitive impairment, or having dementia based on clinical assessments. Using metagenomic sequencing and gene pathway analyses, we found that certain microbial-encoded metabolic pathways correlated with worse cognitive performance. Specifically, genes involved in the urea cycle, polyamine synthesis, or the metabolism of methionine and cysteine predicted worse cognitive performance. Our study suggests that the gut microbiome composition may be linked to cognitive impairment along the AD continuum and points to microbial metabolic pathways that may potentiate disease.Publication Metadata only Racial and Ethnic Differences in Unplanned Cesarean Birth Among Women Veterans Receiving VA Maternity Care(2026-05-23)BACKGROUND: Cesarean birth is associated with higher maternal morbidity and mortality than vaginal birth. Unplanned cesarean births, which occur after labor onset, reflect intrapartum decision-making and care processes that may vary across clinical settings. Prior research has demonstrated racial and ethnic disparities in unplanned cesarean birth in civilian populations, but these patterns have not been well characterized among women Veterans. Such disparities may extend to Veterans receiving maternity care through the Department of Veterans Affairs (VA) Community Care Network (CCN). This study examined racial and ethnic differences in unplanned cesarean birth among Veterans receiving obstetric care in the VA CCN. METHODS: We conducted a retrospective cohort study of 314 nulliparous Veterans with singleton, term deliveries through the VA CCN between 2016 and 2021 who completed both prenatal and postpartum telephone-based surveys. Planned cesarean births were excluded. Poisson regression with robust variance estimation was used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for unplanned cesarean birth by race/ethnicity. RESULTS: The overall rate of unplanned cesarean birth was 26.4%. Compared with White Veterans, non-Hispanic Black Veterans had a 75% higher risk of unplanned cesarean birth (RR 1.75, 95% CI: 1.14-2.68), which persisted after adjustment for clinical risk factors (adjusted RR [aRR] 1.59, 95% CI: 1.04-2.42). Non-Hispanic Veterans identifying as other races also had higher adjusted risk (aRR 1.83, 95% CI: 1.04-3.21). Hispanic Veterans had a similar risk of unplanned cesarean birth compared with White Veterans (aRR 0.97, 95% CI: 0.54-1.77). CONCLUSIONS: Non-Hispanic Black and other race Veterans experienced higher risk of unplanned cesarean birth than White Veterans after adjustment for key clinical risk factors. These findings suggest that differences in labor management, care processes, or delivery contexts within the CCN may contribute to observed disparities. Further research is needed to examine quality, decision-making, and equity across CCN-affiliated maternity care settings.Publication Metadata only Long-term comparative analysis of AAV9-mediated gene replacement therapies for spinal muscular atrophy in mice(2026-05-23)Spinal muscular atrophy (SMA) results from a deficiency of the survival motor neuron (SMN) protein. Zolgensma, an adeno-associated virus (AAV)-based SMN1 gene-replacement therapy, is approved for SMA, though its long-term efficacy and safety remain uncertain. This study compares a Zolgensma-like benchmark vector with a 2nd-generation vector featuring a codon-optimized SMN1 transgene under the control of an endogenous SMN1 promoter. In SMA mice, intracerebroventricular delivery of the 2nd-generation vector improved survival and phenotypic outcomes compared with the benchmark. However, motor impairment was observed in wild-type mice 20 months post-injection with the 2nd-generation vector. Notably, cardiac thrombosis and hepatocellular carcinoma were associated with the benchmark vector, but not with the 2nd-generation vector. While AAV-related tumorigenesis appears to be species-specific to mice, these findings underscore the need for careful long‑term monitoring in patients treated with Zolgensma.