eScholarship@UMassChan
eScholarship@UMassChan is a digital archive for UMass Chan Medical School's research and scholarship, including journal articles, theses, datasets and more. We welcome submissions from our faculty, staff, and students. eScholarship@UMassChan is a service of the Lamar Soutter Library, Worcester, MA, USA. See also our open access journal publishing services.
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Recent Publications
Publication Open Access MORC3 represses a tandem repeat enhancer to regulate interferon(2026-06-05)The antiviral protein MORC3 is frequently inhibited by viruses. To counteract viral antagonism, MORC3 represses a noncanonical pathway of type-I-interferon (IFN) such that viral inhibition of MORC3 triggers ( > 10,000-fold) IFN induction. How MORC3 represses this pathway, and why IFN induction upon MORC3 loss is so potent without canonical IRF3/7 transcription factors, is unknown. Here, we show that MORC3 restricts chromatin accessibility at tandem repeat elements harboring up to 61 homotypic transcription factor motifs. One such element becomes a potent enhancer of IFNB1 upon MORC3 loss. Its motif cluster contains 45 PU.1 binding sites and is necessary and sufficient for MORC3-mediated repression and enhancer activity upon MORC3 loss. PU.1 recruits MORC3 to repress this enhancer by recruiting DAXX and enabling H3.3 incorporation. Upon MORC3 loss, PU.1 drives IRF3/7-independent IFN induction. Other restricted tandem repeats contain homotypic motif clusters of SPI, AP-1, and SP/KLF transcription factors. Our findings uncover a TF motif cluster-driven repression mechanism by MORC3 at tandem repeats, enabling specific repression of an IFNB1 enhancer such that viral antagonism of MORC3 induces interferon.Publication Metadata only Clinician and Family Perspectives on the Use of Single Maintenance and Reliever Therapy for Children(2026-06-03)BACKGROUND: Single maintenance and reliever therapy (SMART) is the guideline-recommended treatment for children with moderate-to-severe asthma, yet it is underutilized in pediatric practice. OBJECTIVE: To understand barriers and facilitators to SMART adoption within pediatric practice. METHODS: We interviewed 52 participants (16 pediatricians, 22 parents, and 16 children). Interviews were conducted until theme saturation, recorded, transcribed, coded and qualitatively analyzed using the Consolidated Framework for Implementation Research. RESULTS: We identified barriers, facilitators and potential solutions to SMART implementation. Participants described barriers at the 1) clinic-level which included lack of clinician training and clinical decision support for SMART, 2) at the family-level which included discomfort transitioning away from traditional albuterol and concern about SMART's effectiveness as a rescue medication, at 3) school-and systems-levels which included poor communication and lack of aligned care plans across community settings like schools, and challenges navigating insurance coverage. Facilitators to SMART implementation included acceptance of SMART as a simpler treatment that could improve asthma symptoms. Proposed solutions to barriers included 1) clinic-level trainings and integrated clinical decision support 2) family-level support for reluctant families, and 3) clear communication between clinics and schools, access to SMART-specific medication orders and action plans, and insurance support. CONCLUSION: Most pediatricians and families reported that SMART is a favorable, simple and acceptable treatment approach for children with asthma. However, pediatricians and families described significant barriers to using guideline-concordant SMART within routine practice. These results could inform targeted efforts to improve the adoption of SMART within pediatric asthma care.Publication Open Access Mean Arterial Pressure at Admission Predicts 28-day Mortality in Patients with Severe Alcohol-associated Hepatitis(2026-06-03)Alcohol-associated hepatitis (AH) is a severe condition with high short-term mortality. Identifying key predictors of poor outcomes is critical for guiding therapeutic strategies. Mean arterial pressure (MAP), a key determinant of tissue perfusion and systemic hemodynamics, may play a pivotal role in prognosis. We analyzed a multicenter, prospective cohort of 323 patients hospitalized with AH, with validation in an independent cohort of 290 patients. Survival was evaluated using Kaplan–Meier curves and compared with the log-rank (Mantel–Cox) test. Cox proportional hazards models were used to estimate hazard ratios (HRs) for mortality, adjusted for MELD score. Mechanistic insights were explored through assessment of cardiovascular biomarkers. A baseline MAP <80 mmHg was associated with significantly higher mortality at both 28 days (27.3% vs 8.0%) and 90 days (40.3% vs 15.6%; p<0.001 for both). This association persisted after adjusting for MELD score, age, and baseline hepatic encephalopathy. The incidence of infections during follow-up was similar across MAP groups (27.6% vs 22.8%), but acute kidney injury (AKI) occurred more frequently in the MAP <80 mmHg group (62% vs 38%, p<0.001). In the validation cohort, patients with MAP <80 mmHg also demonstrated significantly lower 28-day transplant-free survival. Although BNP and plasma renin levels were altered in patients with AH, they did not correlate with MAP values. Conclusion: A baseline MAP <80 mmHg is an independent predictor of short- and mid-term mortality in patients with AH. Strategies aimed at restoring hemodynamic stability may improve outcomes in this high-risk population.Publication Open Access Alcohol abstinence precipitates alcohol seeking and aversion-resistant intake in association with increased BNST activity(2026-06-03)Alcohol Use Disorder (AUD) is defined by a common diagnostic framework, yet individuals show diverse drinking patterns and relapse vulnerabilities during abstinence, reflecting neurobiological heterogeneity. The bed nucleus of the stria terminalis (BNST) is well positioned to contribute to this variability. To understand how BNST activity co-segregates with individual alcohol behavior trajectories, we used the Structured Tracking of Alcohol Reinforcement (STAR) operant task to phenotype C57BL/6J mice as high, low, or aversion-resistant ethanol drinkers. During initial self-administration, dBNST cFos+ counts correlated with intake, linking dBNST activation to operant drinking. Using in vivo fiber photometry, we found that aversion-resistant drinkers displayed elevated dBNST calcium transients during drinking bouts despite similar intake across groups, consistent with heightened dBNST recruitment. Forced abstinence uncovered prominent phenotype-specific adaptations, where ethanol seeking during protracted, but not early, abstinence predicted aversion-resistant intake. High and low drinkers reduced seeking behavior across abstinence, whereas aversion-resistant drinkers persisted. Consistently, dBNST calcium transients increased during protracted abstinence seeking only in aversion-resistant drinkers, highlighting phenotype-specific plasticity. Comparing mice exposed to abstinence versus only operant training showed that abstinence itself potentiates aversion-resistant intake. Finally, these dBNST dynamics were ethanol-specific, as saccharin drinking more closely reflected activity for high drinkers. Together, these findings reveal that ethanol abstinence precipitates ethanol seeking and aversion-resistant intake, associated with phenotypic dBNST calcium dynamics. Because causality was not established, future studies are needed to define mechanistic contributions of dBNST activity to phenotypic behaviors. By uncovering how dBNST activity adapts in aversion-resistant drinkers, this work offers insight into AUD heterogeneity.Publication Open Access Dermatologic Conditions and Incident Anxiety in Young Adults: Propensity Score-Matched Retrospective Cohort Study(2026-06-03)BACKGROUND: Dermatologic conditions such as acne, psoriasis, and dermatitis commonly affect young adults and may contribute to psychological distress. While prior studies have suggested an association between skin disease and anxiety, longitudinal population-level evidence in young adults remains limited. OBJECTIVE: This study aimed to examine the association between common dermatologic conditions and the incidence of anxiety among young adults using a large electronic health record-based cohort. METHODS: We conducted a retrospective cohort study using the TriNetX Research Network, including young adults aged 18 to 22 years with and without a qualifying dermatologic diagnosis between 2019 and 2020. The index date was defined as the first dermatologic diagnosis for exposed individuals and a qualifying ambulatory visit for controls. Individuals with a prior diagnosis of anxiety were excluded. Propensity score matching was used to balance demographic characteristics and ambulatory visit history between cohorts. Incident anxiety diagnoses were assessed at 1, 3, and 5 years following the index date. Cumulative incidence, absolute risk differences, risk ratios, and time-to-event analyses were evaluated. RESULTS: After propensity score matching, 169,720 individuals were included in each cohort. Young adults with dermatologic conditions consistently exhibited a higher incidence of anxiety across all time points. At 1 year, anxiety occurred in 3.9% (5838/149,464) of individuals in the dermatologic condition group compared with 3.4% (3237/95,020) of controls. By 3 years, incidence increased to 11.8% (17,559/149,464) of individuals vs 10.4% (9906/95,020) of controls, and by 5 years to 16.8% (25,184/149,464) of individuals vs 15.5% (14,712/95,020) of controls. Absolute risk differences widened over time, from 0.50 to 1.40 percentage points. Time-to-event analyses demonstrated a modest but consistent increase in hazard, with hazard ratios ranging from 1.12 to 1.14 (all P<.001). CONCLUSIONS: In this large, propensity score-matched cohort of young adults, common dermatologic conditions were associated with a small but persistent increase in the incidence of anxiety over time. Although absolute differences were modest, the consistency of findings across multiple analytic approaches highlights the importance of considering psychological well-being as part of comprehensive care for young adults with dermatologic conditions.