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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Publication Open Access UMCCTS Newsletter, December 2025(UMass Chan Medical School, 2025-12-01)This is the December 2025 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.Publication Open Access GrantCheck-an AI Solution for Guiding Grant Language to New Policy Requirements: Development Study(2025-11-27)BACKGROUND: Academic institutions face increasing challenges in grant writing due to evolving federal and state policies that restrict the use of specific language. Manual review processes are labor-intensive and may delay submissions, highlighting the need for scalable, secure solutions that ensure compliance without compromising scientific integrity. OBJECTIVE: This study aimed to develop a secure, artificial intelligence-powered tool that assists researchers in writing grants consistent with evolving state and federal policy requirements. METHODS: GrantCheck (University of Massachusetts Chan Medical School) was built on a private Amazon Web Services virtual private cloud, integrating a rule-based natural language processing engine with large language models accessed via Amazon Bedrock. A hybrid pipeline detects flagged terms and generates alternative phrasing, with validation steps to prevent hallucinations. A secure web-based front end enables document upload and report retrieval. Usability was assessed using the System Usability Scale. RESULTS: GrantCheck achieved high performance in detecting and recommending alternatives for sensitive terms, with a precision of 1.00, recall of 0.73, and an F-score of 0.84-outperforming general-purpose models including GPT-4o (OpenAI; F=0.43), Deepseek R1 (High-Flyer; F=0.40), Llama 3.1 (Meta AI; F=0.27), Gemini 2.5 Flash (Google; F=0.58), and even Gemini 2.5 Pro (Google; F=0.72). Usability testing among 25 faculty and staff yielded a mean System Usability Scale score of 85.9 (SD 13.4), indicating high user satisfaction and strong workflow integration. CONCLUSIONS: GrantCheck demonstrates the feasibility of deploying institutionally hosted, artificial intelligence-driven systems to support compliant and researcher-friendly grant writing. Beyond administrative efficiency, such systems can indirectly safeguard public health research continuity by minimizing grant delays and funding losses caused by language-related policy changes. By maintaining compliance without suppressing scientific rigor or inclusivity, GrantCheck helps protect the pipeline of research that advances biomedical discovery, health equity, and patient outcomes. This capability is particularly relevant for proposals in sensitive domains-such as social determinants of health, behavioral medicine, and community-based research-that are most vulnerable to evolving policy restrictions. As a proof-of-concept development study, our implementation is tailored to one institution's policy environment and security infrastructure, and findings should be interpreted as preliminary rather than universally generalizable.Publication Open Access Association of Socioeconomic Position with Incident Hypertension Hospitalization and Blood Pressure Control among Participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study(2025-11-26)Background: The rate of hypertension hospitalizations is increasing among US adults. Individuals with low socioeconomic position are more likely to have high blood pressure (BP), which may increase their risk of hypertension hospitalization and adverse post-discharge outcomes. Methods: We analyzed data from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study, which enrolled 5,115 adults aged 18 to 30 years from 4 urban US communities in 1985-1986. Hospitalizations were identified by self-report during study exams and annual interviews, with hypertension hospitalizations determined through medical record review, through August 2020. Socioeconomic position included education, family income, having private health insurance, and neighborhood deprivation assessed at the last study visit prior to the hypertension hospitalization. Uncontrolled BP (≥140/90 mmHg) was determined at the first CARDIA study visit after hypertension hospitalization. Results: Overall, 67 CARDIA participants were hospitalized for hypertension. The hazard ratio of hypertension hospitalization among participants who had less than high school versus high school or more education was 3.12 [95%CI: 1.78, 5.48], whose family income was <$25,000 versus ≥$25,000 was 2.43 [95%CI: 1.44, 4.11], who had no private versus private insurance was 2.58 [95%CI: 1.56, 4.28] and those in tertile 3 versus tertile 1 of neighborhood deprivation index (most versus least deprived) was 3.06 [95%CI: 1.23, 7.58]. Among 46 participants who attended a CARDIA study visit following hospital discharge, 23 (50%) had uncontrolled BP. Conclusion: Adults with low socioeconomic position were more likely to be hospitalized for hypertension. Uncontrolled BP was common following hypertension hospitalization.Publication Metadata only Intracerebroventricular SPAST-AAV9 gene therapy prevents the manifestation of symptoms in a mouse model of SPG4 Hereditary Spastic Paraplegia(2025-11-26)Hereditary Spastic Paraplegia type 4 is characterized by gait impairments, progressive spasticity and weakness of the lower limbs, resulting from degeneration of the corticospinal tracts. The disease is caused by mutations of the SPAST gene, which encodes a major isoform of spastin called M87 and a minor isoform called M1. Owing to its N-terminal hydrophobic domain not shared by M87, M1 is the isoform that becomes toxic when mutated. Loss-of-function of either M1 or M87 or both may also play a role in the disease, sensitizing corticospinal motor neurons to the toxicity of mutant M1. Here we pursued silence-and-replace gene therapy, which addresses both gain-of-toxicity and loss-of-function components of the disease. We generated an adeno-associated serotype 9 viral vector containing micro-RNA to stop the expression from the endogenous SPAST gene and cDNA to express healthy human M1 and M87. The vector was introduced by intracerebroventricular injections into newborn pups of SPAST-C448Y, a mouse model of the disease that expresses human mutant spastin and displays adult-onset corticospinal degeneration and gait defects. The treatment successfully replaced both isoforms of endogenous spastin with healthy spastin, at physiological levels, and prevented the onset and progression of corticospinal degeneration and gait defects.Publication Restricted Prospective SARS-CoV-2 additional vaccination in immunosuppressant-treated individuals with autoimmune diseases in a randomized controlled trial(2025-11-25)BACKGROUND: Individuals with autoimmune diseases (AD) on immunosuppressants often have suboptimal responses to COVID-19 vaccine. We evaluated the efficacy and safety of additional COVID-19 vaccines in those treated with mycophenolate mofetil/mycophenolic acid (MMF/MPA), methotrexate (MTX), and B cell-depleting therapy (BCDT), including the impact of withholding MMF/MPA and MTX. METHODS: In this open-label, multicenter, randomized trial, 22 participants taking MMF/MPA, 26 taking MTX, and 93 treated with BCDT who had suboptimal antibody responses to initial COVID-19 vaccines (2 doses of BNT162b2 or mRNA-1273 or 1 dose of AD26.COV2.S) received an additional homologous vaccine. Participants taking MMF/MPA and MTX were randomized (1:1) to continue or withhold treatment around vaccination. The primary outcome was the change in anti-Wuhan-Hu-1 receptor-binding domain (RBD) concentrations at 4 weeks post-additional vaccination. Secondary outcomes included adverse events, COVID-19 , and AD activity through 48 weeks. RESULTS: Additional vaccination increased anti-RBD concentrations in participants taking MMF/MPA and MTX , irrespective of immunosuppressant withholding. BCDT-treated participants also demonstrated increased anti-RBD concentrations, albeit lower than MMF/MPA- and MTX-treated cohorts. COVID-19 occurred in 33% of participants; infections were predominantly mild and included only three non-fatal hospitalizations. Additional vaccination was well-tolerated, with low frequencies of severe disease flares and adverse events. CONCLUSION: Additional COVID-19 vaccination is effective and safe in individuals with ADs treated with immunosuppressants, regardless of whether MMF/MPA or MTX is withheld. CLINICALTRIALS: gov (NCT05000216; registered August 6, 2021: https://clinicaltrials.gov/ct2/show/NCT05000216).