27941 research outputs found
Sort by
Alcohol Use in the US Deaf Community: Identifying Gaps and Building Solutions
Get PDFDeaf and Hard of Hearing (DHH) individuals experience disproportionately high rates of alcohol use disorder (AUD) yet face persistent barriers to culturally and linguistically appropriate care. To better understand recovery experiences, twenty-two semi-structured interviews were conducted with DHH adults in recovery (n = 15) and Deaf recovery service providers (n = 7). Using a grounded theory approach within a community-engaged framework, we identified multiple external barriers, including lack of ASL-accessible services, interpreter funding constraints, inaccessible recovery materials, and systemic inequities, as well as internal barriers such as co-occurring mental health conditions, learned helplessness, and isolation. Facilitators included peer and family support, ASL-fluent providers, skill-building, and personal accountability, while motivators included relational turning points, health concerns, and future goals. Findings underscore the need for culturally responsive, empowerment-focused interventions and directly inform the development of DeafMET, a tailored adaptation of Motivational Enhancement Therapy for DHH individuals.Master of Science in Clinical InvestigationNo embarg
Central Nervous System Manifestations of Long COVID: A Systematic Review
Get PDFSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been one of the most widespread and devastating global pandemics, impacting hundreds of millions of people worldwide. After the cessation of active infection, the disease continues to have a disabling impact due to the persistence of fatigue, brain fog, anxiety, and depression - among the most common symptoms. This study explores the progression of neurological symptoms over 12 months and beyond following an initial diagnosis of COVID-19. Through an electronic search of eligible studies from PubMed, the Cochrane Trial Register, and Google Scholar, 10 studies were included for qualitative analysis. The systematic review highlights the similarities and differences in findings across the included studies. Olfactory dysfunction was prevalent in 0.9%-51% of individuals, and taste impairment was observed in 1.1%-21.3%. At 12 months, anxiety was more prevalent (3.5%-29%) than depression (3.5%-26%). Fatigue was the predominant neurocognitive complaint in 56% of individuals with severe COVID-19. Nearly half of individuals reported sleep difficulties. Memory impairment, followed by headaches and dizziness, also constitutes neurocognitive symptoms reported at 12 months. Our study found that there is a significant neurological burden one year following the diagnosis of COVID-19. Further studies exploring the pathological mechanisms of long-term COVID-19 are necessary to better delineate the mechanisms behind several long-term neurological manifestations of COVID-19.No embarg
Bacterial Determinants of Antibiotic Efficacy: A Functional Genetics and Comparative Genomics Study of Mycobacterium tuberculosis
No full textSuccessful tuberculosis (TB) treatment requires at least six months of combination therapy. Even with this prolonged treatment, failure and relapse still occur in 5–10% of cases and are often linked to the emergence of multidrug resistance. Therefore, a deeper understanding of bacterial determinants of antibiotic efficacy is essential to uncover novel mechanisms of antibiotic resistance and to facilitate the development of more effective combinatorial TB therapies. In this work, I combined bacterial functional genetics and genomics to investigate the mechanisms influencing antibiotic efficacy in Mycobacterium tuberculosis (Mtb). First, I leveraged a library of conditional knockdown mutants to characterize Mtb chemical-genetic interactions (CGIs) in mouse TB infection and treatment models. This work uncovered a range of synergistic and antagonistic CGIs specific to the infection environment, revealing novel targets for combinatorial TB therapeutics. Specifically, we identified previously unrecognized determinants of Mtb susceptibility to pyrazinamide (PZA), showing increased PZA efficacy in thiamine and purine metabolism mutants, and reduced activity in mutants of the ESX-3 type VII secretion system. Second, using a combination of genomic analysis and in vitro experimentation, I identified simple sequence repeat (SSR) indels associated with decreased antibiotic susceptibility during TB infection. Notably, we identified triplet SSR indels in ppe53 and ponA1 that are enriched in drug-resistant TB and confer intermediate in vitro multidrug resistance. Together, this work defines infection-specific mechanisms of antibiotic activity, identifies potential targets for combinatorial TB drug development, and reveals a previously unrecognized role for triplet SSRs as determinants of intermediate antibiotic resistance in Mtb.Immunology and Microbiology6 months2025-12-0
Prediction of persistent incomplete occlusion of intracranial aneurysms treated with woven EndoBridge device
Get PDFWhile the Woven EndoBridge (WEB) device has transformed the treatment of wide-neck intracranial aneurysms, incomplete occlusion remains a significant challenge requiring better understanding of contributing factors. A retrospective analysis was conducted on multicenter data from patients who underwent WEB device treatment for intracranial aneurysms between January 2011 and December 2022. Using machine learning models, Cox regression, and time-stratified analyses, we evaluated factors associated with persistent incomplete occlusion, defined as non-improving Raymond-Roy Occlusion Classification grade 2 or 3 at final follow-up. Among 813 patients (607 with < 24 months follow-up, 206 with ≥ 24 months), machine learning analysis identified aneurysm height, Acom location, neck diameter, and pretreatment mRS as predictors of persistent incomplete occlusion. On Cox regression. larger aneurysm neck diameter (HR 1.13, 95% CI 1.01-1.27, p = 0.027) and height (HR 1.14, 95% CI 1.02-1.26, p = 0.017), and radial access (HR 2.68, 95% CI 1.76-4.07, p < 0.001) increased, while posterior circulation location (HR 0.56, 95% CI 0.37-0.84, p = 0.005) decreased the risk of persistent incomplete occlusion. Time-stratified analysis revealed that in short-term follow-up (< 24 months), larger aneurysm neck diameter (OR 1.28, 95% CI 1.08-1.52, p = 0.004) increased the risk of incomplete occlusion. In long-term follow-up (≥ 24 months), smoking (OR 2.69, 95% CI 1.04-7.00, p = 0.04), higher pre-treatment mRS (OR 1.78, 95% CI 1.15-2.76, p = 0.009), and immediate flow stagnation (OR 0.33, 95% CI 0.11-0.96, p = 0.04) increased, while older age (OR 0.94, 95% CI 0.90-0.98, p = 0.002) and WEB-DL (OR 0.06, p < 0.001) and SLS devices (OR 0.02, p = 0.003) decreased the risk of persistent incomplete occlusion. Aneurysm characteristics and device type significantly influence long-term WEB treatment outcomes.No embarg
Harnessing and Re-Engineering AAVrh32.33: From Skin Tropism to Immune-Evasive Vector Design
No full textSkin diseases are highly prevalent, yet many remain without durable therapeutic options. While recent advances have introduced gene therapy as a promising alternative, adeno associated virus, one of the most successful gene therapy platforms to date, has not been fully explored for skin-targeted delivery.
Here, we found that AAVrh32.33 exhibits a strong and previously unrecognized ability to target the skin. Systemic administration in mice resulted in efficient transduction of dermal fibroblasts and hair follicle bulge stem cells, two long-lived compartments capable of supporting sustained expression. AAVrh32.33-mediated transgene expression persisted for up to two years following a single injection. To reduce the known immunogenicity of AAVrh32.33, we modified the capsid by disrupting a dominant CD8⁺ T-cell epitope (IDPΔ), which diminished peptide-specific responses while preserving dermal tropism.
In human skin explants, the IDPΔ variant also transduced stromal cells effectively, with expression primarily in dermal fibroblasts and fibroblast-lineage precursors, underscoring its translational relevance. Systemic administration of chemokine-encoding vectors resulted in localized expression in healthy skin as well as in the atopic dermatitis (AD) mouse model, while avoiding major systemic alterations, demonstrating that this platform can deliver immune-modulating genes directly to diseased skin without broad off-target effects.
Together, these findings establish AAVrh32.33 and its IDPΔ variant as promising platforms for durable gene delivery to the skin, enabling targeted modulation of cutaneous immune pathways and offering relevance for conditions such as vitiligo, AD, and primary cicatricial alopecia where long-term reshaping of the dermal microenvironment is critical.Interdisciplinary Graduate Program1 year2026-12-1
Tuning Hyaluronic Acid Microstructures by Engineered Amphiphilicity: From Dynamically Cross-Linked Gels to Multilayered Nanoparticles
No full textAmphiphilic biopolymers are of interest for regenerative medicine applications due to their potential to interact with both hydrophobic and hydrophilic bioactive molecules and self-assemble into well-defined microstructures. We show that the amphiphilicity and microstructures of hydrophilic hyaluronic acid (HA) can be explicitly tuned by the stoichiometric integration of cholesterol to azide-functionalized HA via strain-promoted azide-alkyne cycloaddition (SPAAC). At low cholesterol contents, the hydrophobic interactions among the cholesterol units dynamically cross-link cholesteryl HA into physical gels showing enhanced and recoverable viscosities. By SPAAC cross-linking of remaining azides, the interdependence of physical and chemical cross-linking of cholesteryl HA is demonstrated. At higher cholesterol contents, cholesteryl HA self-assembles into multilamellar nanoparticles (NPs) composed of a core of alternately packed cholesterol-rich and HA-rich layers and a hydrated HA-rich outer layer. The amphiphilic NPs not only readily encapsulate hydrophobic compounds but also protect hydrophilic vitamin C from fast degradation in aqueous media. Rapid internalization of cholesteryl HA NPs by rat bone marrow-derived stromal cells and robust osteogenesis induced by NPs preloaded with dexamethasone and vitamin C were demonstrated. From viscoelastic physical gels, dual-cross-linked gels, to multilamellar NPs, cholesteryl HA with tailored amphiphilicity can be leveraged as versatile macromolecular building blocks for a wide range of regenerative medicine applications.No embarg
Knowledge-Guided Machine Learning for Precision Medicine: New Methods for Robust Biomarker Discovery and Interpretable Risk Stratification from High-Dimensional Omics Data
No full textPrecision medicine aims to integrate individual molecular information with clinical profiles to improve disease prediction and treatment. However, biomedical omics data are typically both high-dimensional and limited in sample size (≫), creating major analytical challenges. Naïve application of "black box" machine learning models to such data can lead to overfitting and statistical instability. This, and their inherent lack of biological interpretability, limits the value of such models in clinical translation.
This work explore the value of integrating biological domain knowledge as a structural constraint to address these challenges. This knowledge-guided paradigm enhances data efficiency, improves statistical robustness, and ensures mechanistic interpretability. To validate this approach, two knowledge-guided computational methods were developed to address critical tasks in precision medicine: biomarker discovery and disease risk prediction.
For biomarker discovery, BAMBI (Biostatistical and Artificial-intelligence Methods for Biomarker Identification) was developed. By combining biologically informed statistical filtering with robust machine learning-based feature selection, BAMBI identifies parsimonious yet highly predictive RNA biomarker panels, outperforming existing methods in small-sample scenarios.
For disease risk stratification, a pathway-guided Graph Neural Network was constructed to predict 10-year cardiovascular disease risk. By embedding pathway structures into the model architecture and incorporating a demographic-guided attention mechanism, this method substantially outperformed the Framingham Risk Score with respect to balanced accuracy and sensitivity while identifying biologically relevant central genes as key risk drivers.
This work demonstrates that integrating biological knowledge into machine learning is a powerful strategy for translating complex omics data into robust, interpretable, and clinically actionable insights.Population Health Sciences2 years2027-11-1
UMCCTS Newsletter, October 2025
Get PDFThis is the October 2025 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.Supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grants UL1 TR001453, TL1 TR001454 and KL2 TR001455.No embarg
Lower Prepregnancy Cardiovascular Health is Associated With Hypertensive Disorders of Pregnancy: The CARDIA Study
No full textBackground: Hypertensive disorders of pregnancy (HDP), including gestational hypertension, preeclampsia, and eclampsia, contribute to increased maternal morbidity and mortality and long-term cardiovascular disease risk. It is unclear whether HDP arises from pregnancy-specific complications or preexisting maternal cardiovascular traits unmasked during pregnancy. This article evaluates whether cardiovascular health before pregnancy, assessed by the American Heart Association's Life's Essential 8 (LE8) score, is associated with HDP risk.
Methods: The CARDIA (Coronary Artery Risk Development in Young Adults) is a longitudinal cohort study of 5115 Black and White men and women, aged 18 to 30 years at baseline (1985-1986), and followed for over 30 years (nBlackWomen=1480; nWhiteWomen=1307). The LE8 score (range, 0-100) was calculated using health behaviors (diet, smoking, physical activity, sleep) and clinical metrics (body mass index, blood pressure, cholesterol, glucose). Cardiovascular health was categorized as low (LE8 <50), moderate (LE8 50-79), or high (LE8 ≥80). HDP was self-reported as gestational hypertension, preeclampsia, or eclampsia in pregnancies lasting ≥23 weeks. Generalized mixed models assessed the association between LE8 and HDP among 2036 pregnancies from 1227 women, adjusting for age, time-varying parity, education, income, follow-up time, cumulative births, and multiple gestation.
Results: Mean baseline age was 24.1 years, 48.7% were Black women, and 19.9% reported HDP. Women with HDP had lower baseline LE8 scores (77.0 versus 79.5; P<0.01). Compared with high cardiovascular health, moderate (odds ratio, 1.78 [95% CI, 1.13-2.81]) and low cardiovascular health (odds ratio, 3.95 [95% CI, 1.05-14.88]) were associated with increased HDP risk.
Conclusions: Lower prepregnancy cardiovascular health is an independent risk factor for HDP. Improving cardiovascular health may reduce HDP risk.No embarg
Higher mortality following SARS-CoV-2 infection in rural versus urban dwellers persists for two years post-infection
Get PDFPrevious studies demonstrated higher short-term mortality among rural compared with urban residents infected with SARS-CoV-2. However, whether this difference persists remains uncertain. This retrospective cohort study analyzed two-year post-COVID-19 mortality by rurality using the National Clinical Cohort Collaborative COVID-19 Enclave, a United States-based longitudinal electronic health record repository. We analyzed mortality among patients infected with SARS-CoV-2 between April 2020 and December 2022, with follow-up until December 2024. Patients were categorized into urban, urban-adjacent rural (UAR), and nonurban-adjacent rural (NAR) groups based on residential ZIP Code. Mortality differences were assessed using Kaplan-Meier analysis and weighted multivariable Cox regression, with weights derived from demographic factors and models adjusted for background clinical risk and social vulnerability. Among 3,082,978 SARS-CoV-2-infected patients, we found a significant association between rurality and increased two-year all-cause mortality post-infection. Adjusted hazards for two-year mortality for UAR and NAR were 1.19 (95% CI 1.18-1.21) and 1.26 (1.22-1.29). A reference cohort of 4,153,216 COVID-19-negative patients showed a modest yet consistent rural mortality penalty, with a similar relative hazard across cohorts, an observed rurality-COVID-19 interaction, and a greater absolute number of deaths following SARS-CoV-2 infection. Our findings emphasize ongoing rural mortality disparities and the importance of public health efforts in rural communities.The UMass Center for Clinical and Translational Science (UMCCTS), UL1TR001453, helped fund this study.No embarg