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 Super-large bore catheter in the treatment of large vessel occlusions: initial multicenter experience(2025-04-11)Purpose: Large bore catheters are increasingly used in mechanical thrombectomy (MT) for large vessel occlusions (LVOs). Objective: To evaluate the efficacy and safety of the super-large bore Cereglide 0.092" (C-92) catheter, featuring the largest inner diameter available. Methods: A multicenter observational study was conducted across 12 comprehensive stroke centers in the United States. Efficacy outcomes included the first pass effect (FPE) and successful reperfusion. FPE was defined as a first MT pass achieving a modified Treatment in Cerebral Infarction (mTICI) score of ≥2c. Successful reperfusion was defined as final mTICI score ≥2c. Safety outcomes involved device-related complications, symptomatic intracranial hemorrhage (sICH), and inpatient mortality. Functional outcomes included modified Rankin Scale (mRS) score at discharge and delta National Institutes of Health Stroke Scale (NIHSS) score. Results: Fifty patients were included. The most common LVO was the first segment of the middle cerebral artery in 31/50 cases (62%). The C-92 reached the thrombus in 41 patients (82%). Median puncture-to-thrombus and puncture-to-reperfusion times were 15 min (IQR 10-25) and 26 min (IQR 15-49), respectively. FPE was achieved in 25/50 (50%) cases, and in 25/41 (61%) cases when the C-92 reached the thrombus. Successful reperfusion occurred in 36/41 patients (88%). There were no vessel perforations, or sICH. Distal embolization occurred in 4/50 (8%) cases, and 4/50 (8%) died. The mRS score at discharge was 3 (IQR 2-6), and the delta NIHSS score was 8 (IQR 5-12). Conclusion: The C-92 catheter demonstrated a safe profile achieving an overall FPE rate of 50%, and favorable functional outcomes in 88% of cases.Publication Protective Factors and Strength-Based Services: Impacts on Long-Term Youth Reoffending(2025-04-09)The Youth Protective Factors Study is an unprecedented, multistate, multiyear examination of which risk and protective factors are most significant when it comes to reoffending—especially for more serious offenses—among youth ages 10 to 23 in the juvenile justice system. This brief is the second in a series that shares key findings from the study to inform juvenile justice supervision, case planning, and service strategies aimed at improving public safety and youth outcomes. Decades of research have shown that addressing the dynamic risk factors underlying youth delinquency, such as negative peer influences, attitudes that support crime, and inadequate supervision at home, is crucial for reducing recidivism. Over the last decade, some practitioners have expressed concerns about the potential limitations of such “deficit”-based approaches and have become interested in whether focusing on youths’ strengths could yield equal, if not greater, benefits for improving their outcomes. Despite this interest, little is known about the impact of positive youth development, strength-enhancing, and asset-based approaches on youth reoffending. The Youth Protective Factors Study addresses this gap by examining protective factors and strength-based services for youth in the justice system in selected counties across three states. Read the first brief, Youth Reoffending: Prevalence and Predictive Risk Factors in Two States, here : https://doi.org/10.13028/219x-vs03Publication Medical decision-making experiences of persons with dementia and their carepartners: a qualitative study(2025-04-09)Background: Persons with dementia (PWD) and their carepartners must often make complex medical decisions, weighing the benefits of medical (surgical and non-surgical) interventions with uncertainty regarding outcomes, both dementia- and non-dementia related, in the short-term and long-term. This study informs gaps in clinical guidance for patient-centered decision-making about medical and surgical interventions for PWD and advancecare planning. Methods: We conducted a qualitative study using thematic analysis based on semi-structured interviews with PWD and carepartners. Results: We interviewed 30 participants (9 PWD, 21 carepartners). Four themes were identified (with related subthemes): 1) PWD and carepartners varied in using decision-making approaches for medical interventions for PWD (a) variations in views about decision-making load; (b) Progressive involvement of carepartners in ACP decision-making as cognition erodes; 2) medical intervention decisions were an inflection point to evaluate values for dyads and involved tradeoffs with implications for end-of-life care and quality of life 3) lack of discussion with clinical team about impact of medical interventions on dementia burdened dyads; 4) decisional quality was facilitated by: (a) a trusting relationship with clinicians; and (b) a multidisciplinary team approach. Conclusion: Most patients with mild-to-moderate dementia and carepartners approach medical intervention decision-making guided by their understanding of the dementia prognosis, but the risks of medical interventions are often unaddressed in discussions with the clinical team, sometimes burdening dyads with undesirable consequences to their quality-of-life. Clinicians should provide dementia-related risks regarding medical intervention outcomes to best facilitate decision-making conversations and advance care planning.Publication A Culturally Tailored Artificial Intelligence Chatbot (K-Bot) to Promote Human Papillomavirus Vaccination Among Korean Americans: Development and Usability Study(2025-04-07)Background: Human papillomavirus (HPV) is the most common sexually transmitted infection (STI) worldwide and is associated with various cancers, including cervical and oropharyngeal cancers. Despite the availability of effective vaccines, significant disparities in HPV vaccination rates persist, particularly among racial and ethnic minorities, such as Korean Americans. Cultural stigma, language barriers, and limited access to tailored health information contribute to these disparities. Objective: This study aimed to develop and evaluate the usability of K-Bot, an artificial intelligence (AI)-powered, culturally tailored, bilingual (Korean and English) chatbot designed to provide culturally sensitive health information about HPV vaccination to Korean immigrants and Korean Americans. Methods: K-Bot was developed using CloudTuring and Google Dialogflow. Its dialogues were created using Centers for Disease Control and Prevention (CDC) evidence-based HPV information and tailored to the Korean American population based on findings from previous studies. The evaluation and refinement process for K-Bot was organized into 3 phases: (1) expert evaluation by a multidisciplinary panel, (2) usability testing, and (3) iterative refinement based on feedback. An online survey collected demographics, HPV awareness, and vaccination status before 6 focus groups (N=21) sessions using semistructured questions guided by Peter Morville's usability framework. Quantitative data were analyzed descriptively, and thematic analysis assessed usability, cultural relevance, and content clarity across 6 dimensions: desirability, accessibility, findability, credibility, usability, and usefulness. Results: Participants had a mean age of 23.7 (SD 4.7) years, with most being female (n=12, 57.1%), second-generation individuals (n=13, 61.9%), and single (n=20, 95.2%). HPV awareness was high (n=19, 90.5%), vaccine knowledge was also high (n=18, 81.8%), but only 11 (52.4%) participants were vaccinated. Feedback-driven refinements addressed usability challenges, including simplifying navigation and adding visual elements. Participants described K-Bot as a promising tool for promoting HPV vaccination among Korean and Korean American users, citing its bilingual functionality and culturally tailored content as key strengths. Evidence-based information was valued, but participants recommended visuals to improve engagement and reduce cognitive load. Accessibility concerns included broken links, and participants proposed enhancements, such as animations, demographic-specific resources, and interactive features, to improve usability and engagement further. Conclusions: Usability testing of K-Bot revealed its potential as a culturally tailored, bilingual tool for promoting HPV vaccination among Korean immigrants and Korean Americans. Participants valued its evidence-based information, cultural relevance, and bilingual functionality but recommended improvements, such as enhanced navigation, visual elements, and interactive features, to boost engagement and usability. These findings support the potential of AI-driven tools to improve health care access by addressing key barriers to care. Further research is needed to evaluate their broader impact and optimize their design and implementation for individuals with diverse health care needs.Publication Molecular mechanisms of drug resistance and compensation in SARS-CoV-2 main protease: the interplay between E166 and L50(2025-04-04)The SARS-CoV-2 main protease (Mpro) is essential for viral replication and is a primary target for COVID-19 antivirals. Direct-acting antivirals such as nirmatrelvir, the active component of Paxlovid, target the Mpro active site to block viral polyprotein cleavage and thus replication. However, drug resistance mutations at the active site residue Glu166 (E166) have emerged during in vitro selection studies, raising concerns about the durability of current antiviral strategies. Here, we investigate the molecular basis of drug resistance conferred by E166A and E166V mutations against nirmatrelvir and the related PF-00835231, individually and in combination with the distal mutation L50F. We found that E166 mutations reduce nirmatrelvir potency by up to 3,000-fold while preserving substrate cleavage, with catalytic efficiency reduced by only up to twofold. This loss of catalytic efficiency was compensated for by the addition of L50F in the double-mutant variants. We have determined three cocrystal structures of the E166 variants (E166A, E166V, and E166V/L50F) bound to PF-00835231. Comparison of these structures with wild-type enzyme demonstrated that E166 is crucial for dimerization and for shaping the substrate-binding S1 pocket. Our findings highlight the mutability of E166, a prime site for resistance for inhibitors that leverage direct interactions with this position, and the potential emergence of highly resistant and active variants in combination with the compensatory mutation L50F. These insights support the design of inhibitors that target conserved protease features and avoid E166 side-chain interactions to minimize susceptibility to resistance. Importance: Drug resistance remains a great challenge to modern medicine. This study investigates SARS-CoV-2 main protease variants E166A and E166V which confer nirmatrelvir resistance. These variants can retain considerable enzymatic activity through combination with the compensatory mutation L50F. For single- and double-mutant variant enzymes, we assessed catalytic efficiency, measured loss in potency for nirmatrelvir and its analog PF-00835231, and cocrystallized with inhibitors to investigate drug resistance caused by these mutations. Our results contribute toward understanding of molecular mechanisms of resistance and combinations of mutations, which pushes toward resistance-thwarting inhibitor design. These principles also apply broadly to many quickly evolving drug targets in infectious diseases.