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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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Recently Published
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Impacts of testing and immunity acquired through vaccination and infection on covid-19 cases in Massachusetts elementary and secondary studentsBackground: During the 2021-22 academic year, Massachusetts supported several in-school testing programs to facilitate in-person learning. Additionally, COVID-19 vaccines became available to all school-aged children and many were infected with SARS-CoV-2. There are limited studies evaluating the impacts of these testing programs on SARS-CoV-2 cases in elementary and secondary school settings. The aim of this state-wide, retrospective cohort study was to assess the impact of testing programs and immunity on SARS-CoV-2 case rates in elementary and secondary students. Methods: Community-level vaccination and cumulative incidence rates were combined with data about participation in and results of in-school testing programs (test-to-stay, pooled surveillance testing). School-level impacts of surveillance testing programs on SARS-CoV-2 cases in students were estimated using generalized estimating equations within a target trial emulation approach stratified by school type (elementary/middle/high). Impacts of immunity and vaccination were estimated using random effects linear regression. Results: Here we show that among N = 652,353 students at 2141 schools participating in in-school testing programs, surveillance testing is associated with a small but measurable decrease in in-school positivity rates. During delta, pooled testing positivity rates are higher in communities with higher cumulative incidence of infection. During omicron, when immunity from prior infection became more prevalent, the effect reversed, such that communities with lower burden of infection during the earlier phases of the pandemic had higher infection rates. Conclusions: Testing programs are an effective strategy for supporting in-person learning. Fluctuating levels of immunity acquired via natural infection or vaccination are a major determinant of SARS-CoV-2 cases in schools.
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One more tribute to Jim - in his own wordsIntroduction: Last Friday evening we had a memorial for our colleague, friend, and mentor, Jim Ledwith. It was a moving service thanks to speakers like Liam Burke, Beth Mazyck, Eric Rosenthal, Phil Fournier, and Abigail Gyamfi. The entire night was made possible due to the hard work of Karen Rayla (and her friend Jackie), Pam Tero, Linda Hollis, Heather Garron, and Linda Cragin - thank you. One of the moving moments of the night was the reading of Jim Ledwith's letter of acceptance when he took over as the Medical Director of the Epworth Free Clinic in 2011. Below we share with you what Jim wrote all those years ago - the words speak volumes to who he was. Also, one of the rooms at the Epworth Free Clinic was dedicated in his name. We have included a photo of the plaque that now hangs in the room. We miss you, Jim. You were the best of us.
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A Novel Mouse Home Cage Lickometer System Reveals Sex- and Housing-Based Influences on Alcohol DrinkingAlcohol use disorder (AUD) is a significant global health issue. Despite historically higher rates among men, AUD prevalence and negative alcohol-related outcomes in women are rising. Loneliness in humans has been associated with increased alcohol use, and traditional rodent drinking models involve single housing, presenting challenges for studying social enrichment. We developed LIQ PARTI (Lick Instance Quantifier with Poly-Animal RFID Tracking Integration), an open-source tool to examine home cage continuous access two-bottle choice drinking behavior in a group-housed setting, investigating the influence of sex and social isolation on ethanol consumption and bout microstructure in C57Bl/6J mice. LIQ PARTI, based on our previously developed single-housed LIQ HD system, accurately tracks drinking behavior using capacitive-based sensors and RFID technology. Group-housed female mice exhibited higher ethanol preference than males, while males displayed a unique undulating pattern of ethanol preference linked to cage changes, suggesting a potential stress or novelty-related response. Chronic ethanol intake distinctly altered bout microstructure between male and female mice, highlighting sex and social environmental influences on drinking behavior. Social isolation with the LIQ HD system amplified fluid intake and ethanol preference in both sexes, accompanied by sex- and fluid-dependent changes in bout microstructure. However, these effects largely reversed upon resocialization, indicating the plasticity of these behaviors in response to social context. Utilizing a novel group-housed home cage lickometer device, our findings illustrate the critical interplay of sex and housing conditions in voluntary alcohol drinking behaviors in C57Bl/6J mice, facilitating nuanced insights into the potential contributions to AUD etiology.
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SSRI use during acute COVID-19 and risk of long COVID among patients with depressionBackground: Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is a poorly understood condition with symptoms across a range of biological domains that often have debilitating consequences. Some have recently suggested that lingering SARS-CoV-2 virus particles in the gut may impede serotonin production and that low serotonin may drive many Long COVID symptoms across a range of biological systems. Therefore, selective serotonin reuptake inhibitors (SSRIs), which increase synaptic serotonin availability, may be used to prevent or treat Long COVID. SSRIs are commonly prescribed for depression, therefore restricting a study sample to only include patients with depression can reduce the concern of confounding by indication. Methods: In an observational sample of electronic health records from patients in the National COVID Cohort Collaborative (N3C) with a COVID-19 diagnosis between September 1, 2021, and December 1, 2022, and a comorbid depressive disorder, the leading indication for SSRI use, we evaluated the relationship between SSRI use during acute COVID-19 and subsequent 12-month risk of Long COVID (defined by ICD-10 code U09.9). We defined SSRI use as a prescription for SSRI medication beginning at least 30 days before acute COVID-19 and not ending before SARS-CoV-2 infection. To minimize bias, we estimated relationships using nonparametric targeted maximum likelihood estimation to aggressively adjust for high-dimensional covariates. Results: We analyzed a sample (n = 302,626) of patients with a diagnosis of a depressive condition before COVID-19 diagnosis, where 100,803 (33%) were using an SSRI. We found that SSRI users had a significantly lower risk of Long COVID compared to nonusers (adjusted causal relative risk 0.92, 95% CI (0.86, 0.99)) and we found a similar relationship comparing new SSRI users (first SSRI prescription 1 to 4 months before acute COVID-19 with no prior history of SSRI use) to nonusers (adjusted causal relative risk 0.89, 95% CI (0.80, 0.98)). Conclusions: These findings suggest that SSRI use during acute COVID-19 may be protective against Long COVID, supporting the hypothesis that serotonin may be a key mechanistic biomarker of Long COVID.
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Investigating the role of p16Ink4a in Alzheimer's Disease pathogenesisAdvancing age is the most significant risk factor for Alzheimer’s Disease (AD), but how aging contributes to AD development remains unclear. Human induced pluripotent stem cell (iPSC) technology has revolutionized AD modeling, enabling the study of AD cellular pathogenesis in patient-derived cells. However, the epigenetic landscape and aging clock are reset to the embryonic state in iPSCs during reprogramming. Thus, current iPSC-based models lack proper cellular aging and do not fully recapitulate AD hallmark pathologies, including amyloid- beta plaques and neurofibrillary tau tangles, observed in human AD brains. My thesis aims to introduce factors of cellular aging to improve iPSC-based modeling of AD pathogenesis. I focus on CDKN2A (p16Ink4a or p16), an important senescence regulator and aging biomarker. I demonstrated that robust induction of p16 in iPSCs reduces cell proliferation and triggers downstream pathways, including focal adhesion and extracellular matrix organization. The inducible approach enables temporal control of p16 expression during the differentiation of iPSCs to neurons. I found that inducible p16 increases tau phosphorylation in iPSC-derived neurons in a cell-autonomous manner, providing a direct link between p16 and an AD-related cell pathology. This robust system provides a powerful resource to improve AD disease modeling to advance our understanding of the impact of aging in AD and develop innovative AD therapeutic drug discovery.
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A mixed-methods study of VA video connect utilization among veterans with diabetes experiencing housing instability during the pandemicIntroduction: Prior to the coronavirus disease-2019 (COVID-19) pandemic the U.S. Department of Veterans Affairs (VA) had the largest telehealth program in the United States. The pandemic motivated providers within the VA to expand telehealth in effort to reduce disrupted care while mitigating risks. The pandemic provides a rare opportunity to examine how to better engage veterans experiencing housing instability (HI) in telehealth diabetes care. Methods: Mixed methods design to examine VA video connect (VVC) diabetes care utilization among veterans experiencing HI from March 1, 2019, to March 1, 2022, combining multivariable regression analyses of VA administrative data with semi-structured interviews. Study aims included: (a) examine changes in diabetes care delivery mode over the peri-pandemic timeframe; (b) identify sociodemographic and clinical characteristics associated with VVC care among veterans with HI; and (c) understand the facilitators and barriers of VVC utilization. Results: Totally, 5904 veterans were eligible for study analysis. Veterans who are female (OR: 1.63; 95% CI: 1.3, 2.0; p < 0.0001), self-identify as Hispanic (OR: 1.44; 95% CI: 1.1, 1.9; p = 0.02), are married (OR: 1.39; 95% CI: 1.2, 1.6; p < 0.0001), and are in VA priority group 1 (OR: 1.21; 95% CI 1.1, 1.4; p = 0.004) were more likely to use VVC the pandemic. Veterans of older age (OR: 0.97; 95% CI: 0.97, 0.98; p < .0001) and rural dwelling (OR: 0.85; 95% CI: 0.7, 1.2; p = 0.04), were less likely to use VVC. Thirteen VA providers and 15 veterans were interviewed. Veterans reported that decisions about using VVC were driven by limitations in in-person care availability, safety, and convenience. Discussion: Telehealth played an important role in providing veterans with HI access to diabetes care during the pandemic. Future interventions should seek to increase education and technology in effort to increase VVC uptake into routine diabetes care to ensure veterans' optimal and equitable access.
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Isolation and focal treatment of brain aneurysms using interfacial fluid trappingCurrent approaches for localized intravascular treatments rely on using solid implants, such as metallic coils for embolizing aneurysms, or on direct injection of a therapeutic agent that can disperse from the required site of action. Here, we present a fluid-based strategy for localizing intravascular therapeutics that leverages surface tension and immiscible fluid interactions, to allow confined and focal treatment at brain aneurysm sites. We first show, computationally and experimentally, that an immiscible phase can be robustly positioned at the neck of human aneurysm models to seal and isolate the aneurysm's cavity for further treatment, including in wide-neck aneurysms. We then demonstrate localized delivery and confined treatment, by selective staining of cell nuclei within the aneurysm cavity as well as by hydrogel-based embolization in patient-specific aneurysm models. Altogether, our interfacial flow-driven strategy offers a potential approach for intravascular localized treatment of cardiovascular and other diseases.
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Aging in AmericaIntroduction: After my piece last week about writing a letter to my past self - I received an email from a former UMass Chan student who was in the FMIG and mentee of mine. She said the piece had motivated her to write a letter to herself on literally her first day of practice after completing residency. I love that. We hand one another along... This week, in the spirit of sharing writing from alumni, I have a piece for you from Dr. Pam Adelstein. She is a long-time writer for FMM, a former resident at Family Health Center of Worcester, the current Director of Family Medicine for Fenway Clinic in Boston, and next week's Putterman Visiting Professor. And also, a great example of a clinician who has continued to reflect on many topics and is often published in Pulse (an online journal where you can experience poetry, prose, haiku, photos, artwork and now podcasts). As Donald Schön wrote: “The reflective practitioner allows [themself] to experience surprise, puzzlement, or confusion in a situation which they find uncertain or unique. They reflect on the phenomenon before them, and on the prior understandings which have been implicit in their behaviour. They carry out an experiment which serves to generate both a new understanding of the phenomenon and a change in the situation.” Amen. (Note: This piece was previously published on Pulse. The prompt was Palliative and Hospice Care. You can view the original here.)
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What is Community Participation?The Center for Community Inclusion and Reflective Collaboration (the CIRC Center) is a research and training center that aims to significantly advance community participation outcomes among young adults (14–26) with serious mental health conditions from populations that have been marginalized or minoritized. The term community participation is used in mental health services and research to refer to community-based activities that promote overall health and wellness. However, many people find this concept to be confusing, vague, and hard to understand. This tip sheet will define “community participation,” describe relevant experiences of young adults (ages 14–26) with serious mental health conditions (SMHC) from populations that have been marginalized, and provide reflections from our various advisory boards of young adults, family members, and professionals in the field.
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Demystifying Civic Engagement: How to Make Your Voice Heard (Beyond Voting!) & 5 Tips to Get StartedThe term “civic engagement” is less intimidating than it sounds! Civic engagement describes the process taken by individuals or groups to identify and address issues of concern within their communities. Civic engagement can take many forms, from individual events such as working the polls, to longer-term, sustained efforts such as joining an advocacy group and educating others around issues that matter to you. This tip sheet outlines 5 ways to get involved in civic engagement that are in addition to voting OR that can be done before you’re old enough to vote.
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Neuropilin-2 expressing cells in breast cancer are S-nitrosylation hubs that mitigate radiation-induced oxidative stressThe high rate of recurrence after radiation therapy in triple-negative breast cancer (TNBC) indicates that novel approaches and targets are needed to enhance radiosensitivity. Here, we report that neuropilin-2 (NRP2), a receptor for vascular endothelial growth factor (VEGF) that is enriched on sub-populations of TNBC cells with stem cell properties, is an effective therapeutic target for sensitizing TNBC to radiotherapy. Specifically, VEGF/NRP2 signaling induces nitric oxide synthase 2 (NOS2) transcription by a mechanism dependent on Gli1. NRP2-expressing tumor cells serve as a hub to produce nitric oxide (NO), an autocrine and paracrine signaling metabolite, which promotes cysteine-nitrosylation of Kelch-like ECH-asssociated protein 1 (KEAP1) and, consequently, nuclear factor erythroid 2-related factor 2 (NFE2L2)-mediated transcription of antioxidant response genes. Inhibiting VEGF binding to NRP2, using a humanized monoclonal antibody (mAb), results in NFE2L2 degradation via KEAP1 rendering cell lines and organoids vulnerable to irradiation. Importantly, treatment of patient-derived xenografts with the NRP2 mAb and radiation resulted in significant tumor necrosis and regression compared to radiation alone. Together, these findings reveal a targetable mechanism of radioresistance and they support the use of NRP2 mAb as an effective radiosensitizer in TNBC.
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UMCCTS Newsletter, October 2024This is the October 2024 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
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iSPARC 2024 Annual Report to the Massachusetts Department of Mental HealthIn fiscal year 2024, iSPARC continued to leverage DMH’s investment to rapidly translate research findings into their implementation within best practices for individuals with lived experience, their families, and the providers who serve them across the Commonwealth. iSPARC’s work has focused on key strategic priorities for DMH. First, this year, the iSPARC Technical Assistance Program contributed to work on elucidating key factors involved in reducing the incidence of inpatient aggression at DMH-funded facilities. iSPARC also made substantial strides in targeting Diversity, Equity, and Inclusion (DEI) within our Center, including workforce enrichment and our research program. During fiscal year 2024, our Center has initiated several new and innovative projects to improve the behavioral health of individuals with mental health disorders.
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Acute and Critical Care Nurses' Roles in Mass Shootings: An Integrative ReviewBackground: From 2018 to 2022, mass shooting incidents in the United States increased by 67.7%. Health care-associated shootings also increased. The role of acute and critical care nurses during shootings is not well defined in the literature. Objective: To identify roles of acute and critical care nurses during mass shooting incidents and provide best-practice recommendations for shooting incidents within a hospital. Methods: The methods of Whittemore, Knafl, and Torraco informed this integrative review. Ovid MEDLINE, CINAHL, and Scopus databases were searched for publications related to acute and critical care nurses, mass shooting incidents, and hospital setting. Results: Of 13 589 articles retrieved, 27 were included; 63% were narrative reviews. The highest level of evidence was an expert consensus panel; next highest was a quasi-experimental study that simulated experiences to test mass casualty incident response. Third highest was a qualitative study that analyzed nurses' experiences during a mass casualty experience. Discussion: The evidence revealed 3 themes: prevention and preparedness, response to incident, and recovery phase. Education and training for acute and critical care nurses about mass shooting incidents are central to defining nurses' roles and best practices for these incidents. Nurses must know Stop the Bleed techniques and run-hide-fight protocols. Additionally, acute and critical care nurses need representation on hospital committees to develop and implement policies and procedures. Conclusions: Hospitals are not immune to mass shooting incidents. Acute and critical care nurses require education including simulations and drills on mass shooting incidents to ensure safety of nurses and patients.
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Office of Communications Records, 1962 - ongoing: A Finding AidThe Office of Communications is the official source of news and information at the University of Massachusetts Medical School (UMMS). The records in this collection consist mainly of Office of Communications documents, publications, and other materials created beginning in 1962.
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Robert W. Finberg Papers: A Finding AidThe Robert W. Finberg Papers chronicle Dr. Finberg’s career as a physician, researcher, teacher, and administrator at UMass Chan Medical School.
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UMass Chan Medical School Yearbook Collection, 1974 – ongoing: A Finding AidThis collection contains Iatros, the annually published yearbook of UMass Chan Medical School. Also included are yearbooks published under the school’s name prior to 2021, the University of Massachusetts Medical School.
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Sandy C. Marks Collection: A Finding AidThe Sandy C. Marks Collection chronicles Dr. Marks’s career as a faculty member at UMass Chan Medical School.
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Medicaid Accountable Care Organizations and Disparities in Pediatric Asthma CareImportance: Nearly 6 million children in the US have asthma, and over one-third of US children are insured by Medicaid. Although 23 state Medicaid programs have experimented with accountable care organizations (ACOs), little is known about ACOs' effects on longstanding insurance-based disparities in pediatric asthma care and outcomes. Objective: To determine associations between Massachusetts Medicaid ACO implementation in March 2018 and changes in care quality and use for children with asthma. Design, setting, and participants: Using data from the Massachusetts All Payer Claims Database from January 1, 2014, to December 31, 2020, we determined child-years with asthma and used difference-in-differences (DiD) estimates to compare asthma quality of care and emergency department (ED) or hospital use for child-years with Medicaid vs private insurance for 3 year periods before and after ACO implementation for children aged 2 to 17 years. Regression models accounted for demographic and community characteristics and health status. Data analysis was conducted between January 2022 and June 2024. Exposure: Massachusetts Medicaid ACO implementation. Main outcomes and measures: Primary outcomes were binary measures in a calendar year of (1) any routine outpatient asthma visit, (2) asthma medication ratio (AMR) greater than 0.5, and (3) any ED or hospital use with asthma. To determine the statistical significance of differences in descriptive statistics between groups, χ2 and t tests were used. Results: Among 376 509 child-year observations, 268 338 (71.27%) were insured by Medicaid and 73 633 (19.56%) had persistent asthma. There was no significant change in rates of routine asthma visits for Medicaid-insured child-years vs privately insured child-years post-ACO implementation (DiD, -0.4 percentage points [pp]; 95% CI, -1.4 to 0.6 pp). There was an increase in the proportion with AMR greater than 0.5 for Medicaid-insured child-years vs privately insured in the postimplementation period (DiD, 3.7 pp; 95% CI, 2.0-5.4 pp), with absolute declines in both groups postimplementation. There was an increase in any ED or hospital use for Medicaid-insured child-years vs privately insured postimplementation (DiD, 2.1 pp; 95% CI, 1.2-3.0 pp), an 8% increase from the preperiod Medicaid use rate. Conclusions and relevance: Introduction of Massachusetts Medicaid ACOs was associated with persistent insurance-based disparities in routine asthma visit rates; a narrowing in disparities in appropriate AMR rates due to reductions in appropriate rates among those with private insurance; and worsening disparities in any ED or hospital use for Medicaid-insured children with asthma compared to children with private insurance. Continued study of changes in pediatric asthma care delivery is warranted in relation to major Medicaid financing and delivery system reforms.
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Disparate impact of risk assessment instruments: A systematic reviewObjective: One concern about the use of risk assessment instruments in legal decisions is the potential for disparate impact by race or ethnicity. This means that one racial or ethnic group will experience harsher legal outcomes than another because of higher or biased risk estimates. We conducted a systematic review of the literature to synthesize research examining the real-world impact of juvenile and adult risk instruments on racial/ethnic disparities in legal decision making. Hypotheses: Given the nature of research synthesis, we did not test formal hypotheses. Method: Our systematic literature search as of July 2023 identified 21 articles that investigated the disparate impact of 13 risk assessment instruments on various legal outcomes. Most of these instruments were actuarial pretrial screening instruments. Results: Our narrative synthesis indicated that there is not strong evidence of risk instruments contributing to greater system disparity. Ten articles indicated that adopting risk instruments did not create (or exacerbate preexisting) disparities, and eight articles found that instrument use reduced disparities in legal decision making. Three articles reported evidence of disparate impact of risk instruments; only one of these studies received a strong study quality assessment score. We observed a scarcity of high-quality articles that employed what we deem to be the gold standard approach for examining the disparate impact of risk instruments (i.e., pretest-posttest design). Conclusion: The evidence signals that risk instruments can contribute to reductions in disparities across multiple stages of legal decision making. Yet study quality remains low and most research has been conducted on decisions during the pretrial stage. More rigorous research on disparate impact across diverse legal decision points and approaches to risk assessment is needed.
