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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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PhD nursing programs: Where are we headed?Thank you for your timely editorial, The PhD in Nursing - Questions about a Credential at a Crossroads. We agree that the future of PhD education in nursing is in peril and needs rapid solutions. Low enrollment and threats of PhD program closures are on the rise. As three former Directors of PhD Programs, we feel it is essential that we do not walk away from PhD education. Here are some of our thoughts.
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Implementing virtual desktops for clinical research at an academic health center: a case reportObjectives: To address the challenges of sharing clinical research data through the implementation of cloud-based virtual desktops, enhancing collaboration among researchers while maintaining data security. Materials and methods: This case study details the deployment of virtual desktops at UMass Chan Medical School (UMass Chan). The process involved forming a Research Informatics Steering Executive workgroup, identifying key requirements, implementing Amazon WorkSpaces, and establishing configurable data management for research support. Results: Key lessons include the significance of collaboration, balancing user-friendliness and functionality, flexibility in data management, maximizing virtual desktop efficiency within budget constraints, and continuous user feedback. The implementation of virtual desktops supports secure collaborative research, advancing medical knowledge and improving healthcare outcomes. Discussion: The structured approach to implementing virtual desktops addresses data security, regulatory compliance, and real-time collaboration challenges. Continuous feedback and iterative improvements have enhanced the system's effectiveness. Conclusion: The successful implementation of virtual desktops at UMass Chan demonstrates the potential for such systems to support secure, collaborative research, offering insights for similar initiatives in other academic health centers.
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Teach creativity in science higher educationLetter to the editor addressing why creativity should be taught in higher education basic science programs.
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Ten simple rules for recognizing data and software contributions in hiring, promotion, and tenureThe ways in which promotion and tenure committees operate vary significantly across universities and departments. While committees often have the capability to evaluate the rigor and quality of articles and monographs in their scientific field, assessment with respect to practices concerning research data and software is a recent development and one that can be harder to implement, as there are few guidelines to facilitate the process. More specifically, the guidelines given to tenure and promotion committees often reference data and software in general terms, with some notable exceptions such as guidelines in [5] and are almost systematically trumped by other factors such as the number and perceived impact of journal publications. The core issue is that many colleges establish a scholarship versus service dichotomy: Peer-reviewed articles or monographs published by university presses are considered scholarship, while community service, teaching, and other categories are given less weight in the evaluation process. This dichotomy unfairly disadvantages digital scholarship and community-based scholarship, including data and software contributions [6]. In addition, there is a lack of resources for faculties to facilitate the inclusion of responsible data and software metrics into evaluation processes or to assess faculty’s expertise and competencies to create, manage, and use data and software as research objects. As a result, the outcome of the assessment by the tenure and promotion committee is as dependent on the guidelines provided as on the committee members’ background and proficiency in the data and software domains. The presented guidelines aim to help alleviate these issues and align the academic evaluation processes to the principles of open science. We focus here on hiring, tenure, and promotion processes, but the same principles apply to other areas of academic evaluation at institutions. While these guidelines are by no means sufficient for handling the complexity of a multidimensional process that involves balancing a large set of nuanced and diverse information, we hope that they will support an increasing adoption of processes that recognize data and software as key research contributions.
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Racial Disparities and Trends in Anticoagulant Use among Ambulatory Care Patients with Atrial Fibrillation and Atrial Flutter in the United States from 2007-2019Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, significantly increasing the risk of stroke. The introduction of direct oral anticoagulants (DOACs) since 2010 has transformed anticoagulation therapy, offering an alternative to warfarin with improved safety profiles. Despite the increased adoption of DOACs, disparities in their use among different racial and ethnic groups in the United States remain understudied. Methods This study utilized a repeated cross-sectional design, analyzing data from the National Ambulatory Medical Care Survey (NAMCS) from 2007 to 2019. The study population included adults diagnosed with AF or atrial flutter (AFL). We analyzed the temporal trends of DOAC and warfarin use from 2007 to 2019. We examined the prevalence of DOAC versus warfarin use and assessed associations between race/ethnicity, patient characteristics, and DOAC utilization from 2011 to 2019. Multivariable modified Poisson regression models were used to calculate adjusted prevalence ratios (aPR) for the associations. Results From 2011 to 2019, NAMCS recorded 3,224 visits involving AF or AFL, representing a weighted estimate of 103.6 million visits. DOAC use increased significantly, with apixaban becoming the predominant anticoagulant by 2016. Non-Hispanic Black patients were less likely to use DOACs compared to non-Hispanic White patients over time (aPR 0.75; 95% CI, 0.63-0.90). Patients with Medicaid insurance were also less likely to use DOACs (aPR 0.14; 95% CI: 0.04-0.46). Conclusion Despite the shift from warfarin to DOACs for AF and AFL treatment, significant racial and socioeconomic disparities persist. Non-Hispanic Black patients and those with Medicaid insurance are less likely to use DOACs. These findings highlight the need for targeted strategies to ensure equitable access to advanced anticoagulant therapies.
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Identification of WNK1 as a Therapeutic Target to Suppress IgH/MYC Expression in Multiple MyelomaMultiple myeloma (MM) remains an incurable hematological malignancy demanding innovative therapeutic strategies. Targeting MYC, the notorious yet traditionally undruggable oncogene, presents an appealing avenue. This thesis aims to identify and characterize novel regulators of MYC expression as therapeutic targets in MM. Using a genome-scale CRISPR/Cas9 screen, we identify the WNK lysine deficient protein kinase 1 (WNK1) as a regulator of MYC expression in MM cells. Genetic and pharmacological inhibition of WNK1 reduces MYC expression and, further, disrupts the MYC-dependent transcriptional program. Mechanistically, WNK1 inhibition attenuates the activity of the immunoglobulin heavy chain (IgH) enhancer, thus reducing MYC transcription when this locus is translocated near the MYC locus. Furthermore, we show in MM cells possessing distinct translocation profiles that WNK1 inhibition also downregulates other oncogenes frequently translocated near the IgH locus, including CCND1, FGFR3, and NSD2, broadening its potential therapeutic implications. WNK1 inhibition profoundly impacts MM cell behaviors, leading to growth inhibition, cell cycle arrest, senescence, and apoptosis. Importantly, the WNK inhibitor WNK463 inhibits MM growth in primary patient samples as well as xenograft mouse models, and exhibits synergistic effects with various anti-MM compounds. Collectively, this study uncovers WNK1 as a promising therapeutic target in MM, and suggests the utility of IgH translocations as useful biomarkers.
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Nirmatrelvir/Ritonavir (Paxlovid) Use Among Individuals at Risk of Severe COVID-19: An Analysis of the National COVID Cohort Collaborative (N3C)Purpose: Paxlovid is effective in reducing COVID-19 hospitalization and mortality. This study characterized Paxlovid use and evaluated racial/ethnic disparities over time among community-dwelling adults at high risk of progression to severe COVID-19 disease. Methods: This retrospective cohort study used the National COVID Cohort Collaborative (N3C) data and included individuals aged 18 years or older diagnosed with COVID-19 between January 2022 and December 2023. The study cohort included nonhospitalized individuals who were at high risk of COVID-19 progression, and selected the first COVID-19 episode in each quarter, including reinfection episodes. Paxlovid use was defined as receiving Paxlovid within ±5 days of a COVID-19 diagnosis. We used descriptive statistics to characterize Paxlovid use overall and by calendar quarter and race/ethnicity. We used a generalized estimating equations (GEE) models to quantify the association of race/ethnicity with Paxlovid use controlling for age, gender, and clinical characteristics. Results: Among 1 264 215 individuals at high risk of disease progression (1 404 607 episodes), Paxlovid use increased from 1.2% in January-March 2022 to 35.1% in October-December 2023. Paxlovid use was more common among non-Hispanic White individuals (23.9%) than non-Hispanic Black (16.5%) and Latinx/e (16.7%) patients. After adjusting age, gender, and clinical characteristics, Paxlovid use was less likely among non-Hispanic Black (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.68-0.70) and Latinx/e (OR 0.72, CI 0.71-0.73) patients than non-Hispanic White patients. Conclusions: Among a large, diverse cohort of community-dwelling individuals with COVID-19, nearly two out of three eligible individuals did not receive Paxlovid, and minoritized racial/ethnic groups were less likely to use Paxlovid than their non-Hispanic White individuals.
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UMCCTS Newsletter, August 2024This is the August 2024 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
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Neighborhood Resources Associated With Psychological Trajectories and Neural Reactivity to Reward After TraumaImportance: Research on resilience after trauma has often focused on individual-level factors (eg, ability to cope with adversity) and overlooked influential neighborhood-level factors that may help mitigate the development of posttraumatic stress disorder (PTSD). Objective: To investigate whether an interaction between residential greenspace and self-reported individual resources was associated with a resilient PTSD trajectory (ie, low/no symptoms) and to test if the association between greenspace and PTSD trajectory was mediated by neural reactivity to reward. Design, setting, and participants: As part of a longitudinal cohort study, trauma survivors were recruited from emergency departments across the US. Two weeks after trauma, a subset of participants underwent functional magnetic resonance imaging during a monetary reward task. Study data were analyzed from January to November 2023. Exposures: Residential greenspace within a 100-m buffer of each participant's home address was derived from satellite imagery and quantified using the Normalized Difference Vegetation Index and perceived individual resources measured by the Connor-Davidson Resilience Scale (CD-RISC). Main outcome and measures: PTSD symptom severity measured at 2 weeks, 8 weeks, 3 months, and 6 months after trauma. Neural responses to monetary reward in reward-related regions (ie, amygdala, nucleus accumbens, orbitofrontal cortex) was a secondary outcome. Covariates included both geocoded (eg, area deprivation index) and self-reported characteristics (eg, childhood maltreatment, income). Results: In 2597 trauma survivors (mean [SD] age, 36.5 [13.4] years; 1637 female [63%]; 1304 non-Hispanic Black [50.2%], 289 Hispanic [11.1%], 901 non-Hispanic White [34.7%], 93 non-Hispanic other race [3.6%], and 10 missing/unreported [0.4%]), 6 PTSD trajectories (resilient, nonremitting high, nonremitting moderate, slow recovery, rapid recovery, delayed) were identified through latent-class mixed-effect modeling. Multinominal logistic regressions revealed that for individuals with higher CD-RISC scores, greenspace was associated with a greater likelihood of assignment in a resilient trajectory compared with nonremitting high (Wald z test = -3.92; P < .001), nonremitting moderate (Wald z test = -2.24; P = .03), or slow recovery (Wald z test = -2.27; P = .02) classes. Greenspace was also associated with greater neural reactivity to reward in the amygdala (n = 288; t277 = 2.83; adjusted P value = 0.02); however, reward reactivity did not differ by PTSD trajectory. Conclusions and relevance: In this cohort study, greenspace and self-reported individual resources were significantly associated with PTSD trajectories. These findings suggest that factors at multiple ecological levels may contribute to the likelihood of resiliency to PTSD after trauma.
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Factors associated with non-adherence to dual-energy x-ray absorptiometry screening during the COVID-19 pandemic in an academic medical centerThis study explored why some elderly females do not adhere to their bone density tests. It found that factors like age, race, marital status, insurance type, social vulnerability index, and vaccination status influence completion of these tests. Addressing these differences could improve the management of bone health in older adults. Purpose: This study investigated factors influencing the cancellation of dual-energy x-ray absorptiometry (DXA) scans among females aged 65 and above during the COVID-19 pandemic. Methods: Utilizing a dataset of 19,066 females from 2021 to 2023, the research employed chi-squared tests and logistic regression analyses to examine demographic, socio-economic, and health-related determinants of DXA scan adherence. Results: Key findings revealed that younger seniors, White patients, married individuals, those with commercial/private or Medicare insurance, and vaccinated persons were more likely to complete DXA scans. In contrast, Asian and African American females, along with those from higher Social Vulnerability Index areas, showed lower completion rates. Conclusion: These results highlight the need for tailored strategies to improve osteoporosis screening adherence, focusing on identified demographic groups to enhance overall healthcare outcomes in osteoporosis management.
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Computationally Detecting Viral Infection and Characterizing Host-Virus Dynamics in scRNA-seq DatasetsViruses pose significant threats to human health, with their impacts varying by type. Advances in single-cell RNA sequencing (scRNA-seq) have enhanced our understanding of viruses and host responses by mapping human and viral transcripts within individual cells. However, ambient RNA contamination complicates the accurate identification of viral infections in scRNA-seq datasets. To address this, we introduced scVirusFinder, a method that uses a zero-inflated negative binomial model followed by a support vector machine classifier to identify virus-infected cells. This approach improves the detection of true viral infections in scRNA-seq datasets of virus infected cells. We applied this method to scRNA-seq data from nasal washes of healthy donors and those with acute influenza during the 2017-18 season. We identified seventeen cell populations, including a novel epithelial cell population with high MHC class II gene expression in infected individuals. Influenza virus infections were found in most cell populations, primarily in epithelial cells and major immune cells such as macrophages and neutrophils. Using viral reads from the scRNA-seq data, we discovered that each donor harbored a unique influenza variant with distinct non-synonymous mutations. Additionally, we observed interferon production and response in infected samples, with type III interferon particularly produced in infected ciliated epithelial cells. This study highlights the challenge of identifying infected cells from scRNA-seq datasets and provides a robust solution applicable to clinical samples, enhancing our understanding of viral infections and paving the way for therapeutic discoveries.
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Exome-wide association analysis identifies novel risk loci for alcohol-associated hepatitisBackground and aims: Alcohol-associated hepatitis (AH) is a clinically severe, acute disease that afflicts only a fraction of patients with alcohol use disorder (AUD). Genomic studies of alcohol-associated cirrhosis (AC) have identified several genes of large effect, but the genetic and environmental factors that lead to AH and AC, and their degree of genetic overlap, remain largely unknown. This study aims to identify genes and genetic variation that contribute to the development of AH. Approach and results: Exome-sequencing of patients with AH (N=784) and heavy drinking controls (N=951) identified exome-wide significant association for AH at PNPLA3, as previously observed for AC in GWAS, although with a much lower effect-size. SNPs of large effect-size at ICOSLG (Chr 21) and TOX4/RAB2B (Chr 14), were also exome-wide significant. ICOSLG encodes a co-stimulatory signal for T-cell proliferation and cytokine secretion and induces B-cell proliferation and differentiation. TOX4 was previously implicated in diabetes and immune system function. Other genes previously implicated in AC did not strongly contribute to AH, and the only prominently implicated (but not exome wide significant) gene overlapping with AUD was ADH1B. Polygenic signals for AH were observed in both common and rare variant analysis and identified genes with roles associated with inflammation. Conclusions: This study has identified two new genes of high effect size with a previously unknown contribution to ALD, and highlights both the overlap in etiology between liver diseases, and the unique origins of AH.
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Minding the margins: Evaluating the impact of COVID-19 among Latinx and Black communities with optimal qualitative serological assessment toolsCOVID-19 disproportionately affected minorities, while research barriers to engage underserved communities persist. Serological studies reveal infection and vaccination histories within these communities, however lack of consensus on downstream evaluation methods impede meta-analyses and dampen the broader public health impact. To reveal the impact of COVID-19 and vaccine uptake among diverse communities and to develop rigorous serological downstream evaluation methods, we engaged racial and ethnic minorities in Massachusetts in a cross-sectional study (April-July 2022), screened blood and saliva for SARS-CoV-2 and human endemic coronavirus (hCoV) antibodies by bead-based multiplex assay and point-of-care (POC) test and developed across-plate normalization and classification boundary methods for optimal qualitative serological assessments. Among 290 participants, 91.4% reported receiving at least one dose of a COVID-19 vaccine, while 41.7% reported past SARS-CoV-2 infections, which was confirmed by POC- and multiplex-based saliva and blood IgG seroprevalences. We found significant differences in antigen-specific IgA and IgG antibody outcomes and indication of cross-reactivity with hCoV OC43. Finally, 26.5% of participants reported lingering COVID-19 symptoms, mostly middle-aged Latinas. Hence, prolonged COVID-19 symptoms were common among our underserved population and require public health attention, despite high COVID-19 vaccine uptake. Saliva served as a less-invasive sample-type for IgG-based serosurveys and hCoV cross-reactivity needed to be evaluated for reliable SARS-CoV-2 serosurvey results. The use of the developed rigorous downstream qualitative serological assessment methods will help standardize serosurvey outcomes and meta-analyses for future serosurveys beyond SARS-CoV-2.
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Implementing a Hybrid Work Model in a University Medical LibraryLike many libraries, the University of Massachusetts Chan Medical School Lamar Soutter Library adopted a hybrid work model when returning to onsite work after being remote during the COVID-19 Pandemic. To inform this model, a Hybrid Work Environment Team used existing metrics, a literature review, and surveyed staff on how they felt about hybrid work. Most Library staff stated that 75%-100% of their work could be completed remotely and the most popular onsite schedule was two or three days a week. The hybrid work model provides benefits of both remote and onsite work and hopefully mitigates the drawbacks of both.
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Systemic and skin-limited delayed-type drug hypersensitivity reactions associate with distinct resident and recruited T cell subsetsDelayed-type drug hypersensitivity reactions are major causes of morbidity and mortality. The origin, phenotype and function of pathogenic T cells across the spectrum of severity requires investigation. We leveraged recent technical advancements to study skin-resident memory T cells (TRM) versus recruited T cell subsets in the pathogenesis of severe systemic forms of disease, SJS/TEN and DRESS, and skin-limited disease, morbilliform drug eruption (MDE). Microscopy, bulk transcriptional profiling and scRNAseq + CITEseq + TCRseq supported in SJS/TEN clonal expansion and recruitment of cytotoxic CD8+ T cells from circulation into skin, along with expanded and non-expanded cytotoxic CD8+ skin TRM. Comparatively, MDE displayed a cytotoxic T cell profile in skin without appreciable expansion and recruitment of cytotoxic CD8+ T cells from circulation, implicating TRM as potential protagonists in skin-limited disease. Mechanistic interrogation in patients unable to recruit T cells from circulation into skin and in a parallel mouse model supported that skin TRM were sufficient to mediate MDE. Concomitantly, SJS/TEN displayed a reduced regulatory T cell (Treg) signature compared to MDE. DRESS demonstrated recruitment of cytotoxic CD8+ T cells into skin like SJS/TEN, yet a pro-Treg signature like MDE. These findings have important implications for fundamental skin immunology and clinical care.
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Living a private lie: intersectional stigma, depression and suicidal thoughts for selected young key populations living with HIV in ZambiaBackground: Limited research has been conducted on the forms, manifestations and effects of intersectional stigma among young HIV-positive men who have sex with men (MSM) and transgender women (TGW) in Zambia. In this study, we aimed to address this gap by elucidating the experiences of these in a small group of young, HIV + MSM and TGW in Zambia. Methods: We applied a mixed-methods design. Data were collected from January 2022 to May 2022. Qualitative data were collected using in-depth interviews while quantitative data were collected using a questionnaire. Qualitative transcripts were coded using thematic analysis while paper-based questionnaire data were entered into Kobo Connect. Descriptive statistics, using chi-squared tests were calculated using Excel. In this paper, we provide a descriptive profile of the sample and then focus on the qualitative findings on intersectional stigma, depression, and contemplation of suicide. Results: We recruited 56 participants from three sites: Lusaka, Chipata, and Solwezi districts. Participants' mean age was 23 years. The study found that 36% of all participants had moderate to significant symptoms of depression, 7% had major depression, 30% had moderate signs of anxiety, 11% had high signs of anxiety, 4% had very high signs of anxiety and 36% had contemplated suicide at least once. A greater proportion of TGW had moderate to significant symptoms of depression (40%) or major depression (10%) compared to MSM, at 33% and 6%, respectively (X2 = 0.65; p = 0.42). Similarly, more TGW (55%) had contemplated suicide than MSM peers (36%, X2=1.87; p = 0.17). In the qualitative data, four emergent themes about the forms, manifestations, and effects of intersectional stigma were (1) HIV, sexual orientation, and gender identity disclosure; (2) Dual identity; (3) Challenges of finding and maintaining sexual partners; (4) Coping and resilience. Overall, having to hide both one's sexuality and HIV status had a compounding effect and was described as living "a private lie." Conclusion: Effectively addressing stigmas and poor mental health outcomes among young HIV-positive MSM and TGW will require adopting a socio-ecological approach that focuses on structural interventions, more trauma-informed and identity-supportive care for young people with HIV, as well as strengthening of authentic community-informed public health efforts.
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To treat or not to treat: a comparative effectiveness analysis of oral anticoagulant outcomes among U.S. nursing home residents with atrial fibrillationBackground: Nursing home residents with atrial fibrillation are at high risk for ischemic stroke, but most are not treated with anticoagulants. This study compared the effectiveness and safety between oral anticoagulant (OAC) users and non-users. Methods: We conducted a new-user retrospective cohort study by using Minimum Data Set 3.0 assessments linked with Medicare claims. The participants were Medicare fee-for-service beneficiaries with atrial fibrillation residing in US nursing homes between 2011 and 2016, aged ≥ 65 years. The primary outcomes were occurrence of an ischemic stroke or systemic embolism (effectiveness), occurrence of intracranial or extracranial bleeding (safety) and net clinical outcome (effectiveness or safety outcomes). Secondary outcomes included total mortality and a net clinical and mortality outcome. Cox proportional hazards and Fine and Grey models estimated multivariable adjusted hazard ratios (aHRs) and sub-distribution hazard ratios (sHRs). Results: Outcome rates were low (effectiveness: OAC: 0.86; non-users: 1.73; safety: OAC: 2.26; non-users: 1.75 (per 100 person-years)). OAC use was associated with a lower rate of the effectiveness outcome (sHR: 0.69; 95% Confidence Interval (CI): 0.61-0.77), higher rates of the safety (sHR: 1.70; 95% CI: 1.58-1.84) and net clinical outcomes (sHR: 1.20; 95% CI: 1.13-1.28) lower rate of all-cause mortality outcome (sHR: 0.60; 95% CI: 0.59-0.61), and lower rate of the net clinical and mortality outcome (sHR: 0.60; 95% CI: 0.59-0.61). Warfarin users, but not DOAC users, had a higher rate of the net clinical outcome versus OAC non-users. Conclusions: Our results support the benefits of treatment with OACs to prevent ischemic strokes and increase longevity, while highlighting the need to weigh apparent benefits against elevated risk for bleeding. Results were consistent with net favorability of DOACs versus warfarin.
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The IR Venn Diagram: Diversity in Technology, Content, Users, and Roles in Specialized Institutional RepositoriesIn this poster, librarians from six academic libraries – representing various sectors including science, technology, engineering, medicine, music, and large universities – collaborated to explore and reflect on the academic IR community that encompasses specialized libraries, collections, and formats. The authors answered self-survey questions and responses were analyzed for visualization in the poster. The poster spotlights diversity in technology, content, users, roles, priorities, and challenges. It also illustrates some of the common threads and opportunities that have relevance and implications in both the special library and the broader IR landscape.
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“I promised them I would be there”: A qualitative study of the changing roles of cultural health navigators who serve refugees during the COVID-19 pandemicCultural health navigators (CHNs) are one type of community health worker (CHW), a front-line cadre critical to mitigating the COVID-19 pandemic among marginalized communities. Yet little is documented about the roles of CHNs serving resettled refugees both before and during the pandemic. The objective of this study was to examine shifts in how CHNs carried out their work with refugee patients at a particular time point in the COVID-19 pandemic. In August 2020, we conducted virtual and serial semi-structured interviews with ten CHNs at a U.S. healthcare system serving ethnically and linguistically diverse refugee communities. We used a thematic analysis approach to code and interpret data. The analysis indicated that CHNs’ descriptions of their work with refugee clients and communities largely mapped onto established CHW roles: cultural mediation, care coordination, system navigation, education, and outreach and social support; however, how CHNs fulfilled their roles shifted dramatically during the pandemic. CHNs were unable to physically navigate patients through the system due to safety measures and telemedicine and deeply felt the loss of providing in-person outreach and social support. To offset constraints, CHNs increased the number and scope of virtual contacts with patients and launched novel education, outreach, and social support strategies. Through their adapted strategies, CHNs nurtured a strong foundation of trust to provide continuous care under challenging circumstances, although they were concerned that the lack of in-person interactions decreased patients' sensitive disclosures. The analysis illuminates the important and often unrecognized work of CHWs and informs ongoing efforts to prioritize community health work in U.S. healthcare policy and practice.
