eScholarship@UMassChan: Recently Published
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Adulting Shorts: The "TEA" on IEPs Part 4This info-comic is for high school students to help them understand what an Individualized Educational Plan or IEP is, what transition planning is, and the importance of the student being involved in them. Part 4 focuses on Mateo leading his IEP meeting. Parts 1 through 3 can be found on our website: https://www.umassmed.edu/TransitionsACR/publication/comic/
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Treating Patients, not DiseasesIntroduction: I am pleased to again have Dr. Bob Singer reach out with his reflection. I love how far our FMM messages travel. Bob was a resident at UMass Family Practice Residency Program from 1978 to 1981 when the Family Health Center of Worcester was called the Family Health and Social Service Center. He then practiced in Everett for years and then moved to Maryland to do geriatric work before retiring. He wrote today's piece after reading the headline and article below. I think it is a nice follow up from last week's theme of relationship as medicine. I had a similar experience to Bob - his words really resonate with me. Researchers Find Evidence Of “Long Cold” Syndrome Following Infection With Variety Of Common Respiratory Viruses NBC News (10/6, Carroll) reported, “The coronavirus isn’t the only pathogen that can cause symptoms that last months, or even years, after an initial infection is overcome, a...study published Friday in The Lancet’s eClinicalMedicine suggests.” According to “an analysis of data from 10,171 U.K. adults, the researchers found evidence of a ‘long cold’ syndrome that can follow infection with a variety of common respiratory viruses, including common cold viruses and influenza.”
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The mobile vaccine equity enhancement program–a model program for enhancing equity in vaccine availability based at a large health care systemThe SARS CoV-2 (COVID-19) pandemic presented unprecedented challenges as communities attempted to respond to the administration of a novel vaccine that faced cold chain logistical requirements and vaccine hesitancy among many, as well as complicated phased rollout plans that changed frequently as availability of the vaccine waxed and waned. The COVID-19 pandemic also disproportionately affected communities of color and communities with barriers to accessing healthcare. In the setting of these difficulties, a program was created specifically to address inequity in vaccine administration with a focus on communities of color and linguistic diversity as well as those who had technological barriers to online sign-up processes common at mass vaccination sites. This effort, the Mobile Vaccine Equity Enhancement Program (MVeeP), delivered over 12,000 vaccines in 24 months through a reproducible set of practices that can inform equity-driven vaccine efforts in future pandemics.
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Leveraging Differences in AI and Human "Vision" to Improve Breast Cancer DetectionScreening mammography is the single most effective test to reduce breast cancer mortality. Despite improvements in mammography technology, including digital breast tomosynthesis, it remains an imperfect test, with one in eight cancers missed at time of interpretation. Supplemental imaging with US, contrast-enhanced MRI, or contrast-enhanced mammography has been recommended in women with higher-than-average risk to improve breast cancer detection. However, challenges arise for women who are not identified as being at higher-than-average risk or who may not have access to these tests. Artificial intelligence (AI) models using deep learning technology have the potential to find cancers not identified by humans, improving the efficacy of screening mammography.
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Lamar Soutter Library Annual Report Fiscal Year 2023Annual report of the Lamar Soutter Library at UMass Chan Medical School, covering fiscal year July 1, 2022-June 30, 2023.
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The Relationship is the MedicineIntroduction: I am writing a short reflection below as a companion piece to last week's story by Merredith. It follows along the lines of sayings in our specialty, like - "Don't just do something, stand there." I created a whole lecture on the power of "Doing Nothing." We all know, it is not really nothing, it is a lot of something, just not things that can be billed for or objectively evaluated necessarily. But they can be powerful.
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Equitable reach: Patient and professional recommendations for interventions to prevent perinatal depression and anxietyObjective: Perinatal depression and anxiety are the most common complications in the perinatal period and disproportionately affect those experiencing economic marginalization. Fewer than 15% of individuals at risk for perinatal depression are referred for preventative counseling. The goal of this study was to elicit patient and perinatal care professionals' perspectives on how to increase the reach of interventions to prevent perinatal depression and anxiety among economically marginalized individuals. Methods: We conducted qualitative interviews with perinatal individuals with lived experience of perinatal depression and/or anxiety who were experiencing economic marginalization (n = 12) and perinatal care professionals and paraprofessionals (e.g., obstetrician/gynecologists, midwives, doulas; n = 12) serving this population. Three study team members engaged a "a coding consensus, co-occurrence, and comparison," approach to code interviews. Results: Perinatal individuals and professionals identified prevention intervention delivery approaches and content to facilitate equitable reach for individuals who are economically marginalized. Factors influential included availability of mental health counselors, facilitation of prevention interventions by a trusted professional, digital health options, and options for mental health intervention delivery approaches. Content that was perceived as increasing equitable intervention reach included emphasizing stigma reduction, using cultural humility and inclusive materials, and content personalization. Conclusions: Leveraging varied options for mental health intervention delivery approaches and content could reach perinatal individuals experiencing economic marginalization and address resource considerations associated with preventative interventions.
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Non-canonical amino acid incorporation into AAV5 capsid enhances lung transduction in miceGene therapy using recombinant adeno-associated virus (rAAV) relies on safe, efficient, and precise in vivo gene delivery that is largely dependent on the AAV capsid. The proteinaceous capsid is highly amenable to engineering using a variety of approaches, and most resulting capsids carry substitutions or insertions comprised of natural amino acids. Here, we incorporated a non-canonical amino acid (ncAA), Nε-2-azideoethyloxycarbonyl-L-lysine (also known as NAEK), into the AAV5 capsid using genetic code expansion, and serendipitously found that several NAEK-AAV5 vectors transduced various cell lines more efficiently than the parental rAAV5. Furthermore, one NAEK-AAV5 vector showed lung-specific transduction enhancement following systemic or intranasal delivery in mice. Structural modeling suggests that the long side chain of NAEK may impact on the 3-fold protrusion on the capsid surface that plays a key role in tropism, thereby modulating vector transduction. Recent advances in genetic code expansion have generated synthetic proteins carrying an increasing number of ncAAs that possess diverse biological properties. Our study suggests that ncAA incorporation into the AAV capsid may confer novel vector properties, opening a new and complementary avenue to gene therapy vector discovery.
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First United States multicenter experience with the new-generation FRED X surface-modified flow diversion stent: feasibility, safety, and short-term efficacyObjective: Flow diversion created a paradigm shift in the treatment of intracranial aneurysms. The new flow redirection endoluminal device with X technology (FRED X) is the latest update of the recent Food and Drug Administration-approved FRED. The FRED X is engineered to reduce material thrombogenicity and enhance vessel healing. In this study, the authors aimed to evaluate the feasibility and early safety and efficacy of the new FRED X. Methods: The authors retrospectively collected and analyzed data from patients who had undergone flow diversion with the new FRED X at four tertiary cerebrovascular centers in the United States from February 2022 through July 2022. Results: Forty-four patients with 45 aneurysms treated using 46 devices comprised the overall study cohort and were divided into two groups: 39 patients with unruptured aneurysms and 5 patients with ruptured aneurysms. The mean patient age was 57.7 ± 9.1 years, and most patients were female (84%). Ninety-one percent of the aneurysms were saccular, with the majority (93%) located in the anterior circulation, specifically the posterior communicating (27%) and carotid ophthalmic (27%) territories. The mean maximum aneurysm diameter was 5.6 ± 4.6 mm, and 20% of the lesions had been previously treated. The mean procedure time was 61.6 minutes, with a mean cumulative fluoroscopy time of 24.6 minutes. Additionally, 7% of the lesions received adjunct treatment. Stent placement was successful in 100% of cases, achieving good wall apposition and complete neck coverage. Further, immediate aneurysm contrast stasis > 90% was observed in 61% of cases. Symptomatic postoperative complications occurred in 3 patients in the unruptured cohort and 1 patient in the ruptured cohort. All patients in the study were discharged on dual antiplatelet regimens with a modified Rankin Scale score of 0. At 6 months after treatment, 89% of cases had adequate occlusion, with < 6% of cases having asymptomatic in-stent stenosis. All patients had excellent functional outcomes. Conclusions: FRED X for the treatment of an intracranial aneurysm is technically feasible alone or in conjunction with intrasaccular embolization. In addition, the study results showed very promising early safety and efficacy. Follow-up studies should establish the long-term safety and efficacy profiles of this new stent.
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Getting Back in the SaddleIntroduction: This week I have a story from Merredith Moreau, a nurse practitioner who works with me at the Homeless Outreach and Advocacy Program at the Family Health Center of Worcester. She told us this story at one of our staff meetings where we share successes to remind us all why we do this work. I also love this reflection as it is exactly what the Family Medicine Moments was intended for - to celebrate our little triumphs that we garner each day, each week, year by year, moment by moment. This is our antidote to burnout - this moment that Merredith has captured below is what helps us to thrive. Pure joy. Enjoy.
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"Like One Long Battle:" Employee Perspectives of the Simultaneous Impact of COVID-19 and an Electronic Health Record TransitionBackground: Healthcare organizations regularly manage external stressors that threaten patient care, but experiences handling concurrent stressors are not well characterized. Objective: To evaluate the experience of Veterans Affairs (VA) clinicians and staff navigating simultaneous organizational stressors-an electronic health record (EHR) transition and the COVID-19 pandemic-and identify potential strategies to optimize management of co-occurring stressors. Design: Qualitative case study describing employee experiences at VA's initial EHR transition site. Participants: Clinicians, nurses, allied health professionals, and local leaders at VA's initial EHR transition site. Approach: We collected longitudinal qualitative interview data between July 2020 and November 2021 once before and 2-4 times after the date on which the health system transitioned; this timing corresponded with local surges of COVID-19 cases. Interviewers conducted coding and analysis of interview transcripts. For this study, we focused on quotes related to COVID-19 and performed content analysis to describe recurring themes describing the simultaneous impact of COVID-19 and an EHR transition. Key results: We identified five themes related to participants' experiences: (1) efforts to mitigate COVID-19 transmission led to insufficient access to EHR training and support, (2) clinical practice changes in response to the pandemic impacted EHR workflows in unexpected ways, (3) lack of clear communication and inconsistent enforcement of COVID-19 policies intensified pre-existing frustrations with the EHR, (4) managing concurrent organizational stressors increased work dissatisfaction and feelings of burnout, and (5) participants had limited bandwidth to manage competing demands that arose from concurrent organizational stressors. Conclusion: The expected challenges of an EHR transition were compounded by co-occurrence of the COVID-19 pandemic, which had negative impacts on clinician experience and patient care. During simultaneous organizational stressors, health care facilities should be prepared to address the complex interplay of two stressors on employee experience.
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Integrating Equity Into Bicycle Infrastructure, Planning, and Programming: A Mixed Methods Exploration of Implementation Among Participants in the Bicycle Friendly Community ProgramIntroduction: Integrating equity considerations into bicycle infrastructure, planning, and programming is essential to increase bicycling and reduce physical inactivity-related health disparities. However, little is known about communities' experiences with activities that promote equity considerations in bicycle infrastructure, planning, and programming or about barriers and facilitators to such considerations. The objective of this project was to gain in-depth understanding of the experiences, barriers, and facilitators that communities encounter with integrating equity considerations into bicycle infrastructure, planning, and programming. Methods: We administered a web-based survey in 2022 to assess communities' experiences with 31 equity-focused activities in 3 areas: 1) community engagement, education, events, and programming (community engagement); 2) data collection, evaluation, and goal setting (data); and 3) infrastructure, facilities, and physical amenities (infrastructure). Respondents were people who represented communities in the US that participated in the League of American Bicyclists' Bicycle Friendly Community (BFC) Program. We then conducted 6 focus groups with a subset of survey respondents to explore barriers and facilitators to implementing equity-focused activities. Results: Survey respondents (N = 194) had experience with a mean (SD) of 5.9 (5.7) equity-focused activities. Focus group participants (N = 30) identified themes related to community engagement (outreach to and engagement of underrepresented communities, cultural perceptions of bicycling, and funding and support for community rides and programs); data (locally relevant data); and infrastructure (political will, community design, and infrastructure). They described barriers and facilitators for each. Conclusion: Communities are challenged with integrating equity into bicycle infrastructure, planning, and programming. Multicomponent strategies with support from entities such as the BFC program will be required to make progress.
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Surface modification of neurovascular stents: from bench to patientFlow-diverting stents (FDs) for the treatment of cerebrovascular aneurysms are revolutionary. However, these devices require systemic dual antiplatelet therapy (DAPT) to reduce thromboembolic complications. Given the risk of ischemic complications as well as morbidity and contraindications associated with DAPT, demonstrating safety and efficacy for FDs either without DAPT or reducing the duration of DAPT is a priority. The former may be achieved by surface modifications that decrease device thrombogenicity, and the latter by using coatings that expedite endothelial growth. Biomimetics, commonly achieved by grafting hydrophilic and non-interacting polymers to surfaces, can mask the device surface with nature-derived coatings from circulating factors that normally activate coagulation and inflammation. One strategy is to mimic the surfaces of innocuous circulatory system components. Phosphorylcholine and glycan coatings are naturally inspired and present on the surface of all eukaryotic cell membranes. Another strategy involves linking synthetic biocompatible polymer brushes to the surface of a device that disrupts normal interaction with circulating proteins and cells. Finally, drug immobilization can also impart antithrombotic effects that counteract normal foreign body reactions in the circulatory system without systemic effects. Heparin coatings have been explored since the 1960s and used on a variety of blood contacting surfaces. This concept is now being explored for neurovascular devices. Coatings that improve endothelialization are not as clinically mature as anti-thrombogenic coatings. Coronary stents have used an anti-CD34 antibody coating to capture circulating endothelial progenitor cells on the surface, potentially accelerating endothelial integration. Similarly, coatings with CD31 analogs are being explored for neurovascular implants.
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Phosphaturic mesenchymal tumor: two cases highlighting differences in clinical and radiologic presentationPhosphaturic mesenchymal tumors are rare, usually benign neoplasms that occur in the soft tissue or bone and are the cause of nearly all cases of tumor-induced osteomalacia. Tumor-induced osteomalacia due to phosphaturic mesenchymal tumor is a challenging diagnosis to make-patients present with variable clinical and radiologic findings and the culprit neoplasm is often small and can occur anywhere head to toe. We present two cases of phosphaturic mesenchymal tumor in the scapular body and plantar foot. In both cases, the patient endured years of debilitating symptoms before a tissue diagnosis was eventually reached. Descriptions of clinical presentation, laboratory workup, surgical resection, and imaging characteristics, with a focus on CT, MRI, and functional imaging, are provided to assist with the diagnosis and management of this rare entity. A brief review of current literature and discussion of the differential diagnoses of phosphaturic mesenchymal tumor is also provided.
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PAM-flexible genome editing with an engineered chimeric Cas9CRISPR enzymes require a defined protospacer adjacent motif (PAM) flanking a guide RNA-programmed target site, limiting their sequence accessibility for robust genome editing applications. In this study, we recombine the PAM-interacting domain of SpRY, a broad-targeting Cas9 possessing an NRN > NYN (R = A or G, Y = C or T) PAM preference, with the N-terminus of Sc + +, a Cas9 with simultaneously broad, efficient, and accurate NNG editing capabilities, to generate a chimeric enzyme with highly flexible PAM preference: SpRYc. We demonstrate that SpRYc leverages properties of both enzymes to specifically edit diverse PAMs and disease-related loci for potential therapeutic applications. In total, the approaches to generate SpRYc, coupled with its robust flexibility, highlight the power of integrative protein design for Cas9 engineering and motivate downstream editing applications that require precise genomic positioning.
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Measuring The Enduring Imprint Of Structural Racism On American NeighborhoodsA long history of discriminatory policies in the United States has created disparities in neighborhood resources that shape ethnoracial health inequities today. To quantify these differences, we organized publicly available data on forty-two variables at the census tract level within nine domains affected by structural racism: built environment, criminal justice, education, employment, housing, income and poverty, social cohesion, transportation, and wealth. Using data from multiple sources at several levels of geography, we developed scores in each domain, as well as a summary score that we call the Structural Racism Effect Index. We examined correlations with life expectancy and other measures of health for this index and other commonly used area-based indices. The Structural Racism Effect Index was more strongly associated with each health outcome than were the other indices. Its domain and summary scores can be used to describe differences in social risk factors, and they provide powerful new tools to guide policies and investments to advance health equity.
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Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration [preprint]Parkinson's disease (PD) targets some dopamine (DA) neurons more than others. Sex differences offer insights, with females more protected from DA neurodegeneration. The mammalian vesicular glutamate transporter VGLUT2 and Drosophila ortholog dVGLUT have been implicated as modulators of DA neuron resilience. However, the mechanisms by which VGLUT2/dVGLUT protects DA neurons remain unknown. We discovered DA neuron dVGLUT knockdown increased mitochondrial reactive oxygen species in a sexually dimorphic manner in response to depolarization or paraquat-induced stress, males being especially affected. DA neuron dVGLUT also reduced ATP biosynthetic burden during depolarization. RNA sequencing of VGLUT+ DA neurons in mice and flies identified candidate genes that we functionally screened to further dissect VGLUT-mediated DA neuron resilience across PD models. We discovered transcription factors modulating dVGLUT-dependent DA neuroprotection and identified dj-1β as a regulator of sex-specific DA neuron dVGLUT expression. Overall, VGLUT protects DA neurons from PD-associated degeneration by maintaining mitochondrial health.
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UMCCTS Newsletter, October 2023This is the October 2023 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
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LGBTQ+ health research guides: a multi-institutional analysis of usage patterns and user information needsObjective: LGBTQ+ health research guides can strengthen the LGBTQ+ community through connecting people to quality health services and information, and previous studies have recommended that health sciences libraries create and maintain these guides. Little evidence exists, though, on how these guides are used and how well they meet the needs of LGBTQ+ users. Using retrospective data retrieved from multiple LGBTQ+ health research guides, we examined the categories of LGBTQ+ health information most used, as well as how often guides were accessed. Based on these results, we hope to find patterns which can lead to best practices for libraries. Methods: Five North American academic health sciences libraries contributed select usage data from their LGBTQ+ health research guides, covering a three-year period (July 2018-June 2021). Data was analyzed in two ways. Firstly, the 20 most-clicked resources from each guide were categorized through open coding, to assess if certain information resource categories were more popular among guide users, allowing for inference of user needs. A time-series analysis was also conducted for two sites, using the Classical Seasonal Decomposition by Moving Averages method, to provide deeper insights into the data. Results: Open coding data showed consumer health information resources were used more often than other health resource categories. Resources from more locally based organizations and those with provider and services information were heavily used, indicating that users may be looking for information connecting to local health services and providers. The time series analysis allowed the potential positive effect of guide promotion to be showcased in ways that would not have been clear from the raw data. Conclusion: This study shows that people are accessing LGBTQ+ consumer health information through academic library research guides, with a preference for local information. Guide usage appears to be positively driven by outreach within one’s institution and to the greater community. Locating external partners may increase guide impact and provide important links to local resources and services.
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Physical activity regulates the immune response to breast cancer by a hematopoietic stem cell-autonomous mechanism [preprint]Physical activity is a modifiable lifestyle factor that is associated with a decreased risk for the development of breast cancer. While the exact mechanisms for the reduction in cancer risk due to physical activity are largely unknown, it is postulated that the biological reduction in cancer risk is driven by improvements in inflammation and immune function with exercise. Hematopoietic stem cells (HSCs) are the progenitor for all of the cells of the immune system and are involved in cancer immunosurveillance through differentiation into cytotoxic cell population. In this study, we investigate the role of physical activity (PA) in a spontaneously occurring model of breast cancer over time, with a focus on tumor incidence, circulating and tumor-infiltrating immune cells as well gene expression profiles of tumors and hematopoietic stem cells. Furthermore, we show that, in addition to a direct effect of PA on the immune cells of tumor-bearing mice, PA reduces the oxidative stress in HSCs of wildtype and tumor-bearing mice, and by doing so, alters the differentiation of the HSCs towards T cells in order to enhance cancer immunosurveillance.