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Welcome to the new eScholarship@UMassChan! eScholarship@UMassChan is a freely available digital repository offering worldwide access to the research and scholarly work of the UMass Chan Medical School community. We welcome submissions from our faculty, researchers, staff, and students. eScholarship@UMassChan is a service of the Lamar Soutter Library, Worcester, MA, USA.
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A tale of two migrations: a medical library case reportLaunched in 2006, the eScholarship@UMassChan institutional repository has been an important digital platform at UMass Chan Medical School, hosting faculty research, student research, and unique original publications and scholarship. In June 2021, UMass Chan’s Lamar Soutter Library decided to migrate eScholarship@UMassChan from the bepress Digital Commons platform to two separate hosted platforms. Most content – over 25,000 items representing faculty and staff publications, theses and dissertations, conference proceedings, and departmental and project collections – moved to Open Repository, a DSpace repository platform hosted by Atmire. The Janeway publishing platform became the new home for the open access, peer-reviewed journals and ebook chapters actively published through eScholarship@UMassChan. Both migrations were completed in September 2022. This lightning talk will briefly cover the migration process, challenges encountered and lessons learned.
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3 Tips to Improve Communication with Your Youth & Young AdultsThis tip sheet provides parents and allies of youth and young adults with lived experience of a mental health condition tips be able to improve their connection with them. This tip sheet was developed as a collaboration between the family member and young adult advisory boards that work with the Transitions to Adulthood Center for Research. The tips are based on advisory board members’ real experiences.
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Introns Safeguard mRNA Expression in the C. elegans Germline against Multiple Surveillance MechanismsOrganisms employ sophisticated systems for genome defense against foreign and potentially harmful elements, while leaving room for gene adaptation. In animals, conserved PIWI Argonautes use genomically encoded small RNA guides (called piRNAs) to detect and silence foreign nucleotide sequences, such as transposons. In Caenorhabditis elegans, the detection of foreign transcripts by PIWI triggers the production of a second class of antisense small RNAs (called 22G-RNAs), which guide worm-specific Argonautes (WAGOs) to direct transcriptional and posttranscriptional silencing. PIWI-piRNA complexes recognize targets via imperfect base-pairing, which could threaten the expression of endogenous host genes. Nevertheless, worms use yet a third small RNA pathway involving the Argonaute CSR-1 to license endogenous germline gene expression and prevent inappropriate silencing by the PIWI pathway. How and why certain genes are licensed remains unknown. Here I show that introns and, by inference, mRNA splicing protect messenger RNAs from germline silencing. Intronless reporters encounter 22G-RNA-dependent and -independent silencing mechanisms, which we collectively termed “intronless silencing.” Genetic studies revealed that primary Argonautes, e.g., PIWI, are not required for the 22G-RNA-dependent intronless silencing mechanism, suggesting that intronless reporters are silenced by default. Nuclear and cytoplasmic WAGOs enabled the transmission of silencing from an intronless allele to a homologous intron-containing allele. The 22G-RNA-independent mechanism not only reduced intronless reporter mRNA levels, compared to the homologous intron-containing genes, but also prevented polyadenylation and nuclear export. Cis-acting elements that promote export from the nucleus nevertheless failed to fully activate expression of intronless reporters, suggesting additional layers of regulation in the small RNA-independent mechanism of intronless silencing. These findings suggest that multiple germline surveillance systems monitor transcript splicing, reveal a protective role of splicing in transcript licensing, and provide evidence for a splicing-dependent, sequence-independent mode of Argonaute programming.
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Trauma-Informed CareThis presentation is part of the PEER Liberia Behavioral Health Lecture Series. It provides an overview for physicians of trauma-informed care, including: What is trauma and how does it affect people’s development, their brains and their behavior? How does a trauma history “show up” in medical settings? How do we respond to it? How do we take care of ourselves when working with people who have had traumatic experiences?
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A Prognostic Model to Predict Survival in Children with Ebola Virus DiseaseRepeated outbreaks of Ebola Virus Disease (EVD) in low-resource settings emphasize the importance of evidence-based guidelines to direct treatment. Previous research has shown that EVD causes high case fatality rates (CFRs) in young children, yet there are limited data focusing on pediatric patients. Here we present a prognostic model to predict mortality in children who are Ebola-positive using information available during the first 48 hours after admission to the treatment center. A logistic regression model was trained on triage data from the Ebola Data Platform, a repository of retrospective patient data compiled from actors that responded to the West African EVD outbreak from 2014-2016. Patients <18 years of age were included in the analysis (N=579) and the CFR was 40%. Overall 13% of data were missing, and multiple imputation was used to estimate missing values. Variable selection using elastic net regularization selected age, CT value, bleeding, breathlessness, bone or muscle pain, anorexia, swallowing problems, and diarrhea as predictors. Bootstrap validation yielded an optimism-corrected area under the curve (AUC) of 0.75 (95% CI: 0.71-0.79). The model was externally validated using data from the current EVD outbreak in the Democratic Republic of the Congo (DRC). While the model’s discriminative ability on the DRC data was similar (AUC=0.75, 95% CI: 0.63-0.87) to the training data, calibration was poor. We recalibrated the model by re-estimating the intercept and slope, and further improved model performance by including aspartate aminotransferase (AST) as a biomarker. The updated model with AST as an added predictor has an AUC of 0.90 (95% CI: 0.77-1). These preliminary results are encouraging but should be interpreted with caution because of limited availability of AST values in the validation data (n=25). The prognostic model described here has promising potential for use in a clinical setting and will continue to be validated as more data becomes available. Future efforts will focus on integrating the validated model into mHealth tools to aid clinicians in making informed, data-driven decisions about patient care.
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Lamar Soutter Library Annual Report Fiscal Year 2022Annual report of the Lamar Soutter Library at UMass Chan Medical School, covering fiscal year July 1, 2021-June 30, 2022.
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Sterilization of Polymeric Implants: Challenges and OpportunitiesDegradable and environmentally responsive polymers have been actively developed for drug delivery and regenerative medicine applications, yet inadequate consideration of their compatibility with terminal sterilization presents notable barriers to clinical translation. This Review discusses industry-established terminal sterilization methods and aseptic processing and contrasts them with innovative approaches aimed at preserving the integrity of polymeric implants. Regulatory guidelines, fiscal considerations, and potential pitfalls are discussed to encourage early integration of sterility regulatory considerations in material designs.
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Ubiety in nursing practice: Making each patient the star of the minuteNurses work in a fast-paced environment with increased expectations and distractions. Ubiety is a new concept that describes how nurses care for one patient at a time amid distractions. The purpose of this study was to explore the experiences of exemplar registered nurses (Daisy Award nurse nominees) in practicing ubiety when caring for patients in an acute care setting. Qualitative data was collected through semistructured interviews and analyzed. "Making each patient the star of the minute" emerged as the main theme and included five subthemes which highlight how nurses practice ubiety: (1) anticipating and managing distractions, (2) putting my whole self in, (3) nurse self-preservation, (4) my nursing identity, and (5) favorable practice environment. Results of this study highlight the importance of developing skills to anticipate patient care needs and supporting individual self-preservation strategies for nurses.
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Web-Based System to Capture Consistent and Complete Real-world Data of Physical Therapy Interventions Following Total Knee Replacement: Design and Evaluation StudyBackground: Electronic health records (EHRs) have the potential to facilitate consistent clinical data capture to support excellence in patient care, quality improvement, and knowledge generation. Despite widespread EHR use, the vision to transform health care system and its data to a "learning health care system" generating knowledge from real-world data is limited by the lack of consistent, structured clinical data. Objective: The purpose of this paper was to demonstrate the design of a web-based structured clinical intervention data capture system and its evaluation in practice. The use case was ambulatory physical therapy (PT) treatment after total knee replacement (TKR), one of the most common and costly procedures today. Methods: To identify the PT intervention type and intensity (or dose) used to treat patients with knee arthritis following TKR, an iterative user-centered design process refined an initial list of PT interventions generated during preliminary chart reviews. Input from practicing physical therapists and national and international experts refined and categorized the interventions. Next, a web-based, hierarchical structured system for intervention and intensity documentation was designed and deployed. Results: The PT documentation system was implemented by 114 physical therapists agreeing to record all interventions at patient visits. Data for 161 patients with 2615 PT visits were entered by 83 physical therapists. No technical problems with data entry were reported, and data entry required less than 2 minutes per visit. A total of 42 (2%) interventions could not be categorized and were recorded using free text. Conclusions: The use of user-centered design principles provides a road map for developing clinically feasible data capture systems that employ structured collection of uniform data for use by multiple practitioners across institutions to complement and augment existing EHRs. Secondarily, these data can be analyzed to define best practices and disseminate knowledge to practice.
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Individuals with Sickle Cell Disease Using SBAR as a Communication Tool: A Pilot StudyBackground: Sickle cell disease (SCD) is a hemoglobinopathy that causes debilitating pain. Patients often report dissatisfaction during care seeking for pain or a sickle cell crisis (SCC). The Theory of Self-Care Management for SCD conceptualizes assertive communication as a self-care management resource that improves healthcare outcomes. Objectives: This pilot study aimed to determine whether adults with SCD could learn to use the Situation, Background, Assessment, Recommendation (SBAR) communication method using a web-based trainer, and it aimed to determine their perceptions of the training. Methods: The participants included n = 18 adults with SCD. Inter-rater reliability (IRR) among three reviewers was used to evaluate the participants’ ability to respond as expected to prompts using SBAR communication within the web-based platform. Content analysis was used to describe the participants’ perspectives of the acceptability of using the SBAR patient–HCP communication simulation. Results: The SBAR IRR ranged from 64 to 94%, with 72% to 94% of the responses being evaluated as the using of the SBAR component as expected. The predominant themes identified were (1) Patient–Provider Communication and Interaction; (2) Patients want to be Heard and Believed; (3) Accuracy of the ED Experience and Incorporating the Uniqueness of each Patient; and (4) the Overall Usefulness of the Video Trainer emerging. Conclusions: This pilot study supported the usefulness and acceptability of a web-based intervention in training adults with SCD to use SBAR to enhance patient–HCP communication. Enhancing communication may mitigate the barriers that individuals with SCD encounter during care seeking and improve the outcomes. Additional studies with larger samples need to be conducted.
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Scrotal UltrasoundThis presentation is part of the PEER Liberia Radiology Lecture Series. It provides an overview for clinicians of scrotal ultrasound, including: normal anatomy and technique, acute scrotal pain investigation, scrotal trauma, evaluation of scrotal swelling or mass, and common incidental findings.
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Investigating Cell-Autonomous Mechanisms of Microglia Dysfunction in PFN1-ALSAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by loss of motor neurons. Cumulative evidence shows that microglia contribute to disease progression, but the underlying mechanisms are unclear. Several ALS-related genes are highly expressed in microglia compared to neurons, including profilin-1 (PFN1). This raises the possibility that ALS-linked PFN1 mutations could induce microglia cell-autonomous dysfunction. Here, I sought to interrogate this possibility by differentiating human pluripotent stem cells (iPSCs) into microglia-like cells (iMGs). My work uncovered that ALS-PFN1 iMGs accumulate undegraded phagocytosed cargo in endo-lysosomal compartments which is recapitulated in vivo. ALS-PFN1 iMGs also exhibit dysregulation in the expression and cellular localization of crucial components of the endo-lysosomal pathway, impairments in the autophagy flux, and accumulation of lipid droplets. Intriguingly, rapamycin treatment ameliorates the accumulation of phagocytosed material in ALS-PFN1 iMGs and rescues the defects in the autophagy pathway, suggesting that an impaired autophagy flux contributes to ALS-PFN1-linked defects in microglial phagocytosis. In vitro experimentation uncovered that PFN1 interacts with phosphatidylinositol-3phosphate, a signaling molecule essential for autophagy and phagocytosis, and that this interaction is altered when PFN1 is mutated in ALS. Collectively, these findings implicate that ALS-PFN1 causes microglia dysfunction by hindering the autophagy flux, perturbing the endo-lysosomal pathway, and, in turn, causing delays in the degradation process during phagocytosis and inducing lipid dysmetabolism. These alterations may be partially driven by ALS-PFN1 distorted interactions with phosphoinositides. My work provides insight into PFN1 biology and opens new perspectives regarding microglia cell-autonomous defects in ALS that may contribute to neurodegeneration.
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Investigating HNF4A in Intestinal Homeostasis and InflammationHepatocyte nuclear factor 4 alpha (HNF4A) is a highly conserved nuclear receptor that has been associated with ulcerative colitis. In mice, HNF4A is indispensable for the maintenance of intestinal homeostasis, yet the underlying mechanisms are poorly characterized. Here we demonstrate that the expression of HNF4A in intestinal epithelial cells (IECs) is required for the proper development and composition of the intraepithelial lymphocyte (IEL) compartment. HNF4A directly regulates expression of immune signaling molecules including butyrophilin-like (Btnl) 1, Btnl6, H2-T3, and Clec2e that control IEC-IEL crosstalk. HNF4A selectively enhances the expansion of natural IELs that are TCRγδ+ or TCRαβ+CD8αα+ to shape the composition of IEL compartment. In the small intestine, HNF4A cooperates with its paralog HNF4G, to drive expression of immune signaling molecules. Moreover, the HNF4A-BTNL regulatory axis is conserved in human IECs. Collectively, these findings underscore the importance of HNF4A as a conserved transcription factor controlling IEC-IEL crosstalk and suggest that HNF4A maintains intestinal homeostasis through regulation of the IEL compartment.
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Feasibility of At-Home Serial Testing Using Over-the-Counter SARS-CoV-2 Tests With a Digital Smartphone App for Assistance: Longitudinal Cohort StudyBackground: The ongoing SARS-CoV-2 pandemic necessitates the development of accurate, rapid, and affordable diagnostics to help curb disease transmission, morbidity, and mortality. Rapid antigen tests are important tools for scaling up testing for SARS-CoV-2; however, little is known about individuals' use of rapid antigen tests at home and how to facilitate the user experience. Objective: This study aimed to describe the feasibility and acceptability of serial self-testing with rapid antigen tests for SARS-CoV-2, including need for assistance and the reliability of self-interpretation. Methods: A total of 206 adults in the United States with smartphones were enrolled in this single-arm feasibility study in February and March 2021. All participants were asked to self-test for COVID-19 at home using rapid antigen tests daily for 14 days and use a smartphone app for testing assistance and to report their results. The main outcomes were adherence to the testing schedule, the acceptability of testing and smartphone app experiences, and the reliability of participants versus study team's interpretation of test results. Descriptive statistics were used to report the acceptability, adherence, overall rating, and experience of using the at-home test and MyDataHelps app. The usability, acceptability, adherence, and quality of at-home testing were analyzed across different sociodemographic, age, and educational attainment groups. Results: Of the 206 enrolled participants, 189 (91.7%) and 159 (77.2%) completed testing and follow-up surveys, respectively. In total, 51.3% (97/189) of study participants were women, the average age was 40.7 years, 34.4% (65/189) were non-White, and 82% (155/189) had a bachelor's degree or higher. Most (n=133/206, 64.6%) participants showed high testing adherence, meaning they completed over 75% of the assigned tests. Participants' interpretations of test results demonstrated high agreement (2106/2130, 98.9%) with the study verified results, with a κ score of 0.29 (P<.001). Participants reported high satisfaction with self-testing and the smartphone app, with 98.7% (157/159) reporting that they would recommend the self-test and smartphone app to others. These results were consistent across age, race/ethnicity, and gender. Conclusions: Participants' high adherence to the recommended testing schedule, significant reliability between participants and study staff's test interpretation, and the acceptability of the smartphone app and self-test indicate that self-tests for SARS-CoV-2 with a smartphone app for assistance and reporting is a highly feasible testing modality among a diverse population of adults in the United States.
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A HaikuI asked and you responded. Thanks to Patrick Tolosky, a PGY2 at Hahnemann Family Health Center, who wrote this brief yet telling haiku about his experience as a resident being transformed into a full-fledged primary care doctor. Two nights ago, at the Cottle lecture for the Worcester District Medical Society, I invoked Atul Gawande and challenged the audience to write something. I then mentioned that writing a 6-word story, 55-word story or a haiku is a pithy way to do this and achieve a sense of satisfaction from your musings at the end of a long clinical day. Patrick gave it a go. See what you think.
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Leveraging Multi-Omic Data to Characterize Cis-Regulatory Elements and Investigate Their Roles in Gene RegulationRegulatory elements are non–coding genomic regions that interact with transcription factors to govern when, where, and how much of each gene is expressed. Understanding regulatory elements is essential to understanding mammalian gene regulation; however, our understanding of regulatory syntax is incomplete. Here, we have leveraged multi-omic data to characterize regulatory elements and investigate their roles in gene regulation. We examined a subset of CG-rich promoters exhibiting ubiquitous chromatin accessibility. While most promoters are cell-type specific, these promoters are enriched in cell-essential genes. To maintain universal transcription, they recruit distinct TFs. Furthermore, ubiquitous and cell-type specific promoters are enriched in different sets of Mendelian disease genes, suggesting different contributions to disease susceptibility. We investigated DNA methylation patterns among different categories of regulatory elements during mouse embryonic development and identified a novel class of highly conserved bivalent enhancers that are hypermethylated in cancers, suggesting a unique underlying mechanism involved in cancer. We developed a method to annotate transcription-initiating enhancers. We found that transcribed enhancers mark core enhancer regions, but flanking enhancers also contribute to overall activity. Next, we examined the evolutionary conservation pattern of regulatory elements across 240 mammal species. While conserved regulatory elements are associated with essential genes, recently evolving elements are involved in a species’ interaction with its surroundings. Finally, we performed genome-wide annotation of chromatin states across hundreds of samples, building a regulatory landscape in human and mouse genomes. Together, these works contribute to the characterization of regulatory elements and demonstrate distinct mechanisms of different regulatory subclasses.
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Lost in Transition: The Journey from Pediatric to Adult Care for Youth with Mental Health ConditionsNearly one out of three (30.6%) young adults (18–25 years) experience mental illness (NIMH). In the United States suicide is the third leading cause of death for young people. Transition age youth (16–25 years) with mental health conditions such as mood disorders, anxiety disorders, and psychotic disorders, experience substantial adversity during the shift from pediatric to adult health care. Research by our team has shown that youth with mental health conditions utilize less outpatient care as they emerge into adulthood. These results echo the American Psychiatric Association position statement that transition age youth are “underserved in current mental health systems”. Understanding provider perspectives to caring for this unique patient population may help to increase health care utilization and quality of care for transition age youth with mental health conditions. This product offers providers real-world tips on what they can do to help and advocate for based on our work.
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Our Work at Its BestIn response to my request for you all to send me your prose, poetry, artwork, etc., Lucy Candib, long time family physician of Family Health Center for Worcester, has sent the photo below. She included these words when she sent it: I have had this photo since around 2006. I don’t know where it came from or who the doctor and patient are. To me it represents the relational quality of our work at its best. We have done some on-line searching and can't identify the subjects or the photographer. I do agree - it does show us at our best. As Ron Epstein would encourage - do some deep looking of the image. Think about what appeals to you. When was the last time you had a moment like this? Was that recent enough? How can you be sure to have this happen often enough, even in our busy schedules and lives.
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Tips to Help People Living with Mental Health Conditions Stop Using Tobacco ProductsApproximately fifty million people living in the U.S. use tobacco products. According to the Massachusetts Department of Public Health, the leading cause of preventable death and disease in the state is smoking. As of 2017, 13.7% of Massachusetts adults were current smokers, with 13.5% of white adults, 15.7% of Black adults, and 18.3% of Hispanic adults reporting smoking cigarettes.1 One study found that an average smoker may attempt to quit 30 or more times before success is achieved with abstinence from smoking for at least one year. This tip sheet provides general and evidence-based tips on how to help individuals living with mental health conditions cease using tobacco products.
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UMCCTS Newsletter, October 2022This is the October 2022 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
