RSS 1.0eScholarship@UMassChan
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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Adulting Shorts: The "TEA" on IEPs Part 3This 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 3 focuses on Mateo creating a career goal and steps to reach it. Parts 1 and 2 can be found on our website: https://www.umassmed.edu/TransitionsACR/publication/comic/
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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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Negative regulation of innate immunity by novel nuclear receptor NHR-42/NR1D1 with implications in infection survival, metabolism, and fitnessDetection of pathogenic signals leads to extensive changes in cellular transcriptional programs mediated by transcription factors. Positive and negative regulators of this host defense response work together to maintain immune homeostasis. Over the past two decades, several evolutionary conserved positive regulators of innate immunity have been identified in C. elegans. However, negative regulators remain unknown, and repression of the host defense response poorly understood. We previously discovered that HLH-30/TFEB is a positive regulator of immunity in C. elegans and murine macrophages after S. aureus infection, respectively. In this study, I identify nhr-42 as a negative regulator of immunity functioning downstream of HLH-30, with major implications for host survival, metabolism, and fitness. In nhr-42 mutants, several host defense genes, such as antimicrobial peptides, C-type lectins, and lysozymes, are upregulated constitutively. This enables nhr-42 mutants to have enhanced survival and lower pathogen burden after infection compared to wild type animals. I show that nhr-42 expression is induced in the pharynx and pharyngeal-intestinal valve after infection. Furthermore, I find that antimicrobial peptides abf-2 and cnc-2 are required for enhanced survival and lower pathogen burden in nhr-42 mutants. Moreover, induction of nhr-42 after infection leads to upregulation of lipid catabolism genes involved in beta-oxidation, driving lipid mobilization. These data show that nhr-42 functions to limit the host defense response to maintain immune homeostasis and reallocate energy resources through lipid mobilization towards other cellular processes. Additionally, I identify Nr1d1 (Rev-Erbα) as a functional homolog of nhr-42. I show that Nr1d1 functions downstream of TFEB to negatively regulate pro-inflammatory cytokines Il-6 and Il1b in macrophages, after S. aureus infection. These data open up new research avenues into mammalian nuclear receptor mediated regulation of immunity.
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Prescribed Medications and Healthcare Resource Utilization in Reproductive-Age Women and Men with Rheumatic DiseaseBackground: Axial spondyloarthritis (axSpA), rheumatoid arthritis (RA), and psoriatic arthritis (PsA) are the most prevalent forms of chronic immune-mediated inflammatory arthritis, affecting approximately 0.3-1.4% of adults in the US. These rheumatic diseases (RD) have an early age of onset and may have a significant impact on women and men of reproductive ages, particularly during pregnancy and the postpartum period. Methods: Using the IBM® MarketScan® Commercial Claims and Encounters Database (2013-2018), this dissertation first described sex differences in time to non-steroidal anti-inflammatory drugs (NSAIDs) or biologic disease modifying antirheumatic drugs (bDMARDs) initiation among patients with axSpA. We then evaluated co-management with rheumatology and bDMARD prescriptions filled during pregnancy among pregnant women with axSpA, RA, and PsA. Finally, we evaluated postpartum depression (PPD) rates among reproductive-age women with axSpA, RA or PsA compared to those without RD. Results: Overall, women experienced a delay in biologic treatment initiation compared with men. Dispensations for bDMARDs during pregnancy were low in the RA/PsA subgroup, and extremely uncommon among those with axSpA, and did not align with recommendations from clinical practice guidelines. While the receipt of rheumatologic care during and after pregnancy among RD patients was low, the prevalence of PPD in women with RD was higher compared to those without any RD. Conclusions: Findings from this dissertation emphasize the need for additional research to improve and prioritize care for reproductive-age women with rheumatic disease, particularly before, during, and after pregnancy. This could be accomplished through patient education, counseling, increased access, screening, and timely referrals to rheumatologists and mental health care specialists through enhanced care coordination of providers.
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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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Approach to Stereotactic Body Radiotherapy for the Treatment of Advanced Hepatocellular Carcinoma in Patients with Child-Pugh B-7 CirrhosisPatients with hepatocellular carcinoma (HCC) with underlying Child-Pugh B-7 cirrhosis benefit from management from an experienced, multidisciplinary team. In patients with localized disease who meet criteria for liver transplant, establishing care at a liver transplant center is crucial. For those awaiting transplant, local bridge therapies have emerged as a strategy to maintain priority status and eligibility. Multiple liver-directed therapies exist to provide locoregional tumor control. The careful selection of locoregional therapy is a multidisciplinary endeavor that takes into account patient factors including tumor resectability, underlying liver function, performance status, previous treatment, tumor location/size, and vascular anatomy to determine the optimal management strategy. Technological advances in external beam radiation therapy have allowed stereotactic body radiation therapy (SBRT) to emerge in recent years as a versatile and highly effective bridge therapy consisting of typically between 3 and 5 high dose, highly focused, and non-invasive radiation treatments. When treating cirrhotic patients with HCC, preserving liver function is of utmost importance to prevent clinical decline and decompensation. SBRT has been shown to be both safe and effective in carefully selected patients with Child-Pugh B cirrhosis; however, care must be taken to prevent radiation-induced liver disease. This review summarizes the evolving role of SBRT in the treatment of HCC in patients with Child-Pugh B-7 cirrhosis.
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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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Extranodal presentation in limited-stage diffuse large Bcell lymphoma as a prognostic marker in three SWOG trials S0014, S0313 and S1001Several recent trials have changed the standard-of-care for patients with limited stage (LS) diffuse large B-cell lymphoma (DLBCL) by minimizing the number of chemoimmunotherapy cycles and/or eliminating the need for radiotherapy without compromising long-term outcomes. However, there may be patient subsets where an abbreviated-treatment approach is insufficient. With this in mind, Bobillo et al., retrospectively reviewed LS DLBCL patients treated at a single institution with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) for four to six cycles with or without radio-therapy. This group reported that an extranodal presentation had shorter progression-free (PFS) and overall survival (OS) compared with nodal presentation. In these patients, consolidative radiotherapy prolonged survival in patients with extranodal disease, especially those with a positive positron emission tomography (PET) scan at the end of chemoimmunotherapy. In response, we analyzed similar patients treated on three consecutive SWOG studies (S0014, S0313, S1001; clinicaltrails gov. Identifier: NCT00005089, NCT00070018, NCT01359592).
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Staff and Veteran Perspectives on Residential Treatment Programs' Responses to COVID-19: A Qualitative Study Guided by the WHO's After Action Review FrameworkHealthcare must rapidly and systematically learn from earlier COVID-19 responses to prepare for future crises. This is critical for VA's Mental Health Residential Rehabilitation and Treatment Programs (RRTPs), offering 24/7 care to Veterans for behavioral health and/or homelessness. We adapted the World Health Organization's After Action Review (AAR) to conduct semi-structured small-group discussions with staff from two RRTPs and Veterans who received RRTP care during COVID-19, to examine COVID-19's impact on these programs. Six thematic categories emerged through qualitative analysis (participant-checked and contextualized with additional input from program leadership), representing participants' recommendations including: Keep RRTPs open (especially when alternative programs are inaccessible), convey reasons for COVID-19 precautions and programming changes to Veterans, separate recovery-oriented programming from COVID-19-related information-sharing, ensure Wi-Fi availability for telehealth and communication, provide technology training during orientation, and establish safe procedures for off-site appointments. AAR is easily applicable for organizations to debrief and learn from past experiences.
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DUX4 expression activates JNK and p38 MAP kinases in myoblastsFacioscapulohumeral muscular dystrophy (FSHD) is caused by misexpression of the DUX4 transcription factor in skeletal muscle that results in transcriptional alterations, abnormal phenotypes and cell death. To gain insight into the kinetics of DUX4-induced stresses, we activated DUX4 expression in myoblasts and performed longitudinal RNA sequencing paired with proteomics and phosphoproteomics. This analysis revealed changes in cellular physiology upon DUX4 activation, including DNA damage and altered mRNA splicing. Phosphoproteomic analysis uncovered rapid widespread changes in protein phosphorylation following DUX4 induction, indicating that alterations in kinase signaling might play a role in DUX4-mediated stress and cell death. Indeed, we demonstrate that two stress-responsive MAP kinase pathways, JNK and p38, are activated in response to DUX4 expression. Inhibition of each of these pathways ameliorated DUX4-mediated cell death in myoblasts. These findings uncover that the JNK pathway is involved in DUX4-mediated cell death and provide additional insights into the role of the p38 pathway, a clinical target for the treatment of FSHD.
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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.
