eScholarship@UMassChan Repository at UMass Chan Medical School


Sherman Center building at UMass Chan Medical School at night

eScholarship@UMassChan is a digital repository 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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  • Building a Community of Practice to Improve Dissemination of Disability Research

    Wnuk, Jean (2024-04-18)
    A Community of Practice brings together groups of people who share a concern, a set of problems, a passion about a topic, and who deepen their knowledge and expertise in this area by interacting on an ongoing basis. In 2022, the Center on Knowledge Translation for Employment Research (CeKTER) developed of a Community of Practice on "S.M.A.R.T. Social Media for Employment Research Dissemination,” This CoP was developed to respond to NIDILRR disability research grantees who have a collective desire to enhance their social media effectiveness. This CoP continues as of April 2024. Using our experience with the "S.M.A.R.T. Social Media for Employment Research Dissemination" CoP this tip sheet offers others guidance on how to develop and sustain a successful CoP.
  • Regulation of Lipolysis by 14-3-3 Proteins on Human Adipocyte Lipid Droplets

    Yang, Qin (2024-04-11)
    Lipid droplets (LDs) in adipocytes are pivotal for systemic lipid metabolism, serving as storage centers during nutritional surplus and as sources of fatty acids when energy is needed. These LDs react to hormonal stimuli like catecholamines and insulin, and their impaired response can lead to dysregulated lipolysis, lipotoxicity, and an increased risk of metabolic diseases. The specific mechanisms behind lipid release in human adipocytes remain largely unexplored. This study aims to elucidate the control of lipid mobilization in human adipocytes. We utilized advanced techniques to generate and differentiate primary progenitor cells on a large scale. Employing proximity labeling with enhanced ascorbate peroxidase (APEX2), we identified the interactome of perilipin 1 (PLIN1), a key LD component protein, under various lipolytic states. Through LC-MS/MS, we discovered 70 proteins interacting specifically with PLIN1. This includes PNPLA2 and LIPE, vital for regulated triglyceride hydrolysis, and four 14-3-3 protein family members (YWHAB, YWHAE, YWHAZ, YWHAG), which are known to regulate diverse signaling pathways. Our functional studies revealed that YWHAB is essential for maximal cyclic adenosine monophosphate (cAMP)-stimulated lipolysis, as its CRISPR-Cas9-mediated knockout mitigates lipolysis through a mechanism independent of insulin signaling. In summary, our use of proximity labeling not only comprehensively mapped the LD proteome in human adipocytes but also unveiled new regulatory mechanisms in adipocyte lipolysis control, specifically involving 14-3-3 proteins.
  • A Pilot Clinical Trial of an Informatics-Informed Mobile Transitional Care Program: the Paramedic Assisted Community Evaluation after Discharge (PACED) Intervention

    O'Connor, Laurel (2024-04-03)
    Introduction: Early rehospitalization of frail older adults after hospital discharge is detrimental to patients and hospital systems. Implementing effective strategies to execute a feasible and effective transitional care plan is challenging. Mobile integrated health (MIH) programs, which deploy mobile assets into the community to care for patients, may present a possible solution to facilitating effective transitional care back to home environments after hospitalization. However, there have been few previous studies investigating MIH models for transitional care delivery. The objective of this project is to assess the implementation and effectiveness of an informatics-supported paramedic-led MIH transitional care program for frail older adults. Methods: Patients 65 and older preparing for discharge from the hospital with an eFrailty index of 0.24 or greater were enrolled to participate in a structured post-discharge transitional home visit conducted by community paramedics within 72 hours of discharge. Demographic and clinical information, as well as healthcare utilization patterns, were recorded at enrollment and 30 days after the index hospitalization. Additionally, a separate control group of patients that were screened for the intervention but excluded due to geographical location of residence were aggregated and their electronic health record data including demographical and outcomes data was abstracted. Categorical group comparisons were conducted using chi-square tests and continuous variables group comparisons were conducted using the Kruskal–Wallis equality-of-populations rank test. Crude and adjusted binomial regressions were used for comparative outcomes. Results: In total 100 subjects were enrolled in the intervention (median age 81, 64% female) and 47 were included in the control group (median age 80, 55.2% female). The recruitment rate was 18.0%. The complete intervention protocol was completed and documented by paramedics for 90 (90.0%) patients. The crude and relative risk of 30-day rehospitalization was decreased in the PACED group compared to the control (RR=0.40, CI 0.19-0.84, p=0.03). There was a non-significant trend toward decreased risk of 30-day ED visits (RR=0.61, CI=0.37-1.37, p=0.23). Paramedics identified medication errors in 34 (34.0%) of the participants; the errors were remediated during the visit in 31 (91.2%). Additionally, 67 (67.0%) of subjects screened positive for high fall risk and 7 subjects (7.0%) screened positive for delirium. Conclusions: This pilot study of MIH intervention transition care program programs was feasible with high protocol fidelity and yields preliminary evidence that the intervention results in a decreased risk of rehospitalization in frail older adults.
  • UMCCTS Newsletter, April 2024

    UMass Center for Clinical and Translational Science (2024-04-01)
    This is the April 2024 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
  • Vocal learning-associated convergent evolution in mammalian proteins and regulatory elements

    Wirthlin, Morgan E; Schmid, Tobias A; Elie, Julie E; Zhang, Xiaomeng; Kowalczyk, Amanda; Redlich, Ruby; Shvareva, Varvara A; Rakuljic, Ashley; Ji, Maria B; Bhat, Ninad S; et al. (2024-03-29)
    Vocal production learning ("vocal learning") is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, anatomical, and neurophysiological data from the Egyptian fruit bat (Rousettus aegyptiacus) with analyses of the genomes of 215 placental mammals. First, we identified a set of proteins evolving more slowly in vocal learners. Then, we discovered a vocal motor cortical region in the Egyptian fruit bat, an emergent vocal learner, and leveraged that knowledge to identify active cis-regulatory elements in the motor cortex of vocal learners. Machine learning methods applied to motor cortex open chromatin revealed 50 enhancers robustly associated with vocal learning whose activity tended to be lower in vocal learners. Our research implicates convergent losses of motor cortex regulatory elements in mammalian vocal learning evolution.
  • Robust thalamic nuclei segmentation from T1-weighted MRI using polynomial intensity transformation

    Vidal, Julie P; Danet, Lola; Péran, Patrice; Pariente, Jérémie; Bach Cuadra, Meritxell; Zahr, Natalie M; Barbeau, Emmanuel J; Saranathan, Manojkumar (2024-03-28)
    Accurate segmentation of thalamic nuclei, crucial for understanding their role in healthy cognition and in pathologies, is challenging to achieve on standard T1-weighted (T1w) magnetic resonance imaging (MRI) due to poor image contrast. White-matter-nulled (WMn) MRI sequences improve intrathalamic contrast but are not part of clinical protocols or extant databases. In this study, we introduce histogram-based polynomial synthesis (HIPS), a fast preprocessing transform step that synthesizes WMn-like image contrast from standard T1w MRI using a polynomial approximation for intensity transformation. HIPS was incorporated into THalamus Optimized Multi-Atlas Segmentation (THOMAS) pipeline, a method developed and optimized for WMn MRI. HIPS-THOMAS was compared to a convolutional neural network (CNN)-based segmentation method and THOMAS modified for the use of T1w images (T1w-THOMAS). The robustness and accuracy of the three methods were tested across different image contrasts (MPRAGE, SPGR, and MP2RAGE), scanner manufacturers (PHILIPS, GE, and Siemens), and field strengths (3 T and 7 T). HIPS-transformed images improved intra-thalamic contrast and thalamic boundaries, and HIPS-THOMAS yielded significantly higher mean Dice coefficients and reduced volume errors compared to both the CNN method and T1w-THOMAS. Finally, all three methods were compared using the frequently travelling human phantom MRI dataset for inter- and intra-scanner variability, with HIPS displaying the least inter-scanner variability and performing comparably with T1w-THOMAS for intra-scanner variability. In conclusion, our findings highlight the efficacy and robustness of HIPS in enhancing thalamic nuclei segmentation from standard T1w MRI.
  • The 20th Annual Gerald F. Berlin Creative Writing Award Ceremony and Readings

    Lamar Soutter Library; Berlin, Richard M (2024-03-26)
    The Gerald F. Berlin Creative Writing Award is funded by a donation from Richard M. Berlin, M.D., a poet and Associate Professor of Psychiatry at UMass Chan Medical School. Dr. Berlin established the Award to encourage creative writing among UMass Chan students and residents, and to honor his father who struggled with a severe chronic illness. 2024 Awards: First Place: "Two True Stories" by Elizabeth (Liz) M. Irvin, MD Candidate, Class of 2026, UMass Chan Medical School. Second Place: "To Be a Body" by Hyein Sarah Lee (she/they), MD/PhD Candidate, GS1, UMass Chan Medical School. Third Place: "Hospital Food" by Abigail DeNike, MD Candidate, Class of 2027, UMass Chan Medical School. Honorable Mention: "Grief Sandwich" by Darya Herscovici, MD Candidate, Class of 2024, UMass Chan Medical School. Honorable Mention: "Shadow" by Alexander Hamel, MD Candidate, Class of 2027, UMass Chan Medical School. Honorable Mention: "His Name is Phil" by Melanie Fu (she/they), MD Candidate, Class of 2027, UMass Chan Medical School.
  • Enhancing Safety and Efficacy of Genome Editing In Vivo with Compact Cas9 and Guide Chemical Modification

    Zhang, Han (2024-03-25)
    Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR/Cas) have revolutionized science and medicine. However, applying the CRISPR/Cas system for in vivo therapeutic genome editing remains challenging due in part to delivery obstacles. Adeno-associated virus (AAV) vectors remain one of the most promising vehicles for gene therapies, particularly in extrahepatic tissues. Nevertheless, employing AAV for in vivo CRISPR/Cas genome editing presents difficulties, including limited packaging capacity, prolonged expression, redosing complexities, modest multiplexing capability, dose-related toxicity, and immunogenicity. This thesis addresses AAV limitations in delivering CRISPR/Cas in vivo in two ways. First, I focus on developing a novel delivery modality in which the CRISPR RNA (crRNA) is delivered in the form of a naked oligonucleotide, separate from AAV-expressed effector and trans-activating crRNA (tracrRNA). I find that a short, fully stabilized oligonucleotide (a ‘protecting oligo’) can significantly enhance the potency, stability, and uptake of a heavily chemically modified crRNA. The establishment of AAV/crRNA co-delivery modality offers a route towards transient editing activity, target multiplexing, guide redosing, and vector inactivation. Second, I use a compact Nme2Cas9 adenine base editor (Nme2-ABE) to engineer a single AAV delivery system for base editing in vivo. The capability to deliver a base editor via a single AAV holds the potential to enhance safety by minimizing immune responses, mitigating dose-related toxicity, and reducing manufacturing complexity.
  • Celebrating and Congratulations!

    Silk, Hugh (2024-03-21)
    Introduction: This week I am celebrating, along with my colleagues, our very successful match into family medicine (and to our residencies)! With 14.02% of UMass Chan students matching into Family Medicine, we exceeded the national average of 12.7% (per AAFP). Family Medicine Proud! This quote from Dr. Victor Johnson, known as the founding father of the College of General Practitioners now the College of Family Physicians in Canada, summarizes their future impact. "I became convinced that the medical profession would be saved not by its organization but by the sum total of the common sense and humanity of its individual practicing members. General practitioners... are the doctors closest to [the] people. They heal more of the broken hearted, repair more of the injured and deprived, and live with the poor and dying who are without influence and hope. As Family Physicians, you are ideally positioned in the health care system to understand patients and their family and community context, and to provide for them a deep connection, compassion, and care." The picture below says it best. These individuals are way more than a statistic. They will make us proud in the way Victor Johnson wanted family doctors to be. Congratulations to these future family physicians and to all who taught, challenged, mentored, coached, consoled, and encouraged them. Take a moment and congratulate yourselves too! Be well.
  • Citizenship status and career self-efficacy: An intersectional study of biomedical trainees in the United States

    Chatterjee, Deepshikha; Nogueira, Ana T; Wefes, Inge; Chalkley, Roger; Sturzenegger Varvayanis, Susi; Fuhrmann, Cynthia N; Varadarajan, Janani; Jacob, Gabrielle A; Gaines, Christiann H; Hubbard, Nisan M; et al. (2024-03-20)
    This study examines the intersectional role of citizenship and gender with career self-efficacy amongst 10,803 doctoral and postdoctoral trainees in US universities. These biomedical trainees completed surveys administered by 17 US institutions that participated in the National Institutes of Health Broadening Experiences in Scientific Training (NIH BEST) Programs. Findings indicate that career self-efficacy of non-citizen trainees is significantly lower than that of US citizen trainees. While lower career efficacy was observed in women compared with men, it was even lower for non-citizen female trainees. Results suggest that specific career interests may be related to career self-efficacy. Relative to US citizen trainees, both male and female non-citizen trainees showed higher interest in pursuing a career as an academic research investigator. In comparison with non-citizen female trainees and citizen trainees of all genders, non-citizen male trainees expressed the highest interest in research-intensive (and especially principal investigator) careers. The authors discuss potential causes for these results and offer recommendations for increasing trainee career self-efficacy which can be incorporated into graduate and postdoctoral training.
  • A machine learning approach for diagnostic and prognostic predictions, key risk factors and interactions

    Nasir, Murtaza; Summerfield, Nichalin S.; Carreiro, Stephanie; Berlowitz, Dan; Oztekin, Asil (2024-03-18)
    Machine learning (ML) has the potential to revolutionize healthcare, allowing healthcare providers to improve patient-care planning, resource planning and utilization. Furthermore, identifying key-risk-factors and interaction-effects can help service-providers and decision-makers to institute better policies and procedures. This study used COVID-19 electronic health record (EHR) data to predict five crucial outcomes: positive-test, ventilation, death, hospitalization days, and ICU days. Our models achieved high accuracy and precision, with AUC values of 91.6%, 99.1%, and 97.5% for the first three outcomes, and MAE of 0.752 and 0.257 days for the last two outcomes. We also identified interaction effects, such as high bicarbonate in arterial blood being associated with longer hospitalization in middle-aged patients. Our models are embedded in a prototype of an online decision support tool that can be used by healthcare providers to make more informed decisions.
  • Over Fartsgrensen

    Gracey, Kristina (2024-03-14)
    Introduction: This week I am grateful to Kristina Gracey, faculty at Barre Family Health Center, for her essay that is both personal and informative. She is an avid and successful runner. Which can be dangerous. She has been thinking about this element of risk and adds a public health perspective to her reflection that I personally admire. Food for thought for possible collective advocacy by us all on this topic.
  • Dual Layer vs Single Layer Woven EndoBridge Device in the Treatment of Intracranial Aneurysms: A Propensity Score-Matched Analysis

    Dmytriw, Adam A; Salim, Hamza; Musmar, Basel; Aslan, Assala; Cancelliere, Nicole M; McLellan, Rachel M; Algin, Oktay; Ghozy, Sherief; Dibas, Mahmoud; Lay, Sovann V; et al. (2024-03-14)
    Background: The Woven EndoBridge (WEB) devices have been used for treating wide neck bifurcation aneurysms (WNBAs) with several generational enhancements to improve clinical outcomes. The original device dual-layer (WEB DL) was replaced by a single-layer (WEB SL) device in 2013. This study aimed to compare the effectiveness and safety of these devices in managing intracranial aneurysms. Methods: A multicenter cohort study was conducted, and data from 1,289 patients with intracranial aneurysms treated with either the WEB SL or WEB DL devices were retrospectively analyzed. Propensity score matching was utilized to balance the baseline characteristics between the two groups. Outcomes assessed included immediate occlusion rate, complete occlusion at last follow-up, retreatment rate, device compaction, and aneurysmal rupture. Results: Before propensity score matching, patients treated with the WEB SL had a significantly higher rate of complete occlusion at the last follow-up and a lower rate of retreatment. After matching, there was no significant difference in immediate occlusion rate, retreatment rate, or device compaction between the WEB SL and DL groups. However, the SL group maintained a higher rate of complete occlusion at the final follow-up. Regression analysis showed that SL was associated with higher rates of complete occlusion (OR: 0.19; CI: 0.04 to 0.8, p = 0.029) and lower rates of retreatment (OR: 0.12; CI: 0 to 4.12, p = 0.23). Conclusion: The WEB SL and DL devices demonstrated similar performances in immediate occlusion rates and retreatment requirements for intracranial aneurysms. The SL device showed a higher rate of complete occlusion at the final follow-up.
  • Reinjury Following Return to Play

    Watts, George J.; Tai, Ryan; Joshi, Ganesh; Garwood, Elisabeth R; Saha, Debajyoti (2024-03-14)
    Radiologists are frequently called on for guidance regarding return to play (RTP) for athletes and active individuals after sustaining a musculoskeletal injury. Avoidance of reinjury is of particular importance throughout the rehabilitative process and following resumption of competitive activity. Understanding reinjury risk estimation, imaging patterns, and correlation of clinical and surgical findings will help prepare the radiologist to identify reinjuries correctly on diagnostic imaging studies and optimize management for a safe RTP.
  • Sampling of healthcare professionals' perspective on point-of-care technologies from 2019-2021: A survey of benefits, concerns, and development

    Orwig, Taylor; Sutaria, Shiv; Wang, Ziyue; Howard-Wilson, Sakeina; Dunlap, Denise; Lilly, Craig M; Buchholz, Bryan; McManus, David D; Hafer, Nathaniel (2024-03-08)
    Point-of-care technology (POCT) plays a vital role in modern healthcare by providing a fast diagnosis, improving patient management, and extending healthcare access to remote and resource-limited areas. The objective of this study was to understand how healthcare professionals in the United States perceived POCTs during 2019-2021 to assess the decision-making process of implementing these newer technologies into everyday practice. A 5-point Likert scale survey was sent to respondents to evaluate their perceptions of benefits, concerns, characteristics, and development of point-of-care technologies. The 2021 survey was distributed November 1st, 2021- February 15th, 2022, with a total of 168 independent survey responses received. Of the respondents, 59% identified as male, 73% were white, and 48% have been in practice for over 20 years. The results showed that most agreed that POCTs improve patient management (94%) and improve clinician confidence in decision making (92%). Healthcare professionals were most concerned with potentially not being reimbursed for the cost of the POCT (37%). When asked to rank the top 3 important characteristics of POCT, respondents chose accuracy, ease of use, and availability. It is important to note this survey was conducted during the COVID-19 pandemic. To achieve an even greater representation of healthcare professionals' point of view on POCTs, further work to obtain responses from a larger, more diverse population of providers is needed.
  • Normative modeling of thalamic nuclear volumes [preprint]

    Young, Taylor; Kumar, Vinod Jangid; Saranathan, Manojkumar (2024-03-08)
    Thalamic nuclei have been implicated in neurodegenerative and neuropsychiatric disorders. Normative models for thalamic nuclear volumes have not been proposed thus far. The aim of this work was to establish normative models of thalamic nuclear volumes and subsequently investigate changes in thalamic nuclei in cognitive and psychiatric disorders. Volumes of the bilateral thalami and 12 nuclear regions were generated from T1 MRI data using a novel segmentation method (HIPS-THOMAS) in healthy control subjects (n=2374) and non-control subjects (n=695) with early and late mild cognitive impairment (EMCI, LMCI), Alzheimer's disease (AD), Early psychosis and Schizophrenia, Bipolar disorder, and Attention deficit hyperactivity disorder. Three different normative modelling methods were evaluated while controlling for sex, intracranial volume, and site. Z-scores and extreme z-score deviations were calculated and compared across phenotypes. GAMLSS models performed the best. Statistically significant shifts in z-score distributions consistent with atrophy were observed for most phenotypes. Shifts of progressively increasing magnitude were observed bilaterally from EMCI to AD with larger shifts in the left thalamic regions. Heterogeneous shifts were observed in psychiatric diagnoses with a predilection for the right thalamic regions. Here we present the first normative models of thalamic nuclear volumes and highlight their utility in evaluating heterogenous disorders such as Schizophrenia.
  • Distribution and bulk flow analyses of the intraflagellar transport (IFT) motor kinesin-2 support an "on-demand" model for Chlamydomonas ciliary length control

    Patel, Mansi B; Griffin, Paul J; Olson, Spencer F; Dai, Jin; Hou, Yuqing; Malik, Tara; Das, Poulomi; Zhang, Gui; Zhao, Winston; Witman, George B.; et al. (2024-03-08)
    Most cells tightly control the length of their cilia. The regulation likely involves intraflagellar transport (IFT), a bidirectional motility of multi-subunit particles organized into trains that deliver building blocks into the organelle. In Chlamydomonas, the anterograde IFT motor kinesin-2 consists of the motor subunits FLA8 and FLA10 and the nonmotor subunit KAP. KAP dissociates from IFT at the ciliary tip and diffuses back to the cell body. This observation led to the diffusion-as-a-ruler model of ciliary length control, which postulates that KAP is progressively sequestered into elongating cilia because its return to the cell body will require increasingly more time, limiting motor availability at the ciliary base, train assembly, building block supply, and ciliary growth. Here, we show that Chlamydomonas FLA8 also returns to the cell body by diffusion. However, more than 95% of KAP and FLA8 are present in the cell body and, at a given time, just ~1% of the motor participates in IFT. After repeated photobleaching of both cilia, IFT of fluorescent kinesin subunits continued indicating that kinesin-2 cycles from the large cell-body pool through the cilia and back. Furthermore, growing and full-length cilia contained similar amounts of kinesin-2 subunits and the size of the motor pool at the base changed only slightly with ciliary length. These observations are incompatible with the diffusion-as-a-ruler model, but rather support an "on-demand model," in which the cargo load of the trains is regulated to assemble cilia of the desired length.
  • Photos of Meaningful Things and Places

    Penumetcha, Venkata "Sai Sri"; Isaac, Tamika; Coderre, Danielle; Silk, Hugh (2024-03-07)
    Introduction: This week I have a visual treat. Last week Sara Shields and I had a session with the PGY1s on the topic of medical humanities and one of the prompts was to go into the hospital and return with a photo of something that is meaningful to you - can be a piece, a thing, a person. The discussion that ensued from these photos was wonderful! I am sharing some of the photos here for you with their title. Enjoy.
  • Introducing Telomere-Dysfunction Induced Cellular Senescence in iPSC-Based Modeling Of Neurodegenerative Diseases

    Neherin, Kashfia (2024-03-06)
    Investigation of disease-associated cellular changes in vitro has leaped forward significantly with the innovation of induced pluripotent stem cell (iPSC) technology. However, resetting the epigenetic landscape and aging clock during reprogramming results in iPSC-differentiated cells resembling fetal cell types instead of adult or aged cells. The lack of cellular aging in iPSC-based models presents a significant drawback in the investigation of age-associated diseases such as Alzheimer’s disease. My thesis aims to introduce proper cellular aging to improve iPSC-based modeling of neurodegeneration. Toward this goal, I created an inducible system to trigger senescence in iPSC-based cell models, as recent studies showed senescence playing a crucial role in aging and neurodegeneration. I utilized CRISPR-interference (CRISPRi) to suppress telomere repeat factor 2 (TERF2), a significant component of the telomere-protecting Shelterin complex. I demonstrated that suppression of TERF2 in iPSCs robustly activated DNA damage response (DDR), p53/p21 signaling, and cellular senescence in an inducible and synchronized manner. The inducible approach allows temporal control of senescence activation throughout differentiation from iPSCs to desired cell types. I applied the CRISPRi-TERF2 approach to iPSC-differentiated neural progenitor cells (NPCs) and showed that suppression of TERF2 efficiently activated DDR, p53/p21 signaling, and cellular senescence in differentiated NPCs. This inducible model of cellular senescence generated in this study will enable the investigation of cellular senescence using isogenic comparisons in the progression of age-associated neurodegeneration and improve disease modeling with a proper cellular aging context to facilitate drug discovery.
  • UMCCTS Newsletter, March 2024

    UMass Center for Clinical and Translational Science (2024-03-01)
    This is the March 2024 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.

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