Recently Published

  • Vascular Extremity Venous Ultrasound

    Tracy, Anastasia (2023-05-25)
    This presentation is part of the PEER Liberia Radiology Lecture Series. It provides an overview of vascular extremity venous ultrasound, including: normal presentation; tips and tricks for successful, high quality scanning; basic scanning protocol; image interpretation; and understanding the importance of accurate sonographic image interpretation as it relates to the development of patient care plans.
  • Applying for a Job: The Young Adults Guide, Revised 2023

    Northeast Massachusetts Community of Practice (2023-05-17)
    This is a tip sheet for youth and young adults with serious mental health conditions about finding, applying for, and interviewing for jobs. This tip sheet was originally published in 2011. It has been updated for 2023.
  • COVID-19 and the Cardiovascular System: Requiem for a Medical Minotaur

    Koupenova, Milka; Chung, Mina K; Bristow, Michael R (2023-05-11)
    The world has finally emerged from the great medical, economic, and social calamity of 2020 to 2022, the COVID-19 pandemic. This Compendium of 10 articles describes various aspects of the effects of SARS-CoV-2 on the cardiovascular system, focusing on the heart. The Minotaur from Greek mythology is an apt metaphor, because this half bull/half man spike-adorned gain of function mutant slaughtered the innocent was nearly impossible to eradicate in his labyrinthian environs, inspired mass fear of the unknown, and ultimately was eliminated by resourceful, determined collaborators.1 Although SARS-CoV-2 infection has not been eliminated, it has been contained to the point of acquiring the status of a manageable infectious disease.
  • UMCCTS Newsletter, May 2023

    UMass Center for Clinical and Translational Science (2023-05-04)
    This is the May 2023 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
  • Renewal of oligodendrocyte lineage reverses dysmyelination and CNS neurodegeneration through corrected N-acetylaspartate metabolism

    Lotun, Anoushka; Li, Danning; Xu, Hongxia; Su, Qin; Tuncer, Serafettin; Sanmiguel, Julio; Mooney, Morgan; Baer, Christina E; Ulbrich, Russell; Eyles, Stephen J; et al. (2023-05-04)
    Myelinating oligodendrocytes are essential for neuronal communication and homeostasis of the central nervous system (CNS). One of the most abundant molecules in the mammalian CNS is N-acetylaspartate (NAA), which is catabolized into L-aspartate and acetate by the enzyme aspartoacylase (ASPA) in oligodendrocytes. The resulting acetate moiety is thought to contribute to myelin lipid synthesis. In addition, affected NAA metabolism has been implicated in several neurological disorders, including leukodystrophies and demyelinating diseases such as multiple sclerosis. Genetic disruption of ASPA function causes Canavan disease, which is hallmarked by increased NAA levels, myelin and neuronal loss, large vacuole formation in the CNS, and early death in childhood. Although NAA's direct role in the CNS is inconclusive, in peripheral adipose tissue, NAA-derived acetate has been found to modify histones, a mechanism known to be involved in epigenetic regulation of cell differentiation. We hypothesize that a lack of cellular differentiation in the brain contributes to the disruption of myelination and neurodegeneration in diseases with altered NAA metabolism, such as Canavan disease. Our study demonstrates that loss of functional Aspa in mice disrupts myelination and shifts the transcriptional expression of neuronal and oligodendrocyte markers towards less differentiated stages in a spatiotemporal manner. Upon re-expression of ASPA, these oligodendrocyte and neuronal lineage markers are either improved or normalized, suggesting that NAA breakdown by Aspa plays an essential role in the maturation of neurons and oligodendrocytes. Also, this effect of ASPA re-expression is blunted in old mice, potentially due to limited ability of neuronal, rather than oligodendrocyte, recovery.
  • International Inter-observer Variability of Breast Density Assessment

    Portnow, Leah H; Choridah, Lina; Kardinah, Kardinah; Handarini, Triwulan; Pijnappel, Ruud; Bluekens, Adriana M J; Duijm, Lucien E M; Schoub, Peter K; Smilg, Pamela S; Malek, Liat; et al. (2023-04-29)
    Objective: To determine variability in visually assessed mammographic breast density categorization among radiologists practicing in Indonesia, the Netherlands, South Africa, and the United States. Methods: Two-hundred consecutive 2D full field digital screening mammograms performed from September-December 2017 were selected and retrospectively reviewed from four global locations for a total of 800 mammograms. Three breast radiologists in each location (team) provided consensus density assessments of all 800 mammograms using BI-RADS® density categorization. Inter-reader agreement was compared using Gwet's AC2 with quadratic weighting across all four density categories and Gwet's AC1 for binary comparison of combined not dense versus dense categories. Variability of distribution between teams was calculated using the Stuart-Maxwell test of marginal homogeneity across all four categories and using McNemar's test for not dense versus dense categories. To compare readers from a particular country on their own 200 mammograms versus the other three teams, density distribution was calculated using conditional logistic regression. Results: For all 800 mammograms, inter-reader weighted agreement for distribution among four density categories is 0.86 (Gwet's AC2 with quadratic weighting 95%, CI 0.85-0.88) and for not dense vs dense categories it is 0.66 (Gwet's AC1 95%, CI 0.63-0.70). Density distribution across four density categories was significantly different when teams were compared to each other and one team versus the other three teams combined (p<0.001). Overall, all readers placed the largest number of mammograms in the scattered and heterogeneous categories. Conclusion: While reader teams from four different global locations had almost perfect inter-reader agreement in BI-RADS® density categorization, variability in density distribution across four categories remains statistically significant.
  • Pilot study of implementing the Shared Healthcare Actions & Reflections Electronic systems in Survivorship (SHARE-S) program in coordination with clinical care

    Sohl, Stephanie J; Sadasivam, Rajani S; Kittel, Carol; Dressler, Emily V; Wentworth, Stacy; Balakrishnan, Kavitha; Weaver, Kathryn E; Dellinger, Rebecca Ann; Puccinelli-Ortega, Nicole; Cutrona, Sarah L; et al. (2023-04-25)
    Introduction: Initial cancer survivorship care planning efforts focused on information sharing demonstrated limited impact on patient health outcomes. We designed the Shared Healthcare Actions & Reflections Electronic Systems in survivorship (SHARE-S) program to enhance survivorship guideline implementation by transitioning some effort from clinicians to technology and patients through supporting health self-management (e.g., healthy lifestyles). Methods: We conducted a single-group hybrid implementation-effectiveness pilot study. SHARE-S incorporated three strategies: (1) e-referral from the clinical team for patient engagement, (2) three health self-management coach calls, and (3) text messages to enhance coaching. Our primary implementation measure was the proportion of patients e-referred who enrolled (target >30%). Secondary implementation measures assessed patient engagement. We also measured effectiveness by describing changes in patient health outcomes. Results: Of the 118 cancer survivor patients e-referred, 40 engaged in SHARE-S (proportion enrolled = 34%). Participants had a mean age of 57.4 years (SD = 15.7), 73% were female, 23% were Black/African American, and 5 (12.5%) were from a rural location. Patient-level adherence to coach calls was >90%. Changes from baseline to follow-up showed at least a small effect (Cohen's d = 0.2) for improvements in: mindful attention, alcohol use, physical activity, fruit and vegetable intake, days of mindfulness practice, depressive symptoms, ability to participate in social roles and activities, cancer-specific quality of life, benefits of having cancer, and positive feelings. Conclusion: The SHARE-S program successfully engaged cancer survivor patients. Once enrolled, patients showed promising improvements in health outcomes. Supporting patient self-management is an important component of optimizing delivery of cancer survivorship care.
  • TIR-1/SARM1 inhibits axon regeneration and promotes axon degeneration

    Czech, Victoria L; O'Connor, Lauren C; Philippon, Brendan; Norman, Emily; Byrne, Alexandra B (2023-04-21)
    Growth and destruction are central components of the neuronal injury response. Injured axons that are capable of repair, including axons in the mammalian peripheral nervous system and in many invertebrate animals, often regenerate and degenerate on either side of the injury. Here we show that TIR-1/dSarm/SARM1, a key regulator of axon degeneration, also inhibits regeneration of injured motor axons. The increased regeneration in tir-1 mutants is not a secondary consequence of its effects on degeneration, nor is it determined by the NADase activity of TIR-1. Rather, we found that TIR-1 functions cell-autonomously to regulate each of the seemingly opposite processes through distinct interactions with two MAP kinase pathways. On one side of the injury, TIR-1 inhibits axon regeneration by activating the NSY-1/ASK1 MAPK signaling cascade, while on the other side of the injury, TIR-1 simultaneously promotes axon degeneration by interacting with the DLK-1 mitogen-activated protein kinase (MAPK) signaling cascade. In parallel, we found that the ability to cell-intrinsically inhibit axon regeneration is conserved in human SARM1. Our finding that TIR-1/SARM1 regulates axon regeneration provides critical insight into how axons coordinate a multidimensional response to injury, consequently informing approaches to manipulate the response toward repair.
  • Neuroimaging

    Chen, Kwan (2023-04-20)
    This presentation is part of the PEER Liberia Radiology Lecture Series. It provides an overview for clinicians of neuroimaging, including anatomy and summary of various cases.
  • A pilot study of robotic surgery case videos for first-year medical student anatomy

    Palleiko, Benjamin A; Maxfield, Mark W; Czerniach, Donald R; Cherng, Nicole B; Giannaris, Eustathia Lela (2023-04-17)
    There has been a recent shift in medical student anatomy education with greater incorporation of virtual resources. Multiple approaches to virtual anatomy resources have been described, but few involve video or images from surgical procedures. In this pilot study, a series of surgical case videos was created using robotic surgery video footage for a first-year medical student anatomy course. Five operations were included that covered thoracic, abdominal, and pelvic anatomy. Students were surveyed at the end of the course regarding their experience with the videos and their perceptions towards a surgical career. Overall, participants agreed that the videos were an effective learning tool, were useful regardless of career interest, and that in the future it would be useful to incorporate additional surgical case videos. Respondents highlighted the importance of audio narration with future videos and provided suggestions for future operations that they would like to see included. In summary, this pilot study describes the creation and implementation of a surgical video anatomy curriculum and student survey results suggest this may be an effective approach to video-based anatomy education for further curricular development.
  • Balance in the In-Between

    Adelstein, Pamela (2023-04-13)
    Introduction: This week we hear from our most avid writer - Pam Adelstein, former resident of Family Health Center of Worcester, and now Medical Director at Fenway Health. She writes regularly for Pulse. Today's piece was previously published there. It takes on the notion of transitions since she has recently experienced a big one. How does one embrace transitions - whether it is from one job to another, or simply from one exam room to another or just getting from work to home. When I graduated from University, the minister at our graduation week ceremony pleaded with us to focus on transitions - that is where the good stuff will happen. Let's see what Pam has to add.
  • Cryo-EM structure of the human cardiac myosin filament [preprint]

    Dutta, Debabrata; Nguyen, Vu; Campbell, Kenneth S; Padrón, Raúl; Craig, Roger (2023-04-12)
    Pumping of the heart is powered by filaments of the motor protein myosin, which pull on actin filaments to generate cardiac contraction. In addition to myosin, the filaments contain cardiac myosin-binding protein C (cMyBP-C), which modulates contractility in response to physiological stimuli, and titin, which functions as a scaffold for filament assembly 1 . Myosin, cMyBP-C and titin are all subject to mutation, which can lead to heart failure. Despite the central importance of cardiac myosin filaments to life, their molecular structure has remained a mystery for 60 years 2 . Here, we have solved the structure of the main (cMyBP-C-containing) region of the human cardiac filament to 6 Å resolution by cryo-EM. The reconstruction reveals the architecture of titin and cMyBP-C for the first time, and shows how myosin's motor domains (heads) form 3 different types of motif (providing functional flexibility), which interact with each other and with specific domains of titin and cMyBP-C to dictate filament architecture and regulate function. A novel packing of myosin tails in the filament backbone is also resolved. The structure suggests how cMyBP-C helps generate the cardiac super-relaxed state 3 , how titin and cMyBP-C may contribute to length-dependent activation 4 , and how mutations in myosin and cMyBP-C might disrupt interactions, causing disease 5, 6 . A similar structure is likely in vertebrate skeletal myosin filaments. The reconstruction resolves past uncertainties, and integrates previous data on cardiac muscle structure and function. It provides a new paradigm for interpreting structural, physiological and clinical observations, and for the design of potential therapeutic drugs.
  • Atypical Fragility Fractures due to Bony or Soft Tissue Phosphaturic Mesenchymal Tumors: A Report of Two Cases

    Clegg, Stephanie M; Eiel, Emily S; Fine, Sara; Gafni, Rachel I; Most, Mathew J (2023-04-12)
    Introduction: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic disorder where patients present with hypophosphatemia, chronic diffuse bone pain, and occasionally fractures. Benign phosphaturic mesenchymal tumors (PMT) are responsible for the TIO and are largely soft tissue tumors. Cases: Two male patients with TIO secondary to PMT were reported-one in the bony scapula and the other in the plantar foot soft tissue. The first case describes a 63-year-old Caucasian male, who sustained an intertrochanteric proximal femur stress fracture and approximately two years of diffuse bone pain and hypophosphatemia. Wide excision of a left scapula boney lesion resulted in immediate resolution of his electrolyte abnormalities and bone pain. Case 2 describes a 58-year-old male with four years of multifocal bone pain and atraumatic fractures. A 68Ga-DOTATATE-positron emission tomography/computed tomography (PET/CT) scan identified a soft tissue tumor in his plantar foot, which was ultimately excised. He also experienced near immediate resolution of his pain and no additional fractures. Conclusion: TIO is a rare condition presenting with chronic multifocal bone pain, stress fractures, and hypophosphatemia. These two cases highlight that the causative tumor may originate in soft tissue or bone. Furthermore, a high index of suspicion, along with fibroblast growth factor-23 testing and DOTATATE-PET/CT localization, can help with diagnosis and minimize treatment delays.
  • Monitoring Diversity in Faculty Using Applicant Flow Data: Lessons Learned

    Rosal, Milagros C; Duncan, Marlina; Hirabayashi, Natasja; Person, Sharina (2023-04-12)
    We applaud Dr Adaugo Amobi’s commentary in this issue of Medical Care regarding physician workforce diversity, the importance of systems to track physician hiring practices in aggregate and over time, and the use of these data to inform efforts to improve workforce diversity.
  • Unmasked

    Chang, Chris (2023-04-06)
    Introduction: This week I share with you a post-pandemic reflection from Chris Chang, former Barre Family Health Center resident, who is now at the Austin Regional Clinic in Austin, Texas. He has written several times before for FMM. The reflection below explores how we return to "normal" after a tumultuous three years. Definitely, not easy. Chris wrote this to me: “After nearly exactly three years, our clinic today moved to optional masking for staff. It was a strange day filled with mixed emotions for me. I'm still working on wrapping my brain around it, and this is part of that process. It is a bookend to the poem "Heroics" that I wrote and sent in near the beginning of the pandemic. Many thanks for keeping the fire burning.”
  • Gliotransmission and adenosine signaling promote axon regeneration

    Wang, Fei; Ruppell, Kendra Takle; Zhou, Songlin; Qu, Yun; Gong, Jiaxin; Shang, Ye; Wu, Jinglin; Liu, Xin; Diao, Wenlin; Li, Yi; et al. (2023-04-06)
    How glia control axon regeneration remains incompletely understood. Here, we investigate glial regulation of regenerative ability differences of closely related Drosophila larval sensory neuron subtypes. Axotomy elicits Ca2+ signals in ensheathing glia, which activates regenerative neurons through the gliotransmitter adenosine and mounts axon regenerative programs. However, non-regenerative neurons do not respond to glial stimulation or adenosine. Such neuronal subtype-specific responses result from specific expressions of adenosine receptors in regenerative neurons. Disrupting gliotransmission impedes axon regeneration of regenerative neurons, and ectopic adenosine receptor expression in non-regenerative neurons suffices to activate regenerative programs and induce axon regeneration. Furthermore, stimulating gliotransmission or activating the mammalian ortholog of Drosophila adenosine receptors in retinal ganglion cells (RGCs) promotes axon regrowth after optic nerve crush in adult mice. Altogether, our findings demonstrate that gliotransmission orchestrates neuronal subtype-specific axon regeneration in Drosophila and suggest that targeting gliotransmission or adenosine signaling is a strategy for mammalian central nervous system repair.
  • UMCCTS Newsletter, April 2023

    UMass Center for Clinical and Translational Science (2023-04-03)
    This is the April 2023 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
  • Radiofrequency Ablation Provides Rapid and Durable Pain Relief for the Palliative Treatment of Lytic Bone Metastases Independent of Radiation Therapy: Final Results from the OsteoCool Tumor Ablation Post-Market Study

    Levy, Jason; David, Elizabeth; Hopkins, Thomas; Morris, Jonathan; Tran, Nam D; Farid, Hamed; Massari, Francesco; O'Connell, William G; Vogel, Alexander; Gangi, Afshin; et al. (2023-04-03)
    Purpose: The OsteoCool Tumor Ablation Post-Market Study (OPuS One) was a prospective, multi-national, single-arm study to investigate safety and effectiveness of radiofrequency ablation (RFA) for palliation of painful lytic bone metastases with 12 months of follow-up. RFA has demonstrated effective palliation of osseous metastases in small clinical studies with short-term follow-up; however, a long-term assessment with robust subject numbers is lacking. Materials and methods: Prospective assessments were conducted at Baseline, 3 days, 1 week, and 1, 3, 6, and 12-months. Pain and quality of life were measured prior to RFA and postoperatively using the Brief Pain Inventory, European Quality of Life-5 Dimension, and European Organization for Research and Treatment of Cancer Care Quality of Life Questionnaire for palliative care. Radiation, chemotherapy and opioid usage, and related adverse events were collected. Results: 206 subjects were treated with RFA at 15 institutions in OPuS One. Worst pain, average pain, pain interference and quality of life significantly improved at all visits starting 3 days post-RFA and sustained to 12 months (P < 0.0001). Post hoc analysis found neither systemic chemotherapy nor local radiation therapy at the index site of RFA influenced worst pain, average pain, or pain interference. Six subjects had device/procedure-related adverse events. Conclusion: RFA for lytic metastases provides rapid (within 3 days) and statistically significant pain and quality of life improvements with sustained long-term relief through 12 months and a high degree of safety, independent of radiation. Level of evidence: 2B, PROSPECTIVE, NON-RANDOMIZED, POST-MARKET STUDY: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors .
  • Challenges in Use of Practice-based Research Networks for a Medical Device Trial to Detect SARS-CoV-2

    Daly, Jeanette M; O'Connor, Laurel; Schmidt, Megan E; Ferrara, Laura K; Parang, Kim; Levy, Barcey T (2023-04-02)
    Introduction/objectives: Primary care practice-based research networks (PBRNs) participated in a point of care (POC) device study funded by by the National Institutes of Health and led by the University of Massachusetts Chan Medical School (UMass) to speed the development, validation, and commercialization of POC tests to detect SARS-CoV-2. The purposes of this study were to describe the characteristics of participating PBRNs and their respective collaborators in this device trial and describe complications challenging its execution. Methods: Semi-structured interviews were conducted with lead personnel from participating PBRNs and UMass. Results: Four PBRNs and UMass were invited to participate and 3 PBRNs and UMass participated. This device trial recruited 321 subjects in 6 months; 65 subjects from PBRNs. Each PBRN and the academic medical center site enrolled and recruited subjects differently. Main challenges identified were having adequate clinic personnel to enroll and aid in consent and questionnaire completion, frequently changing inclusion/exclusion criteria, use of the digital electronic data collection platform, and having access to a -80°C freezer to store supplies. Discussion: This trial involved numerous researchers, primary care clinic leaders and staff, and academic center sponsored program staff and attorneys resulting in a resource-intensive endeavor to enroll 65 subjects in the real-world clinical setting of primary care PBRNs with the academic medical center enrolling the rest. Multiple obstacles to standing up the study were encountered by the PBRNS. Conclusions: Primary care PBRNs rely largely on the goodwill established between academic health centers and participating practices. For future investigations involving device studies, collaborating PBRN leaders should assess whether recruitment criteria may change, obtain detailed lists of equipment needed, and/or know if the study is likely to be halted suddenly to appropriately prepare their member practices.
  • The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models

    Rozowsky, Joel; Gao, Jiahao; Borsari, Beatrice; Yang, Yucheng T; Galeev, Timur; Gürsoy, Gamze; Epstein, Charles B; Xiong, Kun; Xu, Jinrui; Li, Tianxiao; et al. (2023-03-30)
    Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of 1,635 open-access datasets from four donors (∼30 tissues × ∼15 assays). The datasets are mapped to matched, diploid genomes with long-read phasing and structural variants, instantiating a catalog of >1 million allele-specific loci. These loci exhibit coordinated activity along haplotypes and are less conserved than corresponding, non-allele-specific ones. Surprisingly, a deep-learning transformer model can predict the allele-specific activity based only on local nucleotide-sequence context, highlighting the importance of transcription-factor-binding motifs particularly sensitive to variants. Furthermore, combining EN-TEx with existing genome annotations reveals strong associations between allele-specific and GWAS loci. It also enables models for transferring known eQTLs to difficult-to-profile tissues (e.g., from skin to heart). Overall, EN-TEx provides rich data and generalizable models for more accurate personal functional genomics.

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