• Adulting Shorts: The “TEA” on IEPs Part 2

      Sudbrock, Emily; Gatesy-Davis, Marina (2022-09-21)
      This 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. This is Part 2 of the story. Find Part 1 here: https://www.umassmed.edu/TransitionsACR/publication/comic/2021/09/tea-on-ieps-part-1/
    • Ultrasound in the Acute Abdomen

      Hoyer, Matt (eScholarship@UMassChan, 2022-09-15)
      This presentation is part of the PEER Liberia Radiology Lecture Series. It provides an overview for clinicians of ultrasound in the acute abdomen.
    • Examining Pregnant Veterans' Acceptance and Beliefs Regarding the COVID-19 Vaccine

      Mattocks, Kristin M.; Kroll-Desrosiers, Aimee R.; Moore Simas, Tiffany A.; Bastian, Lori A; Marteeny, Valerie; Walker, Lorrie; Sheahan, Kate; Elwy, A Rani (2022-08-30)
      Background: Pregnant persons have received mixed messages regarding whether or not to receive COVID-19 vaccines as limited data are available regarding vaccine safety for pregnant and lactating persons and breastfeeding infants. Objective: The aims of this study were to examine pregnant Veteran's acceptance of COVID-19 vaccines, along with perceptions and beliefs regarding vaccine safety and vaccine conspiracy beliefs. Design and participants: We conducted a cross-sectional survey of pregnant Veterans enrolled in VA care who were taking part in an ongoing cohort study at 15 VA medical centers between January and May 2021. Main measures: Pregnant Veterans were asked whether they had been offered the COVID-19 vaccine during pregnancy, and whether they chose to accept or refuse it. Additional questions focused on perceptions of COVID-19 vaccine safety and endorsements of vaccine knowledge and conspiracy beliefs. Logistic regression was utilized to examine predictors of acceptance of a vaccine during pregnancy. Key results: Overall, 72 pregnant Veterans were offered a COVID-19 vaccine during pregnancy; over two-thirds (69%) opted not to receive a vaccine. Reasons for not receiving a vaccine included potential effects on the baby (64%), side effects for oneself (30%), and immunity from a past COVID-19 infection (12%). Those who received a vaccine had significantly greater vaccine knowledge and less belief in vaccine conspiracy theories. Greater knowledge of vaccines in general (aOR: 1.78; 95% CI: 1.2-2.6) and lower beliefs in vaccine conspiracies (aOR: 0.76; 95% CI: 0.6-0.9) were the strongest predictors of acceptance of a COVID-19 vaccine during pregnancy. Conclusions: Our study provides important insights regarding pregnant Veterans' decisions to accept the COVID-19 vaccine, and reasons why they may choose not to accept the vaccine. Given the high endorsement of vaccine conspiracy beliefs, trusted healthcare providers should have ongoing, open discussions about vaccine conspiracy beliefs and provide additional information to dispel these beliefs.
    • Investigating Proteolytic Processing of Ataxin 2, a Neurodegenerative Disease Associated Protein

      Patrick Emery; Chitre, Monika (UMass Chan Medical School, 2022-08-08)
      Ataxin 2 (ATXN2) is a ubiquitously expressed mRNA binding protein involved in the development and progression of spinocerebellar ataxia 2 (SCA2) and amyotrophic lateral sclerosis (ALS). In the context of both neurodegenerative diseases, its N-terminal polyglutamine (polyQ) domain is mutated and expanded in length. Several other polyQ proteins, such as huntingtin (Htt), ataxin 3 (ATXN3), and ataxin 7 (ATXN7), undergo proteolytic processing that produces toxic fragments containing their polyQ domains. Investigating how ATXN2 is regulated by proteolysis is hindered by the lack of available molecular biological tools such as N-terminal ATXN2 antibodies to target and analyze the endogenous N-terminus of ATXN2. To circumvent this challenge, I developed a transient overexpression model of N-terminally tagged ATXN2 in HEK293E cells. Here, I demonstrate that both wild-type and mutant ATXN2 are targets of N-terminal proteolysis. I confirmed that ATXN2 produces an independent polyQ cleavage fragment like other polyQ proteins through basic molecular biology approaches such as Western blotting and immunoprecipitation. Additionally, I identified the specific region that is both necessary and sufficient for cleavage to occur via deletion mapping with multiple truncated ATXN2 mutants and reporter constructs. Further definition of ATXN2 as a target of proteolytic cleavage aligns it with other neurodegenerative polyQ proteins, and proteolysis is currently a less explored avenue of research for ATXN2-related disease development, progression, and therapeutic modalities. This work reveals a novel site that directs cleavage of ATXN2 and provides a potential avenue of investigation for how ATXN2 posttranslational modifications contribute to the progression of SCA2 and ALS.
    • UMCCTS Newsletter, August 2022

      UMass Center for Clinical and Translational Science (UMass Chan Medical School, 2022-08-04)
      This is the August 2022 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
    • Journal of eScience Librarianship (JeSLIB) Publishing Process

      Raboin, Regina Fisher (eScholarship@UMassChan, 2022-08-02)
      Describes the roles and responsibilities, author guidelines, and peer review process for the Journal of eScience Librarianship.
    • International Controlled Study of Revascularization and Outcomes Following COVID-Positive Mechanical Thrombectomy

      Dmytriw, Adam A.; Kuhn, Anna L.; Puri, Ajit S.; Jabbour, Pascal (2022-07-12)
      BACKGROUND: Previous studies suggest that the mechanisms and outcomes in COVID-19-associated stroke differ from those with non-COVID-19 strokes, but there is limited comparative evidence focusing on these populations. Therefore, we aimed to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors. METHODS: A cross-sectional, international multicenter retrospective study of consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable adjusted analysis was conducted. RESULTS: In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p < 0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (mTICI 3), COVID-19 was associated with lower odds of complete revascularization [OR=0.33; 95% CI=0.23-0.48; p < 0.001], which persisted on multivariable modelling with adjustment for other predictors [aOR=0.30; 95% CI=0.12-0.77; p=0.012]. Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p < 0.001). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and suffered higher morbidity/mortality rates.
    • Data and Code from "Show me the data! Data sharing practices demonstrated in published research at the University of Massachusetts Chan Medical School"

      Grynoch, Tess (2022-07-11)
      Data extracted from articles published by UMass Chan researchers to determine where and how data was being shared. Code from the analysis is also included.
    • UMCCTS Newsletter, July 2022

      UMass Center for Clinical and Translational Science (2022-07-11)
      This is the July 2022 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
    • COVID-19: a gray swan's impact on the adoption of novel medical technologies

      Dunlap, Denise; Santos, Roberto S.; Lilly, Craig M.; Teebagy, Sean; Hafer, Nathaniel S.; Buchholz, Bryan O.; McManus, David D. (2022-07-08)
      The COVID-19 pandemic offers a unique context and opportunity to investigate changes in healthcare professional perceptions towards the adoption of novel medical technologies, such as point-of-care technologies (POCTs). POCTs are a nascent technology that has experienced rapid growth as a result of COVID-19 due to their ability to increase healthcare accessibility via near-patient delivery, including at-home. We surveyed healthcare professionals before and during COVID-19 to explore whether the pandemic altered their perceptions about the usefulness of POCTs. Our network analysis method provided a structure for understanding this changing phenomenon. We uncovered that POCTs are not only useful for diagnosing COVID-19, but healthcare professionals also perceive them as increasingly important for diagnosing other diseases, such as cardiovascular, endocrine, respiratory, and metabolic diseases. Healthcare professionals also viewed POCTs as facilitating the humanization of epidemiology by improving disease management/monitoring and strengthening the clinician-patient relationship. As the accuracy and integration of these technologies into mainstream healthcare delivery improves, hurdles to their adoption dissipate, thereby encouraging healthcare professionals to rely upon them more frequently to diagnose, manage, and monitor diseases. The technological advances made in POCTs during COVID-19, combined with shifting positive perceptions of their utility by healthcare professionals, may better prepare us for the next pandemic.
    • Gliotransmission Orchestrates Neuronal Type-specific Axon Regeneration

      Yang Xiang; Wang, Fei (UMass Chan Medical School, 2022-06-30)
      Why closely related neuronal types differ in their axon regenerative abilities remains elusive. Here, I demonstrate gliotransmission determines such a difference in Drosophila larval sensory neurons. Axotomy activates ensheathing glia, which signal to regenerative neurons through the gliotransmitter adenosine, to mount regenerative programs including neuronal activity and Ras. Surprisingly, ensheathing glia do not signal to non-regenerative neurons. Such neuronal type-specific responses to gliotransmission result from specific expression of adenosine receptors in regenerative neurons. Disrupting gliotransmission impedes regeneration of regenerative neurons. Strikingly, reconstitution of gliotransmission in non-regenerative neurons enables them to regenerate. Furthermore, activation of an adenosine receptor in adult mice promotes both regeneration and survival of retinal ganglion cells, uncovering a conserved pro-regenerative role of adenosine receptors. My studies demonstrate gliotransmission as a novel mechanism by which glia instruct axon regeneration, with neuronal type-specificity, and suggest targeting purinergic signaling as a new strategy for mammalian central nervous system repair.
    • The Impact of the COVID-19 Pandemic on the Clubhouse Model

      McKay, Colleen E.; Corcoran, Joel D (2022-06-29)
      The COVID-19 pandemic posed challenges to the traditional Clubhouse Model of Psychosocial Rehabilitation (Clubhouse). The COVID-19 pandemic forced many Clubhouses around the world to rapidly pivot from face-to-face services and support programs at the Clubhouse to hybrid or virtual services. The Clubhouse community quickly mobilized to establish new structures to maintain connections with Clubhouse members and provide them with essential supports. This brief describes adaptations that Clubhouses made during the COVID-19 pandemic. We also describe supports offered by Clubhouse International to inform their international network about innovative approaches and best practices for Clubhouses during the COVID-19 pandemic.
    • Super large-bore ingestion of clot (SLIC) leads to high first pass effect in thrombectomy for large vessel occlusion

      Massari, Francesco; Dabus, Guilherme; Cortez, Gustavo M.; Singh, Jasmeet; Kuhn, Anna L.; Naragum, Varun; Anagnostakou, Vania; Hanel, Ricardo A.; Gounis, Matthew J.; Puri, Ajit S. (2022-06-22)
      BACKGROUND: Super large-bore aspiration (SLBA) has shown high rates of complete clot ingestion. OBJECTIVE: To report the initial clinical feasibility, safety, and efficacy of this novel SLBA insert combination-super large-bore ingestion of clot (SLIC) technique for stroke. METHODS: We performed a retrospective review of three comprehensive stroke center databases. The SLIC technique entails a triaxial assembly of an 8 Fr 0.106'' Base Camp catheter, 0.088'' catheter extender (HiPoint), and an insert catheter (Tenzing 8) that completely consumes the inner diameter of the 0.088'' SLBA catheter. The HiPoint catheter is delivered over the Tenzing 8 to the face of the embolus, which is withdrawn, while aspirating through the Base Camp and HiPoint catheters as a single assembly. RESULTS: Thirty-three consecutive patients with large vessel occlusion were treated with SLIC. The median age was 70 years (30-91) and 17 were male (51.5%). The median presenting National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT score was 21 (1-34) and 8 (5-10), respectively. There was 100% success in delivering the 0.088'' catheter to the site of the occlusion. The successful revascularization rate (modified Thrombolysis in Cerebral Infarction (mTICI) score > /=2B) was 100% within a single pass in most cases (82%). Final mTICI > /=2C was achieved in 94.1% of occlusions, with 73.5% mTICI 3 recanalization. The rate of first pass effect in achieving excellent reperfusion (mTICI > /=2C) was 70.5%. There were no adverse events or postprocedural symptomatic hemorrhages. CONCLUSIONS: Our initial experience with the SLIC technique resulted in achieving a first pass effect (mTICI > /=2C) in 70.5%. Navigation of the SLBA catheter extender over the Tenzing insert was successful and safe in this early experience.
    • Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and Cancer: US Preventive Services Task Force Recommendation Statement

      US Preventive Services Task Force; Mangione, Carol M.; Pbert, Lori (2022-06-21)
      Importance: According to National Health and Nutrition Examination Survey data, 52% of surveyed US adults reported using at least 1 dietary supplement in the prior 30 days and 31% reported using a multivitamin-mineral supplement. The most commonly cited reason for using supplements is for overall health and wellness and to fill nutrient gaps in the diet. Cardiovascular disease and cancer are the 2 leading causes of death and combined account for approximately half of all deaths in the US annually. Inflammation and oxidative stress have been shown to have a role in both cardiovascular disease and cancer, and dietary supplements may have anti-inflammatory and antioxidative effects. Objective: To update its 2014 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on the efficacy of supplementation with single nutrients, functionally related nutrient pairs, or multivitamins for reducing the risk of cardiovascular disease, cancer, and mortality in the general adult population, as well as the harms of supplementation. Population: Community-dwelling, nonpregnant adults. Evidence Assessment: The USPSTF concludes with moderate certainty that the harms of beta carotene supplementation outweigh the benefits for the prevention of cardiovascular disease or cancer. The USPSTF also concludes with moderate certainty that there is no net benefit of supplementation with vitamin E for the prevention of cardiovascular disease or cancer. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of supplementation with multivitamins for the prevention of cardiovascular disease or cancer. Evidence is lacking and the balance of benefits and harms cannot be determined. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of supplementation with single or paired nutrients (other than beta carotene and vitamin E) for the prevention of cardiovascular disease or cancer. Evidence is lacking and the balance of benefits and harms cannot be determined. Recommendation: The USPSTF recommends against the use of beta carotene or vitamin E supplements for the prevention of cardiovascular disease or cancer. (D recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the use of multivitamin supplements for the prevention of cardiovascular disease or cancer. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the use of single- or paired-nutrient supplements (other than beta carotene and vitamin E) for the prevention of cardiovascular disease or cancer. (I statement).
    • Defining the substrate envelope of SARS-CoV-2 main protease to predict and avoid drug resistance

      Shaqra, Ala M.; Zvornicanin, Sarah N.; Huang, Qiu Yu J.; Lockbaum, Gordon J.; Knapp, Mark; Tandeske, Laura; Bakan, David T.; Flynn, Julia M.; Bolon, Daniel N.; Moquin, Stephanie; et al. (2022-06-21)
      Coronaviruses can evolve and spread rapidly to cause severe disease morbidity and mortality, as exemplified by SARS-CoV-2 variants of the COVID-19 pandemic. Although currently available vaccines remain mostly effective against SARS-CoV-2 variants, additional treatment strategies are needed. Inhibitors that target essential viral enzymes, such as proteases and polymerases, represent key classes of antivirals. However, clinical use of antiviral therapies inevitably leads to emergence of drug resistance. In this study we implemented a strategy to pre-emptively address drug resistance to protease inhibitors targeting the main protease (M(pro)) of SARS-CoV-2, an essential enzyme that promotes viral maturation. We solved nine high-resolution cocrystal structures of SARS-CoV-2 M(pro) bound to substrate peptides and six structures with cleavage products. These structures enabled us to define the substrate envelope of M(pro), map the critical recognition elements, and identify evolutionarily vulnerable sites that may be susceptible to resistance mutations that would compromise binding of the newly developed M(pro) inhibitors. Our results suggest strategies for developing robust inhibitors against SARS-CoV-2 that will retain longer-lasting efficacy against this evolving viral pathogen.
    • Interventional oncology update

      Newbury, Alex; Ferguson, Chantal M.; Valero, Daniel Alvarez; Kutcher-Diaz, Roberto; McIntosh, Lacey J.; Karamanian, Ara; Harman, Aaron (2022-06-20)
      Interventional Oncology (IO) is a subspecialty field of Interventional Radiology bridging between diagnostic radiology and the clinical oncology team, addressing the diagnosis and treatment of cancer. There have been many exciting advancements in the field of IO in recent years; far too many to cover in a single paper. To give each topic sufficient attention, we have limited the scope of this review article to four topics which we feel have the potential to drastically change how cancer is treated managed in the immediate future.
    • Clinical Diagnoses and Outcomes After Diagnostic Breast Ultrasound by Nurses and General Practitioner Physicians in Rural Rwanda

      Pace, Lydia E.; Dusengimana, Jean-Marie Vianney; Hategekimana, Vedaste; Rugema, Vestine; Umwizerwa, Aline; Frost, Elisabeth; Kwait, Dylan; Schleimer, Lauren E.; Huang, ChuanChin; Shyirambere, Cyprien; et al. (2022-06-20)
      PURPOSE: To scale up early detection of breast cancer in low- and middle-income countries, research is needed to inform the role of diagnostic breast ultrasound performed by nonradiologists in resource-constrained settings. The authors examined 2-year clinical follow-up and outcomes among women who underwent diagnostic breast ultrasound performed by nonradiologist clinicians participating in a breast ultrasound training and mentorship program at a rural Rwandan hospital. METHODS: Imaging findings, management plans, and pathologic results were prospectively collected during the training using a standardized form. Data on follow-up and outcomes for patients receiving breast ultrasound between January 2016 and March 2017 were retrospectively collected through medical record review. RESULTS: Two hundred twenty-nine breast palpable findings (199 patients) met the study's eligibility criteria. Of 104 lesions initially biopsied, 38 were malignant on initial biopsy; 3 lesions were identified as malignant on repeat biopsy. All 34 patients ultimately diagnosed with cancer received initial recommendations for either biopsy or aspiration by trainees. The positive predictive value of trainee biopsy recommendation was 34.8% (95% confidence interval, 24.8%-45.0%). The sensitivity of trainees' biopsy recommendation for identifying malignant lesions was 92.7% (95% confidence interval, 84.2%-100%). Of 46 patients who did not receive biopsy and were told to return for clinical or imaging follow-up, 37.0% did not return. CONCLUSIONS: Trained nonradiologist clinicians in Rwanda successfully identified suspicious breast lesions on diagnostic breast ultrasound. Loss to follow-up was common among patients instructed to return for surveillance, so lower biopsy thresholds, decentralized surveillance, or patient navigation should be considered for patients with low- or intermediate-suspicion lesions.
    • Comprehensive fitness landscape of SARS-CoV-2 M(pro) reveals insights into viral resistance mechanisms

      Flynn, Julia; Samant, Neha; Nachum, Gily S.; Bakan, David T.; Yilmaz, Nese Kurt; Schiffer, Celia A.; Moquin, Stephanie A.; Dovala, Dustin; Bolon, Daniel N. (2022-06-20)
      With the continual evolution of new strains of SARS-CoV-2 that are more virulent, transmissible, and able to evade current vaccines, there is an urgent need for effective anti-viral drugs SARS-CoV-2 main protease (M(pro)) is a leading target for drug design due to its conserved and indispensable role in the viral life cycle. Drugs targeting M(pro) appear promising but will elicit selection pressure for resistance. To understand resistance potential in M(pro), we performed a comprehensive mutational scan of the protease that analyzed the function of all possible single amino acid changes. We developed three separate high-throughput assays of M(pro) function in yeast, based on either the ability of M(pro) variants to cleave at a defined cut-site or on the toxicity of their expression to yeast. We used deep sequencing to quantify the functional effects of each variant in each screen. The protein fitness landscapes from all three screens were strongly correlated, indicating that they captured the biophysical properties critical to M(pro) function. The fitness landscapes revealed a non-active site location on the surface that is extremely sensitive to mutation making it a favorable location to target with inhibitors. In addition, we found a network of critical amino acids that physically bridge the two active sites of the M(pro) dimer. The clinical variants of M(pro) were predominantly functional in our screens, indicating that M(pro) is under strong selection pressure in the human population. Our results provide predictions of mutations that will be readily accessible to M(pro) evolution and that are likely to contribute to drug resistance. This complete mutational guide of M(pro) can be used in the design of inhibitors with reduced potential of evolving viral resistance.
    • School Nurse Perspectives on School-Supervised Asthma Therapy: A Qualitative Study

      Hoque, Shushmita; Luther, Janki; Mizrahi, Raphael; Gerald, Lynn B.; Phipatanakul, Wanda; Lemon, Stephenie C.; Rosal, Milagros C.; Byatt, Nancy; Pbert, Lori; Trivedi, Michelle K. (2022-06-16)
      Background: School-supervised asthma therapy improves asthma outcomes for children, yet this strategy is not widely utilized. School nurses play a vital role in this intervention, yet their perspectives on school-supervised asthma therapy have not been thoroughly examined. Objectives: To examine the perspectives of school nurses participating in school-supervised asthma therapy and identify key facilitators, barriers, and proposed solutions that will facilitate the uptake of this strategy. Methods: We used purposeful sampling to recruit 12 school nurses participating in Asthma Link, a real-world application of school-supervised asthma therapy, between 2017 and 2019. We performed semistructured interviews with school nurses to elicit their perspectives on the facilitators, barriers, and proposed solutions to barriers to Asthma Link implementation. Interview transcripts were analyzed using qualitative descriptive methodology to identify major themes. Results: School nurses identified facilitators for Asthma Link adoption, including the ease of integrating supervised therapy into school nurse routines, recognition of benefits for families with limited resources, and satisfaction participating in preventive care. School nurses identified barriers, including communication challenges with families and providers, families not reliably bringing medication to school, limited nursing staff in schools, and increased school nurse turnover. School nurses proposed specific solutions to these barriers, including appointing Asthma Link liaisons within pediatric practices, incentivizing families to bring medicine to school, and partnering new school nurses with those experienced in delivering Asthma Link to overcome staffing issues and promote program fidelity. Conclusions: School nurse perspectives on the facilitators, barriers, and solutions to barriers are important for understanding how to promote real-world implementation of school-supervised asthma therapy. The themes identified in this study will be utilized to refine our protocol for Asthma Link to facilitate real-world adoption of this evidence-based strategy.
    • Ultrasound of the Endometrium, Parts 1 and 2

      Harris, Robert D. (2022-06-16)
      This presentation is part of the PEER Liberia Radiology Lecture Series. It provides an overview for clinicians of ultrasound of the endometrium, including histology, accurate endometrial measurements, and endometrial abnormalities.