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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  • Individual Development Plan for Career Development Professionals

    Ismael, Amber; Campbell, Brian; Chremos, Ioannis Vasileios; Fuhrmann, Cynthia N; Nordell, Shawn (2024-06-21)
    The Individual Development Plan for Career Development Professionals is an IDP worksheet to guide individuals who are pursuing careers in graduate/postdoctoral career development through the process of creating their own IDP. The worksheet is designed as an IDP tool for all career levels, including those preparing to enter this field, practitioners seeking to grow within their current positions, or those looking to advance or pursue a career transition. The tool includes prompts to guide one through exercises that help one assess their skills, values, interests, progress and growth; set goals and define an action plan; and consider the resources, mentorship, and community that they may need to help develop a fulfilling career. Though designed for professionals in the career development field, this tool may also be helpful for those in other academic administration or education roles. This tool was designed by members of the Professional Development Committee of the Graduate Career Consortium, an international member organization to help individuals advance the field of graduate and postdoctoral career and professional development.
  • Racial Disparities and Trends in Anticoagulant Use among Ambulatory Care Patients with Atrial Fibrillation and Atrial Flutter in the United States from 2007-2019 [preprint]

    Kan, Vincent; Lapane, Kate L; McManus, David D; Baek, Jonggyu; Darling, Chad E; Alcusky, Matthew J (2024-06-15)
    Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, significantly increasing the risk of stroke. The introduction of direct oral anticoagulants (DOACs) since 2010 has transformed anticoagulation therapy, offering an alternative to warfarin with improved safety profiles. Despite the increased adoption of DOACs, disparities in their use among different racial and ethnic groups in the United States remain understudied. Methods This study utilized a repeated cross-sectional design, analyzing data from the National Ambulatory Medical Care Survey (NAMCS) from 2007 to 2019. The study population included adults diagnosed with AF or atrial flutter (AFL). We analyzed the temporal trends of DOAC and warfarin use from 2007 to 2019. We examined the prevalence of DOAC versus warfarin use and assessed associations between race/ethnicity, patient characteristics, and DOAC utilization from 2011 to 2019. Multivariable modified Poisson regression models were used to calculate adjusted prevalence ratios (aPR) for the associations. Results From 2011 to 2019, NAMCS recorded 3,224 visits involving AF or AFL, representing a weighted estimate of 103.6 million visits. DOAC use increased significantly, with apixaban becoming the predominant anticoagulant by 2016. Non-Hispanic Black patients were less likely to use DOACs compared to non-Hispanic White patients over time (aPR 0.75; 95% CI, 0.63-0.90). Patients with Medicaid insurance were also less likely to use DOACs (aPR 0.14; 95% CI: 0.04-0.46). Conclusion Despite the shift from warfarin to DOACs for AF and AFL treatment, significant racial and socioeconomic disparities persist. Non-Hispanic Black patients and those with Medicaid insurance are less likely to use DOACs. These findings highlight the need for targeted strategies to ensure equitable access to advanced anticoagulant therapies.
  • Depressive Symptoms in Adolescence as a Predictor of Young Adult Employment Quality: Findings from the National Longitudinal Study of Adolescent to Adult Health

    Sabella, Kathryn (2024-06-13)
    This study uses longitudinal data from a nationally representative sample of adolescents, The National Longitudinal Study of Adolescent to Adult Health, to investigate the association between depressive symptomatology in adolescence and indicators of employment quality in young adulthood. A better understanding of the long-term impacts of adolescent depressive symptoms on employment quality during young adulthood would inform our understanding of how economic and mental health trajectories of individuals with a history of depression unfold.
  • Correction of multiplexing artefacts in multi-pinhole SPECT through temporal shuttering, de-multiplexing of projections, and alternating reconstruction

    Pells, Sophia; Zeraatkar, Navid; Kalluri, Kesava S; Moore, Stephen C; May, Micaehla; Furenlid, Lars R; Kupinski, Matthew A; Kuo, Phillip H; King, Michael A (2024-06-06)
    Objective.Single-photon emission computed tomography (SPECT) with pinhole collimators can provide high-resolution imaging, but is often limited by low sensitivity. Acquiring projections simultaneously through multiple pinholes affords both high resolution and high sensitivity. However, the overlap of projections from different pinholes on detectors, known as multiplexing, has been shown to cause artefacts which degrade reconstructed images.Approach.Multiplexed projection sets were considered here using an analytic simulation model of AdaptiSPECT-C-a brain-dedicated multi-pinhole SPECT system. AdaptiSPECT-C has fully adaptable aperture shutters, so can acquire projections with a combination of multiplexed and non-multiplexed frames using temporal shuttering. Two strategies for reducing multiplex artefacts were considered: an algorithm to de-multiplex projections, and an alternating reconstruction strategy for projections acquired with a combination of multiplexed and non-multiplexed frames. Geometric and anthropomorphic digital phantoms were used to assess a number of metrics.Main results.Both de-multiplexing strategies showed a significant reduction in image artefacts and improved fidelity, image uniformity, contrast recovery and activity recovery (AR). In all cases, the two de-multiplexing strategies resulted in superior metrics to those from images acquired with only mux-free frames. The de-multiplexing algorithm provided reduced image noise and superior uniformity, whereas the alternating strategy improved contrast and AR.Significance.The use of these de-multiplexing algorithms means that multi-pinhole SPECT systems can acquire projections with more multiplexing without degradation of images.
  • UMCCTS Newsletter, June 2024

    UMass Center for Clinical and Translational Science (2024-06-03)
    This is the June 2024 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
  • ACR Appropriateness Criteria® Female Breast Cancer Screening: 2023 Update

    Niell, Bethany L; Jochelson, Maxine S; Amir, Tali; Brown, Ann; Adamson, Megan; Baron, Paul; Bennett, Debbie L; Chetlen, Alison; Dayaratna, Sandra; Freer, Phoebe E; et al. (2024-06-01)
    Early detection of breast cancer from regular screening substantially reduces breast cancer mortality and morbidity. Multiple different imaging modalities may be used to screen for breast cancer. Screening recommendations differ based on an individual's risk of developing breast cancer. Numerous factors contribute to breast cancer risk, which is frequently divided into three major categories: average, intermediate, and high risk. For patients assigned female at birth with native breast tissue, mammography and digital breast tomosynthesis are the recommended method for breast cancer screening in all risk categories. In addition to the recommendation of mammography and digital breast tomosynthesis in high-risk patients, screening with breast MRI is recommended. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
  • Apheresis practice variation during the COVID-19 pandemic: Results of a survey

    Tanhehco, Yvette C; Alsammak, Mohamed; Chhibber, Vishesh; Ibeh, Nnaemeka; Li, Yanhua; Stephens, Laura D; Noland, Daniel K; Wu, Ding Wen; Zantek, Nicole D; DeChristopher, Phillip J; et al. (2024-06-01)
    Background: The COVID-19 pandemic affected healthcare delivery across all specialties including apheresis. To describe the changes in apheresis service practices that occurred during the pandemic, the American Society for Apheresis (ASFA) Apheresis Medicine Attending Physician Subcommittee conducted a survey study. Study design and methods: A 32-question survey was designed and distributed to 400 ASFA physician members on September 7, 2022. Attending physicians responded to questions about whether and how apheresis service practices changed during the COVID-19 pandemic compared with the time period prior to the pandemic in terms of: (1) procedure types and volumes, (2) patient consultation workflow, and (3) the use of telemedicine. Descriptive analyses were reported as number and frequency of responses. Results: The survey response rate was 13.8% (55/400). Of these respondents, 96.4% (53/55) were attending physicians. The majority of respondents (42/53, 79.2%) indicated that the types of procedures performed during COVID-19 compared to pre-pandemic did not change. Most frequently for apheresis procedure volume, respondents reported: no change in their monthly inpatient volume (21/47, 44.7%) and a decrease in their monthly outpatient volume (28/46, 60.9%). Prior to COVID-19, 75.0% (30/40) of respondents performed consultations at bedside for inpatients and 67.4% (29/43) performed consultations at bedside for outpatients. Bedside consultations decreased in both settings during the pandemic but were still most frequently performed by attending physicians. At the same time, the use of telemedicine increased for 15.4% of survey respondents during COVID-19. Conclusion: Some, but not all, respondents observed or made changes to their apheresis service during the COVID-19 pandemic. A subset of changes, such as increased utilization of telemedicine, may persist.
  • Kinetics of Pre-mRNA 3’ End Cleavage

    Torres Ulloa, Leslie (2024-05-31)
    3’ end cleavage and polyadenylation are required steps in pre-mRNA maturation. The rate at which 3’ end cleavage occurs can determine the temporal availability of mRNA for subsequent function throughout the cell and is likely tightly regulated. While there are numerous high-throughput methods for global profiling of RNA maturation rates, the study of pre-mRNA 3’ end cleavage kinetics has remained limited to low-throughput approaches, and the temporal regulation of polyadenylation site choice that determines the composition of the 3’ UTRs of mRNAs remains poorly understood. This research project seeks to address this gap by introducing a novel genome-wide, site-specific methodology for estimating rates of pre-mRNA 3’ end cleavage, using metabolic labeling of nascent RNA, high-throughput sequencing, and mathematical modeling. Using in-silico simulations of nascent RNA-seq data, we show that our approach can accurately and precisely estimate cleavage half-lives for both constitutive and alternative sites. In Drosophila melanogaster S2 cells, we find that cleavage rates are fast but highly variable across sites, with alternative events being slowest. This variability in rates is underpinned by distinctive sequence elements, where an A-rich region upstream of the cleavage site, a U-rich element downstream of the cleavage site, and a higher density of polyadenylation signals, lead to faster cleavage reactions. Assessment of Polymerase II dynamics around cleavage sites reveals that cleavage rates are associated with the localization of RNA Polymerase II at the end of a gene and faster cleavage leads to quicker degradation of downstream read-through RNA. This approach for estimating pre-mRNA 3’ end cleavage kinetics opens new possibilities in the study of co-transcriptional regulation of mRNA expression and transcription termination across cellular states.
  • SARS-CoV-2 infection is associated with an increase in new diagnoses of schizophrenia spectrum and psychotic disorder: A study using the US national COVID cohort collaborative (N3C)

    Rahman, Asif; Russell, Michael; Zheng, Wanhong; Eckrich, Daniel; Ahmed, Imtiaz (2024-05-30)
    Amid the ongoing global repercussions of SARS-CoV-2, it is crucial to comprehend its potential long-term psychiatric effects. Several recent studies have suggested a link between COVID-19 and subsequent mental health disorders. Our investigation joins this exploration, concentrating on Schizophrenia Spectrum and Psychotic Disorders (SSPD). Different from other studies, we took acute respiratory distress syndrome (ARDS) and COVID-19 lab-negative cohorts as control groups to accurately gauge the impact of COVID-19 on SSPD. Data from 19,344,698 patients, sourced from the N3C Data Enclave platform, were methodically filtered to create propensity matched cohorts: ARDS (n = 222,337), COVID-19 positive (n = 219,264), and COVID-19 negative (n = 213,183). We systematically analyzed the hazard rate of new-onset SSPD across three distinct time intervals: 0-21 days, 22-90 days, and beyond 90 days post-infection. COVID-19 positive patients consistently exhibited a heightened hazard ratio (HR) across all intervals [0-21 days (HR: 4.6; CI: 3.7-5.7), 22-90 days (HR: 2.9; CI: 2.3 -3.8), beyond 90 days (HR: 1.7; CI: 1.5-1.)]. These are notably higher than both ARDS and COVID-19 lab-negative patients. Validations using various tests, including the Cochran Mantel Haenszel Test, Wald Test, and Log-rank Test confirmed these associations. Intriguingly, our data indicated that younger individuals face a heightened risk of SSPD after contracting COVID-19, a trend not observed in the ARDS and COVID-19 negative groups. These results, aligned with the known neurotropism of SARS-CoV-2 and earlier studies, accentuate the need for vigilant psychiatric assessment and support in the era of Long-COVID, especially among younger populations.
  • Variation in Depth of Sedation Targeted and Achieved among Mechanically Ventilated Patients and Associated Outcomes

    Rucci, Justin M (2024-05-30)
    Introduction: Sedative agents are commonly administered to patients receiving mechanical ventilation (MV). Practice guidelines recommend provision of light sedation within validated scoring systems (e.g., Richmond Agitation Sedation Scale [RASS]), but recognize some circumstances require deeper sedation. The real-world approaches to depth of sedation, and the impact of hospital sedation practices on patient outcomes, remain uncharacterized. Methods: We used the US based eICU collaborative research database to identify adult patients who received MV > 24 hours, who did not have a diagnosis that may require sedatives for indications other than facilitating MV, and who had recorded RASS goals and scores. We used mixed effects regression models to determine factors associated with initial RASS goals and rates of RASS score-goal concordance. We organized hospitals into quartiles of risk-adjusted RASS score-goal concordance, and used g-computation to evaluate differences in ventilator free days (VFD) at hospital day 28. Results: We identified a study sample of 1,650 adult patients (at 21 hospitals) who met inclusion/exclusion criteria. Hospital-level risk-adjusted initial RASS goals ranged from -1.4 to 0.2, and hospital-level risk-adjusted RASS score-goal concordance ranged from 27% to 64%. Patients admitted to hospitals in the highest quartile of score-goal concordance (quartile 4) were generally targeted for deeper sedation (median RASS goal -1.31) than patients admitted to hospitals in the lowest quartile (quartile 1) (median RASS goal -0.58). Compared to patients admitted to quartile 1 hospitals, patients at quartile 4 hospitals experienced fewer VFDs (adjusted incidence risk difference -2.4, 95% CI -4.26 to -0.36). Conclusion: US hospitals prescribe RASS goals in line with guideline recommendations for light sedation, but there is wide variation in achieving these RASS goals. Hospitals with higher RASS score-goal concordance typically prescribed deeper RASS goals, and patients admitted to these hospitals experienced fewer VFD.
  • Disparities in Palliative Care Use for Patients With Blood Cancer Who Died in the Hospital

    Hsieh, Tien-Chan; Yeo, Yee Hui; Zou, Guangchen; Zhou, Chan; Ash, Arlene S. (2024-05-27)
    Background: Palliative care can enhance quality of life during a terminal hospitalization. Despite advances in diagnostic and treatment tools, blood cancers lag behind solid malignancies in palliative use. It is not clear what factors affect palliative care use in blood cancer. Methods: We used the 2016 to 2019 National Inpatient Sample to identify demographic and socioeconomic factors associated with receiving palliative care among patients over age 18 with any malignant hematological diagnosis during a terminal hospitalization lasting at least 3 days, excluding those receiving a stem cell transplant. Results: Palliative care use was documented 54% of the time among 49,720 weighted cases (9944 distinct individual hospitalizations), approximately evenly distributed across the years 2016-2019. Palliative care use was lowest in 2016 (51%) and highest in 2018 (58%), and increased with age, reaching 58% for those 80 years and older. Men and women were similarly likely to receive care. Patients of Hispanic ethnicity and African Americans received less palliative care (47% and 49%, respectively), as did those insured by Medicaid (48%), and those admitted to small or rural hospitals (52% and 47%, respectively). Charges for hospitalizations with palliative care were 19% lower than for those without it. Conclusions: This study highlights disparities in palliative care use among blood-cancer patients who died in the hospital. It seems likely that many of the 46% who did not receive palliative care could have benefitted from it. Interventions are likely needed to achieve equitable access to ideal levels of palliative care services in late-stage blood cancer.
  • Facilitating Culturally Competent Breast Imaging Care in South Asian Patients

    Sharma, Nidhi; Mehta, Tejas S; Wahab, Rifat A; Patel, Miral M (2024-05-24)
    South Asians are a rapidly growing subset of the Asian population in the United States. They comprise people from multiple countries with diverse beliefs, languages, and cultural identities and values. The incidence of breast cancer is rising in South Asian women in the United States, with earlier onset and predilection for HER2-enriched tumors. Despite the rising incidence of breast cancer, participation in screening remains lower than other populations. Health care inequities in South Asian women are multifactorial and may be due to traditional health beliefs and practices, language barriers, cultural differences, and lack of overall awareness. Developing a culturally sensitive environment in breast imaging clinic practice can lead to improved patient care and adherence. Given the scarcity of data specific to the South Asian population in United States, there is a need for health service researchers and practice leaders to obtain more high-quality data to understand the needs of South Asian patient populations.
  • Maternal and Perinatal Factors Associated With Childhood Brain Tumors: A Case-Control Study in Vietnam

    Pham, Huy Ngoc; Goldberg, Robert J.; Pham, Loc Quang; Nguyen, Hoa L; Pham, Dao Anh; Mai, Linh Thi Thuy; Phung, Toi Lam; Hung, Doan Quoc; Dong, He Van; Duong, Ha Dai (2024-05-23)
    Introduction: Brain cancer is the leading cause of cancer-related deaths in children and the majority of childhood brain tumors are diagnosed without determination of their underlying etiology. Little is known about risk factors for childhood brain tumors in Vietnam. The objective of this case-control study was to identify maternal and perinatal factors associated with brain tumors occurring in young Vietnamese children and adolescents. Methods: We conducted a hospital-based case-control study at Viet Duc University Hospital in Hanoi, Vietnam. Cases consisted of children with brain tumors aged 0-14 years old admitted to the hospital from January 2020 to July 2022 while the controls were age and sex-matched hospitalized children diagnosed with head trauma. Perinatal characteristics were abstracted from hospital medical records and maternal medical, behavioral, and sociodemographic factors were collected through in-person interviews. Conditional logistic regression models were used to examine maternal and perinatal factors associated with childhood brain tumors. Results: The study sample included 220 children (110 cases and 110 controls) whose average age was 8.9 years and 41.8% were girls. Children born to mothers aged greater than 30 years at the time of the child's birth had a higher risk of childhood brain tumors compared to those born to mothers aged from 18 to 30 years old (OR = 2.55; 95% CI: 1.13-5.75). Additionally low maternal body mass index prior to the current pregnancy of <18.5 kg/m2 significantly increased the odds of having a child with a brain tumor in relation to normal maternal body mass index from 18.5-22.9 kg/m2 (OR = 3.19; 95% CI: 1.36 - 7.50). Conclusion: Advanced maternal age and being markedly underweight were associated with an increased odds of having a child with a brain tumor. A population-based study with larger sample size is needed to confirm and extend the present findings.
  • SLIGHT shield dataset on effect of chest shielding during phototherapy in premature infants on the incidence of patent ductus arteriosus

    Amin, Sanjiv; Mannan, Javed (2024-05-23)
    The SLIGHT shield dataset reflects the results from a double blind randomized trial on the effect of chest shielding during phototherapy in premature infants on the incidence of patent ductus arteriosus. All preterm infants ≤ 29 weeks GA or weighing ≤1000 grams at birth admitted to our neonatal intensive care unit (NICU) within the first 24 hours of life were eligible for the study and randomized to chest shield placement or sham shield placement during phototherapy treatment. Enrollment occurred from August 1, 2015 to April 13, 2018. The primary outcome was the incidence of sPDA diagnosed via clinical parameters by the investigator team during the period from 24 hours after initiating phototherapy to 3 days after stopping phototherapy. Secondary outcomes consistent of echo based parameters : 1) ductal diameter with a left to right or bidirectional shunt across the PDA 2) left atrium (LA) to aortic root (AO) diameter ratio (LA/AO) and 3) LA volume. Additional secondary outcomes included the following: 1) surgical ligation of PDA, 2) chronic lung disease (CLD), 3) retinopathy of prematurity (ROP), 4) intraventricular hemorrhage (IVH), 5) peak levels of total serum bilirubin and 6) duration of phototherapy. Baseline/demographc data as well as clinical data were also obtained. Study participants self-reported three items assessing religiosity: strength/comfort from religion, petition prayers for health, and awareness of intercessory prayers by others. All cause-mortality within 2-years of hospital discharge was ascertained by review of medical records at participating study hospitals and from death certificates. Cox proportional hazards models were used to estimate the multivariable adjusted risk of 2-year all-cause mortality.
  • A Case Study Identifying Barriers to Breast Cancer Screening and Strategies for Improved Access and Participation in an Underserved Community

    Vijayaraghavan, Gopal R (2024-05-20)
    A complex interplay of racial, ethnic, and social determinants are the drivers for disparity in access to screening, quality of care and health outcomes in diverse populations.
  • Spatial Transcriptomics Reconstruction of Mouse Olfactory System

    Wang, I-Hao (2024-05-20)
    The olfactory system is crucial for animals in tasks such as foraging, mate selection, and predator avoidance due to its ability to detect and distinguish a vast array of environmental chemicals. Mice detect these chemicals via olfactory receptor (OR) proteins, which are uniquely expressed by olfactory sensory neurons (OSNs); each OSN expresses only one OR type. OSNs with the same OR converge their axons to a specific location in the olfactory bulb (OB), forming a structure known as a glomerulus. This precise organization ensures a consistent, spatially invariant pattern of glomerular activation for each odorant, playing a likely role in the brain's decoding of odor identities. Nevertheless, the exact locations of most glomeruli are unknown, and the mechanisms that create consistent glomerular maps across different animals are not fully understood. In this study, we leveraged spatial transcriptomics and machine learning to map the majority of glomerular positions within the mouse OB. Furthermore, single-cell RNA sequencing revealed distinct transcriptional profiles for each OSN type, characterized not only by their OR gene but also by a unique set of axon guidance genes. These profiles can predict the eventual location of each OSN's glomerulus within the olfactory bulb. We also identified a correlation between the spatial distribution of glomeruli and the characteristics of their corresponding ORs, suggesting a chemotopic arrangement in the mouse olfactory system. Additionally, we probed the complexity of the OB by creating a spatially resolved cell atlas through spatial single-cell transcriptomics, revealing the identity and distribution of neuron subtypes that contribute to odor perception.
  • Working Together to Mint DOIs on Demand for a DSpace Repository

    Grynoch, Tess; Palmer, Lisa A. (2024-05-20)
    Background: Digital Object Identifiers (DOIs) are a key persistent identifier in the publishing landscape to ensure discoverability and citation of research products. Minting DOIs can be a time-consuming task for repository librarians. This process can be automated since the metadata for DOIs is already in the repository record and DataCite, a DOI minting organization, and Open Repository, a DSpace repository platform, both have application programming interfaces (APIs). Previous software has enabled bulk DOI minting. However, the institutional repository contains a mixture of original materials (dissertations, reports, data, etc.) and previously published materials such as journal articles and preprints. Description: An institutional repository librarian and her librarian colleague with Python experience embarked on a pair programming project to create a script to mint DOIs on demand in DataCite for individual items in the institution’s Open Repository instance. The pair met for one hour each week to develop and test the script. The institutional repository librarian lent invaluable insight into both platforms and the metadata variations the code would need to account for. The project was also a great learning opportunity for both librarians to improve their Python coding skills. This project will be evaluated in terms of how the time spent creating the code compares to the time it takes to mint DOIs manually as well as metadata enhancements and accuracy in DataCite. Program Conclusion: This poster will share the final Python script and highlight the takeaways from this approach for both the institutional repository librarian and the coding librarian. Final evaluation is forthcoming.
  • Safety and clinical outcomes of endovascular therapy versus medical management in late presentation of large ischemic stroke

    Mujanovic, Adnan; Strbian, Daniel; Demeestere, Jelle; Marto, João Pedro; Puetz, Volker; Nogueira, Raul G; Abdalkader, Mohamad; Nagel, Simon; Raymond, Jean; Ribo, Marc; et al. (2024-05-17)
    Introduction: The benefit of endovascular therapy (EVT) among stroke patients with large ischemic core (ASPECTS 0-5) in the extended time window outside of trial settings remains unclear. We analyzed the effect of EVT among these stroke patients in real-world settings. Patients and methods: The CT for Late Endovascular Reperfusion (CLEAR) study recruited patients from 66 centers in 10 countries between 01/2014 and 05/2022. The extended time-window was defined as 6-24 h from last-seen-well to treatment. The primary outcome was shift of the 3-month modified Rankin scale (mRS) score. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality. Outcomes were analyzed with ordinal and logistic regressions. Results: Among 5098 screened patients, 2451 were included in the analysis (median age 73, 55% women). Of patients with ASPECTS 0-5 (n = 310), receiving EVT (n = 209/310) was associated with lower 3-month mRS when compared to medical management (median 4 IQR 3-6 vs 6 IQR 4-6; aOR 0.4, 95% CI 0.2-0.7). Patients undergoing EVT had higher sICH (11.2% vs 4.0%; aOR 4.1, 95% CI 1.2-18.8) and lower mortality (31.6% vs 58.4%, aOR 0.4; 95% CI 0.2-0.9) compared to medically managed patients. The relative benefit of EVT was comparable between patients with ASPECTS 0 and 5 and 6-10 in the extended time window (interaction aOR 0.9; 95% CI 0.5-1.7). Conclusion: In the extended time window, patients with ASPECTS 0-5 may have preserved relative treatment benefit of EVT compared to patients with ASPECTS 6-10. These findings are in line with recent trials showing benefit of EVT among real-world patients with large ischemic core in the extended time window. Trial registration number:; Unique identifier: NCT04096248.
  • ADAM9 promotes type I interferon-mediated innate immunity during encephalomyocarditis virus infection

    Bazzone, Lindsey E; Zhu, Junji; King, Michael; Liu, GuanQun; Guo, Zhiru; MacKay, Christopher R; Kyawe, Pyae P; Qaisar, Natasha; Rojas-Quintero, Joselyn; Owen, Caroline A; et al. (2024-05-16)
    Viral myocarditis, an inflammatory disease of the heart, causes significant morbidity and mortality. Type I interferon (IFN)-mediated antiviral responses protect against myocarditis, but the mechanisms are poorly understood. We previously identified A Disintegrin And Metalloproteinase domain 9 (ADAM9) as an important factor in viral pathogenesis. ADAM9 is implicated in a range of human diseases, including inflammatory diseases; however, its role in viral infection is unknown. Here, we demonstrate that mice lacking ADAM9 are more susceptible to encephalomyocarditis virus (EMCV)-induced death and fail to mount a characteristic type I IFN response. This defect in type I IFN induction is specific to positive-sense, single-stranded RNA (+ ssRNA) viruses and involves melanoma differentiation-associated protein 5 (MDA5)-a key receptor for +ssRNA viruses. Mechanistically, ADAM9 binds to MDA5 and promotes its oligomerization and thereby downstream mitochondrial antiviral-signaling protein (MAVS) activation in response to EMCV RNA stimulation. Our findings identify a role for ADAM9 in the innate antiviral response, specifically MDA5-mediated IFN production, which protects against virus-induced cardiac damage, and provide a potential therapeutic target for treatment of viral myocarditis.
  • Exploring the relationship between school-supervised asthma therapy and social determinants of health in pediatric asthma care

    Al-Halbouni, Layana; Ryan, Grace W; Radu, Sonia; Spano, Michelle; Sabnani, Reshma; Phipatanakul, Wanda; Gerald, Lynn B; Garg, Arvin; Pbert, Lori; Trivedi, Michelle (2024-05-16)
    Background: Social determinants of health (SDoH), including access to care, economic stability, neighborhood factors, and social context, strongly influence pediatric asthma outcomes. School-supervised asthma therapy (SST) is an evidence-based strategy that improves asthma outcomes, particularly for historically marginalized children, by providing support for daily medication adherence in school. However, little is known about the relationship between these programs and the adverse SDoH commonly affecting underrepresented minority and marginalized children with asthma. Methods: We examined qualitative data from interviews (n = 52) conducted between 2017 and 2020 with diverse multi-level partners involved in Asthma Link, a SST intervention. Participants included end-users (children and their parents), deliverers (school nurses and pediatric providers), and systems-level partners (e.g., insurers, legislators, and state officials). We used inductive coding to determine themes and subthemes and deductive coding using the Healthy People 2030 SDoH framework. Results: Three themes emerged: (1) SST mitigates adverse SDoH (improves access to preventive healthcare and asthma health literacy), (2) SST benefits children experiencing specific adverse SDoH (provides a consistent medication routine to children with unstable family/housing situations) and (3) specific adverse SDoH impede SST implementation (economic instability, culture and language barriers). Conclusion: This study suggests an important relationship between SDoH and SST that warrants further evaluation in our future work on this community-based asthma intervention. Moreover, our findings underscore the importance of measuring SDoH in the implementation and evaluation of pediatric asthma interventions, particularly given the strong influence of these social factors on child health outcomes.

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