tbuckley/cabot-search huggingface dataset:
SARS-CoV-2 infection induces beta cell transdifferentiation
Authors: Xuming Tang, Skyler Uhl, Tuo Zhang, Dongxiang Xue, Bo Li, J. Jeya Vandana, Joshua A. Acklin, Lori L. Bonnycastle, Narisu Narisu, Michael R. Erdos, Yaron Bram, Vasuretha Chandar, Angie Chi Nok Chong, Lauretta A. Lacko, Zaw Min, Jean K. Lim, Alain C. Borczuk, Jenny Xiang, Ali Naji, Francis S. Collins, Todd Evans, Chengyang Liu, Benjamin R. tenOever, Robert E. Schwartz, Shuibing Chen
Journal: Cell Metabolism (2021)

Recent clinical data have suggested a correlation between coronavirus disease 2019 (COVID-19) and diabetes. Here, we describe the detection of SARS-CoV-2 viral antigen in pancreatic beta cells in autopsy samples from individuals with COVID-19. Single-cell RNA sequencing and immunostaining from ex vivo infections confirmed that multiple types of pancreatic islet cells were susceptible to SARS-CoV-2, eliciting a cellular stress response and the induction of chemokines. Upon SARS-CoV-2 infection, beta cells showed a lower expression of insulin and a higher expression of alpha and acinar cell markers, including glucagon and trypsin1, respectively, suggesting cellular transdifferentiation. Trajectory analysis indicated that SARS-CoV-2 induced eIF2-pathway-mediated beta cell transdifferentiation, a phenotype that could be reversed with trans-integrated stress response inhibitor (trans-ISRIB). Altogether, this study demonstrates an example of SARS-CoV-2 infection causing cell fate change, which provides further insight into the pathomechanisms of COVID-19.
Predictive modelling for COVID-19 outbreak control: lessons from the navy cluster in Sri Lanka
Authors: N. W. A. N. Y. Wijesekara, Nayomi Herath, K. A. L. C. Kodituwakku, H. D. B. Herath, Samitha Ginige, Thilanga Ruwanpathirana, Manjula Kariyawasam, Sudath Samaraweera, Anuruddha Herath, Senarupa Jayawardena, Deepa Gamge
Journal: Military Medical Research (2021)

Abstract In response to an outbreak of coronavirus disease 2019 (COVID-19) within a cluster of Navy personnel in Sri Lanka commencing from 22nd April 2020, an aggressive outbreak management program was launched by the Epidemiology Unit of the Ministry of Health. To predict the possible number of cases within the susceptible population under four social distancing scenarios, the COVID-19 Hospital Impact Model for Epidemics (CHIME) was used. With increasing social distancing, the epidemiological curve flattened, and its peak shifted to the right. The observed or actually reported number of cases was above the projected number of cases at the onset; however, subsequently, it fell below all predicted trends. Predictive modelling is a useful tool for the control of outbreaks such as COVID-19 in a closed community.
Two distinct phenotypes of t(5;12)(q33;p13) myeloid malignancy associated with variable isoforms of TEL-PDGF beta R mRNA.
Authors: Yagasaki F, Yoshida S, Yamazaki H, Nakao S, Nagai K, Jinnai I, Murohashi I, Bessho M, Hirashima K
Journal: Blood (1997)
Abstract 16064: Mechanical Left Ventricular Venting is Associated With Improved Survival in Adults Undergoing Venoarterial Extracorporeal Life Support: An ELSO Registry Analysis
Authors: Jose I Nunez, Brooks Willar, Kevin Kennedy, Peter Rycus, Joseph Tonna, Marwa Sabe, Navin K Kapur, Shahzad Shaefi, Arthur R Garan, Edward W Grandin
Journal: Circulation (2020)

Introduction: Venoarterial extracorporeal life support (VA-ECLS) imposes increased afterload on the left ventricle (LV), potentially provoking LV distension and impaired ventricular recovery. Prior studies have suggested a survival benefit with LV mechanical venting (MV), but multi-center data are lacking. Methods: We queried the ELSO registry for adults undergoing VA-ECLS and stratified them by the use of MV, including intra-aortic balloon pump and percutaneous ventricular assist device. We excluded patients with pulmonary embolism, heart transplant, congenital and valvular heart disease, aortic disease, and central cannulation. The primary outcome was in-hospital mortality. Secondary outcomes were on-support mortality and major adverse events, including bleeding, hemolysis, ischemic stroke, limb ischemia, and renal injury. We used multivariable logistic regression modeling to adjust for relevant clinical covariates. Results: Among 12734 patients undergoing VA-ECLS, 3353 (26.3%) received MV devices. Patients with MV were older (mean age 56.3 vs 52.7 years), more often male (76.3% vs 68.5%), and more often supported for acute myocardial infarction (43.0% vs 21.7%), p&lt;0.001 for all. Prior to ECLS, patients with MV had lower rates of cardiac arrest (51.7% vs 55.1%) but more commonly needed &gt;2 vasopressors (41.8% vs 27.2%) and had a higher incidence of acute renal (17.1% vs 10.5%), liver (4.4% vs 3.1%), and respiratory failure (20.9% vs 15.9%), p&lt;0.001 for all. Crude on-support (41.6% vs 47.8%, p&lt;0.001) and in-hospital (56.7% vs 59.2%, p=0.01) mortality were lower in the MV group. In multivariable modeling, MV was associated with a significantly lower odds of mortality but higher odds of adverse events including medical and cannula site bleeding, hemolysis, limb ischemia and renal injury (Figure). Conclusions: Among adults supported with peripheral VA-ECLS, LV MV was associated with lower mortality despite a higher rate of important adverse events.
Abstract 16664: Aortic Valve Calcification is Prognostic for Mild Cognitive Impairment
Authors: Hojune E Chung, Jessica Chen, Jared L Christensen, Dhairyasheel S Ghosalkar, Cullen Soares, Alice Chu, Nishant R Shah, Wen-Chih Wu, Gaurav Choudhary, Alan R Morrison
Journal: Circulation (2020)

Introduction: While an association between vascular disease and dementia has been identified, few studies have assessed the longitudinal relationship between aortic valve calcification (AVC) and mild cognitive impairment (MCI). We recently found AVC to be associated with increased atherosclerotic events, and we sought to determine the prognostic value of AVC derived from low dose, lung cancer screening computed tomography (LCSCT) for MCI in a moderate-to-high atherosclerotic risk cohort. Methods: This was a single site, retrospective analysis of 1401 U.S. veterans (65 years [IQI: 61, 68] years; 97% male), who underwent quantification of AVC from LCSCT indicated for smoking history. Exclusion criteria included lung cancer, prior aortic valve replacement and prior MCI diagnosis. The primary outcome was new diagnosis of MCI identified by objective testing (Mini-Mental Status Exam or Montreal Cognitive Assessment) or by ICD coding. Secondary outcome was nonfatal cerebrovascular accident (CVA). Time-to-event analysis was carried out using AVC as a continuous and a categorical variable, and multivariate adjustment included age, diabetes mellitus, glomerular filtration rate &lt;60 mL/min, coronary artery disease, and prior CVA. Results: Over a 5-year follow up, 110 patients (8%) were newly diagnosed with MCI and 45 patients (3%) had CVA. By Cox regression, AVC was predictive of MCI (HR: 1.15 [1.07 -1.24], p&lt;0.001) and the association remained significant after multivariate adjustment (HR: 1.09 [1.01-1.18], p=0.026). Non-zero AVC tertiles were: 0.1-115; 116-427; and ≥428 Agatston Units. AVC was associated with MCI at increasing tertiles, and after multivariate analysis, the association remained significant (HR: 1.89 [1.09-3.28], p=0.024 and HR: 1.80 [1.01-3.20], p=0.047; tertiles 2 and 3, respectively). AVC was also associated with CVA (HR: 1.17 [1.05-1.32], p=0.006); however, the association lost significance after multivariate adjustment (HR: 1.12 [0.99-1.26], p=0.080). Conclusions: To our knowledge, this is the first study demonstrating that quantification of AVC from LCSCT is predictive of MCI. The association may be in part due to atherosclerotic thromboembolic events as there was a trend toward increasing nonfatal CVA in this population.
Abstract 14793: Association Between Cardiac Ejection Fraction and the Size of Stroke
Authors: Muhammad M Alvi, Tamra Ranasinghe, Yasser Kabbani, Mohamad Adnan Alkhouli, Abdul Rahman Tarabishy
Journal: Circulation (2020)

Introduction: Heart failure with low ejection fraction (EF) is a known risk factor for stroke. Low EF is associated with increased risk of thrombus formation and is accompanied with 2 to 3 fold increased risk of stroke. This can happen even in the absence of atrial fibrillation. Hypothesis: Our hypothesis was that size of the stroke will be larger in patients with reduction in EF as compared with cardioembolic strokes in preserved EF. The worse the EF, the more stagnation of blood and poor cardiac output leading higher risk of thrombus formation. It’s also likely that the group with reduced EF form a larger thrombus leading to larger stroke as compared to the group with preserved EF. Methods: For our analysis, we retrospectively reviewed charts for 49 acute ischemic stroke patients without atrial fibrillation. We used transthoracic echocardiogram to determine the EF. There are 25 patients with preserved EF, cutoff &gt; 50%. There were 24 patients in reduced EF group. Both groups were matched for age and cardiovascular risk factors. Infarct volume was manually calculated from T1 MRI using BrainLab software. Results: There is an inverse correlation between EF and infarct volume (r=-.283, p=.048) meaning patients with reduced EF had greater infarct volume. Median infarct volume is higher in reduced EF group (median volume = 36 cm 3 ) compared to patients with preserved EF (median volume = 11 cm 3 ) (p=.117). Conclusions: In our patient’s sample, there seems to be an inverse correlation between EF and size of stroke. Patients with reduced EF were associated with larger strokes. Larger studies need to be performed to establish a correlation.
Evaluation of Oncology Hospital at Home: Unplanned Health Care Utilization and Costs in the Huntsman at Home Real-World Trial
Authors: Kathi Mooney, Karen Titchener, Benjamin Haaland, Lorinda A. Coombs, Brock O'Neil, Richard Nelson, Jordan P. McPherson, Anne C. Kirchhoff, Anna C. Beck, John H. Ward
Journal: Journal of Clinical Oncology (2021)

Patients with cancer experience high rates of morbidity and unplanned health care utilization and may benefit from new models of care. We evaluated an adult oncology hospital at home program's rate of unplanned hospitalizations and health care costs and secondarily, emergency department (ED) use, length of hospital stays, and intensive care unit (ICU) admissions during the 30 days after enrollment.We conducted a prospective, nonrandomized, real-world cohort comparison of 367 hospitalized patients with cancer-169 patients consecutively admitted after hospital discharge to Huntsman at Home (HH), a hospital-at-home program, compared with 198 usual care patients concurrently identified at hospital discharge. All patients met clinical criteria for HH admission, but those in usual care lived outside the HH service area. Primary outcomes were the number of unplanned hospitalizations and costs during the 30 days after enrollment. Secondary outcomes included length of hospital stays, ICU admissions, and ED visits during the 30 days after enrollment.Groups were comparable except that more women received HH care. In propensity-weighted analyses, the odds of unplanned hospitalizations was reduced in the HH group by 55% (odds ratio, 0.45, 95% CI, 0.29 to 0.70; P < .001) and health care costs were 47% lower (mean cost ratio, 0.53; 95% CI, 0.39 to 0.72; P < .001) over the 30-day period. Secondary outcomes also favored HH. Total hospital stay days were reduced by 1.1 days (P = .004) and ED visits were reduced by 45% (odds ratio, 0.55; 95% CI, 0.33 to 0.92; P = .022). There was no evidence of a difference in ICU admissions (P = .972).This oncology hospital at home program shows initial promise as a model for oncology care that may lower unplanned health care utilization and health care costs.
Abstract MP62: Longitudinal Measures Of Blood Pressure And Subclinical Atrial Arrhythmias: The Multi-ethnic Study Of Atherosclerosis And The Atherosclerosis Risk In Communities Study
Authors: Barbara N Harding, Faye L Norby, Susan R Heckbert, Barbara McKnight, Bruce M Psaty, Elsayed Z Soliman, James Floyd, Lin Y Chen
Journal: Circulation (2021)

Purpose: High blood pressure (BP) is a well-known risk factor for atrial fibrillation (AF), but a single BP measurement may provide limited information about AF risk in older adults. We evaluated whether longitudinal measures of BP were associated with subclinical arrhythmias after adjustment for more conventional BP measures such as a single cross-sectional BP value. Methods: This study included 1,256 Multi-Ethnic Study of Atherosclerosis (MESA) and 1,948 Atherosclerosis Risk in Communities study (ARIC) participants who underwent extended ambulatory electrocardiographic monitoring and who were free of clinically-detected cardiovascular disease, including AF. Using BP measurements from six exams (2000-2018 in MESA, 1987-2017 in ARIC), we examined cross-sectional BP at the most recent exam, individual long-term mean BP from exams 1-5, BP trend during exams 1-5, and visit-to-visit variability during exams 1-5 in systolic BP (SBP) and pulse pressure (PP) for each participant. Logistic regression models were used to examine BP exposures in relation to subclinical AF and linear regression models were used to examine BP exposures in relation to frequency of supraventricular ectopy. Models adjusted for participant demographics, height, weight, diabetes, antihypertensive medication use and cross-sectional BP. Results from each study were combined with inverse variance-weighted meta-analysis. Results: At Exam 6, the mean age was 73 years in MESA and 79 years in ARIC, and 4% had subclinical AF. A 10 mmHg higher cross-sectional SBP and a 10 mmHg higher cross-sectional PP were associated with less AF (odds ratio [OR] SBP 0.86, 95% confidence interval [CI] 0.76, 0.96 and OR PP 0.73, 95% CI 0.63, 0.84). In contrast, a 4 mmHg higher visit-to-visit variability in SBP was associated with a greater prevalence of subclinical AF (OR 1.20, 95% CI 1.02, 1.38) and with a greater frequency of premature atrial contractions/hour (8%, 95% CI 1%, 15%). For PP as well, a 4 mmHg higher visit-to-visit variability was associated with a greater prevalence of AF (OR 1.18, 95% CI 1.00-1.37). In addition, a 10 mmHg higher long-term mean PP was associated with a greater prevalence of subclinical AF (OR 1.36, 95% CI 1.08-1.70). Conclusion: Our results indicate that information on BP assessed longitudinally for several years, especially visit-to-visit BP variability, is associated with a greater prevalence of subclinical atrial arrhythmias, while cross-sectional BP values alone were not associated with a greater prevalence of subclinical atrial arrhythmias. Prior longitudinal BP assessment, rather than current BP, may be more helpful in identifying older adults who are at higher risk of atrial arrhythmias.
Abstract 13301: Clinical Implications of Hepatic Hemodynamic Evaluation by Abdominal Ultrasonographic Imaging in Patients With Heart Failure
Authors: Yu Hotsuki, Akiomi YOSHIHISA, Yasuhiro Ichijo, Koichiro Watanabe, Yu Sato, Yusuke Kimishima, Tetsuro Yokokawa, Tomofumi Misaka, Masayoshi Oikawa, Atsushi Kobayashi, Yasuchika Takeishi
Journal: Circulation (2020)

Background: It has been reported that liver stiffness assessed by transient elastography is correlated with right atrial pressure (RAP), which is an important hemodynamic parameter in patients with heart failure (HF). We aimed to clarify clinical implications of hepatic hemodynamic evaluation (liver congestion and hypoperfusion) by abdominal ultrasonography in patients admitted for the treatment of decompensated HF. Methods and Results: We performed abdominal ultrasonography, right-heart catheterization (RHC), and echocardiography in HF patients (n=342) at stable condition after treatment, then followed up for cardiac events such as cardiac death and re-hospitalization due to worsening HF. Regarding liver congestion, liver stiffness assessed by shear wave elastography of the liver (SWE) was significantly correlated with RAP determined by RHC (R=0.343, P&lt;0.01) and right atrial end systolic area determined by echocardiography (R=0.293, P&lt;0.01). With regard to liver hypoperfusion, peak systolic velocity (PSV) of the celiac artery was correlated with cardiac index determined by RHC (R=0.291, P&lt;0.001) and tricuspid annular plane systolic excursion determined by echocardiography (R=0.251, P=0.004). Importantly, cardiac event rate was highest in HF patients with high SWE and low PSV ( Figure , subset 4). In the Cox proportional hazard analysis, the combination of high SWE and low PSV was a strong predictor of cardiac events (HR 4.811, 95% CI 1.562-14.818). Conclusions: Abdominal ultrasonography based evaluations of intrahepatic congestion and hypoperfusion predict adverse prognosis in HF patients.
Outbreaks Associated with Treated Recreational Water — United States, 2015–2019
Authors: Michele C. Hlavsa, Samaria K. Aluko, Allison D. Miller, John Person, Megan E. Gerdes, Sooji Lee, Joseph P. Laco, Elizabeth J. Hannapel, Vincent R. Hill
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Outbreaks associated with treated recreational water can be caused by pathogens or chemicals in aquatic venues such as pools, hot tubs, water playgrounds, or other artificially constructed structures that are intended for recreational or therapeutic purposes.For the period 2015-2019, public health officials from 36 states and the District of Columbia (DC) voluntarily reported 208 outbreaks associated with treated recreational water.Almost all (199; 96%) of the outbreaks were associated with public (nonbackyard) pools, hot tubs, or water playgrounds.These outbreaks resulted in at least 3,646 cases of illness, 286 hospitalizations, and 13 deaths.Among the 155 (75%) outbreaks with a confirmed infectious etiology, 76 (49%) were caused by Cryptosporidium (which causes cryptosporidiosis, a gastrointestinal illness) and 65 (42%) by Legionella (which causes Legionnaires' disease, a severe pneumonia, and Pontiac fever, a milder illness with flu-like symptoms).Cryptosporidium accounted for 2,492 (84%) of 2,953 cases resulting from the 155 outbreaks with a confirmed etiology.All 13 deaths occurred in persons affected by a Legionnaires' disease outbreak.Among the 208 outbreaks, 71 (34%) were associated with a hotel (i.e., hotel, motel, lodge, or inn) or a resort, and 107 (51%) started during June-August.Implementing recommendations in CDC's Model Aquatic Health Code (MAHC) (1) can help prevent outbreaks associated with treated recreational water in public aquatic venues.An outbreak associated with recreational water is the occurrence of similar illness in two or more persons whose illnesses are epidemiologically linked by location and time of exposure to 1) recreational water or 2) pathogens or chemicals aerosolized or volatilized into the air from recreational water.Public health officials in U.S. jurisdictions (the 50 states, DC, U.S. territories, and freely associated states) voluntarily report outbreaks to CDC via the National Outbreak Reporting System.This report examines data on outbreaks that were associated with treated recreational water and reported by February 4, 2021, and for which the first illness occurred during 2015-2019.Data on each outbreak include earliest illness onset date, count of cases of illness, counts of hospitalizations and deaths, etiology, and setting (e.g., hotel) and venue (e.g., pool, hot tub, or water playground) of the outbreak exposure.This
Lipid-nanoparticle-encapsulated mRNA vaccines induce protective memory CD8 T cells against a lethal viral infection
Authors: Cory J. Knudson, Pedro Alves-Peixoto, Hiromi Muramatsu, Colby Stotesbury, Lingjuan Tang, Paulo J.C. Lin, Ying K. Tam, Drew Weissman, Norbert Pardi, Luis J. Sigal
Journal: Molecular Therapy (2021)

It is well established that memory CD8 T cells protect susceptible strains of mice from mousepox, a lethal viral disease caused by ectromelia virus (ECTV), the murine counterpart to human variola virus. While mRNA vaccines induce protective antibody (Ab) responses, it is unknown whether they also induce protective memory CD8 T cells. We now show that immunization with different doses of unmodified or N(1)-methylpseudouridine-modified mRNA (modified mRNA) in lipid nanoparticles (LNP) encoding the ECTV gene EVM158 induced similarly strong CD8 T cell responses to the epitope TSYKFESV, albeit unmodified mRNA-LNP had adverse effects at the inoculation site. A single immunization with 10 μg modified mRNA-LNP protected most susceptible mice from mousepox, and booster vaccination increased the memory CD8 T cell pool, providing full protection. Moreover, modified mRNA-LNP encoding TSYKFESV appended to green fluorescent protein (GFP) protected against wild-type ECTV infection while lymphocytic choriomeningitis virus glycoprotein (GP) modified mRNA-LNP protected against ECTV expressing GP epitopes. Thus, modified mRNA-LNP can be used to create protective CD8 T cell-based vaccines against viral infections. It is well established that memory CD8 T cells protect susceptible strains of mice from mousepox, a lethal viral disease caused by ectromelia virus (ECTV), the murine counterpart to human variola virus. While mRNA vaccines induce protective antibody (Ab) responses, it is unknown whether they also induce protective memory CD8 T cells. We now show that immunization with different doses of unmodified or N(1)-methylpseudouridine-modified mRNA (modified mRNA) in lipid nanoparticles (LNP) encoding the ECTV gene EVM158 induced similarly strong CD8 T cell responses to the epitope TSYKFESV, albeit unmodified mRNA-LNP had adverse effects at the inoculation site. A single immunization with 10 μg modified mRNA-LNP protected most susceptible mice from mousepox, and booster vaccination increased the memory CD8 T cell pool, providing full protection. Moreover, modified mRNA-LNP encoding TSYKFESV appended to green fluorescent protein (GFP) protected against wild-type ECTV infection while lymphocytic choriomeningitis virus glycoprotein (GP) modified mRNA-LNP protected against ECTV expressing GP epitopes. Thus, modified mRNA-LNP can be used to create protective CD8 T cell-based vaccines against viral infections.