tbuckley/cabot-search huggingface dataset:
Abstract 14567: Detection of Acute Cellular Rejection in Pediatric Heart Transplantation: A Pilot Cardiac Magnetic Resonance Imaging Study
Authors: Steven C Greenway, Frederic Dallaire, Paul F Kantor, Anne I Dipchand, Rajiv R Chaturvedi, Monali Warade, Eugenie Riesenkampff, Shi-Joon Yoo, Lars Grosse-Wortmann
Journal: Circulation (2015)

Introduction: The diagnosis of significant acute cellular rejection (ACR) after heart transplantation (HT) prompts an immediate change in management and is associated with adverse outcome. Endomyocardial biopsy (EMB) is the gold standard for the detection of ACR but has important limitations. The purpose of this study was to evaluate cardiac magnetic resonance imaging (CMR) as a non-invasive tool to detect ACR in pediatric patients after HT. Methods: In this single centre prospective cohort study, 30 pediatric HT recipients underwent CMR at the time of surveillance EMB. Their CMR results were compared to 14 non-HT pediatric controls. Ventricular volumes and ejection fraction, native T1 times and T2-weighted signal intensities were compared between patients and controls and between patients with (grade 2 R) and without (grade 0 R/1 R) significant ACR according to standard criteria. Extracellular volumes (ECV) and the presence of late gadolinium enhancement (LGE) were compared between the two HT groups. Results: There were no significant demographic differences between the patient groups. Transplant patients were on average 11 ± 6.1 years of age and were 31.5 ± 41.3 months post-transplant. Significant (grade 2 R) ACR was an infrequent event in our population (5/30, 17%). Compared to controls, heart rate (100.3 ± 16.4 bpm) and brain natriuretic peptide (60.8 ± 100.7 ng/L) were significantly elevated post-HT but did not differentiate between grades of ACR. Ventricular volumes, ejection fractions, LGE prevalence, ECVs, native T1 times and T2 signal intensities were not significantly altered by ACR. Conclusions: We describe the myocardial characteristics of pediatric HT recipients by CMR. Although limited by the small number of patients with significant ACR the results of this pilot study suggest that current CMR imaging protocols are insufficient to reliably identify ACR-related changes in pediatric HT.
Activation of EP4 receptor limits transition of acute to chronic heart failure in lipoxygenase deficient mice
Authors: Vasundhara Kain, Kevin A. Ingle, Namakkal S. Rajasekaran, Ganesh V. Halade
Journal: Theranostics (2021)

Aim: Immune responsive 12/15 lipoxygenase (12/15LOX)-orchestrate biosynthesis of essential inflammation-resolution mediators during acute inflammatory response in post-myocardial infarction (MI). Lack of 12/15LOX dampens proinflammatory mediator 12-(S)-hydroxyeicosatetraenoic acid (12-(S)-HETE), improves post-MI survival, through the biosynthesis of endogenous mediators epoxyeicosatrienoic acids (EETs; cypoxins) to resolve post-MI inflammation. However, the mechanism that amplifies cypoxins-directed cardiac repair in acute heart failure (AHF) and chronic HF (CHF) remains of interest in MI-directed renal inflammation. Therefore, we determined the role of EETs in macrophage-specific receptor activation in facilitating cardiac repair in 12/15LOX deficient mice experiencing HF. Methods and Results: Risk-free young adult (8 -12 week-old) male C57BL/6J wild-type mice (WT; n = 43) and 12/15LOX-/- mice (n = 31) were subjected to permanent coronary artery ligation and monitored at day (d)1, d5 (as acute HF), and d28 to d56 (8 weeks; chronic HF) post-surgery maintaining no-MI mice that served as d0 naïve controls. Left ventricle (LV) infarcted area of 12/15LOX-/- mice displayed an increase in expression of prostanoid receptor EP4 along with monocyte chemoattractant protein-1 CCL2 in AHF and CHF. The transcriptome analysis of isolated leukocytes (macrophages/neutrophils) from infarcted LV revealed a higher expression of EP4 on reparative macrophages expressing MRC-1 in 12/15LOX-/- mice. Deletion of 12/15LOX differentially modulated the miRNA levels, downregulating miR-23a-3p (~20 fold; p < 0.05) and upregulating miR-125a-5p (~160 fold; p < 0.05) in AHF which promoted polarization of the macrophages towards reparative phenotype. Furthermore, 12/15LOX deletion markedly attenuated renal inflammation with reduced levels of NGAL and KIM-1 and apoptotic markers in the kidney during CHF. Conclusion: In risk-free mice during physiological cardiac repair, absence of 12/15LOX promoted reparative macrophages with marked activation of EP4 signaling thereby improving post-MI survival and limiting renal inflammation in acute and advanced HF. The future studies are warranted to advance the role of EETs in macrophage receptor biology.
Conditioned medium from adipose-derived stem cells attenuates ischemia/reperfusion-induced cardiac injury through the microRNA-221/222/PUMA/ETS-1 pathway
Authors: Tzu-Lin Lee, Tsai-Chun Lai, Shu-Rung Lin, Shu-Wha Lin, Yu-Chen Chen, Chi-Ming Pu, I-Ta Lee, Jaw-Shiun Tsai, Chiang-Wen Lee, Yuh-Lien Chen
Journal: Theranostics (2021)

Rationale: Cardiovascular diseases, such as myocardial infarction (MI), are the leading causes of death worldwide. Reperfusion therapy is the common standard treatment for MI. However, myocardial ischemia/reperfusion (I/R) causes cardiomyocyte injury, including apoptosis and fibrosis. We aimed to investigate the effects of conditioned medium from adipose-derived stem cells (ADSC-CM) on apoptosis and fibrosis in I/R-treated hearts and hypoxia/reoxygenation (H/R)-treated cardiomyocytes and the underlying mechanisms. Methods: ADSC-CM was collected from ADSCs. The effects of intramuscular injection of ADSC-CM on cardiac function, cardiac apoptosis, and fibrosis examined by echocardiography, Evans blue/TTC staining, TUNEL assay, and Masson's trichrome staining in I/R-treated mice. We also examined the effects of ADSC-CM on apoptosis and fibrosis in H/R-treated H9c2 cells by annexin V/PI flow cytometry, TUNEL assay, and immunocytochemistry. Results: ADSC-CM treatment significantly reduced heart damage and fibrosis of I/R-treated mice and H/R-treated cardiomyocytes. In addition, the expression of apoptosis-related proteins, such as p53 upregulated modulator of apoptosis (PUMA), p-p53 and B-cell lymphoma 2 (BCL2), as well as the fibrosis-related proteins ETS-1, fibronectin and collagen 3, were significantly reduced by ADSC-CM treatment. Moreover, we demonstrated that ADSC-CM contains a large amount of miR-221/222, which can target and regulate PUMA or ETS-1 protein levels. Furthermore, the knockdown of PUMA and ETS-1 decreased the induction of apoptosis and fibrosis, respectively. MiR-221/222 overexpression achieved similar results. We also observed that cardiac I/R markedly increased apoptosis and fibrosis in miR-221/222 knockout (KO) mice, while ADSC-CM decreased these effects. The increased phosphorylation of p38 and NF-κB not only mediated myocardial apoptosis through the PUMA/p53/BCL2 pathway but also regulated fibrosis through the ETS-1/fibronectin/collagen 3 pathway. Conclusions: Overall, our results show that ADSC-CM attenuates cardiac apoptosis and fibrosis by reducing PUMA and ETS-1 expression, respectively. The protective effect is mediated via the miR-221/222/p38/NF-κB pathway.
MO01.12 Association of Opioid Use with Survival in Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitor Therapy
Authors: J. Mock, E. Wynter, P. Young, A. Sytov, O. Elghawy, R. Gentzler, W. Novicoff, L. Martin, R. Hall
Journal: Journal of Thoracic Oncology (2021)
Development and Validation of a Machine Learning Model to Predict Near-Term Risk of Iatrogenic Hypoglycemia in Hospitalized Patients
Authors: Nestoras N. Mathioudakis, Mohammed S. Abusamaan, Ahmed F. Shakarchi, Sam Sokolinsky, Shamil Fayzullin, John McGready, Mihail Zilbermint, Suchi Saria, Sherita Hill Golden
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Accurate clinical decision support tools are needed to identify patients at risk for iatrogenic hypoglycemia, a potentially serious adverse event, throughout hospitalization. <h3>Objective</h3> To predict the risk of iatrogenic hypoglycemia within 24 hours after each blood glucose (BG) measurement during hospitalization using a machine learning model. <h3>Design, Setting, and Participants</h3> This retrospective cohort study, conducted at 5 hospitals within the Johns Hopkins Health System, included 54 978 admissions of 35 147 inpatients who had at least 4 BG measurements and received at least 1 U of insulin during hospitalization between December 1, 2014, and July 31, 2018. Data from the largest hospital were split into a 70% training set and 30% test set. A stochastic gradient boosting machine learning model was developed using the training set and validated on internal and external validation. <h3>Exposures</h3> A total of 43 clinical predictors of iatrogenic hypoglycemia were extracted from the electronic medical record, including demographic characteristics, diagnoses, procedures, laboratory data, medications, orders, anthropomorphometric data, and vital signs. <h3>Main Outcomes and Measures</h3> Iatrogenic hypoglycemia was defined as a BG measurement less than or equal to 70 mg/dL occurring within the pharmacologic duration of action of administered insulin, sulfonylurea, or meglitinide. <h3>Results</h3> This cohort study included 54 978 admissions (35 147 inpatients; median [interquartile range] age, 66.0 [56.0-75.0] years; 27 781 [50.5%] male; 30 429 [55.3%] White) from 5 hospitals. Of 1 612 425 index BG measurements, 50 354 (3.1%) were followed by iatrogenic hypoglycemia in the subsequent 24 hours. On internal validation, the model achieved a C statistic of 0.90 (95% CI, 0.89-0.90), a positive predictive value of 0.09 (95% CI, 0.08-0.09), a positive likelihood ratio of 4.67 (95% CI, 4.59-4.74), a negative predictive value of 1.00 (95% CI, 1.00-1.00), and a negative likelihood ratio of 0.22 (95% CI, 0.21-0.23). On external validation, the model achieved C statistics ranging from 0.86 to 0.88, positive predictive values ranging from 0.12 to 0.13, negative predictive values of 0.99, positive likelihood ratios ranging from 3.09 to 3.89, and negative likelihood ratios ranging from 0.23 to 0.25. Basal insulin dose, coefficient of variation of BG, and previous hypoglycemic episodes were the strongest predictors. <h3>Conclusions and Relevance</h3> These findings suggest that iatrogenic hypoglycemia can be predicted in a short-term prediction horizon after each BG measurement during hospitalization. Further studies are needed to translate this model into a real-time informatics alert and evaluate its effectiveness in reducing the incidence of inpatient iatrogenic hypoglycemia.
The PRISMA 2020 statement: an updated guideline for reporting systematic reviews
Authors: Matthew J Page, Joanne E McKenzie, Patrick M Bossuyt, Isabelle Boutron, Tammy C Hoffmann, Cynthia D Mulrow, Larissa Shamseer, Jennifer M Tetzlaff, Elie A Akl, Sue E Brennan, Roger Chou, Julie Glanville, Jeremy M Grimshaw, Asbjørn Hróbjartsson, Manoj M Lalu, Tianjing Li, Elizabeth W Loder, Evan Mayo-Wilson, Steve McDonald, Luke A McGuinness, Lesley A Stewart, James Thomas, Andrea C Tricco, Vivian A Welch, Penny Whiting, David Moher
Journal: BMJ (2021)

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.
TS01.03 Efficacy and Safety Data From a Phase 1/2 Trial of Tislelizumab in Chinese Patients With Non-Small Cell Lung Cancer (NSCLC)
Authors: Q. Zhou, J. Zhao, J. Wang, Q. Zhang, H. Pan, L. Shen, Y. Yuan, Y. Bai, T. Liu, Y. Gao, Y. Li, J. Zhang, Y.-L. Wu
Journal: Journal of Thoracic Oncology (2021)
SARS-CoV-2: vaccines in the pandemic era
Authors: Dan-Dan Li, Qi-Han Li
Journal: Military Medical Research (2021)

Abstract Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused millions of infections and deaths worldwide since its emergence in December 2019. As there is little or no natural immunity in the human population or specific anti-COVID-19 drugs, researchers from the government, academia and industry are developing vaccines at an unprecedented speed to halt the pandemic. In this review, the results of animal experiments and clinical trials on several vaccine technical platforms are summarized, and several challenges are also discussed to further promote the development, evaluation and application of vaccines during the challenging situation of the global pandemic.
Nanomedicine for the treatment of diabetes-associated cardiovascular diseases and fibrosis
Authors: Xiao-Min Luo, Cen Yan, Ying-Mei Feng
Journal: Advanced Drug Delivery Reviews (2021)

Cardiomyopathy and fibrosis are the main causes of heart failure in diabetes patients. For therapeutic purposes, a delivery system is required to enhance antidiabetic drug efficacy and specifically target profibrotic pathways in cardiomyocytes. Nanoparticles (NPs) have distinct advantages, including biocompatibility, bioavailability, targeting efficiency, and minimal toxicity, which make them ideal for antidiabetic treatment. In this review, we overview the latest information on the pathogenesis of cardiomyopathy and fibrosis in diabetes patients. We summarize how NP applications improve insulin and liraglutide efficacy and their sustained release upon oral administration. We provide a comprehensive review of the results of NP clinical trials in diabetes patients and of animal studies investigating the effects of NP-mediated anti-fibrotic treatments. Collectively, the application of advanced NP delivery systems in the treatment of cardiomyopathy and fibrosis in diabetes patients is a promising and innovative therapeutic strategy.
Neuroinvasion of SARS-CoV-2 in human and mouse brain
Authors: Eric Song, Ce Zhang, Benjamin Israelow, Alice Lu-Culligan, Alba Vieites Prado, Sophie Skriabine, Peiwen Lu, Orr-El Weizman, Feimei Liu, Yile Dai, Klara Szigeti-Buck, Yuki Yasumoto, Guilin Wang, Christopher Castaldi, Jaime Heltke, Evelyn Ng, John Wheeler, Mia Madel Alfajaro, Etienne Levavasseur, Benjamin Fontes, Neal G. Ravindra, David Van Dijk, Shrikant Mane, Murat Gunel, Aaron Ring, Syed A. Jaffar Kazmi, Kai Zhang, Craig B. Wilen, Tamas L. Horvath, Isabelle Plu, Stephane Haik, Jean-Leon Thomas, Angeliki Louvi, Shelli F. Farhadian, Anita Huttner, Danielle Seilhean, Nicolas Renier, Kaya Bilguvar, Akiko Iwasaki
Journal: The Journal of Experimental Medicine (2021)

Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus on the consequences of CNS infections. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in infected and neighboring neurons. However, no evidence for type I interferon responses was detected. We demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate SARS-CoV-2 neuroinvasion in vivo. Finally, in autopsies from patients who died of COVID-19, we detect SARS-CoV-2 in cortical neurons and note pathological features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and an unexpected consequence of direct infection of neurons by SARS-CoV-2.
Machine learning-based prediction of adverse events following an acute coronary syndrome (PRAISE): a modelling study of pooled datasets
Authors: Fabrizio D'Ascenzo, Ovidio De Filippo, Guglielmo Gallone, Gianluca Mittone, Marco Agostino Deriu, Mario Iannaccone, Albert Ariza-Solé, Christoph Liebetrau, Sergio Manzano-Fernández, Giorgio Quadri, Tim Kinnaird, Gianluca Campo, Jose Paulo Simao Henriques, James M Hughes, Alberto Dominguez-Rodriguez, Marco Aldinucci, Umberto Morbiducci, Giuseppe Patti, Sergio Raposeiras-Roubin, Emad Abu-Assi, Gaetano Maria De Ferrari, Francesco Piroli, Andrea Saglietto, Federico Conrotto, Pierluigi Omedé, Antonio Montefusco, Mauro Pennone, Francesco Bruno, Pier Paolo Bocchino, Giacomo Boccuzzi, Enrico Cerrato, Ferdinando Varbella, Michela Sperti, Stephen B. Wilton, Lazar Velicki, Ioanna Xanthopoulou, Angel Cequier, Andres Iniguez-Romo, Isabel Munoz Pousa, Maria Cespon Fernandez, Berenice Caneiro Queija, Rafael Cobas-Paz, Angel Lopez-Cuenca, Alberto Garay, Pedro Flores Blanco, Andrea Rognoni, Giuseppe Biondi Zoccai, Simone Biscaglia, Ivan Nunez-Gil, Toshiharu Fujii, Alessandro Durante, Xiantao Song, Tetsuma Kawaji, Dimitrios Alexopoulos, Zenon Huczek, Jose Ramon Gonzalez Juanatey, Shao-Ping Nie, Masa-aki Kawashiri, Iacopo Colonnelli, Barbara Cantalupo, Roberto Esposito, Sergio Leonardi, Walter Grosso Marra, Alaide Chieffo, Umberto Michelucci, Dario Piga, Marta Malavolta, Sebastiano Gili, Marco Mennuni, Claudio Montalto, Luigi Oltrona Visconti, Yasir Arfat
Journal: The Lancet (2021)
Assessment of Day-7 Postexposure Testing of Asymptomatic Contacts of COVID-19 Patients to Evaluate Early Release from Quarantine — Vermont, May–November 2020
Authors: Amanda Jones, Veronica Fialkowski, Lauren Prinzing, Jeffrey Trites, Patsy Kelso, Mark Levine
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

On May 8, 2020, the Vermont Department of Health (VDH) issued a Health Update* recommending shortening the duration of quarantine for persons exposed to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19).Exposed persons who were in quarantine could be tested by polymerase chain reaction (PCR) on or after quarantine day 7.Those who had remained asymptomatic throughout quarantine and who received a negative SARS-CoV-2 PCR test result on or after day 7 could end quarantine.This policy was based on a report suggesting that symptom onset occurs within this time frame in approximately three quarters of COVID-19 cases (1) and on consultation of the Vermont Health Commissioner with the U.S. Surgeon General.VDH implemented this policy to minimize restrictions on state residents, recognizing that some reduction could occur in the prevention benefit of quarantine to contain the spread of SARS-CoV-2.State-run SARS-CoV-2 testing sites were made available to increase access to no-cost testing and facilitate implementation of this policy.During August 1-December 1, among persons seeking testing at a VDH SARS-CoV-2 testing site, 36% stated that their reason for seeking testing was to end quarantine early (VDH, unpublished data, December 7, 2020), indicating that persons were aware of and following the policy and using the testing services provided.To assess the effectiveness of this policy, VDH analyzed testing data for contacts of persons with a COVID-19 diagnosis.During May 8-November 16, VDH identified 8,798 exposed contacts of COVID-19 patients; 3,983 (45%) had sought testing within 14 days of their exposure, with day 0 defined as the date of last exposure noted in the case investigation record.Among these persons, 2,200 (55%) who received testing on days 7-10 were included in this analysis; 977 (44.9%) of these contacts had a specimen collected for testing on day 7.Among these, 34 (3%) had test results that were positive, 940 (96%) had results that were negative, and three (<1%) had results that were indeterminate (Table ).Among the 34 contacts who received a positive SARS-CoV-2 PCR test result on day 7 after exposure, 12 (35%) were asymptomatic.The remaining 22 contacts with positive test results were symptomatic at the time of testing; approximately one half had developed symptoms on days 4-7 * https://www.healthvermont.gov/sites/default/files/documents/pdf/HAN-COVID-19-ChangetoQuarantine.pdf.
Mitochondrial metabolic reprogramming controls the induction of immunogenic cell death and efficacy of chemotherapy in bladder cancer
Authors: Bianca Oresta, Chiara Pozzi, Daniele Braga, Rodolfo Hurle, Massimo Lazzeri, Piergiuseppe Colombo, Nicola Frego, Marco Erreni, Cristina Faccani, Grazia Elefante, Matteo Barcella, Giorgio Guazzoni, Maria Rescigno
Journal: Science Translational Medicine (2021)

Immunogenic cell death induced through metabolic reprogramming by intravesical chemotherapy in bladder cancer is associated with treatment success.
Cardiac myosin‐binding protein <scp>C</scp> in the diagnosis and risk stratification of acute heart failure
Authors: Nikola Kozhuharov, Desiree Wussler, Thomas Kaier, Ivo Strebel, Samyut Shrestha, Dayana Flores, Albina Nowak, Zaid Sabti, Thomas Nestelberger, Tobias Zimmermann, Joan Walter, Maria Belkin, Eleni Michou, Pedro Lopez Ayala, Danielle M. Gualandro, Dagmar I. Keller, Assen Goudev, Tobias Breidthardt, Christian Mueller, Michael Marber
Journal: European Journal of Heart Failure (2021)

Cardiac myosin-binding protein C (cMyC) seems to be even more sensitive in the quantification of cardiomyocyte injury vs. high-sensitivity cardiac troponin, and may therefore have diagnostic and prognostic utility.In a prospective multicentre diagnostic study, cMyC, high-sensitivity cardiac troponin T (hs-cTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma concentrations were measured in blinded fashion in patients presenting to the emergency department with acute dyspnoea. Two independent cardiologists centrally adjudicated the final diagnosis. Diagnostic accuracy for acute heart failure (AHF) was quantified by the area under the receiver operating characteristic curve (AUC). All-cause mortality within 360 days was the prognostic endpoint. Among 1083 patients eligible for diagnostic analysis, 51% had AHF. cMyC concentrations at presentation were higher among AHF patients vs. patients with other final diagnoses [72 (interquartile range, IQR 39-156) vs. 22 ng/L (IQR 12-42), P < 0.001)]. cMyC's AUC was high [0.81, 95% confidence interval (CI) 0.78-0.83], higher than hs-cTnT's (0.79, 95% CI 0.76-0.82, P = 0.081) and lower than NT-proBNP's (0.91, 95% CI 0.89-0.93, P < 0.001). Among 794 AHF patients eligible for prognostic analysis, 28% died within 360 days; cMyC plasma concentrations above the median indicated increased risk of death (hazard ratio 2.19, 95% CI 1.66-2.89; P < 0.001). cMyC's prognostic accuracy was comparable with NT-proBNP's and hs-cTnT's. cMyC did not independently predict all-cause mortality when used in validated multivariable regression models. In novel multivariable regression models including medication, age, left ventricular ejection fraction, and discharge creatinine, cMyC remained an independent predictor of death and had no interactions with medical therapies at discharge.Cardiac myosin-binding protein C may aid physicians in the rapid triage of patients with suspected AHF.
OA03.04 Tislelizumab Plus Chemotherapy vs Chemotherapy Alone as First-line Treatment for Advanced Squamous Non-Small Cell Lung Cancer
Authors: J. Wang, S. Lu, C. Hu, Y. Sun, K. Yang, M. Chen, J. Zhao, G. Yu, X. Zhou, G. Feng, Y. Pan, Y. Yu, J. Zhang, L. Liang, X. Lin, J. Cui
Journal: Journal of Thoracic Oncology (2021)