tbuckley/cabot-search huggingface dataset:
Correlation of Coronary Artery Calcium and Invasive Coronary Angiographically in Patients with Atypical Angina Pectoris (CACICA - Trial)
Authors: Majed Elshenat, Mohammed Balosha, Mohammed Habib
Journal: Clinical Cardiology and Cardiovascular Interventions (2019)

OBJECTIVES This study correlated the multi - detector computed tomography (MDCT) calcium scores with the results of coronary angiography in diabatic and/or hypertensive patients with atypical angina pectoris in order to assess its value to predict or exclude significant coronary artery disease (CAD). BACKGROUND Muti-detector computed tomography is a sensitive method to detect coronary calcium. However, it is unclear whether it may play a role as a filter before invasive procedures in patients with atypical angina pectoris. METHODS A total of 150 patients (116 men and 34 women) with diabetic and/or hypertension for at least 5 years and atypical angina pectoris from a single center were included in our study. patients underwent calcium screening with MDCT and have calcium score more than 100 , then all patient underwent invasive coronary angiography. RESULTS The Mean age was 62±5.7 and 77.3% were male, 78% of men and 88.2 % of women revealed significant coronary stenoses (&gt; 50% lumen narrowing of left main trunk stenosis and &gt; 70% stenosis of any epicardial coronary artery). Significant correlation between calcium scoring and significant coronary artery stenosis was seen (P: 0001). A 70% were DM, 90% were hypertensive and 61.3% were HTN and DM. The LAD artery was the most stenotic artery by 53.3% followed by RCA (37.3%) and finally LCX (30.7%). one significant coronary artery was 42% followed by two significant CAD (26.7%), while 9.3% included three-vessel disease. The significant coronary artery diseases was increased with age ( P: 0003). CONCLUSIONS Coronary calcium proved to have good diagnostic performance for significant coronary artery stenosis in patient with atypical angina pectoris.
A Population Cohort Study to Evaluate the Risk of Ischemic Stroke Among Individuals with a New Diagnosis of Cancer Compared to Matched Cancer-Free Controls: Impact of Prior Stroke History
Authors: Deborah M Siegal, Joshua O. Cerasuolo, Marc Carrier, Peter L. Gross, Moira Kapral, Ronda Lun, Michel Shamy, Rinku Sutradhar
Journal: Blood (2021)
AZD4573 Effectively Induces Apoptosis in r/r MCL As a Monotherapy or in Combination with Acalabrutinib
Authors: Justine Roderick, Scott Boiko, Courtney L Andersen, Huiling Liang, Gregory Dowdell, Corinne Reimer, Lisa Drew, Danielle M Townsley, Justin Cidado
Journal: Blood (2021)
RON Kinase Is a Novel Therapeutic Target for Philadelphia-Negative Myeloproliferative Neoplasms
Authors: Lindsay Meg Gurska, Rachel Okabe, Meng Maxine Tong, Daniel Choi, Kristina Ames, Shira Glushakow-Smith, Allison Montoya, Ellen Tein, Haiying Cheng, Swati Goel, Balazs Halmos, Kira Gritsman
Journal: Blood (2021)
Preliminary Analysis of the MM21 Trial: Response Adaptive Salvage Treatment with Daratumumab-Lenalidomide-Dexamethasone (DRd) for Newly Diagnosed Transplant Eligible Multiple Myeloma Patients Failing Front-Line Bortezomib-Based Induction Therapy
Authors: Sueh-li Lim, John Reynolds, Hang Quach, Anna Hutchinson, Ian H Kerridge, Jane Estell, Wojt Janowski, Craig Thomas Wallington-Beddoe, Anna Kalff, Flora Yuen, Andrew Spencer
Journal: Blood (2021)
New Zealand’s covid-19 policy switch will harm vulnerable people
Authors: Johan M van Schalkwyk
Journal: BMJ (2021)

<h3>ABSTRACT</h3> This study examines the within-participants effects of web advertising and product publicity and the between-participants effects of similar versus varied web product publicity and advertising messages on audiences9 perceived trust, message believability, and attitudes toward web advertising and product publicity. The results suggest that perceptions of trust toward the marketing communication forms are the most influential factors when integrating product publicity and advertising. When audiences determine their perceived trust toward advertising and product publicity messages, it does not really matter what the messages are. Positive increments in attitude toward the article and message believability toward the advertisement are evident, however, in the varied messages condition, compared to the similar messages condition.
Abstract 11160: Transcriptional Profiling by Direct Digital Mrna Detection Indicates Heart Failure Recovery is Incomplete Post Lvad Therapy
Authors: Kajari Dhar, Fang Qiu, Hesham Basma, John Um, Brian D Lowes
Journal: Circulation (2021)

Introduction: Recovery from end-stage heart failure (HF) with left ventricular assist device (LVAD) therapy remains uncommon. In this study we compared targeted gene expression profiles of pre LVAD, post LVAD and non-failing (NF) hearts utilizing direct mRNA detection of HF specific genes. Our goal was to identify molecular mechanisms involved in HF and responses to LVAD therapy. Method: Myocardial RNAs were isolated from non-ischemic dilated cardiomyopathy patients at LVAD placement and during transplant (n=10) along with NF controls (n=6). NanoString analysis was used to compare gene expression between groups for 126 heart failure specific genes. NanoString mRNA raw count data were preprocessed and normalized using nSolver 4.0 Analysis Software. At least a 2 fold change in gene expression with a FDR adjusted p&lt;0.05 was considered as significant. Ingenuity Pathway Analysis (IPA) was completed to understand the biological pathways involved. Results: Our sample population was 90% male, average age of 56 and 100% Caucasian. In the HF populations average ejection fraction was low &lt;25% and average NYHA was 3.5. In HF, expressions of contractile muscle (MYH6), ion channels protein (KCNIP2) and Ca ATPase (SERCA2) were significantly down regulated when compared to NF controls. Natriuretic peptides (NPPA, NPPB), troponin 1 (TNNI3), nuclear kinases (WEE) and metabolic genes (ATRNL1) were upregulated compared to NF hearts. These differential changes in gene expression persisted post LVAD therapy. There were no significant changes in gene expression between pre and post LVAD HF patients. Ingenuity pathway analysis revealed that these changes in gene expression predispose to arrhythmias. Conclusion: Transcriptional changes in HF specific genes persist in many patients post LVAD therapy contributing to incomplete recovery of end stage heart failure and ongoing risk of arrhythmias. These genes are involved in contractile function, calcium handling and ion channels. Direct digital mRNA detection allows for serial analysis of targeted HF specific genes without reverse transcription and amplification of resultant cDNA. New therapies are needed to reverse adverse molecular changes and improve outcomes in heart failure patients who receive LVADs.
The Genomic Landscape of Plasmablastic Lymphoma (PBL) - an L.L.M.P.P. Project
Authors: Jasper Wong, Brett Collinge, Laura K Hilton, Susana Ben-Neriah, Graham W. Slack, Pedro Farinha, James R. Cook, Itziar Salaverria, Elías Campo, German Ott, Andreas Rosenwald, Catalina Amador, Elaine S. Jaffe, Timothy C. Greiner, Philipp Raess, Joo Y. Song, Giorgio Inghirami, Dennis D. Weisenburger, Wing (John) C. Chan, Harald Holte, Klaus Beiske, Kai Fu, Jan Delabie, Stefania Pittaluga, Andrew L. Feldman, Kerry J. Savage, Andrew J. Mungall, Christian Steidl, Lisa M. Rimsza, Ryan D Morin, David W. Scott
Journal: Blood (2021)
A Case of Lung Adenocarcinoma Response to Alectinib Harboring a Rare EML4-ALK Variant, Exon 6 of EML4 Fused to Exon 18 of ALK
Authors: Lirong Liu, Fangfang Hou, Yufeng Liu, Wenzhu Li, Haibo Zhang
Journal: Journal of the National Comprehensive Cancer Network (2022)

More than 20 types of ALK fusion variant subtypes have been identified, including different fusion partner genes or EML4-ALK fusions with different breakpoints. However, different ALK fusions show different sensitivities to ALK-tyrosine kinase inhibitors (ALK-TKIs) and the emergence of rare fusions brings great challenges to the target therapy in clinic. We report a rare EML4-ALK (E6;A18) fusion in a patient with lung adenocarcinoma that responded well to alectinib. This is the second case of this rare variant reported but the first report of response to an ALK-TKI. This evidence is the first to show that alectinib may be effective for this rare fusion type of non-small cell lung cancer, and these findings have important implications for drug selection in patients with this subtype. Further studies are needed to understand the function of this variant.
Phenotypic High-Risk Disease in the Context of Carfilzomib and Lenalidomide Combination Induction Therapy for Newly Diagnosed Transplant-Eligible Myeloma Patients
Authors: Charlotte Pawlyn, Faith E Davies, Tom Menzies, Rowena Henderson, Gordon Cook, Matthew W Jenner, John R Jones, Martin F. Kaiser, Roger G Owen, Mark T Drayson, David Cairns, Gareth J. Morgan, Graham Jackson
Journal: Blood (2021)
Dissection of Bone Marrow Microenvironment By Single Cell RNA Sequencing in Warm AIHA Patients: A Proof-of-Concept Analysis
Authors: Bruno Fattizzo, Matteo Claudio Da Via', Juri Alessandro Giannotta, Paola Bianchi, Luca Baldini, Niccolo Bolli, Wilma Barcellini
Journal: Blood (2021)
Abstract 11557: Referral to Coronary Angiography Among Patients With Moderate or Severe Ischemia: Implications for the ISCHEMIA Trial
Authors: Mouaz H AlMallah, Fatimah Masoudi, Amjad Ahmed, Ahmed Aljizeeri
Journal: Circulation (2018)

Background: The ISCHEMIA trial is evaluating the impact of optimal medical therapy (OMT) versus OMT and revascularization among patients with moderate to severe ischemia. However, there is limited ...
Racial Disparities in Telemedicine Uptake during the COVID-19 Pandemic Among Patients with Hematologic Malignancies in the United States
Authors: Natalia Neparidze, Krystal W. Lau, Xiaoliang Wang, Amy J. Davidoff, Scott F. Huntington, Omer Hassan Jamy, Gregory Calip, Harsh Shah, Deborah M. Stephens, Rebecca A. Miksad, Ravi Parikh, Samuel Takvorian, Gaurav Goyal, Erlene K Seymour
Journal: Blood (2021)
A Randomized Crossover Trial Comparing Glucose Control During Moderate-Intensity, High-Intensity, and Resistance Exercise With Hybrid Closed-Loop Insulin Delivery While Profiling Potential Additional Signals in Adults With Type 1 Diabetes
Authors: Barbora Paldus, Dale Morrison, Dessi P. Zaharieva, Melissa H. Lee, Hannah Jones, Varuni Obeyesekere, Jean Lu, Sara Vogrin, André La Gerche, Sybil A. McAuley, Richard J. MacIsaac, Alicia J. Jenkins, Glenn M. Ward, Peter Colman, Carmel E.M. Smart, Rowen Seckold, Bruce R. King, Michael C. Riddell, David N. O’Neal
Journal: Diabetes Care (2021)

OBJECTIVE To compare glucose control with hybrid closed-loop (HCL) when challenged by high intensity exercise (HIE), moderate intensity exercise (MIE), and resistance exercise (RE) while profiling counterregulatory hormones, lactate, ketones, and kinetic data in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS This study was an open-label multisite randomized crossover trial. Adults with type 1 diabetes undertook 40 min of HIE, MIE, and RE in random order while using HCL (Medtronic MiniMed 670G) with a temporary target set 2 h prior to and during exercise and 15 g carbohydrates if pre-exercise glucose was &amp;lt;126 mg/dL to prevent hypoglycemia. Primary outcome was median (interquartile range) continuous glucose monitoring time-in-range (TIR; 70–180 mg/dL) for 14 h post–exercise commencement. Accelerometer data and venous glucose, ketones, lactate, and counterregulatory hormones were measured for 280 min post–exercise commencement. RESULTS Median TIR was 81% (67, 93%), 91% (80, 94%), and 80% (73, 89%) for 0–14 h post–exercise commencement for HIE, MIE, and RE, respectively (n = 30), with no difference between exercise types (MIE vs. HIE; P = 0.11, MIE vs. RE, P = 0.11; and HIE vs. RE, P = 0.90). Time-below-range was 0% for all exercise bouts. For HIE and RE compared with MIE, there were greater increases, respectively, in noradrenaline (P = 0.01 and P = 0.004), cortisol (P &amp;lt; 0.001 and P = 0.001), lactate (P ≤ 0.001 and P ≤ 0.001), and heart rate (P = 0.007 and P = 0.015). During HIE compared with MIE, there were greater increases in growth hormone (P = 0.024). CONCLUSIONS Under controlled conditions, HCL provided satisfactory glucose control with no difference between exercise type. Lactate, counterregulatory hormones, and kinetic data differentiate type and intensity of exercise, and their measurement may help inform insulin needs during exercise. However, their potential utility as modulators of insulin dosing will be limited by the pharmacokinetics of subcutaneous insulin delivery.
Abstract PO-017: Application of oncolytic adenovirus to desmoplastic pancreatic cancer
Authors: Elora Hossain, Fumihiro Higashino
Journal: Cancer Research (2021)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the highly malignant tumors with the poorest prognosis worldwide. The five-year survival rate of pancreatic cancer patients is 5%. PDAC comprises a dense fibrotic stroma with an extracellular matrix produced by activated-human pancreatic stellate cells (HPSC), which helps tumor growth, infiltration and metastasis. It is the main reason for chemotherapy resistance since fibrotic stroma is impenetrable for drug delivery. AU-rich elements (ARE) are RNA elements commonly present in the 3’-UTR of certain mRNAs that encode many early response genes or growth-related genes such as proto-oncogenes. ARE enhances the rapid decay of mRNAs, and the fate of ARE-mRNA is controlled by ARE-binding proteins HuR. ARE-mRNA is stabilized in most types of cancers mediate by binding with HuR, which exports target ARE-mRNA to the cytoplasm. We have developed E4orf6-deficient adenovirus dl355 as an oncolytic virus. E4orf6 is a viral gene essential for viral replication and contributes to viral replication by stabilizing ARE-mRNA in infected cells. Therefore, dl355 can replicate only in cancer cells in which ARE-mRNA is stabilized and lyses the cells. If ARE-mRNA is stabilized not only in PDAC but also in the activated-HPSC, dl355 may be effective for surrounding fibrosis. We found that HuR was relocalized in the cytoplasm of human PDAC and HPSC activated by TGFβ-1. The co-culture enhanced HuR export of MIA PaCa-2 with activated-HPSC. Inhibition of HuR function using CMLD-2 reagent inactivated the growth, invasion and metastasis activities of PDAC. The proliferative and cytopathic effects of dl355 were very high with PDAC and even with activated-HPSC compared to quiescent cells. These results indicate that oncolytic adenovirus dl355 shows potentiality to kill both pancreatic cancer cells and activated-pancreatic stellate cells where an abundance of HuR in the cytoplasm. dl355 has the potential to overcome several critical hurdles proposed by the tumor microenvironment of desmoplastic pancreatic tumors. Citation Format: Elora Hossain, Fumihiro Higashino. Application of oncolytic adenovirus to desmoplastic pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-017.
Immune Profiling of Multiple Myeloma Patients Treated with Daratumumab Monotherapy: Acquired and Primary Daratumumab-Resistance Is Associated with NK Cell Exhaustion
Authors: Christie P.M. Verkleij, Kristine A. Frerichs, Carolien Duetz, Sonja Zweegman, Paola M. Homan-Weert, Monique C. Minnema, Annemiek Broyl, Mark-David Levin, Gerard M.J. Bos, Marie José Kersten, Saskia K. Klein, Medya M. Shikhagaie, Maria Krevvata, Tineke Casneuf, Yann Abraham, Raluca I. Verona, Tina Smets, Greet Vanhoof, Diana Cortes-Selva, Laure van Steenbergen, Diego Vieyra, Pieter Sonneveld, Tuna Mutis, Niels W.C.J. van de Donk
Journal: Blood (2021)
PATH-08. PROGNOSTIC IMPLICATIONS FROM LONG-TERM SURVIVORS (LTS) OF GLIOBLASTOMA
Authors: Nicole Briceno, Zied Abdullaev, Elizabeth Vera, Anna Choi, Alexa Christ, Ewa Grajkowska, Heather Leeper, Jason Levine, Matthew Lindsley, Jennifer Reyes, Lisa Boris, Eric Burton, Nicole Lollo, Marissa Panzer, Marta Penas-Prado, Valentina Pillai, Brett Theeler, Jing Wu, Lily Polskin, Antonios Papanicolau-Sengos, Martha Quezado, Kenneth Aldape, Mark Gilbert, Terri Armstrong
Journal: Neuro-Oncology (2021)

Abstract Glioblastoma (GBM) is the most aggressive primary brain malignancy with &amp;lt; 45% living a year beyond diagnosis which drops to 7% at five years. However, there have been reports of long-term survivors (LTS) living three to ten years beyond diagnosis. Few studies have reported on molecular factors in tumors from LTS cohorts. We identified GBM (IDH1/2 wildtype) patients living at least 3 years post diagnosis (N=25), including 16 with pre-treatment tumor tissue, from our Natural History Study. Available pre- or post-treatment tumors were analyzed with targeted panel sequencing and methylation analysis for classification, MGMT promoter status and copy number changes. Classical clinical prognostic features such as limited resection or older age did not preclude long-term survival as patients with tumor biopsy (n=1) or subtotal resection (n= 5) and patients &amp;gt; 60 were included in the LTS cohort. Furthermore, tumors with molecular features typically associated with poor prognosis were also in this GBM LTS group. MGMT promoter was unmethylated in 17% of tumors; EGFRvIII mutation in 13%, EGFR amplification in 33%, CDKN2A homozygous loss in 30% and complete chromosome 7 gain with 10 loss in 55%. Additionally, the methylation classifier found a higher-than-expected incidence of mesenchymal tumors (29%) and RTK II (57%). Tumors had a higher percent of TP53 mutations (44%) but lower pTERT (76%) compared to TCGA. These data suggest an individual patient’s prognosis cannot easily be predetermined based on classical clinical and molecular data. This underscores the need for further analyses to discover additional factors leading to their unexpected, prolonged survival and elucidate the role of factors typically associated with poor prognosis. Future work will include RNA-sequencing and germline whole genome sequencing to determine tumor specific gene expression and identify any possible genomic alterations that confer improved survival.
Abstract PO-123: Development of a 3D biomimetic metastatic liver niche model for pancreatic cancer
Authors: Mahsa Pahlavan, Weikun Xiao, Flora Eun, Chang-Il Hwang, Reginald Hill
Journal: Cancer Research (2021)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the 3rd leading cause of cancer death in the United States with a 5-year survival rate of only 7%. Early diagnosis is very difficult and thus 53% of PDAC patients are diagnosed after metastasis has already occurred with liver being the most frequently affected site. Therefore, it is urgent to understand the mechanism that leads to PDAC metastasis in liver in order to develop potential therapeutics. Research shows that environment that comprises the metastatic niche has unique features that facilitate tumor growth and chemoresistance. Differences between the tumor microenvironment (TME) of the primary site and the metastatic site may be a key reason why metastatic tumors are highly resistant to standard treatment. However, most current models only recreate the primary tumor environment, while a proper model which recapitulates the key features of the metastatic niche to study liver metastasis (LM) is still missing. To address this problem, we aim to design a biomimetic model that specifically recapitulates the liver premetastatic niche (PMN). Our 3D model accomplishes this by using 1) a collagen rich extracellular matrix (ECM) that mimics the metastatic site, 2) LM-derived fibroblasts, 3) and LM organoids derived from a mouse model of PDAC. Our preliminary results showed that primary PDAC organoids require CAFs derived from primary PDACs to exhibit chemoresistance. In contrast, LM organoids did not require primary CAFs to exhibit the same level of chemoresistance. This suggests that there are cell intrinsic factors that promote chemoresistance in LM organoid in addition to possible cell extrinsic factors from the PMN. In this research we investigate the role of LM-derived CAFs and PDAC-derived exosomes in liver PMN development and study their effect on growth and chemoresistance of LM organoids. Results of this research will help us to develop strategies specifically tailored to overcome the factors which promote chemoresistance in the PMN. Citation Format: Mahsa Pahlavan, Weikun Xiao, Flora Eun, Chang-Il Hwang, Reginald Hill. Development of a 3D biomimetic metastatic liver niche model for pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-123.
Cigarette Smoke and E-Cigarette Aerosols Lead to Clonal Expansion of Tet2 -/- and Dnmt3a R878H Cells In Vivo
Authors: Gajalakshmi Ramanathan, Rebecca Johnson, Jane Huishien Chen, Aaron Jia-En Huang, Bishop Bliss, Michael T. Kleinman, Angela Fleischman
Journal: Blood (2021)
Lipid nanoparticle chemistry determines how nucleoside base modifications alter mRNA delivery
Authors: Jilian R. Melamed, Khalid A. Hajj, Namit Chaudhary, Daria Strelkova, Mariah L. Arral, Norbert Pardi, Mohamad-Gabriel Alameh, Jason B. Miller, Lukas Farbiak, Daniel J. Siegwart, Drew Weissman, Kathryn A. Whitehead
Journal: Journal of Controlled Release (2021)

Therapeutic mRNA has the potential to revolutionize the treatment of myriad diseases and, in 2020, facilitated the most rapid vaccine development in history. Among the substantial advances in mRNA technology made in recent years, the incorporation of base modifications into therapeutic mRNA sequences can reduce immunogenicity and increase translation. However, experiments from our lab and others have shown that the incorporation of base modifications does not always yield superior protein expression. We hypothesized that the variable benefit of base modifications may relate to lipid nanoparticle chemistry, formulation, and accumulation within specific organs. To test this theory, we compared IV-injected lipid nanoparticles formulated with reporter mRNA incorporating five base modifications (ψ, m1ψ, m5U, m5C/ψ, and m5C/s2U) and four ionizable lipids (C12-200, cKK-E12, ZA3-Ep10, and 200Oi10) with tropism for different organs. In general, the m1ψ base modification best enhanced translation, producing up to 15-fold improvements in total protein expression compared to unmodified mRNA. Expression improved most dramatically in the spleen (up to 50-fold) and was attributed to enhanced protein expression in monocytic lineage splenocytes. The extent to which these effects were observed varied with delivery vehicle and correlated with differences in innate immunogenicity. Through comparison of firefly luciferase and erythropoietin mRNA constructs, we also found that mRNA modification-induced enhancements in protein expression are limited outside of the spleen, irrespective of delivery vehicle. These results highlight the complexity of mRNA-loaded lipid nanoparticle drug design and show that the effectiveness of mRNA base modifications depend on the delivery vehicle, the target cells, and the site of endogenous protein expression.