tbuckley/cabot-search huggingface dataset:
BIOM-37. ELUCIDATION OF THE TRANSCRIPTOMIC CONSEQUENCES OF KLF4 AND TRAF7 MUTATIONS IN SECRETORY MENINGIOMAS
Authors: Signe Michaelsen, Paul Cloos, Helle Broholm, Jens Johansen, Ulvi Ahmedov, Tiit Mathiesen, Lasse Kristensen, Bjarne Kristensen, Klaus Hansen
Journal: Neuro-Oncology (2021)

Abstract Secretory meningioma (SM) is a benign histological meningioma subtype frequently located in the central skull-base, complicating surgical removal, highlighting the need of gentle targeting treatment alternatives. SM tumors arise from the arachnoid layer in the meninges and are associated with a hotspot p.K409Q mutation in KLF4 combined with different mutations in TRAF7. The objective of this study was to identify how KLF4 and TRAF7 mutations alter signaling in SM tumors. The study includes 16 FFPE samples from SM tumors and three arachnoid cysts as normal-tissue reference. All tissues were histologically confirmed, followed by genomic sequencing of KLF4, TRAF7, NF2 and TERT-promoter (C220T/C228T) using a customized NGS panel. Gene expression profiles were analyzed using NanoString Pan-cancer Progression and Pan-cancer Pathways panels, which resulted in measurement of 1,202 unique transcripts over background level. All 16 SM tumors presented the KLF4p.K409Q mutation, of which 12 had mutation in TRAF7 (four being p.N520S), while no cysts had mutations in these genes. Neither tumors nor cysts had NF2 or TERT-promoter mutations. PCA analysis showed different RNA expression profiles for SM tumors and cysts, while TRAF7 mutation was without influence on the overall gene expression patterns in the tumors. Sub-analysis found increased KLF4 expression in TRAF7-mutated SM tumors versus non-mutated tumors and cysts at the RNA level, while TRAF7 expression was stable in all samples. In total 98 genes were found differentially expressed (54 up- and 44 downregulated) with a log2-fold change over 1 and an adjusted p-value under 0.05 in tumors versus cysts. Further analyses are planned to explore and validate these results. In conclusion, we find that the KLF4p.K409Q mutation correlates more strongly with SM histology, than the TRAF7 mutation, and that SM tumors have gene expressions profiles that are distinct from normal arachnoid tissue for a number of disease relevant genes.
Concomitant Deletion of Short Arm (del 1p) and Amplification or Gain (1q21) of Chromosome 1 By Fluorescence in Situ Hybridization (FISH) Is Associated with Poor Clinical Outcome
Authors: Meera Mohan, Zimu Gong, Samantha Kendrick, Sharmilan Thanendrarajan, Carolina Schinke, Daisy Alapat, Guido Tricot, Fenghuang Zhan, Frits van Rhee, Jeffery R. Sawyer, Erming Tian, Maurizio Zangari
Journal: Blood (2021)
Abstract 11140: Mitral Valve Repair with the Mitraclip System in Patients with Cardiogenic Shock
Authors: Caleb Chiang, Konstantinos Voudris, Clifford J Kavinsky, Hussam Suradi
Journal: Circulation (2021)

Introduction: The presence of significant mitral regurgitation (MR) in patients with cardiogenic shock (CS) patients is associated with worse prognoses. Limited data exists on the effect of percutaneous mitral valve repair (PMVR) with MitraClip in this population. Hypothesis: We examined short term outcomes of MitraClip PMVR in patients with CS and MR at 30 days and six months. Methods: Single-center, retrospective study of patients with CS and MR undergoing PMVR between January 2015 and December 2020. All patients were followed up for 6 months. Baseline and procedural characteristics as well as 30-day and six-months outcomes of all-cause mortality, heart failure hospitalizations, stroke, new atrial fibrillation, new pacemaker placement, and improvement in MR severity ≥2 grades were assessed. Results: A total of 20 patient were included for analysis. The mean age was 72.8 ± 11.1 years; 9 patients (45%) were men. MR was due to primary pathology in 9 patients (45%), functional in 2 (10%) and mixed in 9 (45%). Characteristics of the population are shown in Table 1. At 30 days all-cause mortality was 20% (n=4), while 2 patients (10%) required HF hospitalization. MR severity improved by at least 2 grades in 10 patients (50%). At six months, all-cause mortality was 40% (n=8), while 4 patients (20%) required heart failure readmission. 10 patients (50%) maintained the improvement in MR severity. There was no incidence of stroke, new atrial fibrillation, or new pacemaker placement at 30 days or 6 months. Conclusions: PMVR with the MitraClip system is a feasible and a safe option for MR in patients with CS. Improved MR severity is maintained at 30 days and 6 months.
A Global Multiregional Proteomic Map of the Human Cerebral Cortex
Authors: Zhengguang Guo, Chen Shao, Yang Zhang, Wenying Qiu, Wenting Li, Weimin Zhu, Qian Yang, Yin Huang, Lili Pan, Yuepan Dong, Haidan Sun, Xiaoping Xiao, Wei Sun, Chao Ma, Liwei Zhang
Journal: Genomics Proteomics & Bioinformatics (2021)

The Brodmann area (BA)-based map is one of the most widely used cortical maps for studies of human brain functions and in clinical practice; however, the molecular architecture of BAs remains unknown. The present study provided a global multiregional proteomic map of the human cerebral cortex by analyzing 29 BAs. These 29 BAs were grouped into 6 clusters based on similarities in proteomic patterns: the motor and sensory cluster, vision cluster, auditory and Broca's area cluster, Wernicke's area cluster, cingulate cortex cluster, and heterogeneous function cluster. We identified 474 cluster-specific and 134 BA-specific signature proteins whose functions are closely associated with specialized functions and disease vulnerability of the corresponding cluster or BA. The findings of the present study could provide explanations for the functional connections between the anterior cingulate cortex and sensorimotor cortex and for anxiety-related function in the sensorimotor cortex. The brain transcriptome and proteome comparison indicates that they both could reflect the function of cerebral cortex, but show different characteristics. These proteomic data are publicly available at the Human Brain Proteome Atlas (www.brain-omics.com). Our results may enhance our understanding of the molecular basis of brain functions and provide an important resource to support human brain research.
Abstract 10004: Novel Coronavirus Disease 2019 Infection in a Cohort of Patients with Phenotypic Hypertrophic Cardiomyopathy
Authors: Leyla Gasimli-Gamache, Marjolein Le, Felicia Cabrera, Jamshid Shirani
Journal: Circulation (2021)

Background: Cardiovascular diseases have been identified as major risk factors for adverse outcomes in patients with novel coronavirus 2019 disease (COVID-19). Patients with genetic diseases of the heart, including those with hypertrophic cardiomyopathy (HCM), have been warned regarding higher risk of adverse outcomes following COVID-19. No specific data, however, has been reported regarding the actual risk of COVID-19 in adults with HCM. We aimed to evaluate incidence and outcomes of COVID-19 in a cohort of adults with HCM followed at one center. Methods: Adults with phenotypic HCM [n=199, age 57±17 years, 55% men, 22% New York Heart Association class &gt;1, 57% obstructive, 9% septal reduction therapy, 22 % positive family history, 41% selectively genotyped (40% positive for pathogenic mutations in MYBPC3, MYH7, and TNNI3 genes), 24% cardioverter-defibrillator implants, 24% paroxysmal or permanent atrial fibrillation (AF), 7% AF ablation] were retrospectively evaluated. Results: Overall, 14 (7%) were diagnosed with COVID-19 [50% men, age 56±16 years, 57% obstructive HCM, 21 % positive family history, 7% genotype positive]. There was no statistically significant demographic or clinical differences between 14 with and 185 without [56% men, age 58±17 years, 57% obstructive, 22 % positive family history, 17% genotype positive] COVID-19. Among those with COVID-19, 4 (27%) were hospitalized and 1 (7%) died of COVID-19. Compared to those with mild disease, hospitalized patients with COVID-19 were older (age 63±13 vs. 53±16 years), more often men (75% vs. 40%) and more often had a positive family history of HCM (50% vs. 10%) without significant differences in other demographic or clinical features. Only 1 patient (7%) was fully vaccinated prior to COVID-19 and had mild symptoms. Currently, 104 (52%) have received at least one dose of a COVID-19 vaccine and 83 (42%) are fully vaccinated. Conclusions: Although COVID-19 infection rate (7%) in this cohort of patients with HCM was below the rate in the general US population (~10%), hospitalization rate (27%) and death rate (7%) were above those noted in the nation (6.7% and 1.8%, respectively). The data confirms the notion that patients with HCM may have higher risk for developing COVID-19 related adverse outcomes.
Long-Term Outcome of Conjunctival Extranodal Marginal Zone Lymphoma: A Large Single-Institution Analysis
Authors: Eduardo Saul, Juan Pablo Alderuccio, Isildinha M. Reis, Wei Zhao, Sunil G. Iyer, Gregor Rodriguez, Amrita Desai, Derek Isrow, Arnold M. Markoe, Izidore S. Lossos
Journal: Blood (2021)
Safety and Efficacy of Aru-1801 in Patients with Sickle Cell Disease: Early Results from the Phase 1/2 Momentum Study of a Modified Gamma Globin Gene Therapy and Reduced Intensity Conditioning
Authors: Michael Grimley, Monika Asnani, Archana Shrestha, Sydney Felker, Carolyn Lutzko, Paritha I. Arumugam, Scott Witting, Jennifer Knight-Madden, Omar Niss, Charles T. Quinn, Chris Lo, Courtney R. Little, Alisa Dong, Punam Malik
Journal: Blood (2021)
Dual BCL-2/BCL-XL Inhibitor Pelcitoclax (APG-1252) Overcomes Intrinsic and Acquired Resistance to Venetoclax in Multiple Myeloma Cells
Authors: Leona Yamamoto, Sanika Derebail, Anil Aktas-Samur, Teru Hideshima, Zuzana Chyra, Chandraditya Chakraborty, Yao Yao, Doriana Gramegna, Eugenio Morelli, Mehmet K. Samur, Jing Deng, Yifan Zhai, Annamaria Gulla, Mariateresa Fulciniti, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2021)
Abstract 9106: Comparing the Risk of Post-Discharge Bleeding from Dual Antiplatelet Therapy, after Percutaneous Coronary Intervention, Between US Black and White Adults
Authors: Brittain F Heindl, Stephen A Clarkson, Chrisly S Dillon, Renuka Narayan, Ebikere Usifo, Mark Beasley, Nita Limdi
Journal: Circulation (2021)

Introduction: Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) reduces myocardial infarctions but increases bleeding. Guidelines recommend using risk scores to assess bleeding risk, but none have been validated in self-reported Black patients. We compared 1) post-discharge bleeding between US Black and White patients, and 2) the ability of three risk scores to predict bleeding between them. Methods: The PRiME-GGAT prospective cohort study enrolled patients (2014-2019) who underwent PCI and followed them for one year. Variables measured at PCI were included in the PRECISE-DAPT, PARIS, and ARC-HBR scores. The outcome was post-discharge BARC 2-5 events. Incidence rates were compared between Black and White patients, using incidence rate ratios (IRRs). Proportional hazards models measured the effect of self-reported Black ethnicity, adjusted for bleeding risk factors. Risk scores were compared between Black and White patients using: 1) IRRs, 2) Harrell’s C-indices, and 3) Kendall’s tau-b coefficients (τ b ). τ b was not measured for the binary ARC-HBR score. Results: Of 1529 included patients, 342 (22.4%) self-reported as Black. The incidence rate was higher among Black patients compared to White patients (22.7 versus 16.3, respectively, per 100 person-years; IRR 1.39; 95% CI, 1.01-1.90). After adjustment, self-reported Black ethnicity was not a predictor of bleeding. For both groups, IRRs were largest for PRECISE-DAPT. Between Black and White patients, respectively, C-index was 0.65 vs. 0.61 for PRECISE-DAPT, 0.63 vs. 0.61 for PARIS, and 0.60 vs. 0.59 for ARC-HBR; and τ b , respectively, was 0.71 vs. 0.64 for PRECISE-DAPT, and 0.79 vs. 0.86 for PARIS. Conclusions: Post-discharge bleeding from DAPT was greater for Black patients, compared with White patients, but this difference was not present after adjustment. PRECISE-DAPT was superior among Black patients, but PARIS was superior among White patients.
Adverse Events Following COVID-19 Vaccination in Transfusion-Dependent -Thalassemia Patients
Authors: Polyxeni Delaporta, Eugenia Lampropoulou, Anastasia Moschoviti, Ilona Binenbaum, Dimitra Kyriakopoulou, Natalia Ioakeimidou, Sofia Chante, Ioannis Papassotiriou, Antonis Kattamis
Journal: Blood (2021)
Targeting the Membrane-Proximal C2-Set Domain of CD33 for Improved CD33-Directed CAR T Cell Therapy
Authors: Salvatore Fiorenza, George S. Laszlo, Tinh-Doan Phi, Margaret C. Lunn, Delaney R. Kirchmeier, Colin D. Godwin, Erik L. Kimble, Cameron J. Turtle, Roland B. Walter
Journal: Blood (2021)
Final Analysis of a Prospective Multicenter Phase II Trial of the Lymphoma Study Association (LYSA) Using Prednisone, Vinblastine, Doxorubicin and Bendamustine (PVAB) Regimen in First Line Therapy for Patients over 60 Years with Advanced-Stage Classical Hodgkin Lymphoma
Authors: Herve Ghesquieres, Rene-Olivier Casasnovas, Emmanuelle Nicolas-Virelizier, Salim Kanoun, Gandhi Laurent Damaj, Vincent Delwail, Arnaud Jaccard, Kamel Laribi, Franck Morschhauser, Christophe Bonnet, Agathe Waultier, Frederique Orsini-Piocelle, Marc Andre, Marguerite Fournier, Fabienne Morand, Alina Berriolo-Riedinger, Diane Damotte, Alexandra Traverse-Glehen, Philippe Quittet, Pauline Brice
Journal: Blood (2021)
Magnitude and temporal trend of acne vulgaris burden in 204 countries and territories from 1990 to 2019: an analysis from the Global Burden of Disease Study 2019*
Authors: H. Chen, T.C. Zhang, X.L. Yin, J.Y. Man, X.R. Yang, M. Lu
Journal: British Journal of Dermatology (2021)

Acne vulgaris is widespread across the world. Mapping the latest magnitudes and temporal trends of acne vulgaris provides the essential foundation for targeted public policies at the national, regional and global levels.In compliance with the framework of the Global Burden of Disease Study 2019, this study aimed to summarize the incidence, prevalence, DALYs and the corresponding secular trends of acne vulgaris by sex and age group in 204 countries from 1990 to 2019.The average annual percentage change was calculated to depict the temporal trends in age-standardized rates (ASRs) of acne vulgaris burden by region, sex and age.Globally, it was estimated that there were 117·4 million [95% uncertainty interval (UI) 103·0-133.7] incident cases of acne vulgaris, 231·2 million (95% UI 208·2-255·5) prevalent cases and 5·0 (95% UI 3·0-7·9) million DALYs, with an increase of approximately 48% compared with 1990. Moreover, the overall ASRs of acne vulgaris increased by approximately 0·55% annually over the past three decades. We observed large disparities in ASRs of acne vulgaris with changing trends in sex, location and age. The ASR of acne vulgaris among women was around 1·3 times that of men, but the sex difference was narrowed because of the pronounced increase among men. The ASRs of acne vulgaris were higher in high-income regions, but the increasing trend was more pronounced in other regions.The burden rate of acne vulgaris continues to increase in almost all countries. Understanding the specific characteristics of acne vulgaris burden is essential to formulate more effective and targeted interventions for controlling acne burden.
Early Relapse after First Line Has a Significant Impact on Overall Survival in Patients with Mantle Cell Lymphoma (MCL)
Authors: Alba Cabirta, Pau Abrisqueta, Carla Sanchez-Ruiz, Sabela Bobillo, Cecilia Carpio, Gloria Iacoboni, Mercedes Gironella Mesa, Marta Julia, Angel Serna, Carlos Palacio, Josep Castellvi, Francesc Bosch, Ana Marin-Niebla
Journal: Blood (2021)
Outcomes of Patients with Chronic Lymphocytic Leukemia (CLL) Treated with the Combination of Ibrutinib (I) and Venetoclax (V; I+V) after Progression on I Alone (V-naïve) or after Progression on Sequential I and V (Double-Refractory)
Authors: Paul J. Hampel, Kari G. Rabe, Timothy G. Call, Wei Ding, Jose F. Leis, Asher Chanan-Khan, Saad S. Kenderian, Eli Muchtar, Yucai Wang, Sikander Ailawadhi, Amber Koehler, Susan M. Schwager, Taimur Sher, Curtis A. Hanson, Min Shi, Daniel L. Van Dyke, Esteban Braggio, Susan L. Slager, Neil E. Kay, Sameer A. Parikh
Journal: Blood (2021)
Abstract 12372: Acute Supplementation of Lactobacillus plantarum 299v Improves Vascular Endothelial Function in Adults With Stable Coronary Artery Disease (CAD)
Authors: Benjamin C Hofeld, Venkata K Puppala, Elise Nelton, Amberly Anger, Rachel A Schneider, Molly Pfeffer, Michael E Widlansky
Journal: Circulation (2021)

Introduction: We have shown that dietary supplementation of L. plantarum 299v (Lp299v) over a six-week period in men with stable CAD improves endothelial function and reduces systemic inflammation....
Abstract 9294: Prognosis of Atrial Fibrillation in Low Gradient Aortic Stenosis
Authors: Nikhil Kolluri, Didem Oguz, Christopher Scott, Juan A Crestanello, Sorin Pislaru, Jeremy J Thaden, Vuyisile T Nkomo
Journal: Circulation (2021)

Introduction: A significant portion of patients with aortic stenosis (AS) have low-gradient AS (LGAS) defined as aortic valve area ≤ 1.0 cm 2 and a trans-aortic mean systolic gradient and peak velocity &lt; 40 mmHg and &lt; 4 m/s, respectively. LGAS has been shown previously to have worse mortality compared to high-gradient AS (HGAS). Etiologies for LGAS include diastolic dysfunction, heart failure, other significant valvular disease, and atrial fibrillation (AF). AF is associated with worse outcomes compared to sinus rhythm (SR) in HGAS. AF is common in LGAS, but whether AF is associated with worse outcomes versus SR in LGAS has not been elucidated. Hypothesis: We hypothesize that AF is associated with higher mortality compared to SR in patients with LGAS. Methods: We retrospectively identified and reviewed charts of patients who were diagnosed with LGAS on transthoracic echocardiogram (TTE) from 2010-2020 at Mayo Clinic. Patient were classified according to rhythm at the time of TTE and history of AF was ascertained among those in SR. Patents were divided into 3 groups; SR without history of AF (group 1), SR with history of AF (group 2), and AF during TTE (group 3). Primary endpoints of overall mortality and cardiac mortality were ascertained. Results: A total of 3400 patients were included: n=2036 in group 1, n=519 in group 2, and n=845 in group 3. After adjusting for age, sex, and the Charlson index, group 2 and group 3 patient had significantly higher overall mortality (HR 1.22 and HR 1.52, respectively, p&lt;0.0001 for both) and cardiac mortality (HR 1.37 and HR 2.05, respectively, p&lt;0.0001 for both), Figure . Conclusions: In LGAS, AF is a significant prognostic indicator of overall mortality and cardiac mortality. LAGS associated with AF may need different management strategies given the higher mortality associated with the presence of AF.
Antibody Response to Vaccination with BNT162b2, mRNA-1273, and ChADOx1 in Patients with Myeloid and Lymphoid Neoplasms
Authors: Jil Rotterdam, Margot Thiaucourt, Juliana Schwaab, Andreas Reiter, Sebastian Kreil, Laurenz Steiner, Henning D. Popp, Wolf-Karsten Hofmann, Karin Bonatz, Catharina Gerhards, Michael Neumaier, Mohamad Jawhar, Susanne Saussele
Journal: Blood (2021)
Prevalence of Allelic Variants and Clonality of IGHV1-69 Expressing B-Cells in Patients with Different Severity of COVID 19 Disease
Authors: Irina Panovska-Stavridis, Nevenka Ridova, Simona Stojanovska, Milena Stevanovic, Tatjana Stojanoska, Ilir Demiri, Nadica Matevska-Geshkovska, Marija Vujovic, Hristina Markoska, Venko Filipce, Aleksandar J. Dimovski, Dimitar G Efremov
Journal: Blood (2021)
Annals Graphic Medicine - The Hospital Makes It Hard to Speak Up for Myself
Authors: Rachel Litchman
Journal: Annals of Internal Medicine (2021)

Web ExclusivesNovember 2021Annals Graphic Medicine - The Hospital Makes It Hard to Speak Up for MyselfFREERachel LitchmanRachel LitchmanUniversity of Wisconsin–Madison, Madison, Wisconsin (R.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G21-0017 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Wisconsin–Madison, Madison, Wisconsin (R.L.)Disclosures: The author has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G21-0017.Author/Illustrator Information: Rachel Litchman is an artist, writer, and student at the University of Wisconsin-Madison (e-mail, [email protected]edu). You can view more of her work at racheldl.com.This article was published at Annals.org on 9 November 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics November 2021Volume 174, Issue 11Page: W107-W112 ePublished: 9 November 2021 Issue Published: November 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
292 Ex vivo profiling of PD-1 blockade using an organotypic tissue slice model in solid tumors
Authors: Lina Ding, Kristin Sullivan, Chensheng Zhou, Jimena Trillo-Tinoco, Anne Lewin, Catherine King, David Nelson, Benjamin Chen, Michaela Bowden
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Tumor explant models provide a powerful ex vivo tool to evaluate complex biological mechanisms in a controlled environment. Ex vivo models retain much of the original tumor biology, heterogeneity, and tumor microenvironment, and therefore provide a useful preclinical platform and functional approach to assess drug responses rapidly and directly. Methods To explore mechanisms of resistance to cancer immunotherapy, we established an organotypic tissue slice Air-Liquid Interface (ALI) ex vivo system utilizing surgical tumor specimens from patients to assess the impact of the clinically utilized anti-PD-1 antibody nivolumab (OPDIVO). In the present study, we built a real-world patient cohort comprised of six tumor types: non-small cell lung cancer, melanoma, pancreatic ductal adenocarcinoma, breast cancer, prostate cancer, and colorectal cancer. We assessed tissue morphology, histology, PD-L1 IHC (CPS and TPS), CD8 T cell topology, proliferation in the tumor and stromal compartments, and secretome profiling. Results Our tumor slice model highly recapitulated features of the original tumor, including tumor architecture, immune phenotypes, and the prognostic markers. To identify responses to aPD-1 treatment, we compared baseline values for the cultured tumor slices with values at different timepoints post treatment. Secretome profiling of tissue explant supernatants using a panel of 94 analytes, revealed alterations to cytokines produced in the tumor microenvironment in response to aPD-1 treatment. We found that soluble expression patterns were associated with T-cell patterns (inflamed, excluded and desert) and PD-L1 score (CPS and TPS) in tumor tissues. These cytokines mediate critical functions across the immune cell cycle. Ongoing efforts to characterize T cell activation, exhaustion, tumor intrinsic responses and microenvironment composition using Imaging Mass Cytometry will be presented. Conclusions In this study, we demonstrated the feasibility of using fresh, surgically resected human tumors to test aPD-1 responses in an ex vivo system. Further, this model system has the potential to drive discovery and translational efforts by evaluating mechanisms of resistance to cancer immunotherapy and evaluate new single agent or combination therapies in the ex vivo setting.