tbuckley/cabot-search huggingface dataset:
Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood
Authors: Shuzhen Chen, Yaping Dong, Xinming Qi, Qiqi Cao, Tao Luo, Zhaofang Bai, Huisi He, Zhecai Fan, Lingyan Xu, Guozhen Xing, Chunyu Wang, Zhichao Jin, Zhixuan Li, Lei Chen, Yishan Zhong, Jiao Wang, Jia Ge, Xiaohe Xiao, Xiuwu Bian, Wen Wen, Jin Ren, Hongyang Wang
Journal: Acta Pharmaceutica Sinica B (2021)

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.
Influenza Vaccine Uptake and Missed Opportunities Among the Medicare-Covered Population With High-Risk Conditions During the 2018 to 2019 Influenza Season
Authors: Bo-Hyun Cho, Cindy Weinbaum, Yuping Tsai, Ram Koppaka
Journal: Annals of Internal Medicine (2021)

Seasonal influenza causes substantial morbidity and mortality among older U.S. adults and those with comorbid health conditions.To describe seasonal influenza vaccine uptake and identify factors associated with missed opportunities for influenza vaccination.Retrospective cohort study.Medicare fee-for-service claims.31.6 million U.S. adults continuously enrolled under Medicare Parts A and B during the 2018 to 2019 influenza season.Influenza vaccine uptake and missed opportunities by patient demographic characteristics, high-risk status (that is, ≥1 condition increasing influenza complication risk), Medicare-Medicaid dual-eligibility status, and health care provider visits (that is, vaccination opportunities).Overall, 50.5% of beneficiaries aged 19 years or older had Medicare claims for influenza vaccination: 31.6% among people aged 19 to 64 years and 54% among people aged 65 years or older. More White beneficiaries were vaccinated (52.9%) than Black (34.9%) or Hispanic (30.4%) beneficiaries. Uptake was higher (56.1%) for beneficiaries with high-risk conditions than for those without (27.6%). Among unvaccinated beneficiaries overall, 77.4% visited a provider during influenza season; among unvaccinated beneficiaries with and without high-risk conditions, 91% and 43%, respectively, had seen a provider at least once. The proportion of beneficiaries with missed opportunities for influenza vaccination was 44.2% and was higher for beneficiaries in the non-high-risk group (59.1%) than those in the high-risk group (42.2%). Uptake was lower and proportions of missed opportunities were higher among beneficiaries in younger age groups, of Black and Hispanic race/ethnicity, without high-risk conditions, or with Medicare-Medicaid dual eligibility.Influenza vaccinations without claims could not be captured. Data on reasons for nonvaccination were unavailable.Influenza vaccination coverage for Medicare beneficiaries continues to be suboptimal, with missed opportunities despite availability of influenza vaccination with no copayment. Disparities persist in vaccination uptake by race/ethnicity.None.
Serological Response to the BNT162b2 mRNA or Chadox-Ncov-19 COVID-19 Vaccine after First and Second Doses in Plasma Cell Disorder Patients: Influence of Host and Disease Factors
Authors: Wei Yee Chan, Lara Howells, William Wilson, Emilie Sanchez, Louise Ainley, Selina J Chavda, Emma Dowling, Nuno Correia, Catherine SY Lecat, Annabel McMillan, Brendan Wisniowski, Shameem Mahmood, Xenofon Papanikolaou, Lydia Lee, Jonathan Sive, Charalampia Kyriakou, Ashutosh D. Wechalekar, Rakesh Popat, Neil K Rabin, Eleni Nastouli, Kwee Yong, Ke Xu
Journal: Blood (2021)
Recruitment of MLL1 Complex Is Essential for SETBP1 to Induce Myeloid Transformation
Authors: Nhu Nguyen, Kristbjorn Orri Gudmundsson, Anthony R. Soltis, Kevin Oakley, Yufen Han, Jaroslaw P. Maciejewski, Patricia Ernst, Clifton L. Dalgard, Yang Du
Journal: Blood (2021)
Hematopoietic Stem Cell Transplantation (HSCT) with Omidubicel Is Associated with Robust Immune Reconstitution and Lower Rates of Severe Infection Compared to Standard Umbilical Cord Blood Transplantation
Authors: Paul Szabolcs, Stuart Levy, Dima Yackoubov, Aviad Pato, Einat Galamidi-Cohen, Mitchell E. Horwitz
Journal: Blood (2021)
Histiocytic Neoplasms, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology
Authors: Ronald S. Go, Eric Jacobsen, Robert Baiocchi, Ilia Buhtoiarov, Erin B. Butler, Patrick K. Campbell, Don W. Coulter, Eli Diamond, Aron Flagg, Aaron M. Goodman, Gaurav Goyal, Dita Gratzinger, Paul C. Hendrie, Meghan Higman, Michael D. Hogarty, Filip Janku, Reem Karmali, David Morgan, Anne C. Raldow, Alexandra Stefanovic, Srinivas K. Tantravahi, Kelly Walkovich, Ling Zhang, Mary Anne Bergman, Susan D. Darlow
Journal: Journal of the National Comprehensive Cancer Network (2021)

Histiocytic neoplasms are rare hematologic disorders accounting for less than 1% of cancers of the soft tissue and lymph nodes. Clinical presentation and prognosis of these disorders can be highly variable, leading to challenges for diagnosis and optimal management of these patients. Treatment often consists of systemic therapy, and recent studies support use of targeted therapies for patients with these disorders. Observation ("watch and wait") may be sufficient for select patients with mild disease. These NCCN Guidelines for Histiocytic Neoplasms include recommendations for diagnosis and treatment of adults with the most common histiocytic disorders: Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai-Dorfman disease.
Abstract 9220: Employing a Convolutional Neural Network Facilitates Unsupervised Clustering of Aortic Outflow Velocity Profiles from Patients With Severe Aortic Stenosis
Authors: Mark Lachmann, Elena Rippen, Gerhard Harmsen, Erion Xhepa, Daniel Rueckert
Journal: Circulation (2021)

Introduction: The aortic outflow velocity profile is key to diagnose severe aortic stenosis (AS), and its shape reflects both aortic valve obstruction and left ventricular contractility. Hypothesis: Hypothesizing that aortic outflow velocity profiles contain more valuable information than can be captured by the human eye, features of the complex geometry of Doppler tracings were extracted by a convolutional neural network (CNN) pre-trained on big data (transfer learning). Methods: After pre-training a CNN (VGG-16) on a large data set (ImageNet data set; 14 million images belonging to 1,000 classes), the convolutional part was employed to transform Doppler tracings to 1D arrays. Principal component analysis (PCA) and k-means clustering of those 1D arrays were performed, and association between cluster and 2-year all-cause mortality was hereinafter assessed. Among 366 eligible patients with pre-procedural echocardiography and right heart catheterization prior to transcatheter aortic valve replacement (TAVR) for severe AS, good quality Doppler tracings from 101 patients were analyzed. Results: Among 101 patients (mean age: 79.3 ± 6.78 years; 49 [48.5%] women), estimated 2-year survival was 83.0% (95% CI: 75.1-91.7%). The convolutional part of the pre-trained VGG-16 model in conjunction with PCA and k-means clustering distinguished 2 shapes of aortic outflow velocity profiles. Kaplan-Meier analysis revealed that mortality in patients from cluster 2 (n = 40 [39.6%]) was significantly increased (HR for 2-year mortality: 3 [95% CI: 1-8.9]). Apart from reduced cardiac output and mean aortic valve gradient (AVG mean ), patients from cluster 2 were also characterized by signs of pulmonary hypertension, impaired right ventricular function and right atrial enlargement. Conventional dichotomization according to AVG mean confirmed that patients with AVG mean &lt; 40 mmHg (n = 54 [53.5%]) decease earlier, but no statistical significance was reached (HR for 2-year mortality: 1.8 [95% CI: 0.59-5.2]). Conclusions: This is a proof-of-principle that transfer learning aids in agnostic interpretation of aortic outflow velocity profiles, thereby holding the promise to refine prognostic resolution for survival after TAVR.
Impact of Allogeneic Hematopoietic Stem Cell Transplantation in First Complete Remission and Additional Cytogenetic Aberrations at Diagnosis on Prognosis in 1256 Pediatric Patients with KMT2A-Rearranged Acute Myeloid Leukemia: A Retrospective Study By the I-BFM-SG
Authors: Romy E. Van Weelderen, Kim Klein, Christine J. Harrison, Hester A. De Groot-Kruseman, Jonas Abrahamsson, Nira Arad-Cohen, Emmanuelle Bart-Delabesse, Barbara Buldini, Barbara De Moerloose, Michael Dworzak, Sarah Elitzur, José M. Fernández Navarro, Marta Fiocco, Robert B. Gerbing, Bianca F. Goemans, Erin Guest, Shau-Yin Ha, Henrik Hasle, Kathy Jackson, Charikleia Kelaidi, Hélène Lapillonne, Guy Leverger, Franco Locatelli, Takako Miyamura, Sophia Polychronopoulou, Mareike Rasche, Jeffrey E. Rubnitz, Jan Stary, Daisuke Tomizawa, Femke Verwer, C. Michel Zwaan, Gertjan J.L. Kaspers
Journal: Blood (2021)
Easix before Conditioning Therapy Predicts Sepsis after Allogeneic Stem Cell Transplantation
Authors: Felix Korell, Nicholas Schreck, Axel Benner, Tobias Liebregts, Stefan Schönland, Ute Hegenbart, Aleksandar Radujkovic, Michael Schmitt, Peter Dreger, Thomas Luft
Journal: Blood (2021)
Updated Results from a Phase II Study of Hyper-CVAD with Sequential Blinatumomab in Adults with Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia
Authors: Nicholas J. Short, Hagop Kantarjian, Farhad Ravandi, Xuelin Huang, Philip A. Thompson, Alessandra Ferrajoli, Tapan M. Kadia, Nitin Jain, Yesid Alvarado, Musa Yilmaz, Joseph D. Khoury, Jeffrey L. Jorgensen, Sa A Wang, Steven M. Kornblau, Marina Konopleva, Guillermo Garcia-Manero, Rebecca Garris, Heather M Schroeder, Anna Milton, Juan Rivera, Glenda Banks, Elias J. Jabbour
Journal: Blood (2021)
Sickle Cell Disease and Cystic Fibrosis Are Associated with Increased Non-Administration of VTE Prophylaxis in Adult Patients
Authors: Kiera Caparon, Jessica Crow, John Lindsley, Brandyn Lau, Michael B. Streiff, Rakhi P. Naik, Sophie M. Lanzkron, Lydia H. Pecker, Peggy Kraus, Elliott Haut, Jiangxia Wang, Kathryn Dane
Journal: Blood (2021)
Clinical performance of high-risk HPV testing on self-samples versus clinician samples in routine primary HPV screening in the Netherlands: An observational study
Authors: Federica Inturrisi, Clare A. Aitken, Willem J.G. Melchers, Adriaan J.C. van den Brule, Anco Molijn, John W.J. Hinrichs, Hubert G.M. Niesters, Albert G. Siebers, Rob Schuurman, Daniëlle A.M. Heideman, Inge M.C.M. de Kok, Ruud L.M. Bekkers, Folkert J. van Kemenade, Johannes Berkhof
Journal: The Lancet Regional Health - Europe (2021)

High-risk human papillomavirus (hrHPV) testing on self-collected samples has potential as a primary screening tool in cervical screening, but real-world evidence on its accuracy in hrHPV-based screening programmes is lacking.In the Netherlands, women aged 30-60 years invited for cervical screening can choose between sampling at the clinician's office (Cervex Brush) or self-sampling at home (Evalyn Brush). HrHPV testing is performed using Roche Cobas 4800. We collected screening test results between January 2017 and March 2018 and histological follow-up until August 2019. The main outcome measures were mean cycle threshold (Ct) value, cervical intraepithelial neoplasia (CIN) grade 3 or cancer (CIN3+) and CIN grade 2 or worse (CIN2+).30,808 women had a self-collected and 456,207 had a clinician-collected sample. In hrHPV-positive women with adequate cytology, Ct values were higher for self-collection than clinician-collection with a mean Ct difference of 1·25 (95% CI 0·98-1·52) in women without CIN2+, 2·73 (1·75-3·72) in CIN2 and 3·59 (3·03-4·15) in CIN3+. The relative sensitivity for detecting CIN3+ was 0·94 (0·90-0·97) for self-collection versus clinician-collection and the relative specificity was 1·02 (1·02-1·02).The clinical accuracy of hrHPV testing on a self-collected sample for detection of CIN3+ is high and supports its use as a primary screening test for all invited women. Because of the slightly lower sensitivity of hrHPV testing on a self-collected compared to a clinician-collected sample, an evaluation of the workflow procedure to optimise clinical performance seems warranted.National Institute for Public Health and the Environment (the Netherlands) and the European Commission.
Radiotherapy (WBRT) or Autologous Stem-Cell Transplantation (ASCT) for Primary CNS Lymphoma in Patients 60 Years of Age and Younger: Long-Term Results of the Intergroup Anocef-Goelams Randomized Phase II Precis Study
Authors: Caroline Houillier, Luc Taillandier, Roch Houot, Olivier Chinot, Cecile Molucon-Chabrot, Anna Schmitt, Rémy Gressin, Choquet Sylvain, Gandhi Laurent Damaj, Julie Abraham, Vincent Delwail, Emmanuel Gyan, Sylvain Dureau, Laurence Sanhes, Jérôme Cornillon, Reda Garidi, Alain Delmer, Marie-laure Tanguy, Ahmad Kanj AL Jijakli, Pierre Morel, Marie-Pierre Moles, Adrien Chauchet, Thomas Gastinne, Loïc Feuvret, Nathalie Cassoux, Valerie Touitou, Damien Ricard, Frédéric Peyrade, Mouna Laadhari, Anne-Sophie Plissonnier, Khe Hoang-Xuan, Carole Soussain
Journal: Blood (2021)
Outcomes in Patients with Poor-Risk Cytogenetics with or without <i>TP53</i> Mutations Treated with Venetoclax Combined with Hypomethylating Agents
Authors: Daniel A. Pollyea, Keith W. Pratz, Andrew H. Wei, Vinod A. Pullarkat, Brian A. Jonas, Christian Recher, Sunil Babu, Andre C. Schuh, Monique Dail, Yan Sun, Jalaja Potluri, Brenda Chyla, Courtney D. DiNardo
Journal: Blood (2021)
Cost-Effectiveness of Lisocabtagene Maraleucel (liso-cel) Versus Axicabtagene Ciloleucel (axi-cel) for Treatment of Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL)
Authors: Christopher Parker, Fei Fei Liu, Kristen Deger, Conrado Franco-Villalobos, Irina Proskorovsky, Scott J Keating, Sonja Sorensen, Emily Dorman
Journal: Blood (2021)
Preliminary Results from the Flu/Cy/Alemtuzumab Arm of the Phase I BALLI-01 Trial of UCART22, an Anti-CD22 Allogeneic CAR-T Cell Product, in Adult Patients with Relapsed or Refractory (R/R) CD22+ B-Cell Acute Lymphoblastic Leukemia (B-ALL)
Authors: Nitin Jain, Gail J. Roboz, Marina Konopleva, Hongtao Liu, Gary J. Schiller, Elias J. Jabbour, Deborah Whitfield, Asifa Haider, Oleg Zernovak, Mark G. Frattini, Carrie Brownstein, Richard A. Larson
Journal: Blood (2021)
Hemostatic Markers, Adamts-13 Profile and Anti-Sars-Cov-2 Antibody Levels in Patients with Immune Thrombotic Thrombocytopenic Purpura Receiving BNT162b2 Vaccination
Authors: Francesca Schieppati, Laura Russo, Marina Marchetti, Elisa Galimberti, Angela Maria Palladino, Sara Gamba, Cristina Verzeroli, Carmen Julia J Tartari, Silvia Bolognini, Chiara Ticozzi, Cinzia Giaccherini, Luca Barcella, Anna Falanga
Journal: Blood (2021)
Abstract 9308: Extreme Gamma Prime Fibrinogen Levels in COVID-19 Patients
Authors: David H Farrell, Matthew Hudkins, Heather Hamilton, Samantha J Underwood, Elizabeth N Dewey, Diana E Kazmierczak, Steven C Kazmierczak, William B Messer, Akram Khan, Martin A Schreiber
Journal: Circulation (2021)

Introduction: COVID-19 disease progression can be accompanied by a "cytokine storm" that leads to secondary sequelae such as thrombosis and acute respiratory distress syndrome. Several inflammatory cytokines have been associated with COVID-19 disease progression, but have far too much daily intra-individual variability to be useful in tracking the course of the disease. In contrast, we have shown that the inflammatory biomarker γ' fibrinogen (γ' Fbg) has a 6-fold lower coefficient of variability compared to other inflammatory markers such as hs-CRP. The aims of the study were to measure γ' Fbg in serial blood samples from COVID-19 patients at a tertiary care medical center in order to investigate its association with clinical measures of disease progression. Hypothesis: Our hypothesis was that γ' Fbg levels would be elevated in COVID-19 patients compared to historical controls, and that the degree of elevation would be associated with disease severity. Methods: COVID-19 patients at a tertiary care medical center were retrospectively enrolled between 3/16/2020 and 8/1/2020. γ' Fbg was measured using the GammaCoeur ELISA (Gamma Diagnostics, Patent Pending). Results: Our results showed that ten out of the eighteen patients with COVID-19 had the highest levels of γ' Fbg ever recorded. The previous highest γ' Fbg level of 80.3 mg/dL was found in a study of 10,601 participants in the ARIC study. γ' Fbg levels were significantly associated with the need for ECMO and mortality. Conclusions: We found that COVID-19 patients can develop extraordinarily high levels of γ' Fbg. This has several important clinical implications. γ' Fbg contains a high affinity binding site for thrombin that binds to anion-binding exosite II on thrombin and protects it from inactivation by heparin. High levels of γ' Fbg therefore provide a reservoir of heparin-resistant clot-bound thrombin when the γ' Fbg is clotted. These findings have potential clinical implications regarding prophylactic anticoagulation of COVID-19 patients and suggest that heparin prophylaxis may be less effective than using other anticoagulants, particularly direct thrombin inhibitors.
Immune-Depleted Tumor Microenvironment Signature Is Associated with BTK Inhibitor Resistance in Mantle Cell Lymphoma
Authors: Preetesh Jain, Krystle Nomie, Vitaly Segodin, Evgeniy Egorov, Yixin Yao, Lucy Navsaria, Holly Hill, Nikita Kotlov, Rashmi Kanagal-Shamanna, Chi Young Ok, Francisco Vega, Shaoying Li, Yuxuan Che, Yijing Li, Viktor Svekolkin, Alexander Bagaev, Felix Frenkel, Ravshan Attaulakhanov, Nathan H. Fowler, Christopher R. Flowers, Michael Wang
Journal: Blood (2021)
Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19
Authors: Sarthak Sinha, Nicole L. Rosin, Rohit Arora, Elodie Labit, Arzina Jaffer, Leslie Cao, Raquel Farias, Angela P. Nguyen, Luiz G. N. de Almeida, Antoine Dufour, Amy Bromley, Braedon McDonald, Mark R. Gillrie, Marvin J. Fritzler, Bryan G. Yipp, Jeff Biernaskie
Journal: Nature Medicine (2021)

Abstract Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin signaling. Dexamethasone during severe COVID-19 affected circulating neutrophils, altered IFN active neutrophils, downregulated interferon-stimulated genes and activated IL-1R2 + neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFN active neutrophils and preferential steroid-induced immature neutrophil expansion, potentially affecting outcomes. Our single-cell atlas (see ‘Data availability’ section) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19.
Pacific: A Phase II Study of Brentuximab Vedotin and Nivolumab Alone and then Combined with Rituximab, Cyclophosphamide, Doxorubicin and Prednisone for Patients with Untreated Primary Mediastinal Large B-Cell Lymphoma
Authors: Raphael E Steiner, Paolo Strati, Christopher R. Flowers, Sattva S. Neelapu, Michael R Green, Loretta Nastoupil, Fredrick B. Hagemeister, Lei Feng, Sairah Ahmed, Ranjit Nair, Luis Fayad, Hun Ju Lee, Maria Alma Rodriguez, Jason R. Westin
Journal: Blood (2021)
BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update
Authors: Maria Reig, Alejandro Forner, Jordi Rimola, Joana Ferrer-Fàbrega, Marta Burrel, Ángeles Garcia-Criado, Robin K. Kelley, Peter R. Galle, Vincenzo Mazzaferro, Riad Salem, Bruno Sangro, Amit G. Singal, Arndt Vogel, Josep Fuster, Carmen Ayuso, Jordi Bruix
Journal: Journal of Hepatology (2021)
The Interferons and Their Inducers: Molecular and Therapeutic Considerations
Authors: Sidney E. Grossberg
Journal: New England Journal of Medicine (1972)

Agents Inhibited by InterferonThe most salient feature of the interferons is their inhibition, in cell culture and in vivo, of the replication and effects of diverse viruses, including RNA and DNA viruses composed of a variety of chemical and immunologic types (Table 1). Their suppressive action is effective against oncogenic viruses as well as those that produce cytocidal effects or remain inapparent during replication. Infections with the DNA viruses, herpes simplex, cytomegalovirus and, to a lesser extent, some adenoviruses, as well as the double-stranded RNA reovirus, are relatively resistant to interferon action although infections with . . .
A FLI1-KLF6 Axis Regulates Aging in Human Hematopoietic Stem and Progenitor Cells and Normalization of KLF6 Levels in Aged Cells Leads to Their Rejuvenation
Authors: Alejandro Roisman, Emmalee R. Adelman, Natalia Weich, Aristeidis G. Telonis, Dean Wade, Daniel Bilbao, Ramiro E Verdun, Maria E. Figueroa
Journal: Blood (2021)