tbuckley/cabot-search huggingface dataset:
31 The prognostic value of transient elastography: a single centre irish study
Authors: S Naimimohasses, O El-Sherif, J O’Connell, B Hynes, H Irish, C Quinn, SJ Miggins, F MacCarthy, D Kevans, M Iqbal, S McKiernan, S Norris
Journal: Gut (2017)

Background  Transient elastography (TE) has facilitated the rapid and non-invasive assessment of hepatic fibrosis. Recent studies have signified its utility in identifying patients with early clinically significant portal hypertension (CSPH), providing valuable prognostic information and has been incorporated in the Baveno VI recommendations.  Aim  The aim of this study was to assess for features of CSPH and evaluate the clinical outcomes in patients with TE scores of ≥10 kPa.  Method  A retrospective review was performed on all patients attending the Hepatology Department in St. James’ Hospital with valid TE measurements≥10 kPa using an ECHO-sens Fibro-scanner with a M2 probe.  Results  A total of 384 (18%) patients had transient elastography scores≥10 kPa. The most common aetiologies were HCV n=237 (61.7%) and NAFLD n=45 (11.7%). A TE score of ≥30 kPa was highly predictive of numerous composite endpoints: liver-related hospital admissions OR8.6 (95% CI 4.1 to 18.0), decompensation OR12.7 (95% CI 5.47 to 29.3) and death OR8.61 (95% CI 2.8 to 26.5). The Baveno VI criteria demonstrated a good predictive value for the presence of oesophageal varices OR2.7 (95% CI 1.39 to 5.26), however, the negative predictive value was poor 79.1% in our mixed patient population.  Conclusions  A TE score threshold of ≥30 kPa demonstrated good predictive value for identifying at risk patients. Although the Baveno VI criteria was useful for the discrimination of patients at risk of developing varices, other factors may also need to be considered in order to improve the negative predictive value.
Cardiac Involvement After Recovering From COVID-19—Reply
Authors: Valentina Puntmann, Eike Nagel
Journal: JAMA Cardiology (2020)

19To the Editor I read with interest the by Puntmann et al 1 regarding the cardiac magnetic resonance (CMR) imaging findings in a group of 100 patients with asymptomatic to a severe course of coronavirus disease 2019 (COVID-19) after a median of 2 to 3 months from diagnosis.I was surprised by the high frequency of cardiac involvement still present in that group, including signs of fibrosis in 78% of patients and ongoing inflammation in 60% of them.The study drew large media attention around the world and brings serious clinical concerns regarding the potential need for in-depth cardiologic screening in all patients after recovering from COVID-19.The recent study by my coauthors and me 2 on persistent subclinical changes in CMR imaging after a median of 7 months from myocarditis in children revealed ongoing active inflammation in 28% of patients and healed myocarditis with persistent scars in 44% of patients.Therefore, a 2-fold lower frequency of persistent myocardial changes, detected later from the onset of the disease, was observed in our group of adolescents with confirmed myocarditis.We did not use T1 and T2 mapping techniques, which are able to detect a subtler myocardial injury or ongoing myocardial inflammation, 3 but the difference was still remarkably large, especially considering asymptomatic or mildly affected patients composed a significant amount of the post-COVID-19 group. 2 Therefore, I would like to raise some comments regarding the study by Puntmann et al, 1 which might explain the high frequency of cardiac involvement detected.First, the application of the modified Lake Louise criteria, 4 requiring the presence of both T1 and T2 relaxation time elevation to diagnose an ongoing inflammation, was not reported in the article, and although T1 and T2 usually rise in parallel, on that occasion, the frequency of ongoing myocarditis, at least theoretically, could range from 38% to 60%.Second, Puntmann et al 1 used reference criteria for cutoff values of elevated T1 and T2 from studies performed on a 3-T Philips scanner, while their study was done on a 3-T Siemens scanner.In my opinion, these values are not interchangeable.The reference ranges reported for a 3-T Philips scanner are much lower than reference values for a 3-T Siemens scanner, which have been summarized in our report 2 and are higher by approximately 100 milliseconds for T1 and 10 milliseconds for T2. 5 Therefore, a cutoff point could have been set too low, leading to many false-positive findings.However, only 3 patients with the most severe course had a myocardial biopsy to verify that hypothesis.
Lyn Kinase Activity Is Required for Akt Mediated Erythroleukemia Cell Differentiation
Authors: Janice H. C. Plani-LAM, Mhairi Maxwell, Neli Slavova-Azmanova, Nicole Kucera, Alison Louw, Jiulia Satiaputra, Susan Wu, Edward Bastow, Cindy Le, Cathy Quilici, Margaret L Hibbs, Evan Ingley
Journal: Blood (2020)
Transmission of SARS-COV-2 Infections in Households — Tennessee and Wisconsin, April–September 2020
Authors: Carlos G. Grijalva, Melissa A. Rolfes, Yuwei Zhu, Huong Q. McLean, Kayla E. Hanson, Edward A. Belongia, Natasha B. Halasa, Ahra Kim, Carrie Reed, Alicia M. Fry, H. Keipp Talbot
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Improved understanding of transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), within households could aid control measures. However, few studies have systematically characterized the transmission of SARS-CoV-2 in U.S. households (1). Previously reported transmission rates vary widely, and data on transmission rates from children are limited. To assess household transmission, a case-ascertained study was conducted in Nashville, Tennessee, and Marshfield, Wisconsin, commencing in April 2020. In this study, index patients were defined as the first household members with COVID-19-compatible symptoms who received a positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test result, and who lived with at least one other household member. After enrollment, index patients and household members were trained remotely by study staff members to complete symptom diaries and obtain self-collected specimens, nasal swabs only or nasal swabs and saliva samples, daily for 14 days. For this analysis, specimens from the first 7 days were tested for SARS-CoV-2 using CDC RT-PCR protocols.† A total of 191 enrolled household contacts of 101 index patients reported having no symptoms on the day of the associated index patient's illness onset, and among these 191 contacts, 102 had SARS-CoV-2 detected in either nasal or saliva specimens during follow-up, for a secondary infection rate of 53% (95% confidence interval [CI] = 46%-60%). Among fourteen households in which the index patient was aged <18 years, the secondary infection rate from index patients aged <12 years was 53% (95% CI = 31%-74%) and from index patients aged 12-17 years was 38% (95% CI = 23%-56%). Approximately 75% of secondary infections were identified within 5 days of the index patient's illness onset, and substantial transmission occurred whether the index patient was an adult or a child. Because household transmission of SARS-CoV-2 is common and can occur rapidly after the index patient's illness onset, persons should self-isolate immediately at the onset of COVID-like symptoms, at the time of testing as a result of a high risk exposure, or at the time of a positive test result, whichever comes first. Concurrent to isolation, all members of the household should wear a mask when in shared spaces in the household.§.
ANGPTL2-containing small extracellular vesicles from vascular endothelial cells accelerate leukemia progression
Authors: Dan Huang, Guohuan Sun, Xiaoxin Hao, Xiaoxiao He, Zhaofeng Zheng, Chiqi Chen, Zhuo Yu, Li Xie, Shihui Ma, Ligen Liu, Bo O. Zhou, Hui Cheng, Junke Zheng, Tao Cheng
Journal: Journal of Clinical Investigation (2020)

Small extracellular vesicles (SEVs) are functional messengers of certain cellular niches that permit noncontact cell communications. Whether niche-specific SEVs fulfill this role in cancer is unclear. Here, we used 7 cell type–specific mouse Cre lines to conditionally knock out Vps33b in Cdh5+ or Tie2+ endothelial cells (ECs), Lepr+ BM perivascular cells, Osx+ osteoprogenitor cells, Pf4+ megakaryocytes, and Tcf21+ spleen stromal cells. We then examined the effects of reduced SEV secretion on progression of MLL-AF9–induced acute myeloid leukemia (AML), as well as normal hematopoiesis. Blocking SEV secretion from ECs, but not perivascular cells, megakaryocytes, or spleen stromal cells, markedly delayed the leukemia progression. Notably, reducing SEV production from ECs had no effect on normal hematopoiesis. Protein analysis showed that EC-derived SEVs contained a high level of ANGPTL2, which accelerated leukemia progression via binding to the LILRB2 receptor. Moreover, ANGPTL2-SEVs released from ECs were governed by VPS33B. Importantly, ANGPTL2-SEVs were also required for primary human AML cell maintenance. These findings demonstrate a role of niche-specific SEVs in cancer development and suggest targeting of ANGPTL2-SEVs from ECs as a potential strategy to interfere with certain types of AML.
IDH2 Inhibitor Therapy in Relapsed and Refractory Acute Myeloid Leukemia: A Single Institution Experience
Authors: Marissa Li, Erika Morsia, Christopher E. Wee, Kristen McCullough, Aref Al-Kali, William J Hogan, Mrinal M. Patnaik, Ayalew Tefferi, Naseema Gangat
Journal: Blood (2020)
High-Dose Chemotherapy (HDC) with Autologous Stem-Cell Transplant (ASCT) with Consolidative Radiation Therapy (RT) for Relapsed or Refractory (R/R) Primary Mediastinal B-Cell Lymphoma (PMBCL): 20-Year Experience at MD Anderson Cancer Center (MDACC)
Authors: Neeraj Saini, Junsheng Ma, Melissa Timmons, Amin M. Alousi, Paolo Anderlini, Borje S. Andersson, Chitra Hosing, Jeremy Ramdial, Partow Kebriaei, Uday R. Popat, Muzaffar H. Qazilbash, Elizabeth J. Shpall, Samer A. Srour, Benigno C. Valdez, Bouthaina S. Dabaja, Chelsea C. Pinnix, Jillian R. Gunther, Farzaneh Maadani, Gabriela Rondon, Richard E. Champlin, Yago Nieto
Journal: Blood (2020)
High Survival in Patients with Myelofibrosis Undergoing a Two-Step Approach to Hematopoietic Stem Cell Transplantation (HSCT): Effects of Donor Source and Pre-HSCT Splenic Therapy on Outcomes
Authors: Shaik Rashid, Matthew Carabasi, Joanne Filicko-O'Hara, John L. Wagner, William O'Hara, Usama Gergis, Neal Flomenberg, Dolores Grosso
Journal: Blood (2020)
Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELY platform
Authors: Christopher T Rentsch, Nicholas J DeVito, Brian MacKenna, Caroline E Morton, Krishnan Bhaskaran, Jeremy P Brown, Anna Schultze, William J Hulme, Richard Croker, Alex J Walker, Elizabeth J Williamson, Chris Bates, Seb Bacon, Amir Mehrkar, Helen J Curtis, David Evans, Kevin Wing, Peter Inglesby, Rohini Mathur, Henry Drysdale, Angel Y S Wong, Helen I McDonald, Jonathan Cockburn, Harriet Forbes, John Parry, Frank Hester, Sam Harper, Liam Smeeth, Ian J Douglas, William G Dixon, Stephen J W Evans, Laurie Tomlinson, Ben Goldacre
Journal: The Lancet Rheumatology (2020)

Hydroxychloroquine has been shown to inhibit entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into epithelial cells in vitro, but clinical studies found no evidence of reduced mortality when treating patients with COVID-19. We aimed to evaluate the effectiveness of hydroxychloroquine for prevention of COVID-19 mortality, as opposed to treatment for the disease.
Safety and Efficacy of Maintenance Treatment Following Allogeneic Hematopoietic Cell Transplant in Acute Myeloid Leukemia and Myelodysplastic Syndrome - a Systematic Review and Meta-Analysis
Authors: Jan Philipp Bewersdorf, Martin S. Tallman, Christina Cho, Amer M. Zeidan, Maximilian Stahl
Journal: Blood (2020)
Anti-CD19 CAR-T for Treatment of Double Expressor and Double Hit Large B-Cell Lymphomas: A Single Institution Real-World Analysis
Authors: Elise A. Chong, Emeline R. Chong, Daniel J. Landsburg, James N. Gerson, Jakub Svoboda, Sunita Dwivedy Nasta, Stefan K. Barta, Alfred L. Garfall, Elizabeth Weber, Marco Ruella, Noelle V. Frey, David L. Porter, Stephen J. Schuster
Journal: Blood (2020)
Incidental Detection of Pancreatic Arteriovenous Malformation by 99mTc-RBC SPECT/CT
Authors: Xu Yang, Wei Wang, Ying Kan, Jigang Yang
Journal: Clinical Nuclear Medicine (2020)

Abstract A patient with multiple episodes of gastrointestinal bleeding underwent 99m Tc-labeled red blood cell scintigraphy to detect the source of bleeding, which showed a focally increased activity in the upper midabdomen. SPECT/CT demonstrated that the activity was located in the pancreatic head. Angiography confirmed the diagnosis of pancreatic arteriovenous malformation. After transarterial embolization therapy, the patient no longer had bleeding episode. Based on the present case, pancreatic arteriovenous malformation should be included as differential diagnosis during 99m Tc–red blood cell scintigraphy.
Paediatricians prioritise work on the climate and health
Authors: Lucy Underwood
Journal: BMJ (2020)

The Royal College of Paediatrics and Child Health has joined a growing coalition of health organisations in declaring a climate emergency and has published a plan to accelerate its work in the area.

The college is already part of the UK Health Alliance on Climate Change—alongside other bodies including the BMJ, BMA, the Lancet, the Royal College of General Practitioners, and several other royal colleges—which advocates …
Lines of Therapy before Autologous Stem Cell Transplant (ASCT) and CAR-T Infusion Affect Outcomes in Aggressive Non-Hodgkin's Lymphoma (NHL)
Authors: Arushi Khurana, Matthew A Hathcock, Thomas M. Habermann, Abdullah S. Al Saleh, Sangeetha Gandhi, Tuan A Truong, Nabila Bennani, Jonas Paludo, Jose C Villasboas, Stephen M. Ansell, David J. Inwards, Luis F. Porrata, Patrick B. Johnston, Ivana Micallef, Yi Lin
Journal: Blood (2020)
Multiple myeloma cells induce lipolysis in adipocytes and uptake fatty acids through fatty acid transporter proteins
Authors: Cristina Panaroni, Keertik Fulzele, Tomoaki Mori, Ka Tat Siu, Chukwuamaka Onyewadume, Allison Maebius, Noopur Raje
Journal: Blood (2021)

Adipocytes occupy 70% of the cellular volume within the bone marrow (BM) wherein multiple myeloma (MM) originates and resides. However, the nature of the interaction between MM cells and adipocytes remains unclear. Cancer-associated adipocytes support tumor cells through various mechanisms, including metabolic reprogramming of cancer cells. We hypothesized that metabolic interactions mediate the dependence of MM cells on BM adipocytes. Here we show that BM aspirates from precursor states of MM, including monoclonal gammopathy of undetermined significance and smoldering MM, exhibit significant upregulation of adipogenic commitment compared with healthy donors. In vitro coculture assays revealed an adipocyte-induced increase in MM cell proliferation in monoclonal gammopathy of undetermined significance/smoldering MM compared with newly diagnosed MM. Using murine MM cell/BM adipocyte coculture assays, we describe MM-induced lipolysis in adipocytes via activation of the lipolysis pathway. Upregulation of fatty acid transporters 1 and 4 on MM cells mediated the uptake of secreted free fatty acids (FFAs) by adjacent MM cells. The effect of FFAs on MM cells was dose dependent and revealed increased proliferation at lower concentrations vs induction of lipotoxicity at higher concentrations. Lipotoxicity occurred via the ferroptosis pathway. Exogenous treatment with arachidonic acid, a very-long-chain FFA, in a murine plasmacytoma model displayed a reduction in tumor burden. Taken together, our data reveal a novel pathway involving MM cell-induced lipolysis in BM adipocytes and suggest prevention of FFA uptake by MM cells as a potential target for myeloma therapeutics.
Abstract 222: The Estrogen-related Receptor (ERR) Drives Cardiac Myocyte Maturation in Cooperation With GATA4
Authors: Tomoya Sakamoto, Shibiao Wan, Kirill Batmanov, Daniel P Kelly
Journal: Circulation Research (2020)

During transition from fetal to adult developmental stages, the heart undergoes robust mitochondrial biogenesis in parallel with growth and structural maturation. Recently we identified a role for ERRα/γ in this broad program of postnatal cardiac maturation. We sought to delineate the mechanisms whereby ERRs coordinate transcriptional regulation of both metabolic and structural genes in the maturation of human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs). CRISPR-based gene deletion studies demonstrated that ERRα/γ is necessary for activation of genes involved in mitochondrial and structural maturation during hiPSC-CM differentiation including mitochondrial function, ion transport, Ca 2+ handling, and the adult sarcomere. Whole-genome RNA-sequencing and ChIP-sequencing (ChIP-seq) studies indicated that ERRγ directly regulates both metabolic and structural genes by remodeling H3K27ac depositions in related enhancer regions. Integration of the ERRγ ChIP-seq data with published hiPSC-CM datasets demonstrated that approximately 50% of super-enhancer regions overlapped ERRγ peaks, suggesting ERR is involved in the maintenance and function of cardiac super-enhancer regions. Corresponding motif analyses and intersection analyses with published GATA4 ChIP-seq datasets suggested that ERRγ cooperates with GATA4 on many structural, but not metabolic targets. Specifically, binding sites for both factors are often co-localized around cardiac contractile, ion channel, and Ca 2+ handling genes, including TNNI3, MYBPC3, MYH7, TTN, KCNQ1, and RYR2 . In contrast, ERRγ sites on target genes involved in mitochondrial maturation such as ATP5B, COX4I1, CPT1B , and FABP3 lacked GATA4 sites. Experiments using luciferase reporters demonstrated functional cooperation between ERRγ and GATA4 that depends on the known ERR coactivator, peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1α). We conclude that the ERR cooperates with GATA4 to drive cardiac structural gene transcription during cardiac differentiation, whereas ERR regulates genes involved in energy metabolism independent of GATA4. Activation of ERR signaling could prove to be an effective tool to drive hiPSC-CM maturation.
A Pilot Trial of Pre-Transplant Risk Stratification and Prophylactic Defibrotide to Prevent Serious Thrombotic Microangiopathy in High-Risk Pediatric Hematopoietic Stem Cell Transplant Patients
Authors: Christine S Higham, Alexis Melton, Sandhya Kharbanda, Jasmeen Dara, Lena E. Winestone, James N Huang, Kristin A. Shimano
Journal: Blood (2020)
Seminal Vesicle Urinary Reflux After TURP Mimicking Vesicular Invasion From Prostate Cancer on 18F-Choline PET/CT
Authors: Saadi Sollaku, Emanuele Casciani, Cristina De Angelis, Viviana Frantellizzi, Gianfranco Gualdi
Journal: Clinical Nuclear Medicine (2020)

Abstract Seminal vesicles are paired secretory glands located posterior to the bladder in men that produce seminal fluid to maintain sperm. Seminal vesicle reflux into the prostatic ducts may be associated with prostatitis in older patients or may represent a very rare complication of transurethral prostate resection in patients with prostatic cancer. This condition is frequently accidentally diagnosed on excretory urography and/or retrograde urethrogram. Clinical presentation includes pain, fever, recurrent epididymitis-prostatitis, and post void dribbling.
RUNX-NFAT Axis As a Novel Therapeutic Target for AML and T Cell Immunity
Authors: Tatsuya Masuda, Hirohito Kubota, Naoya Sakuramoto, Asuka Hada, Ayaka Horiuchi, Asami Sasaki, Kanako Takeda, Mizuho Takeda, Hidemasa Matsuo, Hiroshi Sugiyama, Souichi Adachi, Yasuhiko Kamikubo
Journal: Blood (2020)
On-Demand Plerixafor with Cyclophosphamide and G-CSF for Hematopoietic Stem-Cell Mobilization in Multiple Myeloma Patients: Preliminary Results of a Prospective Observational Study (MOZOBL06877)
Authors: Roberto Mina, Francesca Bonello, Giuseppe Milone, Maria Teresa Petrucci, Chiara Nozzoli, Velia Bongarzoni, Andrea Capra, Francesco Pisani, Giusy Cetani, Alessandra Malfitano, Delia Rota Scalabrini, Stelvio Ballanti, Roberto M. Lemoli, Patrizia Tosi, Daniele Derudas, Tommaso Caravita di Toritto, Massimo Offidani, Pellegrino Musto, Paolo Corradini, Michele Cavo, Mario Boccadoro, Alessandra Larocca
Journal: Blood (2020)
Reduction in CMR Derived Extracellular Volume With Patisiran Indicates Cardiac Amyloid Regression
Authors: Marianna Fontana, Ana Martinez-Naharro, Liza Chacko, Dorota Rowczenio, Janet A. Gilbertson, Carol J. Whelan, Svetla Strehina, Thirusha Lane, James Moon, David F. Hutt, Peter Kellman, Aviva Petrie, Philip N. Hawkins, Julian D. Gillmore
Journal: JACC. Cardiovascular imaging (2020)
Validation of ELN2017 Risk Stratification in a Post-Hoc Analysis of the Prospective Biomarker-Based Gimema AML1310 Protocol
Authors: Raffaele Palmieri, Francesco Buccisano, Alfonso Piciocchi, Valentina Arena, Anna Candoni, Lorella MA Melillo, Valeria Calafiore, Roberto Cairoli, Paolo De Fabritiis, Gabriella Storti, Prassede Salutari, Francesco Lanza, Giovanni Martinelli, Mario Luppi, Saveria Capria, Luca Maurillo, Maria Ilaria Del Principe, Giovangiacinto Paterno, Maria Teresa Voso, Tiziana Ottone, Serena Lavorgna, Paola Fazi, Marco Vignetti, William Arcese, Adriano Venditti
Journal: Blood (2020)
Preliminary Results from a Phase II Study of Response-Adapted Therapy with Copanlisib and Rituximab for Untreated Follicular Lymphoma
Authors: Rahul Lakhotia, Christopher Melani, Jagan R. Muppidi, Stefania Pittaluga, James D. Phelan, Lydia L. Chou, Sarah Evans, Seth M. Steinberg, William D. Figg, Elaine S. Jaffe, Louis M. Staudt, Wyndham H. Wilson, Mark Roschewski
Journal: Blood (2020)
Immunogenomics of Aplastic Anemia: The Role of HLA Somatic Mutations and the HLA Evolutionary Divergence
Authors: Simona Pagliuca, Carmelo Gurnari, Hassan Awada, Cassandra M Kerr, Bhumika J. Patel, Laila Terkawi, Misam Zawit, Sunisa Kongkiatkamon, Pedro H Prata, Ashwin Kishtagari, Adam Wahida, Thomas Laframboise, Valeria Visconte, Regis Peffault De Latour, Jaroslaw P. Maciejewski
Journal: Blood (2020)