tbuckley/cabot-search huggingface dataset:
METTL3-mediated <i>N</i><sup>6</sup>-methyladenosine modification governs pericyte dysfunction during diabetes-induced retinal vascular complication
Authors: Long Suo, Chang Liu, Qiu-Yang Zhang, Mu-Di Yao, Yan Ma, Jin Yao, Qin Jiang, Biao Yan
Journal: Theranostics (2021)

Rationale: Microvascular complication is a major cause of morbidity and mortality among the patients with diabetes.Pericyte dysfunction is the predominant pathological manifestation of microvascular complication.N 6 -methyladenosine (m 6 A) serves as the most prevalent modification in eukaryotic mRNAs.However, the role of m 6 A RNA modification in pericyte dysfunction is still unclear.Methods: Quantitative polymerase chain reactions and western blots were conducted to detect the change of m 6 A RNA modification in pericytes and mouse retinas following diabetic stress.MTT assay, transwell migration assay, caspase 3/7 activity assay, calcein-AM/propidium iodide (PI) staining, and TUNEL staining were conducted to determine the role of METTL3 in pericyte biology in vitro.Retinal trypsin digestion, vascular permeability assay, and IB4-NG2 double immunofluorescent staining were conducted to determine the role of METTL3 in retinal pericyte dysfunction and vascular complication.RNA sequencing, RNA pull-down assays and immunoblots were conducted to clarify the mechanism of METTL3-mediated pericyte dysfunction and vascular complication. Results:The levels of m 6 A RNA methylation were significantly up-regulated in pericytes and mouse retinas following diabetic stress, which were caused by increased expression of METTL3.METTL3 regulated the viability, proliferation, and differentiation of pericytes in vitro.Specific depletion of METTL3 in pericytes suppressed diabetes-induced pericyte dysfunction and vascular complication in vivo.METTL3 overexpression impaired pericyte function by repressing PKC-η, FAT4, and PDGFRA expression, which was mediated by YTHDF2-dependent mRNA decay.Conclusion: METTL3-mediated m 6 A methylation epigenetically regulates diabetes-induced pericyte dysfunction.METTL3-YTHDF2-PKC-η/FAT4/PDGFRA signaling axis could be therapeutically targeted for treating microvascular complications.
Surpass-ET Trial: A Phase 3, Open-Label, Multicenter, Randomized, Active-Controlled Study to Assess Pharmacokinetics and Compare the Efficacy, Safety, and Tolerability of P1101 Vs Anagrelide As Second Line Therapy for Essential Thrombocythemia
Authors: Ruben A. Mesa, Norio Komatsu, Harinder Gill, Jie Jin, Sung-Eun Lee, Hsin-An Hou, Toshiaki Sato, Albert Qin, Raymond Urbanski, Weichung Shih, Oleh Zagrijtschuk, Craig Zimmerman, Srdan Verstovsek
Journal: Blood (2021)
Clinical-Scale Production and Characterization of Ntla-5001 - a Novel Approach to Manufacturing CRISPR/Cas9 Engineered T Cell Therapies
Authors: Daniel Cossette, Shloka Aiyer, Casey Kimball, Chris Luby, Jason Zarate, Justin Eng, Vinita Doshi, Riley Cole, Nikunja Kolluri, Shreelekha Jaligama, Noah Gardner, Kristy Wood, Eliana Clark
Journal: Blood (2021)
The Tetraspanin CD53 Protects Hematopoietic Stem Cells Following Cellular Stress through Induction of DREAM Complex-Mediated Quiescence
Authors: Zev J. Greenberg, Darlene A. Monlish, Qian Dong, Luana Chiquetto Paracatu, Michael P. Rettig, Wei Yang, Weikai Li, Laura G. Schuettpelz
Journal: Blood (2021)
Disrupting Mitohormesis As a Novel Therapeutic Strategy for Multiple Myeloma (MM) Including Those with High Risk Disease and Proteosome Inhibitor Resistance
Authors: Serges P Tsofack, Danielle C Croucher, Benjamin G Barwick, Zhihua Li, Ahmed Aman, Dennis Tao, Ellen nong Wei, Laura Garcia Prat, Aaron D Schimmer, Suzanne Trudel
Journal: Blood (2021)
Rituximab Maintenance Benefits Less for Follicular Lymphoma Patients with Low Risk of the Follicular Lymphoma International Index
Authors: Tingyu Wang, Ru Li, Rui Lv, Ying Yu, Jiawen Chen, Wenjie Xiong, Qi Wang, Wei Liu, Wenyang Huang, Weiwei Sui, Gang An, Yan Xu, Dehui Zou, Jianxiang Wang, Lugui Qiu, Shuhua Yi, Yi Wang
Journal: Blood (2021)
Abstract 9480: Vagus Nerve Stimulation Exerts Cardioprotection Against Doxorubicin-Induced Cardiotoxicity Through Improving Cardiac Mitochondrial Function and Autonomic Tone
Authors: Nanthip Prathumsap, Benjamin Ongnok, Thawatchai Khuanjing, Apiwan Arinno, Chayodom Maneechote, Nattayaporn Apaijai, Titikorn Chunchai, Busarin Arunsak, Sasiwan Kerdphoo, Krekwit Shinlapawittayatorn, Siriporn Chattipakorn, Nipon Chattipakorn
Journal: Circulation (2021)

Introduction: Cardiac sympathovagal imbalance is a common pathologic finding in patients receiving doxorubicin (DOX), and is considered as a cardiovascular risk factor. Growing evidence demonstrates that cardiac autonomic modulation by vagus nerve stimulation (VNS) exerted cardioprotection in both myocardial ischemia/reperfusion injury and heart failure models. However, the cardioprotection of VNS in DOX-induced cardiotoxicity has never been investigated. Hypothesis: Increased cardiac parasympathetic activity by VNS attenuates the sympathovagal imbalance and mitochondrial dysfunction , thereby improving left ventricular (LV) function. Methods: Rats were divided into a sham group and a VNS group. Two weeks after cervical VNS implantation, all rats were subdivided into 3 groups: control (CON), DOX-treated group (3 mg/kg/day, ip, 6 doses) without VNS (DOX+Sham: DS), and DOX-treated group with VNS (DOX+VNS: DV). VNS was activated simultaneously with the first dose of DOX (20 Hz, 500 μs pulse width, 0.5-0.75 mA, turn ON 14 s and turn OFF 48 s (23% duty cycle), and was maintained for 30 days. At the end of the study protocol, cardiac biochemical and functional analyses were evaluated. Results: DOX treatment increased cardiac mitochondrial ROS production, mitochondrial depolarization, and mitochondrial swelling, leading to left ventricular systolic (%LVFS) and diastolic (E/A ratio) dysfunctions (Fig 1). Moreover, LF/HF ratio was increased in DOX-treated rats, indicating cardiac autonomic imbalance (Fig 1F). Interestingly, VNS could effectively protect the Dox-treated heart by alleviating all of those impaired parameters (Fig 1). Conclusions: VNS protects against DOX-induced cardiotoxicity by improving cardiac mitochondrial function and attenuating cardiac autonomic dysfunctions, leading to improved LV function. Thus, enhancing parasympathetic activity by VNS could be a novel therapeutic approach to prevent DOX-induced cardiotoxicity.
Low Density of CD3+ Tumor-Infiltrating Lymphocytes Is Predictive of a Poor Prognosis in Diffuse Large B-Cell Lymphoma Independently of MYC and BCL2 Double Expression Status: A Potential Utility of Immunoscore Based on Whole-Slide Image Analysis
Authors: Bogyeong Han, Jeemin Yim, Sojung Lim, Cheol Lee, Tae Min Kim, Kim Sehui, Yoon Kyung Jeon
Journal: Blood (2021)
Systematic reviews and Cochrane Collaboration
Authors: D. M Mackay, P Badrinath
Journal: BMJ (2001)

We are deeply concerned about the potential humanitarian consequences of war in Afghanistan.Afghanistan is one of the poorest countries in the world with a life expectancy of only 43 years, and a death rate in those under 5 of 257 per 1000 live births.1 Drought and conflict in the region and have already generated over four million displaced people.Since the attack on the World Trade Centre and Pentagon thousands more have left Afghanistan's cities, making the situation even worse.The withdrawal of all international aid, including essential food supplies provided by the World Food Programme, owing to the threat of military action, is most likely to result in famine and increased death rates in the camps for internally displaced people.The human impact, particularly on children, could dwarf even the death toll arising from the terrorist attacks.We therefore urge the UK government to give priority to protecting the health of the Afghan population to prevent a further humanitarian disaster.
Abstract 8899: DOAC Use for Stroke Prevention in Patients with Atrial Fibrillation and Elevated Body Mass Index
Authors: Adam Foglesong, Justin Armstrong, Ramy Mando, Alexandra Halalau
Journal: Circulation (2021)

Background: The incidence of comorbid obesity and atrial fibrillation (AF) has been increasing. Direct Oral Anticoagulants (DOACs) have become the first-line agents for cerebrovascular accident (CVA) prophylaxis in patients with AF due to their superior efficacy and lower bleeding risk when compared to coumadin. The incidence of acute ischemic CVA while on a DOAC in the non-obese population is 1.2%. Evidence on the efficacy of DOACs in preventing AF related CVAs in the obese population is limited. Methods: Electronic medical records from 8 hospitals within the same health system were queried. Patients age &gt; 18 years with a BMI &gt; 40 kg/mm 2 and AF on a DOAC (Rivaroxaban, Apixaban, or Dabigatran) were included in our study. Individual charts from 2010 to 2020 were reviewed for neuroimaging (computed tomography and MRI) following the start date of a DOAC confirming the presence or absence of an acute hemorrhagic or ischemic CVA. Results: We included 1935 patients in the study. Acute ischemic CVA was noted in 17 patients (0.9%) by head CT (11/17 confirmed by MRI). Hemorrhagic CVA was noted in one patient (0.1%) by head CT. 155 (8%) had a head CT without evidence of CVA, of which, 5 (3.2 %) had evidence of an acute ischemic CVA by MRI. Therefore, 22 patients (1.1%) had evidence of acute ischemic CVA on neuroimaging. The remainder of patients (N = 1762, 91.1%) did not have indications for neuroimaging and were considered to have successful CVA prophylaxis. In total, 1912 (98.8%) of patients with a BMI &gt; 40 treated with a DOAC for AF did not demonstrate neuroimaging evidence of CVA. Conclusions: Although we expected to find higher CVA rates due to ineffective anticoagulation in the obese population, DOACs appear to be an effective therapy for CVA prophylaxis in obese patients with AF. The incidence of acute ischemic CVA in the obese population while on a DOAC is comparable to the non-obese population. Further prospective studies are needed to confirm the findings of this analysis.
Systematic Literature Review of the Indirect Costs, Humanistic Burden, Patient or Caregiver Preference, and Qualitative Outcomes in Beta-Thalassemia
Authors: Yesim Aydinok, Sneha Purushotham, Aylin Yucel, Sohan Deshpande, Barbara Potrata, Myrto Trapali, Mrinalini Dixit, Farrukh Shah
Journal: Blood (2021)
Current Pulmonology. Volume 1.
Journal: Annals of Internal Medicine (1979)

1.Oxygen Transport...1
2.Adaptations to Hyoxia: Lessons From Operation Everest II...23
3.Work of Breathiong in the Criitically III Patient...51
4.Early Intervention in Chronic Obstruuctivve Pulmonary Disease...87
5.Proteinase Inhibitors in the Lung...109
6.Advances in Smoking Cessation Treatment...139
7.Acute Lung Injury: Mechanisms and Potential Therapy...199
8.Flail Chest/Pulmonary Contusion: A Surgical Critical Care Challenge...223
9.Interpretation of Lung Function Test...261
10.Pulmonary Transplantation...297
Platelet Factor 4 (PF4) Modulates the Prothrombotic Nature of Neutrophil-Extracellular Traps (NETs): Therapeutic Implications of a NET-Stabilization Strategy
Authors: Anh T.P. Ngo, Irene Yarovoi, Guohua Zhao, Amrita Sarkar, Lubica Rauova, M. Anna Kowalska, Mortimer Poncz, Kandace Gollomp
Journal: Blood (2021)
Cost-effectiveness of domiciliary non-invasive ventilation in patients with chronic obstructive pulmonary disease
Authors: James Hall, Alice Margaret Turner, Janine Dretzke, David Moore, Sue Jowett
Journal: Thorax (2021)

Background Chronic obstructive pulmonary disease (COPD) is a chronic disease associated with recurring exacerbations, which influence morbidity and mortality for the patient, while placing significant resource burdens on healthcare systems. Non-invasive ventilation (NIV) in a domiciliary setting can help prevent admissions, but the economic evidence to support NIV use is limited. Methods A Markov model-based cost-utility analysis from the UK National Health Service perspective compared the cost-effectiveness of domiciliary NIV with usual care for two end-stage COPD populations; a stable COPD population commencing treatment with no recent hospital admission; and a posthospital population starting treatment following admission to hospital for an exacerbation. Hospitalisation rates in patients receiving domiciliary NIV compared with usual care were derived from randomised controlled studies in a recent systematic review. Other model parameters were updated with recent evidence. Results At the threshold of £20 000 per quality-adjusted life-year (QALY) domiciliary NIV is 99.9% likely cost-effective in a posthospital population, but unlikely (4%) to be cost-effective in stable populations. The incremental cost-effective ratio (ICER) was £11 318/QALY gained in the posthospital population and £27 380/QALY gained in the stable population. Cost-effectiveness estimates were sensitive to longer-term readmission and mortality risks, and duration of benefit from NIV. Indeed, for stable Global Initiative for Chronic Obstructive Lung Disease (GOLD) for stage 4 patients, or with higher mortality and exacerbation risks, ICERs were close to the £20 000/QALY threshold. Conclusion Domiciliary NIV is likely cost-effective for posthospitalised patients, with uncertainty around the cost-effectiveness of domiciliary NIV in stable patients with COPD on which further research should focus.
AML-specific cytotoxic antibodies in patients with durable graft versus leukemia responses
Authors: M. Gillissen, M. Kedde, G. de Jong, E. Yasuda, S. Levie, A. Bakker, C.B. Yvonne, K. Wagner, J. Villaudy, M. Bohne, D. Speijer, P. Hensbergen, P. van Helden, T. Beaumont, H. Spits, M. Hazenberg
Journal: Clinical Cancer Research (2017)
A Phase II Study of CPX-351 Plus Venetoclax in Patients with Relapsed/Refractory (R/R) or Newly Diagnosed Acute Myeloid Leukemia (AML)
Authors: Kunhwa Kim, Hagop Kantarjian, Gautam Borthakur, Koichi Takahashi, Nicholas J. Short, Courtney D. DiNardo, Elias J. Jabbour, Kelly S. Chien, Naval Daver, Naveen Pemmaraju, Nitin Jain, Lade Adewale, Guillermo Montalban-Bravo, William G. Wierda, Srdan Verstovsek, Marina Konopleva, Farhad Ravandi, Tapan M. Kadia
Journal: Blood (2021)
Abstract 8964: Remnant Cholesterol in Patients With Established Cardiovascular Disease Predicts Cardiovascular Events Both Among Patients With Type 2 Diabetes and Among Non-Diabetic Subjects
Authors: Arthur Mader, Lukas Sprenger, Alexander Vonbank, Barbara Larcher, Maximilian Maechler, Beatrix Mutschlechner, Magdalena Benda, Andreas Leiherer, Axel Muendlein, Heinz Drexel, Christoph H Saely
Journal: Circulation (2021)

Introduction: Remnant cholesterol, which is calculated as total cholesterol minus LDL cholesterol minus HDL cholesterol has attracted interest as a marker of cardiovascular event risk. Hypothesis: We hypothesize that remnant cholesterol has the power to predict cardiovascular events in patients with established cardiovascular disease. Methods: We enrolled 1822 consecutive patients with established cardiovascular disease, including 1472 with angiographically proven stable CAD and 350 with sonographically proven peripheral artery disease. Prospectively, cardiovascular events were recorded over a mean follow-up period of 6.2±3.2 years. Results: At baseline, remnant cholesterol was significantly higher in patients with T2DM (n=608) than in non-diabetic subjects (27±25 vs. 21±21 mg/dl; p&lt;0.001). During follow-up, 584 of our patients suffered cardiovascular events; the event rate was significantly higher in patients with T2DM than in non-diabetic subjects (45.4 vs. 32.2%; p&lt;0.001). Remnant cholesterol in Cox regression models adjusting for age, sex, hypertension, smoking, body mass index and LDL cholesterol independently predicted cardiovascular events in the total study population (standardized adjusted HR 1.15 [1.07-1.23]; p&lt;0.001), and in patients with T2DM as well as in non-diabetic subjects (standardized adjusted HRs 1.17 [1.03-1.34]; p=0.013 and 1.12 [1.01-1.23]; p=0.028, respectively). Conclusions: From our data we conclude that remnant cholesterol in patients with established cardiovascular disease predicts cardiovascular events both among patients with T2DM and among non-diabetic subjects.
Novel CRISPR-Associated Gene-Editing Systems Discovered in Metagenomic Samples Enable Efficient and Specific Genome Engineering for Cell Therapy Development
Authors: Gregory J. Cost, Rebecca C. Lamothe, Meghan D. Storlie, Andres Rivas, Diego A. Espinosa, Daniela S. A. Goltsman, Lisa Alexander, Cristina N. Butterfield, Christopher T. Brown, Brian C. Thomas
Journal: Blood (2021)
Final Analysis of Keynote-170: Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma (PMBCL)
Authors: Pier Luigi Luigi Zinzani, Catherine Thieblemont, Vladimir Melnichenko, Krimo Bouabdallah, Jan Waleswski, Alejandro Majlis, Laura Fogliatto, Alejandro Martin Garcia-Sancho, Beth Christian, Zafer Gulbas, Muhit Özcan, Guilherme Fleury Perini, Gilles Salles, Margaret A. Shipp, Seth Thompson, Samhita Chakraborty, Patricia Marinello, Philippe Armand
Journal: Blood (2021)
The Atlas of Blood Cancer Genomes (ABCG) Project: A Comprehensive Molecular Characterization of Leukemias and Lymphomas
Authors: Cassandra Love, Raju Pillai, Sarah L. Ondrejka, Govind Bhagat, Amy Chadburn, Matthew McKinney, Jean L. Koff, Dina Sameh Soliman, Magdalena Czader, Abner Louissaint, Shaoying Li, Choon Kiat Ong, Amir Behdad, Andrew M. Evens, Yasodha Natkunam, Peter H. Norgaard, Sirpa Leppa, Eric Tse, Jennifer R Chapman, Catalina Amador, Yuri Fedoriw, Agata M. Bogusz, Andrew G Evans, Rashmi S. Goswami, Ridas Juskevicius, Mina L. Xu, Kikkeri N Naresh, Barbara Xiong, Adam Snowden, Anabel Thurman, Eileen Smith, Tushar Dave, Rachel Kositsky, Devang Thakkar, Veronica Russell, Caroline J Roth, Sandeep Dave
Journal: Blood (2021)
A Novel Allogeneic Cell Therapy That Targets Pathogenic Autoantibodies for the Treatment of Immune Thrombocytopenia
Authors: Sunita Patel-Hett, Silvia Giannini, Christian Peters, Brad Dykstra, Marcus Lehmann, Ashley J Russo, Dora E Kohnke, Ryan Carpenter, Lindsay Tomczak, Douglas Lazarus, Sayaka Masuko, Amanda Leung, Angelique Meredith, Sophia Pete, Po-Shun Lee, Dean Falb
Journal: Blood (2021)
Gut microbiota: sculptors of the intestinal stem cell niche in health and inflammatory bowel disease
Authors: Manasvini Markandey, Aditya Bajaj, Nicholas Edward Ilott, Saurabh Kedia, Simon Travis, Fiona Powrie, Vineet Ahuja
Journal: Gut Microbes (2021)

Intestinal epithelium represents a dynamic and diverse cellular system that continuously interacts with gut commensals and external cues. Intestinal stem cells, which lie at the heart of epithelial renewal and turnover, proliferate to maintain a steady stem cell population and differentiate to form functional epithelial cell types. This rather sophisticated assembly-line is maintained by an elaborate micro-environment, sculpted by a myriad of host and gut microbiota-derived signals, forming an intestinal stem cell niche. This complex, yet crucial signaling niche undergoes dynamic changes during homeostasis and chronic intestinal inflammation. Inflammatory bowel disease refers to a chronic inflammatory response toward pathogenic or commensal microbiota, in a genetically susceptible host. Compositional and functional alterations in gut microbiota are pathognomonic of IBD.The present review highlights the modulatory role of gut microbiota on the intestinal stem cell niche during homeostasis and inflammatory bowel disease. We discuss the mechanisms of direct action of gut commensals (through microbiota-derived or microbiota-influenced metabolites) on ISCs, followed by their effects via other epithelial and immune cell types.
Gilteritinib (GILT) Monotherapy with Addition of Decitabine (DEC) in Non-Responders in Older Newly Diagnosed (ND) FLT3 Mutated Acute Myeloid Leukemia (AML) Patients Having High and Low Variant Allele Frequency (VAF): A Phase 2/1b Sub-Study of the Beat AML Master Trial
Authors: Elie Traer, Ying Huang, Alice S. Mims, Eytan M. Stein, Maria R. Baer, Wendy Stock, Tibor Kovacsovics, William Blum, Martha L. Arellano, Gary J. Schiller, Rebecca L. Olin, James M. Foran, Mark R. Litzow, Tara L. Lin, Prapti Patel, Matthew C. Foster, Robert L. Redner, Zeina Al-Mansour, Christopher R. Cogle, Michael M. Boyiadzis, Ronan Swords, Robert H. Collins, Jo-Anne Vergilio, Nyla A. Heerema, Leonard Rosenberg, Ashley O. Yocum, Sonja Marcus, Timothy Chen, Franchesca Druggan, Mona Stefanos, Theophilus J Gana, Abigail B. Shoben, Brian J. Druker, Amy Burd, John C. Byrd, Ross L. Levine, Uma Borate
Journal: Blood (2021)
A Phase 2/3 Randomized, Placebo-Controlled, Open-Label, Multi-Center Trial of Lenzilumab to Improve the Safety and Efficacy of CAR-T Cell Therapy in Adults with Relapsed or Refractory Large B-Cell Lymphoma (The SHIELD Study)
Authors: Saad S. Kenderian, Cameron Durrant, Dale Chappell, Omar Ahmed, Adrian Kilcoyne
Journal: Blood (2021)
Risk of Progression in Chronic Phase - Chronic Myeloid Leukemia (CML) Patients Eligible for Tyrosine Kinase Inhibitor Discontinuation (TFR-PRO study): Preliminary Results
Authors: Sarit Assouline, Maria Cristina Miggiano, Elisabetta Abruzzese, Chiara Elena, Giovanni Caocci, Susanne Saussele, Francesca Lunghi, Alberto Alvarez-Larran, Barbara Mora, Sigi Petrela, Laura Antolini, Carlo Gambacorti-Passerini, Alessandra Iurlo
Journal: Blood (2021)
A Calreticulin Neoepitope-Directed Monoclonal Antibody Can Overcome JAK Inhibitor Resistance and Block TPO-Independent Megakaryocyte Differentation
Authors: Denis Tvorogov, Chloe AL Thompson-Peach, Johannes Foßelteder, Mara Dottore, Frank Stomski, Kelly SY Lim, Suraiya A Onnesha, David M Ross, Andreas Reinisch, Daniel Thomas, Angel F. Lopez
Journal: Blood (2021)
Glofitamab (Glofit) in Combination with Polatuzumab Vedotin (Pola): Phase Ib/II Preliminary Data Support Manageable Safety and Encouraging Efficacy in Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Martin Hutchings, Anna Sureda, María José Terol, Francesc Bosch Albareda, Paolo Corradini, Thomas Stauffer Larsen, Antonio Rueda Dominguez, Anesh Panchal, Alessia Bottos, David Carlile, Yanjie Wang, Audrey Filézac De L'Étang, Maneesh Tandon, Gila Sellam, Giuseppe Gritti
Journal: Blood (2021)