tbuckley/cabot-search huggingface dataset:
Sult2b1 deficiency exacerbates ischemic stroke by promoting pro-inflammatory macrophage polarization in mice
Authors: Yan Wang, Haojie Jin, Yafang Wang, Yang Yao, Cuixia Yang, Jihong Meng, Xiaomu Tan, Yu Nie, Lixiang Xue, Baohui Xu, Heng Zhao, Feng Wang
Journal: Theranostics (2021)

Rationale: Stroke is a leading causes of human death worldwide. Ischemic damage induces the sterile neuroinflammation, which directly determines the recovery of patients. Lipids, a major component of the brain, significantly altered after stroke. Cholesterol sulfate, a naturally occurring analog of cholesterol, can directly regulate immune cell activation, indicating the possible involvement of cholesterol metabolites in neuroinflammation. Sulfotransferase family 2b member 1 (Sult2b1) is the key enzyme that catalyzes the synthesis of cholesterol sulfate. This study aimed to investigate the function of Sult2b1 and cholesterol sulfate in the neuroinflammation after ischemic stroke. Methods and Results: Sult2b1-/- and wild-type mice were subjected to transient middle cerebral artery occlusion. Our data showed that Sult2b1-/- mice had larger infarction and worse neurological scores. To determine whether immune cells were involved in the worsening stroke outcome in Sult2b1-/- mice, bone marrow transplantation, immune cell depletion, and adoptive monocyte transfer were performed. Combined with CyTOF and immunofluorescence techniques, we demonstrated that after stroke, the peripheral monocyte-derived macrophages were the dominant cell type promoting the pro-inflammatory status in Sult2b1-/-mice. Using primary bone marrow-derived macrophages, we showed that cholesterol sulfate could attenuate the pro-inflammatory polarization of macrophages under both normal and oxygen-glucose deprivation conditions by regulating the levels of nicotinamide adenine dinucleotide phosphate (NADPH), reactive oxygen species (ROS), and activating the AMP-activated protein kinase (AMPK) - cAMP responsive element-binding protein (CREB) signaling pathway. Conclusions:Sult2b1-/- promoted the polarization of macrophages into pro-inflammatory status. This trend could be attenuated by adding cholesterol sulfate, which promotes the polarization of macrophages into anti-inflammatory status by metabolic regulation. In this study, we established an inflammation-metabolism axis during the macrophage polarization after ischemic stroke.
Evidence of a Synergistic Cross-Talk between the B Cell Receptor (BCR) and Nicotinamide Phosphoribosyl Transferase (NAMPT) in Richter's Syndrome Patient-Derived Xenograft Models: Therapeutic Implications
Authors: Vincenzo Gianluca Messana, Nicoletta Vitale, Matteo Rovere, Lucia Renzullo, Francesca Arruga, Tiziana Vaisitti, Silvia Deaglio
Journal: Blood (2021)
Pathogenic Germline Variants in Multiple Myeloma
Authors: Santiago Thibaud, Aaron Etra, Ryan Subaran, Zachry Soens, Scott Newman, Rong Chen, Ajai Chari, Hearn Jay Cho, Sundar Jagannath, Deepu Madduri, David T. Melnekoff, Shambavi Richard, Joshua Richter, Larysa Sanchez, Kuan-lin Huang, Alessandro Lagana, Samir Parekh, Kenan Onel
Journal: Blood (2021)
Safe and Efficient Engraftment of CRISPR-Based ELANE Mono-Allelic Knocked out HSCs in Mice: Evidence for a Novel Treatment for ELANE Neutropenia
Authors: Lital Povodovski, Vahagn Makaryan, Peter Sabo, Yosef Dicken, Asael Herman, Rafi Emmanuel, David C. Dale
Journal: Blood (2021)
Exploring Interest in and Feasibility of a Lifestyle Intervention for Multiple Myeloma Patients
Authors: Abigail Kerschner, Allen Hodge, Alexis Williams, Patrica Sheean, Kathleen Jensik, Alexis Visotcky, Parameswaran Hari, Meera Mohan, Saurabh Chhabra, Anita D'Souza, Melinda Stolley
Journal: Blood (2021)
The regulatory and modulatory roles of TRP family channels in malignant tumors and relevant therapeutic strategies
Authors: Tiecheng Zhong, Wenxin Zhang, Hongjie Guo, Xiaohui Pan, Xi Chen, Qiaojun He, Bo Yang, Ling Ding
Journal: Acta Pharmaceutica Sinica B (2021)

Transient receptor potential (TRP) channels are one primary type of calcium (Ca2+) permeable channels, and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with the regulation of cardiovascular and neuronal systems. Nowadays, however, accumulating evidence shows that those TRP channels are also responsible for tumorigenesis and progression, inducing tumor invasion and metastasis. However, the overall underlying mechanisms and possible signaling transduction pathways that TRP channels in malignant tumors might still remain elusive. Therefore, in this review, we focus on the linkage between TRP channels and the significant characteristics of tumors such as multi-drug resistance (MDR), metastasis, apoptosis, proliferation, immune surveillance evasion, and the alterations of relevant tumor micro-environment. Moreover, we also have discussed the expression of relevant TRP channels in various forms of cancer and the relevant inhibitors' efficacy. The chemo-sensitivity of the anti-cancer drugs of various acting mechanisms and the potential clinical applications are also presented. Furthermore, it would be enlightening to provide possible novel therapeutic approaches to counteract malignant tumors regarding the intervention of calcium channels of this type.
High Levels of Circulating Tumor Cells Are Associated with Increased Bone Marrow Proliferation in Newly Diagnosed Multiple Myeloma Patients
Authors: Cathelijne Fokkema, Madelon M.E. de Jong, Sabrin Tahri, Zoltan Kellermayer, Chelsea den Hollander, Michael Vermeulen, Natalie Papazian, Mark van Duin, Michiel J.W. Wevers, Mathijs A. Sanders, Vincent H.J. van der Velden, Pieter Sonneveld, Annemiek Broyl, Tom Cupedo
Journal: Blood (2021)
Phase 2 Results of Urinary-Derived Human Chorionic Gonadotropin/Epidermal Growth Factor As Treatment for Life-Threatening Acute Gvhd
Authors: Shernan G Holtan, Celalettin Ustun, Andrea Hoeschen, Julianne Feola, Qing Cao, Parth Gandhi, Wes Mosher, Chi Chen, Arne Slungaard, Armin Rashidi, Erica D. Warlick, Mukta Arora, Veronika Bachanova, Fiona He, Brian C. Betts, Gregory M. Vercellotti, Claudio G. Brunstein, Najla H El Jurdi, Ashish O. Gupta, Murali Janakiram, Joseph E. Maakaron, Angela Panoskaltsis-Mortari, Daniel J. Weisdorf, Margaret L. MacMillan
Journal: Blood (2021)
Recombinant CD19 Glycomutant Accurately and Reproducibly Detects CD19-Directed CAR-T Cells By Flow Cytometry
Authors: Delaney R. Kirchmeier, Alyssa Sheih, Salvatore Fiorenza, Alexandre V. Hirayama, Cassie Chou, Erik Kimble, Jordan Gauthier, Alison Williams, Jason Price, Colin Correnti, Cameron J. Turtle
Journal: Blood (2021)
Ixazomib, Daratumumab and Low Dose Dexamethasone in Intermediate-Fit Patients with Newly Diagnosed Multiple Myeloma (NDMM); Results of Induction Treatment of the Phase II HOVON 143 Study
Authors: Kaz Groen, Claudia A.M. Stege, Kazem Nasserinejad, Koen de Heer, Roel J.W. Van Kampen, Maria B.L. Leijs, Noortje Thielen, Matthijs Westerman, Ka Lung Wu, Inge Ludwig, Djamila Issa, Gerjo A. Velders, Marie-Christiane Vekemans, Niels W.C.J. van de Donk, Gert-Jan Timmers, Pieter Sonneveld, Maarten R. Seefat, Fransien Croon-de Boer, Lidwine W. Tick, Ellen van der Spek, Esther G.M. De Waal, Maaike Sohne, Paula F Ypma, Inger S. Nijhof, Saskia K. Klein, Mark-David Levin, Sonja Zweegman
Journal: Blood (2021)
Abstract 14299: Impact of Gender on Hospital Outcomes in Various Types of ST Elevation Myocardial Infarction (STEMI)
Authors: Karthik Gangu, Aniesh Bobba, Sindhu R Avula, Alexander Shinn, Shruthi Pulimamidi, jay shah, fnu marium, Syed Ali
Journal: Circulation (2021)

Introduction: Prior evidence demonstrated that women &lt;75 years with acute coronary syndrome hospitalization have higher short-term mortality compared to men. In this study, we investigated gender-related hospital outcomes based on the location of STEMI. Methods: We performed a retrospective study utilizing 2016-2018 National Inpatient Sample database. We included patients aged 18 or older admitted to the hospital with the principal diagnosis of STEMI. This was further subdivided into Inferior STEMI (IMI) and Noninferior STEMI (NIMI). Diagnoses were obtained utilizing ICD 10 CM codes. A multivariate logistic regression model was used to analyze the effect of gender on mortality. Poisson regression was used to analyze length of stay (LOS) . Outcomes were adjusted to age, race, insurance status, elixhauser comorbidities, hospital location and characteristics. Results: A total of 438,060 patients were included in the study, of which 231,485 had IMI and 206,575 had NIMI. IMI group had 30.65% women compared to 29.45% in NIMI group. Women were significantly older when compared to men (66.8 vs 61.2 and 67.5 vs 61.2). Women younger than 85 yrs had higher odds of in hospital mortality in both the groups when compared to men (Table 1). Adjusted LOS was 0.94 day (p &lt;0.001) higher in both the groups for female sex. Conclusions: Our study shows that female gender was an independent predictor of hospital mortality and higher LOS regardless of the location STEMI.
Patients with Multiple Myeloma and Prior COVID-19 Have Superior Antibody Responses Against Sars-Cov-2 Compared with Fully Vaccinated Myeloma Patients with the BNT162b2 Vaccine
Authors: Maria Gavriatopoulou, Evangelos Terpos, Panagiotis Malandrakis, Ioannis Ntanasis-Stathopoulos, Alexandros Briasoulis, Sentiljana Gumeni, Despina Fotiou, Eleni-Dimitra Papanagnou, Magdalini Migkou, Foteini Theodorakakou, Evangelos Eleutherakis-Papaiakovou, Nikolaos Kanellias, Ioannis P. Trougakos, Efstathios Kastritis, Meletios-Athanasios Dimopoulos
Journal: Blood (2021)
Letermovir Is Effective for Prevention of Cytomegalovirus Reactivation in HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide
Authors: Takahide Ara, Yuta Hasegawa, Hiroyuki Ohigashi, Souichi Shiratori, Atsushi Yasumoto, Hideki Goto, Junichi Sugita, Masahiro Onozawa, Masao Nakagawa, Kaoru Kahata, Daigo Hashimoto, Takanori Teshima
Journal: Blood (2021)
Awareness, Knowledge, and Preferences of United States (US) Patients with Chronic Lymphocytic Leukemia (CLL) and Their Caregivers Related to Finite Duration (FD) Therapy and Minimal (Measurable) Residual Disease (MRD)
Authors: Dr. Brian Koffman, Chris Stewart, Liza Avruch, Neil Bailey, Robyn Brumble, John C. Byrd, Alexey V. Danilov, Matthew S. Davids, Richard Furman, Nitin Jain, Neil E. Kay, Nicole Lamanna, Anthony R. Mato, Alan Skarbnik, Chaitra S. Ujjani, John M. Pagel
Journal: Blood (2021)
Clinical Features Associated with Long-Term Ruxolitinib Exposure in Myelofibrosis and Predictive Role of Neutrophils
Authors: Lucia Masarova, Prithviraj Bose, Naveen Pemmaraju, Lingsha Zhou, Sherry A. Pierce, Zeev E. Estrov, Hagop Kantarjian, Srdan Verstovsek
Journal: Blood (2021)
Impact of Allogeneic Hematopoietic Cell Transplantation (HCT) As Consolidation Following CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy for Treatment of Relapsed Acute Lymphoblastic Leukemia (ALL)
Authors: Jae H Park, Sarah Nikiforow, Soyoung Kim, Zhen-Huan Hu, Amy Moskop, Sairah Ahmed, Muhammad Bilal Abid, Talha Badar, Christopher Bredeson, Valerie Brown, Mitchell S. Cairo, Miguel Díaz, Bhagirathbhai Dholaria, Siddhartha Ganguly, Natalie S Grover, Rabi Hanna, Peiman Hematti, Mira A Kohorst, Hillard Lazarus, Lazaros J. Lekakis, Frederick L. Locke, Hemant S. Murthy, Alberto Mussetti, Michael A. Pulsipher, Muna Qayed, Ran Reshef, David A Rizzieri, Maria Queralt Salas, Bipin B. Savani, Akshay Sharma, Kirk R. Schultz, Monica Thakar, Cameron Turtle, Jean A. Yared, John L. Wagner, Xianmiao Qiu, Marcelo C Pasquini, Miguel-Angel Perales
Journal: Blood (2021)
On Masks and Emotion Recognition
Authors: Dimitri A. Christakis
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
A Machine Learning-Based Predictive Model for Outcome of COVID-19 in Kidney Transplant Recipients
Authors: Ignacio Revuelta, Francisco-Javier Santos-Arteaga, Enrique Montagud-Marrahi, Pedro Ventura-Aguiar, Debora Di Caprio, David Cucchiari, Beatriu Bayès, Esteban Poch, Federico Oppenheimer, Fritz Diekmann
Journal: Journal of the American Society of Nephrology (2020)

Purpose: Health systems need tools to deal with COVID-19, especially for high-risk population,such as transplant recipients. Predictive models are necessary to improve management of patients and optimize resources. Methods: A retrospective study of hospitalized transplant patients due to COVID-19 was evaluated(March 3-April 24,2020). Admission data were integrated to develop a prediction model to evaluate a composite-event defined as Intensive Care Unit admission or intensification treatment with antiinflamatory agents. Predictions were made using a Data Envelopment Analysis(DEA)-Artificial Neural Network(ANN) hybrid, whose accuracy relative to several alternative configurations has been validated through a battery of clustering techniques. Results: Of 1006 recipients with a planned or an unscheduled visit during the observation period, thirty-eight were admitted due to COVID-19. Twenty-five patients(63.2%) exhibited poor clinical course(mortality rate:13.2%), within a mean of 12 days of admission stay. Cough as a presenting symptom(P=0.000), pneumonia(P=0.011), and levels of LDH(P=0.031) were admission factors associated with poor outcomes. The prediction hybrid model working with a set of 17 input variables displays an accuracy of 96.3%, outperforming any competing model, such as logistic regression(65.5%) and Random forest(denoted by Bagged Trees,44.8%). Moreover, the prediction model allows us to categorize the evolution of patients through the values at hospital admission. Conclusions: The prediction model based in Data Envelopment Analysis-Artificial Neural Network hybrid forecasts the progression towards severe COVID-19 disease with an accuracy of 96.3%, and may help to guide COVID-19 management by identification of key predictors that permit a sustainable distribution of resources in a patient-centered model. Improving efficiency and patient parformance in the AAN with DEA, we can get high accurancy even with no-big cohorts. (Table Presented).
How can we relieve current pressures on NHS hospitals?
Authors: Chris Ham
Journal: BMJ (2021)

How can we relieve current pressures on NHS hospitals?We should learn from previous local initiatives and ensure they are sufficiently resourced, writes Chris Ham Chris Ham co-chair 1The unfolding crisis in health and social care took a turn for the worse this week with the release of a report by the Association of Ambulance Chief Executives on the unprecedented pressures in urgent and emergency care. 1 The Association's analysis demonstrated that patients are being harmed by delays in handover between ambulance services and hospital clinicians, resulting in "a position that is totally unacceptable to all involved in patient care."Publication of the report coincided with news that the Secretary of State for Health and Social Care, Sajid Javid, is establishing a "war room" focused on improving NHS performance. 2 The war room is being advised by Michael Barber who led the Labour government's work on public service reform under Tony Blair.Barber's extensive experience will be tested to the limits at a time when all parts of the health and care system are working at full stretch and new targets are likely to be counterproductive.
Abstract 9073: Profiling of Metabolic Remodeling in Rat Model of Pressure Overload Induced Early Systolic Dysfunction and in Progression to Overt Systolic Heart Failure
Authors: Antoine H Chaanine, Patrice Delafontaine, David W Busija
Journal: Circulation (2021)

Introduction: We have previously shown left ventricular (LV) structural and hemodynamic differences in two models of rat pressure overload induced moderate remodeling and early systolic dysfunction (MOD) and overt systolic heart failure (SHF). The MOD and SHF phenotypes develop 8 weeks post ascending aortic banding via a vascular clip, area of 2 mm 2 and 1.5 mm 2 , respectively. Hypothesis: Metabolic remodeling play significant role in the development of MOD and SHF phenotypes, but is more evident in SHF than MOD. Methods: Shotgun proteomics and phospho-(p)-proteomics and non-targeted metabolomics analysis was performed in LV myocardium tissue from Sham, MOD and SHF using liquid chromatography mass spectrometry (LC-MS); n=3 biological samples per group. Raw proteomics, p-proteomics and metabolomics MS data were uploaded into Qlucore bioinformatics software for statistical analysis and data visualization. Statistically analyzed data were then uploaded into Ingenuity Pathway Analysis bioinformatics software for data validation and assessment of highly enriched canonical pathways related to metabolism that were up or down-regulated in MOD and SHF relative to Sham. Some of the proteomics and p-proteomics data were validated by immunoblotting. Results: Canonical pathways of oxidative phosphorylation, fatty acid β-oxidation, Kreb’s cycle, branched-chain amino acid and amino acid (Glutamine and Tryptophan) degradation were downregulated in MOD vs Sham and were further downregulated in SHF vs MOD. Whilst glycogen degradation and glucose degradation were upregulated in MOD and SHF vs Sham, but more so in MOD than SHF. Metabolomics data revealed that long chain and very long chain acyl-carnitines were decreased in abundance in MOD and SHF relative to Sham, while short and medium chain acyl-carnitines were decreased in abundance in SHF only. Moreover, Isoleucine degradation and glycolysis decreased and Taurine biosynthesis increased in SHF vs MOD. p-Proteomics data showed mild decrease in protein kinase A (PKA) and AMPK signaling in MOD vs Sham, which were more profoundly decreased in SHF than MOD. Conclusion: The interplay between PKA and AMPK signaling play an important role in metabolic remodeling and transitioning from MOD to SHF phenotype.
Abstract 9719: Structured Patient Education Improves Adherence with Wearable Cardiac Defibrillators
Authors: Eldon L Matthia, Michael L Setteducato, Steven J Ross, Aaron E Brice, Mark E Panna, David E Winchester
Journal: Circulation (2021)

Background: The wearable-cardioverter defibrillator (WCD) tradename LifeVest has emerged as a temporary alternative to implantable cardioverter-defibrillator therapy. However, patient adherence can be variable. We sought to investigate if standardized device education and patient follow-up phone calls could lead to increased adherence. Methods: Patients prescribed a WCD from July 2017 to July 2018 comprised the pre-intervention group. The initial post-intervention group from January 2019 to May 2019 enrolled 32 patients. Each patient received standardized device education using a video presentation, and we sought to call each patient within 7 days of discharge to answer questions and administer a questionnaire. 14 patients comprised the second post-intervention group from March 2020 to May 2020, which received refined education with both a video presentation and 30-minute, standardized, hands-on training with the LifeVest representative, as well as similar follow-up phone calls for all patients within 7 days of discharge. Results: The pre-intervention group had a median wear time of 19.46 hours/day. In the first post-intervention group, all patients received standardized education; however, only 17 patients were contacted via phone due to time constraints. Patients with standardized education-only had a median wear time 21.55 hours/day, while patients who received both interventions had a median wear time of 23.01 hours/day. The increase in median wear time in pre-intervention compared to post-intervention groups was statistically significant (p= 0.0056) There was no significant difference between the two post-intervention groups (p=0.5485). In the second intervention group, median wear time significantly increased to 22.00 hours/day compared to the pre-intervention group (p=0.0244). Conclusions: Implementing standardized device education can improve median WCD wear time. The addition of post-discharge follow-up phone call did lead to improved mean and median wear times, but this was not statistically significant. Similar strategies could be cheaply and easily adopted at other centers in an effort to improve WCD adherence.
Targeting protumor factor chitinase-3-like-1 secreted by Rab37 vesicles for cancer immunotherapy
Authors: Pei-Shan Yang, Min-Hua Yu, Ya-Chin Hou, Chih-Peng Chang, Shao-Chieh Lin, I-Ying Kuo, Pei-Chia Su, Hung-Chi Cheng, Wu-Chou Su, Yan-Shen Shan, Yi-Ching Wang
Journal: Theranostics (2021)

Background: Chitinase 3-like-1 (CHI3L1) is a secretion glycoprotein associated with the immunosuppressive tumor microenvironment (TME).The secretory mode of CHI3L1 makes it a promising target for cancer treatment.We have previously reported that Rab37 small GTPase mediates secretion of IL-6 in macrophages to promote cancer progression, whereas the roles of Rab37 in the intracellular trafficking and exocytosis of CHI3L1 are unclear.Methods: We examined the concentration of CHI3L1 in the culture medium of splenocytes and bone marrow derived macrophages (BMDMs) from wild-type or Rab37 knockout mice, and macrophage or T cell lines expressing wild type, active GTP-bound or inactive GDP-bound Rab37.Vesicle isolation, total internal reflection fluorescence microscopy, and real-time confocal microscopy were conducted.We developed polyclonal neutralizing-CHI3L1 antibodies (nCHI3L1 Abs) to validate the therapeutic efficacy in orthotopic lung, pancreas and colon cancer allograft models.Multiplex fluorescence immunohistochemistry was performed to detect the protein level of Rab37 and CHI3L1, and localization of the tumor-infiltrating immune cells in allografts from mice or tumor specimens from cancer patients.Results: We demonstrate a novel secretion mode of CHI3L1 mediated by the small GTPase Rab37 in T cells and macrophages.Rab37 mediated CHI3L1 intracellular vesicle trafficking and exocytosis in a GTP-dependent manner, which is abolished in the splenocytes and BMDMs from Rab37 knockout mice and attenuated in macrophage or T cell lines expressing the inactive Rab37.The secreted CHI3L1 activated AKT, ß-catenin and NF-κB signal pathways in cancer cells and macrophages to foster a protumor TME characterized by activating M2 macrophages and increasing the population of regulatory T cells.Our developed nCHI3L1 Abs showed the dual properties of reducing tumor growth/metastases and eliciting an immunostimulatory TME in syngeneic orthotopic lung, pancreas and colon tumor models.Clinically, high plasma level or intratumoral expression of CHI3L1 correlated with poor survival in 161 lung cancer, 155 pancreatic cancer and 180 colon cancer patients.Conclusions: These results provide the first evidence that Rab37 mediates CHI3L1 secretion in immune cells and highlight nCHI3L1 Abs that can simultaneously target both cancer cells and tumor microenvironment.