tbuckley/cabot-search huggingface dataset:
Preexisting Mutations in Hematopoietic Stem Cells in Patients with Therapy-Related Myeloid Neoplasms
Authors: Mariam Ibañez, Maria López-Pavía, Esperanza Such, Blanca Navarro, Alexander Neef, Javier Marco, Mireia Boluda-Navarro, Marta Llop, Claudia Sargas, Beatricce De Matteo, Alessandro Liquori, Elisa Gonzalez, Andres Jerez, David Valcárcel, Julia Montoro, Maria Díez-Campelo, Jesús-María Hernández-Rivas, Jesus M Hernández-Sánchez, Teresa Bernal Del Castillo, Alejandra Sanjuan, Pau Montesinos, Eva Barragán, Miguel A. Sanz, José Cervera, Guillermo Sanz
Journal: Blood (2017)
Abstract 1663: Essential Role of Non-Sterol Pathway in the Proliferation of Vascular Smooth Muscle Cells: A Comparative Study on the Disruption of 3-Hydroxy-3-Methylglutaryl CoenzymeA Reductase or Squalene Synthase
Authors: Fumiko Tazoe, Hiroaki Yagyu, Naoki Itabashi, Ken Ohashi, Ryu-ichi Tozawa, Tshihiro Inaba, Shuichi Nagashima, Hideki Kato, Zolzaya Khadbaatar, Jun-ichi Osuga, Shun Ishibashi
Journal: Circulation (2006)

The 3-hydroxy-3-methylglutaryl coenzymeA reductase (HMGCoAR) and squalene synthase (SS) are key enzymes for cholesterol biosynthesis in tissues. Although both HMGCoAR and SS are involved in the gen...
The mechanism of action of N-acetylcysteine (NAC): The emerging role of H2S and sulfane sulfur species
Authors: Brandán Pedre, Uladzimir Barayeu, Daria Ezeriņa, Tobias P. Dick
Journal: Pharmacology & Therapeutics (2021)

Initially adopted as a mucolytic about 60 years ago, the cysteine prodrug N-acetylcysteine (NAC) is the standard of care to treat paracetamol intoxication, and is included on the World Health Organization's list of essential medicines. Additionally, NAC increasingly became the epitome of an "antioxidant". Arguably, it is the most widely used "antioxidant" in experimental cell and animal biology, as well as clinical studies. Most investigators use and test NAC with the idea that it prevents or attenuates oxidative stress. Conventionally, it is assumed that NAC acts as (i) a reductant of disulfide bonds, (ii) a scavenger of reactive oxygen species and/or (iii) a precursor for glutathione biosynthesis. While these mechanisms may apply under specific circumstances, they cannot be generalized to explain the effects of NAC in a majority of settings and situations. In most cases the mechanism of action has remained unclear and untested. In this review, we discuss the validity of conventional assumptions and the scope of a newly discovered mechanism of action, namely the conversion of NAC into hydrogen sulfide and sulfane sulfur species. The antioxidative and cytoprotective activities of per- and polysulfides may explain many of the effects that have previously been ascribed to NAC or NAC-derived glutathione.
Treatment of sickle cell disease by increasing oxygen affinity of hemoglobin
Authors: Eric R. Henry, Belhu Metaferia, Quan Li, Julia Harper, Robert B. Best, Kristen E. Glass, Troy Cellmer, Emily B. Dunkelberger, Anna Conrey, Swee Lay Thein, H. Franklin Bunn, William A. Eaton
Journal: Blood (2021)
Flow Cytometry Immunophemotyping Evaluation in the Diagnosis of Acute Lymphoblastic Leukemia in Patients from Rio Grande Do Norte State, Brazil
Authors: Gabriela Va Alves, Aldair Paiva, Valéria Sf Sales, Dany Gkc Silva, Irian G Farkatt, Edvis Santos Soares Serafim, Lavoisier C Silva, Hugo Diogenes De Oliveira Paiva, Geraldo Barroso Cavalcanti
Journal: Blood (2017)
Annals Graphic Medicine - Dr. Mom: Women in Medicine Awards
Authors: Grace E. Farris
Journal: Annals of Internal Medicine (2021)

Web ExclusivesJuly 2021Annals Graphic Medicine - Dr. Mom: Women in Medicine AwardsFREEGrace E. Farris, MDGrace E. Farris, MDUniversity of Texas, Austin, Texas (G.E.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G21-0035 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Texas, Austin, Texas (G.E.F.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G21-0024.Author/Illustrator Information: Grace E. Farris, MD, is an assistant professor of medicine at Dell Medical School at the University of Texas in Austin, Texas. You can view her work at her website: www.farrisgrace.com.About Dr. Mom: In Dr. Mom, physician and cartoonist Grace Farris examines work–life balance while mothering and doctoring. Dr. Mom appears monthly in Annals Graphic Medicine at Annals.org.This article was published at Annals.org on 22 June 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics July 2021Volume 174, Issue 7Page: W78-W79 ePublished: 22 June 2021 Issue Published: July 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Clinical characteristics, time course, treatment and outcomes of patients with immune checkpoint inhibitor-associated myocarditis
Authors: Igor Puzanov, Poornima Subramanian, Yan V Yatsynovich, David M Jacobs, Maya R Chilbert, Umesh C Sharma, Fumito Ito, Steven G Feuerstein, Filip Stefanovic, Benjamin Switzer, Mark D Hicar, Anne B Curtis, Edward J Spangenthal, Grace K Dy, Marc S Ernstoff, Pankit Vachhani, Brian J Page, Nikhil Agrawal, Arjun Khunger, Ankita Kapoor, Alexander Hattoum, Jerome J Schentag
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Immune checkpoint inhibitors (ICI) have emerged as a front-line therapy for a variety of solid tumors. With the widespread use of these agents, immune-associated toxicities are increasingly being recognized, including fatal myocarditis. There are limited data on the outcomes and prognostic utility of biomarkers associated with ICI-associated myocarditis. Our objective was to examine the associations between clinical biomarkers of cardiomyocyte damage and mortality in patients with cancer treated with ICIs. Methods We retrospectively studied 23 patients who developed symptomatic and asymptomatic troponin elevations while receiving ICI therapy at a National Cancer Institute-designated comprehensive cancer center. We obtained serial ECGs, troponin I, and creatine kinase-MD (CK-MB), in addition to other conventional clinical biomarkers, and compared covariates between survivors and non-survivors. Results Among patients with myocarditis, higher troponin I (p=0.037) and CK-MB (p=0.034) levels on presentation correlated with progression to severe myocarditis. Higher troponin I (p=0.016), CK (p=0.013), and CK-MB (p=0.034) levels were associated with increased mortality, while the presence of advanced atrioventricular block on presentation (p=0.088) trended toward increased mortality. Weekly troponin monitoring lead to earlier hospitalization for potential myocarditis (p=0.022) and was associated with decreased time to steroid initiation (p=0.053) and improved outcomes. Conclusions Routine troponin surveillance may be helpful in predicting mortality in ICI-treated patients with cancer in the early phase of ICI therapy initiation. Early detection of troponin elevation is associated with earlier intervention and improved outcomes in ICI-associated myocarditis. The recommended assessment and diagnostic studies guiding treatment decisions are presented.
Front-Line Treatment with Second-Generation Tyrosine Kinase Inhibitors Following By Allo-Transplantation Benefits Patients with Better Survival Inph-Positive Acute Lymphoblastic Leukemia
Authors: Guo-Pan Yu, Fang Chen, Dan Xu, Changxin Yin, Qifa Liu, Jing Sun, Zhiping Fan, Qiang Wang, Liu Xiaoli, Qianli Jiang
Journal: Blood (2017)
Unique molecular signatures typify skin inflammation induced by chemical allergens and irritants
Authors: Marine‐Alexia Lefevre, Audrey Nosbaum, Aurore Rozieres, Vanina Lenief, Amandine Mosnier, Angèle Cortial, Margaux Prieux, Simon De Bernard, Julien Nourikyan, Pierre‐Emmanuel Jouve, Laurent Buffat, Florence Hacard, Marie‐Christine Ferrier‐Lebouedec, Pauline Pralong, Charles Dzviga, Anne Herman, Marie Baeck, Jean‐François Nicolas, Marc Vocanson
Journal: Allergy (2021)

Skin exposure to chemicals may induce an inflammatory disease known as contact dermatitis (CD). Distinguishing the allergic and irritant forms of CD often proves challenging in the clinic.To characterize the molecular signatures of chemical-induced skin inflammation, we conducted a comprehensive transcriptomic analysis on the skin lesions of 47 patients with positive patch tests to reference contact allergens and nonallergenic irritants.A clear segregation was observed between allergen- and irritant-induced gene profiles. Distinct modules pertaining to the epidermal compartment, metabolism, and proliferation were induced by both contact allergens and irritants; whereas only contact allergens prompted strong activation of adaptive immunity, notably of cytotoxic T-cell responses. Our results also confirmed that: (a) unique pathways characterize allergen- and irritant-induced dermatitis; (b) the intensity of the clinical reaction correlates with the magnitude of immune activation. Finally, using a machine-learning approach, we identified and validated several minimal combinations of biomarkers to distinguish contact allergy from irritation.These results highlight the value of molecular profiling of chemical-induced skin inflammation for improving the diagnosis of allergic versus irritant contact dermatitis.
Retrospective cohort study investigating extent of pertussis transmission during a boarding school outbreak, England, December 2017 to June 2018
Authors: Matt Edmunds, Rachel Mearkle, Jennifer Folliard, Charlotte Anderson, Sooria Balasegaram, Nastassya Chandra, Clare Sawyer, Norman K Fry, Sonia Ribeiro, Gemma Palmer, Michael Morgan, Gill Underhill, Nusreen Ahmad, Simon Friar, Andre Charlett, David Litt, Colin S Brown, Gayatri Amirthalingam
Journal: Eurosurveillance (2021)

On 1 May 2018, a pertussis outbreak was declared and widespread vaccination recommended at an all-female secondary boarding school in southern England. We conducted a retrospective cohort study to determine the extent of pertussis transmission and identify risk factors in this semi-closed population. Of 504 students and staff assessed before post-exposure vaccination, 48% (n = 240) had evidence of pertussis. A sub-analysis of 409 students found that both residential dormitory (p = 0.05) and school year (p = 0.03) were associated with pertussis, with odds decreasing by 11% for each increase in school year (95% confidence interval: 0.7–20.2). Odds of pertussis were 1.7 times higher in those assumed to have received acellular vaccines for their primary course compared with those assumed to have received whole-cell vaccines (based on date of birth), although this difference was not significant (p = 0.12). Our findings support the need for timely, widespread vaccination following identification of cases among adolescents in a semi-closed United Kingdom (UK) setting and to review the evidence for the introduction of an adolescent pertussis booster to the UK routine vaccination programme.
Separation of the Ca<sub>V</sub>1.2‐Ca<sub>V</sub>1.3 calcium channel duo prevents type 2 allergic airway inflammation
Authors: Nicolas Giang, Marion Mars, Marc Moreau, Jose E. Mejia, Grégory Bouchaud, Antoine Magnan, Marine Michelet, Brice Ronsin, Geoffrey G. Murphy, Joerg Striessnig, Jean‐Charles Guéry, Lucette Pelletier, Magali Savignac
Journal: Allergy (2021)

Voltage-gated calcium (Cav 1) channels contribute to T-lymphocyte activation. Cav 1.2 and Cav 1.3 channels are expressed in Th2 cells but their respective roles are unknown, which is investigated herein.We generated mice deleted for Cav 1.2 in T cells or Cav 1.3 and analyzed TCR-driven signaling. In this line, we developed original fast calcium imaging to measure early elementary calcium events (ECE). We also tested the impact of Cav 1.2 or Cav 1.3 deletion in models of type 2 airway inflammation. Finally, we checked whether the expression of both Cav 1.2 and Cav 1.3 in T cells from asthmatic children correlates with Th2-cytokine expression.We demonstrated non-redundant and synergistic functions of Cav 1.2 and Cav 1.3 in Th2 cells. Indeed, the deficiency of only one channel in Th2 cells triggers TCR-driven hyporesponsiveness with weakened tyrosine phosphorylation profile, a strong decrease in initial ECE and subsequent reduction in the global calcium response. Moreover, Cav 1.3 has a particular role in calcium homeostasis. In accordance with the singular roles of Cav 1.2 and Cav 1.3 in Th2 cells, deficiency in either one of these channels was sufficient to inhibit cardinal features of type 2 airway inflammation. Furthermore, Cav 1.2 and Cav 1.3 must be co-expressed within the same CD4+ T cell to trigger allergic airway inflammation. Accordingly with the concerted roles of Cav 1.2 and Cav 1.3, the expression of both channels by activated CD4+ T cells from asthmatic children was associated with increased Th2-cytokine transcription.Thus, Cav 1.2 and Cav 1.3 act as a duo, and targeting only one of these channels would be efficient in allergy treatment.
Anti–Double‐Stranded DNA Antibodies Recognize DNA Presented on HLA Class II Molecules of Systemic Lupus Erythematosus Risk Alleles
Authors: Hideaki Tsuji, Koichiro Ohmura, Hui Jin, Ryota Naito, Noriko Arase, Masako Kohyama, Tadahiro Suenaga, Shuhei Sakakibara, Yuta Kochi, Yukinori Okada, Kazuhiko Yamamoto, Hitoshi Kikutani, Akio Morinobu, Tsuneyo Mimori, Hisashi Arase
Journal: Arthritis & Rheumatology (2021)

Objective Specific HLA class II alleles are associated with susceptibility to systemic lupus erythematosus (SLE). The role of HLA class II molecules in SLE pathogenesis remains unclear, although anti‐DNA antibodies are specific to SLE and correlate with disease activity. We previously demonstrated that misfolded proteins bound to HLA class II molecules are specific targets for the autoantibodies produced in autoimmune diseases. This study was undertaken to validate our hypothesis that DNA binds to HLA class II molecules in a manner similar to that of misfolded proteins and that DNA bound to HLA class II molecules is involved in SLE pathogenesis. Methods We analyzed the binding of DNA to HLA class II molecules, as well as the response of cells expressing anti‐DNA B cell receptors (BCRs) to cells expressing the DNA/HLA class II complex. Results Efficient binding of DNA to HLA class II molecules was observed in risk alleles of SLE, such as HLA–DRB1*15:01. The efficiency of DNA binding to each HLA–DR allele was positively associated with the risk of SLE conferred by the HLA–DR allele. In addition, reporter cells carrying anti‐DNA BCRs were activated by cells expressing DNA/HLA class II complexes. Conclusion These results provide evidence that DNA bound to HLA class II molecules is involved in SLE pathogenesis.
Hepatic X‐Box Binding Protein 1 and Unfolded Protein Response Is Impaired in Weanling Mice With Resultant Hepatic Injury
Authors: Alyssa Kriegermeier, Angela Hyon, Meredith Sommars, Susan Hubchak, Brian LeCuyer, Xiaoying Liu, Grant Barish, Richard M. Green
Journal: Hepatology (2021)

The unfolded protein response (UPR) is a coordinated cellular response to endoplasmic reticulum (ER) stress that functions to maintain cellular homeostasis. When ER stress is unresolved, the UPR can trigger apoptosis. Pathways within the UPR influence bile acid metabolism in adult animal models and adult human liver diseases, however, the UPR has not been studied in young animal models or pediatric liver diseases. In this study we sought to determine whether weanling age mice had altered UPR activation compared with adult mice, which could lead to increased bile acid-induced hepatic injury.We demonstrate that after 7 days of cholic acid (CA) feeding to wild-type animals, weanling age mice have a 2-fold greater serum alanine aminotransferase (ALT) levels compared with adult mice, with increased hepatic apoptosis. Weanling mice fed CA have increased hepatic nuclear X-box binding protein 1 spliced (XBP1s) expression, but cannot increase expression of its protective downstream target's ER DNA J domain-containing protein 4 and ER degradation enhancing α-mannoside. In response to tunicamycin induced ER stress, young mice have blunted expression of several UPR pathways compared with adult mice. CA feeding to adult liver-specific XBP1 knockout (LS-XBP1-/- ) mice, which are unable to resolve hepatic ER stress, leads to increased serum ALT and CCAAT/enhancer binding homologous protein, a proapoptotic UPR molecule, expression to levels similar to CA-fed LS-XBP1-/- weanlings.Weanling mice have attenuated hepatic XBP1 signaling and impaired UPR activation with resultant increased susceptibility to bile acid-induced injury.
Validated Prediction Model for the Development of Primary Open-Angle Glaucoma in Individuals with Ocular Hypertension
Authors: Mae O Gordon, Valter Torri, Stefano Miglior, Julia A Beiser, Irene Floriani, J Philip Miller, Feng Gao, Ingrid Adamsons, Davide Poli, Ralph B D'Agostino, Michael A Kass
Journal: Ophthalmology (2006)
Abstract 331: Novel Electrocardiogram Features and Dichotomous Variables to Predict Resuscitation Outcomes During Chest Compressions
Authors: Jason Coult, Jennifer E Blackwood, Thomas Rea, Peter Kudenchuk, Heemun Kwok
Journal: Circulation (2019)

Objective: Analysis of the ventricular fibrillation (VF) ECG to predict patient outcomes can potentially improve defibrillation timing and monitor prognosis during resuscitation. However, accurate ECG analysis requires pausing CPR. We evaluated strategies to predict patient outcomes during CPR using novel ECG features, adaptive filtering, and dichotomous variables. Methods: We collected a 5-s VF ECG segment during chest compressions prior to 2137 shocks in 942 out-of-hospital VF arrests. Using training segments from 376 patients (40%), we designed ten features of the VF ECG to characterize amplitude, time-frequency energy, and complexity. Features were calculated with and without adaptive filtering. We used support vector machine and logistic models to combine ECG features with dichotomous variables presumed available during treatment: age&lt;60, sex, and prior shock success. Using segments from 566 patients (60%) for validation, we evaluated performance of individual variables and the combined model. For comparison, we also computed the amplitude spectrum area (AMSA) ECG metric. Performance was characterized by area under the receiver operating characteristic curve (AUC) to predict return of organized rhythm after shock and survival with Cerebral Performance Category of 1-2. Results: Of individual ECG variables, filtering improved amplitude features, and the best performance was observed using high-frequency energy features above CPR artifact frequencies (Table 1). Of dichotomous variables, age&lt;60 predicted survival but not return of rhythm, and prior shock success was more indicative of return of rhythm than survival. The combined model had improved performance versus AMSA for predicting return of rhythm (AUC=0.74 vs. 0.66, p&lt;0.001) and survival (AUC=0.75 vs. 0.70, p&lt;0.001). Conclusion: Combining ECG characteristics, adaptive filtering, and dichotomous variables may improve prediction of defibrillation outcomes during uninterrupted CPR.
Abstract SY22-02: Personalized cancer vaccines: Antigen selection and translation into the clinic
Authors: Nina Bhardwaj
Journal: Cancer Research (2021)

Abstract Personalized cancer vaccination targets specific cancer mutations of the individual patient's tumor, also referred to as neoantigens. Such “bespoke” vaccines are now being tested in multiple cancers and in combination with checkpoint inhibitors. This session will discuss our computational methods for antigenic epitope prediction, antigen selection (personalized and shared neoantigens derived from frame-shift mutations), validation in vitro and in vivo and future directions for the field. Citation Format: Nina Bhardwaj. Personalized cancer vaccines: Antigen selection and translation into the clinic [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY22-02.
Design and Usability Evaluations of a 3D‐Printed Implantable Drug Delivery Device for Acute Liver Failure in Preclinical Settings
Authors: Shin‐Young Kim, Ginam Han, Da‐Bin Hwang, Dong‐Hoon Won, Yoo‐Sub Shin, Changuk Kim, Jeon Min Kang, Jung‐Hoon Park, Hyun‐Do Jung, Wooram Park, Jun‐Won Yun
Journal: Advanced Healthcare Materials (2021)

Abstract Acute liver failure (ALF) requiring liver transplantation is a disease that occurs due to rapid hepatocellular dysfunction. As liver transplantation has various limitations, including donor scarcity, high cost, and immuno‐incompatibility, continuous local delivery of biopharmaceuticals to the liver tissue can be a promising ALF treatment option. Here, the in vivo safety and usability of a 3D‐printed implantable drug delivery device for effective ALF treatment is evaluated. The implantable reservoir consists of a 3D‐printed container and a semipermeable membrane for repeated administrations of drugs, specifically to the liver tissue. The physical stability and function of the 3D‐printed reservoir are confirmed by the mechanical properties and in vitro drug release test, respectively. In mice implanted with the reservoir system, mortality, weight changes, clinical signs, hematological and serum biochemical changes, and organ weight changes are not observed, suggesting no foreign body reaction. The usability of the reservoir system is further evaluated using an ALF model of 70% hepatectomized mice treated with N ‐acetylcysteine through the system, showing cell‐specific regeneration and significant liver injury alleviation. Overall, the 3D‐printed reservoir system is safe for studying the therapeutic potential of ALF treatment, and it can be used for the delivery of various active pharmaceutical ingredients.
Uprooting race-based assumptions in biomedical journal articles
Authors: Angela Aifah, Deborah Onakomaiya, Ashlin Rakhra, Gbenga Ogedegbe
Journal: Trends in Molecular Medicine (2021)

Coronavirus disease 2019 (COVID-19) has exacerbated the structural inequities in healthcare and the challenges of translating research into public discourse. This article highlights key antiracist considerations, presents previously noted core challenges, and provides recommendations for writing and reporting. Importantly, this article contributes to combating racialized science in the biomedical community.
Risk Stratification for Imminent Risk of Death at the Time of Palliative Radiotherapy Consultation
Authors: Susan Y. Wu, Emily Yee, Harish N. Vasudevan, Shannon E. Fogh, Lauren Boreta, Steve E. Braunstein, Julian C. Hong
Journal: JAMA Network Open (2021)

This cohort study of patients with advanced cancer who received palliative radiotherapy within 30 days of death assesses models of prognostic criteria for providing radiotherapy at the end of life and compares outcomes with similar prognostic tools.