tbuckley/cabot-search huggingface dataset:
Abstract PO-004: Basal-like, Classical A, and Classical B subtypes of pancreatic cancer show distinct immuno-suppressive molecular profiles
Authors: Emily L. LaPlante, Dongliang Liu, Aleksandar Milosavljevic, Qizhi Yao
Journal: Cancer Research (2021)

Abstract With recent advances in distinguishing Pancreatic Ductal Adenocarcinoma (PDAC) subtypes based on transcriptional profiles, it is becoming clear that different subtypes have distinct therapeutic responses– e.g. Basal-like tumors tend to show less response to chemotherapy than Classical tumors. Here, we asked if the Basal-like, Classical A, and Classical B PDAC subtypes show distinct immuno-suppressive molecular profiles of relevance for targeted immunotherapy of PDAC. Toward this goal, we leveraged two large, public sequencing cohorts – TCGA and ICGC. To accommodate the large variation in cell type composition among the tumors across these cohorts, we applied the novel expression deconvolution (XDec) method to computationally deconvolute the bulk RNA-seq profiles. The method identified cell-type composition of each tumor and identified distinct Basal-like, Classical A, and Classical B subtypes, thus allowing classification of each tumor based on the state of its constituent cancer cell fraction. We further extended the method to also infer cell-type specific gene expression for each tumor sample and to identify correlation of cell-type specific gene expression levels across cohorts. Using the extended method, we determined that Basal-like cancer cells are CD274 high, Classical B cancer cell CD274 expression correlated strongly with MSLN and RELA (a recently proposed mechanism controlling PD-L1), and Classical A cancer cells had low CD274 expression. Because heterotypic interactions may also contribute toward an immuno-suppressive microenvironment, we next correlated expression levels between cancer and stromal cell types. Cancer cell MSLN expression correlated strongly with stromal CD274 expression which also correlated with stromal IFNGR1 and IFNγ. Using co-culture experiments we validated the causative relationship between cancer cell MSLN and stromal INFGR1 and CD274. Taken together, our results suggest that PDAC subtypes have distinct therapeutic vulnerabilities, with Basal-like and MSLN-high Classical B patients more likely to respond to PD-L1 targeting therapies. Moreover, we provided a methodological advance by extending the XDec method and by making it web-accessible, thus allowing the community to derive hypotheses testable in cell line models by performing correlations of cell-type specific gene expression levels deconvoluted from bulk RNA-seq profiles of PDAC patient tumors. Citation Format: Emily L. LaPlante, Dongliang Liu, Aleksandar Milosavljevic, Qizhi Yao. Basal-like, Classical A, and Classical B subtypes of pancreatic cancer show distinct immuno-suppressive molecular profiles [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-004.
Independent SAGE can be judged on its successes just as the UK government can be judged on its failures
Authors: Andrew Watterson
Journal: BMJ (2021)

Members of the Independent Scientific Advisory Group for Emergencies (Independent SAGE) will be rightly regarded as independent analysts, not “rebels,” by many external observers like me.1 Their evidence based reports are valuable syntheses of research. Their related advice is of practical use. Some people, whose own covid-19 messages are often confused, contradictory, flawed, and wrong, might try to interpret Independent SAGE’s direct and clear …
Allosteric SHP2 Inhibitor RMC4550 Synergizes with Venetoclax in FLT3 and KIT Mutant Acute Myeloid Leukemia
Authors: Bogdan Popescu, Carlos Stahlhut, Theodore C. Tarver, Timothy T. Ferng, Cheryl Peretz, Sydney Wishner, Paul Phojanakong, Veronica Steri, Eric B. Wong, Jose M. Rivera, Elliot Stieglitz, Catherine C. Smith
Journal: Blood (2021)
Allogeneic Hematopoietic Stem Cell Transplantation (allo HSCT) in Patients with IPSS Low or Intermediate-1 Myelodysplastic Syndrome (MDS): A Prospective Multicenter Phase II Study Based on Donor Availability By the GFM &amp; SFGM-TC "MDS-ALLO-Risk"
Authors: Marie Sebert, Cendrine Chaffaut, Sylvain Thepot, Corentin Orvain, Thomas Cluzeau, Michael Loschi, Pierre Peterlin, Patrice Chevallier, Maud d'Aveni, Marie-Thérèse Rubio, Odile Beyne Rauzy, Anne Huynh, Amandine Charbonnier, Nathalie Fegueux, Gaelle Fossard, Stephanie N'guyen-Quoc, Sophie Park, Rosa Sapena, Fatiha Chermat, Lionel Ades, Sylvie Chevret, Pierre Fenaux, Marie Robin
Journal: Blood (2021)
Abstract 10923: Heart Rate Turbulence and Severity of Atherosclerotic Coronary Lesion in Patients with History of Myocardial Infarction
Authors: Amayak Kevorkov, Ergashali Tursunov
Journal: Circulation (2021)

Introduction: Prediction of adverse outcomes in patients after myocardial infarction (MI) remains a serious and not completely resolved problem, which pushes researchers to search for new technologies. One of the relatively promising non-invasive methods for predicting sudden coronary death in patients with coronary heart disease may be an assessment of heart rate turbulence (HRT). Hypothesis: to study the association between components of heart rate turbulence (HRT) and severity of atherosclerotic coronary lesion assessed by the SYNTAX and SYNTAX II Scores in patients with a history of myocardial infarction. Methods: study enrolled 106 patients with a history of MI in the mean age of 63.6±8.3 years (median age 64 [58; 69] years). The severity of coronary lesions was estimated by diagnostic selective coronary angiography with an assessment of SYNTAX and SYNTAX II Scores. All patients underwent 24-h Holter ECG monitoring. HRT was determined using two indicators: Turbulence Onset (To, %) and Turbulence Slope (Ts, ms/RRi). Results: after HRT quantification measurements were as follows: To= -1.28±1.75% (-1.09 [-2.21; -0.40]); Ts= 4.98±4.51 ms/RRi (3.66 [1.65; 7.24]). Mean SYNTAX Score was 16.8±8.5 (16.0 [10.0; 21.5]); SYNTAX Score II PCI - 30.8±8.9 (30.2 [24.7; 37.0]); SYNTAX Score II CABG - 23.8±7.7 (23.6 [19.0; 29.1]); 4 year PCI mortality - 9.4±9.1% (6.9 [4.4; 11.9]); 4 year CABG mortality - 5.0±3.7% (4.1 [2.8; 6.4]). Spearmen analysis revealed positive correlation between To (r=0.266; p=0.047) and SYNTAX Score II PCI and estimated 4-year PCI mortality rate (r=0.267; p=0.047). Negative correlation relationships were observed between Ts indicator and SYNTAX Score II PCI (r= -0.539; p&lt;0.001), SYNTAX Score II CABG (r= -0.318; p=0.017), 4-year PCI mortality rate (r= -0.539; p&lt;0.001) and 4-year CABG mortality rate (r= -0.348; p=0.008). There were no significant correlations between the rests of the analyzed indicators. Conclusions: Components of HRT have an association with SYNTAX and SYNTAX II scores. In patients with a history of MI, progressive impairment of baroreflex activity, as evidenced by changes in HRT parameters may indicate a more pronounced lesion of coronary arteries.
Safety and Efficacy of Venetoclax-Based Treatment in Elderly CLL Patients: A Retrospective Study from the Filo Group
Authors: Charlotte Doublet, Marie-Sarah Dilhuydy, Emmanuelle Ferrant, Pierre Feugier, Alexandra Fayault, Philippine Robert, Stephane Lepretre, Alain Delmer, Cécile Tomowiak, Romain Guieze, Kamel Laribi, Marguerite Vignon, Aline Clavert, Fontanet Bijou, Daniel Re, Diane Lara, Fatiha Merabet, Emmanuelle Tchernonog, Caroline Dartigeas, Anne-Sophie Michallet, Anne Quinquenel
Journal: Blood (2021)
Variations in Guidelines for Diagnosis of Child Physical Abuse in High-Income Countries
Authors: Flora Blangis, Slimane Allali, Jérémie F. Cohen, Nathalie Vabres, Catherine Adamsbaum, Caroline Rey-Salmon, Andreas Werner, Yacine Refes, Pauline Adnot, Christèle Gras-Le Guen, Elise Launay, Martin Chalumeau, Daniela Karall, Per Ashorn, Andreas Werner, Thomas Fischbach, Jacob Urkin, Federica Zanetto, Patrick Theisen, Helena Porfirio, Concepción Sanchez-Pina, Paolo Ramelli 
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The highly variable practices observed regarding the early detection and diagnostic workup of suspected child physical abuse contribute to suboptimal care and could be partially related to discrepancies in clinical guidelines. <h3>Objective</h3> To systematically evaluate the completeness, clarity, and consistency of guidelines for child physical abuse in high-income countries. <h3>Evidence Review</h3> For this systematic review, national or regional guidelines that were disseminated from 2010 to 2020 related to the early detection and diagnostic workup of child physical abuse in infants aged 2 years or younger by academic societies or health agencies in high-income countries were retrieved. The definitions of sentinel injuries and the recommended diagnostic workup (imaging and laboratory tests) for child physical abuse were compared. Data were analyzed from July 2020 to February 2021. <h3>Findings</h3> Within the 20 included guidelines issued in 15 countries, 168 of 408 expected statements (41%) were missing and 10 statements (4%) were unclear. Among 16 guidelines characterizing sentinel injuries, all of them included skin injuries, such as bruises, hematoma, or burns, but only 8 guidelines (50%) included intraoral injuries and fractures. All 20 guidelines agreed on the indication for radiological skeletal survey, head computed tomography, and head magnetic resonance imaging but differed for those of bone scintigraphy, follow-up skeletal survey, spinal magnetic resonance imaging, cranial ultrasonography, chest computed tomography, and abdominal ultrasonography and computed tomography. Additionally, 16 guidelines agreed on exploring primary hemostasis and coagulation but not on the tests to perform, and 8 guidelines (50%) mentioned the need to investigate bone metabolism. <h3>Conclusions and Relevance</h3> These findings suggest that guidelines for the diagnosis of child physical abuse in infants were often clear but lacked completeness and were discrepant on major issues. These results may help identify priorities for well-designed original diagnostic accuracy studies, systematic reviews, or an international consensus process to produce clear and standardized guidelines to optimize practices and infant outcomes.
IMMU-51. SINGLE-CELL ANALYSIS OF TUMOR-ASSOCIATED MICROGLIA AND MACROPHAGES FROM HUMAN GLIOBLASTOMA
Authors: Atul Anand, Rikke Sick Andersen, Mark Burton, Dylan Scott Lykke Harwood, Frantz Rom Poulsen, Bo Halle, Christian Bonde Pedersen, Torben Kruse, Mads Thomassen, Bjarne Kristensen
Journal: Neuro-Oncology (2021)

Abstract Patients with glioblastoma, the most frequent and malignant primary brain tumor type, have a poor prognosis with a median survival of 14 months. A major therapeutic problem is chemoresistance. In surgically removed glioblastoma tissue, tumor-associated microglia and macrophages (TAMs) constitute up to 30 % of the total cells. TAMs are capable of secreting cytokines, chemokines and growth factors, thereby influencing the tumor microenvironment. However, the existence of different TAM subtypes and their role in glioblastoma is not fully comprehended and rarely considered therapeutically. This could explain why many glioblastoma clinical trials fail despite of promising preclinical results. This project aims to interrogate the existence and characteristics of different TAM subtypes in human glioblastoma biopsies in order to identify novel subpopulations and therapeutic targets. To study the heterogeneity in TAMs, CD11b+ cells were isolated from glioblastoma patient′s tissue, and single-cell RNA sequencing was performed using the 10X Genomics Chromium platform for single-cell generation and an Illumina NovaSeq6000 system for sequencing. We have sequenced TAMs from three glioblastomas and CD11b+ cells from brain tissue adjacent to two brain metastases samples. In the filtered data set of almost 71,000 CD11b+ cells, we were able to identify recently described TAM populations, such as an interferon-induced, a phagocytic, a hypoxic and a proliferating subset. Interestingly, we also discovered potential novel TAM subsets, such as a pro-angiogenic subset. We have detected a TAM population which is more complex than the established M1 and M2 phenotypes, constituting novel TAM subsets. We are currently investigating these findings to validate specific markers associated with these subpopulations, and for the identification of novel clinically relevant targets.
Outcomes from Returning Individual versus Only Study-Wide Biomonitoring Results in an Environmental Exposure Study Using the Digital Exposure Report-Back Interface (DERBI)
Authors: Julia Green Brody, Piera M. Cirillo, Katherine E. Boronow, Laurie Havas, Marj Plumb, Herbert P. Susmann, Krzysztof Z. Gajos, Barbara A. Cohn
Journal: Environmental Health Perspectives (2021)

Study participants want to receive their biomonitoring results for environmental chemicals, and ethics guidelines encourage reporting back. However, few studies have quantitively assessed participants' responses to individual exposure reports, and digital methods have not been evaluated.We isolated effects of receiving personal results vs. only study-wide findings and investigated whether effects differed for Black participants.We randomly assigned a subset of 295 women from the Child Health and Development Studies, half of whom were Black, to receive a report with personal environmental chemical results or only study-wide (aggregate) findings. Reports included results for 42 chemicals and lipids and were prepared using the Digital Exposure Report-Back Interface (DERBI). Women were interviewed before and after viewing their report. We analyzed differences in website activity, emotional responses, and intentions to participate in future research by report type and race using Wilcoxon rank sum tests, Wilcoxon-Pratt signed ranks tests, and multiple regression.The personal report group spent approximately twice as much time on their reports as the aggregate group before the post-report-back interview. Among personal-report participants (n=93), 84% (78) viewed chemical group information for at least one personal result highlighted on their home page; among aggregate-report participants (n=94), 66% (62) viewed any chemical group page. Both groups reported strong positive feelings (curious, informed, interested, respected) about receiving results before and after report-back and mild negative feelings (helpless, scared, worried). Although most participants remained unworried after report-back, worry increased by a small amount in both groups. Among Black participants, higher post report-back worry was associated with having high levels of chemicals.Participants were motivated by their personal results to access online information about chemical sources and potential health effects. Report-back was associated with a small increase in worry, which could motivate appropriate action. Personal report-back increased engagement with exposure reports among Black participants. https://doi.org/10.1289/EHP9072.
Sixty seconds on . . . Big Bird
Authors: Elisabeth Mahase
Journal: BMJ (2021)

According to his official Twitter account Big Bird has been vaccinated against SARS-CoV-2. In a post on 6 November, the Muppet said,1 “I got the covid-19 vaccine today! My wing is feeling a little sore, but it’ll give my body an extra protective boost that keeps me and others healthy.”

No, Big Bird was joined by Elmo and Rosita—a Mexican character on …
DHEA-induced PSA production in human LNCaP prostate cancer cells is inhibited by both androgen receptor and estrogen receptor antagonists
Authors: Julia T. Arnold, Hanh D. Le, Kimberly K. McFann, Marc R. Blackman
Journal: Cancer Research (2005)

3192  Supplemental use of over-the-counter preparations of dehydroepiandrosterone (DHEA) by men, in the hope that it will retard the aging process, may pose a risk for increasing prostate cancer, as DHEA is a precursor to the more potent androgens, testosterone (T) and dihydrotestosterone (DHT), as well as the potent estrogen, estradiol (E2). We recently reported that DHEA stimulates cell growth and gene and protein expression in human LNCaP prostate cancer epithelial cells, which contain a mutant form of the androgen receptor (AR), and that its effects are delayed and reduced compared with those of DHT and T, but similar to those of E2, (Am J Physiol (Endocrinol), in press). In the present study, we investigated the extent to which DHEA-modulated effects in LNCaP cells are mediated via the AR and/or estrogen receptor β (ERβ), by evaluating cell proliferation and prostate specific antigen (PSA) production in LNCaP cells treated with DHEA, DHT, or E2 in the absence or presence of an AR antagonist (Casodex®-bicalutamide) or an ER antagonist (ICI 182,780). Casodex inhibited DHEA-induced (100nM) cell proliferation by 93% (p
Patient and Caregiver Attitudes Towards Gene Therapy for Sickle Cell Disease: A Need for Partnership and Education
Authors: Akshay Sharma, Amanda Young, Yvonne Carroll, Belinda Mandrell, Mary Caples, Jami Gattuso, Lauren Jerkins, Lakiea Bailey, Benjami Wilfond, Yoram Unguru, Yian Guo, Yimei Li, Liza-Marie Johnson
Journal: Blood (2021)
Single Cell RNA Sequencing in Patients Enrolled in a Selinexor Clinical Trial Reveals Overexpression of Alternative Nuclear Export Pathways Associated with Resistance to Selinexor in Refractory Multiple Myeloma
Authors: Yael C Cohen, Mor Zada, Shuang-Yin Wang, Ohad S. Bentur, Evgeni Chubar, Amos Cohen, Noa Lavi, Hila Magen, Moshe Gatt, Miri Zektser, Merav Leiba, Galia Stemer, Tamir Shragai, Irit Avivi, Assaf Weiner, Ido Amit
Journal: Blood (2021)
Abstract 236: Lactate Level at the Scene of Injury can Accurately Predict the Need for Massive Transfusion
Authors: Takayuki Ogura, Mio Okada, Keita Kanehata
Journal: Circulation (2018)

Introduction: The lactate has been widely recognized as a marker of tissue hypoxia/hypoperfusion. Hyperlactatemia is common among patients requiring critical care, and lactate levels and their trend may be reliable markers of illness severity and mortality. Elevated plasma lactate levels have been recommended as a parameter for hemodynamic resuscitation. The aim of this study is to investigate the predictive value of the lactate levels at the scene of injury for the need for Massive Transfusion (MT). Patients and Methods: A single-center retrospective diagnostic study was conducted. The records of the emergency medical service (EMS) between Sep. 2012 and Apr. 2017 were reviewed and adult high-energy trauma patients transported by the EMS were included. The data about the lactate levels and the need for MT (10 units or more of packed red blood cells transfusion within 24 hours of injury) was collected, and the predictive value of the lactate levels at the scene of injury was analyzed by the area under the receiver operating characteristic curve (AUROC). Our EMS system is always with specialized emergency physician, and lactate level was measured by portable equipment. Results: 1039 patients were enrolled and 1025 patients were analyzed after exclusion of 14 patients with insufficient data. The mean age was 55.0 years, 77.6% male, 98.1% blunt trauma, and 6.6% underwent MT. The AUROC of the lactate levels at the scene of injury for MT was 0.91 [95% confidential interval; 0.90-0.93]. Conclusion: The lactate levels at the scene of injury can accurately predict the need for Massive Transfusion. The further investigation is warranted.
Internal and External Validation of the High-2-Low Model: A Predictive Score for Venous Thromboembolism after Allogeneic Transplant
Authors: Ang Li, Kylee L Martens, Daniel Nguyen, Gabriela Rondon, Christopher I Amos, Stephanie J. Lee, Ryan Basom, Chris Davis, David A. Garcia, Richard E. Champlin, Elizabeth J. Shpall, Cristhiam Mauricio Rojas Hernandez, Partow Kebriaei
Journal: Blood (2021)
Time-Limited Venetoclax and Ibrutinib for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (R/R CLL) Who Have Undetectable MRD - Primary Analysis from the Randomized Phase II Vision HO141 Trial
Authors: Carsten Utoft Niemann, Julie Dubois, Christian Brieghel, Sabina Kersting, Lisbeth Enggaard, Gerrit J Veldhuis, Rogier Mous, Clemens Mellink, Johan A Dobber, Christian Bjørn Poulsen, Henrik Frederiksen, Ann Janssens, Ida Schjødt, Ellen C Dompeling, Juha Ranti, Mattias Mattsson, Mar Bellido, Kazem Nasserinejad, Hoa Thi Tuyet Tran, Mark-David Levin, Arnon P. Kater
Journal: Blood (2021)
Identification of Novel Targets Based on Splicing Alterations for Undruggable RAS/CDK Signaling Cascade in Multiple Myeloma
Authors: Sophia Adamia, Zuzana Chyra, Morgan O'Keefe, Shruti Bhatt, Kenneth Wen, Geoffrey G Fell, Yu-Tzu Tai, Anthony G. Letai, Ivane Abiatari, David M. Dorfman, Teru Hideshima, Kenneth C. Anderson
Journal: Blood (2021)
Platelet-Rich Plasma Injection vs Sham Injection and Tendon Dysfunction in Patients With Chronic Midportion Achilles Tendinopathy—Reply
Authors: Rebecca S. Kearney, Matthew L. Costa
Journal: JAMA (2021)

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Phase 1/dose expansion trial of brentuximab vedotin and lenalidomide in relapsed or refractory diffuse large B-cell lymphoma
Authors: Jeffrey P. Ward, Melissa M. Berrien-Elliott, Felicia Gomez, Jingqin Luo, Michelle Becker-Hapak, Amanda F. Cashen, Nina D. Wagner-Johnston, Kami Maddocks, Matthew Mosior, Mark Foster, Kilannin Krysiak, Alina Schmidt, Zachary L. Skidmore, Sweta Desai, Marcus P. Watkins, Anne Fischer, Malachi Griffith, Obi L. Griffith, Todd A. Fehniger, Nancy L. Bartlett
Journal: Blood (2021)
The Addition of Rituximab to Cyclophosphamide, Doxorubicine, Vincristine and Prednisone (CHOP) Prolongs Overall Survival in Previously Untreated Mantle Cell Lymphoma: A Long Term Pooled Trials Analysis
Authors: Luca Fischer, Linmiao Jiang, Joerg Bittenbring, Kai Hübel, Christian Schmidt, Johannes Duell, Bernd Metzner, Jürgen Krauter, Bertram Glass, Andreas Hüttmann, Kerstin Schaefer-Eckart, Wolfram Klapper, Wolfgang Hiddemann, Michael Unterhalt, Martin H. Dreyling, Eva Hoster
Journal: Blood (2021)
Circular RNA Dysregulation Characterizes Symptomatic T-LGL Leukemia Patients with <i>STAT3</i> Mutation
Authors: Alessia Buratin, Cristina Vicenzetto, Vanessa Rebecca Gasparini, Andrea Binatti, Antonella Teramo, Giulia Calabretto, Gregorio Barilà, Enrico Gaffo, Francesco Piazza, Gianpietro Semenzato, Renato Zambello, Stefania Bortoluzzi
Journal: Blood (2021)