tbuckley/cabot-search huggingface dataset:
The Immune Response in Multiple Sclerosis
Authors: Sofía Rodríguez Murúa, Mauricio F. Farez, Francisco J. Quintana
Journal: Annual Review of Pathology Mechanisms of Disease (2021)

Multiple sclerosis (MS) is a chronic autoimmune, inflammatory, and neurodegenerative disease that affects the central nervous system (CNS). MS is characterized by immune dysregulation, which results in the infiltration of the CNS by immune cells, triggering demyelination, axonal damage, and neurodegeneration. Although the exact causes of MS are not fully understood, genetic and environmental factors are thought to control MS onset and progression. In this article, we review the main immunological mechanisms involved in MS pathogenesis.
50P Efficacy and safety of pemigatinib in Chinese patients with unresectable, advanced/ recurrent or metastatic intrahepatic cholangiocarcinoma with FGFR2 fusion or rearrangement that failed to prior systemic therapy
Authors: G-M. Shi, X-Y. Huang, T-F. Wen, T-Q. Song, M. Kuang, H-B. Mou, L-Q. Bao, H-T. Zhao, H. Zhao, X-L. Feng, B. Zhang, T. Peng, Y. Zhang, X. Li, H. Yu, Y. Cao, Y. Luo, Y. Wang, J. Fan, J. Zhou
Journal: Annals of Oncology (2021)
1526MO GEMMK: A phase I study of gemcitabine (gem) and pembrolizumab (pem) in patients (pts) with leiomyosarcoma (LMS) and undifferentiated pleomorphic sarcoma UPS)
Authors: A. Smrke, A. Ostler, A. Napolitano, M. Vergnano, B. Asare, N. Fotiadis, K. Thway, S. Zaidi, A.B. Miah, W. van der Graaf, S. Gennatas, C. Benson, P.H. Huang, R.L. Jones
Journal: Annals of Oncology (2021)
Abstract 535: Proteomics Analysis Identifies Positive Transcription Elongation Factor b as a Novel GATA-4-binding Partner Involved in Hypertrophic Responses in Cardiomyocytes
Authors: Yoichi Sunagawa, Tatsuya Morimoto, Teruhisa Kawamura, Tomohide Takaya, Hiromichi Wada, Akira Shimatsu, Koji Hasegawa, Masatoshi Fujita, Toru Kita
Journal: Circulation (2007)

Introduction: A zinc finger protein GATA-4 is one of the factors involved in transcriptional regulation during myocardial cell hypertrophy. In response to hypertrophic stimuli, GATA-4 forms a large complex with ERK, NFATc and an intrinsic histone acetyltransferase, p300. Disruption of this complex results in the inhibition of hypertrophic responses in cardiomyocytes. Hypothesis: We assessed the hypothesis that proteomics analysis may identify novel GATA-4-binding partners required for myocardial cell hypertrophy. Methods: GATA-4 was stably expressed as FLAG-HA-epitope fusion in HeLa cells by retroviral transduction. GATA-4 complex was purified from nuclear extracts of these cells by sequential immunoprecipitation with an anti-FLAG antibody followed by an anti-HA antibody (Tandem Affinity Purification). Results: By mass spectrometric analyses, we identified 73 GATA-4 binding proteins, including histone modifying factors, methyltransferase, HDAC and unknown proteins. One was cyclin-dependent kinases-9 (cdk9), a component of Positive Transcription Elongation Factor b (P-TEFb). Immunoblotting analyses demonstrated that GATA-4 formed a complex with p300, cdk9 and cyclin T1, another component of P-TEFb. A dominant-negative form of p300 disrupted the interaction of GATA-4 with cdk9 or cyclin T1. Conversely, a dominant-negative form of cdk9 and a cdk9 kinase inhibitor, 5,6-dichloro-1-h-ribofuranosyl-benzimidazole (DRB) inhibited p300-induced activation of GATA-4-dependent transcription as well as the acetylation of GATA-4. Stimulation of cardiomyocytes with phenylephrine (PE) increased the binding of GATA-4/p300 with cdk9 or cyclin T1. DN-cdk9 and DRB not only disrupted the complex of GATA-4/p300 with cdk9 or cyclin T1, but also repressed PE-induced hypertrophic responses such as myofibrillar organization, increase in cell size and promoter activation of the endothelin-1 and atrial natriuretic factors in cardiomyocytes. Conclusion: These findings demonstrate that cdk9 and cyclin T1 form a functional protein complex with GATA-4/p300 and that this large complex is a prerequisite for hypertrophic responses in cardiac myocytes.
960MO Clinical outcomes and immune responses in a phase I/II study of personalized, neoantigen-directed immunotherapy in patients with advanced MSS-CRC, GEA and NSCLC
Authors: D.V. Catenacci, C-Y. Liao, S. Maron, B.J. Solomon, A. Mahipal, M.L. Johnson, D. Carbone, B.S. Henick, B. Johnson, S. Roychowdhury, K. Mody, D.H. Ahn, E. Bournazou, D. Schenk, S. Kounlavouth, L. Kraemer, G. Talbot, R. Rousseau, A.R. Ferguson, A. Spira
Journal: Annals of Oncology (2021)
103P Rate of BRCA1/2 pathogenic variants according to family and personal history of cancer in a large cohort of triple-negative breast cancer (TNBC) patients (pts) younger than 60 years of age
Authors: S. Zovato, G. Griguolo, S. Agata, S. Tognazzo, M.V. Dieci, L. Matricardi, G. Crivellari, F. Miglietta, E. Alducci, L. Moserle, P.F. Conte, M. Montagna, V. Guarneri
Journal: Annals of Oncology (2021)
Abstract 12979: NPA7: First-in-Class Bispecific GC-A/MasR Activating Peptide That Enhances Cardiorenal Function and Suppresses Renin and Aldosterone In Vivo via Subcutaneous Delivery
Authors: Shinobu Sugihara, Tomoko Ichiki, Yang Chen, Gail J Harty, Seethalakshimi R Iyer, Shuchong Pan, S J Sangaralingham, Daniel J McCormick, BurnettJohn C
Journal: Circulation (2018)

Introduction: Bispecific drugs have emerged as highly efficacious medicines as they are designed to target two separate signaling pathways. We engineered a bispecific peptide NPA7 to co-activate th...
1379P Margetuximab (M) with retifanlimab (R) in HER2+, PD-L1+ 1st-line unresectable/metastatic gastroesophageal adenocarcinoma (GEA): MAHOGANY cohort A
Authors: D.V. Catenacci, H. Park, B.Y. Shim, S.T. Kim, D-Y. Oh, A. Spira, S. Ulahannan, E.J. Avery, P.M. Boland, J. Chao, H.C. Chung, F. Gardner, S.J. Klempner, K-W. Lee, S.C. Oh, J. Peguero, M.B. Sonbol, J. Sun, M.K. Rosales, Y-K. Kang
Journal: Annals of Oncology (2021)
Cost-Effectiveness of Magnetic Resonance Imaging Screening for Women With Extremely Dense Breast Tissue
Authors: H Amarens Geuzinge, Marije F Bakker, Eveline A M Heijnsdijk, Nicolien T van Ravesteyn, Wouter B Veldhuis, Ruud M Pijnappel, Stéphanie V de Lange, Marleen J Emaus, Ritse M Mann, Evelyn M Monninkhof, Petra K de Koekkoek-Doll, Carla H van Gils, Harry J de Koning
Journal: JNCI Journal of the National Cancer Institute (2021)

Extremely dense breast tissue is associated with increased breast cancer risk and limited sensitivity of mammography. The DENSE trial showed that additional magnetic resonance imaging (MRI) screening in women with extremely dense breasts resulted in a substantial reduction in interval cancers. The cost-effectiveness of MRI screening for these women is unknown.We used the MISCAN-breast microsimulation model to simulate several screening protocols containing mammography and/or MRI to estimate long-term effects and costs. The model was calibrated using results of the DENSE trial and adjusted to incorporate decreases in breast density with increasing age. Screening strategies varied in the number of MRIs and mammograms offered to women ages 50-75 years. Outcomes were numbers of breast cancers, life-years, quality-adjusted life-years (QALYs), breast cancer deaths, and overdiagnosis. Incremental cost-effectiveness ratios (ICERs) were calculated (3% discounting), with a willingness-to-pay threshold of €22 000.Calibration resulted in a conservative fit of the model regarding MRI detection. Both strategies of the DENSE trial were dominated (biennial mammography; biennial mammography plus MRI). MRI alone every 4 years was cost-effective with €15 620 per QALY. Screening every 3 years with MRI alone resulted in an incremental cost-effectiveness ratio of €37 181 per QALY. All strategies with mammography and/or a 2-year interval were dominated because other strategies resulted in more additional QALYs per additional euro. Alternating mammography and MRI every 2 years was close to the efficiency frontier.MRI screening is cost-effective for women with extremely dense breasts, when applied at a 4-year interval. For a willingness to pay more than €22 000 per QALY gained, MRI at a 3-year interval is cost-effective as well.
Illness and injury among Norwegian Para athletes over five consecutive Paralympic Summer and Winter Games cycles: prevailing high illness burden on the road from 2012 to 2020
Authors: Kathrin Steffen, Benjamin Clarsen, Hilde Gjelsvik, Lars Haugvad, Anu Koivisto-Mørk, Roald Bahr, Hilde Moseby Berge
Journal: British Journal of Sports Medicine (2021)

To describe the illness and injury pattern of Norwegian Para athletes over five consecutive Paralympic Summer and Winter Games cycles and to identify which health problems should be targeted in risk management plans with respect to impairment types.We monitored athletes from 12 to 18 months prior to each Game using a weekly online questionnaire (Oslo Sports Trauma Research Center-H2 (OSTRC-H2)). We asked them to report all health problems they had experienced in the preceding 7 days, irrespective of their consequences on their sports participation or performance and whether they had sought medical attention.Between 2011 and 2020, 94 candidate athletes were included in this monitoring programme and prepared to represent Norway; of these, 66 (71%) were finally selected for multiple Paralympic Games. The overall response rate to the weekly questionnaires was 87%. At any given time during the five observation cycles, 37% of the athletes (95% CI 36% to 38%) reported having at least one health problem. Athletes with neurological impairments (n=51) lost 10 days per year due to respiratory problems (95% CI 9 to 11) compared with 9 days (8-10) among those with musculoskeletal impairments (n=37). Gastrointestinal problems caused a time loss of on average 4 days per year in athletes with neurological impairments versus 1 day in athletes with musculoskeletal impairments (mean difference 2.7 days, 2.1-3.3). Musculoskeletal injuries generated a high burden for both athlete groups, in particular, to the elbow, shoulder and lumbosacral regions.At any given time, nearly two out of five elite Norwegian Para athletes reported at least one health problem. Respiratory tract and other infections; gastrointestinal problems, injuries to the shoulder, elbow and lumbosacral regions represented the greatest health burden. Our findings can help guide the allocation of clinical resources, which should include a broad network of medical specialists, together with dieticians and physiotherapists, to meet the health challenges in Para athletes.
692P Characterization of the tumor immune microenvironment in early-stage clear cell renal cell carcinoma (ccRCC): Prognostic value of an M0-macrophage enriched subtype
Authors: M. Farha, R. Vince, S. Nallandinghal, J. Stangl-Kremser, D. Triner, T. Morgan, G. Palapattu, A. Udager, S. Salami
Journal: Annals of Oncology (2021)
Lineage tracing and single-cell analysis reveal proliferative Prom1+ tumour-propagating cells and their dynamic cellular transition during liver cancer progression
Authors: Lei Zhou, Ken HO Yu, Tin Lok Wong, Zhao Zhang, Chun Ho Chan, Jane HC Loong, Noelia Che, Hua Jian Yu, Kel Vin Tan, Man Tong, Elly S Ngan, Joshua WK Ho, Stephanie Ma
Journal: Gut (2021)

Hepatocellular carcinoma (HCC) has high intratumoral heterogeneity, which contributes to therapeutic resistance and tumour recurrence. We previously identified Prominin-1 (PROM1)/CD133 as an important liver cancer stem cell (CSC) marker in human HCC. The aim of this study was to investigate the heterogeneity and properties of Prom1+ cells in HCC in intact mouse models.We established two mouse models representing chronic fibrotic HCC and rapid steatosis-related HCC. We performed lineage tracing post-HCC induction using Prom1C-L/+; Rosa26tdTomato/+ mice, and targeted depletion using Prom1C-L/+; Rosa26DTA/+ mice. Single-cell RNA sequencing (scRNA-seq) was carried out to analyse the transcriptomic profile of traced Prom1+ cells.Prom1 in HCC tumours marks proliferative tumour-propagating cells with CSC-like properties. Lineage tracing demonstrated that these cells display clonal expansion in situ in primary tumours. Labelled Prom1+ cells exhibit increasing tumourigenicity in 3D culture and allotransplantation, as well as potential to form cancers of differential lineages on transplantation. Depletion of Prom1+ cells impedes tumour growth and reduces malignant cancer hallmarks in both HCC models. scRNA-seq analysis highlighted the heterogeneity of Prom1+ HCC cells, which follow a trajectory to the dedifferentiated status with high proliferation and stem cells traits. Conserved gene signature of Prom1 linage predicts poor prognosis in human HCC. The activated oxidant detoxification underlies the protective mechanism of dedifferentiated transition and lineage propagation.Our study combines in vivo lineage tracing and scRNA-seq to reveal the heterogeneity and dynamics of Prom1+ HCC cells, providing insights into the mechanistic role of malignant CSC-like cells in HCC progression.
273P Talazoparib (TALA) for patients with germline BRCA1/2 mutated (gBRCA1/2mut) advanced breast cancer (ABC): Characteristics of patients who experienced hematologic toxicity in the phase III EMBRACA trial
Authors: S.A. Hurvitz, H.S. Rugo, J. Ettl, M. Martin, H. Roche, K-H. Lee, A. Goodwin, T. Usari, S. Lanzalone, C.A. Guenzel, J. Blum, J.K. Litton
Journal: Annals of Oncology (2021)
External validation of prognostic scores for COVID-19: a multicenter cohort study of patients hospitalized in Greater Paris University Hospitals
Authors: Yannis Lombardi, Loris Azoyan, Piotr Szychowiak, Ali Bellamine, Guillaume Lemaitre, Mélodie Bernaux, Christel Daniel, Judith Leblanc, Quentin Riller, Olivier Steichen, Pierre-Yves Ancel, Alain Bauchet, Nathanael Beeker, Vincent Benoit, Romain Bey, Aurélie Bourmaud, Stéphane Bréant, Anita Burgun, Fabrice Carrat, Charlotte Caucheteux, Julien Champ, Sylvie Cormont, Julien Dubiel, Catherine Duclos, Loic Esteve, Marie Frank, Nicolas Garcelon, Alexandre Gramfort, Nicolas Griffon, Olivier Grisel, Martin Guilbaud, Claire Hassen-Khodja, François Hemery, Martin Hilka, Anne Sophie Jannot, Jerome Lambert, Richard Layese, Léo Lebouter, Damien Leprovost, Ivan Lerner, Kankoe Levi Sallah, Aurélien Maire, Marie-France Mamzer, Patricia Martel, Arthur Mensch, Thomas Moreau, Antoine Neuraz, Nina Orlova, Nicolas Paris, Bastien Rance, Hélène Ravera, Antoine Rozes, Pierre Rufat, Elisa Salamanca, Arnaud Sandrin, Patricia Serre, Xavier Tannier, Jean-Marc Treluyer, Damien Van Gysel, Gael Varoquaux, Jill-Jênn Vie, Maxime Wack, Perceval Wajsburt, Demian Wassermann, Eric Zapletal
Journal: Intensive Care Medicine (2021)
Axonal marker neurofilament light predicts long-term outcomes and progressive neurodegeneration after traumatic brain injury
Authors: Neil S. N. Graham, Karl A. Zimmerman, Federico Moro, Amanda Heslegrave, Samia Abed Maillard, Adriano Bernini, John-Paul Miroz, Cornelius K. Donat, Maria Yanez Lopez, Niall Bourke, Amy E. Jolly, Emma-Jane Mallas, Eyal Soreq, Mark H. Wilson, Gavin Fatania, Dylan Roi, Maneesh C. Patel, Elena Garbero, Giovanni Nattino, Camelia Baciu, Enrico Fainardi, Arturo Chieregato, Primoz Gradisek, Sandra Magnoni, Mauro Oddo, Henrik Zetterberg, Guido Bertolini, David J. Sharp
Journal: Science Translational Medicine (2021)

Axonal injury after TBI can be reliably quantified using plasma NfL, which predicts long-term functional outcomes and progressive neurodegeneration.
1589P Safety of the BNT162b2 mRNA COVID-19 vaccine in oncologic patients undergoing numerous cancer treatment options
Authors: M. Zemel, W. Kian, E.H. Kestenbaum, W. Alguayn, D. Levitas, A.A. Sharb, W. Shalata, K. Rouvinov, L. Nesher, A. Yakobson
Journal: Annals of Oncology (2021)
673P Cabozantinib-nivolumab (CN) vs. nivolumab-cabozantinib (NC) in patients (pts) with metastatic clear cell renal cell carcinoma (mRCC) following one prior VEGFR tyrosine kinase inhibitor (TKI): The CABIR multicentric matching-adjusted study
Authors: Y. Vano, L. Phan, G. Gravis, I. Korakis, F. Schlürmann, D. Maillet, M. Bennamoun, N. Houede, D. Topart, D. Borchiellini, P. Barthelemy, R. Ratta, T. Ryckewaert, A. Hasbini, S. Hans, S. Emambux, S. Cournier, E. Braychenko, R-T. Elaidi, S.M. Oudard
Journal: Annals of Oncology (2021)
Emerging Therapeutics, Technologies, and Drug Development Strategies to Address Patient Nonadherence and Improve Tuberculosis Treatment
Authors: Maria Garcia-Cremades, Belen P. Solans, Natasha Strydom, Bernard Vrijens, Goonaseelan Colin Pillai, Craig Shaffer, Bruce Thomas, Rada M. Savic
Journal: The Annual Review of Pharmacology and Toxicology (2021)

Imperfect medication adherence remains the biggest predictor of treatment failure for patients with tuberculosis. Missed doses during treatment lead to relapse, tuberculosis resistance, and further spread of disease. Understanding individual patient phenotypes, population pharmacokinetics, resistance development, drug distribution to tuberculosis lesions, and pharmacodynamics at the site of infection is necessary to fully measure the impact of adherence on patient outcomes. To decrease the impact of expected variabilityin drug intake on tuberculosis outcomes, an improvement in patient adherence and new forgiving regimens that protect against missed doses are needed. In this review, we summarize emerging technologies to improve medication adherence in clinical practice and provide suggestions on how digital adherence technologies can be incorporated in clinical trials and practice and the drug development pipeline that will lead to more forgiving regimens and benefit patients suffering from tuberculosis.
Serious infections in patients with rheumatoid arthritis and psoriatic arthritis treated with tumour necrosis factor inhibitors: data from register linkage of the NOR-DMARD study
Authors: Ingrid Egeland Christensen, Siri Lillegraven, Pawel Mielnik, Gunnstein Bakland, Liz Loli, Joe Sexton, Till Uhlig, Tore K Kvien, Sella A Provan
Journal: Annals of the Rheumatic Diseases (2021)

To estimate the incidence of serious infections (SIs) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated with tumour necrosis factor inhibitor (TNFi), and compare risk of SIs between patients with RA and PsA.We included patients with RA and PsA from the NORwegian-Disease Modifying Anti-Rheumatic Drug registry starting TNFi treatment. Crude incidence rates (IRs) and IR ratio for SIs were calculated. The risk of SIs in patients with RA and PsA was compared using adjusted Cox-regression models.A total of 3169 TNFi treatment courses (RA/PsA: 1778/1391) were identified in 2359 patients. Patients with RA were significantly older with more extensive use of co-medication. The crude IRs for SIs were 4.17 (95% CI 3.52 to 4.95) in patients with RA and 2.16 (95% CI 1.66 to 2.81) in patients with PsA. Compared with the patients with RA, patients with PsA had a lower risk of SIs (HR 0.59, 95% CI 0.41 to 0.85, p=0.004) in complete set analysis. The reduced risk in PsA versus RA remained significant after multiple adjustments and consistent across strata based on age, gender and disease status.Compared with patients with RA, the risk of SIs was significantly lower in patients with PsA during TNFi exposure.
1007P T-cells transgenic for a highly potent PRAME-specific TCR and a chimeric PD1-41BB co-stimulatory receptor represent a promising approach for the treatment of solid tumors
Authors: M. Bürdek, I. Fetzer, N. Sailer, M. Salvermoser, D. Brechtefeld, K. Mutze, S. Raffegerst, M. Braun, R. Goedkoop, S. Wilde, D. Sommermeyer
Journal: Annals of Oncology (2021)
The dual PPARα/γ ligand TZD18 inhibits cell growth and induces apoptosis in human Bcr-Abl positive CML cell lines >in vitro
Authors: Peiying Yang, Diana Chan, Mary Vijjeswarapu, Carrie Cartwright, Lorenzo Cohen, Zhiqiang Meng, Luming Liu, Robert A. Newman
Journal: Cancer Research (2006)

3852  Chan su, the dried toad venom or the dried secretion from the skin glands of Bufo bufo gargarizans Cantor or B. melanotictus Schneider, has long been used as a therapeutic agent for cancer treatment in China and other Asian countries. Huachansu, an injectable form of Chan su, is a sterilized hot water extract of dried toad skin. Since 1991, huachansu has been officially approved as a regimen for treatment of cancer in China. However, the selectivity and mechanism of anti-cancer activity of huachansu have not been fully elucidated. The goals of our current study were to investigate the cytotoxicity of huachansu alone as well as the polar and non-polar compartments of huachansu and cardiac glycosides derived from huachansu against various cancer cells. In addition, we explored mechanisms associated with this extract’s antiproliferative activity. The inhibitory effects of three different lots of huachansu were tested in four different human cell lines including hepatoma (Hep 3B), colon (HT29), pancreatic (Panc-1) and melanoma (BRO) cells. The relative growth inhibitory activity on the growth of cancer cells for all three lots of huachansu was ranked as Panc-1 > HT29 > BRO > Hep3B cells. The inhibitory effect of the non-polar fraction (lipid soluble) of huachansu was much stronger than that of the polar compartment (water soluble) with IC50 of 1.75 mg /ml versus 31.25 mg (raw material)/ml, respectively. These data suggest that huachansu’s antitumor activity is mainly attributed to the lipid-soluble components. Because cardiac glycosides are one of the lipid soluble components in huachansu, we next tested the relative cytotoxicity of three different cardiac glycosides derived from huachansu, including bufalin, cinobufagin, and resibufogenin against BRO cells. The IC50 values of bufalin, cinobufagin, and resibufogenin in BRO cells were 16.7, 20.1 and 700 ng/ml, respectively. When BRO cells were treated with huachansu (1 to 25 mg/ml) for 24 hr, huachansu induced cell cycle arrest in the G2/M-phase. Furthermore, huachansu as well as bufalin down-regulated Bcl-2 expression, yet up-regulated BAX protein in BRO cells in a concentration-dependent manner. In addition, our preliminary data also demonstrated that huachansu (10 mg/ml) significantly reduced B23 (neucleophosmin), pAKT and STAT3 expression. Concomitantly, it up-regulated several cell signaling pathways such as SRC, MAPK, and Raf, which is attributed to the stress-mediated cell response of huachansu cardiac glycosides. Taken together, these results suggest that cardiac glycosides, such as bufalin, are responsible for huachansu induced cell death in BRO cells. Whether other components in huachansu also contribute to its anti-proliferative activity requires further investigation. This research was supported in part by NCI R21 CA108084-01, International Center of TCM for Cancer.
Social bonding and music: Evidence from lesions to the ventromedial prefrontal cortex
Authors: Amy M. Belfi
Journal: Behavioral and Brain Sciences (2021)

Abstract The music and social bonding (MSB) hypothesis suggests that damage to brain regions in the proposed neurobiological model, including the ventromedial prefrontal cortex (vmPFC), would disrupt the social and emotional effects of music. This commentary evaluates prior research in persons with vmPFC damage in light of the predictions put forth by the MSB hypothesis.