tbuckley/cabot-search huggingface dataset:
Society for Immunotherapy of Cancer clinical and biomarkers data sharing resource document: Volume I—conceptual challenges
Authors: Sergio Rutella, Michael A Cannarile, Sacha Gnjatic, Bruno Gomes, Justin Guinney, Vaios Karanikas, Mohan Karkada, John M Kirkwood, Beatrix Kotlan, Giuseppe V Masucci, Els Meeusen, Anne Monette, Aung Naing, Vésteinn Thorsson, Nicholas Tschernia, Ena Wang, Daniel K Wells, Timothy L Wyant, Alessandra Cesano
Journal: Journal for ImmunoTherapy of Cancer (2020)

The sharing of clinical trial data and biomarker data sets among the scientific community, whether the data originates from pharmaceutical companies or academic institutions, is of critical importance to enable the development of new and improved cancer immunotherapy modalities. Through data sharing, a better understanding of current therapies in terms of their efficacy, safety and biomarker data profiles can be achieved. However, the sharing of these data sets involves a number of stakeholder groups including patients, researchers, private industry, scientific journals and professional societies. Each of these stakeholder groups has differing interests in the use and sharing of clinical trial and biomarker data, and the conflicts caused by these differing interests represent significant obstacles to effective, widespread sharing of data. Thus, the Society for Immunotherapy of Cancer (SITC) Biomarkers Committee convened to identify the current barriers to biomarker data sharing in immuno-oncology (IO) and to help in establishing professional standards for the responsible sharing of clinical trial data. The conclusions of the committee are described in two position papers: Volume I—conceptual challenges and Volume II—practical challenges, the first of which is presented in this manuscript. Additionally, the committee suggests actions by key stakeholders in the field (including organizations and professional societies) as the best path forward, encouraging the cultural shift needed to ensure responsible data sharing in the IO research setting.
Resveratrol induced DNA methylation in ER+ breast cancer
Authors: Wenyi Qin, Weizhu Zhu, Edward Sauter
Journal: Cancer Research (2005)

2750  Background: Aberrant DNA methylation patterns, which display global hypomethylation and local promoter hypermethylation in tumor suppressor and growth regulatory genes, are a feature of most cancers, including breast malignancy. Epigenetic fluctuations in the degree of CpG islands represent an important mechanism by which gene function is selectively activated or silenced, as a result of modifying the binding of transcription factors and methyl-DNA binding proteins. A wide range of dietary compounds, such as resveratrol, can lead to global alterations in DNA methylation. Since dietary compounds are likely to induce epigenetic rather than mutational events, assessing changes in methylation, represent excellent targets to elucidate how diet factors may modify cancer risk and tumor behavior. Resveratrol, a compound commonly found in red wine and in the Japanese knotweed plant, possesses recognized health benefits for a wide range of human diseases including cancer. Resveratrol acts as an estrogen receptor (ER) antagonist in the presence of estrogen, leading to growth inhibition of ER positive breast cancer in a dose-dependant fashion. In the absence of estradiol, resveratrol has both agonist and antagonist effects depending on the dose used. Our goal was to determine the dose-dependant methylation effects of resveratrol on ER+ breast cancer cells. Methods: MCF-7 cells were treated with 5μM, 50 μM and 100 μM of resveratrol for 36 hours, DNA and RNA were extracted and differential methylation hybridization assays were conducted to screen an array containing 8716 CpG island tags for changes in methylation. Real-time PCR was also performed to assess expression levels of DNMT1 and DNMT3b, two of the three major isoforms of identified DNA methyltransferases, based on resveratrol treatment. Results and Conclusion: 65 loci have a two-fold or greater change in methylation status. Nine of the loci are genes with known identities, one of which is the tumor suppressor gene DLC-1 which is hypermethylated in various cancers. DLC-1 was demethylated following resveratrol treatment. DNMT1 and DNMT3b levels were inhibited by resveratrol in a dose dependant fashion. Resveratrol induces methylation changes in a variety of CpG islands, including those known to be altered in human cancer. This suggests that alterations in methylation may be an important mechanism by which resveratrol provides protective effects in human disease, including ER+ breast cancer.
Central Airway Tree Dysanapsis Extends to the Peripheral Airways
Authors: Motahareh Vameghestahbanati, Miranda Kirby, Naoya Tanabe, Dragoş M. Vasilescu, Wim Janssens, Stephanie Everaerts, Bart M. Vanaudenaerde, Andrea Benedetti, James C. Hogg, Benjamin M. Smith
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Blinatumomab after R-CHOP Debulking Therapy for Patients with Richter Transformation: Preliminary Results of the Multicenter Phase 2 Blinart Trial from the Filo Group
Authors: Romain Guieze, Loic Ysebaert, Lysiane Molina, Damien Roos-Weil, Anne-Sophie Michallet, Benedicte Hivert, Julie Gay, Alain Saad, Luc Mathieu Fornecker, Julien Broséus, Valérie Rouille, Laëtitia Auvray, Alain Jacques Delmer, Pierre Feugier
Journal: Blood (2020)
Five-Year Follow-Up of Ibrutinib Plus Rituximab Vs Placebo Plus Rituximab for Waldenstrom's Macroglobulinemia: Final Analysis From the Randomized Phase 3 iNNOVATETM Study
Authors: Christian Buske, Alessandra Tedeschi, Judith Trotman, Ramón García-Sanz, David MacDonald, Veronique Leblond, Béatrice Mahé, Charles Herbaux, Jeffrey V. Matous, Constantine S. Tam, Leonard T. Heffner, Marzia Varettoni, M. Lia Palomba, Chaim Shustik, Efstathios Kastritis, Steven P. Treon, Jerry Ping, Bernhard Hauns, Israel Arango-Hisijara, Meletios A Dimopoulos
Journal: Blood (2020)
Pre-Transplant Gene Expression May Predict Risk of Graft Versus Host Disease
Authors: Merav Bar, Darawan Rinchai, Mohammed Toufiq, Mohammed Elanbari, Dhanya Kizhakayil, Harshitha Shobha Manjunath, Rebecca Mathew, Irene M Cavattoni, Sabine Forer, Clarisa Brown, Nancy Miles, Sara Tomei, Chiara Cugno, Damien Chaussabel, Sara Deola
Journal: Blood (2020)
Dual CXCR4 and E-Selectin Inhibition (GMI-1359) Rapidly Increases AML Cellular Motility Prior to Intravasation and Vascular Niche Depletion Observed By Intravital Bone Marrow Two-Photon Microscopy
Authors: Tomasz Zal, Malgorzata Anna Zal, Mateusz Rytelewski, Kyung Hee Chang, Rodrigo Jacamo, William E. Fogler, John L. Magnani, Michael Andreeff
Journal: Blood (2020)
AMT-060 Gene Therapy in Adults with Severe or Moderate-Severe Hemophilia B Confirm Stable FIX Expression and Durable Reductions in Bleeding and Factor IX Consumption for up to 5 Years
Authors: Frank W.G. Leebeek, Karina Meijer, Michiel Coppens, Peter Kampmann, Robert Klamroth, Roger Schutgens, Giancarlo Castaman, Erhard Seifried, Joachim Schwaeble, Halvard Bönig, Eileen K Sawyer, Wolfgang A. Miesbach
Journal: Blood (2020)
Optimized Management of Nivolumab and Ipilimumab in Advanced Renal Cell Carcinoma: A Response-Based Phase II Study (OMNIVORE)
Authors: Rana R. McKay, Bradley A. McGregor, Wanling Xie, David A. Braun, Xiao Wei, Christos E. Kyriakopoulos, Yousef Zakharia, Benjamin L. Maughan, Tracy L. Rose, Walter M. Stadler, David F. McDermott, Lauren C. Harshman, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2020)

In this phase II response-adaptive trial, we investigated the rational application of immune checkpoint blockade in renal cell carcinoma (RCC; ClinicalTrials.gov identifier: NCT03203473).
Use of Venetoclax (VEN) and Hypomethylating Agents (HMA) in Newly Diagnosed Acute Myeloid Leukemia (AML) in the United States (US) - Real World (RW) Response, Treatment Duration, Dose and Schedule Modifications
Authors: William Donnellan, Tao Xu, Esprit Ma, Huan Jin, Melissa Montez, Michelle Choi, Grace Ku, Raj Anand Rajeswaran, Giridharan Ramsingh, Evelyn M. Flahavan
Journal: Blood (2020)
Oxidative stress and lipid peroxidation- induced etheno-dA, etheno-dC and malondialdehyde-dG adducts in human breast epithelium and lymphocytes.
Authors: Jagadeesan Nair, Xin Sun, Karl-Heinrich Adzersen, Helmut Bartsch
Journal: Cancer Research (2006)

5230  Endogenously generated DNA adducts are formed by oxidative stress and lipid peroxidation and are implicated in human cancers including breast cancer. In order to assess the formation of such DNA damage in the target organ and in surrogate samples, we have investigated the steady state levels of three endogenously formed DNA adducts: 1,N6-ethenodeoxyadenosine (edA), 3,N4-ethenodeoxyadenosine (edC) and malondialdehyde-deoxyguanosine adduct 3-(2-deoxy-beta-d-erythro-pentofuranosyl)pyrimido[1,2-alpha]purin-10(3H)one (M1dG), were measured in DNA isolated from lymphocytes and from breast ductal epithelial cells from the same subject. Female breast tissue samples were obtained after surgical reduction mammoplasty (RM, n=5), from asymptomatic tissue after surgery for benign breast diseases (BBD, n=6) and from non-tumorous tissue from breast cancer patients (BC, n=12). The DNA adducts were quantified using our immuno-enriched 32P-postlabelling methods. The mean edA and edC levels were significantly higher (p
Abstract 308: Reductive Carboxylation Contributes to Cardiac Adaptation in Response to the Oncometabolite D2-hydroxyglutarate
Authors: Anja Karlstaedt, Brandon Faubert, Heidi M Vitrac, Rebecca L Salazar, Benjamin D Gould, Ralph DeBerardinis, Heinrich Taegtmeyer
Journal: Circulation Research (2020)

Cancer cells rewire metabolism to support tumor growth and proliferation. In isocitrate dehydrogenase (IDH) 1 and 2 mutant tumors, increased plasma levels of the oncometabolite D-2-hydroxyglutarate (D2-HG) are associated with systemic effects, including myopathy. D2-HG causes inhibition of alpha-ketoglutarate dehydrogenase (AKGDH), which is associated with reduced cardiac contractile function. How tumor cells influence the metabolism of cardiomyocytes remains mostly unknown. Specific cancer cells use glutamine-dependent reductive carboxylation to circumvent defective mitochondrial metabolism by producing citrate and acetyl-CoA for lipid synthesis, which tumors require for growth. Here, we explore the hypothesis that inhibition of AKGDH by the oncometabolite D2-HG increases glutamine-dependent reductive carboxylation in the heart. We combined ex vivo rat heart perfusions with mass-spectrometry-based stable isotope tracer studies and in silico metabolic flux analysis. In response to D2-HG-mediated inhibition of AKGDH, we observed an increased reductive carboxylation of alpha-ketoglutarate to citrate rather than oxidative decarboxylation. This pathway increases glutamine uptake and glutamine-derived citrate formation in both working rat heart perfusions and cultured adult mouse ventricular cardiomyocytes. When we perfused rat hearts with 13C-labelled D2-HG, we observed a similarly increased formation of citrate. To identify which IDH isoform is responsible for redirecting carbon flux, we modulated IDH1, 2, and 3 in adult mouse ventricular cardiomyocytes using siRNAs. Reduced expression of IDH1 impaired reductive formation of citrate. Importantly, we observed a significant correlation between reductive citrate formation and epigenetic modifications of histones, including increased histone 3 lysine 9 acetylation and di-methylation. To explore these observations, we conducted ChIP-sequencing and identified distinct transcriptional remodeling. Taken together, we demonstrate how oncometabolic stress in the heart causes redirection of central carbon metabolism via reductive carboxylation, and provide evidence of how reductive-citrate formation may induce epigenetic modifications in the heart.
Return-to-Play Guidelines for Athletes After COVID-19 Infection
Authors: Dina N. Greene, Alan H. B. Wu, Allan S. Jaffe
Journal: JAMA Cardiology (2020)

Diana Santos-Ferreira, MD, MMed, IOC Dip Sp Phy; Rita Tomás, MD, MS, IOC Dip Sp Phy; Hélder Dores, PhD
FRI0612-HPR EFFECT OF THERMOFORMABLE ORTHOSES ON FOOT FUNCTION IN RHEUMATOID ARTHRITIS PATIENTS: PRELIMINARY RESULTS FROM AN OPEN CLINICAL TRIAL.
Authors: I. Aachari, H. Rkain, F. Safaa, L. Benzakour, T. Latifa, N. Alami, R. Guieu, Y. Jammes, N. Hajjaj-Hassouni, F. Allali
Journal: Annals of the Rheumatic Diseases (2020)

Background: Orthoses and footwear can play an important role in managing foot pathology in patients whose systemic disease is controlled. Foot orthoses are frequently prescribed in clinical practice as an intervention for people with rheumatoid arthritis (RA). Objectives: The aim of our study is to evaluate the impact of thermoformable orthoses on the functional index of the foot (FFI) in patients with rheumatoid arthritis. Methods: We conducted an open clinical trial, having consecutively included 14 patients (85.7% female, average age 54.8 ± 10 years) suffering from rheumatoid arthritis (median progression time of 9 years [5 - 12]). The average DAS28 was 2.7 ± 1.2 and the functional impact objectified by the Health Assessment Questionnaire (HAQ) was on average 0.9 ± 0.7. The median deadline from the start of RA and the onset of the foot problem was 3 years [0 – 7,75]. The foot problem was bilateral in 100% of the cases and inaugural in 85.7% of the cases. We evaluated the functional impact of foot injury for all our patients at baseline and 8 weeks after the use of thermoformable orthoses, based on the FFI (Foot function Index) measuring the impact of foot pathology on function in terms of pain, disability and activity limitation. The comparison of the FFI domains before and after the use of orthoses was carried out using parametric or nonparametric paired tests using The SPSS statistical software. Results: With the use of foot orthoses, FFI values decreased in all subscales (p=0,024) (pain, disability and activity limitation). This reduction was significant for disability (0,011) but not for pain and activity limitation. There were no significant correlations between the global FFI and the progression of RA, the duration of foot damage and the functional impact measured by the HAQ. Table 1. The comparison of the FFI domains before and after the use of orthoses. p significatif if&lt; 0,05; Test used: Non-parametric test for two linked samples. Conclusion: Foot orthoses were effective as an adjuvant in the management of rheumatoid foot. They significantly reduced disability as measured by the FFI. The absence of factors associated with pain and limitation of activity could possibly be related to the small sample size. Disclosure of Interests: None declared
Analysis of Genomic Landscape of Large Granular Lymphocyte Leukemia Reveals Etiologic Insights
Authors: HeeJin Cheon, Jeffrey C Xing, David S Chung, Mariella F Toro, Cait E Hamele, Thomas L. Olson, David J Feith, Aakrosh Ratan, Thomas P. Loughran
Journal: Blood (2020)
Association of Maternal Prepregnancy Body Mass Index With Fetal Growth and Neonatal Thalamic Brain Connectivity Among Adolescent and Young Women
Authors: Marisa N. Spann, Dustin Scheinost, Tianshu Feng, Kristiana Barbato, Seonjoo Lee, Catherine Monk, Bradley S. Peterson
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Higher maternal prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is associated with adverse long-term outcomes for offspring, including obesity, poorer cognitive and social abilities, and increased risk of psychiatric disorders. Less clear is whether higher maternal BMI disrupts fetal growth and brain development. <h3>Objective</h3> To investigate the association of maternal prepregnancy BMI with fetal growth and neonatal functional connectivity. <h3>Design, Setting, and Participants</h3> This prospective longitudinal cohort study was conducted from 2012 to 2017. Participants included nulliparous pregnant adolescent and young adult women, aged 14 to 19 years who were recruited in the second trimester through Columbia University Irving Medical Center and Weill Cornell Medical College. Women received routine prenatal care and had no major health problems at the time of recruitment. Data were analyzed from January 2018 to March 2020. <h3>Exposures</h3> Maternal prepregnancy BMI. <h3>Main Outcomes and Measures</h3> The main outcomes were fetal growth, measured as estimated fetal weight, and neonatal functional connectivity, measured using magnetic resonance imaging. Prepregnancy BMI and fetal ultrasonographic measurements were obtained from electronic health record review. Resting-state brain imaging data were acquired in infants within the first month of postnatal life. Functional connectivity was measured using intrinsic functional distribution and seed-based methods. <h3>Results</h3> Among 129 women recruited, 105 had ultrasonographic data from at least 2 points and were included in analyses. The mean (SD) age at delivery was 17.82 (1.31) years. Maternal prepregnancy BMI was positively associated with the slope of estimated fetal weight (β = 0.668; 95% CI, 0.163 to 1.175;<i>P</i> = .01) but not with fetal head circumference (β = −0.004; 95% CI, −0.024 to 0.016;<i>P</i> = .70). In a subsample of 45 infants with magnetic resonance imaging data, maternal prepregnancy BMI was positively correlated with global connectivity in the left thalamus. Using this thalamic region as a seed, higher maternal BMI was associated with greater local thalamic (both hemispheres) and lower frontothalamic connectivity. <h3>Conclusions and Relevance</h3> These results suggest that maternal prepregnancy BMI was associated with the development of regulation of body weight and thalamic functional brain connectivity in offspring even during fetal development.
Bone Marrow (BM) Delivery of Genetically-Modified (gm) Adult CD34+ Hematopoietic Stem and Progenitor Cells (HSPC) Improves Homing and Engraftment of Short-Term Progenitors over Long-Term Repopulating Hematopoietic Stem Cells
Authors: Sydney Felker, Archana Shrestha, Punam Malik
Journal: Blood (2020)
Male-Biased Spliceosome Mutations in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Impair pDC Activation and Apoptosis
Authors: Katsuhiro Togami, Sun Sook Chung, Vikas Madan, Christopher M. Kenyon, Lucia Cabal-Hierro, Justin Taylor, Sunhee Kim, Gabriel K Griffin, Mahmoud Ghandi, Jia Li, Yvonne Y. Li, Fanny Angelot-Delletre, Sabeha Biichle, Michael Seiler, Silvia Buonamici, Scott B Lovitch, Abner Louissaint, Elizabeth A Morgan, Fabrice Jardin, Pier Paolo Piccaluga, David M. Weinstock, Peter S. Hammerman, Henry Yang, Marina Konopleva, Naveen Pemmaraju, Francine Garnache-Ottou, Omar Abdel-Wahab, H. Phillip Koeffler, Andrew A Lane
Journal: Blood (2020)
Abstract 249: Plasma Exosomes Impair Angiogenesis in Ischemic Hind Limb of Diabetic Mice- Role of Histone Methylation
Authors: Zhongjian Cheng, May M Truongcao, Chunlin Wang, Venkata NS Garikipati, Yan Tang, Maria Cimini, Cindy Benedict, Grace Huang, Vandana Mallaredy, David Goukassian, Suresh K Verma, Walter J Koch, Raj Kishore
Journal: Circulation Research (2020)

Background: Critical limb ischemia (CLI) is one of most prevenient cardiovascular disease in diabetic patients. Recent evidence suggests that altered cargo and function of plasma exosomes (plasma-Exo) may play an important role in diabetes-induced cardiovascular complications. Here, we tested the hypotheses that inhibition of exosome biosynthesis/release improves ischemic hind limb (IHL) repair in db/db mice. Methods: Plasma-Exo from db/+ and db/db mice were isolated by density-gradient ultracentrifugation. Unilateral IHL in mice was conducted by ligation of left femoral artery. Blood perfusion in IHL was measured by Laser Doppler Imager. Results: Diabetic plasma-Exo impaired tube formation/migration of human microvascular endothelial cells (HMVECs) and blood perfusion in IHL of C57BL/6J mice. Exosome inhibitor GW4869 improved blood flow, capillary density, cell survival, and rescued necrosis of toe/toenail and fibrosis in IHL muscle of db/db mice. Mechanistically, diabetic plasma-Exo decreased secretion of pro-angiogenic factor Ang I&amp;II, artemin, FGF2 and IGFBP1&amp;2, and increased repressive transcriptional mark H3K27me3 and its methylase enhancer of zest homolog-2 (EZH2) in HMVECs. EZH2 inhibitor GSK343 rescued diabetic plasma-Exo-impaired tube formation and secretion of FGF2/artemin from HMVECs. Moreover, GW4869 reduced EZH2 and H3K27me3 protein expression in lung microvascular ECs of IHL db/db mice. Finally, diabetic plasma-Exo increased H3K27me3 level at promoter of artemin and FGF2. Conclusions: Diabetic plasma-Exo impair angiogenesis and IHL injury repair. Diabetic plasma-Exo impair reparative property of ECs via, at least in part, enhancement of EZH2/H3K27me3/artemin and FGF2 cascade. Inhibition of plasma-Exo biosynthesis/secretion improve IHL repair in db/db mice. Plasma-Exo may be a novel target for prevention/treatment of CLI in diabetic patients.
Fatty acid metabolism underlies venetoclax resistance in acute myeloid leukemia stem cells
Authors: Brett M. Stevens, Courtney L. Jones, Daniel A. Pollyea, Rachel Culp-Hill, Angelo D’Alessandro, Amanda Winters, Anna Krug, Diana Abbott, Madeline Goosman, Shanshan Pei, Haobin Ye, Austin E. Gillen, Michael W. Becker, Michael R. Savona, Clayton Smith, Craig T. Jordan
Journal: Nature Cancer (2020)
Interim Results of an Open-Label Phase IB/II Multi-Arm Study of OX40 Agonist Monoclonal Antibody (mAb), Anti-PDL1 Mab, Smoothened Inhibitor, Anti-CD33 Mab, Bcl-2 Inhibitor, and Azacitidine As Single-Agents and As Combinations for Relapsed/Refractory Acute Myeloid Leukemia
Authors: Nicholas J. Short, Tapan M. Kadia, Courtney D. DiNardo, Naveen Pemmaraju, Gautam Borthakur, Guillermo Garcia-Manero, Elias Jabbour, Koji Sasaki, Ghayas C. Issa, Guillermo Montalban-Bravo, Prithviraj Bose, Jan A. Burger, Darla Miller, Lynette Alexander-Williams, Farhad Ravandi, Marina Konopleva, Hagop M. Kantarjian, Naval Daver
Journal: Blood (2020)
Phototherapy-based combination strategies for bacterial infection treatment
Authors: Guoqing Wei, Guang Yang, Yi Wang, Hezhong Jiang, Yiyong Fu, Guang Yue, Rong Ju
Journal: Theranostics (2020)

The development of nanomedicine is expected to provide an innovative direction for addressing challenges associated with multidrug-resistant (MDR) bacteria. In the past decades, although nanotechnology-based phototherapy has been developed for antimicrobial treatment since it rarely causes bacterial resistance, the clinical application of single-mode phototherapy has been limited due to poor tissue penetration of light sources. Therefore, combinatorial strategies are being developed. In this review, we first summarized the current phototherapy agents, which were classified into two functional categories: organic phototherapy agents (