tbuckley/cabot-search huggingface dataset:
Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial
Authors: Etienne Garin, Lambros Tselikas, Boris Guiu, Julia Chalaye, Julien Edeline, Thierry de Baere, Eric Assenat, Vania Tacher, Corentin Robert, Marie Terroir-Cassou-Mounat, Denis Mariano-Goulart, Giuliana Amaddeo, Xavier Palard, Antoine Hollebecque, Marilyne Kafrouni, Hélène Regnault, Karim Boudjema, Serena Grimaldi, Marjolaine Fourcade, Hicham Kobeiter, Eric Vibert, Samuel Le Sourd, Lauranne Piron, Danièle Sommacale, Sophie Laffont, Boris Campillo-Gimenez, Yan Rolland, Etienne Garin, Julien Edeline, Corentin Robert Robert, Samuel Le Sourd, Xavier Palard, Sophie Laffont, Boris Campillo-Gimenez, Yan Rolland, Marc Pracht, Valérie Ardisson, Laurence Lenoir, Karim Boudjema, Lambros Tselikas, Thierry De Baere, Marie Terroir-Cassou-Mounat, Antoine Hollebecque, Serena Grimaldi, Frederic Deschamps, Michel Ducreux, Maximiliano Gelli, Eric Vibert, Boris Guiu, Lauranne Piron, Marilyne Kafrouni, Marjolaine Fourcade, Eric Assenat, Denis Mariano-Goulart, Christophe Cassinotto, Carole Allimant, Julia Chalaye, Hélène Regnault, Giuliana Amaddeo, Danièle Sommacale, Hicham Kobeiter, Vania Tacher, Sophie Bonnot-Lours, Margarita Marie, Emmanuel Itti, Lionel Lerman, Mukedaisi Abulizi, Alain Luciani, Charlotte E. Costentin, Milan Milliner
Journal: The Lancet. Gastroenterology & hepatology (2020)
Body Mass Index and Clinical Factors Associated with Monoclonal Gammopathy of Undetermined Significance (MGUS) Progression in Olmsted County, Minnesota
Authors: Geffen Kleinstern, Dirk Larson, Cristine Allmer, Aaron D. Norman, Jason P Sinnwell, S. Vincent Rajkumar, Angela Dispenzieri, Robert A. Kyle, Susan L. Slager, Shaji K. Kumar, Celine M. Vachon
Journal: Blood (2020)
Striking Association of Lymphoid Enhancing Factor (LEF1) Overexpression and <i>DUSP22</i> rearrangements in Anaplastic Large Cell Lymphoma
Authors: Aishwarya Ravindran, Andrew L. Feldman, Rhett P. Ketterling, Surendra Dasari, Karen Rech, Ellen D. McPhail, Paul J Kurtin, Min Shi
Journal: Blood (2020)
Increase in Mortality and Second Neoplasms in Chronic Lymphocytic Leukemia with Pro/Pro Genotype of TP53 Codon 72
Authors: Martin Cabero-Becerra, Jose Antonio Garcia Vela, Pedro Sanchez-Godoy, Angel Arias-Arias, Miguel Piris-Villaespesa, Nuria Pérez - Sanz, Sara Nova-Gurumeta, Belen Fernández-Cuevas, Jose A. Garcia-Marco
Journal: Blood (2020)
High-Grade B-Cell Lymphomas with MYC and BCL2 Translocations Lack Tumor-Associated Macrophages and PD-L1 Expression: A Possible Noninflamed Subgroup
Authors: Marie Fredslund Breinholt, Douglas NP de Oliveira, Tobias Wirenfeldt Klausen, Lone Schejbel, Anne Ortved Gang, Mette Ø Pedersen, Mette Vestergaard Elbæk, Erik Clasen-Linde, Signe Ledou Nielsen, Helle Knudsen, Estrid Hogdall, Peter H. Norgaard
Journal: Blood (2020)
Social Determinants of Health and Diabetes: A Scientific Review
Authors: Felicia Hill-Briggs, Nancy E. Adler, Seth A. Berkowitz, Marshall H. Chin, Tiffany L. Gary-Webb, Ana Navas-Acien, Pamela L. Thornton, Debra Haire-Joshu
Journal: Diabetes Care (2020)

Decades of research have demonstrated that diabetes affects racial and ethnic minority and low-income adult populations in the U.S. disproportionately, with relatively intractable patterns seen in these populations’ higher risk of diabetes and rates of diabetes complications and mortality (1). With a health care shift toward greater emphasis on population health outcomes and value-based care, social determinants of health (SDOH) have risen to the forefront as essential intervention targets to achieve health equity (2–4). Most recently, the COVID-19 pandemic has highlighted unequal vulnerabilities borne by racial and ethnic minority groups and by disadvantaged communities. In the wake of concurrent pandemic and racial injustice events in the U.S., the American College of Physicians, American Academy of Pediatrics, Society of General Internal Medicine, National Academy of Medicine, and other professional organizations have published statements on SDOH (5–8), and calls to action focus on amelioration of these determinants at individual, organizational, and policy levels (9–11).

In diabetes, understanding and mitigating the impact of SDOH are priorities due to disease prevalence, economic costs, and disproportionate population burden (12–14). In 2013, the American Diabetes Association (ADA) published a scientific statement on socioecological determinants of prediabetes and type 2 diabetes (15). Toward the goal ofunderstanding and advancing opportunities for health improvement among the population with diabetes through addressing SDOH, ADA convened the current SDOH and diabetes writing committee, prepandemic, to review the literature on 1 ) associations of SDOH with diabetes risk and outcomes and 2 ) impact of interventions targeting amelioration of SDOH on diabetes outcomes. This article begins with an overview of key definitions and SDOH frameworks. The literature review focuses primarily on U.S.-based studies of adults with diabetes and on five SDOH: socioeconomic status (education, income, occupation); neighborhood and physical environment (housing, built environment, toxic environmental …
Bendamustine-Bortezomib-Dexamethasone (BVD) in Heavily Pretreated Multiple Myeloma: Old/New in NOVEL Agents' Era
Authors: Claudio Cerchione, Lucio Catalano, Davide Nappi, Stefano Rocco, Salvatore Palmieri, Anna Emanuele Pareto, Gerardo Musuraca, Alessandro Lucchesi, Fabrizio Pane, Felicetto Ferrara, Giovanni Martinelli
Journal: Blood (2020)
Updated results of single-agent ibrutinib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL).
Authors: Christian Grommes, Igor T. Gavrilovic, Thomas Joseph Kaley, Craig Nolan, Antonio Marcilio Padula Omuro, Julia Wolfe, Elena Pentsova, Vaios Hatzoglou, Ingo K. Mellinghoff, Lisa Marie DeAngelis
Journal: Journal of Clinical Oncology (2017)

7515 Background: PCNSL is an aggressive primary brain tumor with median progression free survival (PFS) after upfront methotrexate-based chemotherapy of 2-3 years. Outcome and treatment options are poor for recurrent/refractory (r/r) disease. Ibrutinib has shown promising clinical response in Mantle cell lymphoma, CLL, Marginal Zone, and Waldenström. This trial investigates Ibrutinib in patients with r/r PCNSL and SCNSL. Methods: Eligible patients had r/r PCNSL or SCNSL, age≥18, ECOG≤2, normal end-organ function, and unrestricted number of CNS directed prior therapies. In patients with SCNSL disease, systemic disease needed to be absent. Results: Twenty-five patients were enrolled (3 at 560 mg; 22 at 840 mg). Median age was 68 (range 21-85); 15 were women. Median ECOG was 1 (0: 2, 1: 15, 2: 8). 64% had PCNSL and 36% SCNSL; 68% had recurrent disease. Seventeen had parenchymal disease, 3 isolated cerebrospinal fluid (CSF) involvement and 5 both. Seven grade 4 adverse events were observed in 7 patients neutropenia (in 3 patients), lymphopenia (2), sepsis (1), and ALT elevation (1). Fourteen patients developed 20 grade 3 toxicities, including lymphopenia in 5 patients, hyperglycemia in 3, ALT elevation in 2, thrombocytopenia in 2, lung infection in 2, AST elevation in 1, neutropenia in 1, urinary tract infection in 1, colitis in 1, febrile neutropenia in 1 and fungal encephalitis in 1. The most common toxicities at any grade were hyperglycemia, thrombocytopenia and anemia of which most were grade 1/2. No grade 5 events have been observed. After a median follow-up of 414 days (range 289-674), 22/25 patients were evaluated for response (3 did not complete at least 15 days of drug treatment). Over all response was 68% (17/22; 77% (17/22) in patient that completed at least 15 days of drug treatment) with 10 CR, 7 PR, 2 SD and 3 PD as best response. The median PFS is 4.6 months (5.4 months in patients that completed at least 15 days of drug treatment; longest: 15.3 months). The median overall survival has not been reached. Conclusions: Patients with CNS lymphoma tolerate Ibrutinib with manageable adverse events. Clinical response was seen in 68% of CNS lymphoma patients. Clinical trial information: NCT02315326.
Single Centre, Retrospective Study to Evaluate Treatment Outcomes Following Tyrosine Kinase Inhibitor for Chronic Gvhd Treatment Including Ruxolitinib, Ibrutinib and Imatinib
Authors: Swe Mar Linn, Omar Abduljalil, Igor Nicolas Novitzky-Basso, RAM V Nampoothiri, Ivan Pasic, Zeyad Al-Shaibani, Wilson Lam, Arjun Law, Fotios Michelis, Armin Gerbitz, Auro Viswabandya, Jeffrey H. Lipton, Rajat Kumar, Jonas Mattson, Dennis Dong Hwan Kim
Journal: Blood (2020)
An Expanded Tool Kit for Modeling the Oncogenic Functions of KRAS
Authors: Kaja Kostyrko, E. Alejandro Sweet-Cordero
Journal: Cancer Discovery (2020)

Abstract Summary: Zafra and colleagues developed new mouse models to study the role of specific KRAS mutations in pancreatic, lung, and colon cancer pathogenesis. Their studies clearly describe the distinct ability of these mutations to drive pathogenesis in a tissue-specific fashion. See related article by Zafra et al., p. 1654.
Risk of Thyroid Dysfunctions with Use of Immune Checkpoint Inhibitors: A Meta-Analysis of Randomized Controlled Trials
Authors: Muhammad Yasir Anwar, Unaiza Faizan, Muhammad Khawar Sana, Muhammad Ans Sharif, Ali Anjum, Hafsa Tahir Chaudry, Sara Ashraf, Muhammad Ashar Ali, Arshia Akbar, Faiz Anwer
Journal: Blood (2020)
Embryonic stem cell-derived mesenchymal stem cells promote colon epithelial integrity and regeneration by elevating circulating IGF-1 in colitis mice
Authors: Jun Xu, Xiaofang Wang, Jiaye Chen, Shengbo Chen, Zhijun Li, Hongbin Liu, Yang Bai, Fachao Zhi
Journal: Theranostics (2020)

Rationale: Mesenchymal stem cells (MSCs) show promising therapeutic potential in treating inflammatory bowel disease (IBD) due to their immunomodulatory and trophic functions. However, their efficacy is influenced by tissue origin, donator condition, isolation, and expansion methods. Here, we generated phenotypically uniform MSCs from human embryonic stem cells (T-MSCs) and explored the molecular mechanisms involved in promoting mucosal integrity and regeneration in colitis mice. Methods: T-MSCs were injected intravenously into mice with dextran sulfate sodium (DSS)-induced colitis, and the in vivo distribution and therapeutic efficacy were evaluated. We performed serum cytokine antibody microarrays to screen potentially effective proteins and examined the therapeutic effect of insulin-like growth factor-1 (IGF-1). Colon epithelial regeneration potential was evaluated, and RNA sequencing was employed to determine the underlying molecular mechanisms. Finally, in vitro IGF-1 stimulation was performed to assess its effect on cell functions and organoid growth. Results: Intravenous administration of T-MSCs alleviated colitis in both acute and chronic DSS mouse models. Labeled T-MSCs were mainly distributed in the lungs, liver, and spleen after systemic infusion. The antibody array analysis of serum cytokines indicated that the IGF-1 level was increased in the treatment group, and serum ELISA further confirmed its elevation in the regeneration stage. Intraperitoneal injection of IGF-1 receptor inhibitors abrogated the anti-inflammatory activity of T-MSCs. The colonic epithelium of the treatment group showed greater regenerative potency than the controls and the IGF1R-PI3K-AKT pathway was up-regulated. RNA sequencing showed that T-MSC treatment contributed to colonic cell integrity and promoted xenobiotic metabolism. In vitro IGF-1 stimulation promoted the growth and proliferation of colon cells and organoids. Conclusions: Intravenous infusion of T-MSCs alleviated colitis in mice by elevating the circulating IGF-1 level. Increased IGF-1 maintained the integrity of epithelial cells and contributed to their repair and regeneration. Our study has identified T- MSCs as a potential cell resource for IBD treatment.
Carfilzomib, Dexamethasone, and Daratumumab Versus Carfilzomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Subgroup Analysis of the Phase 3 Candor Study in Patients with Early or Late Relapse
Authors: Katja Weisel, George F. Geils, Lionel Karlin, Peter Mollee, Tae-Hoon Chung, Chang-Ki Min, Kazutaka Sunami, Amanda Goldrick, Belle Fang, Jessica Fowler, Maria-Victoria Mateos
Journal: Blood (2020)
The Expression of Chromosome Region Maintenance Protein 1 (CRM1) in Large Cell Lymphoma
Authors: Jithma P. Abeykoon, Paul J. Hampel, Rebecca L. King, Adam J Wood, Melissa C. Larson, Kevin E. Nowakowski, Saurabh Zanwar, Aishwarya Ravindran, Matthew J. Maurer, Linda Wellik, Jonas Paludo, Brian K. Link, James R. Cerhan, Xiaosheng Wu, Thomas M. Habermann, Thomas E. Witzig
Journal: Blood (2020)
Abstract 16356: Hyperuricemia is an Independent Risk Factor for Cardiovascular Disease; A Sub-Analysis for REAL-CAD Study
Authors: Masanari Kuwabara, Tetsuji Kaneko, Ikki Komatsu, Nobuyuki Komiyama, Yasuo Ohashi, Ryozo Nagai, Satoshi Iimuro
Journal: Circulation (2019)

Introduction: REAL-CAD study showed that high-dose (4 mg/d) compared with low-dose (1 mg/d) pitavastatin therapy significantly reduced cardiovascular events in patients with stable coronary artery ...
SAT0195 ABNORMITY TFH SUBSETS INDICATE DISEASE ACTIVITY WHILE SIROLIMUS THERAPY RESTORES THE PD-1+ICOS+TFH/ACTIVATED TFR BALANCE IN PRIMARY SJOGREN’S SYNDROME PATIENTS
Authors: Y. Wang, J. Luo, C. Gao, X. C. Zhao
Journal: Annals of the Rheumatic Diseases (2020)

Background: Immune imbalance between follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells is a characteristic of primary Sjogren’s syndrome (pSS) [1]. The heterogeneity among Tfh and Tfr can be elucidated by separating them into different subsets based on the expression molecular characteristics. Objectives: The aim of this study was to investigate the role of Tfh and Tfr subsets, and to evaluate the effects of sirolimus on these cells. Methods: In this study, we enrolled 51 pSS patient and 26 healthy controls (HCs), and analyzed the frequencies and absolute counts of circulating Tfh and Tfr subsets, and serum levels of cytokines. Within these patients, analyses of above T cells in twelve patients before and after treatment with sirolimus. Clinical indicators and correlations with follicular T cells were systematically analyzed. The diagnostic value for CD4+CXCR5+T cells was evaluated by the areas under the receiver operating characteristic curves (AUC). Results: Patients with pSS had higher frequencies and absolute numbers of PD-1+ICOS+Tfh cells, but lower levels of activated Tfr cells cells, thereby resulting in elevated ratios of PD-1+ICOS+Tfh/activated Tfr. In addition, PD-1+Tfh cells levels were lower in pSS patients than in HCs. Interestingly, the ratio of PD-1+ICOS+Tfh/activated Tfr was a strong predictor of pSS diagnosis. However, sirolimus therapy resulted in significant reductions in PD-1+ICOS+Tfh cells and the PD-1+ICOS+Tfh/activated Tfr ratio in pSS patients. We also found increased numbers of PD-1+ICOS+Tfh cells were associated with B cells, while decreased numbers of Tfr and their subsets were strongly associated with aTreg cells in pSS patients. The ESSDAI [2] was positively correlated with PD-1+ICOS+Tfh cell frequency, but was negatively correlated with PD-1+Tfh cell count. Conclusion: These findings suggest that the PD-1+ICOS+Tfh cell:activated Tfr cell ratio and PD-1+Tfh cells constitute potential novel biomarkers for pSS, and Tfr cells and subsets resemble derived aTreg cells. Furthermore, the PD-1+ICOS+Tfh cells as a biomarker of disease activity and provide new ground to verify the therapeutic implications of sirolimus as an innovative drug in pSS. References: [1]Fonseca VR, Romão VC, Agua-Doce A, Santos M, López-Presa D, Ferreira AC, et al. The Ratio of Blood T Follicular Regulatory Cells to T Follicular Helper Cells Marks Ectopic Lymphoid Structure Formation While Activated Follicular Helper T Cells Indicate Disease Activity in Primary Sjogren’s Syndrome. Arthritis Rheumatol 2018; 70:774-784. [2]Seror R, Ravaud P, Bowman SJ, Baron G, Tzioufas A, Theander E, et al. EULAR Sjogren’s syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren’s syndrome. Ann Rheum Dis 2010; 69:1103–9. Disclosure of Interests: None declared
Robert William Walker Paterson
Authors: Ian Paterson
Journal: BMJ (2020)

Robert William Walker Paterson (“Robin”) was born in Blantyre, Lanarkshire, on 26 May 1938, the only child of William and Jessie Paterson. William Paterson was the chemist in Blantyre while Jessie worked during the war as a nurse at Hairmyres Hospital. Robin attended Hamilton Primary School from 1942 to 1949 and then Hamilton Academy from 1949 to 1951 before being transferred as a boarder to Strathallan School in Perthshire, where he spent five happy years. This latter move was made on account of his studies suffering somewhat because of his keen interest in sports. He proceeded …
Cidofovir, a Choice for Salvage Treatment of CMV Infection in the Patients with Haploidentical Hematopoitic Stem Cell Transplantation
Authors: Zhao Yin, Na Xu, Ling Jiang, Pengcheng Shi, Zhiping Fan, Fen Huang, Qifa Liu, Jing Sun, Guopan Yu
Journal: Blood (2020)
Abstract PO-130: The mitochondrial protein ATAD3A promotes cisplatin resistance in oral squamous cell carcinoma
Authors: Liwei Lang, Leslie Duncan, Caleb Jensen, Chloe Shay, Yong Teng
Journal: Cancer Research (2020)

Abstract Cisplatin is well-known for its damaging effect on nuclear DNA, leading to cell death due to blockage of DNA replication and transcription, but this activity cannot fully explain why cisplatin displays cytotoxicity in post-mitotic tissues, suggesting other mechanisms may be in play. Many studies have challenged the current model of cisplatin resistance, however, the precise mechanism behind is still unknown. Here, we report that the mitochondrial protein ATAD3A functions as an oncogene in oral squamous cell carcinoma (OSCC), promoting cell proliferation and enhancing the ability of colony formation and anchorage-independent growth. Moreover, ATAD3A is involved in cisplatin resistance in OSCC, and knockdown of ATAD3A enhanced the sensitivity of OSCC cells to cisplatin. It appears that ATAD3A-mediated cisplatin resistance is regulated by other mechanisms rather than its expression levels, as evidenced by overexpression of a Walker A (WA) dead mutant of ATAD3A leads to a suppression in OSCC cell growth and resensitizes cisplatin-resistant OSCC cells to this drug, indicating a potent dominant-negative effect of defective ATP-binding of ATAD3A in chemotherapy. Our study demonstrates for the first time that ATAD3A plays an oncogenic role in OSCC and abrogating its ATP-binding ability may represent a promising regimen for better treatment of patients with OSCC, especially for those who suffer from cisplatin-resistance. Citation Format: Liwei Lang, Leslie Duncan, Caleb Jensen, Chloe Shay, Yong Teng. The mitochondrial protein ATAD3A promotes cisplatin resistance in oral squamous cell carcinoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-130.
Clinical Characteristics and Follow-up Post-Surgery of Women with Bia-ALCL Operated at a Single Institution
Authors: Paola Ghione, Joshua Vorstenbosch, Peter G. Cordeiro, Maria E. Arcila, Alison J. Moskowitz, Colette Owens, Natasha Galasso, Jonas A. Nelson, Ahmet Dogan, Colleen M. McCarthy, Steven M. Horwitz
Journal: Blood (2020)
Diagnosis-to-Treatment Interval Is an Important Prognostic Factor with a Time-Dependent Effect Predicting Event-Free Survival after 12 Months from First-Line Treatment in Newly Diagnosed Diffuse Large B-Cell Primary CNS Lymphoma
Authors: Marie-Charlotte Laude, Edith Julia, Emmanuelle Nicolas-Virelizier, Gabriel Antherieu, Violaine Safar, Philippe Rey, Emmanuelle Ferrant, Alexandra Traverse-Glehen, Catherine Chassagne-Clément, David Meyronet, Anne Lazareth, Helene Lequeu, Camille Golfier, Gabriel Brisou, Dana Ghergus, Pierre Sesques, Lionel Karlin, Gilles Salles, Emmanuel Bachy, François Ducray, Fadhela Bouafia, Youenn Drouet, Herve Ghesquieres
Journal: Blood (2020)
Lenalidomide As Maintenance Therapy after R-CHOP Has No Protecting Effect for Central Nervous System Relapse in Frontline Treatment of Diffuse Large B-Cells Lymphoma. an Ancillary Studies of the Remarc Study
Authors: Sophie Bernard, Hervé Ghesquieres, Rene-Olivier Casasnovas, Maria Gomes Da Silva, Pierre Feugier, Franck Morschhauser, Judith Trotman, Richard Greil, Dolores Caballero, Sebastian Grosicki, Koen Van Eygen, Christiane Copie, Corinne Haioun, Catherine Thieblemont
Journal: Blood (2020)
Abstract MP112: Optogenetic Manipulation of Macrophage Electrical Excitability Modulates Cardiac Rhythm in Developing Zebrafish
Authors: Shannon E Martin, Jessica Plavicki
Journal: Circulation Research (2020)

Despite the unremitting research surrounding heart development and disease, congenitalheart defects (CHD) remain the most common birth defect worldwide. Arrhythmias are aleading cause of morbidity and mortality in CHD patients, though the etiologies ofarrhythmia are not well understood. Notably, there have been considerable advances inour understanding of cardiac macrophage biology in both regulating developmentalprocesses and modulating adult cardiac conduction. However, it is not known 1) whenmacrophage-derived signals influence heart electrical function, nor 2) if macrophages areintegral to the development and function of the embryonic or juvenile conduction system.Using transparent zebrafish, a genetically tractable and well-established developmentalmodel, we employ advanced microscopy techniques to visualize cardiac macrophages inreal-time and in vivo throughout heart development. We demonstrate here that embryoniccardiac macrophages display synchronous calcium activity in-time with heartbeat. Usingoptogenetics to stimulate macrophage electrical activity via light-gated ion channels, weshow that macrophage-specific expression of channelrhodopsin, a cation channel, orhalorhodopsin, a chloride channel, can directly influence heartrate. Thus, embryonicmacrophages can functionally manipulate cardiac rhythm in developing zebrafish.Further, loss of embryonic macrophages, either through drug-inducible ablation orembryonic macrophage genetic mutation, disrupts organization of both the embryonic andadult ventricular myocardium. We therefore hypothesize cardiac macrophages arefunctionally important in embryonic conduction and fetal heart development, such thatembryonic macrophage loss negatively impacts long-term cardiac health. This work willprovide novel insight into potential contributing factors of cardiac developmentaldysregulation and macrophages as targets of intervention for arrhythmia.