tbuckley/cabot-search huggingface dataset:
Low-Dose Total Skin Electron Beam Therapy as Part of a Multimodality Regimen for Treatment of Sézary Syndrome
Authors: Joseph S. Durgin, Neha N. Jariwala, Maria Wysocka, Kevin K. Zhang, Amit Maity, Bernice Benoit, John P. Plastaras, Daniel J. Lewis, Jaclyn M. Rosenthal, Jessica E. Teague, Sara Berg, Christina Del Guzzo, Ellen J. Kim, Carmela Vittorio, Paul L. Haun, Sara S. Samimi, Jennifer Villasenor-Park, Joanne Inverso, Rachael A. Clark, Alain H. Rook
Journal: JAMA Dermatology (2020)

Sézary syndrome (SS) is an advanced form of cutaneous T-cell lymphoma with few long-term remissions observed.To profile 3 patients with SS who have experienced long-term remission following the addition of low-dose total skin electron beam therapy (TSEBT) to systemic regimens of extracorporeal photopheresis, bexarotene, and interferon-γ.This is a retrospective case series with additional investigations of patient-donated samples to assess therapeutic response. The study was conducted at the University of Pennsylvania Cutaneous Lymphoma Clinic and follows 3 patients with stage IVA1 CD4+ SS who presented to the clinic between November 1, 2009, and November 1, 2017, and who had a history of SS that was refractory to multimodality systemic therapy prior to receiving low-dose TSEBT.Patients were treated in a multimodality fashion with combined extracorporeal photopheresis, bexarotene, interferon-γ, and low-dose TSEBT.To characterize treatment responses in these patients, the extent of skin disease was measured with the modified severity weighted assessment tool. Blood disease was measured with flow cytometric assessments of Sézary cell count, CD4:CD8 ratio, and high throughput sequencing of the T-cell receptors. To assess for restoration of immune function, we measured markers of immune exhaustion, including PD-1 (programmed cell death 1), TIGIT (T-cell immunoreceptor with immunoglobulin and ITIM domains), CTLA4 (cytotoxic T-lymphocyte-associated protein 4), TOX (thymocyte selection-associated high mobility group box protein), and Foxp3 (forkhead box P3) on circulating CD4 and CD8 T cells, along with production capacity of interferon-γ by lymphocytes following activation stimuli.Following administration of low-dose TSEBT and maintenance of the other therapies, remissions ranged from 24 to 30 months, with complete responses in 2 patients ongoing. Markers of immune exhaustion including PD-1, TIGIT, CTLA4, TOX, and Foxp3 were significantly reduced from baseline following TSEBT, along with enhanced production capacity of interferon-γ by lymphocytes following activation stimuli. High throughput sequencing demonstrated near-complete eradication of the circulating clone among 2 of 3 patients with stable levels in 1.We describe 3 patients who achieved long-term clinical and molecular remissions following low-dose TSEBT as part of a multimodality regimen for treatment of SS. As long-term remissions in SS are uncommon, this approach demonstrates promise, and clinical trials should be considered.
The Relative Risk of Prognostic Factors of Age Stratified Multiple Myeloma
Authors: Chenxing Du, Yi Wang, Xue-Han Mao, Yuting Yan, Jiahui Liu, Huishou Fan, Yan Xu, Weiwei Sui, Shuhui Deng, Fu Mingwei, Chengwen Li, Jiawei Zhao, Shuhua Yi, Dehui Zou, Yaozhong Zhao, Lugui Qiu, Gang An
Journal: Blood (2020)
Gene deficiency or pharmacological inhibition of PDCD4-mediated FGR signaling protects against acute kidney injury
Authors: Xu Jing, Dandan Ren, Fei Gao, Ye Chen, Xiao Wu, Yue Han, Qingsheng Han, Liang Li, Xiaojie Wang, Wei Tang, Yan Zhang
Journal: Acta Pharmaceutica Sinica B (2020)

Recent studies have shown that programmed cell death 4 (PDCD4) modulates distinct signal transduction pathways in different pathological conditions. Despite acute and chronic immune responses elicited by ischemia contributing to the functional deterioration of the kidney, the contributions and mechanisms of PDCD4 in acute kidney injury (AKI) have remained unclear. Using two murine AKI models including renal ischemia/reperfusion injury (IRI) and cisplatin-induced AKI, we found that PDCD4 deficiency markedly ameliorated renal dysfunction and inflammatory responses in AKI mice. Consistently, upregulation of PDCD4 was also confirmed in the kidneys from patients with biopsy confirmed acute tubular necrosis from a retrospective cohort study. Moreover, we found that overexpression of Fgr, a member of the tyrosine kinase family, dramatically aggravated renal injury and counteracted the protective effects of PDCD4 deficiency in AKI mice. We discovered that FGR upregulated NOTCH1 expression through activating STAT3. Most importantly, we further found that systemic administration of ponatinib, a tyrosine kinase inhibitor, significantly ameliorated AKI in mice. In summary, we identified that PDCD4 served as an important regulator, at least in part, of FGR/NOTCH1-mediated tubular apoptosis and inflammation in AKI mice. Furthermore, our findings suggest that ponatinib-mediated pharmacologic targeting of this pathway had therapeutic potential for mitigating AKI.
IMAGINE—IMpact Assessment of Guidelines Implementation and Education: The Next Frontier for Harmonising Urological Practice Across Europe by Improving Adherence to Guidelines
Authors: Philip Cornford, Emma Jane Smith, Steven MacLennan, Nuno Pereira-Azevedo, Monique J. Roobol, Nicolaas Lumen, Louise Fullwood, Eilidh Duncan, Jennifer Dunsmore, Karin Plass, Maria J. Ribal, Thomas Knoll, Anders Bjartell, Hendrick Van Poppel, James N’Dow, Alberto Briganti, Karl Dorfinger, Irene Resch, Mischinger Johannes, Isabel Heidegger, Christophe Assenmacher, Thierry Roumeguère, Karel Decaestecker, Lieven Goeman, Thomas Adams, Marincho Georgiev, Krassimir Yanev, Marincho Georgiev, Aleksandar Timev, Igor Tomašković, Tomislav Kuliš, Stavros Charalampous, Dimitris Kontaxis, Marko Babjuk, Roman Zachoval, Tomáš Pitra, Vojtěch Novák, Lars Lund, Martin Kivi, Peep Baum, Toomas Tamm, Pritt Veskimae, Rauno Okas, Kanerva Lahdensuo, Kimmo Taari, Heikki Seikkula, Pyry Jämsä, Xavier Gamé, George Fournier, Alexandre Ingels, Gaelle Fiard, Guillaume Ploussard, Jens Rassweiler, Stefanie Schmidt, Jennifer Kranz, Susanne Krege, Ioannis Gkialas, Anthanasios Dellis, Nikolaos Ferakis, Dionysios Mitropoulos, Peter Ryan, John Paul Sweeney, Eamonn Rogers, Derek Hennessy, Niall. F. Davis, Walter Artibani, Francesco Porpiglia, Salvatore Giuseppe Voce, Maurizio Brausi, Maria A. Cerruto, Francesco Esperto, Matteo Manfredi, Mindaugas Jievaltas, Aušvydas Patašius, Albertas Čekauskas, Stasys Auškalnis, Peter Mulders, Frank Martens, Kathleen W.M. D'Hauwers, Piotr Chlosta, Anna Katarzyna Czech, Katarzyna Gronostaj, Mikołaj Przydacz, Pedro Coelho Nunes, Luís Abranches-Monteiro, Ricardo Pereira e Silva, Frederica Furriel, Pedro Gomes Monteiro, Ioanel Sinescu, Cristian Surcel, Catalin Baston, Robert Ionut Stoica, Vlad Olaru, Boris Kollárik, Ivan Mincik, Ľuboš Rybár, Viktor Kováčik, Ivan Perečinský, Boris Kosuta, Marko Zupancic, Milena Taskovska, Uros Kacjan, Andraz Miklavzina, Manuel Esteban Fuertes, Mario Alvarez-Maestro, Antoni Vilaseca, Rodrigo García-Baquero, Lotta Renström Koskela, Johan Styrke, Gezim Galiqi, Bilbil Hoxha, Evisa Zhapa, Rezart Xhani, Sergey Fanarjyan, Ruben Hovhannisyan, Avoyan E. Armen, Rafael Badalyan, Mustafa Hiroš, Davor Tomić, Damir Aganović, Archil Chkhotua, David Nikoleishvili, Zara Tchanturaia, Sigurdur Gudjónsson, Eirikur Orri Gudmundsson, Rafn Hilmarsson, Emil Ceban, Vitalii Ghicavii, Adrian Tanase, Vladislav Vasiliev, Dragoljub Perovic, Marko Vukovic, Stanisavljevic Rade, Nenad Radovic, Emil Nasufovic, Yuri Alyaev, Igor Korneyev, Sergei Kotov, Vigen Malkhasyan, Dragoslav Basic, Miodrag Aćimović, Saša Vojinov, Aleksandar Vuksanovic, Uroš Bumbaširević, Bojan Čegar, Branko Stanković, Hansjörg Danuser, Tullio Sulser, Valentin Zumstein, Ates Kadioglu, Hakan Kilicarslan, Nusret Can Cilesiz, Erhan Demirelli, Bülent Önal, Aydin Mungan, Serdar Tekgül, Levent Türkeri, Adil Esen, Oleksandr Shulyak, Sergiy Vozianov, Alexandr Shulyak, Serhii Volkov, Andrii Nesterchuk
Journal: European Urology (2020)
AB0067 CHONDROCALCINOSIS IS ASSOCIATED WITH A SPECIFIC EFFECT ON THE CHONDROCYTE PHENOTYPE THAT MARKEDLY DIFFERS FROM OA
Authors: F. Meyer, M. Bollmann, U. Kornak, J. Bertrand
Journal: Annals of the Rheumatic Diseases (2020)

Background: Calcification of cartilage with BCP crystals is a common finding during osteoarthritis (OA) and is directly linked to the severity of the disease and hypertrophic differentiation of chondrocytes. Chondrocalcinosis (CC) is associated with CPPD crystal formation. There is only little knowledge about the effect of CPPD crystals on chondrocytes. Objectives: The aim of this study was to investigate the chondrocyte phenotype in CC cartilage and the effect of CPPD crystals on chondrocytes. Methods: Cartilage samples of patients with CC were used and compared with samples of severe OA patients without chondrocalcinosis and healthy cartilage samples served as control. Radiological presence of chondrocalcinosis was evaluated using standard X-ray pictures, as well as macroscopically inspection. The cartilage samples were stained using von Kossa/Safranin-orange staining. These stainings were used for OA severity scoring using the Chambers-Score. FTIR analyses was performed to distinguish CPPD and BCP crystals in cartilage. Chondrocyte differentiation markers were evaluated using Collagen 2 and X, as well as Sox9 and aggrecan as markers for chondrocyte hypertrophic differentiation in immunohistochemistry and qRT-PCR. TUNEL staining was performed to investigate cell death. In vivo results were validated using qRT-PCR for the expression of the respective genes after stimulation of C28 chondrocytes with CPPD and BCP crystals. Results: Radiologically detectable cartilage calcifications were evident in chondrocalcinosis patients, but absent in OA patients without CC. CPPD crystals were detected on the cartilage surface, whereas BCP crystals were detected in the pericellular matrix of hypertrophic chondrocytes. CC cartilage exhibited an increased collagen X expression compared to healthy cartilage, as well as to severe OA cartilage containing BCP calcification. Interestingly, aggrecan and collagen 2 were not reduced in CC cartilage, but markedly reduced in OA cartilage. TUNEL positive cells were significantly increased in CPPD cartilage compared to OA cartilage, although the histological OA severity was lower. qRT-PCR indicated no relevant influence of CPPD crystals on hypertrophic marker genes, whereas BCP crystals significantly induced hypertrophic differentiation. Conclusion: BCP and CPPD crystals seem to trigger differential effects on the chondrocyte phenotype. BCP crystals induce hypertrophic differentiation, which is not induced by CPPD crystals. Acknowledgments: The project was funded by theDeutsche Rheumastifung by the sponsor Dr. Sigrid Schuler. Disclosure of Interests: Franziska Meyer: None declared, Miriam Bollmann: None declared, Uwe Kornak: None declared, Jessica Bertrand Grant/research support from: Pfizer, Speakers bureau: Pfizer
Abstract PO-131: Inter-tumoral heterogeneity of progressive disease in melanoma patients treated with pembrolizumab
Authors: Brian Topp, Rukmini Kumar, Kapil Mayawala, Dinesh de Alwis, Matt D. Hellmann, Alexandra Snyder
Journal: Cancer Research (2020)

Abstract Introduction: In clinical trials of patients treated with pembrolizumab, RECIST-defined progressive disease (PD) is often assumed to reflect generalized lack or loss of efficacy. However, mixed lesion-level responses within a given patient may reflect more clinically and immunobiologically-relevant heterogeneity than has been previously appreciated. To examine the heterogeneity and clinical impact of progressive disease, we characterized the patient-level and lesion-level responses in 511 patients with melanoma treated with pembrolizumab. Methods: Of 655 patients with melanoma treated with pembrolizumab in KEYNOTE-001 (NCT01295827), 511 patients had at least two scans and qualified for analysis. Patients were categorized as primary progression (RECIST-defined PD at first scan) or secondary progression (RECIST-defined PD as second scan or beyond). The percent change in diameter of overall and individual target lesions were examined, as well as patterns and timing of progression in non-target and new lesions. Results: Of 511 patients, 308 (60%) developed progression at some point during the study (primary progression 211/308, 69%; secondary progression 97/308, 31%). Of patients with primary progression, 105 (50%) had increased tumor burden (&amp;gt;20% sum growth), while 90 (43%) had stable tumor burden (-30-+20% sum change) and 16 (8%) had decreased tumor burden (&amp;gt;-30% sum decrease). Lesion-level heterogeneity was substantial, with 167 (79%) of patients having at least one shrinking metastasis despite primary progression. In patients with secondary progression, timing of onset was variable (median 56 weeks, +/- 35 weeks). Only 15% of patients with acquired resistance, (5% of patients with PD), displayed rebound of all lesions. The remaining patients displayed rebound of a subset of lesions (38%) and/or appearance of new metastatic lesions (46%). Lesion-level responses that have been achieved often persisted at/after onset of secondary progression. Conclusions: Patterns of progression to pembrolizumab are heterogeneous. In primary progression, there is evidence of some lesion-level benefit in the majority of patients. In secondary progression, many lesions demonstrate continued benefit despite isolated/oligo sites of progression. Consideration of these patterns may inform optimal treatment strategies. Lesion-specific analysis of biomarkers may be necessary to improve correlative analyses and response prediction. Citation Format: Brian Topp, Rukmini Kumar, Kapil Mayawala, Dinesh de Alwis, Matt D. Hellmann, Alexandra Snyder. Inter-tumoral heterogeneity of progressive disease in melanoma patients treated with pembrolizumab [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-131.
Abstract 103: TBX20 Activates Cardiac Maturation Gene Programs Promoting Direct Human Cardiac Reprogramming
Authors: Yang Zhou, Yawen Tang, Vladimir G Fast, Lianzhong Zhao, Rui Lu, Jianyi Zhang
Journal: Circulation Research (2020)

Direct cardiac reprogramming to generate induced cardiomyocyte like cells (iCMs) from fibroblasts has emerged as a promising therapeutic strategy for the treatment of heart failure, which is still the leading cause of mortality and morbidity in developed countries. While much is known regarding iCMs generated from mouse cells, the adaptation of direct cardiac reprogramming to human cells is hurdled with low efficiency and poor quality because of intrinsic differences between species. Recently, our single cell transcriptomic analysis during human direct cardiac reprogramming demonstrated the immature features of human iCMs (hiCMs) compared to endogenous cardiomyocytes (CMs) at the transcriptome level, suggesting that key factors required for CM maturation remain unidentified. We then utilized computational analyses of genomic and epigenomic data to identify the regulators underexpressed in hiCMs comparing to CMs derived from human heart tissue or stem cell differentiation. Among them, the top hit is T-box family transcription factor TBX20, whose role in direct cardiac reprogramming remains to be explored. Supplementing TBX20 in reprogramming cocktails, we found significantly increased sarcomeric protein expression, like αMHC and αActinin in hiCMs and the formation of well-organized myofibrils. TBX20’s effect has also been supported by transcriptomic analysis, where we found TBX20 activates a large number of underexpressed genes associated with sarcomere structure and ion channels, such as MYH7 , MYL2 , MYBPC3, SCN5A and KCNQ1 , suggesting that TBX20 likely enhances maturation and contractility of hiCMs. We also found that TBX20 cannot replace any of the reprogramming factors, suggesting that its potential role is complimentary to and interacting with the current cocktail. Moreover, known TBX20 targets showed inconsistent alteration in TBX20-transduced hiCMs, suggesting its novel regulation in a direct reprogramming setting. These findings assign a novel reprogramming factor TBX20 playing an essential role in generating mature hiCMs by establishing gene programs associated with cardiac muscle contractility.
Characteristics of Different Splicing Factor Mutation Hotspots in Myelofibrosis
Authors: Franco Castillo Tokumori, Chetasi Talati, Najla E. Al Ali, David A. Sallman, Seongseok Yun, Kendra L. Sweet, Eric Padron, Jeffrey E. Lancet, Rami Komrokji, Andrew T. Kuykendall
Journal: Blood (2020)
Oligodendrocyte-derived extracellular vesicles as antigen-specific therapy for autoimmune neuroinflammation in mice
Authors: Giacomo Casella, Javad Rasouli, Alexandra Boehm, Weifeng Zhang, Dan Xiao, Larissa Lumi Watanabe Ishikawa, Rodolfo Thome, Xing Li, Daniel Hwang, Patrizia Porazzi, Sudheer Molugu, Hsin-Yao Tang, Guang-Xian Zhang, Bogoljub Ciric, Abdolmohamad Rostami
Journal: Science Translational Medicine (2020)

Extracellular vesicles from oligodendrocytes restore antigen-specific immune tolerance in mice models of multiple sclerosis.
Stable Pulmonary Function after Haploidentical Stem Cell Transplantation with Post-Transplant Cyclophosphamide: A Single Center Experience
Authors: Annalisa Paviglianiti, Simona Sestili, Antonio Bianchessi, Eolia Brissot, Mara Memoli, Remy Duléry, Anne Banet, Zoe Van De Wyngaert, Ramdane Belhocine, Tounes Ledraa, Florent Malard, Mohamad Mohty
Journal: Blood (2020)
Model Based Approach to Evaluate Isatuximab Monthly Dosing Regimen in Relapsed/Refractory Multiple Myeloma Patients
Authors: Hoai-Thu Thai, Nadia Gaudel-Dedieu, Marc Cerou, Bernard Sebastien, Helgi van de Velde, Dorothee Semiond, Christine Veyrat-Follet
Journal: Blood (2020)
Excellent Outcomes of Patients of Middle Eastern Ethnic Origin with Autologous Haemopoietic Stem Cell Transplantation and COVID-19: Does a Dampened Immune System Protect Against Severe COVID-19?
Authors: Imran K Tailor, Syed Y Altaf, Nawal F Alshehry, Alaa M Alser, Mohammed Marei, Mansour Alfayez, Ibraheem Motabi, Syed Ziauddin A Zaidi
Journal: Blood (2020)
Feasibility of Outpatient Autologous Stem Cell Transplantation in Multiple Myeloma and Risk Factors Predicting Hospital Admission
Authors: Kristin Larsen, Meera Mohan, Clyde Bailey, Kerri Hill, Horace Spencer, Mathew Kottarathara, Richa Parikh, Shadiqul Hoque, Amani Erra, Angel Mitma, Pankaj Mathur, Guido Tricot, Sharmilan Thanendrarajan, Maurizio Zangari, Frits van Rhee, Carolina D. Schinke
Journal: Blood (2020)
Early Results from a Phase 1/2 Study of Aru-1801 Gene Therapy for Sickle Cell Disease (SCD): Manufacturing Process Enhancements Improve Efficacy of a Modified Gamma Globin Lentivirus Vector and Reduced Intensity Conditioning Transplant
Authors: Michael Grimley, Monika Asnani, Archana Shrestha, Sydney Felker, Carolyn Lutzko, Paritha I. Arumugam, Scott Witting, Jennifer Knight-Madden, Omar Niss, Charles T. Quinn, Chris Lo, Courtney R Little, Joseph W. McIntosh, Punam Malik
Journal: Blood (2020)
Checkpoint Inhibition before Axicabtagene Ciloleucel Cell Therapy in Primary Mediastinal B-Cell Lymphoma (PMBCL) Treated in Real Life Setting
Authors: Annalisa Chiappella, Anna Dodero, Anna Guidetti, Filippo Bagnoli, Vanessa Aragona, Anna Maria Barbui, Stefania Bramanti, Matteo Giovanni Carrabba, Federica Sorà, Pierluigi Zinzani, Chiara Monfrini, Cristiana Carniti, Paolo Corradini
Journal: Blood (2020)
Initial Results from a Biomarker-Directed Phase 2 Trial of SY-1425, a Potent and Selective RARα Agonist, in Combination with Azacitidine in Relapsed/Refractory Acute Myeloid Leukemia
Authors: Eytan M. Stein, Stephane De Botton, Thomas Cluzeau, Arnaud Pigneux, Jane L. Liesveld, Rachel J. Cook, Philippe Rousselot, David A Rizzieri, Thorsten Braun, Dale L. Bixby, Gail J. Roboz, Delphine Lebon, Mael Heiblig, Michael J. Kelly, Angela Volkert, Li Zhou, Qing Kang-Fortner, David A. Roth, Pierre Peterlin
Journal: Blood (2020)
HP0025 The influence of hand function on daily activities in patients with rheumatic disease
Authors: LL Reinseth
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Summary</h3> Part I of this study explores how grip strength and total finger flexion of the hand in patients with rheumatic disease influence the abilities to perform daily activities. The second part of the study examines what kind of hand exercises which give the best results. Part III shows to what extent an improvement of grip strength may improve the performance of daily tasks. <h3>Methods</h3> In Part I, the grip strength are tested with a Martin Vigorimeter. The measurement of the total finger flexion is done with a ruler. The level of ability in performing daily activities is measured according to the definitions of "The Assessment of Motor and Process Skills" (AMPS) in 229 in – patients with rheumatic disease. In Part II, 194 patients have carried out a four weeks program of balanced, resistive exercises for the hand with therapeutic putty and was tested for grip strength. 153 patients out of these was tested for total finger flexion. A group of 5 patients have carried out a four weeks program for the hands, of Range of Motion (ROM) – exercises, without any resistance added. In Part III, 13 patients are tested with the Grip Ability Test (The GAT – Test) to see if they have accomplished increased abilities in performing daily activities after four weeks of resistive hand exercises. <h3>Controls</h3> 5 in-patients at the same centre, did not attend to the hand exercise groups, but participated in the other exercise programme for all the in-patients (Pool exercises and physical therapy). <h3>Results for Part I</h3> The analysis shows significant results both on the connexion between the grip strength and the total finger flexion and the ability to perform daily activities. Grip strength was proved to be a more important factor for performing the tasks of daily living than total finger flexion. <h3>Results Part II</h3> Those who carried out hand exercises with therapeutic putty (n = 194), accomplished an increase of 27% in grip strength. Those who also were tested for total finger flexion (n = 153), had increased the ROM of the total finger flexion with an average of 14%. Those who only carried out ROM exercises, increased 1% of grip strength and 11% in range of motion. The control group, which did not participate in any kind of hand exercise, had increased the grip strength with 1,5%, but had no change in ROM of the hand. <h3>Results Part III</h3> The GAT-test (the Grip Ability Test) showed a significant improvement of the level of ability to perform daily activities for those who had increased their grip strength.
R-CHOP Versus R-Bendamustine with or without Rituximab Maintenance in Newly Diagnosed Follicular Lymphoma Patients with High SUV at Baseline PET
Authors: Patrizia Mondello, Paolo Strati, Reid W Merryman, Erel Joffe, Marco Ruella, Venkatraman Seshan, Frederique St Pierre, Ajay Major, Priyanka Pophali, Megan Fiasconaro, Carrie I Ho, Eleanor Neal, Chao-Ming Lai, Gabriela Spilberg, Saurabh Rajguru, Jakub Svoboda, Thomas E. Witzig, Sonali M. Smith, Philippe Armand, Loretta J. Nastoupil, Stephen M. Ansell, Andrew D Zelenetz, Anas Younes, Gilles Salles
Journal: Blood (2020)