tbuckley/cabot-search huggingface dataset:
Maternal Red Blood Cell Alloimmunization Managed with Intrauterine Blood Transfusion: Predictors of Poor Outcome
Authors: Evangelia Vlachodimtropoulou Koumoutsea, Maciej W. Garbowski, Tim VanMieghem, Shelley Solomon, Nimrah Abbasi, Gareth Seaward, Rory Windrim, Johannes Keunen, Edmond Kelly, Nadine Shehata, Greg Ryan
Journal: Blood (2020)
Do autoantibody-responses mature between presentation with arthralgia suspicious for progression to rheumatoid arthritis and development of clinically apparent inflammatory arthritis? A longitudinal serological study
Authors: Fenne Wouters, Ellis Niemantsverdriet, Nazike Salioska, Annemarie L Dorjée, René E M Toes, Annette H M van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2020)

Several nested case-control studies have shown that autoantibody-response maturation in rheumatoid arthritis (RA) precedes clinical arthritis development.1–3 This suggests a role in disease triggering. However, nested case-control studies have, similar to case-control studies, the disadvantage that controls are selected and that prospective data from non-progressing patients in a similar predisease stage are absent. The phase preceding clinically apparent inflammatory arthritis (IA) can be distinguished into an asymptomatic and symptomatic (ie, clinically suspect arthralgia, CSA) subphase. It is unknown whether autoantibody-response maturation occurs in the symptomatic phase. Likewise, its role in progression to clinical arthritis is undetermined; if autoantibody-response maturation relates to disease development, maturation is expected to be more pronounced in patients with CSA that progress compared with patients with CSA that do not. To better understand the relation between autoantibody-response maturation in time and development of clinical arthritis (RA/IA), we performed a longitudinal study on autoantibody-response maturation in patients with CSA that did and did not progress.

In serum from 147 patients with CSA, we determined with in-house ELISAs the presence and levels of IgM, IgG, IgA anti-citrullinated, anti-carbamylated and anti-acetylated protein antibodies (ACPA, anti-CarP, AAPA), resulting in nine autoantibody measurements per patient per timepoint. Autoantibody-response maturation was defined as increase in number of autoantibody reactivities or isotypes, and/or increase in autoantibody levels. Patients with CSA with paired samples at first presentation at the outpatient clinic and at IA development (n=55) or else after 2 years (n=92) were selected. Analyses were repeated with the outcome RA (the subgroup of patients with IA that fulfilled …
Construction of tantalum/poly(ether imide) coatings on magnesium implants with both corrosion protection and osseointegration properties
Authors: Kwang-Hee Cheon, Cheonil Park, Min-Ho Kang, In-Gu Kang, Min-Kyu Lee, Hyun Lee, Hyoun-Ee Kim, Hyun-Do Jung, Tae-Sik Jang
Journal: Bioactive Materials (2020)

Poly(ether imide) (PEI) has shown satisfactory corrosion protection capability with good adhesion strength as a coating for magnesium (Mg), a potential candidate of biodegradable orthopedic implant material. However, its innate hydrophobic property causes insufficient osteoblast affinity and a lack of osseointegration. Herein, we modify the physical and chemical properties of a PEI-coated Mg implant. A plasma immersion ion implantation technique is combined with direct current (DC) magnetron sputtering to introduce biologically compatible tantalum (Ta) onto the surface of the PEI coating. The PEI-coating layer is not damaged during this process owing to the extremely short processing time (30 s), retaining its high corrosion protection property and adhesion stability. The Ta-implanted layer (roughly 10-nm-thick) on the topmost PEI surface generates long-term surface hydrophilicity and favorable surface conditions for pre-osteoblasts to adhere, proliferate, and differentiate. Furthermore, in a rabbit femur study, the Ta/PEI-coated Mg implant demonstrates significantly enhanced bone tissue affinity and osseointegration capability. These results indicate that Ta/PEI-coated Mg is promising for achieving early mechanical fixation and long-term success in biodegradable orthopedic implant applications.
CXCR4-Expressing Anti-CD25 CAR T-Cells Effectively Eliminate Human AML Cells In Vivo
Authors: Ari Itoh-Nakadai, Yoriko Saito, Mariko Murasawa-Tomizawa, Hiroshi Kajita, Takehisa Matsumoto, Masashi Matsuda, Takashi Watanabe, Mikako Shirouzu, Osamu Ohara, Haruhiko Koseki, Leonard Shultz, Fumihiko Ishikawa
Journal: Blood (2020)
Identification of LAG3+ T Cell Populations in the Tumor Microenvironment of Classical Hodgkin Lymphoma and B-Cell Non-Hodgkin Lymphoma
Authors: Katsuyoshi Takata, Tomohiro Aoki, Lauren C. Chong, Katy Milne, Tomoko Miyata-Takata, Karanvir Singh, Talia Goodyear, Pedro Farinha, Graham W. Slack, Laurie H. Sehn, Kerry J. Savage, Brad H Nelson, David W. Scott, Christian Steidl
Journal: Blood (2020)
High-Resolution Manometry Thresholds and Motor Patterns Among Asymptomatic Individuals
Authors: Arvind Rengarajan, Benjamin D. Rogers, Zhiqin Wong, Salvatore Tolone, Daniel Sifrim, Jordi Serra, Edoardo Savarino, Sabine Roman, Jose M. Remes-Troche, Rosa Ramos, Julio Perez de la Serna, Ans Pauwels, Ana Maria Leguizamo, Yeong Yeh Lee, Osamu Kawamura, Jamal Hayat, Albis Hani, Sutep Gonlachanvit, Daniel Cisternas, Dustin Carlson, Serhat Bor, Shobna Bhatia, Luiz Abrahao, John Pandolfino, C. Prakash Gyawali
Journal: Clinical Gastroenterology and Hepatology (2020)
Abstract IA20: Aberrant leukemic developmental hierarchies and MRD-specific targeting informed by single-cell biophysical and molecular profiling
Authors: Peter S. Winter, Andrew Navia, Haley Strouf, Mahnoor Mirza, Jennyfer Galvez-Reyes, Nolawit Mulugeta, Laura Bilal, Nezha Senhaji, Peter Dennis, Catharine S. Leahy, Kay Shigemori, Foster Powers, Alejandro Gupta, Nicholas Calistri, Alex Van Scoyk, Kristen Jones, Huiyun Liu, Kristen E. Stevenson, Robert Kimmerling, Mark Stevens, David M. Weinstock, Scott R. Manalis, Mark A. Murakami, Alex K. Shalek
Journal: Cancer Research (2020)

Abstract Targeted inhibitors of essential oncogenic kinases induce high rates of clinical response but cure few patients due to the persistence of minimal residual disease (MRD). BCR-ABL mutant leukemias are a classic example of this paradigm where patients usually achieve deep remissions followed by near inevitable relapses. Multiple factors have been shown to influence how an individual patient’s leukemic cells will navigate treatment including differentiation state, mutational background, and communication with the microenvironment. Here, we use BCR-ABL-rearranged acute lymphoblastic leukemia (BCR-ABL ALL) to interrogate cell-autonomous features leading to therapeutic resistance using low-input single-cell assays. Specifically, we use a combination of primary samples and PDX models to dissect aberrant developmental hierarchies and monitor leukemic cell transcriptional and biophysical phenotype at pretreatment, MRD, and relapse. Using machine learning, we relate malignant B cells to normal development, allowing us to define leukemic developmental programs and demonstrate that these have consequences for the time to progression as well as the genetic alterations seen at relapse. Further, we determine that there are unique biophysical features tied to leukemic developmental states and that these integrative properties co-evolve with transcriptional state over the course of treatment. Finally, we demonstrate in PDX studies that it may be possible to intercept relapse by targeting specific features of MRD cells. Together, these data suggest that significant developmental hierarchies exist in ALL, tumor subpopulations can be identified directly within MRD, and their phenotypic and molecular characterization can be exploited to therapeutic effect. Citation Format: Peter S. Winter, Andrew Navia, Haley Strouf, Mahnoor Mirza, Jennyfer Galvez-Reyes, Nolawit Mulugeta, Laura Bilal, Nezha Senhaji, Peter Dennis, Catharine S. Leahy, Kay Shigemori, Foster Powers, Alejandro Gupta, Nicholas Calistri, Alex Van Scoyk, Kristen Jones, Huiyun Liu, Kristen E. Stevenson, Robert Kimmerling, Mark Stevens, David M. Weinstock, Scott R. Manalis, Mark A. Murakami, Alex K. Shalek. Aberrant leukemic developmental hierarchies and MRD-specific targeting informed by single-cell biophysical and molecular profiling [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 IA20.
Local Activator and T Cell Engager (αBCMA x αPD-L1 x αCD3) with Enhanced Tumor Killing and Minimal Cytokine Release for the Treatment of Multiple Myeloma
Authors: Melissa Vrohlings, Stephanie Jungmichel, Jan Müller, David Senn, Thomas Schleier, Fabian Scheifele, Severin Wendelspiess, Christian Leisner, Maria-Theresa Krauth, Ulrich Jaeger, Leonardo J. Borras
Journal: Blood (2020)
Abstract IA10: Uncovering the ecology of glioblastoma with spatial digital profiling and single cell genotyping
Authors: Kacper A. Walentynowicz, Shreya Yadav, Cristina Vincentelli, Michalina Janiszewska
Journal: Cancer Research (2020)

Abstract Glioblastoma (GBM) remains one of the biggest challenges in oncology, with median survival of ~15 months. Extreme heterogeneity of the GBM cells within each tumor results in resistance to most of the available therapies. Understanding the relationships between the heterogenous populations of GBM cells and the diverse niches they rely on is key to developing more effective treatment for this aggressive brain tumor. Analysis of the spatial localization of cells with different properties can shed light on their microenvironmental preferences, interactions and potential vulnerabilities. Therefore, we set out to profile 20 GBM cases using methods allowing for single-cell assessment of select genomic features and protein marker expression in intact tissue samples from each tumor. We constructed a tissue microarray (TMA), containing four distant areas from each tumor block to represent the intratumor heterogeneity within each tumor fragment. Based on multicolor immunofluorescent staining with markers of glial cells, immune cells and vasculature, we selected 96 regions of interest, which were then subject to digital spatial profiling for 90 protein markers associated with glioblastoma biology, neurobiology and immunology. Pearson’s correlation and Shannon index calculation based on our profiling results showed that majority of the regions cluster by their tumor of origin, however several highly diverse tumors were also identified. To link the diversity of the protein expression found with the digital spatial profiling with underlying genomic alterations, using the same TMA slide, we performed multiplexed fluorescence in situ hybridization for genes most frequently amplified in GBM. Automated quantification allowed us to collect information from 38,000 individual cells. Based on the presence or absence of the amplifications each cell was assigned a genotype. Since mutation in hTERT promoter has been reported as one of the drivers of GBM, we used STAR-FISH, an in situ single-cell mutation detection assay, to record the frequency and spatial localization of cells harboring this mutation on our TMA. Our datasets provide a unique opportunity to link single-cell genetic diversity to the phenotypic heterogeneity of the tumor cells and their microenvironment. Spatial localization of cells with distinct genotypes allows us to further dissect the interactions between the distinct subclones of GBM cells and uncover their novel dependencies. Citation Format: Kacper A. Walentynowicz, Shreya Yadav, Cristina Vincentelli, Michalina Janiszewska. Uncovering the ecology of glioblastoma with spatial digital profiling and single cell genotyping [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 IA10.
Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods
Authors: Berislav Bošnjak, Saskia Catherina Stein, Stefanie Willenzon, Anne Katrin Cordes, Wolfram Puppe, Günter Bernhardt, Inga Ravens, Christiane Ritter, Christian R. Schultze-Florey, Nina Gödecke, Jörg Martens, Hannah Kleine-Weber, Markus Hoffmann, Anne Cossmann, Mustafa Yilmaz, Isabelle Pink, Marius M. Hoeper, Georg M. N. Behrens, Stefan Pöhlmann, Rainer Blasczyk, Thomas F. Schulz, Reinhold Förster
Journal: Cellular and Molecular Immunology (2020)

Neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into cells via surface-expressed angiotensin-converting enzyme 2 (ACE2). We used a surrogate virus neutralization test (sVNT) and SARS-CoV-2 S protein-pseudotyped vesicular stomatitis virus (VSV) vector-based neutralization assay (pVNT) to assess the degree to which serum antibodies from coronavirus disease 2019 (COVID-19) convalescent patients interfere with the binding of SARS-CoV-2 S to ACE2. Both tests revealed neutralizing anti-SARS-CoV-2 S antibodies in the sera of ~90% of mildly and 100% of severely affected COVID-19 convalescent patients. Importantly, sVNT and pVNT results correlated strongly with each other and to the levels of anti-SARS-CoV-2 S1 IgG and IgA antibodies. Moreover, levels of neutralizing antibodies correlated with the duration and severity of clinical symptoms but not with patient age. Compared to pVNT, sVNT is less sophisticated and does not require any biosafety labs. Since this assay is also much faster and cheaper, sVNT will not only be important for evaluating the prevalence of neutralizing antibodies in a population but also for identifying promising plasma donors for successful passive antibody therapy.
Tumor Associated Antigen Specific T Cells Given in Combination with Nivolumab for the Treatment of Hodgkin Lymphoma
Authors: Hema Dave, Mimi Mai, Madeline Terpilowski, Keri Toner, Maja Stanojevic, Morgan Galligan, Abeer Shibli, Melanie Grant, Christopher Lazarski, Philip Y Maglo, Nan Zhang, Jay Tanna, Richard F. Ambinder, Martha Glenn, Patrick Hanley, Catherine M. Bollard
Journal: Blood (2020)
SIRT1 and HSP90alpha Are Functionally Linked and Control Mitotic Chromosome Segregation and Cell Viability in a Subset of Dlbcls
Authors: Emilia Bialopiotrowicz, Monika Noyszewska-Kania, Ewa Jabłońska, Tomasz Sewastianik, Monika Stańczak, Anna Szumera-Ciećkiewicz, Katarzyna Borg, Aleksandra Bluszcz, Sonia Dębek, Monika Prochorec-Sobieszek, Anna Polak, Patryk Górniak, Maciej Szydlowski, Przemyslaw Juszczynski
Journal: Blood (2020)
Updated Analysis of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma (NDMM): The Phase 3 Maia Study
Authors: Shaji K. Kumar, Thierry Facon, Saad Z. Usmani, Torben Plesner, Robert Z. Orlowski, Cyrille Touzeau, Supratik Basu, Nizar J. Bahlis, Hartmut Goldschmidt, Michael E. O'Dwyer, Christopher P. Venner, Katja Weisel, Cyrille Hulin, Lionel Karlin, Meir Preis, Annemiek Broyl, William Renwick, Markus Hansson, Maria Krevvata, Jianping Wang, Rian Van Rampelbergh, Jon Ukropec, Clarissa M. Uhlar, Rachel Kobos, Aurore Perrot
Journal: Blood (2020)
<i>Pegaspargase Re-Challenge after Grade 2 Hypersensitivity Reaction in Childhood Acute Lymphoblastic Leukemia: Results from DFCI 16-001</i>
Authors: Lynda M. Vrooman, Yael Flamand, Victoria Koch, Melissa A. Burns, Sarah M. Cronholm, Sarah K. Hunt, Peter D. Cole, Lisa M. Gennarini, Justine M. Kahn, Kara M. Kelly, Bruno Michon, Donna S. Neuberg, Andrew E. Place, Thai Hoa Tran, Jennifer J.G. Welch, Kristen E. Stevenson, Stephen E. Sallan, Lewis B. Silverman
Journal: Blood (2020)
Specific Correction of the Intron-22 Inverted Factor VIII Gene in Autologous Blood Outgrowth Endothelial Cells from Patients with Severe Hemophilia A
Authors: Long V. Dinh, Eli Fine, Afshin Ameri, Bernadette W. Luu, Satish Kumar, Vincent P. Diego, Joanne E. Curran, Juan M Peralta, Henry Mead, Miguel A. Escobar, Sarah Williams-Blangero, John Blangero, Jerry S. Powell, Timothy C. Nichols, Robert P. Hebbel, Tom E. Howard
Journal: Blood (2020)
Roto-translation equivariant convolutional networks: Application to histopathology image analysis
Authors: Maxime W. Lafarge, Erik J. Bekkers, Josien P.W. Pluim, Remco Duits, Mitko Veta
Journal: Medical Image Analysis (2020)

Rotation-invariance is a desired property of machine-learning models for medical image analysis and in particular for computational pathology applications. We propose a framework to encode the geometric structure of the special Euclidean motion group SE(2) in convolutional networks to yield translation and rotation equivariance via the introduction of SE(2)-group convolution layers. This structure enables models to learn feature representations with a discretized orientation dimension that guarantees that their outputs are invariant under a discrete set of rotations. Conventional approaches for rotation invariance rely mostly on data augmentation, but this does not guarantee the robustness of the output when the input is rotated. At that, trained conventional CNNs may require test-time rotation augmentation to reach their full capability. This study is focused on histopathology image analysis applications for which it is desirable that the arbitrary global orientation information of the imaged tissues is not captured by the machine learning models. The proposed framework is evaluated on three different histopathology image analysis tasks (mitosis detection, nuclei segmentation and tumor detection). We present a comparative analysis for each problem and show that consistent increase of performances can be achieved when using the proposed framework.
Abstract 469: Thymosin Beta4 Enhancing Therapeutic Efficacy of Human Adipose-derived Stem Cells in Mouse Ischemic Hindlimb Model
Authors: Jong-ho Kim, Hyung Joon Joo, Soon Jun Hong
Journal: Circulation Research (2020)

Thymosin Beta4 (Tβ4) is a G-actin sequestering protein that contributes to diverse cellular activities, such as migration and angiogenesis. In this study, the beneficial effects of combined cell therapy with Tβ4 and human adipose-derived stem cells (hASCs) in a mouse ischemic hindlimb model were investigated. We observed that exogenous treatment with Tβ4 enhanced endogenous TMSB4X mRNA expression and promoted morphological changes (increased cell length) in hASCs. Interestingly, Tβ4 induced the active state of hASCs by up-regulating intracellular signaling pathways including the PI3K/AKT/mTOR and MAPK/ERK pathways. Treatment with Tβ4 significantly increased cell migration and sprouting from microbeads. Moreover, additional treatment with Tβ4 promoted the endothelial differentiation potential of hASCs by up-regulating various angiogenic genes. To evaluate the in vivo effects of the Tβ4-hASCs combination on vessel recruitment, dorsal window chambers were transplanted, and the co-treated mice were found to have a significantly increased number of microvessel branches. Transplantation of hASCs in combination with Tβ4 was found to improve blood flow and attenuate limb or foot loss post-ischemia compared to transplantation with hASCs alone. Taken together, the therapeutic application of hASCs combined with Tβ4 could be effective in enhancing endothelial differentiation and vascularization for treating hindlimb ischemia.
Immunophenotyping of Baseline Bone Marrow Reveals a Specific Pattern of Immune Cells Associated with Greater Depth and Sustained Response in Newly Diagnosed Patients Randomized to Krd or Ktd Followed By Carfilzomib Maintenance or Control (AGMT MM 02 Study)
Authors: Irene Manrique, Richard Greil, Johannes Andel, Siegfried Sormann, Bernd L. Hartmann, Klaus Podar, Alexander Egle, Andreas Petzer, Niklas Zojer, Reinhard Ruckser, Boris Bozic, Clemens A. Schmitt, Sigrid Machherndl-Spandl, Hermine Agis, Martin Schreder, Maria-Theresa Krauth, Christoph Tinchon, Michael Fillitz, Thomas Melchardt, Bruno Paiva, Heinz Ludwig
Journal: Blood (2020)
Efficacy and Safety of Isatuximab in Relapsed Refractory Multiple Myeloma: A Systematic Review
Authors: Mydah Sajid Hashmi, Ali Jaan, Muhammad Ans Sharif, Summera Aziz, Zahoor Ahmed, Karun Neupane, Muhammad Salman Faisal, Israr Khan, Arshia Akbar, Faiz Anwer
Journal: Blood (2020)
Abstract 210: Reprogramming Mouse Fibroblasts Into Cardiac Progenitor Cells Using Crispr Technique Targeting Endogenic Genes
Authors: Yi-gang Wang, Lin Jiang, Jialiang Liang, Wei Huang, Christian Paul
Journal: Circulation Research (2020)

Background and Objective: CRISPR tools that allow for precise manipulation of individual loci have not been used in generation of i nduced c ardiac p rogenitor c ells ( iCPC s). This study was designed to determine the feasibility and effectiveness of reprogramming fibroblasts into iCPC using CRISPR activation (CRISPRa) system. Methods: Tail-tip fibroblasts (TTFs) were isolated from Nkx2-5 cardiac enhancer GFP reporter mice. A gRNA pool targeting 17 progenitor genes was synthesized and transduced with dCas9-VP64 lentivirus into TTFs ( Fig.1A ). The phenotype of iCPCs was then characterized by immunostaining and FACS of progenitor markers. Finally, the cardiac-lineage differentiation potential of iCPCs was determined by immunostaining and electrophysiological assay under defined induction mediums. Results: iCPCs with GFP expression were formed in TTFs after transduction of CRISPRa targeting Isl1, Gata4, Baf60c, Tbx5 and Nkx2-5 (Fig.1B), while GFP was not activated by control virus. Cardiac progenitor markers were activated in iCPCs as shown by immunostaining (Fig.1C). The generation efficiency of Flk1-postive iCPCs induced by CRISPRa was ~60% as showed by FACS. iCPCs can be differentiated into cardiomyocytes as identified by immunostaining of cardiac-specific markers (Fig.1D). The iCPC-derived cardiomyocytes displayed spontaneous beating and showed cardiac action potentials (Fig.1E). Conclusion: The CRISPRa system is an efficient and specific way to generate iCPCs, which could provide a novel source of cells for cardiac regenerative medicine. Conversion of fibroblasts into cardiac progenitors poses a novel therapeutic option for repair of myocardial infarction.
The Outcome of Patients with Advanced Phase Chronic Myeloid Leukemia with and without Allogeneic Hemopoietic Stem Cell Transplantation
Authors: Elena V. Morozova, Julia J. Vlasova, Maria V. Barabanshikova, Axel R. Zander, Ksenia Jurovskaya, Tatyana L. Gindina, Ildar Barhatov, Sergey N. Bondarenko, Ivan S. Moiseev, Ludmila S Zubarovskaya, Aleksandr D. Kulagin
Journal: Blood (2020)
Hydroxyurea Reduces Neutrophil Extracellular Trap Formation in Myeloproliferative Neoplasms
Authors: Ernesto J Cuenca, Nieves García Gisbert, Ascensión M de Los Reyes-García, Cristina Aroca, Lorena Martinez-Montesinos, Marcio Andrade, Sonia Aguila, Pedro J Guijarro-Carrillo, Rosa Cifuentes-Riquelme, Rocio González-Conejero, Constantino Martínez, Vicente Vicente, Alberto Alvarez-Larrán, Beatriz Bellosillo, Raul Teruel-Montoya, Francisca Ferrer Marin
Journal: Blood (2020)
Odronextamab (REGN1979), a Human CD20 x CD3 Bispecific Antibody, Induces Durable, Complete Responses in Patients with Highly Refractory B-Cell Non-Hodgkin Lymphoma, Including Patients Refractory to CAR T Therapy
Authors: Rajat Bannerji, John N. Allan, Jon E. Arnason, Jennifer R. Brown, Ranjana Advani, Stephen M. Ansell, Susan M. O'Brien, Johannes Duell, Peter Martin, Robin M. Joyce, Jingjin Li, Dina M. Flink, Min Zhu, David M. Weinreich, George D. Yancopoulos, Andres Sirulnik, Aafia Chaudhry, Srikanth R. Ambati, Max S. Topp
Journal: Blood (2020)