tbuckley/cabot-search huggingface dataset:
Comparison of Outcomes after Haploidentical Relative and HLA Matched Unrelated Donor Transplantation with Post-Transplant Cyclophosphamide Containing Gvhd Prophylaxis Regimens
Authors: Mahasweta Gooptu, Andrew St. Martin, Rizwan Romee, Mukta Arora, Monzr M. Al Malki, Joseph H. Antin, Christopher Bredeson, Claudio G. Brunstein, Saurabh Chhabra, Ephraim J. Fuchs, Nilanjan Ghosh, Michael R. Grunwald, Yoshihiro Inamoto, Christopher G. Kanakry, Natasha Kekre, Joseph P. McGuirk, Ian K. McNiece, Rohtesh S. Mehta, Marco Last Mielcarek, Filipo Milano, Dipenkumar Modi, Ran Reshef, Mark A. Schroeder, Robert J. Soiffer, Scott R. Solomon, Edmund K. Waller, Mary Eapen
Journal: Blood (2020)
Abstract 356: Rice Bran Extracts and Its Active Compound, γ-oryzanol, Prevent Particulate Matters-induced Endothelium Senescence
Authors: Dal-Seong Gong, Kushal Sharma, KI-WOON KANG, Min-Ho Oak
Journal: Circulation Research (2020)

Particulate matters (PMs) derived from are known to be responsible for a wide range of diseases. Recent studies have indicated that long-term exposure PMs is associated with several cardiovascular diseases, at least in part, by increase of inflammation, oxidative stress and nitric oxide (NO) balance disturbance. The present study was to investigate the protective effect of rice bran and its active compound, γ-oryzanol (γ-Orz), on PMs-induced premature endothelial senescence, and if then, to explore the underlying mechanism. Premature senescence was induced in porcine coronary arterial endothelial cells (PCAECs) by incubating 30 μg/mL of PM10. Senescence-associated β-galactosidase (SA-β-gal) activity, oxidative stress, expression level of cell cycle regulatory proteins, nicotinamide adenine dinucleotide phosphate(NADPH) oxidase, and local angiotensin system (LAS) component were evaluated. The result showed that senescence associated-β-gal activity in the PMs-treated PCAECs was attenuated by rice bran extracts (RBEs) and its major constituent, γ-Orz. Pretreatment with γ-Orz inhibited PMs-induced oxidative stress in PCAECs. Similarly, γ-Orz restored the cell proliferation of PCAECs by inhibiting PMs -induced cell cycle arrest. Western blot analyses revealed that cell cycle regulatory protein such as p53, p16, and p21 in senescent PCAECs treated with γ-Orz were reduced from PMs-exposed cells. In addition, γ- Orz prevented senescence associated NADPH oxidase, LAS activity of PM10-exposed cells. Pretreatment of γ-Orz restored PM10-induced endothelial dysfunction by upregulation of endothelial NO synthase expression. The present study demonstrated that γ-Orz protects against PMs induced PCAECs senescence, potentially through abrogating oxidative stress pathway. Taken together, this study can serve as a pharmacological use of rice bran extracts and γ-Orz for the prevention and/or treatment of air pollution-associated coronary artery diseases.
A behavioral model for mapping the genetic architecture of gut-microbiota networks
Authors: Libo Jiang, Xinjuan Liu, Xiaoqing He, Yi Jin, Yige Cao, Xiang Zhan, Christopher H. Griffin, Claudia Gragnoli, Rongling Wu
Journal: Gut Microbes (2020)

The gut microbiota may play an important role in affecting human health. To explore the genetic mechanisms underlying microbiota-host relationships, many genome-wide association studies have begun to identify host genes that shape the microbial composition of the gut. It is becoming increasingly clear that the gut microbiota impacts host processes not only through the action of individual microbes but also their interaction networks. However, a systematic characterization of microbial interactions that occur in densely packed aggregates of the gut bacteria has proven to be extremely difficult. We develop a computational rule of thumb for addressing this issue by integrating ecological behavioral theory and genetic mapping theory. We introduce behavioral ecology theory to derive mathematical descriptors of how each microbe interacts with every other microbe through a web of cooperation and competition. We estimate the emergent properties of gut-microbiota networks reconstructed from these descriptors and map host-driven mutualism, antagonism, aggression, and altruism QTLs. We further integrate path analysis and mapping theory to detect and visualize how host genetic variants affect human diseases by perturbing the internal workings of the gut microbiota. As the proof of concept, we apply our model to analyze a published dataset of the gut microbiota, showing its usefulness and potential to gain new insight into how microbes are organized in human guts. The new model provides an analytical tool for revealing the "endophenotype" role of microbial networks in linking genotype to end-point phenotypes.
Allogeneic Stem Cell Transplantation for Diffuse Large B Cell Lymphoma Can Achieve Durable Remissions: An Australasian Bone Marrow Transplant Recipient Registry Study
Authors: Pietro R Di Ciaccio, Matthew Greenwood, Glen A Kennedy, Sam Milliken, David Gottlieb, David Ritchie, Duncan Purtill, Stephen R Larsen, Andrew Spencer, Travis Perera, David T Yeung, Simon Durrant, Andrew Butler, Anne-Marie Watson, Hock Choong Lai, Richard Doocey, Hugh J. Goodman, Ian H. Kerridge, Christopher Arthur, Cameron Curley, Caroline Stewart, Kenneth P. Micklethwaite, Jennifer Collins, Julian Cooney, Nada Hamad
Journal: Blood (2020)
Real Life Treatment Alterations of Frontline Therapies in Classic Hodgkin's Lymphoma
Authors: Samer Al Hadidi, Ranjit Nair, Raphael E Steiner, Sairah Ahmed, Paolo Strati, Simrit Parmar, Swami P. Iyer, Jillian R. Gunther, Chelsea C. Pinnix, Bouthaina S. Dabaja, Yago Nieto, Felipe Samaniego, Branko Cuglievan, Preetesh Jain, Penny Fang, Roberto N. Miranda, Jeffrey Medeiros, Lei Feng, Hubert Chuang, Michael Wang, Hun Ju Lee
Journal: Blood (2020)
Clinicopathologic Comparison of Plasmablastic Lymphoma Patients According HIV-Status: Peruvian Experience
Authors: Jule F Vasquez, Cesar Samanez-Figari, Lourdes Lopez, Shirley Quintana, Rolig Aliaga, Yinno Custodio, Cindy Alcarraz, Daniel J Enriquez, Daniela Dueñas, Antonio Carrasco, Claudio Flores, Carlos Barrionuevo, Luis Cuellar
Journal: Blood (2020)
FRI0217 Predictive value of ophtalmological tests in the diagnosis of secondary sjÖgren syndrome in rheumatoid arthritis patients
Authors: JJ Alegre-Sancho, C Fernández-Carballido, JA Román-Ivorra, L Abad, B Pérez, A Pérez
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To determine the usefulness of different ophtalmological tests as predictive tools in the diagnosis of Secondary Sjögren Syndrome (SSS) in patients with Rheumatoid Arthritis. <h3>Methods</h3> 123 patients with RA were included in a transversal study. Xerophtalmia was assessed in 116 patients by Schirmer's test. Moreover, determination of tear film break-up (BUT) and Rose Bengal staining (Bijsterveld grading scale) were performed in 92 patients. Sicca symptoms, unstimulated salivary flow measurement, and testing for rheumatoid factor and antinuclear, anti-Ro/SSA and anti-La/SSB antibodies were also collected. Minor salivary gland biopsies were performed in 66 patients and graded according to Chisholm-Mason grading system. Statistical analysis was performed to determine sensitivity and specificity of each of the ophtalmological tests in the diagnosis of SSS by EEC criteria. <h3>Results</h3> Prevalence of SSS was 39.7% according to EEC criteria, and 20.3% according to modified EEC criteria. Sensitivity and specificity statistical studies showed the following results: <h3>Conclusion</h3> Among ophtalmological tests used to assess xerophtalmia, a positive Schirmer's test is the best predictor of the occurrence of SSS in patients with RA.
Safety and Efficacy of CD19 CAR T-Cells for Pediatric Relapsed Acute Lymphoblastic Leukemia with Active CNS Involvement
Authors: Elad Jacoby, Sara Ghorashian, Britta Julia Vormoor, Barbara De Moerloose, Nicole Bodmer, Michael Maschan, Asaf David Yanir, Bella Bielorai, Srdan Rogosic, Olga Molostova, Claudia Rossig, Amos Toren, Arend von Stackelberg, Jean-Pierre Bourquin
Journal: Blood (2020)
Comparison of Fixed Vs ALC-Based Doses of Thymoglobulin® (ATG) in Pediatric Patients with Acute Leukemia Given αβhaplo-HSCT: Impact on Immune Reconstitution at Day 90
Authors: Giulia Barbarito, David C Shyr, Gopin Saini, Linda Oppizzi, Y. Lucy Liu, Rachana Patil, Jaap-Jan Boelens, Alice Bertaina
Journal: Blood (2020)
BCX9930, an Oral Factor D Inhibitor, for the Potential Treatment of Alternative Pathway Mediated Diseases: Interim Results of a Phase 1 Study in Healthy Subjects
Authors: Matthew Davidson, Amanda Mathis, Stuart Mair, Diane Gesty-Palmer, Melanie Cornpropst, William P. Sheridan, Xilin Chen, David Reynolds, Cynthia Parker, Yarlagadda S. Babu
Journal: Blood (2020)
Semiautomatic VWF Multimer Densitometric Analysis: Validation of the Clinical Accuracy and Clinical Implications in Von Willebrand Disease
Authors: Ferdows Atiq, Johan Boender, Marjon H. Cnossen, Johanna G van der Bom, Karin Fijnvandraat, Joke de Meris, Moniek P.M. de Maat, Karin P.M. Van Galen, Britta A.P. Laros-Van Gorkom, Karina Meijer, Jeroen C.J. Eikenboom, Frank W.G. Leebeek
Journal: Blood (2020)
Boiling histotripsy and in-situ CD40 stimulation improve the checkpoint blockade therapy of poorly immunogenic tumors
Authors: Mohit Pratap Singh, Sri Nandhini Sethuraman, Craig Miller, Jerry Malayer, Ashish Ranjan
Journal: Theranostics (2020)

Background: Advanced stage cancers with a suppressive tumor microenvironment (TME) are often refractory to immune checkpoint inhibitor (ICI) therapy. Recent studies have shown that focused ultrasound (FUS) TME-modulation can synergize ICI therapy, but enhancing survival outcomes in poorly immunogenic tumors remains challenging. Here, we investigated the role of focused ultrasound based boiling histotripsy (HT) and in-situ anti-CD40 agonist antibody (αCD40) combinatorial therapy in enhancing therapeutic efficacy against ICI refractory murine melanoma. Methods: Unilateral and bilateral large (~330-400 mm3) poorly immunogenic B16F10 melanoma tumors were established in the flank regions of mice. Tumors were exposed to single local HT followed by an in-situ administration of αCD40 (HT+ αCD40: HT40). Inflammatory signatures post treatment were assessed using pan-cancer immune profiling and flow cytometry. The ability of HT40 ± ICI to enhance local and systemic effects was determined by immunological characterization of the harvested tissues, and by tumor growth delay of local and distant untreated tumors 4-6 weeks post treatment. Results: Immune profiling revealed that HT40 upregulated a variety of inflammatory markers in the tumors. Immunologically, HT40 treated tumors showed an increased population of granzyme B+ expressing functional CD8+ T cells (~4-fold) as well as an increased M1 to M2 macrophage ratio (~2-3-fold) and CD8+ T: regulatory T cell ratio (~5-fold) compared to the untreated control. Systemically, the proliferation rates of the melanoma-specific memory T cell population were significantly enhanced by HT40 treatment. Finally, the combination of HT40 and ICI therapy (anti-CTLA-4 and anti-PD-L1) caused superior inhibition of distant untreated tumors, and prolonged survival rates compared to the control. Conclusions: Data suggest that HT40 reprograms immunologically cold tumors and sensitizes them to ICI therapy. This approach may be clinically useful for treating advanced stage melanoma cancers.
FRI0254 Churg-strauss syndrome (css) in a series of 14 patients: a twelve years experience
Authors: J Mazzotti, G Riccio, E Venegoni, P Bottero
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Between 1988 and 2000 14 patients affected by CSS have been followed. Our series included 9 females and 5 males, the mean age at the diagnosis was 54 years (range 21–78), the mean follow up period was 95 months (range 60–141). Four criteria were simultaneneously satisfied in all patients at the diagnosis, according to the vasculitis ACR classification. The most important clinical manifestations exept for asthma, eosinophilia and paranasal sinus abnormality costantly present, were arthralgias, cutaneous nodules, peripheral neuropathy. Renal and gastroinestinal disease was observed only in one patient, cardiovascular and central nervous system involvement was respectively seen in 2 and 3 cases. Out of the 5 patients tested for ANCA, 2 resulted positive; prednisone treatment was started in 11 of the 14 patients at the mean dosage of 1 mg/kg/day, whereas at the 3 remaining patients was associated Cyclophosphamide at the dosage of 2 mg/kg/day. Only in one case IVIG pulse at the dosage of 1 gr/kg/for 5 days was started with good result. The most recurrent side effects were urinary infections (3 cases), pulmonary infections (2 cases), tubercolosis (2 cases), diabetis (2 cases), Herpes Zoster (3 cases). Remissions were observed in all patients, relapses were seen though well controlled by the increase of the steroid therapy. 3 patients died: 1 for mesenteric vasculitis, 1 for respiratory insufficiency and the last one for reasons not correlated to the disease. As reported in letterature, also in our experience survival is influenced by the systemic involvement of the disease and by FFS (Five factors score: combination of renal, cardiac, neurologic, gastrointestinal involvement plus proteinuria). In our series survival at 120 months was 75%, the worst prognostic index was seen in patients with FFS &gt; 1. <h3>Objectives</h3> <h3>Methods</h3> <h3>Results</h3> <h3>Conclusion</h3>
Clonal Hematopoiesis By HLA Class I Allele-Lacking Hematopoietic Stem Cells and Concomitant Aberrant Stem Cells Is Rarely Associated with Clonal Evolution to Secondary Myelodysplastic Syndrome and Acute Myeloid Leukemia in Patients with Acquired Aplastic Anemia
Authors: Kohei Hosokawa, Hiroki Mizumaki, Takeshi Yoroidaka, Hiroyuki Maruyama, Tatsuya Imi, Noriaki Tsuji, Ryota Urushihara, Mikoto Tanabe, Yoshitaka Zaimoku, Mai Anh Thi Nguyen, Dung Cao Tran, Ken Ishiyama, Hirohito Yamazaki, Takamasa Katagiri, Kazuyoshi Hosomichi, Atsushi Tajima, Fumihiro Azuma, Seishi Ogawa, Shinji Nakao
Journal: Blood (2020)
Mutant Isocitrate Dehydrogenase 1 Inhibitor Ivosidenib in Combination With Azacitidine for Newly Diagnosed Acute Myeloid Leukemia
Authors: Courtney D. DiNardo, Anthony S. Stein, Eytan M. Stein, Amir T. Fathi, Olga Frankfurt, Andre C. Schuh, Hartmut Döhner, Giovanni Martinelli, Prapti A. Patel, Emmanuel Raffoux, Peter Tan, Amer M. Zeidan, Stéphane de Botton, Hagop M. Kantarjian, Richard M. Stone, Mark G. Frattini, Frederik Lersch, Jing Gong, Diego A. Gianolio, Vickie Zhang, Aleksandra Franovic, Bin Fan, Meredith Goldwasser, Scott Daigle, Sung Choe, Bin Wu, Thomas Winkler, Paresh Vyas
Journal: Journal of Clinical Oncology (2020)

Ivosidenib is an oral inhibitor of the mutant isocitrate dehydrogenase 1 (IDH1) enzyme, approved for treatment of IDH1-mutant (mIDH1) acute myeloid leukemia (AML). Preclinical work suggested that addition of azacitidine to ivosidenib enhances mIDH1 inhibition-related differentiation and apoptosis.This was an open-label, multicenter, phase Ib trial comprising dose-finding and expansion stages to evaluate safety and efficacy of combining oral ivosidenib 500 mg once daily continuously with subcutaneous azacitidine 75 mg/m2 on days 1-7 in 28-day cycles in patients with newly diagnosed mIDH1 AML ineligible for intensive induction chemotherapy (ClinicalTrials.gov identifier: NCT02677922).Twenty-three patients received ivosidenib plus azacitidine (median age, 76 years; range, 61-88 years). Treatment-related grade ≥ 3 adverse events occurring in > 10% of patients were neutropenia (22%), anemia (13%), thrombocytopenia (13%), and electrocardiogram QT prolongation (13%). Adverse events of special interest included all-grade IDH differentiation syndrome (17%), all-grade electrocardiogram QT prolongation (26%), and grade ≥ 3 leukocytosis (9%). Median treatment duration was 15.1 months (range, 0.3-32.2 months); 10 patients remained on treatment as of February 19, 2019. The overall response rate was 78.3% (18/23 patients; 95% CI, 56.3% to 92.5%), and the complete remission rate was 60.9% (14/23 patients; 95% CI, 38.5% to 80.3%). With median follow-up of 16 months, median duration of response in responders had not been reached. The 12-month survival estimate was 82.0% (95% CI, 58.8% to 92.8%). mIDH1 clearance in bone marrow mononuclear cells by BEAMing (beads, emulsion, amplification, magnetics) digital polymerase chain reaction was seen in 10/14 patients (71.4%) achieving complete remission.Ivosidenib plus azacitidine was well tolerated, with an expected safety profile consistent with monotherapy with each agent. Responses were deep and durable, with most complete responders achieving mIDH1 mutation clearance.
A High Throughput Quantitative Seroproteomics Analysis of Multiple Myeloma Patients on Tagraxofusp Therapy Identifies Novel Cytokine-Assisted Mechanism of Action
Authors: Arghya Ray, Yan Song, Ting DU, Clifton C. Mo, Arturo Olguin, Janice Chen, Christopher Brooks, Tariq I. Mughal, Paul G. Richardson, Dharminder Chauhan, Kenneth Anderson
Journal: Blood (2020)
A Pilot Study of Acalabrutinib with Bendamustine/Rituximab Followed By Cytarabine/Rituximab (R-ABC) for Untreated Mantle Cell Lymphoma
Authors: Daniel Guy, Marcus Watkins, Fei Wan, Nancy L. Bartlett, Amanda F Cashen, Todd A Fehniger, Armin Ghobadi, Neha Mehta-Shah, Brad S. Kahl
Journal: Blood (2020)
Drivers of and Obstacles to the Adoption of Toxicogenomics for Chemical Risk Assessment: Insights from Social Science Perspectives
Authors: Guillaume Pain, Gordon Hickey, Matthieu Mondou, Doug Crump, Markus Hecker, Niladri Basu, Steven Maguire
Journal: Environmental Health Perspectives (2020)

Background: Some 20 y ago, scientific and regulatory communities identified the potential of omics sciences (genomics, transcriptomics, proteomics, metabolomics) to improve chemical risk assessment through development of toxicogenomics. Recognizing that regulators adopt new scientific methods cautiously given accountability to diverse stakeholders, the scope and pace of adoption of toxicogenomics tools and data have nonetheless not met the ambitious, early expectations of omics proponents. Objective: Our objective was, therefore, to inventory, investigate, and derive insights into drivers of and obstacles to adoption of toxicogenomics in chemical risk assessment. By invoking established social science frameworks conceptualizing innovation adoption, we also aimed to develop recommendations for proponents of toxicogenomics and other new approach methodologies (NAMs). Methods: We report findings from an analysis of 56 scientific and regulatory publications from 1998 through 2017 that address the adoption of toxicogenomics for chemical risk assessment. From this purposeful sample of toxicogenomics discourse, we identified major categories of drivers of and obstacles to adoption of toxicogenomics tools and data sets. We then mapped these categories onto social science frameworks for conceptualizing innovation adoption to generate actionable insights for proponents of toxicogenomics. Discussion: We identify the most salient drivers and obstacles. From 1998 through 2017, adoption of toxicogenomics was understood to be helped by drivers such as those we labeled Superior scientific understanding, New applications, and Reduced cost & increased efficiency but hindered by obstacles such as those we labeled Insufficient validation, Complexity of interpretation, and Lack of standardization. Leveraging social science frameworks, we find that arguments for adoption that draw on the most salient drivers, which emphasize superior and novel functionality of omics as rationales, overlook potential adopters' key concerns: simplicity of use and compatibility with existing practices. We also identify two perspectives—innovation-centric and adopter-centric—on omics adoption and explain how overreliance on the former may be undermining efforts to promote toxicogenomics. https://doi.org/10.1289/EHP6500
Abstract 228: Inflammasome-Primed Neutrophils Return to the Bone Marrow to Stimulate Leukocytosis Following Myocardial Infarction
Authors: Prabhakara R Nagareddy, Gopalkrishna Sreejit, Man K Lee, Baskaran Athmanathan, Greg A Quaife-Ryan, Ahmed Abdel-Latif, Enzo R Porrello, Andrew Murphy
Journal: Circulation Research (2020)

Myocardial infarction (MI) triggers myelopoiesis resulting in heightened number of neutrophils in the circulation. However, the mechanism that sustain their number and recruitment to the infarcted heart are unclear. Here, we show that in a mouse model of MI (permanent ligation of LAD), neutrophils are rapidly recruited to the infarct, where they release specific alarmins, S100A8 and S100A9. These alarmins acting either in an autocrine or paracrine manner, primed the Nod Like Receptor (NLR) family Pyrin Domain Containing 3 (Nlrp3) inflammasome in naïve neutrophils via their interaction with the Toll Like Receptor (TLR) 4. The interaction did not result in the release of IL1β systemically. However, the primed neutrophils, loaded with pro-interleukin-1β (IL-1β) returned to the bone marrow (BM) in a CXCR4 (C-X-C-motif chemokine receptor 4)- dependent manner. While at the BM, the primed-neutrophils released IL-1β through Gasdermin D pores and, stimulated granulopoiesis in a cell-autonomous manner. Strategies aimed at preventing the Nlrp3 inflammasome-priming or re-entry of the primed neutrophils to the BM dampened MI-induced granulopoiesis and markedly improved cardiac function. In subjects with acute ST-elevation myocardial infarction (STEMI), the number of neutrophils in the circulation increased both at the time of admission and following revascularization. Most importantly, patients with higher peak neutrophil counts demonstrated significantly higher incidence of major adverse cardiovascular events (MACE) during the one year follow up period. Similar to mouse data, the plasma levels of IL-1β did not change in STEMI patients at any time. However, the circulating neutrophils carried greater amounts of pro-IL-1β confirming our mouse data that granulopoiesis is likely not induced by systemic but locally delivered IL-1β by reverse migrating neutrophils. These data reveal a new paradigm of how circulatory cells establish direct communication between organs by delivering signaling molecules directly at the sites of action rather through systemically.
Pyruvate Kinase Controls Signal Strength in the Insulin Secretory Pathway
Authors: Sophie L. Lewandowski, Rebecca L. Cardone, Hannah R. Foster, Thuong Ho, Evgeniy Potapenko, Chetan Poudel, Halena R. VanDeusen, Sophia M. Sdao, Tiago C. Alves, Xiaojian Zhao, Megan E. Capozzi, Arnaldo H. de Souza, Ishrat Jahan, Craig J. Thomas, Craig S. Nunemaker, Dawn Belt Davis, Jonathan E. Campbell, Richard G. Kibbey, Matthew J. Merrins
Journal: Cell Metabolism (2020)
Updated Safety and Efficacy Results from a Phase 2 Study of Acalabrutinib, Venetoclax and Obinutuzumab (AVO) for Frontline Treatment of Chronic Lymphocytic Leukemia (CLL)
Authors: Matthew S. Davids, Benjamin L. Lampson, Svitlana Tyekucheva, Jennifer L. Crombie, Samuel Ng, Austin I. Kim, Matthew Weinstock, Jessica Lowney, Samantha Pazienza, Josie Montegaard, Victoria Patterson, Caron A. Jacobson, Ann S. LaCasce, Philippe Armand, Jon E. Arnason, David C. Fisher, Jennifer R. Brown
Journal: Blood (2020)