tbuckley/cabot-search huggingface dataset:
Pharmacokinetic-Guided Prophylaxis with Rurioctocog Alfa Pegol Improves Bleeding Rates over Standard Prophylaxis: Real-World Observational Data from the Ahead German Study
Authors: Robert Klamroth, Karin Kurnik, Swee Wenning, Carmen Escuriola-Ettingshausen, Stephan Regensburger, Leilei Tang, Joan Gu, Randy Guerra, Johannes Oldenburg
Journal: Blood (2021)
Beta-Catenin Forms Repressive Complexes with Ikzf1 and Ikzf3 to Orchestrate Tumor-Suppression in B-Cell Malignancies
Authors: Kadriye Nehir Cosgun, Mark E. Robinson, Lai N. Chan, Matthew Hur, Etienne Leveille, Joo Song, Wing (John) C. Chan, Markus Müschen
Journal: Blood (2021)
High-dose chemoradiotherapy followed by autologous bone marrow transplantation as consolidation therapy during first complete remission in adult patients with poor-risk aggressive lymphoma: a pilot study [see comments]
Authors: A Nademanee, GM Schmidt, MR O'Donnell, DS Snyder, PA Parker, A Stein, E Smith, JA Lipsett, I Sniecinski, K Margolin
Journal: Blood (1992)
Comprehensive Secretome Profiling Elucidates Novel Disease Biology and Identifies Pre-Infusion Candidate Biomarkers to Predict the Development of Severe Cytokine Release Syndrome in Pediatric Patients Receiving CART19
Authors: Caroline Diorio, Rawan Shraim, Regina M. Myers, Chakkapong Burudpakdee, Allison Barz Leahy, Richard Aplenc, Michele P. Lambert, Hamid Bassiri, Edward M Behrens, Vanessa E. Gonzalez, Fang Chen, Bruce L Levine, Shannon L. Maude, Amanda M. DiNofia, Alix E. Seif, J. Joseph Melenhorst, Simon F Lacey, Carl H June, David Barrett, Stephan A. Grupp, David T. Teachey
Journal: Blood (2021)
Real Life Study on Allogeneic Hematopoietic Cell Transplantation Practice According to International Guidelines and Its Impact on Survival in Acute Myeloid Leukemia French Population
Authors: Loic Abed, Morgane Mounier, Marie Robin, Stephanie Nguyen Quoc, Nicole Raus, Anna Berceanu, Sylvain Chantepie, Arnaud Pigneux, Edouard Forcade, Jacques-Olivier Bay, Sylvie Francois, Gaëlle Guillerm, Jean-Baptiste Mear, Denis Caillot, Mohamad Mohty, Remy Dulery, Nathalie Contentin, Charlotte Jubert, Alain Monnereau, Sebastien Orazio, Xavier Troussard, Edouard Cornet, Mohamad Sobh, Marc Maynadie, Mauricette Michallet
Journal: Blood (2021)
Abstract 9098: The Relationship Between Linoleic Acid (LA) and Dihomo-Gamma-Linolenic Acid (DGLA) as Indicator of Delta-6-Desaturase Activity
Authors: Dennis W Nilsen, Peder L Myhre, Are Annesoenn Kalstad, Erik Berg Schmidt, Harald Arnesen, Ingebjorg Seljeflot
Journal: Circulation (2021)

Introduction: Low levels of dihomo-gamma-linolenic acid (DGLA) have been shown to predict total death in patients hospitalized with an acute coronary syndrome. DGLA is converted from gamma-linolenic acid (GLA) by the enzyme elongase, following a slower and rate-limiting conversion from linoleic acid (LA) to GLA by the action of delta-6-desaturase. This would suggest that DGLA levels are (strongly) associated with delta-6-desaturase activity. Furthermore, a high ratio of LA to DGLA (LA:DGLA) has been claimed to reflect reduced delta-6-desaturase activity. Hypothesis/Aim: To evaluate the relationship between LA:DGLA ratio and DGLA levels in patients with a recent myocardial infarction (MI). Methods: Baseline samples from the OMEMI (Omega-3 Fatty acids in Elderly with Myocardial Infarction) trial* in which a total of 1027 patients, aged 70 to 82 years, were included 2-8 weeks after an MI, were obtained. The total fatty acid profile was determined in serum phospholipids and relative concentrations (wt%) of LA, GLA and the LA:DGLA ratio (used as a surrogate for delta-6-desaturase activity) were evaluated across quartiles of concentrations of DGLA. Results: Levels of GLA were low compared to other n-6 fatty acids and followed the same trend as DGLA, consistent with a rapid turnover from GLA (Table 1). Furthermore, there was a steady decrease in the LA:DGLA ratio across the quartiles of DGLA, with approximately 50% lower levels in the highest compared to the lowest quartile of DGLA. Conclusion: We found a strong inverse relationship between DGLA and the LA:DGLA ratio in patients with a recent MI, indicating that the LA:DGLA ratio may serve as a measure of delta-6-desaturase activity. * Circulation 2021; 143(6): 528-39.
Patients Diagnosed with Myelodysplastic Syndromes Display Lower Bone Mass: Assessment Using Bone Marrow Biopsies Manually and with Artificial Intelligence
Authors: Albert Kolomansky, Roy Malka, Edo Cohen-Karlik, Gal Barequet, Sagi Tauber, Itay Kalev, Ruben Wolhandler, Yoav Gaulan, Roee Esquira, Moni Shahar, Yishai Mansour, Amir Globerson, Drorit Neumann, Moshe Mittelman, Howard S. Oster
Journal: Blood (2021)
Progression-Free Survival Outcomes By Response Status for Bortezomib, Melphalan, and Prednisone with or without Daratumumab in Newly Diagnosed Multiple Myeloma: Pooled Subgroup Analysis of Octans and Alcyone
Authors: Jianxiang Wang, Weijun Fu, Soo-Mee Bang, Honghui Huang, Kihyun Kim, Wei Li, Gang An, Je-Jung Lee, Zhen Cai, Jie Jin, Yafei Wang, CS Chim, Paula Rodriguez-Otero, Anna Marina Liberati, Hiroyuki Takamatsu, Jae Hoon Lee, Meletios A. Dimopoulos, Susan Wroblewski, Robin Carson, Ming Qi, Jianping Wang, Yang Song, Bin Jia, Xue Yang, Wenyu Liu, Yunan Li, Renyi Zhang, Jian Hou
Journal: Blood (2021)
Abstract PO-037: Development of an RGD CRISPR-modified <i>Clostridium novyi</i> NT spores as an intravenous oncotherapy
Authors: Kaitlin M. Dailey, Krysten Vance, Kyle McAndrews, Reed I. Jacobson, Jandro Delgado, Paige R. Johnson, Taylor M. Woolery, Megan Orr, Jiha Kim, Sanku Mallik, Kenneth W. Bayles, Michael A. Hollingsworth, Amanda E. Brooks
Journal: Cancer Research (2021)

Abstract The efficacy of current oncotherapeutics is largely limited by an inability to access avascular tissues, which is in part responsible for forty years of stagnant pancreatic cancer statistics where the median survival remains a mere six months. Oncolytic bacteria such as Clostridium novyi-NT overcome this challenge with its ultrasensitive, innate affinity for hypoxic/necrotic areas found at the center of solid tumors and their metastases. While preclinical and clinical data from intratumoral injections of C. novyi-NT are promising, many tumors are inaccessible to such injections. Preclinical trials of analogous IV injections have uncovered other obstacles such as rapid clearance of C. novyi-NT by the immune system independent of septic complications. To mitigate rapid clearance, CRISPR/Cas9n was used to genetically modify a non-toxic form of C. novyi-NT to express a tumor targeting RGD peptide on the spore surface. Through this novel, first of its kind, methodology, spores with stronger affinity to a surface coated with the targeted binding partner of RGD, aVb3 integrin, have been generated. Importantly, there was no statistically significant difference in the genetically modified spore’s capacity for sporulation or germination when compared to unmodified C. novyi-NT spores, nor was a difference in lytic capacity observed, suggesting no relevant off-target effects from genomic modification. Biodistribution and efficacy of non-toxic RGD-modified spores was evaluated in an immunocompetent, syngeneic, pancreatic cancer murine model. Ongoing efforts to characterize the biodistribution and efficacy of the intravenously injected RGD-modified C. novyi-NT include the application of multiplex immunofluorescence, laser microdissection, and live, whole animal imaging. Supported as a pilot project by funds from NIH COBRE grant 1P20GM109024, Doctoral Dissertation Funds to KMD from NDSU, and by discretionary funds from investigators at UNMC. Citation Format: Kaitlin M. Dailey, Krysten Vance, Kyle McAndrews, Reed I. Jacobson, Jandro Delgado, Paige R. Johnson, Taylor M. Woolery, Megan Orr, Jiha Kim, Sanku Mallik, Kenneth W. Bayles, Michael A. Hollingsworth, Amanda E. Brooks. Development of an RGD CRISPR-modified Clostridium novyi NT spores as an intravenous oncotherapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-037.
Use of Red Blood Cell Phenotypes for Second Line Therapy Selection in Sickle Cell Disease
Authors: Celeste K. Kanne, Ashwin P Patel, Minke A.E. Rab, Brigitte A. van Oirschot, Jennifer Bos, Evelyn Kendall Williams, Meredith E. Fay, Kirby S. Fibben, Wilbur A. Lam, Richard van Wijk, Vivien A. Sheehan
Journal: Blood (2021)
<i>FLT3 ITD and NUP98</i> translocations Cooperate to Induce Type I Interferon Signaling That Impedes Hematopoietic Progenitor Differentiation
Authors: Yanan LI, Wei Yang, Priscilla Rodriguez-Lopez, Riddhi M Patel, Emily B Casey, Elisabeth Denby, Jeffrey A. Magee
Journal: Blood (2021)
Identification of Biomarkers That Are Associated with Clinical Complications of Hemoglobin SC Disease and Sickle Cell Anemia
Authors: Minke A.E. Rab, Celeste K. Kanne, Mitchel C. Berrevoets, Jennifer Bos, Brigitte A. van Oirschot, Erik Teske, Roger E.G. Schutgens, Gerard Pasterkamp, Richard van Wijk, Eduard J. Van Beers, Vivien A. Sheehan
Journal: Blood (2021)
Nutritional reprogramming of mouse liver proteome is dampened by metformin, resveratrol, and rapamycin
Authors: David G. Le Couteur, Samantha M. Solon-Biet, Benjamin L. Parker, Tamara Pulpitel, Amanda E. Brandon, Nicholas J. Hunt, Jibran A. Wali, Rahul Gokarn, Alistair M. Senior, Gregory J. Cooney, David Raubenheimer, Victoria C. Cogger, David E. James, Stephen J. Simpson
Journal: Cell Metabolism (2021)
Abstract 9486: Effect of Statin Therapy on Cognitive Decline and Incident Dementia in Older Adults
Authors: Zhen Zhou, Joanne Ryan, Michael E Ernst, Sophia Zoungas, Andrew M Tonkin, Robyn L Woods, John J McNeil, Christopher Reid, Andrea J Curtis, Rory Wolfe, Jo Wrigglesworth, Raj C Shah, Elsdon Storey, Anne Murray, Suzanne G Orchard, Mark R Nelson
Journal: Circulation (2021)

Background: The neurocognitive effect of statins in older adults remains uncertain. Objectives: To investigate the associations of statin use with cognitive decline and incident dementia among older adults. Methods: This analysis included 18,846 participants (aged ≥65 years) from a randomized trial of aspirin (ASPirin in Reducing Events in the Elderly, ASPREE). At baseline, participants had no experience of a CVD event, major physical disability, or diagnosed dementia, and were followed for a median (IQR) of 4.7 (3.5-5.6) years. Outcome measures included incident dementia and its subclassifications (probable Alzheimer’s disease [AD]; mixed presentations), changes in domain-specific cognition (global cognition, memory, language and executive function, psychomotor speed) and the composite of these domains. We examined the associations of baseline statin use with dementia using Cox proportional-hazards models, and with cognitive change using linear mixed-effects models, adjusting for confounders. The role of statin lipophilicity was also examined. Results: Compared with no statin, baseline statin use was not associated with incident dementia (adjusted HR [95%CI]: 1.16 [0.97-1.40]), probable AD (1.33 [1.00-1.77]) or mixed presentations of dementia (1.06 [0.82-1.35]) ( Table 1 ). Nor was it associated with changes in composite or domain-specific cognitive function scores over time ( Table 2 ). No differences were found in any outcomes between hydrophilic and lipophilic statin users ( Tables 1 &amp; 2 ). Conclusions: In healthy adults aged ≥65 years without diagnosed dementia, statin therapy over 4.7 years was not associated with incident dementia or cognitive decline.
Biologic Basis of the Impact of Autologous Hematopoietic Cell Transplantation in Multiple Myeloma Treated with Quadruplet Therapy
Authors: Susan Bal, Saurabh Chhabra, Natalie S. Callander, Eva Medvedova, Bhagirathbhai Dholaria, Rebecca W. Silbermann, Kelly N. Godby, Binod Dhakal, Smith Giri, Anita d'Souza, Timothy M. Schmidt, Aric C. Hall, Pamela Hardwick, Robert F. Cornell, Parameswaran Hari, Luciano J. Costa
Journal: Blood (2021)
Discovery and Preclinical Characterization of CC-95251, an Anti-SIRPα Antibody That Enhances Macrophage-Mediated Phagocytosis of Non-Hodgkin Lymphoma (NHL) Cells When Combined with Rituximab
Authors: Henry Chan, Christina Trout, David Mikolon, Preston Adams, Roberto Guzman, Gustavo Fenalti, Konstantinos Mavrommatis, Mahan Abbasian, Lawrence Dearth, Brian Fox, Pallavur Sivakumar, Kandasamy Hariharan
Journal: Blood (2021)
Clinical Outcomes of Solid Organ Transplant Patients with Epstein-Barr Virus-Driven (EBV +) Post-Transplant Lymphoproliferative Disorder (PTLD) Who Fail Rituximab Plus Chemotherapy: A Multinational, Retrospective Chart Review Study
Authors: Vikas Dharnidharka, Dhanalakshmi Thirumalai, Ulrich Jaeger, Weizhi Zhao, Daan Dierickx, Pengcheng Xun, Periana Minga, Ahmed Sawas, Natalia Sadetsky, Paul Chauvet, Erin Sundaram, Arie Barlev, Heiner Zimmermann, Ralf Ulrich Trappe
Journal: Blood (2021)
Abstract 9031: Blood-Based Epigenetic Markers of FKBP5 Gene Methylation in Patients With Dilated Cardiomyopathy
Authors: KENTO WADA, Tomofumi Misaka, Tetsuro Yokokawa, Yusuke Kimishima, Takashi Kaneshiro, Masayoshi Oikawa, Akiomi Yoshihisa, Yasuchika Takeishi
Journal: Circulation (2021)

Background: Blood-based DNA methylation patterns are linked to types of diseases. FKBP5, a protein cochaperone, is known to be associated with the inflammatory response, but the regulatory mechanisms by leukocyte FKBP5 DNA methylation in DCM patients remain unclear. Methods and Results: The present study enrolled DCM patients (n = 31) and age- and sex-matched control subjects (n = 43). We assessed FKBP5 CpG methylation of CpG islands at the 5’ side as well as putative promoter regions by methylation-specific quantitative polymerase chain reaction using leukocyte DNA isolated from the peripheral blood. FKBP5 CpG methylation levels at the CpG island of the gene body and the promoter regions were significantly decreased in DCM patients. Leukocyte FKBP5 and IL-1β mRNA expression levels were significantly higher in DCM patients than in controls. The protein expressions of DNMT1 and DNMT3A in leukocytes were significantly reduced in DCM patients. In vitro methylation assay revealed that FKBP5 promoter activity was inhibited at the methylated conditions in response to immune stimulation, suggesting the decreased FKBP5 CpG methylation was functionally associated with elevation of FKBP5 mRNA expressions. Histological analysis using a mouse model with pressure overload showed that FKBP5-expressing cells were substantially infiltrated in the myocardial interstitium in the failing hearts, indicating a possible role of FKBP5 expressions of immune cells in the cardiac remodeling. Conclusions: Our findings demonstrate a link between specific CpG hypomethylation of leukocyte FKBP5 and DCM. Blood-based epigenetic modification in FKBP5 may be a novel molecular mechanism that contributes to the pathogenesis of DCM.
Helping Patients Integrate Research Evidence—Reply
Authors: FA McAlister, SE Straus, GH Guyatt, RB Haynes
Journal: JAMA (2000)

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Choice of Frontline Tyrosine-Kinase Inhibitor in Very Elderly Patients with Chronic Myeloid Leukemia: A "Campus CML" Study
Authors: Roberto Latagliata, Isabella Capodanno, Maria Cristina Miggiano, Cristina Bucelli, Francesco Cavazzini, Sabrina Leonetti Crescenzi, Sabina Russo, Gioia Colafigli, Mario Annunziata, Federica Sora, Massimiliano Bonifacio, Luigiana Luciano, Giovanni Caocci, Giuseppina Loglisci, Chiara Elena, Rikard Mullai, Imma Attolico, Gianni Binotto, Elena Crisà, Alessandra Iurlo, Paolo Sportoletti, Ambra Di Veroli, Anna Rita Scortechini, Annapaola Leporace, Alessandro Maggi, Monica Crugnola, Fabio Stagno, Rosaria Sancetta, Pamela Murgano, Davide Rapezzi, Debora Luzi, Monica Bocchia, Carmen Fava, Alessandra Malato, Jolanda Donatella Vincelli, Elisabetta Abruzzese, Giuseppe Nicola Saglio, Giorgina Specchia, Massimo Breccia, Mario Tiribelli
Journal: Blood (2021)
Effect of β-Blocker Withdrawal on Functional Capacity in Heart Failure and Preserved Ejection Fraction
Authors: Patricia Palau, Julia Seller, Eloy Domínguez, Clara Sastre, Jose María Ramón, Rafael de La Espriella, Enrique Santas, Gema Miñana, Vicent Bodí, Juan Sanchis, Alfonso Valle, F. Javier Chorro, Pau Llácer, Antoni Bayés-Genís, Julio Núñez
Journal: Journal of the American College of Cardiology (2021)

Chronotropic incompetence has shown to be associated with a decrease in exercise capacity in heart failure with preserved ejection fraction (HFpEF), yet β-blockers are commonly used in HFpEF despite the lack of robust evidence. This study aimed to evaluate the effect of β-blocker withdrawal on peak oxygen consumption (peak Vo2) in patients with HFpEF and chronotropic incompetence. This is a multicenter, randomized, investigator-blinded, crossover clinical trial consisting of 2 treatment periods of 2 weeks separated by a washout period of 2 weeks. Patients with stable HFpEF, New York Heart Association functional classes II and III, previous treatment with β-blockers, and chronotropic incompetence were first randomized to withdrawing from (arm A: n = 26) versus continuing (arm B: n = 26) β-blocker treatment and were then crossed over to receive the opposite intervention. Changes in peak Vo2 and percentage of predicted peak Vo2 (peak Vo2%) measured at the end of the trial were the primary outcome measures. To account for the paired-data nature of this crossover trial, linear mixed regression analysis was used. The mean age was 72.6 ± 13.1 years, and most of the patients were women (59.6%) in New York Heart Association functional class II (66.7%). The mean peakVo2 and peak Vo2% were 12.4 ± 2.9 mL/kg/min, and 72.4 ± 17.8%, respectively. No significant baseline differences were found across treatment arms. Peak Vo2 and peak Vo2% increased significantly after β-blocker withdrawal (14.3 vs 12.2 mL/kg/min [Δ +2.1 mL/kg/min]; P < 0.001 and 81.1 vs 69.4% [Δ +11.7%]; P < 0.001, respectively). β-blocker withdrawal improved maximal functional capacity in patients with HFpEF and chronotropic incompetence. β-blocker use in HFpEF deserves profound re-evaluation. (β-blockers Withdrawal in Patients With HFpEF and Chronotropic Incompetence: Effect on Functional Capacity [PRESERVE-HR]; NCT03871803; 2017-005077-39)
Gilteritinib Versus Salvage Chemotherapy for Relapsed/Refractory <i>FLT3</i>-Mutated Acute Myeloid Leukemia: A Phase 3, Randomized, Multicenter, Open-Label Trial in Asia
Authors: Jianxiang Wang, Bin Jiang, Jian Li, Ligen Liu, Xin Du, Hao Jiang, Jianda Hu, Menghe Yuan, Taishi Sakatani, Takeshi Kadokura, Masato Takeuchi, Shunsuke Izuka, Larisa Girshova, Jerome Tan, Sergey N. Bondarenko, Lily LL Wong, Archrob Khuhapinant, Elena Martynova, Nahla Hasabou, Ramon V. Tiu
Journal: Blood (2021)
55 Baseline glycolytic tumor burden predicts response and survival in NSCLC and melanoma patients treated with immune checkpoint inhibitors
Authors: Saulo Silva, Carlos Wagner Wanderley, Jose Flavio Marin, Mariana De Macedo, Ellen Nascimento, Fernanda Antonacio, Fernando Cunha, Gilberto de Castro
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Tumor metabolic remodeling is considered one of the hallmarks of cancers and has been implicated in immune evasion. Highly glycolytic tumors can lead to immune suppression by both nutrient competition and toxic metabolite accumulation. Immune checkpoint inhibitors (ICIs) are essential in treating melanoma and non-small cell lung cancer (NSCLC) patients, but novel predictive biomarkers can significantly contribute to clinical practice. Herein we analyzed the predictive and prognostic value of baseline metabolic tumor volumes in NSCLC and melanoma patients treated with ICIs. Methods This retrospective, single-center study includes patients with metastatic NSCLC or melanoma and a baseline 18F-FDG-PET/CT (PET) performed before ICI. PET studied parameters were SUV (maximum standardized uptake value), wMTV (whole metabolic tumor value), and wTLG (whole total lesion glycolysis). Best response rates were analyzed through RECIST. High or low glycolytic tumor burden (GTB) patients were defined according to SUV, wMTV, and wTLG cut-offs that best discriminate progressive disease. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and curves were compared with log-rank. Results Among 151 patients included, 107 had NSCLC and 44 melanoma. Regarding NSCLC patients, there was a significant correlation between GTB and responses among all PET parameters (figure 1). Noteworthily, only one patient with a low wTLG (&lt;146) showed progressive disease after ICIs (figure 2C). In regard to the potential in predicting response to ICIs, the area under the curve (AUC) obtained for each glycolytic parameter was higher than that for PD-L1 expression (figure 2D-H). Furthermore, when patients were categorized according to ICI exposure (1st or ≥ 2nd line), AUC for glycolytic parameters was higher in ≥ 2nd line versus 1st line (figure 3). Lastly, a low GTB was associated with improved PFS (figure 4) and OS (figure 5).Regarding melanoma patients, wMTV and wTLG were significantly associated with response (figure 6), and a low GTB was significantly associated with improved PFS and OS (figure 7). Abstract 55 Figure 1 Abstract 55 Figure 2 Abstract 55 Figure 3 Abstract 55 Figure 4 Abstract 55 Figure 5 Abstract 55 Figure 6 Abstract 55 Figure 7 Conclusions GTB accessed through a baseline PET is associated with survival and response to ICIs in NSCLC and melanoma patients, suggesting that the tumor metabolism might impact immune responses and be a promising predictive tool. Ethics Approval The study obtained ethics approval by Sírio-Libanês Hospital institutional review board. Study participants were not required to give an informed consent before taking part.