tbuckley/cabot-search huggingface dataset:
Thrombin Generation to Predict the Risk of Venous Thromboembolism Recurrence, Major Bleeding and Death in the Elderly: A Prospective Multicenter Cohort Study
Authors: Kristina Vrotniakaite-Bajerciene, Sereina Rütsche, Sara Calzavarini, Claudia Quarroz, Odile Stalder, Marie Mean, Marc Righini, Jürg Hans Beer, Beat Frauchiger, Joseph Osterwalder, Nils Kucher, Christian Matter, Marc Husmann, Martin Banyai, Markus Aschwanden, Lucia Mazzolai, Olivier Hugli, Nicolas Rodondi, Drahomir Aujesky, Anne Angelillo-Scherrer
Journal: Blood (2021)
FLT3 Inhibitors Induce p53 Instability Due to Increased Interaction between p53 and MDM2 By Inhibiting STAT5 Phosphorylation in Acute Myeloid Leukemia
Authors: Han Zhong Pei, Xiaomei Zhuang, Ming Yang, Yao Guo, Zhiguang Chang, Dengyang Zhang, Yuming Zhao, Liuting Yu, Bo Lu, Xiaojun Xu, Yun Chen, Zhizhuang Joe Zhao
Journal: Blood (2021)
Zanubrutinib in Combination with Venetoclax for Patients with Treatment-Naïve (TN) Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) with del(17p): Early Results from Arm D of the SEQUOIA (BGB-3111-304) Trial
Authors: Alessandra Tedeschi, Emmanuelle Ferrant, Ian W. Flinn, Constantine S. Tam, Paolo Ghia, Tadeusz Robak, Jennifer R. Brown, Vanitha Ramakrishnan, Tian Tian, Sowmya B. Kuwahara, Jason C. Paik, Aileen Cohen, Jane Huang, Peter Hillmen
Journal: Blood (2021)
Elevated Enhancer-Oncogene Contacts and Higher Oncogene Expression Levels By Recurrent <i>CTCF</i> inactivating Mutations in T Cell Acute Lymphoblastic Leukemia
Authors: Willem K. Smits, Carlo Vermeulen, Rico Hagelaar, Shunsuke Kimura, Eric Vroegindeweij, Jessica G.C.A.M. Buijs-Gladdines, Ellen Van De Geer, Marjon J.A.M. Verstegen, Erik Splinter, Simon V. van Reijmersdal, Arjan Buijs, Niels Galjart, Winfried Van Eyndhoven, Max Jan Van Min, Roland P Kuiper, Patrick Kemmeren, Charles G. Mullighan, Wouter De Laat, Jules P.P. Meijerink
Journal: Blood (2021)
Abstract 11808: Visit-to-visit Blood Pressure Variability Predicts Recurrence of Atrial Fibrillation in Patients With Hypertension
Authors: Naoko Hijioka, Masashi Kamioka, Amami Kazuaki, Shinya Yamada, Takashi Kaneshiro, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2019)

Introduction: Visit-to-visit blood pressure variability (VV-BPV) has been shown to be associated with cardiovascular risk in patients with hypertension (HT). However, it remains unclear whether the...
<i>Tfr2</i> Genetic Deletion Makes Transfusion-Independent a Murine Model of Transfusion-Dependent β-Thalassemia
Authors: Simona Maria Di Modica, Violante Olivari, Emanuele Tanzi, Mariateresa Pettinato, Maria Rosa Lidonnici, Alessia Pagani, Francesca Tiboni, Giuliana Ferrari, Laura Silvestri, Stefano Rivella, Antonella Nai
Journal: Blood (2021)
SAMHD1 Performs Tumor-Promoting Effects in Diffuse Large B-Cell Lymphoma By Inhibiting DNA Damage and Sting-Mediated Cell Pyroptosis
Authors: Yiqing Cai, Xiangxiang Zhou, Shunfeng Hu, Tiange Lu, Xiaomin Chen, Mengfei Ding, Xin Wang
Journal: Blood (2021)
The membrane-associated E3 ubiquitin ligase MARCH3 downregulates the IL-6 receptor and suppresses colitis-associated carcinogenesis
Authors: Heng Lin, Lu Feng, Kai-Sa Cui, Lin-Wen Zeng, Deng Gao, Long-Xiang Zhang, Wen-Hua Xu, Yu-Hao Sun, Hong-Bing Shu, Shu Li
Journal: Cellular and Molecular Immunology (2021)
Abstract 9055: Vascular Age in Patients With Familial Hypercholesterolemia and/or Elevated Lipoprotein(a) Treated With Lipoprotein Apheresis
Authors: Maya S Safarova, Lauryn Gorby, Anne Nugent, Julie-Ann Dutton, Patrick M Moriarty
Journal: Circulation (2021)

Introduction: The 2020 ASE guidelines indicate that an average mean carotid intima-media thickness (CIMT) ≥75th percentile for the patient’s age, sex, race/ethnicity is indicative of increased risk of atherosclerotic cardiovascular disease (ASCVD). With each 10 μm/year reduction of CIMT progression there is a relative risk reduction in the ASCVD event rate by 9% (95% confidence interval, 0.87-0.94). Published nomograms of CIMT percentiles determine “vascular age,” defined as the age at which the composite CIMT value for an individual would represent the median value. Hypothesis: Lipid-modifying treatment with lipoprotein apheresis (LA) over the course of 10 years will affect vascular age in patients with baseline elevated CIMT due to severe hypercholesterolemia. Methods: Ten individuals (mean age 60±9 years, 70% female) with familial hypercholesterolemia and/or elevated lipoprotein(a) [Lp(a)] were treated every two weeks with LA (Liposorber, Kaneka, Japan) between 2005 and 2020 (median duration, 12 years). Results: Acute effects of LA included reduction in LDL-C and Lp(a) levels by a median of 72±8% and 75±7%, respectively. The proportion of patients with average mean CIMT ≥75th percentile was 8/10 at the time of apheresis initiation. LA resulted in mean CIMT reduction of –40μm (IQR, –50 to 20). This translated into 70% (7/10) of cases demonstrating composite mean CIMT below their expected vascular age. The follow-up mean CIMT strongly correlated only with the baseline Lp(a) levels. The number of patients with CIMT above their “vascular age” decreased from 80% to 30% over treatment course. The rate of ASCVD was 37.5 per 1000 person-years while on LA. Conclusions: While annual CIMT progression rates average 15 μm/y, an increase in CIMT seen with advanced age and severe hypercholesterolemia was halted with LA with an estimated annual rate of change in mean common CIMT of –4 μm/y and maximum CIMT of –3μm /y. This analysis demonstrates positive impact of LA on vascular age.
Autologous Haematopoietic Stem Cell Transplantation in Waldenström Macroglobulinemia: A Single-Centre 18-Year Experience
Authors: Suzanne O Arulogun, Charalampia Kyriakou, Jackie Horder, Fiona Newrick, Aisha S Patel, Ali Rismani, Kwee Yong, Ashutosh D. Wechalekar, Shirley D'Sa
Journal: Blood (2021)
Slow Recovery from Inbreeding Depression Generated by the Complex Genetic Architecture of Segregating Deleterious Mutations
Authors: Paula E Adams, Anna B Crist, Ellen M Young, John H Willis, Patrick C Phillips, Janna L Fierst
Journal: Molecular Biology and Evolution (2021)

The deleterious effects of inbreeding have been of extreme importance to evolutionary biology, but it has been difficult to characterize the complex interactions between genetic constraints and selection that lead to fitness loss and recovery after inbreeding. Haploid organisms and selfing organisms like the nematode Caenorhabditis elegans are capable of rapid recovery from the fixation of novel deleterious mutation; however, the potential for recovery and genomic consequences of inbreeding in diploid, outcrossing organisms are not well understood. We sought to answer two questions: 1) Can a diploid, outcrossing population recover from inbreeding via standing genetic variation and new mutation? and 2) How does allelic diversity change during recovery? We inbred C. remanei, an outcrossing relative of C. elegans, through brother-sister mating for 30 generations followed by recovery at large population size. Inbreeding reduced fitness but, surprisingly, recovery from inbreeding at large populations sizes generated only very moderate fitness recovery after 300 generations. We found that 65% of ancestral single nucleotide polymorphisms (SNPs) were fixed in the inbred population, far fewer than the theoretical expectation of ∼99%. Under recovery, 36 SNPs across 30 genes involved in alimentary, muscular, nervous, and reproductive systems changed reproducibly across replicates, indicating that strong selection for fitness recovery does exist. Our results indicate that recovery from inbreeding depression via standing genetic variation and mutation is likely to be constrained by the large number of segregating deleterious variants present in natural populations, limiting the capacity for recovery of small populations.
Subsequent Malignant Neoplasms of the Gastrointestinal Tract after Blood or Marrow Transplantation - a BMTSS Report
Authors: Andrew McDonald, Chen Dai, Lindsey Hageman, Wendy Landier, Jessica Wu, Elizabeth Schlichting, Nora Balas, Liton F. Francisco, Alysia Bosworth, Hok Sreng Te, Lennie Wong, Donna Salzman, Ravi Bhatia, Daniel J. Weisdorf, Stephen J Forman, Mukta Arora, Saro H. Armenian, Smita Bhatia
Journal: Blood (2021)
Myeloid Leukemia Dependencies at CTCF-Enriched Long Noncoding RNA Loci
Authors: Michelle Ng, Lonneke Verboon, Hasan Issa, Raj Bhayadia, Oriol Alejo, Dorit Borchert, Eniko Regenyi, Dirk Reinhardt, Marie-Laure Yaspo, Dirk Heckl, Jan-Henning Klusmann
Journal: Blood (2021)
Abstract 9207: Safety and Efficacy of Catheter Ablation of Atrial Fibrillation in Octogenarians: Insights from the UC San Diego AF Ablation Registry
Authors: Omar M Aldaas, Douglas J Darden, Praneet Mylavarapu, Frederick Han, Kurt S Hoffmayer, David E Krummen, Gordon Ho, Farshad Raissi, Gregory K Feld, Jonathan C Hsu
Journal: Circulation (2021)

Introduction: Catheter ablation improves outcomes in symptomatic atrial fibrillation (AF) patients. However, it’s safety and efficacy in the very elderly (≥80 years old) is not well described. Hypothesis: Catheter ablation of atrial fibrillation in the very elderly is safe and effective. Methods: We performed a retrospective study of all patients who underwent radiofrequency catheter ablation enrolled in the University of California, San Diego AF Ablation Registry. The primary outcome was freedom from atrial arrhythmias on or off antiarrhythmic drugs (AAD). Results: Of 847 patients, 42 (5.0%) were 80 years of age or greater with a median age of 81.5 (80,82.3) and 805 (95.0%) were less than 80 years of age with a median age of 64.4 (57.6,70.2). Among those who were ≥80 years old, 29 were undergoing de novo ablation (69.0%) whereas in the younger cohort, 518 (64.5%) were undergoing de novo ablation (p=0.548). There were no statistically significant differences in fluoroscopy (p=0.406) or procedure times (p=0.076), antiarrhythmic drug use (p=0.611), or procedural complications (p=0.500) between groups. After multivariable adjustment, there were no statistically significant differences in recurrence of atrial arrhythmias on or off AAD (Adjusted Hazard Ratio (AHR) 0.75 (95% CI 0.45-1.23); p=0.252] ( Figure 1) , all-cause hospitalizations [AHR 0.86 (95% CI 0.46-1.60); p=0.626] or all-cause mortality [AHR 4.48 (95% CI 0.59-34.07); p=0.147] between octogenarians and the younger cohort. Conclusion: In this registry analysis, catheter ablation of AF appears similarly effective and safe in patients 80 years or older when compared to a younger cohort.
Systemic IL-15 promotes allogeneic cell rejection in patients treated with natural killer cell adoptive therapy
Authors: Melissa M. Berrien-Elliott, Michelle Becker-Hapak, Amanda F. Cashen, Miriam Jacobs, Pamela Wong, Mark Foster, Ethan McClain, Sweta Desai, Patrick Pence, Sarah Cooley, Claudio Brunstein, Feng Gao, Camille N. Abboud, Geoffrey L. Uy, Peter Westervelt, Meagan A. Jacoby, Iskra Pusic, Keith E. Stockerl-Goldstein, Mark A. Schroeder, John F. DiPersio, Patrick Soon-Shiong, Jeffrey S. Miller, Todd A. Fehniger
Journal: Blood (2021)
Machine-Learning Based Early Warning System for Prediction for Disseminated Intravascular Coagulation after Allogeneic Hematopoietic Stem Cell Transplantation: A Nationwide Multicenter Study
Authors: Zhuo-Yu An, Ye-Jun Wu, Yun He, Xiao-Lu Zhu, Yan Su, Chen-Cong Wang, Tian-Xiao Han, Hai-Xia Fu, Feng-Rong Wang, Xiao-Dong Mo, Yu Wang, Xiang-Yu Zhao, Yuan-Yuan Zhang, Wei Han, Huan Chen, Yao Chen, Chen-Hua Yan, Jing-Zhi Wang, Ting-Ting Han, Yu-Hong Chen, Yi-Fei Cheng, Ying-Jun Chang, Lan-Ping Xu, Kai-Yan Liu, Xiao Jun Huang, Xiaohui Zhang
Journal: Blood (2021)
Aggregation‐Induced Emission Luminogens with Photoresponsive Behaviors for Biomedical Applications
Authors: Jiaqiang Wang, Liyao Zhang, Zhen Li
Journal: Advanced Healthcare Materials (2021)

Fluorescent biomedical materials can visualize subcellular structures and therapy processes in vivo. The aggregation-induced emission (AIE) phenomenon helps suppress the quenching effect in the aggregated state suffered by conventional fluorescent materials, thereby contributing to design strategies for fluorescent biomedical materials. Photoresponsive biomedical materials have attracted attention because of the inherent advantages of light; i.e., remote control, high spatial and temporal resolution, and environmentally friendly characteristics, and their combination with AIE facilitates development of fluorescent molecules with efficient photochemical reactions upon light irradiation. In this review, organic compounds with AIE features for biomedical applications and design strategies for photoresponsive AIE luminogens (AIEgens) are first summarized briefly. Applications are then reviewed, with the employment of photoresponsive and AIE-active molecules for photoactivation imaging, super-resolution imaging, light-induced drug delivery, photodynamic therapy with photochromic behavior, and bacterial targeting and killing being discussed at length. Finally, the future outlook for AIEgens is considered with the aim of stimulating innovative work for further development of this field.
Rituximab Plus Bendamustine and Cytarabine (R-BAC) in Elderly Patients with Newly Diagnosed Mantle Cell Lymphoma: Long Term Follow-up and Mrd Results of a Phase 2 Study from the Fondazione Italiana Linfomi
Authors: Maria Chiara Tisi, Luca Nassi, Caterina Patti, Michele Spina, Simone Ferrero, Monica Tani, Barbara Botto, Anna Lia Molinari, Benedetta Puccini, Emanuele Cencini, Alice Di Rocco, Claudio Chini, Chiara Ghiggi, Renato Zambello, Manuela Zanni, Roberta Sciarra, Martina Ferrante, Caterina Stelitano, Alessandro Re, Stefano Volpetti, Vittorio Ruggero Zilioli, Annalisa Arcari, Francesco Merli, Carlo Visco
Journal: Blood (2021)
Incidence and prediction of HBsAg seroclearance in a prospective multi‐ethnic HBeAg‐negative chronic hepatitis B cohort
Authors: Norah A. Terrault, Abdus S. Wahed, Jordan J. Feld, Stewart L. Cooper, Mark G. Ghany, Mauricio Lisker‐Melman, Robert Perrillo, Richard K. Sterling, Mandana Khalili, Raymond T. Chung, Philip Rosenthal, Robert J. Fontana, Arif Sarowar, Daryl T. Y. Lau, Junyao Wang, Anna S. Lok, Harry L. A. Janssen
Journal: Hepatology (2021)

Achieving HBsAg loss is an important landmark in the natural history of chronic hepatitis B (CHB). A more personalized approach to prediction of HBsAg loss is relevant in counseling patients. This study sought to develop and validate a prediction model for HBsAg loss based on quantitative HBsAg levels (qHBsAg) and other baseline characteristics.The Hepatitis B Research Network (HBRN) is a prospective cohort including 1240 untreated HBeAg-negative patients (1150 adults, 90 children) with median follow-up of 5.5 years. Incidence rates of HBsAg loss and hepatitis B surface antibody (anti-HBs) acquisition were determined, and a predictor score of HBsAg loss using readily available variables was developed and externally validated.Crude incidence rates of HBsAg loss and anti-HBs acquisition were 1.6 and 1.1 per 100 person-years (PY); 67 achieved sustained HBsAg loss for an incidence rate of 1.2 per 100 PY. Increased HBsAg loss was significantly associated with older age, non-Asian race, HBV phenotype (inactive CHB vs. others), HBV genotype A, lower HBV-DNA levels, and lower and greater change in qHBsAg. The HBRN-SQuARe (sex,∆quantHBsAg, age, race) score predicted HBsAg loss over time with area under the receiver operating characteristic curve (AUROC) (95% CIs) at 1 and 3 years of 0.99 (95% CI: 0.987-1.00) and 0.95 (95% CI 0.91-1.00), respectively. In validation in another cohort of 1253 HBeAg-negative patients with median follow-up of 3.1 years, HBRN SQuARe predicted HBsAg loss at 1 and 3 years with AUROC values of 0.99 (0.98-1.00) and 0.88 (0.77-0.99), respectively.HBsAg loss in predominantly untreated patients with HBeAg-negative CHB can be accurately predicted over a 3-year horizon using a simple validated score (HBRN SQuARe). This prognostication tool can be used to support patient care and counseling.
PATH-16. EVALUATION OF SEX-BASED DIFFERENCES IN CLINICAL OUTCOMES AND TUMOR GENOMICS IN PATIENTS WITH NEWLY DIAGNOSED IDH-WILDTYPE GLIOBLASTOMA RECEIVING CHEMORADIATION
Authors: Diana Shi, Mary Jane Lim-Fat, Amin Nassar, Jared Woods, Gilbert Youssef, William Pisano, Sydney Whorral, Marie Allen, Daniel Cagney, Shyam Tanguturi, Daphne Haas-Kogan, Ayal Aizer, J Ricardo McFaline-Figueroa, Ugonma Chukwueke, Eudocia Quant Lee, David Reardon, Lakshmi Nayak, Wenya Linda Bi, Rameen Beroukhim, Keith Ligon, Brian Alexander, Patrick Wen, Rifaquat Rahman
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND We evaluated sex-based differences in clinical outcomes and tumor genomics in patients with newly-diagnosed GBM. METHODS We reviewed 665 IDH-wild type GBM patients with Karnofsky Performance Status (KPS) ≥60 treated at our institution from 2010-2019 including; 585 patients with targeted exome sequencing of 447 cancer associated genes (OncoPanel). Deleterious mutations were defined as homozygous deletions or loss of function mutations of known tumor suppressors (as reported in TCGA, ≥ 3 times in the COSMIC database, or predicted as “damaging” in SIFT and/or “probably damaging” in Polyphen 2) or known oncogenic mutations in proto-oncogenes (reported in TCGA or ≥ 3 times in COSMIC). RESULTS There were 384 (57.7%) males and 281 (42.3%) females. Median OS was 22.5 months for females and 19.3 months for males (hazard ratio [HR] 0.81, 95% CI 1.03-1.48, p = 0.02). On multivariable analysis adjusted for age, KPS ≥90, extent of resection, and MGMT methylation status, female sex (adjusted hazard ratio 0.78, 95% CI [0.64-0.95], p = 0.015) was associated with improved OS. Superior OS in females was observed in MGMT-unmethylated patients (HR 0.69, 95% CI [0.54-0.90], p = 0.005) but not MGMT-methylated patients. Thirteen genes were deleteriously altered in ≥5% of our cohort: CDK4 (12.1% male vs. 7.8% female), CDKN2A (46.5% vs. 45.7%), CDKN2B (41.8% vs. 43.3%), EGFR (34.7% vs. 40.0%, MTAP (18.2% vs. 18.8%), NF1 (11.5% vs. 9.4%), PTEN (28.2% vs. 29.8%), TP53 (28.2% vs. 30.2%), RB1 (5.6% vs. 6.5%), MDM4 (6.2% vs. 5.7%), ATM (5.9% vs. 3.7%), MDM2 (7.4% vs. 4.1%), PIK3R1 (6.2% vs. 4.1%). There were no differences in frequency of mutations in these individual genes between males and females (χ 2 [1, N=585] = 0.05-2.86, p = 0.09-0.86). CONCLUSIONS Female sex is associated with improved survival. We did not identify sex-based differences in deleterious genomic alterations amongst commonly altered genes in GBM.
Protection of Human Factor V from Activated Protein C Using a Monoclonal Antibody-Biochemical Characterization and Evaluation Using a Mouse Injury Model
Authors: Sean Quinn, Lacramioara Ivanciu, Robert J. Davidson, Francis Ayombil, Jeffrey Crosby, Alexey Revenko, Robert A. MacLeod, Brett P Monia, Rodney M. Camire
Journal: Blood (2021)
Serologic Testing for Hepatitis B
Authors: Maroun M. Sfeir, Mary Snayd
Journal: JAMA (2021)

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EXTH-50. THE COMPLEXITIES OF FATTY ACID DESATURATION IN GLIOBLASTOMA
Authors: Nicole Oatman, Biplab Dasgupta
Journal: Neuro-Oncology (2021)

Abstract Fatty acid desaturation is an enzymatic reaction in which a double bond is introduced into an acyl chain. Monounsaturated fatty acids (MUFA) are essential components of membrane. The most abundant MUFA-synthesizing enzyme is the delta 9 desaturate called Stearoyl Co-A Desaturase (SCD and SCD5 in humans, and SCD1-4 in mice). SCD desaturates Stearoyl-CoA (C18) and palmitoyl-CoA (C16) to oleoyl-CoA (C18:1) and palmitoyl-CoA (C16:1), respectively. SCD is often upregulated and a therapeutic target in cancer. We made an unexpected discovery that that median expression of SCD is low in glioblastoma relative to normal brain due to hypermethylation and monoallelic co-deletion with the tumor suppressor PTEN in a subset of patients. Cell lines from this subset, expressed nearly undetectable SCD yet they retained residual SCD enzymatic activity. Surprisingly, these lines evolved to survive independent of SCD through unknown mechanisms. On the other hand, cell lines that escaped such genetic and epigenetic alterations expressed higher levels of SCD and were highly dependent on SCD for survival. Finally, we identify that SCD-dependent lines acquire resistance through a previously unknown mechanism that involved drug-induced target (SCD) upregulation by the transcription factor FOSB. Accordingly, FOSB inhibition blunted acquired resistance and extended survival of tumor bearing mice treated with SCD inhibitor. Our findings reveal an intriguing feature of the cancer genome that may be used to stratify PTEN deleted cancer patients for SCD inhibitor therapy. A recent study showed that some cancer cells can use another MUFA-synthesizing enzyme FADS2 to bypass the SCD reaction. However, our data shows that the SCD inhibitor- resistant GBM lines are also FADS2-independent. Our targeted and untargeted metabolomics studies revealed unexpected findings that cannot be explained by conventional wisdom, and may lead to identification of novel lipogenic targets in GBM.
Efficacy of Severe Acute Respiratory Syndrome Coronavirus-2 Vaccine in Patients With Thoracic Cancer: A Prospective Study Supporting a Third Dose in Patients With Minimal Serologic Response After Two Vaccine Doses
Authors: Valérie Gounant, Valentine Marie Ferré, Ghassen Soussi, Charlotte Charpentier, Héloïse Flament, Nadhira Fidouh, Gilles Collin, Céline Namour, Sandra Assoun, Alexandra Bizot, Zohra Brouk, Eric Vicaut, Luis Teixeira, Diane Descamps, Gérard Zalcman
Journal: Journal of Thoracic Oncology (2021)
Outcomes for Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Treated with Frontline HCVAD-Based Chemotherapy
Authors: Naveen Pemmaraju, Nathaniel R Wilson, Guillermo Garcia-Manero, Koji Sasaki, Joseph D. Khoury, Nitin Jain, Gautam Borthakur, Farhad Ravandi, Naval Daver, Tapan M. Kadia, Courtney D. DiNardo, Elias J. Jabbour, Sherry A. Pierce, John Villarreal, Muzaffar H. Qazilbash, Marina Konopleva, Hagop Kantarjian
Journal: Blood (2021)