tbuckley/cabot-search huggingface dataset:
Abstract 10243: Meta-Analysis of Direct Oral Anticoagulants versus Vitamin K Antagonists in Patients with Atrial Fibrillation and Bioprosthetic Valves
Authors: Yujiro Yokoyama, Alexandros Briasoulis, Hiroki Ueyama, Makoto Mori, Masao Iwagami, Naoki Misumida, Hisato Takagi, Toshiki Kuno
Journal: Circulation (2021)

Objective: The optimal anticoagulation strategy for patients with bioprosthetic valves and atrial fibrillation remain uncertain. Thus, we conducted a meta-analysis using updated evidence comparing direct anticoagulants (DOAC) and vitamin K antagonist (VKA) in patients with bioprosthetic valves and atrial fibrillation. Methods: MEDLINE and EMBASE were searched through March, 2021 to identify randomized control trials (RCT) and observational studies that investigated the outcomes of DOAC and VKA in patients with bioprosthetic valves and atrial fibrillation. The outcomes of interest were all-cause death, major bleeding, and stroke or systemic embolism. Results: Our analysis included 4 RCTs and 6 observational studies which enrolled a total of 6,405 patients with bioprosthetic valves and atrial fibrillation assigned to the DOAC group (n =2,142) and VKA (n =4,263). Pooled analysis demonstrated the similar rates of all-cause death (HR [95% confidence interval [CI]] =0.90 [0.77-1.05]; P =0.18; I 2 =0%)between the DOAC and VKA groups. However, the rates of major bleeding were significantly lower in the DOAC group compared to the VKA group (HR [95% CI] =0.66 [0.48-0.89]; P =0.006; I 2 =0%) (Figure), while the rates of stroke or systemic embolism were similar (HR [95% CI] =0.72 [0.44-1.17]; P =0.18; I 2 =39%). Conclusion: DOAC was associated with lower rates of major bleeding without increasing the risk of stroke or systemic embolism or all-cause death compared to VKA in patients with bioprosthetic valves and atrial fibrillation.
Outcome without any adjuvant systemic treatment in stage I ER+/HER2− breast cancer patients included in the MINDACT trial
Authors: J M N Lopes Cardozo, D Byng, C A Drukker, M K Schmidt, M A Binuya, L J van 't Veer, F Cardoso, M Piccart, C H Smorenburg, C Poncet, E J T Rutgers
Journal: Annals of Oncology (2021)
Cost-Effectiveness of Screening Mammography Beyond Age 75 Years
Authors: John T. Schousboe, Brian L. Sprague, Linn Abraham, Ellen S. O’Meara, Tracy Onega, Shailesh Advani, Louise M. Henderson, Karen J. Wernli, Dongyu Zhang, Diana L. Miglioretti, Dejana Braithwaite, Karla Kerlikowske
Journal: Annals of Internal Medicine (2021)

Background: The cost-effectiveness of screening mammography beyond age 75 years remains unclear. Objective: To estimate benefits, harms, and cost-effectiveness of extending mammography to age 80, 85, or 90 years according to comorbidity burden. Design: Markov microsimulation model. Data Sources: SEER (Surveillance, Epidemiology, and End Results) program and Breast Cancer Surveillance Consortium. Target Population: U.S. women aged 65 to 90 years in groups defined by Charlson comorbidity score (CCS). Time Horizon: Lifetime. Perspective: National health payer. Intervention: Screening mammography to age 75, 80, 85, or 90 years. Outcome Measures: Breast cancer death, survival, and costs. Results of Base-Case Analysis: Extending biennial mammography from age 75 to 80 years averted 1.7, 1.4, and 1.0 breast cancer deaths and increased days of life gained by 5.8, 4.2, and 2.7 days per 1000 women for comorbidity scores of 0, 1, and 2, respectively. Annual mammography beyond age 75 years was not cost-effective, but extending biennial mammography to age 80 years was ($54 000, $65 000, and $85 000 per quality-adjusted life-year [QALY] gained for women with CCSs of 0, 1, and ≥2, respectively). Overdiagnosis cases were double the number of deaths averted from breast cancer. Results of Sensitivity Analysis: Costs per QALY gained were sensitive to changes in invasive cancer incidence and shift of breast cancer stage with screening mammography. Limitation: No randomized controlled trials of screening mammography beyond age 75 years are available to provide model parameter inputs. Conclusion: Although annual mammography is not cost-effective, biennial screening mammography to age 80 years is; however, the absolute number of deaths averted is small, especially for women with comorbidities. Women considering screening beyond age 75 years should weigh the potential harms of overdiagnosis versus the potential benefit of averting death from breast cancer. Primary Funding Source: National Cancer Institute and National Institutes of Health.
Abstract 14012: Trends of Cannabis Use Disorder and Its Impact on Outcomes of Acute Ischemic Stroke: 2007-2018
Authors: Nithin Kurra, Renu Cheriyan, Ifeanyi Munonye, Krupa Patel, Saral Desai, Ntasha Roy, Ahmed M Ali, Abhinay Theli, Achint Patel, Abhishek Lunagariya
Journal: Circulation (2021)

Background: Cannabis is one of the most extensively cultivated illicit drugs internationally. Its legalization and decriminalization in some states of the U.S. has increased its usage. Despite its widespread use, cannabinoid-related cerebrovascular disease is underreported. There are contradicting studies regarding the risk of Acute Ischemic Stroke (AIS) and its outcomes among cannabis users. Hypothesis: Our analysis estimates concurrent Cannabis Usage Disorder (CUD) trends among AIS patients and its impact on AIS outcomes. Methods: Study cohort was derived from the Nationwide Inpatient Sample (NIS) for the years 2007-2018. Hospitalizations due to AIS in the age group of 18-49 were identified using previously validated ICD-9-CM/ICD-10-CM codes. Cochran Armitage trend test and multivariable survey logistic regression modeling were then utilized to analyze temporal trends, predictors, and outcomes. Results: Out of a total 406,987 hospitalizations due to AIS from 2007-2018, 19,614 (4.82%) had concurrent CUD. AIS hospitalizations with concurrent CUD have increased from 3.3% in 2007 to 6.6% in 2018 with a yearly increase of 10% (OR 1.1; 95%CI 1.1-1.1; p&lt;0.01). In multivariable regression analysis, age group 18-34 (OR 2.5; 95% CI 2.3-2.7; p&lt; 0.01); male (OR 1.5; 95%CI 1.4-1.6; p&lt;0.01), African American (OR 2.1; 95% CI 1.9 -2.2, p&lt;0.01), lower socio-economic group (OR 1.3; 95% CI 1.2-1.5, p&lt;0.01), West region (OR 1.5; 95% CI 1.3-1.7, p&lt;0.01), Weight loss (OR 1.3; 95% CI 1.1-1.6, p=0.01), Depression (OR 1.2; 95% CI 1.1-1.3, p =0.001) and other psychiatric disorders were associated with concurrent CUD among AIS patients. After adjusting with confounding factors, CUD was not associated with higher in-hospital mortality (OR 1.0; 95% CI 0.9-1.1, p=0.21) and discharge to facility. Conclusion: Our results show that between 2007 and 2018, hospitalizations due to AIS with concurrent CUD has doubled. This association is significantly higher among 18-34 age group, males, African American, Western US and with concomitant psychiatric disorders. However, CUD was not associated with poor outcomes in AIS. Our study highlights underlying demographic trends and emphasizes the need for further studies to identify the causal association of cannabis use and AIS.
Efficacy of Front-Line Ibrutinib Versus Fludarabine, Cyclophosphamide and Rituximab (FCR) in Patients with CLL. a Multicenter "Real-World" Study
Authors: Yair Herishanu, Shai Levi, Neta Goldschmidt, Fortunato Morabito, Osnat Bairey, Giovanni Del Poeta, Tomer Ziv Baran, Riva Fineman, Francesca Romana Mauro, Odit Gutwein, Gianluigi Reda, Rosa Ruchlemer, Paolo Sportoletti, Luca Laurenti, Lev Shvidel, Marta Coscia, Tamar Tadmor, Marzia Varettoni, Ariel Aviv, Roberta Murru, Andrei Breaster, Yotam Bronstein, Annalisa Chiarenza, Andrea Visentin, Daniela Pietrasanta, Giacomo Loseto, Antonella Zucchetto, Riccardo Bomben, Jacopo Olivieri, Antonino Neri, Davide Rossi, Gianluca Gaidano, Livio Trentin, Robin Foa, Antonio Cuneo, Valter Gattei, Massimo Gentile
Journal: Blood (2021)
Abstract 11263: Multiple Inflammation Biomarkers and Incident Coronary Heart Disease Risk Among Black and White US Adults: The REGARDS Study
Authors: Oluwasegun P Akinyelure, Lisandro Colantonio, Ninad S Chaudhary, Suzanne E Judd, Mary Cushman, Neil Zakai, Edmond K Kabagambe, Virginia J Howard, Monika Safford, Marguerite M Irvin
Journal: Circulation (2021)

Introduction: Inflammation biomarkers have been individually associated with increased risk of coronary heart disease (CHD). However, little is known of the association between multiple inflammation biomarker counts in the high-risk category and incident CHD risk. Methods: We used data from the REasons for Geographic and Racial Differences in Stroke study, an ongoing national cohort of 30,239 Black and White US adults aged ≥45 years recruited in 2003-2007. Baseline levels of C-reactive protein (hsCRP), white blood cell count (WBC) and serum albumin were divided into tertiles. High-risk categories of hsCRP and WBC were defined as levels above the 3 rd tertile (3.75 mg/dL and 6.31 x 10 9 cells/L, respectively) and albumin levels below the 1 st tertile (4.0 g/dL). Four mutually exclusive groups were derived corresponding to having 0, 1, 2 or 3 biomarkers in the high-risk category. Outcome was a composite of incident non-fatal myocardial infarction and fatal CHD. Results: Of 15,738 participants free of CHD at baseline (mean age 63.1 years, 65.3% female, 40.8% black), 38.9% (n = 6,121) had 0, 36.6% (n = 5,765) had 1, 19.7% (n = 3,107) had 2, 4.7% (n = 745) had 3 inflammation biomarkers in the elevated levels. With median follow-up of 10.5 years, 902 (5.7%) participants had incident CHD. The rates of incident CHD and 95% confidence intervals (CI) per 1000 person years increased progressively for individuals with 0, 1, 2, and 3 inflammation biomarkers in the high-risk category: 4.4 (95% CI: 3.9-5.0), 6.3 (95% CI: 5.7-7.0), 8.9 (95% CI: 7.8-10.0), and 10.3 (95% CI: 7.7-12.8), respectively. The fully adjusted hazard ratios (95% CI) for incident CHD associated with 1, 2 and 3 versus no inflammation biomarker in the high-risk category were 1.28 (1.08-1.51), 1.71 (1.42-2.06), and 1.90 (1.43-2.54), respectively (P trend &lt; 0.001) (Table). Conclusions: The count of inflammation biomarkers in the high-risk category is associated with increased risk of CHD independent of traditional risk factors.
EXTH-60. PRECLINICAL STUDY OF PAMIPARIB, A CNS-PENETRANT PARP INHIBITOR, IN IDH1/2 MUTATED GLIOMAS
Authors: Christopher Hong, Ranjini Sundaram, Ranjit Bindra
Journal: Neuro-Oncology (2021)

Abstract Our group has demonstrated that IDH1/2 mutated gliomas harbor intrinsic homologous recombination (HR) defects mediated by the oncometabolite, 2-HG, rendering them sensitive to PARP inhibitors. Here, we studied the efficacy of pamiparib, a CNS-penetrant PARP inhibitor with potent PARP trapping ability, in combination with temozolomide (TMZ) and radiation therapy (RT) in IDH1/2 mutated gliomas. We also studied the pharmacokinetics of BGB290 to demonstrate CNS penetrance. We performed a series of DNA repair functional studies with in vitro short- and long-term viability assays, as well as in vivo studies utilizing an orthotopically injected rat glioma model with bioluminescence. Pharmacokinetics was measured with a previously validated LCMS/MS technique. Short-term and long-term viability assays in paired isogenic IDH1 wildtype and mutant cell lines showed the IDH1 mutation conferred enhanced sensitivity to pamiparib with several-fold decreases in IC50, as well as TMZ and RT as expected. Combination treatment with pamiparib and TMZ or RT also demonstrated synergistic interactions in these same cell lines, dependent upon IDH1 mutation status. An ELISA assay confirmed PARylation inhibition by pamiparib at the nanomolar range in a dose-dependent manner. Pharmacokinetic analysis demonstrated favorable CNS penetration with tumor:plasma ratios ( &amp;gt;0.20) observed with low (3 mg/kg) and high (6 mg/kg) doses of pamiparib, orally administered BID to rats harboring intrinsic rat glioma intracranial tumors. These levels persisted between 2 and 8 hours after last dosing. Pamiparib also selectively penetrated tumors over normal brain with normal brain:plasma ratios under 0.20. These data suggest pamiparib may selectively target IDH1/2 mutated gliomas and act synergistically with TMZ and RT to exploit intrinsic HR defects associated with these tumors. Pharmacokinetic analysis suggest favorable CNS penetration after standard bid oral administration. As such, these results lay the groundwork for study of pamiparib with TMZ and/or RT in patients with IDH1/2 mutated gliomas.
ASER: Animal Sex Reversal Database
Authors: Yangyang Li, Zonggui Chen, Hairong Liu, Qiming Li, Xing Lin, Shuhui Ji, Rui Li, Shaopeng Li, Weiliang Fan, Haiping Zhao, Zuoyan Zhu, Wei Hu, Yu Zhou, Daji Luo
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract Sex reversal, representing extraordinary sexual plasticity during the life cycle, not only triggers reproduction in animals but also affects reproductive and endocrine system-related diseases and cancers in humans. Sex reversal has been broadly reported in animals; however, an integrated resource hub of sex reversal information is still lacking. Here, we constructed a comprehensive database named ASER (Animal Sex Reversal) by integrating sex reversal-related data of 18 species from teleostei to mammalia. We systematically collected 40,018 published papers and mined the sex reversal-associated genes (SRGs), including their regulatory networks, from 1611 core papers. We annotated homologous genes and computed conservation scores for whole genomes across the 18 species. Furthermore, we collected available RNA-seq datasets and investigated the expression dynamics of SRGs during sex reversal or sex determination processes. In addition, we manually annotated 550 in situ hybridization (ISH), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC) images of SRGs from the literature and described their spatial expression in the gonads. Collectively, ASER provides a unique and integrated resource for researchers to query and reuse organized data to explore the mechanisms and applications of SRGs in animal breeding and human health. The ASER database is publicly available at http://aser.ihb.ac.cn/.
Abstract 10681: Effect of Low vs. High Home-Based Walking Exercise on Physical Activity in Patients with Peripheral Artery Disease: The Lite Randomized Clinical Trial
Authors: Joshua Slysz, Bonnie Spring, W. Jack Rejeski, Todd Manini, Jack Guralnik, Daniel E Forman, Lu Tian, Lihui Zhao, Dongxue Zhang, Mary M McDermott
Journal: Circulation (2021)

Objective: In a randomized clinical trial of people with lower extremity peripheral artery disease (PAD), to test whether walking exercise conducted at a pace without ischemic leg symptoms improved physical activity more than walking exercise conducted at a pace that induced ischemic leg symptoms and more than an attention control group. Methods &amp; Results: In the LITE multi-centered clinical trial, 305 participants with PAD (69±40 years, 181 (59%) black, 146 (48%) female) were randomized to: 1) walking exercise conducted at a comfortable pace without ischemic leg symptoms (low-intensity), 2) walking exercise conducted at a pace eliciting ischemic leg symptoms (high-intensity), or 3) an attention-control group for 12-months. Physical activity (i.e., activity counts per minute) was a pre-specified secondary outcome. Both exercise groups were asked to walk for exercise in an unsupervised setting for up to 5 times/week for up 50 minutes/session. Physical activity was measured for up to 10 days using an ActiGraph accelerometer at baseline, 6-month, and 12-month follow-up. Low intensity exercise increased physical activity significantly less than high intensity exercise at 6-month follow-up (-74 counts per minute, 95% CI: -123, -26, P=0.003; Table 1) and 12-month follow-up (-47 counts per minute, 95% CI: -79, -15, P=0.004; Table 1). High intensity exercise increased physical activity significantly more than control at 6-month follow-up (+104 counts per minute, 95% CI: 48, 162, P&lt;0.001; Table 1) and 12-month follow-up (+55 cpm, 95% CI: 18, 93, P=0.004; Table 1). There was no difference between the low intensity group and control at 6-month or 12-month follow-up (Table 1). Conclusion: These results support home-based walking exercise conducted at a pace that induces ischemic leg symptoms, but not walking exercise conducted at a comfortable pace without ischemic leg symptoms, to improve physical activity in people with PAD.
Two-Year Follow-up of Transcend NHL 001, a Multicenter Phase 1 Study of Lisocabtagene Maraleucel (liso-cel) in Relapsed or Refractory (R/R) Large B-Cell Lymphomas (LBCL)
Authors: Jeremy S. Abramson, M. Lia Palomba, Leo I. Gordon, Matthew A. Lunning, Michael Wang, Jon E. Arnason, Enkhtsetseg Purev, David G. Maloney, Charalambos Andreadis, Alison R. Sehgal, Scott R. Solomon, Nilanjan Ghosh, Ana Kostic, Yeonhee Kim, Ken Ogasawara, Christine Dehner, Tanya Siddiqi
Journal: Blood (2021)
Isolation of nanobodies with potential to reduce patients' IgE binding to Bet v 1
Authors: Ines Zettl, Tatiana Ivanova, Maria R. Strobl, Christina Weichwald, Oksana Goryainova, Evgenia Khan, Marina V. Rutovskaya, Margarete Focke‐Tejkl, Anja Drescher, Barbara Bohle, Sabine Flicker, Sergei V. Tillib
Journal: Allergy (2021)

Recent studies showed that a single injection of human monoclonal allergen-specific IgG antibodies significantly reduced allergic symptoms in birch pollen-allergic patients. Since the production of full monoclonal antibodies in sufficient amounts is laborious and expensive, we sought to investigate if smaller recombinant allergen-specific antibody fragments, that is, nanobodies, have similar protective potential. For this purpose, nanobodies specific for Bet v 1, the major birch pollen allergen, were generated to evaluate their efficacy to inhibit IgE-mediated responses.A cDNA-VHH library was constructed from a camel immunized with Bet v 1 and screened for Bet v 1 binders encoding sequences by phage display. Selected nanobodies were expressed, purified, and analyzed in regards of epitope-specificity and affinity to Bet v 1. Furthermore, cross-reactivity to Bet v 1-homologues from alder, hazel and apple, and their usefulness to inhibit IgE binding and allergen-induced basophil activation were investigated.We isolated three nanobodies that recognize Bet v 1 with high affinity and cross-react with Aln g 1 (alder) and Cor a 1 (hazel). Their epitopes were mapped to the alpha-helix at the C-terminus of Bet v 1. All nanobodies inhibited allergic patients' polyclonal IgE binding to Bet v 1, Aln g 1, and Cor a 1 and partially suppressed Bet v 1-induced basophil activation.We identified high-affinity Bet v 1-specific nanobodies that recognize an important IgE epitope and reduce allergen-induced basophil activation revealing the first proof that allergen-specific nanobodies are useful tools for future treatment of pollen allergy.
QOLP-04. THE KETOGENIC DIET PLUS STANDARD CARE FOR RECENTLY DIAGNOSED GLIOBLASTOMA: A PHASE 1 SAFETY AND FEASIBILITY TRIAL
Authors: Jethro Hu, L J Amaral, Gillian Gresham, Thomas Nelson, Amelia Welborn, Laura Lockshon, Mourad Tighiouart, Sungjin Kim, Brandon Noorvash, Alexandra Mack, Jeremy Rudnick, Surasak Phuphanich, Scott Irwin, Stephen Freedland
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION There is abundant interest in the potential therapeutic and supportive role of a ketogenic diet (KD) for glioblastoma patients. We conducted a single-arm phase 1 trial to assess the safety and feasibility of KD plus standard-of-care (SOC) in glioblastoma patients (NCT03451799). METHODS Adults within 3 months of diagnosis participated in a 16-week intervention of a classic 3:1 KD (grams fat : grams carbohydrate + protein) with dietitian support. Blood glucose and ketone levels were assessed twice daily (Keto-Mojo), with remote monitoring of daily weight and activity (Fitbit). The primary objective was to assess safety (weight stability, CTCAE) and feasibility (maintaining ketosis &amp;gt; 0.3mM for &amp;gt; 50% of study period). Secondary objectives included assessments of progression-free survival (PFS), overall survival (OS), health-related quality of life (HRQOL), and cognition (MoCA). RESULTS From 04/2018-02/2021, 14 patients were evaluable: female:male, 8:6, median age 55 years, KPS 80, BMI 24.5. MGMT promoter methylation: 6 present, 7 absent, 1 indeterminate. Adherence to KD was high, with all patients maintaining ketosis ( &amp;gt; 0.3mM) &amp;gt; 50% and 11 patients maintaining ketosis &amp;gt; 85% of study days. Adverse events (&amp;gt; Grade 2) potentially attributable to KD: appetite loss (Grade 2: 2); fatigue (Grade 2: 5); flu-like symptoms (Grade 2: 1); constipation (Grade 2: 5, Grade 3: 1). No patients were removed from study for safety reasons. HRQOL was stable, with improvements in role function (not statistically significant). MoCA score improved in 10/14 patients. Median PFS and OS from KD initiation were 11.7 and 29.1 months, respectively. CONCLUSION Our findings suggest that a supervised KD plus SOC is safe and feasible in glioblastoma patients. KD was well-tolerated with encouraging trends in HRQOL and cognition. PFS and OS in this small trial compare favorably to historical control. A multicenter phase 2 trial powered to assess efficacy is planned.
BIOM-43. CROSS-PLATFORM ROBUSTNESS IN THE GLUCOCORTICOID RESPONSE PHARMACODYNAMIC BIOMARKER
Authors: Emily Tang, John Wiencke, Gayathri Warrier, Helen Hansen, Lucie McCoy, Terri Rice, Paige Bracci, Margaret Wrensch, Jennie Taylor, Jennifer Clarke, Devin Koestler, Lucas Salas, Brock Christensen, Karl Kelsey, Annette Molinaro
Journal: Neuro-Oncology (2021)

Abstract The neutrophil dexamethasone methylation index (NDMI) is an algorithm-based biomarker to assess individuals’ exposures to dexamethasone, a synthetic glucocorticoid commonly administered for inflammation. Cortisol is the main endogenous glucocorticoid that controls vital processes including the immune response and lipid and carbohydrate metabolism. Variations in the NDMI score reflect individuals’ sensitivities of exposures to both exogenous and endogenous glucocorticoids, and this biomarker was trained using elastic net regression on Illumina’s most recent DNA methylation beadarray, the EPIC array, which contains 850,000 cytosine-guanine (CpG) sites. While technology for microarray research continues to advance over time, researchers are capable of conducting more comprehensive epigenome-wide association studies (EWAS). However, many studies are still run and archived using Illumina’s historical 450K platform with approximately 450,000 CpGs, and there are fewer published databases using the 850K EPIC array. To evaluate the cross-platform bioinformatic comparability, we performed elastic net regression modeling using predictors available in the 450K to train the NDMI. Among the 135 pre-surgery glioma cases from the UCSF Immune Profiles Study (IPS), NDMI scores between the 450K and 850K model were strongly correlated (r = 0.99, p &amp;lt; 0.0001). In the 311 controls from the UCSF Adult Glioma Study (AGS), similar correlations were observed (r = 0.96, p &amp;lt; 0.0001). We observe that NDMI remains a robust tool using historical 450K data and conclude that this algorithmic tool is capable of detecting the variations in individuals’ responses to dexamethasone.