tbuckley/cabot-search huggingface dataset:
Abstract 9416: Monocyte Subsets and Exercise Capacity in Patients With Atrial Fibrillation With Preserved Left Ventricular Function
Authors: farhan Shahid, Gregory Lip, Eduard Shantsila
Journal: Circulation (2021)

Introduction: Monocytes play important roles in inflammation, angiogenesis and tissue repair in cardiovascular disease. This study examined differences in monocyte subset numbers, subsequent markers of inflammation and cardiac fibrosis in patients with permanent atrial fibrillation and preserved left ventricular function with regards to peak exercise capacity (cardiopulmonary exercise testing and 6 minute walk test), quality of life and hospitalisation. Furthermore, the effects of spironolactone vs placebo on the quantitative measurement of these potential biomarkers were assessed in a double blind randomised study over a 2 year period. Methods: Three monocyte subsets [CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2- (Mon3)] were analysed by flow cytometry and ELISA to quantify makers of fibrosis in the form of Galectin 3, Type III Procollagen Peptide and Type I Procollagen Peptide. SPSS software was used to carry out statistical analysis of all 250 patients in the study cohort using stepwise multivariant linear regression analysis. Independent samples T testing between spironolactone and placebo groups were carried out. Results: Monocyte subsets CD16 Mon3 (p=0.001) and CD42 MPA3 (p=0.030) were found to be predictors of peak VO 2 . Comparison of monocyte subsets at end of study showed no differences between Mon1 (p=0.86), Mon2 (p=0.66) or Mon3 (p=0.81) subsets and their subsequent makers of inflammation and fibrosis between the treatment and placebo control group. This held true for further markers of cardiac fibrosis with regards to 6 minute walk test , quality of life assessment and hospitalisation. Conclusions: This study shows that monocyte subsets can be potential biomarkers of exercise capacity which in the form of cardiopulmonary testing is known to have morbidity and mortality implications. CD16 Mon3 were significantly related to beneficial outcomes with regards to a peak exercise capacity in respect to VO 2 max (higher CD16 Mon3 count associated with higher peak VO 2 performance). Spironolactone has no impact on primary or secondary outcome in this study.
NMD abnormalities during brain development in the Fmr1-knockout mouse model of fragile X syndrome
Authors: Tatsuaki Kurosaki, Hitomi Sakano, Christoph Pröschel, Jason Wheeler, Alexander Hewko, Lynne E. Maquat
Journal: Genome biology (2021)

Abstract Background Fragile X syndrome (FXS) is an intellectual disability attributable to loss of fragile X protein (FMRP). We previously demonstrated that FMRP binds mRNAs targeted for nonsense-mediated mRNA decay (NMD) and that FMRP loss results in hyperactivated NMD and inhibition of neuronal differentiation in human stem cells. Results We show here that NMD is hyperactivated during the development of the cerebral cortex, hippocampus, and cerebellum in the Fmr1 -knockout (KO) mouse during embryonic and early postnatal periods. Our findings demonstrate that NMD regulates many neuronal mRNAs that are important for mouse brain development. Conclusions We reveal the abnormal regulation of these mRNAs in the Fmr1 -KO mouse, a model of FXS, and highlight the importance of early intervention.
10 Tertiary lymphoid structure in pancreatic ductal adenocarcinoma; a potential target in an immunologically inert malignancy
Authors: Kasimu Adoke, Sanusi Haruna
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Tertiary lymphoid structure (TLS) are immune aggregates with various degrees of organization that forms outside of secondary lymphoid organ in response to chronic inflammation, infection or tumours. 1 2 TLS like secondary lymphoid organ, has defined T cell zones, B cell zones, high endothelial venules (HEV) and matured dendritic cells. They have been shown to correlate with increase patient survival in many tumours. Pancreatic ductal carcinoma (PDAC) is generally believed to be immunologically inert, low tumour mutation burden (TMB) and poor response to checkpoint blockade. Recent findings in some patients with PDAC shows significant intratumoral cytotoxic T cell infiltration and a high Inflammatory signature. Since current immunotherapy aim to enhance CD 8+ T cells, we aim to investigate the contribution of humoral immunity in patients with TLS in PDAC. Methods Tissue blocks were obtained from departmental archive and sections were cut and stained with routine H&amp;E of all patients who underwent surgery for pancreatic cancer from 2015–2021 at Federal Medical Centre Birnin Kebbi. Serial sections were done at 5µ and four immunohistochemical stains CD 3, CD8, CD20 and PD-L1 were used. Statistical analysis was done using spss version 24. Results A total of nine cases of PDAC were diagnosed during the period with a Male Female ratio of 1:1.25 with an age range of 40–68 years and a mean age of 57.7±8.4. Five cases (55.6%) of PDAC showed TLS with marked expression of CD20 B+ cells seen in all five cases (figures 1 and 2). Also expressed are CD 8+ cytotoxic T cells and PD-L1. Prognosis was better in patients with TLS compare with those without TLS. Abstract 10 Figure 1 TLS in pancreatic ductal adenocarcinoma. Abstract 10 Figure 2 CD 20 stain in TLS Conclusions TLS can be a potential therapeutic target to explore in the future for treatment of some cancers including PDAC through induction of TLS formation in inert tumours or B lymphocyte specific target. References Pitzalis C, Jones GW, Bombardieri M, Jones S. Ectopic lymphoid like structures in infection, cancer and autoimmunity. Nat Rev Immunol 2014; 14 : 447–462. Neyt K, Perros F, Geurtsvan C, Hammad H. Lambrecht B. Tertiary lymphoid organs in infection and autoimmunity. Trends Immunol 2012; 33 : 297–305. Ethics Approval Ethical Approval was obtained for this study with Ethics number KSHREC Registration Number:104:6/2019 Consent N/A
A Hierarchical‐Structured Mineralized Nanofiber Scaffold with Osteoimmunomodulatory and Osteoinductive Functions for Enhanced Alveolar Bone Regeneration
Authors: Yang He, Mi Tian, Xilin Li, Jianwen Hou, Song Chen, Guang Yang, Xian Liu, Shaobing Zhou
Journal: Advanced Healthcare Materials (2021)

Abstract Alveolar bone resorption is a major cause of teeth loss and jeopardizes the osseointegration of dental implants, greatly affecting patient's quality of life and health. It is still a great challenge to completely regenerate the alveolar bone defect through traditional guided bone regeneration (GBR) membranes due to their limited bioactivity and regeneration potential. Herein, a new hierarchical‐structured mineralized nanofiber (HMF) scaffold, which is combined with both anisotropic and isotropic nanofibrous surface topography and the mineralized particles, is fabricated via a simple template‐assisted electrospinning technology and in situ mineralization method. This HMF scaffold can not only directly induce osteogenic differentiation of bone mesenchymal stem cells (osteoinduction), but also stimulate macrophage toward pro‐healing (M2) phenotype‐polarization with an elevated secretion of the pro‐healing cytokines, eventually enhancing the osteogenesis (osteoimmunomodulation). The results of in vivo rat alveolar bone defect repair experiments demonstrate that as compared with the combination of commercial Bio‐Gide and Bio‐Oss, the single HMF scaffold shows comparable or even superior bone repair effect, with better tissue‐integration and more suitable degradation time and accompanied by a simplified operation.
Adverse Outcomes in Acute Myeloid Leukemia Are Associated with Tumor Cell-Mediated Immunosuppression
Authors: Francesca Ferraro, Christopher A Miller, Keegan A Christensen, Nichole M Helton, Michelle O'Laughlin, Robert Fulton, Jessica Kohlschmidt, Ann-Kathrin Eisfeld, Bloomfield Clara, Sai Mukund Ramakrishnan, Lukas D Wartman, John Welch, Matthew Christopher, Sharon E Heath, Peter Westervelt, Jack D Baty, Jacqueline E. Payton, Michael Retting, Daniel C. Link, Matthew J. Walter, John F. DiPersio, Ryan Day, Geoffrey L. Uy, Matthew Schuelke, David H Spencer, Timothy J Ley
Journal: Blood (2021)
Adaptive Hydrogels Based on Nanozyme with Dual‐Enhanced Triple Enzyme‐Like Activities for Wound Disinfection and Mimicking Antioxidant Defense System
Authors: Yang Li, Rongzhan Fu, Zhiguang Duan, Chenhui Zhu, Daidi Fan
Journal: Advanced Healthcare Materials (2021)

Bacterial infection and oxidative stress are two critical problems for chronic infected wound healing. Here, molybdenum disulfide nanosheets (MoS2 NSs) with triple enzyme-like activities are loaded onto carbon nanotubes (CNTs) and incorporated into multifunctional hydrogels aiming to eradicate bacteria and eliminate free radicals. The nanozyme activities of MoS2 are significantly enhanced through CNTs and near-infrared irradiation. The hydrogel exhibits significant antibacterial performance attributed to the peroxidase-like activity (catalyzing hydrogen peroxide (H2 O2 ) into hydroxyl free radicals (•OH)) under acidic conditions, glutathione loss, and photothermal therapy. Additionally, the nanozyme can mimic the superoxide-like activity to transform the superoxide radicals (O2•- ) into H2 O2 and oxygen (O2 ), then H2 O2 is further depleted into O2 via the catalase-like activity, benefitting from which and •OH scavenging ability, the hydrogel shows excellent scavenging free radical ability in neutral environment and provides abundant O2 for wound healing. The multifunctional hydrogel, crosslinked by dynamic boron ester bonds, exhibits adhesiveness, self-healing, and shape-adaptivity, which can fill the cavity of irregular wounds and promote the nanozyme to play the role with maximum efficiency. The hydrogels notably accelerate the skin reconstruction through killing bacteria, clearing ROS, promoting collagen deposition and angiogenesis.
Azacitidine (AZA) for Patients with Vexas and Myelodysplastic Syndrome (MDS): Data from the French Vexas Registry
Authors: Thibault Comont, Maël Heiblig, Jeremie Dion, Etienne Riviere, Louis Terriou, Julien Rossignol, Virginie Rieu, Guillaume Le Guenno, Alexis Mathian, Achille Aouba, Julien Vinit, Benjamin Terrier, Olivier Kosmider, Sophie Georgin-Lavialle, Pierre Fenaux, Arsene Mekinian
Journal: Blood (2021)
Venetoclax and Azacitidine in the Treatment of Patients with Relapsed/Refractory Myelodysplastic Syndrome
Authors: Amer M. Zeidan, Uma Borate, Daniel A. Pollyea, Andrew M. Brunner, Fernando Roncolato, Jacqueline S. Garcia, Robin J Filshie, Olatoyosi Odenike, Anne-Marie Watson, Ravi Krishnadasan, Ashish Bajel, Kiran Naqvi, Jiuhong Zha, Leah Hogdal, Ying Zhou, David Hoffman, Steve Kye, Guillermo Garcia-Manero
Journal: Blood (2021)
Abstract 9563: Preventive Therapy Changes Following Coronary Computed Tomography Angiography versus Invasive Coronary Angiography in Patients With Nonobstructive Coronary Artery Disease
Authors: Nare Torosyan, Brandon Schwartz, Billy Chen, Joseph Ebinger, Heidi Gransar, Alan Rozanski, C N Bairey Merz, Daniel Berman
Journal: Circulation (2021)

Introduction: Coronary computed tomography angiography (CCTA) in SCOT-HEART led to increased preventive therapy for coronary artery disease (CAD). We hypothesized that atherosclerosis on CCTA would lead to greater preventive therapy changes compared to invasive coronary angiography (ICA). Methods: We studied 429 consecutive patients with available electronic health records and nonobstructive CAD (1-69% epicardial stenosis) by CCTA for assessment of chest pain or exertional dyspnea (n=143), ICA (n=142), or no CAD on CCTA (n=144). Changes in preventive therapies were assessed at 6 weeks and 6 months. Statin intensification was defined as change to greater LDL-lowering capacity. Intensification of antiplatelet agents, ACEI/ARB, or beta-blockers was defined as increased dose. Pairwise comparisons were made with Bonferroni adjustment. Results: There was no difference in age or gender in nonobstructive CAD patients ( Table ). ICA patients had more baseline therapies. Six week statin initiation was more common (p=0.006) in CCTA nonobstructive group, but not statin intensification (p=0.24) ( Table ). Six month LDL lowering was observed in CCTA (114±40 to 94±39 mg/dL, p&lt;0.001), but not ICA (95±41 to 87±36 mg/dL, p=0.10) nonobstructive patients. Younger age (OR 0.96; 95% CI 0.93-0.99, p=0.006), but not modality (CCTA compared to ICA OR 1.12; 95% CI 0.60-2.07, p=0.73) was associated with statin initiation or intensification at 6 weeks in nonobstructive patients. Greater change in therapies was found in nonobstructive patients by both modalities vs normal coronaries ( Table ). Conclusions: Nonobstructive CAD on CCTA is associated with greater statin initiation, but not intensification, at 6 weeks and lowering of LDL compared to ICA. Antiplatelet, beta-blocker, or ACEI/ARB prescriptions were not different in nonobstructive CAD by CCTA vs ICA. More preventive therapy changes occurred in nonobstructive CAD by either modality vs normal coronaries.
Abstract 10016: Potential of Stress T1 Mapping for Detection of Microvascular Dysfunction Without Contrast Agents
Authors: Hisanori Kosuge, Shoko Hachiya, Yasuhiro Fujita, Satoshi Hida, Taishiro Chikamori
Journal: Circulation (2021)

Introduction: Ischemia of hypertrophic myocardium due to microvascular dysfunction is related to worse prognosis in hypertrophic cardiomyopathy (HCM). Stress T1 mapping is a novel cardiac magnetic resonance (CMR) method without contrast agents to be able to assess myocardial blood flow. Hypothesis: We assessed the hypothesis that stress T1 mapping can detect microvascular dysfunction in HCM patients. Methods: Forty-one consecutive subjects without history of coronary artery disease (mean age : 60±3 years, 25 HCM patients, 10 concentric left ventricular hypertrophy (LVH) patients and 6 control subjects) underwent CMR at 3T including cine imaging, rest and adenosine stress T1 mapping, and late gadolinium enhancement (LGE). Native and stress T1 values were measured as an averaged T1 values in the septum of 3 short-axis slices of base-to-apex left ventricle myocardium and T1 reactivity (ΔT1) was calculated as follows: ΔT1 (%) = (T1stress - T1rest)/T1rest х 100. Thirteen HCM patients underwent phase-contrast imaging of coronary sinus flow during rest and adenosine stress to assess coronary flow reserve (CFR). Results: Native T1 values in HCM patients (1271±12ms) showed no significant differences compared with LVH (1225±13ms, p=0.0877) and control subjects (1243±8ms, p=0.534), but ΔT1 in HCM patients (4.00±0.36%) was significantly lower than that in control subjects (5.97±0.41%, p=0.0272), but not in LVH patients (4.95±0.29%, p=0.265, Figure 1). In HCM patients, native T1 values and ΔT1 showed no significant differences between LGE-positive (n=19) and LGE-negative (n=6) groups (native T1: 1274±15ms vs. 1260±20ms, p=0.632, ΔT1: 4.55±0.79% vs. 3.82±0.41%, p=0.394). A moderate positive correlation between ΔT1 and CFR was seen (β=0.697, p=0.0398). Conclusions: T1 reactivity (ΔT1) was reduced in HCM patients compared to control subjects. Stress T1 mapping is a promising CMR method for the assessment of microvascular dysfunction without contrast agents.
Brain Volume Alterations Using 3tesla Magnetic Resonance and Neuropsychological Findings in Gaucher Disease Patients
Authors: Maria Giulia Tullo, Francesca Caramia, Gianmarco Tessari, Carlo Di Bonaventura, Rosaria Turchetta, Emanuele Cerulli Irelli, Anna Teresa Giallonardo, Rocco Plateroti, Giovanna Palumbo, Nicola Monaco, Valeria Filipponi, Marcella Nebbioso, Patrizia Mancini, Cecilia Guariglia, Fiorina Giona
Journal: Blood (2021)
HHV-6 in the Lymphoma Microenvironment: Both Chicken and Egg?
Authors: Genevieve M Crane, Dmitry Tychinin, Anton Karelin, Aleksandr Cherdintsev, Olga Kudryashova, Evgeniy Egorov, Sandrine Degryse, Nikita Kotlov, Alexander Bagaev, Joseph Casano, Jonathan Reichel, Lisa Giulino Roth, Mikhail Roshal, Sakellarios Zairis, Raul Rabadan, Olivier Elemento, Giorgio Inghirami, Ethel Cesarman
Journal: Blood (2021)
Abstract 9200: In-Hospital Outcomes and Readmission Rates of Transcatheter Aortic Valve Replacement in Mixed Aortic Valve Disease
Authors: Phillip Rubin, Jelani Grant, Louis T Vincent, Sharde F Chambers, Bertrand Ebner, Jennifer Maning, Odunayo Olorunfemi, Rosario A Colombo, JOAO F BRAGHIROLI
Journal: Circulation (2021)

Introduction: Transcatheter Aortic Valve Replacement (TAVR) is indicated in patients with severe aortic stenosis (AS) and is increasingly performed in patients with combined AS and aortic regurgitation. We evaluated in-hospital outcomes and readmission rates after TAVR in patients with mixed aortic valve disease (MAVD). Methods: A total of 100,573 TAVR procedures were identified between 2011-2017 using ICD-9 and -10 codes from the Nationwide Readmissions Database (NRD). We separated patients into two cohorts, those with MAVD and those with pure AS. Primary outcome was post-TAVR all-cause inpatient mortality; secondary outcomes included rates of 30- and 90-day readmissions, paravalvular leak (PVL), permanent pacemaker (PPM) insertion, acute kidney injury, major bleeding, postoperative ischemic stroke, total cost of hospitalization and length of hospital stay. Results: A total of 3,260 patients had MAVD (median age 83 years, 43.5% women). In-hospital mortality (2.5% vs 2.6%, p=0.531), rates of PVL (1.0% vs 1.3%, p=0.056) and hospital length of stay (5.8±7.8 vs. 6.7±7.8, p=0.126) were similar between the MAVD and pure AS groups. 30- (0.5% vs. 8.8%, p&lt;0.001) and 90-day readmission rates (0.8% vs. 16.0%, p&lt;0.001), major bleeding (7.4% vs. 9.6%, p&lt;0.001), acute kidney injury (12.9% vs. 15.1%, p&lt;0.001), postoperative ischemic stroke (2.0% vs. 5.7%, p&lt;0.001) and mechanical circulatory support use (1.9% vs. 4.5%, p&lt;0.001) were less prevalent in the MAVD cohort. Using logistic regression, MAVD was not predictive of mortality in patients undergoing TAVR (adjOR: 1.25, 95% CI; 0.99 to 1.57, p=0.056), however MAVD was associated with: decreased odds of 30- (adjOR: 0.05, 95% CI; 0.03 to 0.08, p&lt;0.001) and 90-day readmission rates (adjOR: 0.04, 95% CI; 0.03 to 0.06, p&lt;0.001), and higher odds of PPM implantation (adjOR: 1.46, 95% CI; 1.29 to 1.65, p&lt;0.001). Conclusion: Despite differences in the aortic valve and left ventricular anatomy (pressure versus volume related adaptive changes) in patients with MAVD and pure AS, TAVR appears safe and feasible. However, patients with MAVD were more likely to have permanent pacemakers implanted. The results of our study warrant further randomized controlled studies to confirm these findings.
Racial and Ethnic Disparities Among Participants in Precision Oncology Clinical Studies
Authors: Christopher M. Aldrighetti, Andrzej Niemierko, Eliezer Van Allen, Henning Willers, Sophia C. Kamran
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Precision oncology is revolutionizing cancer care, allowing for personalized treatments to improve outcomes. Cancer research has benefitted from well-designed studies incorporating precision medicine objectives, but it is unclear if these studies are representative of the diverse cancer population. <h3>Objective</h3> To evaluate racial and ethnic representation in breast, prostate, lung, and colorectal cancer studies incorporating precision oncology objectives in the Clinicaltrials.gov registry and compare with the incidence of these cancer types in racial and ethnic minority groups in the US population. <h3>Design, Setting, and Participants</h3> This cross-sectional study identified US-based breast, prostate, lung, and colorectal cancer studies incorporating precision oncology objectives for reporting of race and ethnicity. The Surveillance, Epidemiology, and End Results and US Census databases were used to determine cancer incidence by race and ethnicity, linked with cancer type and median year of enrollment for each trial. Data were collected and analyzed between December 2020 and April 2021. <h3>Main Outcomes and Measures</h3> The expected number of participants per study by each racial and ethnic group was calculated based on the corresponding US-based proportion. Under- and overrepresentation was defined as the ratio of the actual number of enrolled cases to the expected number of cases for each trial by cancer type. Ratios above 1 indicated overrepresentation while a ratio below 1 indicated underrepresentation. Random-effects meta-analysis of representation ratios of individual trials was performed to weigh each individual study. <h3>Results</h3> Of 93 studies encompassing 5867 enrollees with race and ethnicity data; 4826 participants (82.3%) were non-Hispanic White, 587 (10.0%) were Black, and 238 (4.1%) were Asian. Per observed-to-expected ratios, White participants were overrepresented in all studies, with a ratio of 1.35 (95% CI, 1.30-1.37), as well as Asian participants, with a ratio of 1.46 (95% CI, 1.28-1.66), while Black participants (ratio, 0.49; 95% CI, 0.45-0.54), Hispanic participants (ratio, 0.24; 95% CI, 0.20-0.28), and American Indian and Alaskan Native participants (ratio, 0.43; 95% CI, 0.24-0.78) were underrepresented. By individual cancer site, White participants were consistently overrepresented in all studies, while Black and Hispanic participants were underrepresented. <h3>Conclusions and Relevance</h3> This analysis found that precision oncology studies for breast, lung, prostate, and colorectal cancers vastly underrepresent racial and ethnic minority populations relative to their cancer incidence in the US population. It is imperative to increase diversity among enrollees so that all individuals may benefit from cancer research breakthroughs and personalized treatments.
Easix Predicts Severe Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neuro-Toxicity Syndrome (ICANS) in Patients Receiving CD19-Directed Chimeric Antigen Receptor T (CAR-T) Cell Therapy
Authors: Felix Korell, Olaf Penack, Michael Schmitt, Carsten Müller-Tidow, Lars Bullinger, Peter Dreger, Thomas Luft
Journal: Blood (2021)
The Serine Threonine Kinase Inhibitor Ots-167 Improves Erythropoiesis through Suppression of Nlk Activity in Diamond Blackfan Anemia Models
Authors: Aya Shibuya, Mark C Wilkes, Manuel Serrano, Johan Flygare, Bert Glader, Anupama Narla, Kathleen M. Sakamoto
Journal: Blood (2021)