tbuckley/cabot-search huggingface dataset:
Dendritic cell targeting with Fc-enhanced CD40 antibody agonists induces durable antitumor immunity in humanized mouse models of bladder cancer
Authors: Christopher S. Garris, Jeffrey L. Wong, Jeffrey V. Ravetch, David A. Knorr
Journal: Science Translational Medicine (2021)

Intravesical immunotherapy using Bacille Calmette-Guérin (BCG) attenuated bacteria delivered transurethrally to the bladder has been the standard of care for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) for several decades. BCG therapy continues to be limited by high rates of disease recurrence and progression, and patients with BCG-unresponsive disease have few effective salvage therapy options besides radical cystectomy, highlighting a need for new therapies. We report that the immune-stimulatory receptor CD40 is highly expressed on dendritic cells (DCs) within the bladder tumor microenvironment of orthotopic bladder cancer mouse models, recapitulating CD40 expression by DCs found in human disease. We demonstrate that local CD40 agonism in mice with orthotopic bladder cancer through intravesical delivery of anti-CD40 agonist antibodies drives potent antitumor immunity and induces pharmacodynamic effects in the bladder tumor microenvironment, including a reduction in CD8
Abstract P028: Increased Cardiometabolic Risk And Autonomic Function Alterations In Normal Weight Obesity
Authors: Alice P Duque, Isadora M Barbosa, Alessandra S Lins, Fernando G de Jesus, Christiane F Araújo, Ilana d Nogueira, Ana Carolina d Carvalho, Grazielle V Huguenin, Andrea R De Lorenzo, Mauro Mediano, Luiz Fernando R Junior
Journal: Circulation (2021)

Introduction: Normal weight obesity (NWO) is defined by the presence of normal body mass index (BMI) with high body fat percentage. In this setting, high body fat seems to affect even non-obese individuals, predicting cardiovascular risk. Hypothesis: High body fat percentage, in eutrophic individuals, affects anthropometry, hemodynamic, autonomic function and cardiometabolic risk. Methods: This cross-sectional study recruited workers of a public hospital from 2018 to 2020. Inclusion criteria: age ≥ 18 yr.; BMI: 18.5 to 24.9 Kg/m 2 . Exclusion criteria: pregnancy/lactating women; BMI &lt; 18.5 Kg/m 2 or ≥ 25 Kg/m 2 . High body fat percentage was categorized, by sex and age, as: 20 to 39 years, &gt;19.9% and &gt;32.9%; 40 to 59 years, &gt;21.9% and &gt;33.9%; and 60 to 79 years, &gt;24.9% and &gt;35.9% for men and women, respectively. Blood assays: fasting glucose, lipid profile and C reactive protein; anthropometry: neck, waist and hip circumferences; bioimpedance: visceral fat area and body fat percentage; hemodynamic parameters: blood pressure and double product; autonomic function: orthostatic test (30:15 ratio), orthostatic hypotension test and heart rate variability (HRV): high and low frequency and sympathovagal index; cardiometabolic risk: body shape index, atherogenic dyslipidemia, atherogenic index, atherogenic index of plasma and Framingham score. Statistical analysis: Mann-Whitney and chi-squared test. P&lt;0.05. Ethics: according to Helsinki declaration, revised in 2013. Results: A total of 52 from 241 volunteers were eutrophic: 23 were NWO, that exhibited higher visceral fat area, anthropometric measures, blood pressure and double product; and worse lipid profile, HRV frequency domain and cardiometabolic risk parameters compared to the 29 with normal body fat percentage (table 1) . Conclusions: NWO individuals have metabolic, hemodynamic, anthropometric and autonomic alterations that, associated with new indexes related to atherogenesis, confirm the early cardiometabolic risk of this profile.
Abstract 12793: Glutathionylation of Erythrocyte Na-K Pump in Heart Failure: A Novel Biomarker That Reflects a Key Oxidative Abnormality In the Heart
Authors: Chia-Chi Liu, Natasha Fry, Keyvan Karimi Galoughi, Helge H Rasmussen, Gemma A Figtree
Journal: Circulation (2012)

Background: Novel biomarkers may aid the diagnosis and surveillance of patients with heart failure (HF), as well as guide effective targeting of therapy. The most promising biomarkers closely corre...
Abstract MP27: Changes In Cardiac Structure And Function Over 25 Years Are Associated With Lower Midlife Cognition: The Cardia Study
Authors: Laure Rouch, Tina Hoang, Feng Xia, Stephen Sidney, Joao Lima, Kristine Yaffe
Journal: Circulation (2021)

Background: Cardiovascular risk factors are associated with worse cognition, yet much less is known about the association of cardiac structure and function and decline over time with cognitive function, even as early as midlife. Method: We included 2256 subjects from the CARDIA (Coronary Artery Risk Development in Young Adults) study (60% women, 44% black). Echocardiograms were repeated at Years 5, 25, 30 (mean age 30, 50, 55 years, respectively) to assess left ventricular (LV) mass (LVM); LV systolic function with LV ejection fraction (LVEF); LV diastolic function with left atrial volume (LAV) and early peak mitral velocity (E)/early peak mitral annular velocity (e’) ratio. Five cognitive domains were assessed at Year 30: verbal memory, verbal fluency, processing speed, executive function, and global cognition. We investigated the association of (1) 25-year change and (2) Year 25 cardiac structure and function on midlife cognition using linear regressions. Results: Over 25 years, LVM and LAV increased with mean change (SD) of 5.7 g/m 2 (21.7) and 9.6 mL/m 2 (7.4) while LVEF decreased by mean (SD) change of 1.5% (9.0). Greater 25-year increase in LVM was associated with lower global cognition, processing speed, executive function, verbal memory, and verbal fluency. Similarly, greater 25-year increase in LAV was associated with lower cognition on most cognitive domains. Adjustment for (1) demographics, education and (2) hypertension, diabetes, smoking did not notably change the results. 25-year decrease in LVEF was not associated with cognition. In addition, higher Year 25 LVM, LAV and E/e’ ratio were significantly associated with worse cognition on most cognitive domains. Conclusion: Midlife altered cardiac structure and adverse changes from early to middle adulthood are associated with lower midlife cognition. Moreover, LV diastolic but not systolic dysfunction is linked to lower cognition. Our results provide novel information linking early to midlife cardiac structure and function to cognition.
174P Breast screening at young age: A real need?
Authors: B. Nunez Garcia, J.C. Sánchez, M. Blanco Clemente, M. Mendez Garcia, M.C. Vega, S. Carmona, B. De la Puente, A.M. Morito Aguilar, M. Provencio Pulla, B. Cantos Sanchez De Ibarguen
Journal: Annals of Oncology (2021)
Abstract 13360: The Association Between Food Insecurity and Cardiovascular Mortality in the United States From 2011 to 2017 - A Longitudinal Analysis
Authors: Stephen Y Wang, Atheendar S Venkataramani, Christina A Roberto, Lauren A Eberly, Peter W Groeneveld, Sameed Ahmed M Khatana
Journal: Circulation (2020)

Introduction: Prior analyses suggest a link between food insecurity and cardiovascular (CV) health but are limited by cross-sectional designs. We investigated whether longitudinal changes in food insecurity are independently associated with CV mortality. Methods: Using National Center for Health Statistics data, we determined annual U.S. county-level age-adjusted CV mortality rates for non-elderly (20-64 years old) and elderly (65 years and older) adults. County-level food insecurity rates were obtained from the Map the Meal Gap project. We examined CV mortality trends by quartiles of average annual percent change (APC) in food insecurity. Using a Poisson fixed effects estimator, we assessed the association between longitudinal changes in food insecurity and CV mortality rates after accounting for time-varying demographic (proportion of residents who were male, black, Hispanic), economic (median household income, unemployment, poverty, education attainment, and housing vacancy rates), and healthcare access (insurance coverage, density of healthcare providers and hospital beds) variables. Results: Between 2011 and 2017, mean food insecurity rates decreased from 14.7% to 13.3%. In counties in the highest quartile of APC for absolute value change in food insecurity, non-elderly CV mortality increased from 82.2(SD=33.9) to 87.4(SD=37.3) per 100,000 individuals (p&lt;0.001), while in counties in the lowest quartile of APC, mortality was stable [60.8(SD=22.2) to 60.0(SD=23.0) per 100,000 individuals, p=0.64]. Elderly CV mortality significantly declined in all quartiles [1643.3(SD=315.7) to 1542.7(SD=299.4) per 100,000 (p&lt;0.001) in the highest quartile and 1408.3(SD=225.9) to 1338.6(SD=213.8) per 100,000 (p&lt;0.001) in the lowest quartile). A 1 percentage point increase in food insecurity was independently associated with a 0.83% (95% CI 0.42 - 1.25, P&lt;0.001) increase in CV mortality for non-elderly adults. This was not significant for elderly adults (-0.06%, 95% CI -0.39 - 0.28, P=0.74). Conclusion: From 2011 to 2017, an increase in food insecurity was independently associated with an increase in CV mortality rates for non-elderly adults in the U.S. Interventions targeting food insecurity may play a role in improving community CV health.
Abstract 13039: Loss of Visceral Adipose Tissue Macrophage Subsets Induces Myocardial Infarction Induced Insulin Resistance: Role of Adiponectin
Authors: Sathish Babu B Vasamsetti, xinyi zhang, Emillie M Coppin, Jonathan Florentin, Sasha Koul, Matthias Gotberg, Andrew S Clugston, Floyd Thoma, John Sembrat, Grant C Bullock, Dennis Kostka, Claudette M St. Croix, Ansuman Chattopadhyay, mauricio rojas, Suresh Mulukutla, Partha Dutta
Journal: Circulation (2020)

Introduction: Myocardial infarction (MI) is the major cause of morbidity and mortality in the western world. Insulin resistance is a major complication in patients with MI. Hypothesis: Loss of visceral adipose tissue (VAT) resident macrophages in MI results in diminished adiponectin production causing systemic insulin resistance. Methods: To understand if MI results in insulin resistance, we analyzed UPMC patient records and identified patients who had normal fasting blood glucose levels on average 15 days before ST elevation myocardial infarction (STEMI) and checked their fasting blood glucose levels 30 days after STEMI. To understand the mechanisms of MI-induced insulin resistance, we used a mouse model of coronary ligation in C57BL/6 mice and analyzed the features of insulin resistance by measuring serum insulin, serum adiponectin, AKT activation status in the liver and muscle. Results: We found that 50% of non-diabetic patients (fasting blood glucose levels 99±2.5 mg/ dl) developed hyperglycemia (141±13 mg/dl) after MI, suggesting that MI causes insulin resistance. Consistently, mice with MI had higher fasting blood insulin, and reduced p-Akt levels in the liver and skeletal muscles confirming insulin resistance. Concomitantly, mice and patients with MI had reduced number of visceral adipose tissue (VAT) resident macrophages. In line with this, MI resulted in marked reduction in the level of macrophage colony stimulating factor (M-CSF), a cytokine required for tissue resident macrophage survival. M-CSF supplementation in mice with MI improved insulin sensitivity and decreased inflammatory phenotype of VAT macrophages. Furthermore, the systemic level of adiponectin, which is reported to augment insulin sensitivity, was profoundly reduced in mice after MI. Specific depletion of VAT resident macrophages resulted in lower levels of adiponectin in the serum, indicating that this macrophage subset is necessary for adiponectin production by adipocytes. Conclusions: Our data demonstrate that diminished M-CSF levels after MI triggers apoptosis of VAT resident macrophages, resulting in reduced adiponectin secretion and systemic insulin resistance.
Forewarned is forearmed: chronic spontaneous urticaria as a potential risk to effective SARS‐CoV‐2 vaccine uptake and global public health
Authors: W.H. Bermingham, M.R. Ardern‐Jones, A.P. Huissoon, M.T. Krishna
Journal: British Journal of Dermatology (2021)

Chronic spontaneous urticaria and angioedema (CSU/A) is a common condition with an estimated global point prevalence of 0.7% (95% C.I, 0.2-1.4)(1), higher in non-White populations. Symptoms present as an 'allergy mimic' but are underpinned by non-specific, non-IgE-mediated mast cell histamine release. The combination of common population prevalence and likelihood of vaccines precipitating symptoms in those with CSU/A presents an immediate risk to the SARS-COV-2 global vaccine program.
Impact of Percutaneous Coronary Intervention on Outcomes in Patients With Heart Failure
Authors: Puja B. Parikh, Deepak L. Bhatt, Varun Bhasin, Stefan D. Anker, Hal A. Skopicki, Bimmer E. Claessen, Gregg C. Fonarow, Adrian F. Hernandez, Roxana Mehran, Mark C. Petrie, Javed Butler
Journal: Journal of the American College of Cardiology (2021)
The Panorama of Cancer Genetics
Authors: Joel S. Bader
Journal: Cancer Research (2021)

Abstract Cancer, a disease of the genome, is caused by a combination of germline predisposing variants and acquired somatic mutations. A unified view of heritable and acquired genetic factors will improve our understanding of cancer occurrence and progression. Fanfani and colleagues provide new insight into heritable cancer risk through a computational method that identifies genes and loci that contribute strongly to cancer heritability; many of these loci also harbor somatic drivers. Beyond improving cancer clinical outcomes, these methods will also be valuable across complex disorders by identifying regions responsible for missing heritability. See related article by Fanfani et al., p. 2588
Abstract 12993: Oral Anticoagulation Prescription Depends on Both Atrial Fibrillation Duration and CHA <sub>2</sub> DS <sub>2</sub> -VASc Score
Authors: Rachel M Kaplan, Paul D Ziegler, Jodi L Koehler, Sean Landman, Shantanu Sarkar, Rod S Passman
Journal: Circulation (2020)

Introduction: Current guideline recommendations for oral anticoagulation (OAC) in patients with atrial fibrillation (AF) are based on CHA 2 DS 2 -VASc score alone. In patients with cardiac implantable electronic devices (CIEDs), it is poorly understood how the interaction between AF duration and CHA 2 DS 2 -VASc score influence the decision to prescribe OAC. Methods: Data from the Optum® de-identified Electronic Health Record dataset were linked to the Medtronic CareLink database of CIEDs. An index date was assigned as the later of 6 months after device implant or 1 year after EHR data availability. CHA 2 DS 2 -VASc score was assessed via EHR data prior to the index date. Maximum daily AF burden (No AF, 6 minutes-23.5 hours, and &gt;23.5 hours) was assessed over the 6 months prior to index date. OAC prescription rates were computed prior to the index date as a function of both AF duration and CHA 2 DS 2 -VASc score. Results: A total of 35,779 patients with CHA 2 DS 2 -VASc scores ≥1 were identified, including 8,581 who were prescribed OAC and 27,198 not prescribed OAC during the observation period. The overall OAC prescription rate among the subset of 12,938 patients with device-detected AF &gt;6 minutes was 36.7% and the rate was nearly 60% higher for patients with a maximum daily AF burden &gt;23.5 hours (45.4%) compared to those with 6 minutes-23.5 hours (28.7%). OAC prescription rates increased monotonically with both increasing AF duration and CHA 2 DS 2 -VASc score, reaching a maximum of 67.2% for patients with AF &gt;23.5 hours and a CHA 2 DS 2 -VASc score ≥5 (Table). Conclusion: In contrast with guideline recommendations, real-world prescription of OAC increased with both increasing duration of AF and CHA 2 DS 2 -VASc score. This mirrors recent evidence demonstrating that stroke risk also increases with both of these features and highlights the need for further research into the role of AF duration, stroke risk, and the need for anticoagulation in patients with devices capable of long-term AF monitoring.
Abstract 15984: Race is Associated With Differences in Aorta Size on Echocardiography
Authors: Troy M Labounty, David S Bach, Eduardo Bossone, Theodore J Kolias
Journal: Circulation (2017)

Introduction: The relationship between race and aortic size on echocardiography is unclear. Hypothesis: There are race-specific differences in aorta size. Methods: We compared aortic size and race ...
Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial
Authors: Johnny Ludvigsson, Zdenek Sumnik, Terezie Pelikanova, Lia Nattero Chavez, Elena Lundberg, Itxaso Rica, Maria A. Martínez-Brocca, Marisol Ruiz de Adana, Jeanette Wahlberg, Anastasia Katsarou, Ragnar Hanas, Cristina Hernandez, Maria Clemente León, Ana Gómez-Gila, Marcus Lind, Marta Ferrer Lozano, Theo Sas, Ulf Samuelsson, Stepanka Pruhova, Fabricia Dietrich, Sara Puente Marin, Anders Nordlund, Ulf Hannelius, Rosaura Casas
Journal: Diabetes Care (2021)

OBJECTIVE To evaluate the efficacy of aluminum-formulated intralymphatic glutamic acid decarboxylase (GAD-alum) therapy combined with vitamin D supplementation in preserving endogenous insulin secretion in all patients with type 1 diabetes (T1D) or in a genetically prespecified subgroup. RESEARCH DESIGN AND METHODS In a multicenter, randomized, placebo-controlled, double-blind trial, 109 patients aged 12–24 years (mean ± SD 16.4 ± 4.1) with a diabetes duration of 7–193 days (88.8 ± 51.4), elevated serum GAD65 autoantibodies, and a fasting serum C-peptide &amp;gt;0.12 nmol/L were recruited. Participants were randomized to receive either three intralymphatic injections (1 month apart) with 4 μg GAD-alum and oral vitamin D (2,000 IE daily for 120 days) or placebo. The primary outcome was the change in stimulated serum C-peptide (mean area under the curve [AUC] after a mixed-meal tolerance test) between baseline and 15 months. RESULTS Primary end point was not met in the full analysis set (treatment effect ratio 1.091 [CI 0.845–1.408]; P = 0.5009). However, GAD-alum–treated patients carrying HLA DR3-DQ2 (n = 29; defined as DRB1*03, DQB1*02:01) showed greater preservation of C-peptide AUC (treatment effect ratio 1.557 [CI 1.126–2.153]; P = 0.0078) after 15 months compared with individuals receiving placebo with the same genotype (n = 17). Several secondary end points showed supporting trends, and a positive effect was seen in partial remission (insulin dose–adjusted HbA1c ≤9; P = 0.0310). Minor transient injection site reactions were reported. CONCLUSION Intralymphatic administration of GAD-alum is a simple, well-tolerated treatment that together with vitamin D supplementation seems to preserve C-peptide in patients with recent-onset T1D carrying HLA DR3-DQ2. This constitutes a disease-modifying treatment for T1D with a precision medicine approach.
Differential usage of transcriptional repressor Zeb2 enhancers distinguishes adult and embryonic hematopoiesis
Authors: Xiao Huang, Stephen T. Ferris, Sunkyung Kim, Mayank N.K. Choudhary, Julia A. Belk, Changxu Fan, Yanyan Qi, Raki Sudan, Yu Xia, Pritesh Desai, Jing Chen, Nghi Ly, Quanming Shi, Prachi Bagadia, Tiantian Liu, Martin Guilliams, Takeshi Egawa, Marco Colonna, Michael S. Diamond, Theresa L. Murphy, Ansuman T. Satpathy, Ting Wang, Kenneth M. Murphy
Journal: Immunity (2021)
Abstract P089: Diabetes Worsens Length Of Stay In Patients With Reduced Ejection Fraction Admitted With Nstemi
Authors: Ebenezer Oni, Zach Port, Olayinka Afolabi Brown, Behnam Bozorgnia, Aman M Amanullah
Journal: Circulation (2021)

Background: Length of stay is an important quality metric and outcome measure in the management of hospitalized patients. We evaluated the association of diabetes in patients admitted for Non-ST Elevation myocardial infarction (NSTEMI) on their length of stay. Hypothesis: the impact of diabetes on length of stay in patients admitted for STEMI Methods: Our study population included patients admitted for NSTEMI in a single center between 08/01/2016 and 09/30/2012. Diabetes (DM) was defined by a documented diagnosis or use of diabetic medication. A higher length of stay (LOS) was defined as spending more than 5 days in the hospital. Results: A total of 720 patients were included in this analysis. The mean age was 66 ± 0.6 years, 50% (n-269) were diabetics, 59% had left ventricular ejection fraction (EF) &lt; 50% and the median LOS was 5 days. A higher number of diabetic patients had LOS&gt; 5days (55%). In an unadjusted logistic regression, diabetics had increased odds of higher LOS, odd ratio (OR) 1.54 ( CI 1.10-2.16 ), p=0.012. After adjusting for confounding variables, the relationship remained significant. When stratified by left ventricular systolic function on admission, the impact of diabetes on length of stay only remained significant in patients with EF less than 50%. See Table 1. Conclusion: The presence of diabetes was significantly associated LOS in NSTEMI, especially for patients admitted with a reduced left ventricular ejection fraction. This study emphases the impact of diabetes on health comes in cardiovascular disease.
Thyroid MALT lymphoma: self-harm to gain potential T-cell help
Authors: Fangtian Wu, Natsuko Watanabe, Maria-Myrsini Tzioni, Ayse Akarca, Chunye Zhang, Yan Li, Zi Chen, Francesco Cucco, Natasha Carmell, Jaeduk Yoshimura Noh, Koichi Ito, Rachel Dobson, Sarah Moody, Wenqing Yao, Wenyan Zhang, Weiping Liu, Hongxiang Liu, Jessica Okosun, Andreas Chott, Yingwen Bi, Shih-Sung Chuang, Markus Raderer, Jian-Yong Li, Teresa Marafioti, Ming-Qing Du
Journal: Leukemia (2021)

Abstract The development of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is driven by chronic inflammatory responses and acquired genetic changes. To investigate its genetic bases, we performed targeted sequencing of 93 genes in 131 MALT lymphomas including 76 from the thyroid. We found frequent deleterious mutations of TET2 (86%), CD274 (53%), TNFRSF14 (53%), and TNFAIP3 (30%) in thyroid MALT lymphoma. CD274 was also frequently deleted, together with mutation seen in 68% of cases. There was a significant association between CD274 mutation/deletion and TNFRSF14 mutation ( p = 0.001). CD274 (PD-L1) and TNFRSF14 are ligands for the co-inhibitory receptor PD1 and BTLA on T-helper cells, respectively, their inactivation may free T-cell activities, promoting their help to malignant B-cells. In support of this, both the proportion of activated T-cells (CD4+CD69+/CD4+) within the proximity of malignant B-cells, and the level of transformed blasts were significantly higher in cases with CD274 / TNFRSF14 genetic abnormalities than those without these changes. Both CD274 and TNFRSF14 genetic changes were significantly associated with Hashimoto’s thyroiditis ( p = 0.01, p = 0.04, respectively), and CD274 mutation/deletion additionally associated with increased erythrocyte sedimentation rate ( p = 0.0001). In conclusion, CD274 / TNFRSF14 inactivation in thyroid MALT lymphoma B-cells may deregulate their interaction with T-cells, promoting co-stimulations and impairing peripheral tolerance.