tbuckley/cabot-search huggingface dataset:
Relationship Between Rheumatoid Arthritis and Pulmonary Function Measures on Spirometry in the UK Biobank
Authors: Lauren Prisco, Matthew Moll, Jiaqi Wang, Brian D. Hobbs, Weixing Huang, Lily W. Martin, Vanessa L. Kronzer, Sicong Huang, Edwin K. Silverman, Tracy J. Doyle, Michael H. Cho, Jeffrey A. Sparks
Journal: Arthritis & Rheumatology (2021)

Objective To investigate the independent relationship of rheumatoid arthritis (RA) to the type and severity of pulmonary patterns on spirometry compared to the pulmonary patterns in general population controls. Methods In this cross‐sectional study, we investigated the association of RA with pulmonary function measures on spirometry among subjects in the UK Biobank who underwent spirometry for research purposes. RA cases were identified based on self‐report and current disease‐modifying antirheumatic drug/glucocorticoid use. Controls were subjects without RA from the general population. Outcome measures included continuous forced expiratory volume in 1 second percent predicted (FEV 1 %) and forced vital capacity percent predicted (FVC%), type of spirometric pattern (restrictive or obstructive), and severity of the restrictive or obstructive pattern. We used multivariable regression to estimate the effects in RA cases compared to the effects in controls, adjusting for age, sex, body mass index, and smoking status/pack‐years. Results Among 350,776 analyzed subjects who underwent spirometry (mean age 56.3 years; 55.8% female; 45.5% ever smokers), we identified 2,008 cases of treated RA. In multivariable analyses, RA was associated with lower FEV 1 % (β = –2.93 [95% confidence interval (95% CI) –3.63, –2.24]), FVC% (β = –2.08 [95% CI –2.72, –1.45]), and FEV 1 /FVC (β = –0.008 [95% CI –0.010, –0.005]) compared to controls. RA was additionally associated with restrictive patterns (odds ratio [OR] 1.36 [95% CI 1.21, 1.52]) and obstructive patterns (OR 1.21 [95% CI 1.07, 1.37]) independent of confounders, and was most strongly associated with severe restrictive and obstructive patterns. Conclusion RA is associated with increased odds of restrictive and obstructive patterns, and this relationship is not explained by confounders, including smoking status. In addition to restrictive lung disease, clinicians should also be aware that airway obstruction may be a pulmonary manifestation of RA.
ULK1 inhibition overcomes compromised antigen presentation and restores antitumor immunity in LKB1-mutant lung cancer
Authors: Jiehui Deng, Aatish Thennavan, Igor Dolgalev, Ting Chen, Jie Li, Antonio Marzio, John T. Poirier, David H. Peng, Mirna Bulatovic, Subhadip Mukhopadhyay, Heather Silver, Eleni Papadopoulos, Val Pyon, Cassandra Thakurdin, Han Han, Fei Li, Shuai Li, Hailin Ding, Hai Hu, Yuanwang Pan, Vajira Weerasekara, Baishan Jiang, Eric S. Wang, Ian Ahearn, Mark Philips, Thales Papagiannakopoulos, Aristotelis Tsirigos, Eli Rothenberg, Justin Gainor, Gordon J. Freeman, Charles M. Rudin, Nathanael S. Gray, Peter S. Hammerman, Michele Pagano, John V. Heymach, Charles M. Perou, Nabeel Bardeesy, Kwok-Kin Wong
Journal: Nature Cancer (2021)
Abstract 16117: Delineating The Prognostic Value of Post PCI FFR in Acute Coronary Syndrome Patients
Authors: Shiv Kumar Agarwal, Srikanth Vallurupalli, Aisha Siraj, Rahil Rafeedheen, Mohammed Eid Madmani, Rimsha Hasan, Mohamed Ayan, Negar Salehi, Srikanth Kasula, Malek Al-Hawwas, Abdul Hakeem, Barry F Uretsky
Journal: Circulation (2019)

Background: Post PCI FFR has prognostic value in both stable CAD and ACS patient population. It is accepted that higher post-PCI FFR leads to better outcomes in both groups. However, comparative da...
Abstract 16947: Barriers to Care in Urban and Rural Dwelling Patients With Adult Congenital Heart Disease
Authors: Lidija B McGrath, Marshall Taunton, Sheldon Levy, Adrienne Kovacs, Craig S Broberg, Abigail Khan
Journal: Circulation (2020)

Introduction: Adult congenital heart disease (ACHD) patients face a unique set of medical, psychological, and social challenges, and access to specialized ACHD care has been shown to improve their outcomes. Rural ACHD patients may represent a uniquely disadvantaged group given their complex health care needs and the distance they must travel to access care. The aim of this study was to investigate the challenges faced by ACHD patients in accessing outpatient cardiac care, with a specific focus on understanding barriers related to distance from care. Methods: This cross-sectional, survey-based study took place in the ACHD clinic at an academic medical center in a metropolitan area. Additional medical information was abstracted in a retrospective manner from the electronic health record. T-tests and Chi-square tests were used to investigate the relationship between variables. Results: A total of 100 patients participated in the study (mean age 40 ± 13 years, 60% female, 18% rural dwelling). The median driving distance to clinic was 20 miles (interquartile range 12 to 77 miles). The most commonly identified barriers to cardiac clinic visits were the financial losses related to taking time off from work (39%), distance of clinic from home (33%), and the weather (33%), whereas finding a ride to clinic, finding childcare, or the time of available clinic appointments were not perceived as significant barriers. As compared to urban dwelling patients, those who were rural dwelling had a lower level of education (p=0.04), more difficulty paying insurance premiums (p&lt;0.001) and copays (p=0.005), and were more likely to identify the distance from clinic (p=0.05) and having to go into the city (p=0.02) as barriers to clinic appointments. Conclusions: Loss of compensation from taking time off work to attend a visit and distance to clinic were the most commonly identified barriers to outpatient cardiac care in this cohort of ACHD patients. These barriers, along with difficulty paying insurance premiums, are more common in rural dwelling patients. Initiatives such as telemedicine visits or providing financial subsidies for travel and treatment could help to expand specialty ACHD care and better serve this growing patient population.
視覚野は眼開口前の末梢駆動から独立性を獲得する【JST・京大機械翻訳】
Authors: Gribizis Alexandra, Ge Xinxin, L Daigle Tanya, B Ackman James, Zeng Hongkui, Lee Daeyeol, C Crair Michael
Journal: Neuron (2019)
Abstract P179: Cardiometabolic Profile Of A Young Adult Population Assisted By A Primary Health Care Unit In Brazil- LAPARC Cohort Study
Authors: Rafael Bellotti Azevedo, Beatriz Deberaldini Marinho, Tomás de Souza Mello, Bruna Gopp Botelho, João Victor Gonçalves de Hollanda, Leonardo Villa Leão Ferreira, Letícia Zarur Junqueira de Andrade, Maíra Kuster Machado, Stephanie S Lilienwald Oei, Daniela Fiuza Gomes Monteiro, Elizabeth Silaid Muxfeldt
Journal: Circulation (2021)

Introduction: Dyslipidemia, Glucose Intolerance (GI), Diabetes Mellitus (DM), and Metabolic Syndrome (MS) are metabolic conditions often asymptomatic and related to high cardiovascular (CV) morbidity and mortality. Nonetheless, these conditions are not commonly screened in younger adults. The LapARC cohort Study is a population-based study to assess CV risk profile in a young adult population. Objective: To evaluate the prevalence of dyslipidemia, DM, GI, and MS in a young adult population enrolled in the Family Health Strategy (FHS) in the center of Rio de Janeiro, Brazil. Methods: Cross-sectional population study that enrolled individuals aged 20-50 years registered in an FHS unit in Rio de Janeiro. Sociodemographic, anthropometric characteristics, and CV risk factors were recorded. Office blood pressure (BP) was obtained by the average of 2 measurements obtained on two different occasions. All participants underwent laboratory evaluation (lipid and glycemic profile) and home blood pressure monitoring (HBPM). Two screening questionnaires for obstructive sleep apnea (OSA): STOP-BANG (SBQ) and Epworth Sleepiness Scale (ESS) were applied. Results: We evaluated 575 individuals [39% male gender; average age: 39.9 ± 8.7 years old]. The most common modifiable CV risk factors were physical inactivity (43.0%), and obesity (25.0%). The prevalence of dyslipidemia was 57.6%. These individuals had a higher prevalence of male gender (42.0% vs 34.0%), MS (25.0% vs 4.0%), and high risk for OSA by ESS (35.0% vs 27%). A total of 91 individuals (15.8%) were diagnosed with MS, being predominantly males (52.0% vs 36.0%), older and obese (46.0% vs 21.0%), with a higher prevalence of dyslipidemia (90.0% vs 52.0%), GI (20.0% vs 5.0%), hypertension (63.0% vs 18.0%) with uncontrolled office and Home BP. They also had a high risk for OSA by SBQ and ESS (25.0% vs 8.0%). Moreover, a total of 55 (9.6%) subjects presented an altered glycemic profile. These individuals were older with a higher prevalence of obesity (38.0% vs 24.0%), hypertension (36.0% vs 23.0%), uncontrolled HBPM (22.0% vs 12.0%) and MS (29.0% vs 13.0%) when compared to normoglycemic patients. Conclusion: This young and apparently healthy population has an adverse cardiometabolic profile, indicating the importance of precocious CV risk stratification. Thus, efficient primary preventive strategies can be implemented to reduce the probability of CV disease development in the future.
Intercountry Differences in Guideline-Directed Medical Therapy and Outcomes Among Patients With Heart Failure
Authors: Michael A Fuery, Fouad Chouairi, James L Januzzi, Gordon W Moe, Cesar Caraballo, Megan McCullough, P Elliott Miller, Samuel W Reinhardt, Katherine Clark, Andrew Oseran, Aidan Milner, Justin Pacor, Peter A Kahn, Avinainder Singh, Neal Ravindra, Avirup Guha, Lina Vadlamani, Neeti S Kulkarni, Mona Fiuzat, G Michael Felker, Christopher M O'Connor, Tariq Ahmad, Justin Ezekowitz, Nihar R Desai
Journal: JACC Heart Failure (2021)
Innovations in Biomaterial Design toward Successful RNA Interference Therapy for Cancer Treatment
Authors: Deidra M. Ward, Aaliyah B. Shodeinde, Nicholas A. Peppas
Journal: Advanced Healthcare Materials (2021)

Abstract Gene regulation using RNA interference (RNAi) therapy has been developed as one of the frontiers in cancer treatment. The ability to tailor the expression of genes by delivering synthetic oligonucleotides to tumor cells has transformed the way scientists think about treating cancer. However, its clinical application has been limited due to the need to deliver synthetic RNAi oligonucleotides efficiently and effectively to target cells. Advances in nanotechnology and biomaterials have begun to address the limitations to RNAi therapeutic delivery, increasing the likelihood of RNAi therapeutics for cancer treatment in clinical settings. Herein, innovations in the design of nanocarriers for the delivery of oligonucleotides for successful RNAi therapy are discussed.
Abstract 13017: Administration of Intramyocardial Chemokine Induce Myocardial Recovery by Modulating the Acute Inflammatory Response to Ischemia
Authors: Rohan Shad Arora, Albert J Pedroza, Nicolas Quach, Robyn Fong, Sandra Kong, Patpilai Kasinpila, Kate M Callon, Julian Howland, Michael P Fischbein, William Hiesinger
Journal: Circulation (2020)

Introduction: We have previously shown that the exogenously injected chemokines induce robust myocardial recovery and angiogenesis after a myocardial infarction (MI). Angiogenesis, however, is a late response, and the acute cellular drivers of chemokine induced recovery remain elusive. Recently it has been shown that an acute macrophage response is central to post-MI recovery after stem-cell injections. As many chemokines act as immunomodulators, we hypothesized that both angiogenic chemokines (SDF-1) and non-angiogenic chemokines of viral origin (vMIP-II) can similarly elicit a macrophage response. Methods: MI was surgically induced in 39 male and female C57BL/6 mice (6-8 weeks old) by ligation of the left anterior descending coronary artery. Mice were randomly assigned to receive intramyocardial injections of PBS (saline), SDF-1, or vMIP-II. Two hearts from each treatment group were explanted at post-operative day 3 (P3) for single cell suspension preparation. Viable cells were used for single cell RNA sequencing (scRNAseq). Echocardiography was performed for all remaining mice at P7 to assess for functional recovery, and hearts were explanted for histology at P14. Results: Treatment with both SDF-1 and vMIP-II led to significant functional recovery assessed via echocardiography at P7, one week in advance of arteriolar collateralization (Ejection Fraction 0.38 ± 0.14 and 0.50 ± 0.15 in SDF-1 and vMIP respectively; 0.27 ± 0.13 in PBS; t-test adjusted p = 0.023). scRNAseq of 7918 captured cells showed a robust acute inflammatory macrophage response at P3 across treatment groups. A robust expansion of Arginase-1 (Arg1+) macrophages - a known M2 anti-inflammatory subtype - was seen specifically in chemokine treated mice at P3 (9% in PBS vs 16.5% in both SDF-1 and vMIP-II). Conclusions: We show that vMIP-II triggers myocardial recovery similar to SDF-1. Furthermore, we show a robust and consistent Arg1+ macrophage response present in both treatment groups.
Cellular and plasma proteomic determinants of COVID-19 and non-COVID-19 pulmonary diseases relative to healthy aging
Authors: Laura Arthur, Ekaterina Esaulova, Denis A. Mogilenko, Petr Tsurinov, Samantha Burdess, Anwesha Laha, Rachel Presti, Brian Goetz, Mark A. Watson, Charles W. Goss, Christina A. Gurnett, Philip A. Mudd, Courtney Beers, Jane A. O’Halloran, Maxim N. Artyomov
Journal: Nature Aging (2021)

We examine the cellular and soluble determinants of coronavirus disease 2019 (COVID-19) relative to aging by performing mass cytometry in parallel with clinical blood testing and plasma proteomic profiling of ~4,700 proteins from 71 individuals with pulmonary disease and 148 healthy donors (25–80 years old). Distinct cell populations were associated with age (GZMK+CD8+ T cells and CD25low CD4+ T cells) and with COVID-19 (TBET−EOMES− CD4+ T cells, HLA-DR+CD38+ CD8+ T cells and CD27+CD38+ B cells). A unique population of TBET+EOMES+ CD4+ T cells was associated with individuals with COVID-19 who experienced moderate, rather than severe or lethal, disease. Disease severity correlated with blood creatinine and urea nitrogen levels. Proteomics revealed a major impact of age on the disease-associated plasma signatures and highlighted the divergent contribution of hepatocyte and muscle secretomes to COVID-19 plasma proteins. Aging plasma was enriched in matrisome proteins and heart/aorta smooth muscle cell-specific proteins. These findings reveal age-specific and disease-specific changes associated with COVID-19, and potential soluble mediators of the physiological impact of COVID-19. Arthur et al. report the biochemical and proteomic (SomaLogic) profiling of plasma and CyTOF immunophenotyping of peripheral blood mononuclear cells from 71 individuals with COVID-19 or other inflammatory pulmonary diseases, and 148 healthy donors aged 25–80 years old. The Resource reveals unique determinants of COVID-19 disease relative to healthy aging and other pulmonary disorders.
Abstract P206: Modeling The Impact Of The Tobacco 21 Policy In El Paso, Texas
Authors: Sonya S Panjwani, Yan Li, Whitney R Garney
Journal: Circulation (2021)

Introduction: On December 20, 2019, the federal Tobacco 21 (T21) law was passed. This new legislation raised the minimum legal purchase age for tobacco products from 18 to 21 years. Thirty-three states in the US have implemented the law, but 19 states have yet to enact it. Public health practitioners and policymakers need more evidence on the impact of the T21 Policy at the local level to encourage adequate enforcement. Objective: To project the health and economic impact of the T21 Policy in El Paso, Texas, which is the focus area of the Heart Racial and Ethnic Approaches to Community Health (REACH) Program implemented by the American Heart Association. Methods: Using an agent-based model of smoking behavior and a microsimulation model of cardiovascular disease, we projected the long-term effects of the T21 Policy on smoking prevalence and cardiovascular health outcomes in El Paso, Texas. Population characteristics and model parameters were estimated based on data from the National Health Interview Survey, US Life Tables, and the National Health and Nutrition Examination Survey. Annual smoking prevalence was derived from the Texas Behavioral Risk Factor Surveillance System and County Health Rankings. The policy effects were determined from established effect sizes from published literature. Results: The estimated prevalence of smoking in El Paso, Texas decreased by 2.7% among 18-24 year olds and by 5.2% among 25-44 year olds in 20 years with the implementation of the T21 policy; these results are statistically significant (p&lt;0.01 for both population groups). Our results also revealed that the T21 Policy could prevent cardiovascular disease such as coronary heart disease (CHD) and stroke. Specifically, compared to the no-policy situation, the policy would prevent 5.4 CHD events (from 305.2 to 299.8) per 1,000 adults and 10.8 stroke events (from 232.6 to 221.8) per 1,000 adults over lifetime. The model also projected a reduction in health care costs due to the T21 Policy, as the estimated lifetime health care costs decreased from $425,672 per person without the T21 Policy to $423,376 per person with the policy. Conclusions: This study provides important information for policymakers to understand the potential impacts of the T21 Policy in El Paso, Texas. The projected decreases in tobacco use, cardiovascular disease, and health care costs as a result of the T21 Policy could assist in advocating for T21 Policy enactment in other areas of the US.
Abstract 16069: Molecular Dynamics Simulations Reveal the Functional Impact of Pathogenic Variants in the LDL Receptor LA 4-6 Repeats
Authors: Jose James, Iftikhar J Kullo
Journal: Circulation (2020)

Introduction: Functional annotation of rare variants is key to the implementation of genomic medicine. We used molecular dynamics (MD) simulations to assess functional consequences of putative pathogenic variants (PVs) in the low-density lipoprotein receptor gene ( LDLR ). LDLR has a multidomain structure with seven LA repeats and local interactions between these repeats influence ligand binding. However, binding and recycling of the receptor-ligand complex require global changes in conformation. Using MD, we investigated the effects of PVs on long-range dynamics and LDL binding. Methods: An LA 4-6 repeat structure was created from a crystal structure of the extracellular domain (PDB: 1N7D). Structures were solvated with a water box containing TIP3P water molecules and simulated using the AMBER software package with the ff14SB forcefield. The wild type (WT) structure was first relaxed using MD; and subsequently PVs D245Y, F181Y and F181G were modeled. Dynamics were simulated for approximately one microsecond. Values for LDL binding for each PV were obtained from a prior study which used a radioisotope uptake assay. Results: WT domains demonstrated a stable conformation based on root mean square deviation. PVs disrupted the normal distribution in all domains significantly (p &lt; 0.0001), broadening it and introducing multiple peaks. Projection along the top principal components (PCs) showed global destabilization with all PVs. The variant with the greatest impact on LDL binding, F181G, adopted a distinct alternate conformation. Comparison between PV and WT subspaces from PCA correlated with LDL binding (R 2 = 0.99, exponential regression). Structural analysis revealed that the LA5 calcium cage is involved in inter-domain salt bridges, which are disrupted in simulations of PVs. Conclusion: MD simulation of LA4-6 repeats in LDLR suggests PVs alter long-range conformational dynamics, and that such dynamics correlate with LDL binding. The impact of PVs on conformational dynamics and binding may be through disruption of interdomain salt bridges that are mediated by the acidic calcium cage. This study demonstrates the potential utility of MD simulations to functionally characterize LDLR variants.
cIAP1/2 antagonism eliminates MHC class I–negative tumors through T cell–dependent reprogramming of mononuclear phagocytes
Authors: Kevin Roehle, Li Qiang, Katherine S. Ventre, Daniel Heid, Lestat R. Ali, Patrick Lenehan, Max Heckler, Stephanie J. Crowley, Courtney T. Stump, Gabrielle Ro, Anže Godicelj, Aladdin M. Bhuiyan, Annan Yang, Maria Quiles del Rey, Tamara Biary, Adrienne M. Luoma, Patrick T. Bruck, Jana F. Tegethoff, Svenja L. Nopper, Jinyang Li, Katelyn T. Byrne, Marc Pelletier, Kai W. Wucherpfennig, Ben Z. Stanger, James J. Akin, Joseph D. Mancias, Judith Agudo, Michael Dougan, Stephanie K. Dougan
Journal: Science Translational Medicine (2021)

T cell–dependent reprogramming of intratumoral macrophages by cIAP1/2 inhibition leads to control of MHC class I–negative pancreatic cancer in mice.
Abstract 15553: The Long-term Outcome Beyond Pulmonary Vein Isolation of Ablation Guided by the Online and Real-time Atrial Fibrillation Imaging System: Extra Mapping Project
Authors: Kensuke Sakata, Yusuke Okuyama, Tomoya Ozawa, Yusuke Fujii, Koichi Kato, Ryo Haraguchi, Shin Inada, Kazuo Nakazawa, Yoshihisa Sugimoto, Kohei Yamashiro, Yoshihisa Nakagawa, Takashi Ashihara
Journal: Circulation (2020)

Introduction: Although modulation of atrial fibrillation (AF) drivers and/or substrates has been proposed as one of the effective ablation strategies for non-paroxysmal AF (Non-PAF), previous meta-analyses showed that ablation, targeting complex fractionated atrial electrogram (CFAE) indirectly-reflecting Non-PAF drivers, had no additional benefit for post-pulmonary vein isolation (PVI) Non-PAF. As an alternative ablation strategy for Non-PAF, rotor ablation has been proposed as one of the potentiated ablation strategies for Non-PAF. However, the optimal ablation strategy is still unclear because reliable method detecting AF drivers remain unsettled in clinical practice. Hypothesis: Because rotors are known as key mechanisms for Non-PAF, we might open the possibility of Non-PAF control by the real-time visualization of wave dynamics during AF ablation. Methods: Consecutive 140 Non-PAF patients were enrolled in this study. The clinically-available online and real-time AF imaging system with high-spatiotemporal density (ExTRa Mapping TM ) developed by our group was applied in case Non-PAF was remained after PVI. Then, we detected and ablated non-passively-activated areas where rotational activations in the form of meandering rotors and/or multiple wavelets assumed to contain Non-PAF drivers were frequently observed (figure, top). The recurrence rate of Non-PAF or atrial tachycardia (AT) after the ablation was compared to that in patients underwent PVI-alone at our hospital. Results: The propensity scores selected each 34 people from ExTRa-strategy group and PVI-alone group (figure, middle). The 24-month freedom ratio from Non-PAF/AT in the matched-ExTRa-strategy group was higher than the matched-PVI-alone group, which was close to significance (p = 0.056) (figure, bottom). Conclusion: The ExTRa Mapping-guided ablation for PVI-refractory Non-PAF might be superior to PVI-alone.
多モード直腸癌試験における転帰測定【JST・京大機械翻訳】
Authors: Fokas Emmanouil, Glynne-Jones Robert, Appelt Ane, Beets-Tan Regina, Beets Geerard, Haustermans Karin, Marijnen Corrie, Minsky Bruce D, Ludmir Ethan, Quirke Phil, Sebag-Montefiore David, Garcia-Aguilar Julio, Gambacorta Maria Antonietta, Valentini Vincenzo, Buyse Marc, Rodel Claus
Journal: The Lancet Oncology (2020)