tbuckley/cabot-search huggingface dataset:
Abstract 16951: Long term Incidence and 30-mortality of Myocardial Infarction in Congenital Heart Disease Survivors Compared With the General Population: A Nationwide Cohort Study
Authors: Morten Olsen, Bradley S Marino, Jonathan R Kaltman, Jørgen Videbæk, William T Mahle, Gail D Pearson, Nicolas L Madsen
Journal: Circulation (2015)

The population of adults with congenital heart disease (CHD) is growing and aging. Some adult CHD survivors have an increased risk of myocardial infarction (MI) due to the specific CHD, and the presence of CHD may impair prognosis following MI depending on CHD severity. Few data exist on the incidence and prognosis of MI in the adult CHD population. We aimed to compare the incidence and mortality of MI in adult survivors of CHD with the general population with attention to the impact of CHD severity. Methods: In this cohort study we used two nationwide population based medical databases to identify individuals diagnosed with CHD in Denmark between 1963 and 1974 (before 15 years of age) and from 1977 to 2012 (at any age). Patients were followed from 1977 to 2012 for first time MI using data from the Danish National Registry of Patients (DNRP). The DNRP is a nationwide hospital discharge registry covering all Danish hospitals. For each CHD subject we identified 10 controls from the general population, matched by sex and birth year. A unique personal identifier assigned at birth and used in all Danish public registries enabled virtually complete follow-up for migration, death or MI. We computed cumulative incidences and hazard ratios (HR) of MI. Subsequently, we computed 30 day-mortality following MI for CHD subjects and controls, as well as the corresponding HR adjusted for age and sex. Results: We identified 14,038 CHD subjects. By 70 years of age, the cumulative incidence of MI was 10% among CHD subjects. The HR of MI among CHD subjects compared with controls was 3.5 (95% CI: 2.9-4.3) below 50 years of age, and 1.9 (95% CI: 1.7-2.2) &gt; 50 years. The 30-day mortality was 16% for the 322 CHD subjects experiencing an MI during follow-up; the corresponding HR comparing 30-day post-MI mortality between CHD subjects and controls was 1.9 (95% CI: 1.4-2.6). Patients with severe CHD had a 30-day post-MI mortality HR of 4.1 (95% CI: 2.2-7.5), somewhat higher than among those with mild and moderate CHD (HR 1.5; 95% CI: 1.1-2.3). Conclusion: Both incidence of MI and post MI 30-day mortality were increased in individuals with CHD compared with the general population. This should be an important consideration for optimizing preventive and acute cardiovascular care for the high-risk adult CHD population.
Abstract 15122: Long-term Outcome After Septal Myectomy in Patients With Hypertrophic Cardiomyopathy Presenting With Cardiac Arrest
Authors: Martin Borggrefe
Journal: Circulation (2014)

Introduction: Surgical myectomy has been shown to improve symptoms and to promote long-term survival of patients with hypertrophic obstructive cardiomyopathy (HCOM). It’s role in prevention of sudd...
Abstract 11830: New Algorithms Reduce Clinician Review Burden and Maintain Diagnostic Yield for Repetitive ECGs in Insertable Cardiac Monitors
Authors: Laura Van Heel, Kevin T Ousdigian, Amber Seiler, Carola Alfaro Vives, Ya-Jian Cheng, John Rogers
Journal: Circulation (2019)

Introduction: With insertable cardiac monitors, clinicians feel compelled to review all ECGs so they don’t miss a true arrhythmia episode for diagnosis, however this is time consuming. Hypothesis: ...
Covid-19: UK had one of Europe’s highest excess death rates in under 65s last year
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Covid-19: UK had one of Europe's highest excess death rates in under 65s last year Gareth IacobucciThe UK had a higher rate of excess deaths among people aged under 65 in 2020 than almost every other country in Europe, new figures from the Office for National Statistics show. 1 By 18 December 2020 only Bulgaria had a higher cumulative excess mortality rate among under 65s (12.3% above the five year average) than the UK (at 7.7%).The ONS report, which looked at data from 26 countries, lays bare covid-19's effects across Europe in 2020 and highlights the differing impact of the first and second waves of the pandemic.
P09.41 Body Mass Index (BMI) Is Associated With Overall Survival in Patients With Metastatic Non-Small Cell Lung Cancer
Authors: M.F. Medeiros, M.D. Spina Donadio, M.F. Simões, D. Maciel Santana, C.I. De Andrade Souza, L.B. Mendes Gomes, M. Petrocchi Corassa, H. De Freitas, V.C. De Lima
Journal: Journal of Thoracic Oncology (2021)
Abstract 3728: Intensive Lipid Lowering with Atorvastatin Provides Early and Sustained Benefit in Patients with Stable Coronary Disease: A Secondary Analysis of the Treating to New Targets (TNT) Study
Authors: John C LaRosa, Scott Grundy, David D Waters
Journal: Circulation (2006)

Background: In TNT, intensive lipid lowering with atorvastatin 80 mg significantly reduced the risk of CV disease compared with atorvastatin 10 mg among patients with stable CHD. This analysis was ...
Ethics Consultation in U.S. Hospitals: Opinions of Ethics Practitioners
Authors: Ellen Fox, Anita J. Tarzian, Marion Danis, Christopher C. Duke
Journal: The American Journal of Bioethics (2021)

To design effective strategies to improve ethics consultation (EC) practices, it is important to understand the views of ethics practitioners. Previous U.S. studies of ethics practitioners have overrepresented the views of academic bioethicists. To help inform EC improvement efforts, we surveyed a random stratified sample of U.S. hospitals, examining ethics practitioners' opinions on EC in general, on their own EC service, on strategies to improve EC, and on ASBH practice standards. Respondents across all categories of hospitals had very positive perceptions of their own ethics consultation service (ECS) and few concerns about quality. Our findings suggest that the ethics-related needs of small, rural, non-teaching hospitals may be very different from those of academic medical centers, and therefore, different approaches to addressing ethical issues might be warranted.
FP03.02 Interim Analysis of Neoadjuvant Chemoradiotherapy and Durvalumab for Potentially Resectable Stage III Non-Small Cell Lung Cancer (NSCLC)
Authors: M.H. Hong, B. Ahn, H.R. Kim, S.M. Lim, S. Lee, S.Y. Park, C.Y. Lee, J.G. Lee, D.J. Kim, S.H. Lee, H.I. Yoon, C.G. Lee, J. Cho, H.S. Shim, T. Kim, B.C. Cho
Journal: Journal of Thoracic Oncology (2021)
PRMT1 is a novel molecular therapeutic target for clear cell renal cell carcinoma
Authors: Jianfeng Wang, Chen Wang, Pan Xu, Xiao Li, Yongning Lu, Di Jin, Xiaomao Yin, Hao Jiang, Jing Huang, Huan Xiong, Fei Ye, Jia Jin, Yu Chen, Yiqian Xie, Zhifeng Chen, Hong Ding, Hao Zhang, Rongfeng Liu, Hualiang Jiang, Kaixian Chen, Zhiyi Yao, Cheng Luo, Yiran Huang, Yuanyuan Zhang, Jin Zhang
Journal: Theranostics (2021)

Background and Objective: Epigenetic alterations are common events in clear cell renal cell carcinoma (ccRCC), and protein arginine methyltransferase 1 (PRMT1) is an important epigenetic regulator in cancers. However, its role in ccRCC remains unclear. Methods: We investigated PRMT1 expression level and its correlations to clinicopathological factors and prognosis in ccRCC patients based on ccRCC tissue microarrays (TMAs). Genetic knockdown and pharmacological inhibition using a novel PRMT1 inhibitor DCPT1061 were performed to investigate the functional role of PRMT1 in ccRCC proliferation. Besides, we confirmed the antitumor effect of PRMT1 inhibitor DCPT1061 in ccRCC cell-derived tumor xenograft (CDX) models as well as patient-derived tumor xenograft (PDX) models. Results: We found PRMT1 expression was remarkably upregulated in tumor tissues and associated with poor pathologic characters and outcomes of ccRCC patients. Furthermore, genetic knockdown and pharmacological inhibition of PRMT1 by a novel potent inhibitor DCPT1061 dramatically induced G1 cell cycle arrest and suppressed ccRCC cell growth. Mechanistically, RNA sequencing and further validation identified Lipocalin2 (LCN2), a secreted glycoprotein implicated in tumorigenesis, as a crucial regulator of ccRCC growth and functional downstream effector of PRMT1. Epigenetic silencing of LCN2 autocrine secretion by PRMT1 deficiency decreased downstream p-AKT, leading to reduced p-RB and cell growth arrest through the neutrophil gelatinase associated lipocalin receptor (NGALR). Moreover, PRMT1 inhibition by DCPT1061 not only inhibited tumor growth but also sensitized ccRCC to sunitinib treatment in vivo by attenuating sunitinib-induced upregulation of LCN2-AKT-RB signaling. Conclusion: Taken together, our study revealed a PRMT1-dependent epigenetic mechanism in the control of ccRCC tumor growth and drug resistance, indicating PRMT1 may serve as a promising target for therapeutic intervention in ccRCC patients.
ALDH1A3 Coordinates Metabolism With Gene Regulation in Pulmonary Arterial Hypertension
Authors: Dan Li, Ning-Yi Shao, Jan-Renier Moonen, Zhixin Zhao, Minyi Shi, Shoichiro Otsuki, Lingli Wang, Tiffany Nguyen, Elaine Yan, David P. Marciano, Kévin Contrepois, Caiyun G. Li, Joseph C. Wu, Michael P. Snyder, Marlene Rabinovitch
Journal: Circulation (2021)

Background: Metabolic alterations provide substrates that influence chromatin structure to regulate gene expression that determines cell function in health and disease. Heightened proliferation of smooth muscle cells (SMC) leading to the formation of a neointima is a feature of pulmonary arterial hypertension (PAH) and systemic vascular disease. Increased glycolysis is linked to the proliferative phenotype of these SMC. Methods: RNA sequencing was applied to pulmonary arterial SMC (PASMC) from PAH patients with and without a BMPR2 (bone morphogenetic receptor 2) mutation versus control PASMC to uncover genes required for their heightened proliferation and glycolytic metabolism. Assessment of differentially expressed genes established metabolism as a major pathway, and the most highly upregulated metabolic gene in PAH PASMC was aldehyde dehydrogenase family 1 member 3 ( ALDH1A3) , an enzyme previously linked to glycolysis and proliferation in cancer cells and systemic vascular SMC. We determined if these functions are ALDH1A3-dependent in PAH PASMC, and if ALDH1A3 is required for the development of pulmonary hypertension in a transgenic mouse. Nuclear localization of ALDH1A3 in PAH PASMC led us to determine whether and how this enzyme coordinately regulates gene expression and metabolism in PAH PASMC. Results: ALDH1A3 mRNA and protein were increased in PAH versus control PASMC, and ALDH1A3 was required for their highly proliferative and glycolytic properties. Mice with Aldh1a3 deleted in SMC did not develop hypoxia-induced pulmonary arterial muscularization or pulmonary hypertension. Nuclear ALDH1A3 converted acetaldehyde to acetate to produce acetyl coenzyme A to acetylate H3K27, marking active enhancers. This allowed for chromatin modification at NFYA (nuclear transcription factor Y subunit α) binding sites via the acetyltransferase KAT2B (lysine acetyltransferase 2B) and permitted NFY-mediated transcription of cell cycle and metabolic genes that is required for ALDH1A3-dependent proliferation and glycolysis. Loss of BMPR2 in PAH SMC with or without a mutation upregulated ALDH1A3, and transcription of NFYA and ALDH1A3 in PAH PASMC was β-catenin dependent. Conclusions: Our studies have uncovered a metabolic-transcriptional axis explaining how dividing cells use ALDH1A3 to coordinate their energy needs with the epigenetic and transcriptional regulation of genes required for SMC proliferation. They suggest that selectively disrupting the pivotal role of ALDH1A3 in PAH SMC, but not endothelial cells, is an important therapeutic consideration.
MA10.06 Healthcare Utilization with an Electronic Patient Reported Outcome (ePRO) tool for Symptom Management in Thoracic Cancers
Authors: M. Roy, T. Fardeen, O. Generalova, E. Hall, K. Cunanan, M. Das, J. Neal, S. Padda, H.A. Wakelee, K. Ramchandran
Journal: Journal of Thoracic Oncology (2021)
Dietary Gluten Intake Is Not Associated With Risk of Inflammatory Bowel Disease in US Adults Without Celiac Disease
Authors: Emily W. Lopes, Benjamin Lebwohl, Kristin E. Burke, Kerry L. Ivey, Ashwin N. Ananthakrishnan, Paul Lochhead, James M. Richter, Jonas F. Ludvigsson, Walter C. Willett, Andrew T. Chan, Hamed Khalili
Journal: Clinical Gastroenterology and Hepatology (2021)
Germline SAMD9L truncation variants trigger global translational repression
Authors: Eric J. Allenspach, Frank Soveg, Laura S. Finn, Lomon So, Jacquelyn A. Gorman, Aaron B.I. Rosen, Suzanne Skoda-Smith, Marsha M. Wheeler, Kaitlyn A. Barrow, Lucille M. Rich, Jason S. Debley, Michael J. Bamshad, Deborah A. Nickerson, Ram Savan, Troy R. Torgerson, David J. Rawlings
Journal: The Journal of Experimental Medicine (2021)

SAMD9L is an interferon-induced tumor suppressor implicated in a spectrum of multisystem disorders, including risk for myeloid malignancies and immune deficiency. We identified a heterozygous de novo frameshift variant in SAMD9L in an infant with B cell aplasia and clinical autoinflammatory features who died from respiratory failure with chronic rhinovirus infection. Autopsy demonstrated absent bone marrow and peripheral B cells as well as selective loss of Langerhans and Purkinje cells. The frameshift variant led to expression of a truncated protein with interferon treatment. This protein exhibited a gain-of-function phenotype, resulting in interference in global protein synthesis via inhibition of translational elongation. Using a mutational scan, we identified a region within SAMD9L where stop-gain variants trigger a similar translational arrest. SAMD9L variants that globally suppress translation had no effect or increased mRNA transcription. The complex-reported phenotype likely reflects lineage-dominant sensitivities to this translation block. Taken together, our findings indicate that interferon-triggered SAMD9L gain-of-function variants globally suppress translation.
P85.01 Activity of Tepotinib in Brain Metastases (BM): Preclinical and Clinical Data in MET Exon 14 (METex14) Skipping NSCLC
Authors: J. Mazieres, R. Veillon, E. Felip, X. Le, M.C. Garassino, T. Stanton, M. Morise, J. Lee, S. Matsumoto, F. De Marinis, T. Wehler, A. Clark, M. Friese-Hamin, C. Stroh, R. Bruns, G. Otto, P. Paik
Journal: Journal of Thoracic Oncology (2021)
Prevalence of clinical signs and symptoms of the masticatory system and their associations in children with sleep bruxism: A systematic review and meta-analysis
Authors: Josiane Pezzini Soares, Juliana Moro, Carla Massignan, Mariane Cardoso, Júnia Maria Serra-Negra, Lucianne Cople Maia, Michele Bolan
Journal: Sleep Medicine Reviews (2021)
P02.14 Radiotherapy-Associated CT Imaging as a Potential Screening Tool for COVID-19
Authors: A. Wu, A. Plodkowski, M. Ginsberg, J. Shin, Q. Laplant, A. Shepherd, N. Shaverdian, V. Ng, Y. Yue, P. Gilbo, D. Gelblum, L. Braunstein, D. Gomez, A. Rimner
Journal: Journal of Thoracic Oncology (2021)
P38.13 Cytology-Histology Concordance for Diagnosis, Histological Subtyping and Molecular Profiling of Lung Cancer
Authors: C. Merkouri, D. Grapsa, I. Tourkantonis, I. Gkiozos, A. Charpidou, G. Tournas, G. Stratakos, E. Politi, K. Syrigos
Journal: Journal of Thoracic Oncology (2021)
The role of GLS1-mediated glutaminolysis/2-HG/H3K4me3 and GSH/ROS signals in Th17 responses counteracted by PPARγ agonists
Authors: Yumeng Miao, Yun Zheng, Yanzhi Geng, Ling Yang, Na Cao, Yue Dai, Zhifeng Wei
Journal: Theranostics (2021)

Background: Peroxisome proliferator-activated receptor gamma (PPARγ) has the ability to counter Th17 responses, but the full mechanisms remain elusive. Herein, we aimed to elucidate this process in view of cellular metabolism, especially glutaminolysis. Methods: MTT, CCK-8, Annexin V-FITC/PI staining or trypan blue exclusion assays were used to analyze cytotoxicity. Flow cytometry and Q-PCR assays were applied to determine Th17 responses. The detection of metabolite levels using commercial kits and rate-limiting enzyme expression using western blotting assays was performed to illustrate the metabolic activity. ChIP assays were used to examine H3K4me3 modifications. Mouse models of dextran sulfate sodium (DSS)-induced colitis and house dust mite (HDM)/lipopolysaccharide (LPS)-induced asthma were established to confirm the mechanisms studied in vitro. Results: The PPARγ agonists rosiglitazone and pioglitazone blocked glutaminolysis but not glycolysis under Th17-skewing conditions, as indicated by the detection of intracellular lactate and α-KG and the fluorescence ratios of BCECF-AM. The PPARγ agonists prevented the utilization of glutamine and thus directly limited Th17 responses even when Foxp3 was deficient. The mechanisms were ascribed to restricted conversion of glutamine to glutamate by reducing the expression of the rate-limiting enzyme GLS1, which was confirmed by GLS1 overexpression. Replenishment of α-KG and 2-HG but not succinate weakened the effects of PPARγ agonists, and α-KG-promoted Th17 responses were dampened by siIDH1/2. Inhibition of KDM5 but not KDM4/6 restrained the inhibitory effect of PPARγ agonists on IL-17A expression, and the H3K4me3 level in the promoter and CNS2 region of the il-17 gene locus down-regulated by PPARγ agonists was rescued by 2-HG and GLS1 overexpression. However, the limitation of PPARγ agonists on the mRNA expression of RORγt was unable to be stopped by 2-HG but was attributed to GSH/ROS signals subsequent to GLS1. The exact role of PPARγ was proved by GW9662 or PPARγ knockout, and the mechanisms for PPARγ-inhibited Th17 responses were further confirmed by GLS1 overexpression in vivo. Conclusion: PPARγ agonists repressed Th17 responses by counteracting GLS1-mediated glutaminolysis/2-HG/H3K4me3 and GSH/ROS signals, which is beneficial for Th17 cell-related immune dysregulation.
Healthcare without borders: A cross-sectional study of immigrant and nonimmigrant children admitted to a large public sector hospital in the Gauteng Province of South Africa
Authors: Gerhard H. Janse van Rensburg, Ute Dagmar Feucht, Jennifer Makin, Nanya le Clus, Theunis Avenant
Journal: PLoS Medicine (2021)

Human migration is a worldwide phenomenon that receives considerable attention from the media and healthcare authorities alike. A significant proportion of children seen at public sector health facilities in South Africa (SA) are immigrants, and gaps have previously been noted in their healthcare provision. The objective of the study was to describe the characteristics and differences between the immigrant and SA children admitted to Kalafong Provincial Tertiary Hospital (KPTH), a large public sector hospital in the urban Gauteng Province of SA.A cross-sectional study was conducted over a 4-month period during 2016 to 2017. Information was obtained through a structured questionnaire and health record review. The enrolled study participants included 508 children divided into 2 groups, namely 271 general paediatric patients and 237 neonates. Twenty-five percent of children in the neonatal group and 22.5% in the general paediatric group were immigrants. The parents/caregivers of the immigrant group had a lower educational level (p < 0.0001 neonatal and paediatric), lower income (neonatal p < 0.001; paediatric p = 0.024), difficulty communicating in English (p < 0.001 neonatal and paediatric), and were more likely residing in informal settlements (neonatal p = 0.001; paediatric p = 0.007) compared to the SA group. In the neonatal group, there was no difference in the number of antenatal care (ANC) visits, type of delivery, gestational age, and birth weight. In the general paediatric group, there was no difference in immunisation and vitamin A supplementation coverage, but when comparing growth, the immigrant group had more malnutrition compared to the SA group (p = 0.029 for wasting). There was no difference in the prevalence of maternal human immunodeficiency virus (HIV) infection, with equally good prevention of mother-to-child transmission (PMTCT) coverage. There was also no difference in reported difficulties by immigrants in terms of access to healthcare (neonatal p = 0.379; paediatric p = 0.246), although a large proportion (10%) of the neonates of immigrant mothers were born outside a medical facility.Although there were health-related differences between immigrant and SA children accessing in-hospital care, these were fewer than expected. Differences were found in parental educational level and socioeconomic factors, but these did not significantly affect ANC attendance, delivery outcomes, immunisation coverage, HIV prevalence, or PMTCT coverage. The immigrant population should be viewed as a high-risk group, with potential problems including suboptimal child growth. Health workers should advocate for all children in the community they are serving and promote tolerance, respect, and equal healthcare access.
Targeting of miR-33 ameliorates phenotypes linked to age-related macular degeneration
Authors: Gopalan Gnanaguru, Alexandre Wagschal, Justin Oh, Kahira L. Saez-Torres, Tong Li, Ryan E. Temel, Mark E. Kleinman, Anders M. Näär, Patricia A. D’Amore
Journal: Molecular Therapy (2021)

Abnormal cholesterol/lipid homeostasis is linked to neurodegenerative conditions such as age-related macular degeneration (AMD), which is a leading cause of blindness in the elderly. The most prevalent form, termed "dry" AMD, is characterized by pathological cholesterol accumulation beneath the retinal pigment epithelial (RPE) cell layer and inflammation-linked degeneration in the retina. We show here that the cholesterol-regulating microRNA miR-33 was elevated in the RPE of aging mice. Expression of the miR-33 target ATP-binding cassette transporter (ABCA1), a cholesterol efflux pump genetically linked to AMD, declined reciprocally in the RPE with age. In accord, miR-33 modulated ABCA1 expression and cholesterol efflux in human RPE cells. Subcutaneous delivery of miR-33 antisense oligonucleotides (ASO) to aging mice and non-human primates fed a Western-type high fat/cholesterol diet resulted in increased ABCA1 expression, decreased cholesterol accumulation, and reduced immune cell infiltration in the RPE cell layer, accompanied by decreased pathological changes to RPE morphology. These findings suggest that miR-33 targeting may decrease cholesterol deposition and ameliorate AMD initiation and progression.
FP13.01 5-Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel in Previously Treated, PD-L1–Positive Advanced NSCLC
Authors: R. Herbst, E. Garon, D. Kim, B.C. Cho, R. Gervais, J.L. Perez-Gracia, J. Han, M. Majem, M.D. Forster, I. Monnet, S. Novello, M.A. Gubens, M. Boyer, W. Su, A. Samkari, E.H. Jensen, B. Piperdi, P. Baas
Journal: Journal of Thoracic Oncology (2021)
Health Care for People Experiencing Homelessness—What Outcomes Matter?
Authors: Kelly M. Doran, Alaina P. Boyer, Maria C. Raven
Journal: JAMA Network Open (2021)

Jenell Stewart, DO, MPH; Kathryn M. Stadeli, MD, MPH; Kristjana H. Ásbjörnsdóttir, PhD, MPH; Margaret L. Green, MD; Giana H. Davidson, MD, MPH; Bryan J. Weiner, PhD; Shireesha Dhanireddy, MD
Covid-19: Officials query data from AstraZeneca’s US vaccine trial
Authors: Zosia Kmietowicz
Journal: BMJ (2021)

Officials query data from AstraZeneca's US vaccine trial Zosia KmietowiczOfficials from the monitoring board overseeing AstraZeneca's latest covid-19 vaccine trial have expressed concern that data released by the company this week may have been out of date and "provided an incomplete view of the efficacy data."AstraZeneca issued an interim analysis of its phase III trial carried out in the US, Chile, and Peru in a press release on 22 March. 1 This showed that the vaccine was 79% effective at preventing symptomatic covid-19 and 100% effective at preventing severe disease and admission to hospital, though the results have yet to be formally peer reviewed.1