tbuckley/cabot-search huggingface dataset:
Cancer-derived exosomal miR-138-5p modulates polarization of tumor-associated macrophages through inhibition of KDM6B
Authors: Jing Xun, Lingfang Du, Ruifang Gao, Long Shen, Dekun Wang, Lichun Kang, Chuan'ai Chen, Zhujun Zhang, Yuying Zhang, Shijing Yue, Shuxin Feng, Rong Xiang, Xue Mi, Xiaoyue Tan
Journal: Theranostics (2021)

Rationale: Differential activation of macrophages correlates closely with tumor progression, and the epigenetic factor lysine demethylase 6B (KDM6B, previously named JMJD3) mediates the regulation of macrophage polarization through an unknown mechanism. Methods: We developed a suspension coculture system comprising breast cancer cells and macrophages and used RT-qPCR and western blotting to measure KDM6B expression. Bioinformatics and luciferase reporter assays were used to identify candidate microRNAs of cancer cells responsible for the downregulation of KDM6B. To determine if exosomes mediated the transfer of miR-138-5p between cancer cells to macrophages, we treated macrophages with exosomes collected from the conditioned medium of cancer cells. The effects of exosomal miR-138-5p on macrophage polarization were measured using RT-qPCR, flow cytometry, and chromatin immunoprecipitation assays. We employed a mouse model of breast cancer, metastatic to the lung, to evaluate the effects on tumor metastasis of macrophages treated with miR-138-5p-enriched exosomes. To develop a diagnostic evaluation index, the levels of exosomal miR-138-5p in samples from patients with breast cancer were compared to those of controls. Results: Coculture of breast cancer cells led to downregulation of KDM6B expression in macrophages. Cancer cell-derived exosomal miR-138-5p inhibited M1 polarization and promoted M2 polarization through inhibition of KDM6B expression in macrophages. Macrophages treated with exosomal miR-138-5p promoted lung metastasis, and the level of circulating exosomal miR-138-5p positively correlated with the progression of breast cancer. Conclusion: Our data suggest that miR-138-5p was delivered from breast cancer cells to tumor-associated macrophages via exosomes to downregulate KDM6B expression, inhibit M1 polarization, and stimulate M2 polarization. Therefore, exosomal miR-138-5p represents a promising prognostic marker and target for the treatment of breast cancer.
Performance Evaluation of Serial SARS-CoV-2 Rapid Antigen Testing During a Nursing Home Outbreak
Authors: Susannah L. McKay, Farrell A. Tobolowsky, Erin D. Moritz, Kelly M. Hatfield, Amelia Bhatnagar, Stephen P. LaVoie, David A. Jackson, K. Danielle Lecy, Jonathan Bryant-Genevier, Davina Campbell, Brandi Freeman, Sarah E. Gilbert, Jennifer M. Folster, Magdalena Medrzycki, Patricia L. Shewmaker, Bettina Bankamp, Kay W. Radford, Raydel Anderson, Michael D. Bowen, Jeanne Negley, Sujan C. Reddy, John A. Jernigan, Allison C. Brown, L. Clifford McDonald, Preeta K. Kutty
Journal: Annals of Internal Medicine (2021)

To address high COVID-19 burden in U.S. nursing homes, rapid SARS-CoV-2 antigen tests have been widely distributed in those facilities. However, performance data are lacking, especially in asymptomatic people.
LEVERAGING MACHINE LEARNING MODELS TO PREDICT IN-HOSPITAL MORTALITY AFTER MITRACLIP
Authors: Chayakrit Krittanawong, Hafeez Ul Hassan Virk, Joshua Hahn, Fu'ad Al-Azzam, Kevin Greason, Ameesh Isath, Bing Yue, Scott Kaplin, Matthew Stewart, Mahboob Alam, Samin Sharma
Journal: Journal of the American College of Cardiology (2021)
Abstract P126: Sex Interacts With Chromosome 6p24 on Coronary Artery Calcium but Not Chromosome 9p21
Authors: Sharon M Lutz, Dawn DeMeo, Matthew Budoff, John E Hokanson
Journal: Circulation (2018)

Introduction: Coronary artery calcium (CAC) is a marker of subclinical atherosclerosis. CAC has been shown to strongly correlate with the amount of atherosclerotic plaque and predicts future coronary disease events and mortality. CAC is a complex heritable trait and levels differ by sex. We investigated the interaction between sex and genome wide association study (GWAS) signals on chromosome 6p24 and 9p21 on Coronary Artery Calcium (CAC) in the COPDGene study. Hypothesis: We assessed the hypothesis that sex would interact with the GWAS signals on CAC. Methods: The COPDGene is a study of 10,192 current and former smokers with at least 10 pack-years of smoking history. CAC was measured using high dose, inspiration chest CT scans, following an established protocol in 8,739 individuals (6,150 non-Hispanic Whites (NHW) and 2,589 African Americans (AA)). We considered sex by SNP interactions on CAC for our previously identified GWAS signals on chromosome 6p24 and chromosome 9p21 using R software adjusting for genetic ancestry using principal components as well as recognized risk factors (age, pack-years of smoking history, BMI, diabetes, high blood pressure, high cholesterol, and steroid use). We used the log transformation of CAC plus 1 as the quantitative phenotype. Results: There was a significant interaction between sex and chromosome 6p24 PHACTR1 [rs9349379] (p=0.023) on CAC among NHW subjects in the COPDGene study. There was a genome-wide significant association for rs9349379 with CAC among male NHW subjects [p-value= 1.21E-8] but not among female NHW subjects [p-value= 0.02]. Overall there was no genome-wide significant association for rs9349379 with CAC among all NHW subjects [p-value= 6.39E-7]. There was no significant interaction between sex and chromosome 9p21 CDKN2B-AS1 [rs10757272] (p-value=0.25) on CAC among NHW COPDGene subjects. Among AA subjects in the COPDGene study, there was not a significant interaction between sex and rs9349379 [ PHACTR1 ] (p-value=0.48) or sex and rs10757272 [ CDKN2B-AS1 ] (p-value=0.21) on CAC. Conclusions: There was a SNP by sex interaction on CAC for chromosome 6p24 with a genome wide significant signal for NHW men but not for NHW women. The chromosome 9p21 signal for CAC did not significantly differ by sex. This study demonstrates the importance of considering gene by sex interactions in genome wide association studies of cardiovascular disease risk.
HEART TRANSPLANTATION OUTCOMES IN ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY: A CONTEMPORARY ANALYSIS OF THE UNITED NETWORK FOR ORGAN SHARING REGISTRY
Authors: Katherine Giuliano, Paul Scheel, Eric Etchill, Steven Hsu, Ilan Wittstein, Harikrishna Tandri, Hugh Calkins, Chun Choi, Kavita Sharma, Ahmet Kilic, Nisha Gilotra, Johns Hopkins
Journal: Journal of the American College of Cardiology (2021)
18F-FDG PET/CT and 68Ga-FAPI-04 PET/CT Findings of Abdominal Leiomyosarcoma
Authors: Yunus Güzel, Canan Can, Nilgün Söğütçü, Ebubekir Gündeş, Cihan Gündoğan
Journal: Clinical Nuclear Medicine (2021)

Abstract A 56-year-old woman presented with abdominal pain and vomiting. Her abdominal CT revealed an retroperitoneal mass in the left upper quadrant of the abdomen. 18 F-FDG PET/CT performed for metabolic characterization showed low to moderate heterogenous FDG uptake. 68 Ga–fibroblast activation protein-specific inhibitor (FAPI)–04 PET/CT performed according to a research carried out in our department showed high heterogenous radiopharmaceutical uptake. The patient was diagnosed with leiomyosarcoma after R0 tumor resection. This case showed that 68 Ga-FAPI-04 PET/CT could be a promising radiopharmaceutical in the evaluation of leiomyosarcomas.
Single-cell transcriptome profiling reveals vascular endothelial cell heterogeneity in human skin
Authors: Qingyang Li, Zhenlai Zhu, Lei Wang, Yiting Lin, Hui Fang, Jie Lei, Tianyu Cao, Gang Wang, Erle Dang
Journal: Theranostics (2021)

Vascular endothelial cells (ECs) are increasingly recognized as active players in intercellular crosstalk more than passive linings of a conduit for nutrition delivery. Yet, their functional roles and heterogeneity in skin remain uncharacterized. We have used single-cell RNA sequencing (scRNA-seq) as a profiling strategy to investigate the tissue-specific features and intra-tissue heterogeneity in dermal ECs at single-cell level. Methods: Skin tissues collected from 10 donors were subjected to scRNA-seq. Human dermal EC atlas of over 23,000 single-cell transcriptomes was obtained and further analyzed. Arteriovenous markers discovered in scRNA-seq were validated in human skin samples via immunofluorescence. To illustrate tissue-specific characteristics of dermal ECs, ECs from other human tissues were extracted from previously reported data and compared with our transcriptomic data. Results: In comparison with ECs from other human tissues, dermal ECs possess unique characteristics in metabolism, cytokine signaling, chemotaxis, and cell adhesions. Within dermal ECs, 5 major subtypes were identified, which varied in molecular signatures and biological activities. Metabolic transcriptome analysis revealed a preference for oxidative phosphorylation in arteriole ECs when compared to capillary and venule ECs. Capillary ECs abundantly expressed HLA-II molecules, suggesting its immune-surveillance role. Post-capillary venule ECs, with high levels of adhesion molecules, were equipped with the capacity in immune cell arrest, adhesion, and infiltration. Conclusion: Our study provides a comprehensive characterization of EC features and heterogeneity in human dermis and sets the stage for future research in identifying disease-specific alterations of dermal ECs in various dermatoses.
Abstract 13976: Dual Antiplatelet Therapy is Not Associated With Better Early-Term Outcomes After Coronary Artery Bypass Grafting
Authors: Jianyu Qu, Heng Zhang, Chenfei Rao, Hanping Ma, Zhe Zheng
Journal: Circulation (2019)

Background: Aspirin has been reported to improve survival and mortality after coronary artery bypass grafting (CABG), however, whether dual antiplatelet therapy (DAPT) further improves patients’ ea...
A BEADED HEART- A RARE CASE OF FIBROMUSCULAR DYSPLASIA PRESENTING AS CARDIAC ARREST
Authors: Naga Vaishnavi Gadela, Mahati Paravathaneni, Surya Aedma, Pranav Mahajan, Dimitrios Drekolias, Ayesha Azmeen, Jason Jacob
Journal: Journal of the American College of Cardiology (2021)
THE ASSOCIATION BETWEEN LOCAL INFLAMMATION AND THE PRESENCE OF UNRECOGNIZED MYOCARDIAL INFARCTION IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE
Authors: Yumi Yasui, Yoshihisa Kanaji, Tomoyo Sugiyama, Masahiro Hoshino, Masao Yamaguchi, Toru Misawa, Masahiro Hada, Tatsuhiro Nagamine, Kai Nogami, Tsunekazu Kakuta
Journal: Journal of the American College of Cardiology (2021)
Fostering healthy aging: The interdependency of infections, immunity and frailty
Authors: Davide L. Vetrano, Federico Triolo, Stefania Maggi, Richard Malley, Thomas A. Jackson, Andrea Poscia, Roberto Bernabei, Luigi Ferrucci, Laura Fratiglioni
Journal: Ageing Research Reviews (2021)

Untangling the interdependency of infections, immunity and frailty may help to clarify their roles in the maintenance of health in aging individuals, and the recent COVID-19 pandemic has further highlighted such priority. In this scoping review we aimed to systematically collect the evidence on 1) the impact of common infections such as influenza, pneumonia and varicella zoster on frailty development, and 2) the role played by frailty in the response to immunization of older adults. Findings are discussed under a unifying framework to identify knowledge gaps and outline their clinical and public health implications to foster a healthier aging. Twenty-nine studies (113,863 participants) selected to answer the first question provided a moderately strong evidence of an association between infections and physical as well as cognitive decline – two essential dimensions of frailty. Thirteen studies (34,520 participants) investigating the second aim, showed that frailty was associated with an impaired immune response in older ages, likely due to immunosenescence. However, the paucity of studies, the absence of tools to predict vaccine efficacy, and the lack of studies investigating the efficacy of newer vaccines in presence of frailty, strongly limit the formulation of more personalized immunization strategies for older adults. The current evidence suggests that infections and frailty repeatedly cross each other pathophysiological paths and accelerate the aging process in a vicious circle. Such evidence opens to several considerations. First, the prevention of both conditions pass through a life course approach, which includes several individual and societal aspects. Second, the maintenance of a well-functioning immune system may be accomplished by preventing frailty, and vice versa. Third, increasing the adherence to immunization may delay the onset of frailty and maintain the immune system homeostasis, beyond preventing infections.
Should masks be worn outdoors?
Authors: Babak Javid, Dirk Bassler, Manuel B Bryant, Muge Cevik, Zeynep Tufekci, Stefan Baral
Journal: BMJ (2021)

Wearing face coverings outside should be normalised because it may reduce transmission of SARS-CoV-2 in some situations—and may encourage mask wearing indoors, where risks are greater—say <b>Babak Javid</b>, <b>Dirk Bassler</b>, and <b>Manuel B Bryant</b>. But <b>Muge Cevik</b>, <b>Zeynep Tufekci</b>, and <b>Stefan Baral</b> argue that outdoor transmission contributes very little to overall infection rates and that efforts should focus on reducing indoor transmission
MITRAL STENOSIS DUE TO MITRAL ANNULAR CALCIFICATION, IMPACT OF FRAILTY AND COMORBIDITIES
Authors: Yoshihito Saijo, Nicholas Chan, Maria Vega Brizneda, Hassan Mehmood Lak, Reza Reyaldeen, Richard Grimm, Brian Griffin, Bo Xu
Journal: Journal of the American College of Cardiology (2021)
Candidate gene approach evaluates associations between OR10J3, FCER1A genes and breast cancer risk
Authors: Ji-Young Lee, Ae kyung Park, Kyoung-mu Lee, Sue Kyung Park, Sohee Han, Wonshik Han, Dong-Young Noh, Keun-Young Yoo, Ho Kim, Robert Welch, Stephen J. Chanock, Nathaniel Rothman, Daehee Kang
Journal: Cancer Research (2008)

1930  Purpose: This study was conducted to evaluate of common variation in candidate genes of breast cancer risk in Korean.  Methods: An Illumina GoldenGate assay was used to genotype1,536 common variants and near 205 genes in 209 cases and 209 controls in Korea. All SNPs chosen for this platform were drawn from the innate immunity-related genes as previously evaluated in relation to cancer risk or those with evidence for functional significance. We performed gene-based and SNPs based tests evaluating the robustness of our results with FDR and Permutation methods.  Results: Gene-based and SNP-based analyses showed promising associations with breast cancer risk for 23 genes: OR10J3, FCER1A, NCF4, CNTNAP1, CTNNB1, KLKB1, ITGB2, ALOX12B, KLK2, IRAK3, KLK4, STAT6, NCF2, CCL1, C1QR1, DEFB1, DLG5, ICAM1, C6, CCR6, TNFSF9, MBP, NOS1. The most significant association with breast cancer risk according to gene-based analyses was observed for the OR10J3 gene. Gene-based analyses firstly showed a significant finding in OR10J3 (p for likelihood ratio test, 1 degrees of freedom (df) =2×10-5). The FDR-adjusted p-value for the association of OR10J3 with breast cancer risk was also significant (global p =0.008 (1 df), p =0.02 (2 df)). Secondly, individual SNP-based analyses were quite concordant with gene-based analyses. Consistent with individual SNP analyses, haplotype analyses revealed two genes (OR10J3, FCER1A) were also strongly associated with reduced risk for breast cancer (global p=2×10-4, p=0.004 respectively). These two SNPs were adjacently located in chromosome 1q23 which was yet well unknown the functional association with breast cancer risk.  Conclusion: Through the highly multiplexed technology, candidate cancer genes and SNPs of OR10J3 and FCER1A have identified the association with breast cancer risks. Further second stage studies are required to confirm these findings, as well as to examine the biological mechanisms for the associations.
A CASE OF FATAL COVID-19 FULMINANT MYOCARDITIS IN A YOUNG WOMAN WITH NO CARDIOVASCULAR MEDICAL HISTORY: GETTING TO THE HEART OF CORONAVIRUS COMPLICATIONS
Authors: Mahmoud Samy Ahmed, Mouhamed Nashawi, Justin Haloot, Hendre Fichardt, Vicken Zeitjian, Anand Prasad, Katherine Dodd
Journal: Journal of the American College of Cardiology (2021)
COVID-19 and Alzheimer’s disease: how one crisis worsens the other
Authors: Xiaohuan Xia, Yi Wang, Jialin Zheng
Journal: Translational Neurodegeneration (2021)

Abstract Alzheimer’s disease (AD) has emerged as a key comorbidity of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The morbidity and mortality of COVID-19 are elevated in AD due to multiple pathological changes in AD patients such as the excessive expression of viral receptor angiotensin converting enzyme 2 and pro-inflammatory molecules, various AD complications including diabetes, lifestyle alterations in AD, and drug-drug interactions. Meanwhile, COVID-19 has also been reported to cause various neurologic symptoms including cognitive impairment that may ultimately result in AD, probably through the invasion of SARS-CoV-2 into the central nervous system, COVID-19-induced inflammation, long-term hospitalization and delirium, and post-COVID-19 syndrome. In addition, the COVID-19 crisis also worsens behavioral symptoms in uninfected AD patients and poses new challenges for AD prevention. In this review, we first introduce the symptoms and pathogenesis of COVID-19 and AD. Next, we provide a comprehensive discussion on the aggravating effects of AD on COVID-19 and the underlying mechanisms from molecular to social levels. We also highlight the influence of COVID-19 on cognitive function, and propose possible routes of viral invasion into the brain and potential mechanisms underlying the COVID-19-induced cognitive impairment. Last, we summarize the negative impacts of COVID-19 pandemic on uninfected AD patients and dementia prevention.
SAFETY OR EFFICACY; CAN OR SHOULD WE HAVE BOTH? TABOO DEVICES IN THE MRI ENVIRONMENT
Authors: Robert W.W. Biederman, Loretta Gevenosky, Huma Samar, Ronald Williams, Richard Lombardi, Moneal Shah, Victor Farah, Francesco Mangini, Christopher Bonnet, Mark Doyle
Journal: Journal of the American College of Cardiology (2021)
Assessment of Catheter Ablation or Antiarrhythmic Drugs for First-line Therapy of Atrial Fibrillation
Authors: Mohit K. Turagam, Daniel Musikantow, William Whang, Jacob S. Koruth, Marc A. Miller, Marie-Noelle Langan, Aamir Sofi, Subbarao Choudry, Srinivas R. Dukkipati, Vivek Y. Reddy
Journal: JAMA Cardiology (2021)

Early rhythm control of atrial fibrillation (AF) with either antiarrhythmic drugs (AADs) or catheter ablation has been reported to improve cardiovascular outcomes compared with usual care; however, the optimal therapeutic modality to achieve early rhythm control is unclear.
CONSTRUCTIVE WORK AND LONGITUDINAL STRAIN-DERIVED APICAL SPARING PATTERN DIFFERENTIATE CARDIAC AMYLOIDOSIS FROM HYPERTROPHIC CARDIOMYOPATHY
Authors: Catherina Tjahjadi, Robert Adam, Philippe Debonnaire, Mathias Claeys, Maarten Desmet, Kensuke Hirasawa, Bogdan Alexandru Popescu, Ruxandra Jurcut, Victoria Delgado, Jeroen Bax, Nina Marsan
Journal: Journal of the American College of Cardiology (2021)
Real‐world drug survival of guselkumab, ixekizumab and secukinumab for psoriasis
Authors: H. Iznardo, E. Vilarrasa, A. López‐Ferrer, L. Puig
Journal: British Journal of Dermatology (2021)

Funding sources: none. Conflicts of interest: E.V. has received consultancy and/or speaker honoraria and/or participated in clinical trials sponsored by AbbVie, Almirall, Boehringer, Celgene, Eli Lilly, Janssen, LEO Pharma, MSD, Novartis, Pfizer and UCB. A.L‐F. has received consultancy and/or speaker honoraria and/or participated in clinical trials sponsored by Novartis, Janssen, MSD, Eli Lilly and Company, Pfizer, Celgene España S.L., Almirall, LEO Pharma, AbbVie and Amgen. L.P. has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Celgene, Eli Lilly and Co., Gebro, Janssen, JS BIOCAD, LEO Pharma, Merck‐Serono, MSD, Mylan, Novartis, Pfizer, Regeneron, Roche, Samsung‐Bioepis, Sandoz, Sanofi and UCB. Dear Editor, Guselkumab is an interleukin (IL)‐23 inhibitor approved for moderate‐to‐severe plaque psoriasis. It has demonstrated safety and efficacy in phase III clinical trials.1–3 However, there are scarce data regarding its drug survival in clinical practice. This retrospective cohort study examined drug survival in 188 patients treated consecutively at the Dermatology Clinic of Hospital de la Santa Creu i Sant Pau for moderate‐to‐severe psoriasis with guselkumab, ixekizumab and secukinumab since these biologics became commercially available in our region (March 2019, January 2017 and November 2015, respectively) until January 2021 (Table 1). Treatment failure was defined as discontinuation or switching to a different systemic or biologic agent due to lack or loss of effectiveness or adverse events. Our main therapeutic goal was absolute Psoriasis Area and Severity Index (PASI) ≤ 2. We also recorded treatment switch, which is offered when absolute PASI ≤ 5 response is not achieved 4–6 months after the start of treatment or is lost for 3–4 months. Documented adverse events were also reviewed. Drug survival probability was assessed using Kaplan–Meier analysis.
Covid-19: Photograph collection records historic vaccine rollout
Authors: Alison Shepherd
Journal: BMJ (2021)

This picture showing a 92 year old man receiving his covid vaccine is among a collection of photographs brought together to showcase the people behind the UK's vaccination effort.Gavin Chestnutt, a GP partner at Ballycastle Medical Practice, Country Antrim, took a ferry to Rathlin Island to give Duncan Smythe his first jab in March.
What Animal Cancers teach us about Human Biology
Authors: Patricia Kattner, Katharina Zeiler, Verena J Herbener, Katia La Ferla-Brühl, Rebecca Kassubek, Michael Grunert, Timo Burster, Oliver Brühl, Anna Sarah Weber, Hannah Strobel, Georg Karpel-Massler, Sibylle Ott, Alexa Hagedorn, Daniel Tews, Ansgar Schulz, Vikas Prasad, Markus D Siegelin, Lisa Nonnenmacher, Pamela Fischer-Posovszky, Marc-Eric Halatsch, Klaus-Michael Debatin, Mike-Andrew Westhoff
Journal: Theranostics (2021)

Cancers in animals present a large, underutilized reservoir of biomedical information with critical implication for human oncology and medicine in general. Discussing two distinct areas of tumour biology in non-human hosts, we highlight the importance of these findings for our current understanding of cancer, before proposing a coordinated strategy to harvest biomedical information from non-human resources and translate it into a clinical setting. First, infectious cancers that can be transmitted as allografts between individual hosts, have been identified in four distinct, unrelated groups, dogs, Tasmanian devils, Syrian hamsters and, surprisingly, marine bivalves. These malignancies might hold the key to improving our understanding of the interaction between tumour cell and immune system and, thus, allow us to devise novel treatment strategies that enhance anti-cancer immunosurveillance, as well as suggesting more effective organ and stem cell transplantation strategies. The existence of these malignancies also highlights the need for increased scrutiny when considering the existence of infectious cancers in humans. Second, it has long been understood that no linear relationship exists between the number of cells within an organism and the cancer incidence rate. To resolve what is known as Peto's Paradox, additional anticancer strategies within different species have to be postulated. These naturally occurring idiosyncrasies to avoid carcinogenesis represent novel potential therapeutic strategies.
VENTRICULAR PACING AT 6 MONTHS FOLLOW UP IN PATIENTS REQUIRING PERMANENT PACEMAKER AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Adnan Kassier, Stefan Jovinge, Maliha Berner, Jennifer Schuitema, Rachel Rogers, Jessica Parker, Nabin ManandharShrestha, Jamie Frost, Poonam Velagapudi, Andre Gauri, William Merhi, Nagib Chalfoun
Journal: Journal of the American College of Cardiology (2021)