tbuckley/cabot-search huggingface dataset:
The Role of the American Heart Association in the Global COVID-19 Pandemic
Authors: Mitchell S.V. Elkind, Robert A. Harrington, Ivor J. Benjamin
Journal: Circulation (2020)

s the United States and the world confront the novel coronavirus (COV-ID-19) pandemic, the American Heart Association (AHA) and its thousands of science volunteers have an important role to play to help stop the spread.That may seem counterintuitive to some, considering that COVID-19 is an infectious disease and the AHA has spent the last nearly 100 years focused on noncommunicable diseases such as cardiovascular diseases (CVDs), stroke, and other vascular disorders.However, COVID-19 is very much a concern of the AHA because patients with underlying cardiovascular conditions appear to face a greater risk of complications.In addition, as an organization dedicated to overall health and well-being, we are very concerned about significant domestic and global health problems. CONTAGIOUS INFECTIONS AND CVDEven before the first outbreak of COVID-19, the AHA and its professional members were aware of evidence suggesting that acute coronary events and strokes could be triggered by common infections. 1,2Respiratory and urinary tract infections, among others, have been associated with a short-term increase in the risk of myocardial infarction and ischemic stroke. 3Influenza in particular is associated with increased risk, and some clinical trials provide additional evidence that the influenza vaccination decreases cardiovascular risk. 1 Since 2006, the AHA and the American College of Cardiology have recommended that patients with CVD receive the influenza vaccination to prevent flu-related respiratory disease and other complications, including cardiovascular events. 3This approach represents the first instance of routine use of anti-infective strategies to reduce CVD.Mechanisms for the increase in risk with influenza remain unclear but may reflect greater cardiovascular stress in the setting of infection, reduced oxygenation in the setting of lung disease, or systemic inflammation with consequent thrombosis or intraplaque disruption predisposing to rupture.Although much remains unknown about COVID-19, it is reasonable to assume that increased risk of cardiovascular events after infection is possible.In China, CVD and hypertension were associated with an increased COVID-19 case fatality rate. 4Among patients who died of COVID-19, substantial cardiac damage was observed. 5Furthermore, it appears that elderly people with coronary heart disease or hypertension are more likely to be infected and to develop more severe symptoms.Surveillance for cardiovascular events after COVID-19 seems very warranted, and this could be an area for future investigation. PREPARING TO MITIGATE SPREADIt is important to understand that we are in a mitigation phase for this pandemic.Mitigation strategies are nonpharmaceutical interventions to help slow the
A CHALLENGING CASE OF TAKAYASU ARTERITIS WITH CATASTROPHIC CORONARY ARTERY DISEASE AND VALVULAR DISEASE REQUIRING CARDIAC TRANSPLANTATION
Authors: Bilal Saqi, Sara Godil, Syed Rafay Ali Sabzwari, Mario Caruso, Sagar Vadhar, Emilee Kurtz, Yasotha Rajeswaran
Journal: Journal of the American College of Cardiology (2020)
Nonpermissive bone marrow environment impairs early B-cell development in common variable immunodeficiency
Authors: Arianna Troilo, Claudia Wehr, Iga Janowska, Nils Venhoff, Jens Thiel, Justyna Rawluk, Natalie Frede, Julian Staniek, Raquel Lorenzetti, Marei-Theresa Schleyer, Georg W. Herget, Lukas Konstantinidis, Miriam Erlacher, Michele Proietti, Nadezhda Camacho-Ordonez, Reinhard Edmund Voll, Bodo Grimbacher, Klaus Warnatz, Ulrich Salzer, Marta Rizzi
Journal: Blood (2020)
<i>MAPK7</i> gene: A target for multimodal therapies.
Authors: Francine Tesser-Gamba, Antonio Sergio Petrilli, Mario Del Giudice Paniago, Maria Teresa Seixas Alves, Reynaldo Jesus Garcia-Filho, Silvia R. C. Toledo
Journal: Journal of Clinical Oncology (2013)

10533 Background: Osteosarcoma (OS) is a class of cancer originating from the bone, affecting mainly children and young adults. In a previous work we observed that the overexpression of MAPK7 gene was significantly associated to tumor progression, a poor response to treatment, and worse overall survival, suggesting that MAPK7 could play an important role in osteosarcoma tumorigenesis. This present study investigated if any genomic structural alteration could be related to MAPK7 overexpression in OS samples. Methods: The MAPK7 gene was fully sequenced in 33 OS samples (15 prechemotherapy,15 post-chemotherapy and 3 OS cell lines) using the 3500 Genetic Analyser (Applied Biosystem) and 15 custom primers pairs that amplified overlapping genomic fragments. Results: From the 30 patient samples analyzed, 16 could not be completely sequenced. Samples containing these deleted regions were significantly correlated to clinical and pathologic features of patients with OS. No deletions were observed in patients with the favorable outcome (non-metastatic at diagnosis, &gt;90% degree of necrosis in the surgical specimen and with complete remission at end of treatment). There was no correlation found between deletions and overexpression in pre-chemotherapy, even in patients that after chemotherapy still overexpressed MAPK7. Conclusions: Progress related to improved survival of patients with OS is at a plateau, and the intensification of therapy or incorporation of new therapeutic agents has not been successful, especially in patients metastatic at diagnosis. To our knowledge, no molecular marker for OS that could be related to its development, evolution or progression has been described yet. Based on our findings, we observed that patients who have no genomic deletion of MAPK7 gene respond better to treatment and have a favorable outcome. Studies available to date suggest that a single targeted therapy may not provide clinically significant anti-tumor effects, therefore we believe that specific inhibitors of the MAPK/ERK pathway are emerging as a relevant addition to multimodal therapies.
WHAT IS THE OPTIMAL DURATION FOR DUAL ANTIPLATELET THERAPY AFTER LEFT MAIN CORONARY ARTERY STENTING
Authors: Jungho Choi, In-Soo Kim, Sungsoo Cho, Jung-Sun Kim, Sung-Jin Hong, Dong-Ho Shin, Chul-Min Ahn, Byeong-Keuk Kim, Young-Guk Ko, Donghoon Choi, Myeong-Ki Hong, Yangsoo Jang
Journal: Journal of the American College of Cardiology (2020)
HSR20-087: Prevalence and Correlates of Psychological Distress in Patients Enrolling on Phase I Clinical Trials Using the NCCN Distress Thermometer and Problem List
Authors: Alexandra Hunt, Elizabeth Handorf, Vipin Khare, Matthew Blau, Yana Chertock, Carolyn Fang, Michael J. Hall, Rishi Jain
Journal: Journal of the National Comprehensive Cancer Network (2020)

"HSR20-087: Prevalence and Correlates of Psychological Distress in Patients Enrolling on Phase I Clinical Trials Using the NCCN Distress Thermometer and Problem List" published on 20 Mar 2020 by National Comprehensive Cancer Network.
Physical activity (PA) and physical function (PF) in adult cancer survivors (CS).
Authors: Peter Crawford Birks, Amir Yashar Tashakkor, Ali Moghaddamjou, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2012)

6085 Background: The longevity of CS is increasing, underscoring the importance of lifestyle modifications and preventive care, consisting of regular PA and maintenance of PF. Our aims were to 1) compare PA and PF among short-term CS, long-term CS and non-cancer controls (NCC) and 2) identify other clinical factors associated with decreased PA and PF. Methods: We identified CS and NCC from the US National Health and Nutrition Examination Survey (NHANES). CS were categorized into &lt;/=5 (short-term) and &gt;5 years (long-term) based on date of diagnosis. Multivariate weighted regression models were constructed to examine for differences in 28 and 26 measures of PA and PF, respectively, while controlling for age, gender, ethnicity, education, income, and other confounders. We explored specific and general PA domains such as aerobic activity and decline from past activity level as well as PF areas including ADLs, IADLs and mobility. Results: In total, 26,185 subjects were identified: 968 short-term CS, 1,367 long-term CS, and 23,832 NCC. For the entire cohort, the mean age was 50 years, 52% were men, and 50% were white. Comparing across the 3 patient groups, CS were generally older than NCC (60 vs 45 years, p&lt;0.01). In terms of PA, short-term CS reported less general activity compared to 1 year ago (OR 0.58, 95%, CI 0.46-0.73, p&lt;0.01) than long-term CS and NCC. In comparison to NCC, both groups of CS also described less current activity than their baseline from 10 years ago (OR 0.63, 95% CI 0.48-0.82, P=0.001 and OR 0.67, 95% CI 0.55-0.83, P=&lt;0.01). There were significant differences among patient groups in several areas of PF (Table). Other factors that were associated with lower PA and PF included advanced age, low education, and low income. Conclusions: PA between CS and NCC were similar, although current activity as compared to that of the preceding year or past decade appears lower in CS, which may reflect their older age. Impairments in several measures of PF were observed among CS, which could impact their quality and quantity of life. [Table: see text]
FACTORS ASSOCIATED WITH UNDER-ENROLMENT OF FEMALES IN CLINICAL TRIALS OF HEART FAILURE WITH REDUCED EJECTION FRACTION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Sera Whitelaw, Shun Fu Lee, Kristen Sullivan, Mohammad Alruwayeh, Yousif Eliyah, Harriette Van Spall
Journal: Journal of the American College of Cardiology (2020)
UTILIZING THE STRUCTURAL HEART TEAM TO IMPROVE OUTCOMES AND EFFICIENCY OF CARE FOR STRUCTURAL HEART PATIENTS
Authors: Morgan Harloff, Sameer Hirji, Edward Percy, Farhang Yazdchi, Alexandra Malarczyk, Siobhan McGurk, Sary Aranki, Prem S. Shekar, Tsuyoshi Kaneko
Journal: Journal of the American College of Cardiology (2020)
A META-ANALYSIS OF SHORT-TERM CASE-FATALITY RATE AMONG WHITE AND BLACK WOMEN WITH ACUTE CORONARY SYNDROMES
Authors: Sabin Filimon, Hanh Nguyen, Robert Joel Goldberg, Lars Wallentin, Jiayi Ni, Cristina Pop, Elena Guadano, Daniel A. Jones, Rathod Krishnaraj, Chiara Betoncello, Corina Grey, Jorge Yarzebski, Lu Hou Tee, Shamanna Iyengar, Khalid AlHabib, Joanna Bryan, Abdulhalim Kinsara, Cohen Gali, Yariv Gerber, Ayman Hammoudeh, Genovefa Kolovou, Shao-Li Wang, John A. Spertus, Thao Huynh
Journal: Journal of the American College of Cardiology (2020)
SINGLE-ENERGY CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY FOR EX-VIVO EVALUATION OF PLAQUE COMPONENTS IN SUDDEN CARDIAC DEATH USING HISTOPATHOLOGY AS GOLD STANDARD
Authors: Umberto Gianni, Sara W. Tantawy, Falone C. Amoa, Aeshita Dwivedi, Yu Sato, Rashmi S. Wijeratne, Emma J. Hollenberg, Omar Al Hussein Alawamlh, Abdallah Elshafeey, Yao Lu, Inge J. van den Hoogen, Alexander R. van Rosendael, A. Maxim Bax, Kazuyuki Yahagi, Sho Torii, Hiroyuki Jinnouchi, Maria Romero, Dipti Surve, Aloke V. Finn, James Earls, James Min, Leslee J. Shaw, David Fowler, Renu Virmani, Fay Lin
Journal: Journal of the American College of Cardiology (2020)
Adjusting for treatment crossover in the METRIC metastatic melanoma (MM) trial for trametinib: Preliminary analysis.
Authors: Keith R. Abrams, Nicholas Latimer, Mayur Amonkar, Ceilidh Stapelkamp, Michelle Casey
Journal: Journal of Clinical Oncology (2013)

9040 Background: In METRIC, a randomized phase III study, trametinib significantly improved PFS (hazard ratio [HR]=0.44 [95% CI 0.31–0.64; p&lt;0.001]) vs chemotherapy (chemo) in patients (pts) with BRAF V600E+ MM and no brain metastases. Median overall survival (OS), a secondary endpoint, has not yet been reached. OS results are likely to underestimate the effect of trametinib as pts progressing on chemo could cross over to experimental treatment (trt). This analysis attempts to adjust for confounding effects of trt crossover on OS in the overall population and first line (1L) subgroup using current METRIC results. Methods: Randomization-based crossover adjustment methods – Rank Preserving Structural Failure Time Models (RPSFTM) and the Iterative Parameter Estimation (IPE) algorithm – were used. We conducted two sets of analyses testing different assumptions regarding the durability of the trt effect. “Trt group” analyses adjusted for crossover under the assumption that the trt effect is maintained until death regardless of trt duration; “On trt – observed” analyses adjusted for crossover under the assumption that the trt effect disappears upon trt discontinuation. Results are presented as HRs. Results: 178 and 95 MM pts were randomized to trametinib and chemo, respectively; 49.5% of chemo pts crossed over to trametinib as of data cut off (Oct. 2011). Median follow-up was 4.9 months and 19.8% deaths occurred across both arms. Crossover adjustment results are presented in the Table. Conclusions: RPSFTM and IPE “trt group” analyses resulted in OS HR point estimates that represented greater trt effects in the overall population and 1L subgroup compared to the unadjusted HRs. Results are exploratory because few deaths have been observed in the current dataset. Future analyses on a mature dataset should produce more robust estimates of the OS trt effect after crossover adjustment. [Table: see text]
17O A first-in-human phase I study of MORAb-202 in patients with folate receptor alpha-positive advanced solid tumors
Authors: J. Sato, T. Shimizu, Y. Fujiwara, K. Yonemori, T. Koyama, A. Shimomura, K. Tamura, S. Iwasa, S. Kondo, K. Sudo, H. Ikezawa, M. Nomoto, R. Nakajima, T. Miura, N. Yamamoto
Journal: Annals of Oncology (2020)
Cardio-toxicity among patients with sarcoma: A Cardio-Oncology Registry.
Authors: Sivan Shamai, Ofer Merimsky, Michal laufer-Perl
Journal: Journal of Clinical Oncology (2019)

e22530 Background: Chemotherapy induced cardio-toxicity has been recognized as a serious side effect since the first introduction to anthracycline (ANT). Cardio-toxicity among patients with breast cancer is well studied but the impact on patients with sarcoma is limited, even though they are exposed to higher ANT doses. The commonly used term for cardio-toxicity is cancer therapeutic related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction (EF) reduction of &gt; 10%, to a value below 53%. Our objective was to estimate the prevalence of CTRCD among patients with sarcoma, to evaluate echocardiography parameters associated with its development and whether CTRCD is associated with mortality. Methods: Data were collected as part of the International Cardio-Oncology Registry (ICOR), enrolling all patients who were evaluated in the cardio-oncology clinic at our institution. All sarcoma patients were enrolled and divided into two groups - CTRCD group vs. "Preserved EF" group. Results: Among 43 consecutive patients, 6 (14%) developed CTRCD. Elevated left ventricular end systolic diameter (p = 0.007) and a trend of reduced Global Longitudinal Strain (p = 0.092) were observed among the CTRCD group. During follow-up, 2 (33%) patients died in the CTRCD group vs. 3 (8.1%) patients in the "Preserved EF" group. In a multivariate analysis, adjusted to age and EF, CTRCD remained a significant predictor for mortality (p = 0.039). Conclusions: CTRCD is an important concern among patients with sarcoma, regardless of baseline risk factors, and is associated with mortality. Echocardiography parameters may provide an early diagnosis of cardio-toxicity.
HEALED PLAQUES IN PATIENTS WITH STABLE ANGINA PECTORIS
Authors: Michele Russo, Francesco Fracassi, Osamu Kurihara, Hyung Oh Kim, Vikas Thondapu, Makoto Araki, Hiroki Shinohara, Tomoyo Sugiyama, Erika Yamamoto, Hang Lee, Rocco Vergallo, Filippo Crea, Luigi M. Biasucci, Taishi Yonetsu, Yoshiyasu Minami, Tsunenari Soeda, Valentin Fuster, Ik-Kyung Jang
Journal: Journal of the American College of Cardiology (2020)
A WIN-WIN SITUATION: URGENT TRANSCATHETER AORTIC VALVE REPLACEMENT (TAVR) IN A PATIENT WITH RECENT MULTIVESSEL PERCUTANEOUS CORONARY INTERVENTION (PCI) FOR A NON-CARDIAC SURGERY
Authors: Woosun Kang, Jishanth Mattumpuram, Ekanka Mukhopadhyay, Sudhir Mungee
Journal: Journal of the American College of Cardiology (2020)
IMPACT OF ADMISSION TO A CARDIOLOGY UNIT ON MORTALITY IN PATIENTS AGED &gt;85 YEARS PRESENTING WITH NON-ST ELEVATION MYOCARDIAL INFARCTION (NSTEMI)
Authors: Alexandra Murphy, Anoop Koshy, Phelia Kunniardy, Georgie Meehan, Jay Ramchand, H.M. Omar Farouque, David Clark, Matias Yudi
Journal: Journal of the American College of Cardiology (2020)
Prognostic value of microRNAs (miRs) expression in stage I-IIIA lung adenocarcinoma (AC).
Authors: Marcin Tomasz Skrzypski, Krzysztof Goryca, Piotr Czapiewski, Ewa Jassem, Wojciech Biernat, Ryszard Pawlowski, Witold Rzyman, Jacek Jassem
Journal: Journal of Clinical Oncology (2013)

11069 Background: About 50% of NSCLC patients (pts) will develop distant metastases following pulmonary resection. Currently, apart from clinical stage at diagnosis, there are no reliable factors to select high-risk pts for adjuvant chemotherapy. We previously demonstrated prognostic value of 22 miRs in frozen samples of early squamous cell lung carcinoma, and the feasibility of their assessment in formalin fixed paraffin embedded (FFPE) samples (Skrzypski et. al. J Clin Oncol 2010;28;15s). In this study, we investigated the expression of 350 microRNAs in operable AC pts. Methods: FFPE tumor samples were obtained from 80 stage I-IIIA pts who underwent curative pulmonary resection, 48% of whom subsequently developed distant metastases. Median follow-up of pts who were disease recurrence-free was 5.8 years (range, 4.0-9.1 years). RNA was isolated from tumor tissue with RecoverAll kit (Ambion). Expression of 350 miRs was analyzed by qRT-PCR (Appliedbiosystems). Raw data were normalized vs. the geometric mean of U6, RNU48 and RNU44 expression. Relative miRs expression was correlated with distant metastases-free survival (MFS) and the mean expression was compared between the groups with and without relapse. Results: Expression of 41 miRs correlated with MFS in Cox regression analysis and 21 of these showed different level in pts with and without relapse in the t-Student test (both at p&lt;0.05 level). The top prognostic miRs included miR-99a* (p=0.006), miR-1255B (p=0.005), miR-1233 (p=0.013) and miR-1303 (p=0.03); all previosly shown to be prognostic in AC or NSCLC. We also found 14 new microRNAs (patent pending) potentially prognostic for relapse in AC. Conclusions: Expression of selected miRs may aid in prediction of distant relapse in AC pts undergoing pulmonary resection.
IATROGENIC HEART CONTRACTIONS
Authors: Sharath Rajagopalan, Mirza Mujadil Ahmad, Abdul Haseeb, Hamza Hafeez, Sangeeta Prabhakar Bhat, Najam Saqib, Muhammad Siddique Pir, Wilson Young, Pranjal Boruah
Journal: Journal of the American College of Cardiology (2020)
CARDIOVASCULAR DISEASE IN ADULT SURVIVORS OF PEDIATRIC CANCERS: ROLE OF A MULTIDISCIPLINARY SURVIVORSHIP CLINIC IN IDENTIFICATION AND CARE
Authors: Nisha Raiker, Malika Ramani, Karen Kinahan, Chen Yeh, Patricia Kaye, Aarati Didwania, Jane Winter, Nausheen Akhter, Vera H. Rigolin
Journal: Journal of the American College of Cardiology (2020)
The importance of interventional timing in the bleomycin model of pulmonary fibrosis
Authors: Philipp Kolb, Chandak Upagupta, Megan Vierhout, Ehab Ayaub, Pierre Simon Bellaye, Jack Gauldie, Chiko Shimbori, Mark Inman, Kjetil Ask, Martin R.J. Kolb
Journal: European Respiratory Journal (2020)

Idiopathic pulmonary fibrosis (IPF) is a complex disease of unknown aetiology, which makes drug development challenging. Single administration of bleomycin directly to the lungs of mice is a widely used experimental model for studying pulmonary fibrogenesis and evaluating the effect of therapeutic antifibrotic strategies. The model works by inducing an early inflammatory phase, which transitions into fibrosis after 5-7 days. This initial inflammation makes therapeutic timing crucial. To accurately assess antifibrotic efficacy, the intervention should inhibit fibrosis without impacting early inflammation.Studies published between 2008 and 2019 using the bleomycin model to investigate pulmonary fibrosis were retrieved from PubMed, and study characteristics were analysed. Intervention-based studies were classified as either preventative (starting <7 days after bleomycin installation) or therapeutic (>7 days). In addition, studies were cross-referenced with current major clinical trials to assess the availability of preclinical rationale.A total of 976 publications were evaluated. 726 investigated potential therapies, of which 443 (61.0%) were solely preventative, 166 (22.9%) were solely therapeutic and 105 (14.5%) were both. Of the 443 preventative studies, only 70 (15.8%) characterised inflammation during the model's early inflammatory phase. In the reported 145 IPF clinical trials investigating 93 compounds/combinations, only 25 (26.9%) interventions had any preclinical data on bleomycin available on PubMed.Since 2008, we observed a shift (from <5% to 37.4%) in the number of studies evaluating drugs in the therapeutic setting in the bleomycin model. While this shift is encouraging, further characterisation of early inflammation and appropriate preclinical therapeutic testing are still needed. This will facilitate fruitful drug development in IPF, and more therapeutic strategies for patients with this devastating disease.
Phylogenetic Modeling of Regulatory Element Turnover Based on Epigenomic Data
Authors: Noah Dukler, Yi-Fei Huang, Adam Siepel
Journal: Molecular Biology and Evolution (2020)

Evolutionary changes in gene expression are often driven by gains and losses of cis-regulatory elements (CREs). The dynamics of CRE evolution can be examined using multispecies epigenomic data, but so far such analyses have generally been descriptive and model-free. Here, we introduce a probabilistic modeling framework for the evolution of CREs that operates directly on raw chromatin immunoprecipitation and sequencing (ChIP-seq) data and fully considers the phylogenetic relationships among species. Our framework includes a phylogenetic hidden Markov model, called epiPhyloHMM, for identifying the locations of multiply aligned CREs, and a combined phylogenetic and generalized linear model, called phyloGLM, for accounting for the influence of a rich set of genomic features in describing their evolutionary dynamics. We apply these methods to previously published ChIP-seq data for the H3K4me3 and H3K27ac histone modifications in liver tissue from nine mammals. We find that enhancers are gained and lost during mammalian evolution at about twice the rate of promoters, and that turnover rates are negatively correlated with DNA sequence conservation, expression level, and tissue breadth, and positively correlated with distance from the transcription start site, consistent with previous findings. In addition, we find that the predicted dosage sensitivity of target genes positively correlates with DNA sequence constraint in CREs but not with turnover rates, perhaps owing to differences in the effect sizes of the relevant mutations. Altogether, our probabilistic modeling framework enables a variety of powerful new analyses.