tbuckley/cabot-search huggingface dataset:
Correction to: Allogeneic hematopoietic stem cell transplantation in elderly patients with acute myeloid leukemia or myelodysplastic syndromes: myth and reality
Authors: A. Sutra Del Galy, A. Marouf, E. Raffoux, M. Robin, D. Michonneau, M. Sébert, F. Sicre de Fontebrune, A. Xhaard, E. Lengline, R. Itzykson, C. Frieri, H. Dombret, P. Fenaux, R. Peffault de Latour, L. Adès, G. Socié
Journal: Leukemia (2021)
FRI0420 ASSOCIATION BETWEEN RED BLOOD CELLS DISTRIBUTION WIDTH AND CARDIOVASCULAR RISK IN OSTEOARTHRITIS
Authors: N. Hammam, G. Salem, D. Fouad, S. Rashad
Journal: Annals of the Rheumatic Diseases (2020)

Background: Osteoarthritis (OA) is the most common joint disease that results in patient’s morbidity and disabilities. There is strong evidence that OA is a significant risk factor for cardiovascular disease (CVD). Red cell distribution width (RDW) blood test is a measure of the variation in red blood cell volume and size. Elevated RDW has recently been found to correlate with CVD risk in patients with and without heart disease and autoimmune diseases. RDW may be a marker for factors driving CVS risk. Objectives: : To investigate whether RDW can serve as a potential parameter for indicating cardiovascular risk in OA patients. Methods: A subsample of 819 OA patients was extracted from 2003-2006 National Health &amp; Nutrition Examination Survey in a cross-sectional study. 63.7% of them were females. Their mean age was 66.4 ± 14.1 yrs. Demographic, medical data, inflammatory markers &amp; lipid panel were obtained. Only patients with Haemoglobin&gt;12 mg/dl were included. Functional limitations were assessed using a physical function questionnaire. Results: Elevated levels of RDW were associated with CVD risk factors in OA patients. 532 (65.8%) OA patients had functional limitations, while 78 (9.5%) and 63 (7.6%) known to have heart attacks or stroke ever. Mean RDW was 12.9±1.1fL. There was a positive significant correlation between RDW &amp; CVD risk factors including body mass index (r=0.17, p&lt;0.001), C-reactive protein (r=0.29, p&lt;0.001), serum uric acid (r=0.12, p&lt;0.001), and functional limitation (0.16, p&lt;0.001). No significant association between RDW &amp; lipid panel was found. In multiple regression analysis controlling for age, sex as covariates, body mass index (β =0.02, 95%CI: 0.01, 0.03, p=0.002), C-reactive protein (β =0.35, 95%CI: 0.26, 0.45, p&lt;0.001), and functional limitation (β =0.18, 95%CI: 0.13, 0.35, p=0.03). Conclusion: In addition to known CVD risk in OA patients, elevated RDW levels should prompt physicians to aggressively screen and treat their patients for modifiable CVS risk factors, in addition to OA. Disclosure of Interests: None declared
Abstract 10574: Three-dimensional Cardiac Mechanics for Prediction of Events in Chagas Disease
Authors: Viviane T Hotta, Maria Cristina D Abduch, Marcelo Luiz C Vieira, Barbara M Ianni, Charles Mady, Edimar A Bocchi
Journal: Circulation (2019)

Introduction: Chagas disease (CD) is an endemic infectious disease that still remains a great economic burden. Three-dimensional speckle tracking (3D STE) may play a role in the evaluation of CD. W...
Splicing-accessible coding 3′UTRs control protein stability and interaction networks
Authors: Marco Preussner, Qingsong Gao, Eliot Morrison, Olga Herdt, Florian Finkernagel, Michael Schumann, Eberhard Krause, Christian Freund, Wei Chen, Florian Heyd
Journal: Genome biology (2020)

Abstract Background 3′-Untranslated regions (3′UTRs) play crucial roles in mRNA metabolism, such as by controlling mRNA stability, translation efficiency, and localization. Intriguingly, in some genes the 3′UTR is longer than their coding regions, pointing to additional, unknown functions. Here, we describe a protein-coding function of 3′UTRs upon frameshift-inducing alternative splicing in more than 10% of human and mouse protein-coding genes. Results 3′UTR-encoded amino acid sequences show an enrichment of PxxP motifs and lead to interactome rewiring. Furthermore, an elevated proline content increases protein disorder and reduces protein stability, thus allowing splicing-controlled regulation of protein half-life. This could also act as a surveillance mechanism for erroneous skipping of penultimate exons resulting in transcripts that escape nonsense mediated decay. The impact of frameshift-inducing alternative splicing on disease development is emphasized by a retinitis pigmentosa-causing mutation leading to translation of a 3′UTR-encoded, proline-rich, destabilized frameshift-protein with altered protein-protein interactions. Conclusions We describe a widespread, evolutionarily conserved mechanism that enriches the mammalian proteome, controls protein expression and protein-protein interactions, and has important implications for the discovery of novel, potentially disease-relevant protein variants.
Menopausal Hormone Therapy and Long-term Breast Cancer Risk
Authors: Christina A. Minami, Rachel A. Freedman
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Human L1 Transposition Dynamics Unraveled with Functional Data Analysis
Authors: Di Chen, Marzia A Cremona, Zongtai Qi, Robi D Mitra, Francesca Chiaromonte, Kateryna D Makova
Journal: Molecular Biology and Evolution (2020)

Long INterspersed Elements-1 (L1s) constitute >17% of the human genome and still actively transpose in it. Characterizing L1 transposition across the genome is critical for understanding genome evolution and somatic mutations. However, to date, L1 insertion and fixation patterns have not been studied comprehensively. To fill this gap, we investigated three genome-wide data sets of L1s that integrated at different evolutionary times: 17,037 de novo L1s (from an L1 insertion cell-line experiment conducted in-house), and 1,212 polymorphic and 1,205 human-specific L1s (from public databases). We characterized 49 genomic features-proxying chromatin accessibility, transcriptional activity, replication, recombination, etc.-in the ±50 kb flanks of these elements. These features were contrasted between the three L1 data sets and L1-free regions using state-of-the-art Functional Data Analysis statistical methods, which treat high-resolution data as mathematical functions. Our results indicate that de novo, polymorphic, and human-specific L1s are surrounded by different genomic features acting at specific locations and scales. This led to an integrative model of L1 transposition, according to which L1s preferentially integrate into open-chromatin regions enriched in non-B DNA motifs, whereas they are fixed in regions largely free of purifying selection-depleted of genes and noncoding most conserved elements. Intriguingly, our results suggest that L1 insertions modify local genomic landscape by extending CpG methylation and increasing mononucleotide microsatellite density. Altogether, our findings substantially facilitate understanding of L1 integration and fixation preferences, pave the way for uncovering their role in aging and cancer, and inform their use as mutagenesis tools in genetic studies.
Abstract 15533: 30-Day Readmission in Patients Undergoing Transcatheter Aortic Valve Replacement With Atrial Fibrillation: A Nationwide Readmission Database Analysis
Authors: Adrija Hajra, Dhrubajyoti Bandyopadhyay, Neel Patel, Sandipan Chakraborty, Birendra Amgai, Raktim Ghosh, Soniya Koirala, Eyal Herzog
Journal: Circulation (2019)

Introduction: The transcatheter aortic valve replacement (TAVR) is an emerging treatment in severe symptomatic aortic stenosis (AS). We undertook this analysis to determine the readmission paramete...
Training of Male and Female Surgical Residents—Reply
Authors: Oksana Babchenko, Katherine Gast
Journal: JAMA Surgery (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Cellular senescence impairs the reversibility of pulmonary arterial hypertension
Authors: Diederik E. van der Feen, Guido P. L. Bossers, Quint A. J. Hagdorn, Jan-Renier Moonen, Kondababu Kurakula, Robert Szulcek, James Chappell, Francesco Vallania, Michele Donato, Klaas Kok, Jaskaren S. Kohli, Arjen H. Petersen, Tom van Leusden, Marco Demaria, Marie-José T. H. Goumans, Rudolf A. De Boer, Purvesh Khatri, Marlene Rabinovitch, Rolf M. F. Berger, Beatrijs Bartelds
Journal: Science Translational Medicine (2020)

The transition from reversible to irreversible pulmonary arterial hypertension involves vascular senescence and can be countered by senolysis.
Prognostic significance of serial molecular annotation in myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (sAML)
Authors: Seongseok Yun, Susan M. Geyer, Rami S. Komrokji, Najla H. Al Ali, Jinming Song, Mohammad Hussaini, Kendra L. Sweet, Jeffrey E. Lancet, Alan F. List, Eric Padron, David A. Sallman
Journal: Leukemia (2020)
Observations of the global epidemiology of COVID-19 from the prepandemic period using web-based surveillance: a cross-sectional analysis
Authors: Fatimah S Dawood, Philip Ricks, Gibril J Njie, Michael Daugherty, William Davis, James A Fuller, Alison Winstead, Margaret McCarron, Lia C Scott, Diana Chen, Amy E Blain, Ron Moolenaar, Chaoyang Li, Adebola Popoola, Cynthia Jones, Puneet Anantharam, Natalie Olson, Barbara J Marston, Sarah D Bennett
Journal: The Lancet Infectious Diseases (2020)

Background Scant data are available about global patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread and global epidemiology of early confirmed cases of COVID-19 outside mainland China. We describe the global spread of SARS-CoV-2 and characteristics of COVID-19 cases and clusters before the characterisation of COVID-19 as a pandemic.Cases of COVID-19 reported between Dec 31, 2019, and March 10, 2020 (ie, the prepandemic period), were identified daily from official websites, press releases, press conference transcripts, and social media feeds of national ministries of health or other government agencies. Case characteristics, travel history, and exposures to other cases were abstracted. Countries with at least one case were classified as affected. Early cases were defined as those among the first 100 cases reported from each country. Later cases were defined as those after the first 100 cases. We analysed reported travel to affected countries among the first case reported from each country outside mainland China, demographic and exposure characteristics among cases with age or sex information, and cluster frequencies and sizes by transmission settings.Among the first case reported from each of 99 affected countries outside of mainland China, 75 (76%) had recent travel to affected countries; 60 (61%) had travelled to China, Italy, or Iran. Among 1200 cases with age or sex information, 874 (73%) were early cases. Among 762 early cases with age information, the median age was 51 years (IQR 35-63); 25 (3%) of 762 early cases occurred in children younger than 18 years. Overall, 21 (2%) of 1200 cases were in health-care workers and none were in pregnant women. 101 clusters were identified, of which the most commonly identified transmission setting was households (76 [75%]; mean 2·6 cases per cluster [range 2-7]), followed by non-health-care occupational settings (14 [14%]; mean 4·3 cases per cluster [2-14]), and community gatherings (11 [11%]; mean 14·2 cases per cluster [4-36]).Cases with travel links to China, Italy, or Iran accounted for almost two-thirds of the first reported COVID-19 cases from affected countries. Among cases with age information available, most were among adults aged 18 years and older. Although there were many clusters of household transmission among early cases, clusters in occupational or community settings tended to be larger, supporting a possible role for physical distancing to slow the progression of SARS-CoV-2 spread.None.
Srag Regulates Autophagy via Integrating into a Preexisting Autophagy Pathway in Testis
Authors: Yibin Cheng, Fengling Lai, Xin Wang, Dantong Shang, Juan Zou, Majing Luo, Xizhong Xia, Hanhua Cheng, Rongjia Zhou
Journal: Molecular Biology and Evolution (2020)

Abstract Spermatogenesis is an essential process for producing sperm cells. Reproductive strategy is successfully evolved for a species to adapt to a certain ecological system. However, roles of newly evolved genes in testis autophagy remain unclear. In this study, we found that a newly evolved gene srag (Sox9-regulated autophagy gene) plays an important role in promoting autophagy in testis in the lineage of the teleost Monopterus albus. The gene integrated into an interaction network through a two-way strategy of evolution, via Sox9-binding in its promoter and interaction with Becn1 in the coding region. Its promoter region evolved a cis element for binding of Sox9, a transcription factor for male sex determination. Both in vitro and in vivo analyses demonstrated that transcription factor Sox9 could bind to and activate the srag promoter. Its coding region acquired ability to interact with key autophagy initiation factor Becn1 via the conserved C-terminal, indicating that srag integrated into preexisting autophagy network. Moreover, we determined that Srag enhanced autophagy by interacting with Becn1. Notably, srag transgenic zebrafish revealed that Srag exerted the same function by enhancing autophagy through the Srag–Becn1 pathway. Thus, the new gene srag regulated autophagy in testis by integrated into preexisting autophagy network.
Identification of Key Genes for the Ultrahigh Yield of Rice Using Dynamic Cross-tissue Network Analysis
Authors: Jihong Hu, Tao Zeng, Qiongmei Xia, Liyu Huang, Yesheng Zhang, Chuanchao Zhang, Yan Zeng, Hui Liu, Shilai Zhang, Guangfu Huang, Wenting Wan, Yi Ding, Fengyi Hu, Congdang Yang, Luonan Chen, Wen Wang
Journal: Genomics Proteomics & Bioinformatics (2020)

Significantly increasing crop yield is a major and worldwide challenge for food supply and security. It is well-known that rice cultivated at Taoyuan in Yunnan of China can produce the highest yield worldwide. Yet, the gene regulatory mechanism underpinning this ultrahigh yield has been a mystery. Here, we systematically collected the transcriptome data for seven key tissues at different developmental stages using rice cultivated both at Taoyuan as the case group and at another regular rice planting place Jinghong as the control group. We identified the top 24 candidate high-yield genes with their network modules from these well-designed datasets by developing a novel computational systems biology method, i.e., dynamic cross-tissue (DCT) network analysis. We used one of the candidate genes, OsSPL4, whose function was previously unknown, for gene editing experimental validation of the high yield, and confirmed that OsSPL4 significantly affects panicle branching and increases the rice yield. This study, which included extensive field phenotyping, cross-tissue systems biology analyses, and functional validation, uncovered the key genes and gene regulatory networks underpinning the ultrahigh yield of rice. The DCT method could be applied to other plant or animal systems if different phenotypes under various environments with the common genome sequences of the examined sample. DCT can be downloaded from https://github.com/ztpub/DCT.
Influence of Clinical Trials of Acute Coronary Syndrome Beyond the Primary Hypothesis
Authors: Leiah M. Luoma, Cynthia M. Westerhout, Christopher B. Granger, Paul W. Armstrong
Journal: JAMA Cardiology (2020)

Conducting a clinical trial involves significant risks, time, and resources. The return on investment for these trials, measured by advancing health care and contributions to the scientific literature, is often uncertain.To assess the long-term effects of major clinical trials of acute coronary syndromes contemporary to the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial, which did not achieve its primary objective.The Cochrane Central Register of Controlled Trials database was screened for clinical trials of acute coronary syndromes (including unstable angina, ST-elevation myocardial infarction, and non-ST-elevation myocardial infarction) with more than 1000 participants and primary results published between January 1, 2005, and December 31, 2009, in Circulation, European Heart Journal, JAMA, Journal of the American College of Cardiology, The Lancet, and The New England Journal of Medicine. For identified trials, bibliographic information, citations, trial name, registration, inclusion diagnosis, intervention type, sample size, primary outcome result, sponsor information, and academic involvement were extracted. To identify secondary analyses, bibliographic information for citing articles, their citations, and their abstracts were extracted. Clinical practice guideline bibliographies for citations of trial publications were reviewed, and the class and level of evidence of resulting recommendations were extracted.Of 784 records screened, 30 were primary publications of 25 clinical trials. Through December 31, 2018, these trials were cited a median of 497 times (interquartile range [IQR], 424-931 citations). Trials that did not achieve their primary objective had fewer primary citations (the number of times that each published journal article with the primary [main] results of a trial was cited) (median, 443 [IQR, 396-468] vs 868 [IQR, 645-1774] citations, P = .006). The frequency of secondary analyses peaked within 5 years of the primary trial at 643. Trials that did not achieve the primary objective had fewer secondary analyses (median, 15 [IQR, 5-31] vs 18 [IQR, 10-43] analyses, P = .44) that were not cited significantly less often (median, 484 [IQR, 191-1299] vs 1124 [IQR, 410-4283] citations, P = .16). All trials were cited by at least 1 clinical practice guideline.This review found that trials that achieved the primary objective were frequently cited. Secondary research activity did not differ by primary result, and the primary trials and secondary analyses contributed to clinical practice recommendations. These data show the long-term importance of clinical trials regardless of primary outcome result.
Population variation in miRNAs and isomiRs and their impact on human immunity to infection
Authors: Maxime Rotival, Katherine J. Siddle, Martin Silvert, Julien Pothlichet, Hélène Quach, Lluis Quintana-Murci
Journal: Genome biology (2020)

Abstract Background MicroRNAs (miRNAs) are key regulators of the immune system, yet their variation and contribution to intra- and inter-population differences in immune responses is poorly characterized. Results We generate 977 miRNA-sequencing profiles from primary monocytes from individuals of African and European ancestry following activation of three TLR pathways (TLR4, TLR1/2, and TLR7/8) or infection with influenza A virus. We find that immune activation leads to important modifications in the miRNA and isomiR repertoire, particularly in response to viral challenges. These changes are much weaker than those observed for protein-coding genes, suggesting stronger selective constraints on the miRNA response to stimulation. This is supported by the limited genetic control of miRNA expression variability (miR-QTLs) and the lower occurrence of gene-environment interactions, in stark contrast with eQTLs that are largely context-dependent. We also detect marked differences in miRNA expression between populations, which are mostly driven by non-genetic factors. On average, miR-QTLs explain approximately 60% of population differences in expression of their cognate miRNAs and, in some cases, evolve adaptively, as shown in Europeans for a miRNA-rich cluster on chromosome 14. Finally, integrating miRNA and mRNA data from the same individuals, we provide evidence that the canonical model of miRNA-driven transcript degradation has a minor impact on miRNA-mRNA correlations, which are, in our setting, mainly driven by co-transcription. Conclusion Together, our results shed new light onto the factors driving miRNA and isomiR diversity at the population level and constitute a useful resource for evaluating their role in host differences of immunity to infection.
Clinical trial in a dish using iPSCs shows lovastatin improves endothelial dysfunction and cellular cross-talk in LMNA cardiomyopathy
Authors: Nazish Sayed, Chun Liu, Mohamed Ameen, Farhan Himmati, Joe Z. Zhang, Saereh Khanamiri, Jan-Renier Moonen, Alexa Wnorowski, Linling Cheng, June-Wha Rhee, Sadhana Gaddam, Kevin C. Wang, Karim Sallam, Jack H. Boyd, Y. Joseph Woo, Marlene Rabinovitch, Joseph C. Wu
Journal: Science Translational Medicine (2020)

Patient-specific iPSCs model endothelial dysfunction in lamin A and C–related dilated cardiomyopathy and identify lovastatin as a therapy.