tbuckley/cabot-search huggingface dataset:
Abstract 13634: Gender Differences in Metabolomic Profiles Associated With Incident Coronary Heart Disease in African Americans: The Jackson Heart Study
Authors: Daniel E Cruz, Bennet Peterson, Debby Ngo, Mark Benson, Zsu Zsu Chen, Usman Tahir, Yan Gao, Thomas J Wang, Clary Clish, Adolfo Correa, James Wilson, Robert E Gerszten
Journal: Circulation (2019)

Introduction: African Americans (AA) suffer disproportionately from coronary heart disease (CHD). Within this demographic, males tend to suffer more than females from incident CHD and suffer cardia...
Epigenetic modulations and lineage plasticity in advanced prostate cancer
Authors: R. Ge, Z. Wang, R. Montironi, Z. Jiang, M. Cheng, M. Santoni, K. Huang, F. Massari, X. Lu, A. Cimadamore, A. Lopez-Beltran, L. Cheng
Journal: Annals of Oncology (2020)
Bacteriophages Isolated from Stunted Children Can Regulate Gut Bacterial Communities in an Age-Specific Manner
Authors: Mohammadali Khan Mirzaei, Md. Anik Ashfaq Khan, Prakash Ghosh, Zofia E. Taranu, Mariia Taguer, Jinlong Ru, Rajashree Chowdhury, Md. Mamun Kabir, Li Deng, Dinesh Mondal, Corinne F. Maurice
Journal: Cell Host & Microbe (2020)

Stunting, a severe and multigenerational growth impairment, globally affects 22% of children under the age of 5 years. Stunted children have altered gut bacterial communities with higher proportions of Proteobacteria, a phylum with several known human pathogens. Despite the links between an altered gut microbiota and stunting, the role of bacteriophages, highly abundant bacterial viruses, is unknown. Here, we describe the gut bacterial and bacteriophage communities of Bangladeshi stunted children younger than 38 months. We show that these children harbor distinct gut bacteriophages relative to their non-stunted counterparts. In vitro, these gut bacteriophages are infectious and can regulate bacterial abundance and composition in an age-specific manner, highlighting their possible role in the pathophysiology of child stunting. Specifically, Proteobacteria from non-stunted children increased in the presence of phages from younger stunted children, suggesting that phages could contribute to the bacterial community changes observed in child stunting.
Supply Chain Optimization and Waste Reduction—Reply
Authors: Cassandra Thiel, Leora I. Horwitz
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
CD8+ T cells and human cerebral malaria: a shifting episteme
Authors: Laurent Rénia, Georges E.R. Grau, Samuel C. Wassmer
Journal: Journal of Clinical Investigation (2020)

Mosquito-transmitted Plasmodium falciparum infection can cause human cerebral malaria (HCM) with high mortality rates. The abundance of infected red blood cells that accumulate in the cerebral vasculature of patients has led to the belief that these brain-sequestered cells solely cause pathogenesis. However, animal models suggest that CD8+ T cells migrate to and accumulate in the brain, directly contributing to experimental cerebral malaria (ECM) mortality. In this issue of the JCI, Riggle et al. explored the brain vasculature from 34 children who died from HCM or other causes and frequently found CD3+ CD8+ T cells in contact with endothelial cells. Further, the authors show that coinfection with HIV enhanced such CD3+ CD8+ T cell luminal distribution. These findings suggest that the mouse model for cerebral malaria may accurately reflect human disease pathology. This study sheds new light on the mechanisms behind blood-brain barrier breakdown in this complicated neurological disease and opens up alternative approaches for treatment.
High frequency of germline <i>RUNX1</i> mutations in patients with<i> RUNX1</i>-mutated AML
Authors: Laura Simon, Jean-François Spinella, Chi-Yuan Yao, Vincent-Philippe Lavallée, Isabel Boivin, Geneviève Boucher, Eric Audemard, Marie-Eve Bordeleau, Sébastien Lemieux, Josée Hébert, Guy Sauvageau
Journal: Blood (2020)
<i>Notes from the Field:</i> Carbapenem-resistant <i>Klebsiella pneumoniae</i> with <i>mcr-1</i> Gene Identified in a Hospitalized Patient — Wyoming, January 2019
Authors: Heather Rhodes, Cody Loveland, Clayton Van Houten, Noah Hull, Alexia Harrist
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

In December of 2018, Wyoming identified the state's first case of carbapenem-resistant Enterobacteriaceae (CRE) containing mcr-1, which is a gene that can make bacteria resistant to colistin, a drug that can be the last resort for some multidrug-resistant infections like CRE.
Phase II study of pembrolizumab and capecitabine for triple negative and hormone receptor-positive, HER2−negative endocrine-refractory metastatic breast cancer
Authors: Ami N Shah, Lisa Flaum, Irene Helenowski, Cesar A Santa-Maria, Sarika Jain, Alfred Rademaker, Valerie Nelson, Dean Tsarwhas, Massimo Cristofanilli, William Gradishar
Journal: Journal for ImmunoTherapy of Cancer (2020)

Response rates to single agent immune checkpoint blockade in unselected pretreated HER2-negative metastatic breast cancer (MBC) are low. However, they may be augmented when combined with chemotherapy.We conducted a single-arm, phase II study of patients with triple negative (TN) or hormone receptor-positive endocrine-refractory (HR+) MBC who were candidates for capecitabine. Patients were treated with pembrolizumab 200 mg intravenously day 1 and capecitabine 1000 mg/m2 by mouth twice daily on days 1-14 of a 21-day cycle. The primary end point was median progression-free survival (mPFS) compared with historic controls and secondary end points were overall response rate (ORR), safety and tolerability. The study had 80% power to detect a 2-month improvement in mPFS with the addition of pembrolizumab over historic controls treated with capecitabine alone.Thirty patients, 16 TN and 14 HR+ MBC, were enrolled from 2017 to 2018. Patients had a median age of 51 years and received a median of 1 (range 0-6) prior lines of therapy for MBC. Of 29 evaluable patients, the mPFS was 4.0 (95% CI 2.0 to 6.4) months and was not significantly longer than historic controls of 3 months. The median overall survival was 15.4 (95% CI 8.2 to 20.3) months. The ORR was 14% (n=4), stable disease (SD) was 41% (n=12) and clinical benefit rate (CBR=partial response+SD>6 months) was 28% (n=8). The ORR and CBR were not significantly different between disease subtypes (ORR 13% and 14%, CBR 25% and 29% for TN and HR+, respectively). The 1-year PFS rate was 20.7% and three patients have ongoing responses. The most common adverse events were low grade and consistent with those seen in MBC patients receiving capecitabine, including hand-foot syndrome, gastrointestinal symptoms, fatigue and cytopenias. Toxicities at least possibly from pembrolizumab included grade 3 or 4 liver test abnormalities (7%), rash (7%) and diarrhea (3%), as well as grade 5 hepatic failure in a patient with liver metastases.Compared with historical controls, pembrolizumab with capecitabine did not improve PFS in this biomarker unselected, pretreated cohort. However, some patients had prolonged disease control.NCT03044730.
Activation of TRPV1 channel antagonizes diabetic nephropathy through inhibiting endoplasmic reticulum-mitochondria contact in podocytes
Authors: Xiao Wei, Xing Wei, Zongshi Lu, Li Li, Yingru Hu, Fang Sun, Yanli Jiang, Huan Ma, Hongting Zheng, Gangyi Yang, Daoyan Liu, Peng Gao, Zhiming Zhu
Journal: Metabolism (2020)
A high-fat diet delays plasmin generation in a thrombomodulin-dependent manner in mice
Authors: Adam Miszta, Anna K. Kopec, Asmita Pant, Lori A. Holle, James R. Byrnes, Daniel A. Lawrence, Kirk C. Hansen, Matthew J. Flick, James P. Luyendyk, Bas de Laat, Alisa S. Wolberg
Journal: Blood (2020)
Myocardial Energetics in Obesity
Authors: Jennifer J. Rayner, Mark A. Peterzan, William D. Watson, William T. Clarke, Stefan Neubauer, Christopher T. Rodgers, Oliver J. Rider
Journal: Circulation (2020)

Obesity is strongly associated with exercise intolerance and the development of heart failure. Whereas myocardial energetics and diastolic function are impaired in obesity, systolic function is usually preserved. This suggests that the rate of ATP delivery is maintained, but this has never been explored in human obesity. We hypothesized that ATP transfer rate through creatine kinase (CK) (kfCKrest) would be increased, compensating for depleted energy stores (phosphocreatine/ATP), but potentially limiting greater ATP delivery during increased workload. We hypothesized that these changes would normalize with weight loss.We recruited 80 volunteers (35 controls [body mass index 24±3 kg/m2], 45 obese [body mass index 35±5 kg/m2]) without coexisting cardiovascular disease. Participants underwent body composition analysis, magnetic resonance imaging of abdominal, liver, and myocardial fat content, left ventricular function, and 31P magnetic resonance spectroscopy to assess phosphocreatine/ATP and CK kinetics, at rest and during dobutamine stress. Obese volunteers were assigned to a dietary weight loss intervention, before reexamination.At rest, although myocardial phosphocreatine/ATP was 14% lower in obesity (1.9±0.3 versus 2.2±0.2, P<0.001), kfCkrest was 33% higher (0.23±0.07 s-1 versus 0.16±0.08 s-1, P=0.002), yielding no difference in overall resting ATP delivery (obese 2.5±0.9 µmol·g-1·s-1 versus control 2.2±1.1 µmol·g-1·s-1, P=0.232). In controls, increasing cardiac workload led to an increase in both kfCK (+86%, P<0.001) and ATP delivery (+80%, P<0.001). However, in obesity, similar stress led to no significant increase in either kfCK (P=0.117) or ATP delivery (P=0.608). This was accompanied by reduced systolic augmentation (absolute increase in left ventricular ejection fraction, obese +16±7% versus control +21±4%, P=0.031). Successful weight loss (-11±5% body weight) was associated with improvement of these energetic changes such that there was no significant difference in comparison with controls.In the obese resting heart, the myocardial CK reaction rate is increased, maintaining ATP delivery despite reduced phosphocreatine/ATP. During increased workload, although the nonobese heart increases ATP delivery through CK, the obese heart does not; this is associated with reduced systolic augmentation and exercise tolerance. Weight loss reverses these energetic changes. This highlights myocardial energy delivery through CK as a potential therapeutic target to improve symptoms in obesity-related heart disease, and a fascinating modifiable pathway involved in the progression to heart failure, as well.
Abstract P3-11-19: Preclinical model of TNBC: Dasatinib attenuates Src pathway signaling and combined with veliparib and carboplatin potently inhibits tumor growth
Authors: yuliang Sun, Xiaoqian Lin, Jennifer Aske, Casey Williams, Mark Abramovitz, Brian Leyland-Jones
Journal: Cancer Research (2020)

Abstract Background: The combination of a poly ADP ribose polymerase (PARP) inhibitor with a DNA-damaging agent has shown promise in treating triple-negative breast cancer (TNBC); however, not all patients respond to this combination. The Src protein kinase modulates multiple cancer cell properties and plays a key role in tumorigenic processes. However, Src inhibitors as single agents have shown limited effects in solid tumors. In this study, we examined the antitumor effects of the Src inhibitor dasatinib, the PARP inhibitor veliparib, and the DNA-damaging agent carboplatin in TNBC cells in vitro and tumors in vivo to try to identify the combination with the most clinical potential. Methods: The BRCA-mutated and PTEN null TNBC cell line, SUM149PT, was used in this study. For in vitro studies, proliferation, cellular apoptosis, and 3D on-top clonogenic growth were measured, tube formation assays and western blot analysis were performed. For in vivo studies, a xenograft model was used to examine treatment responses, and immunohistochemical analysis was performed. Results: Surprisingly, treatment with the combination of veliparib plus carboplatin led to an increase in Src phosphorylation. Importantly, addition of dasatinib attenuated Src overexpression induced by veliparib plus carboplatin and further inhibited the downstream signaling of Src, thereby enhancing the antitumor efficacy of veliparib plus carboplatin. In an SUM149PT xenograft model, the triple combination of dasatinib with veliparib plus carboplatin showed greater tumor growth inhibitory effects compared with single agents or double combinations. No systemic toxicity was observed in mice treated with the triple combination. Conclusion: Here, we provide novel evidence that veliparib combined with carboplatin drives Src activation in the preclinical model tested. Moreover, we provide provocative in vitro and in vivo data highlighting the potential for increasing therapeutic efficacy by combining dasatinib with veliparib and carboplatin in BRCA-mutated and PTEN null TNBC. Citation Format: yuliang Sun, Xiaoqian Lin, Jennifer Aske, Casey Williams, Mark Abramovitz, Brian Leyland-Jones. Preclinical model of TNBC: Dasatinib attenuates Src pathway signaling and combined with veliparib and carboplatin potently inhibits tumor growth [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-11-19.
Abstract 19079: Cd13 and Ror2 Markers of Pre-Cardiac Mesoderm
Authors: Rhys Skelton, Bevin Brady, Irving Weissman, David A Elliott, Reza Ardehali
Journal: Circulation (2013)

The human heart has a limited regenerative capacity and there is an unmet demand for improved therapies for myocardial disease. Human embryonic stem cell (hESC) derived cardiomyocytes have potential to facilitate the development of both cell-based and pharmaceutical treatments. To date many studies have focused on the efficient generation of cardiomyocytes from hESCs. However, its clinical use has been limited by technical challenges, including the inability to isolate a pure population of cardiovascular progenitors capable of robust engraftment and regeneration. To this end, we have attempted to identify surface markers that facilitate isolation of cardiac mesoderm and cardiovascular progenitors from differentiating hESCs. Lineage-specific reporter hESC lines (MIXL1-GFP and NKX2.5-GFP) were utilized to test prospective isolation of early cardiac progenitors using two novel cell surface markers, CD13 and ROR2. A distinct population of cells co-expressing CD13 and ROR2 was isolated after 3 days of hESC differentiation which exhibited a transcriptional profile similar to primitive streak/mesoderm cells. Gene expression analysis and immunostaining confirmed the enrichment of mesodermal cells and near complete removal of endodermal, ectodermal and undifferentiated cells. To quantify the extent of cardiovascular progenitors generated from CD13/ROR2 expressing cells, an NKX2.5-GFP reporter hESC line was used and the double positive cells were sorted after 3 days and maintained in culture for 14 days. The majority of these cells showed enrichment for cardiovascular cells based on gene and protein expression, phenotype, and transplantation studies. By enabling retrieval of early mesoderm precursors from heterogeneous differentiated hESC populations, we anticipate CD13 and ROR2 should have utility in enriching for subsequent cardiac potential_the necessary first developmental step towards creating purified cardiomyocytes from hESC.
Genomic Characterization of Endothelial Enhancers Reveals a Multifunctional Role for NR2F2 in Regulation of Arteriovenous Gene Expression
Authors: Samir Sissaoui, Jun Yu, Aimin Yan, Rui Li, Onur Yukselen, Alper Kucukural, Lihua Julie Zhu, Nathan D. Lawson
Journal: Circulation Research (2020)

Rationale: Significant progress has revealed transcriptional inputs that underlie regulation of artery and vein endothelial cell fates. However, little is known concerning genome-wide regulation of this process. Therefore, such studies are warranted to address this gap. Objective: To identify and characterize artery- and vein-specific endothelial enhancers in the human genome, thereby gaining insights into mechanisms by which blood vessel identity is regulated. Methods and Results: Using chromatin immunoprecipitation and deep sequencing for markers of active chromatin in human arterial and venous endothelial cells, we identified several thousand artery- and vein-specific regulatory elements. Computational analysis revealed that NR2F2 (nuclear receptor subfamily 2, group F, member 2) sites were overrepresented in vein-specific enhancers, suggesting a direct role in promoting vein identity. Subsequent integration of chromatin immunoprecipitation and deep sequencing data sets with RNA sequencing revealed that NR2F2 regulated 3 distinct aspects related to arteriovenous identity. First, consistent with previous genetic observations, NR2F2 directly activated enhancer elements flanking cell cycle genes to drive their expression. Second, NR2F2 was essential to directly activate vein-specific enhancers and their associated genes. Our genomic approach further revealed that NR2F2 acts with ERG (ETS-related gene) at many of these sites to drive vein-specific gene expression. Finally, NR2F2 directly repressed only a small number of artery enhancers in venous cells to prevent their activation, including a distal element upstream of the artery-specific transcription factor, HEY2 (hes related family bHLH transcription factor with YRPW motif 2). In arterial endothelial cells, this enhancer was normally bound by ERG, which was also required for arterial HEY2 expression. By contrast, in venous endothelial cells, NR2F2 was bound to this site, together with ERG, and prevented its activation. Conclusions: By leveraging a genome-wide approach, we revealed mechanistic insights into how NR2F2 functions in multiple roles to maintain venous identity. Importantly, characterization of its role at a crucial artery enhancer upstream of HEY2 established a novel mechanism by which artery-specific expression can be achieved.
Ethnic disparities in maternal care
Authors: Lilian Anekwe
Journal: BMJ (2020)

Black and ethnic minority women are paying with their lives for the lack of action on racial bias, reports Lilian Anekwe Maternal health—or lack of it—is one of the starkest examples of racial health inequalities in the United Kingdom and in the United States. Work in the UK by University of Oxford researchers found that between 2014 and 2016 the rate of maternal death in pregnancy was 8 in 100 000 white women, compared with 15 in 100 000 Asian women and 40 in 100 000 black women (box 1).1 It's a similar picture in the US, where African-American, Native American, and Alaska native women die of pregnancy related causes at a rate three times that of white women, according to a May 2019 report by the Centers for Disease Control.2 Box 1 ### Problems in maternal careRETURN TO TEXT
EUS-guided detection and internal drainage of an open pancreaticocutaneous fistula after acute necrotizing pancreatitis
Authors: Armelle Schoch, Jérôme Rivory, Olivier Monneuse, Nada Nargues, Thierry Ponchon, Mathieu Pioche
Journal: Endoscopy (2020)

Endoscopic ultrasound (EUS)-guided drainage is one of the leading methods for the management of pancreatic fluid collections (PFCs) and fistulas [1] [2]. However, it is technically challenging to find a fistula, which is usually smaller than a collection since the fluid discharges spontaneously.
Safety and efficacy of the maximum tolerated dose of givinostat in polycythemia vera: a two-part Phase Ib/II study
Authors: Alessandro Rambaldi, Alessandra Iurlo, Alessandro M. Vannucchi, Richard Noble, Nikolas von Bubnoff, Attilio Guarini, Bruno Martino, Antonio Pezzutto, Giuseppe Carli, Marianna De Muro, Stefania Luciani, Mary Frances McMullin, Nathalie Cambier, Jean-Pierre Marolleau, Ruben A. Mesa, Raoul Tibes, Alessandro Pancrazzi, Francesca Gesullo, Paolo Bettica, Sara Manzoni, Silvia Di Tollo
Journal: Leukemia (2020)
Extracellular vesicles from myelodysplastic mesenchymal stromal cells induce DNA damage and mutagenesis of hematopoietic stem cells through miRNA transfer
Authors: Mathieu Meunier, Audrey Guttin, Sarah Ancelet, David Laurin, Johanna Zannoni, Christine Lefebvre, Sylvie Tondeur, Virginie Persoons, Mylène Pezet, Karin Pernet-Gallay, Florent Chuffart, Sophie Rousseaux, Quentin Testard, Julien Thevenon, Claire Jouzier, Jean-François Deleuze, Karine Laulagnier, Rémy Sadoul, Christine Chatellard, Pierre Hainaut, Benoît Polack, Jean-Yves Cahn, Jean-Paul Issartel, Sophie Park
Journal: Leukemia (2020)
Antibiotic use during pregnancy increases offspring asthma severity in a dose‐dependent manner
Authors: Moumen M. Alhasan, Alissa M. Cait, Markus M. Heimesaat, Michael Blaut, Robert Klopfleisch, Alexander Wedel, Thomas M. Conlon, Ali Ö. Yildirim, Elisa B. Sodemann, William W. Mohn, Stefan Bereswill, Melanie L. Conrad
Journal: Allergy (2020)

The use of antibiotics during pregnancy is associated with increased allergic asthma risk in the offspring, and given that approximately 25% of pregnant women are prescribed antibiotics, it is important to understand the mechanisms contributing to this phenomenon. Currently, there are no studies that directly test this association experimentally. Our objective was to develop a mouse model in which antibiotic treatment during pregnancy results in increased offspring asthma susceptibility.Pregnant mice were treated daily from gestation day 8-17 with an oral solution of the antibiotic vancomycin, and three concentrations were tested. At weaning, offspring were subjected to an adjuvant-free experimental asthma protocol using ovalbumin as an allergen. The composition of the gut microbiome was determined in mothers and offspring with samples collected from five different time points; short-chain fatty acids were also analyzed in allergic offspring.We found that maternal antibiotic treatment during pregnancy was associated with increased offspring asthma severity in a dose-dependent manner. Furthermore, maternal vancomycin treatment during pregnancy caused marked changes in the gut microbiome composition in both mothers and pups at several different time points. The increased asthma severity and intestinal microbiome changes in pups were also associated with significantly decreased cecal short-chain fatty acid concentrations.Consistent with the "Developmental Origins Hypothesis," our results confirm that exposure to antibiotics during pregnancy shapes the neonatal intestinal environment and increases offspring allergic lung inflammation.