tbuckley/cabot-search huggingface dataset:
Dual Bronchodilators and β-Blockade for Cardiovascular Risk in Chronic Obstructive Pulmonary Disease—Reply
Authors: Meng-Ting Wang, Yun-Han Wang, Chen-Liang Tsai
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
The One Health stewardship of colistin as an antibiotic of last resort for human health in South Africa
Authors: Marc Mendelson, Adrian Brink, Joey Gouws, Nontombi Mbelle, Vinny Naidoo, Troy Pople, Natalie Schellack, Moritz van Vuuren, Helen Rees, Shabir Banoo, Khotso Bokaba, Marius Collins, Kim Faure, Maryke Herbst, Beyers Hoek, Ruth Lancaster, Jeanette Lotter, Mike Modisane, Mahlodi Mohlala, Ernest Mokantla, Adelaide Molatuli, Margaret Molefe, Griffith Molewa, Kefiloe Mompati, Lesiba Moshiga, Shyamli Munbodh, Portia Nkambule, Camilla Patterson, Darshana Reddy, Alice Sigobondhla, Suraiya Suliman, Gerry Swan
Journal: The Lancet Infectious Diseases (2018)
P497Altered myocardial function and perfusion in a swine model of diastolic dysfunction with multiple co-morbidities
Authors: O Sorop, J Van De Wouw, RWA Van Drie, I Heinonen, V J De Beer, J Van Der Velden, W A Linke, J A Joles, D J Duncker
Journal: Cardiovascular Research (2018)

After an Acute Myocardial Infarction (AMI), Ischemia-Reperfusion (I/R) injury is responsible for a critical decrease in the number of viable cardiomyocytes (hCMs).Human myocardium harbors a population of endogenous cardiac stem/progenitor cells (hCSCs) that is activated upon I/R injury, contributing to myocardial repair through the establishment of an auto/paracrine molecular crosstalk between hCSCs and hCMs in stress.Clinical trials involving transplantation of hCSCs into the infarcted myocardium have demonstrated the potential of these cells.Although some improvements have been reported regarding increase in viable myocardium and improved tissue contractility, extensive data indicates that transplanted cells do not survive in the myocardium and this has led to the postulation of a paracrine mechanism for the observed beneficial effects.Using the same cells currently employed in the allogenous hCSCs transplantation clinical trial CARE-MI (EUDRA 2013-001358-81), our work aims at setting up an in vitro human I/R injury model using by using 3D culture approached combined with stirred tank bioreactor technology, in order to better decipher the mechanisms of action of hCSCs upon AMI using proteomic tools.By using aggregates of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) and a microcarreir based culture of hCSCs, injury setup was performed in bioreactors, allowing paracrine crosstalk between the two cell types via a reciprocal medium exchange via a perfusion system.Ischemia was mimicked by substituting growth media by Ischemia Mimetic Solution and placing the cells at 0% O2 for 5 hours.In the reperfusion step, cells were placed back in their physiological culture conditions (3% O2).The effect of I/R injury in hCSCs was accessed by quantitative total proteome analysis (using LC-MS) at different time points.Growth factor secretion, cells' viability, as well as hCSCs proliferation was also monitored in this co-culture system.Our first experiments in monolayer static systems showed that this model is able to recapitulate important features of I/R, including hCSC proliferation activation and a protective effect of hCSCs in hiPSC-CMs survival.Upon injury, proteome of hCSCs was enriched in proteins related to cell cycle regulation inhibition, proliferation through EGF signaling, gluthathione-mediated reactive oxygen species detoxification and paracrine signalling pathways.This system will allow further understanding on the molecular landscape of the myocardium during AMI, namely regarding hCSCs regenerative response and hCMs survival.The knowledge generated in this work will hopefully potentiate the development of novel molecular and cell-based therapies for myocardium regeneration.
CTEP #8342 autophagy modulation with antiangiogenic therapy: A phase I trial of sunitinib (Su) and hydroxychloroquine (HCQ).
Authors: Nataliya Melnyk, Xiaoqi Xie, Danny Ju Yong Koh, Megha Rajpal, Rebecca Anne Moss, Darlene Gibbon, James M. Cleary, Minh-Thu Tran, Pamela Scott, Mark N. Stein, Antoinette R. Tan, Shari Adams, Diana C. Lindquist, Pamela Jo Harris, Naoko Takebe, Hongxia Lin, Joseph Aisner, Eileen White, Robert S. DiPaola, Janice M. Mehnert
Journal: Journal of Clinical Oncology (2013)

2553 Background: Angiogenesis inhibitors promote autophagy, a response to nutrient deprivation in which autophagosomes (AP) and lysosomes fuse to recycle intracellular constituents, leading to sustained tumor viability. We hypothesized that the VEGF-R2, c-kit, PDGFR inhibitor Su induces autophagy. The autophagy inhibitor HCQ may then interfere with autophagy dependent tumor survival, possibly improving patient (pt) outcomes. Methods: This trial determined the MTD of Su+HCQ in pts with advanced malignancies using a 3+3 design. Su 50 mg qd was given in 4 week on/2 week off cycles (C) with daily HCQ in escalating dose cohorts. A MTD expansion cohort of 12 pts was also enrolled. Modulation of autophagy was measured by changes in the AP marker light chain-3 (LC3)II/I ratio in paired PBMC samples from C1 and C2. Results: 21 pts, median age 59, PS 0 (7), 1 (13) or 2 (1) enrolled, including 5 colon, 2 renal and 5 sarcomatous tumors. 4 DLTs were observed: 3 DLTs (gr 3 confusion, gr 3 colon fistula, gr 3 thrombocytopenia) in DL2 (50 mg Su, 200 mg bid HCQ), and 1 DLT (gr 3 dehydration) in DL1 (50 mg Su, 200 mg HCQ). DL1 was thus declared the MTD. Gr 3/ 4 toxicities included: related to Su, thrombocytopenia (14%), fatigue (19%), neutropenia (14%), hypertension (14%), intestinal perforation (10%); related to HCQ, fatigue (14%). PK data of Su alone, its active metabolite SU012662 and the total were evaluated using noncompartmental analysis. Cmax and AUCs of the active metabolite SU012662 significantly increased (p&lt;0.005) during C2 relative to C1, indicating drug-drug interactions between HCQ and Su. 9 of 21 (43%) had stable disease for &gt; 3 cycles (median 73 days). Inconsistent autophagy modulation was seen in PBMCs. LC3 immunohistochemistry on baseline tumor blocks to assess individual tumor autophagy levels is in progress. Conclusions: pK interaction between Su and HCQ resulting in accumulation of Su metabolites may be responsible for the predominantly Su-associated toxicities observed which prohibited further HCQ dose escalation. Lack of evidence for autophagy modulation is likely due to the inability to escalate HCQ to doses necessary to induce autophagy inhibition. Further study of this combination seems unwarranted. Clinical trial information: NCT00813423.
Combined IFN-γ and TNF-α release assay for differentiating active tuberculosis from latent tuberculosis infection
Authors: Ji Yeun Kim, Joung Ha Park, Min-Chul Kim, Hye Hee Cha, Na-Young Jeon, Seong Yeon Park, Min-Jae Kim, Yong Pil Chong, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Jun Hee Woo, Sung-Han Kim
Journal: Journal of Infection (2018)
Effects of Exposure to Acetaminophen and Ibuprofen on Fetal Germ Cell Development in Both Sexes in Rodent and Human Using Multiple Experimental Systems
Authors: Pablo Hurtado-Gonzalez, Richard A. Anderson, Joni Macdonald, Sander van den Driesche, Karen Kilcoyne, Anne Jørgensen, Chris McKinnell, Sheila Macpherson, Richard M. Sharpe, Rod T. Mitchell
Journal: Environmental Health Perspectives (2018)

Background: Analgesic exposure during pregnancy may affect aspects of fetal gonadal development that are targeted by endocrine disruptors. Objectives: We investigated whether therapeutically relevant doses of acetaminophen and ibuprofen affect germ cell (GC) development in human fetal testes/ovaries using in vitro and xenograft approaches. Methods: First-trimester human fetal testes/ovaries were cultured and exposed to acetaminophen or ibuprofen (7 d). Second-trimester human fetal testes were xenografted into mice and exposed to acetaminophen (1 or 7 d), or ibuprofen (7 d). To determine mechanism of action, a human GC tumor–derived cell line (NTera2) exhibiting fetal GC characteristics was used in addition to in vitro and in vivo rat models. Results and Discussion: Gonocyte (TFAP2C+) number was reduced relative to controls in first-trimester human fetal testes exposed in vitro to acetaminophen (–28%) or ibuprofen (–22%) and also in ovaries exposed to acetaminophen (–43%) or ibuprofen (–49%). Acetaminophen exposure reduced gonocyte number by 17% and 30% in xenografted second-trimester human fetal testes after treatment of host mice for 1 or 7 d, respectively. NTera2 cell number was reduced following exposure to either analgesic or prostaglandin E2 (PGE2) receptor antagonists, whereas PGE2 agonists prevented acetaminophen-induced reduction in NTera2 cell number. Expression of GC pluripotency genes, and genes that regulate DNA/histone methylation, also differed from controls following analgesic and PGE2 receptor antagonist exposures. Gene expression changes were observed in rat fetal testis/ovary cultures and after in vivo acetaminophen exposure of pregnant rats. For example, expression of the epigenetic regulator TET1, was increased following exposure to acetaminophen in human NTera2 cells, rat fetal testis/ovary cultures, and in fetal testes and ovaries after in vivo exposure of pregnant rats, indicating translatability across experimental models and species. Conclusions: Our results demonstrate evidence of PGE2-mediated effects of acetaminophen and ibuprofen on GC/NTera2 cells, which raises concerns about analgesic use during human pregnancy that warrant further investigation. https://doi.org/10.1289/EHP2307
Molecular diversity of HBV and HDV amino-acid sequences involved in HDV virion morphogenesis according to HBV and HDV genotypes: study of 1590 clinical strains
Authors: A. Gerber, S. Dziri, S. Brichler, C. Alloui, D. Roulot, Z. Ben Abdesselam, F. Le Gal, E. Gordien
Journal: Journal of Hepatology (2018)
Reduction in polyamine catabolism leads to spermine‐mediated airway epithelial injury and induces asthma features
Authors: V. Jain, S. Raina, A. P. Gheware, R. Singh, R. Rehman, V. Negi, T. Murray Stewart, U. Mabalirajan, A. K. Mishra, R. A. Casero, A. Agrawal, B. Ghosh
Journal: Allergy (2018)

Airway epithelial injury is a crucial component of acute and severe asthma pathogenesis and a promising target for treatment of refractory asthma. However, the underlying mechanism of epithelial injury remains poorly explored. Although high levels of polyamines, mainly spermine, have been found in asthma and comorbidity, their role in airway epithelial injury and the cause of their altered levels in asthma have not been explored.We measured key polyamine metabolic enzymes in lung samples from normal and asthmatic subjects and in mice with OVA-induced allergic airway inflammation (AAI). Polyamine metabolism was modulated using pharmacologic/genetic modulators. Epithelial stress and apoptosis were measured by TSLP levels and TUNEL assay, respectively.We found loss of the polyamine catabolic enzymes spermidine/spermine-N (1)-acetyltransferase-1 (SAT1) and spermine oxidase (SMOX) predominantly in bronchial epithelial cells (BECs) of human asthmatic lung samples and mice with AAI. In naïve mice, SAT1 or SMOX knockdown led to airway hyper-responsiveness, remodeling, and BEC apoptosis. Conversely, in mice with AAI, overexpression of either SAT1 or SMOX alleviated asthmatic features and reduced TSLP levels and BEC apoptosis. Similarly, while pharmacological induction of SAT1 and SMOX using the polyamine analogue bis(ethyl)norspermine (BENSPM) alleviated asthmatic features with reduced TSLP levels and BEC apoptosis, pharmacological inhibition of these enzymes using BERENIL or MDL72527, respectively, worsened them. Spermine accumulation in lungs correlated with BEC apoptosis, and spermine treatment caused apoptosis of human BEAS-2B cells in vitro.Spermine induces BEC injury. Induction of polyamine catabolism may represent a novel therapeutic approach for asthma via reversing BEC stress.
Abstract 15955: Central Arterial Hemodynamics of Hypertension at High Altitude: The INTERVENCION Trial
Authors: Josefina Medina-Lezama, Offdan Narvaez Guerra, Karela Herrera Enriquez, Mardelangel Zapata Ponze De Leon, Angely J Rondon Rodríguez, Sandra Pérez Moscoso, Julio A Chirinos
Journal: Circulation (2016)

Background:  Altitude above sea level is a key regulator of cardiovascular function. Whereas much is known about the short-term cardiovascular effects of altitude, data are lacking about the differences in the patterns of hypertension between populations living at low and high altitude. Hemodynamic patterns of hypertension can provide important clues about vascular status. Mean arterial pressure is dependent on microvascular resistance and cardiac output, whereas pulsatile hemodynamics are dependent on large and medium-sized conduit artery function.   Methods:  We performed an analysis of the baseline measurements in the INTERVENCION study, a prospective randomized multicenter trial which enrolled subjects with untreated hypertension at low altitude (LA,  3500 m) in Peru. At each altitude level, enrollment was stratified by age group and gender to achieve an equal distribution. Central pressure profiles were measured with carotid high-fidelity arterial tonometry (Millar tonometer and Sphygmocor device).   Results:  Age, gender and body mass index in the sample did not differ between altitude levels. Despite similar mean arterial pressure (LA: 106.3±1.9; IA: 107.9±1.3; HA: 104.3±1.1; P=0.12), central systolic pressure was progressively lower with increasing altitude (SL: 144.8±3.3; IA: 139.2±2.2; HA: 133.7±1.7; P=0.007). This was due to both a lower amplitude of the first systolic peak (forward pressure) (LA=47.8±1.7; IA=42.2±1.4; HA: 38.1±1.3 mmHg; P   Conclusions:  Despite similar levels of mean pressure, we demonstrate for the first time, marked altitude-related differences in central hemodynamics in hypertension. Hypertensives living chronically at increasing altitude demonstrated less adverse pulsatile hemodynamics, which may translate in differences in cardiovascular risk and response to therapy.
Massive upper gastrointestinal bleeding post-Whipple’s surgery from anastomotic varices due to mesenteric hypertension
Authors: Yu Wong, Farah Irani, Malcolm Tan, Melissa Teo
Journal: Endoscopy (2018)

A 45-year-old man was admitted with hematemesis. He had undergone Whipple's surgery 7 years previously for a 5-cm serous cystadenoma of the pancreatic head. Upon presentation, he was hypotensive (blood pressure 82/59 mmHg) and tachycardic (110 beats/min), with a hemoglobin of 6.8 g/dL. Gastroscopy revealed bleeding anastomotic varices alongside the gastrojejunal anastomosis ([Fig. 1]). Hemostasis was secured with a Boston Resolution clip ([Video 1]). Computed tomography (CT) scanning, followed by mesenteric angiography in the portal venous phase and CT arterioportography showed proximal superior mesenteric vein (SMV) occlusion, with a large collateral vein draining the small bowel into the anastomotic varices, which decompressed via the enlarged left coronary vein (LCV) into a patent portal vein ([Fig. 2]). The occluded SMV was recanalized, dilated to 8 mm, and stented with a 7 × 29-mm Omnilink stent via a transhepatic approach, thereby re-establishing antegrade flow with subsequent collapse of the collateral vein and anastomotic varices ([Fig. 3]).
Tumor suppressor BAP1 is essential for thymic development and proliferative responses of T lymphocytes
Authors: Teresita L. Arenzana, Steve Lianoglou, Akiko Seki, Celine Eidenschenk, Tommy Cheung, Dhaya Seshasayee, Thijs Hagenbeek, Arivazhagan Sambandam, Rajkumar Noubade, Ivan Peng, Justin Lesch, Jason DeVoss, Xiumin Wu, Wyne P. Lee, Patrick Caplazi, Joshua Webster, Jinfeng Liu, Victoria C. Pham, David Arnott, Jennie R. Lill, Zora Modrusan, Anwesha Dey, Sascha Rutz
Journal: Science Immunology (2018)

Loss of function of the nuclear deubiquitinating enzyme BRCA1-associated protein-1 (BAP1) is associated with a wide spectrum of cancers. We report that tamoxifen-induced BAP1 deletion in adult mice resulted in severe thymic atrophy. BAP1 was critical for T cell development at several stages. In the thymus, BAP1 was required for progression through the pre-T cell receptor checkpoint. Peripheral T cells lacking BAP1 demonstrated a defect in homeostatic and antigen-driven expansion. Deletion of BAP1 resulted in suppression of E2F target genes and defects in cell cycle progression, which was dependent on the catalytic activity of BAP1, but did not require its interaction with host cell factor-1 (HCF-1). Loss of BAP1 led to increased monoubiquitination of histone H2A at Lys119 (H2AK119ub) throughout the T cell lineage, in particular in immature thymocytes, but did not alter trimethylation of histone H3 at Lys27 (H3K27me3). Deletion of BAP1 also abrogated B cell development in the bone marrow. Our findings uncover a nonredundant function for BAP1 in maintaining the lymphoid lineage.
Hepamet Score: a new non-invasive method for NAFLD-related fibrosis screening in clinical practice
Authors: J. Ampuero, Rocío Aller, Rocío Gallego-Durán, Jesús Banales, J. Crespo, E. Vilar-Gomez, S. Petta, C. Garcia-Monzon, N. Mora-Cuadrado, M. Castellanos-Fernandez, A. Craxi, María Jesús Pareja, Raúl Jiménez-Agüero, J. Caballería, María T.A. Loste, D. Escudero-García, J. Gómez-Camarero, José L.C. Panero, D.A. De Luis Román, L.G. Fabian, V. Di Marco, Águeda Gónzalez-Rodriguez, M. Latorre, A. Albillos, Victor Aguilar-Urbano, J. Salmerón, José L. Olcoz-Goñi, P. Aspichueta, Álvaro Santos-Laso, O. Lo Iacono, P. Iruzubieta, I. Graupera, M. García-Torres, E. Badia-Aranda, J.A. Guerra, Rubén Francés, H. Pastor, E. Del Pozo-Maroto, M. Diago, R. Martin-Mateos, S. Benlloch, C. Fernández-Rodríguez, F.J.G.-S. Rey, P. Estevez, R.J. Andrade, J. Turnés, M.R. Gomez
Journal: Journal of Hepatology (2018)
Germ line tissues for optimal detection of somatic variants in myelodysplastic syndromes
Authors: Eric Padron, Markus C. Ball, Jamie K. Teer, Jeffrey S. Painter, Sean J. Yoder, Chaomei Zhang, Ling Zhang, Lynn C. Moscinski, Dana E. Rollison, Steven D. Gore, Rafael Bejar, Matthew J. Walter, Mikkael A. Sekeres, Rami S. Komrokji, Pearlie K. Epling-Burnette
Journal: Blood (2018)
26A-to-I editing of microRNA-487b alters target gene selection and promotes neovascularization after ischemia
Authors: RVCT Van Der Kwast, E Van Ingen, L Parma, HAB Peters, PHA Quax, AYN Nossent
Journal: Cardiovascular Research (2018)

Introduction: microRNA miR487b has been shown to play an important role in cardiovascular pathology, despite having relatively few putative targets.Adenosine-to-inosine (A-to-I) editing of microRNAs by ADARs can cause a shift in target-site selection.Purpose: To investigate whether miR487b is subject to A-to-I editing during ischemia and how this affects the pool of target genes of miR487b.Methods: and Results: cDNA was prepared from muscle tissue of C57BL/6 mice subjected to hind limb ischemia.Using Sanger sequencing and sequence specific endonuclease digestion, we identified and confirmed A-to-I editing in the seed sequence of miR487b.Subsequent quantification revealed post-ischemic regulation of miR487b editing.In the ischemic gastrocnemius, primary-miR487b editing increased from 6.760.4% before to 11.761.6%(P¼0.02)one day after ischemia.Edited primary-miR487b is processed into a mature microRNA, miR487b-ED, which is also upregulated following ischemia.Primary human vascular cells were used to show that miR487b editing is conserved in human miR487b and that its precursor associates with both ADAR1 and -2.With specific in vitro siRNA knockdowns, we found that both ADAR1 and -2 can edit miR487b.The 3'UTR of IRS1 contains a binding site for both miR487b and miR487b-ED, whereas BMP1 contains six separate binding sites for miR487b-ED.Luciferase reporter gene assays using both endogenous and mutated IRS1 and BMP1 binding sites demonstrated that editing of miR487b's seed sequence does result in a complete shift in target site selection.In an identical context, binding of miR487b-ED induced stronger luciferase silencing than miR487b binding.Furthermore, a subset of putative target genes were validated to confirm specific regulation by either miR487b or miR487b-ED in gain-of-function experiments using primary human vascular cells.In contrast to wildtype miR487b's target pool, miR487b-ED's novel targetome is enriched for angiogenesis-associated pathways.Indeed, microRNA overexpression experiments showed that miR487b-ED causes a 2-fold increase in neovascularization compared to miR487b in an ex vivo aortic ring sprouting assay and also increases wound healing in scratch assays on both human vascular endothelial cells and fibroblasts.Finally, whole exome microarray was performed to measure average targetome expression after hind limb ischemia.We found that only miR487b-ED's targetome is actively repressed during active neovascularization after ischemia.Conclusions: MiR487b is edited in its seed-sequence in both mice and humans.Editing of miR487b is upregulated after ischemia and causes a shift in target gene selection, resulting in a novel, pro-angiogenic microRNA, miR487b-ED, with a unique targetome.Our results demonstrate that microRNA-editing plays an active role in neovascularization.