tbuckley/cabot-search huggingface dataset:
Ninety-Day Outcome Assessment After Transcatheter and Surgical Aortic Valve Replacement—Is the Juice Worth the Squeeze?
Authors: Michael Mack, Karim Al-Azizi, Michael J. Reardon
Journal: JAMA Cardiology (2019)

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 Cardiology 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 Cardiology journal
Efficacy of empagliflozin on heart failure and renal outcomes in patients with atrial fibrillation: data from the EMPA‐REG OUTCOME trial
Authors: Michael Böhm, Jonathan Slawik, Martina Brueckmann, Michaela Mattheus, Jyothis T. George, Anne Pernille Ofstad, Silvio E. Inzucchi, David Fitchett, Stefan D. Anker, Nikolaus Marx, Christoph Wanner, Bernard Zinman, Subodh Verma
Journal: European Journal of Heart Failure (2019)
Abstract C18: TGF-beta blockade paradoxically activates non-SMAD signaling
Authors: S. Mazher Husain, Rita Kansal, Marcus A. Alvarez, Evan S. Glazer
Journal: Cancer Research (2019)

Abstract Transforming growth factor-beta (TGF-B) activates a receptor leading to a critical signaling cascade in pancreatic ductal adenocarcinoma (PDAC) that results in cancer progression through epithelial-to-mesenchymal transition (EMT) and therapeutic resistance. This signaling is through both the canonical SMAD and non-SMAD proteins. Clinically, there exists a TGF-B paradox where TGF-B is a tumor suppressor in nonmetastatic PDAC but a tumor promotor in metastatic PDAC. We hypothesized that TGF-B receptor blockade helps explain the paradox leading to EMT and therapeutic resistance due to non-SMAD signaling. We investigated expression of proteins involved in non-SMAD TGF-B signaling in human PDAC cell lines with Western blot and in patient-derived organoids with immunofluorescence. Inhibition of the TGF-B receptor type 1 with galunisertib resulted in increased phospho-MAPK14 and phospho-Akt compared to controls. In metastatic PDAC, we also demonstrated that this results in increased levels of the activate beta-catenin complex. There were no changes to SMAD2 or SMAD3 phosphorylation. Our work demonstrates that despite blocking of the TGF-B receptor 1, phosphorylation of MAPK14 increases leading to non-SMAD signaling through Akt. Our data demonstrate that beta-catenin is the effector molecule for cancer progression. Our results also demonstrate a possible mechanism for the development of therapeutic resistance in patients with PDAC who undergo TGF-B receptor inhibition therapy. Citation Format: S. Mazher Husain, Rita Kansal, Marcus A. Alvarez, Evan S. Glazer. TGF-beta blockade paradoxically activates non-SMAD signaling [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C18.
Abstract PR10: Enhancing the effect of autophagy inhibition for pancreatic cancer treatment
Authors: Kirsten L. Bryant, Jennifer E. Klomp, Ye S. Lee, Clint A. Stalnecker, Kajal R. Grover, A. Cole Edwards, Sen Peng, Mariaelena Pierobon, Emanuel F. Petricoin, Nhan Tran, Alec C. Kimmelman, Adrienne D. Cox, Channing J. Der
Journal: Cancer Research (2019)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by KRAS- and autophagy-dependent tumorigenic growth. We determined the role of mutationally activated KRAS, found in ~95% of PDAC, in supporting autophagy. Surprisingly, acute KRAS suppression, which blocks proliferation, was associated with increased rather than decreased autophagic flux. Pharmacologic inhibition of ERK MAPK phenocopied the genetic silencing of KRAS and also increased autophagic flux. We speculated that the loss of ERK-driven metabolic processes may induce compensatory mechanisms to increase autophagy. Addressing a mechanism for ERK suppression-increased autophagy, we describe three mechanisms: 1) ERK inhibition-mediated increased transcription of autophagy and lysosomal genes, 2) ERK inhibitor-induced AMPK activation and suppression of mTOR signaling, and 3) ERK inhibition-facilitated decreased glycolytic flux. We then addressed whether ERK inhibition increased PDAC dependence on autophagy. Supporting this possibility, we found that cotreatment with the autophagy inhibitor chloroquine (CQ) synergistically enhanced ERK inhibitor-mediated antiproliferative activity. Similarly, genetic or pharmacologic inhibition of specific regulators of autophagy also enhanced ERK inhibitor activity. Encouraged by the synergistic relationship between ERK and autophagy inhibition, we performed a CRISPR/Cas-9 mediated genetic loss of function screen in the presence of CQ to determine additional sensitizers as well as mediators of resistance to autophagy inhibition. Top sensitizers included multiple mediators of the DNA damage response. One such sensitizing gene was CHEK1, which encodes the CHK1 serine/threonine kinase, required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to DNA damage. Accordingly, we showed that treatment with prexasertib, a clinical candidate CHK1 inhibitor, increased autophagic flux in PDAC cells and synergized with CQ to decrease PDAC cell proliferation and increase apoptosis. We conclude that concurrent suppression of multiple metabolic processes, to block compensatory rebound activities, will be needed for effective PDAC treatment. This abstract is also being presented as Poster B07. Citation Format: Kirsten L. Bryant, Jennifer E. Klomp, Ye S. Lee, Clint A. Stalnecker, Kajal R. Grover, A. Cole Edwards, Sen Peng, Mariaelena Pierobon, Emanuel F. Petricoin III, Nhan Tran, Alec C. Kimmelman, Adrienne D. Cox, Channing J. Der. Enhancing the effect of autophagy inhibition for pancreatic cancer treatment [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr PR10.
An Oxygen Self‐Evolving, Multistage Delivery System for Deeply Located Hypoxic Tumor Treatment
Authors: Wei Jiang, Xiaoxue Han, Taixing Zhang, Diya Xie, Hao Zhang, Yong Hu
Journal: Advanced Healthcare Materials (2019)

The hypoxia-induced resistance to radiotherapy (RT) is a great threat to cancer patients. Therefore, overcoming the hypoxia tumor microenvironment is a vital issue. Herein, spindle-shaped CuS@CeO2 core-shell nanoparticles combining self-supplied oxygen, photothermal ability, and RT sensitive to cancer therapy are introduced. The spindle shape of CuS@CeO2 core-shell nanoparticles can potentiate their tumor penetration and subsequent internalization by cancer cells. The presence of CeO2 , functioning as a nanoenzyme, catalyzes the endogenous H2 O2 in tumor tissue into O2 , which remodels the hypoxic microenvironment into one susceptible to RT. CuS nanoparticles encapsulated in CeO2 undergo a steady release and deep tumor penetration, allowing the regression of lesions less affected by RT. Furthermore, in vitro and in vivo studies reveal that the design not only mitigates the dosage of RT, but more importantly allows the entire tumor to be treated without relapses.
Correction: Effects of Varenicline on Smoking Cessation in Adults With Stably Treated Current or Past Major Depression
Journal: Annals of Internal Medicine (2013)

In their cost-effectiveness analysis of treatment versus observation for low-risk prostate cancer, Hayes and colleagues (1) conclude that watchful waiting is less costly and more effective in terms of quality-adjusted life expectancy than the standard treatment of surgery or radiation.Their base-case results depend heavily on a hazard ratio (HR) for prostate cancer-specific death of 1.48 for treatment versus watchful waiting, which was obtained from an HR observed in the low-risk subgroup in PIVOT (Prostate Cancer Intervention Versus Observation Trial).However, the 95% CI on this HR was extremely wide (0.42 to 5.24) because only 10 deaths from prostate cancer occurred in PIVOT in this subgroup (6 in the treatment group vs. 4 in the watchful waiting group).That such a pivotal parameter in the model was derived from such an unstable estimate should make readers cautious in interpreting the model's findings.Furthermore, the point estimate used, besides being unstable, lacks credulity.As the authors stated, it is already controversial that men with low-risk prostate cancer, who comprise up to 70% of men with clinically localized disease and have less than a 6% risk for prostate cancer-specific death through 15 years, are being routinely treated with radiation or surgery, given the fact that these treatments are known to greatly reduce quality of life (impotence and incontinence) and consume substantial health care resources.However, if it were widely accepted that such treatments also were associated with a 50% increase in the risk for prostate cancer death (or death from treatment for this condition) compared with observation only, this situation would move well past controversial-it would be one of the greatest medical scandals in the United States in recent decades.Solid evidence for such an increased risk is clearly not available yet.
Etiology, Risk Factors, and Biomarkers in Systemic Sclerosis with Interstitial Lung Disease
Authors: Dinesh Khanna, Donald P. Tashkin, Christopher P. Denton, Elisabetta A. Renzoni, Sujal R. Desai, John Varga
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Section:ChooseTop of pageAbstract <<PathogenesisGenetics and EpigeneticsRisk Factors for the Deve...Blood Serum and BAL Fluid...Comparison with IPFConclusionsReferencesCITING ARTICLES
In acute ischemic stroke with potentially salvageable tissue, thrombectomy at 6 to 16 h increased living at home
Authors: Graeme J. Hankey
Journal: Annals of Internal Medicine (2019)

Source Citation Tate WJ, Polding LC, Kemp S, et al. Thrombectomy results in reduced hospital stay, more home-time, and more favorable living situations in DEFUSE 3. Stroke. 2019;50:2578-81. 31288666
Author Correction: Human–machine partnership with artificial intelligence for chest radiograph diagnosis
Authors: Bhavik N. Patel, Louis Rosenberg, Gregg Willcox, David Baltaxe, Mimi Lyons, Jeremy Irvin, Pranav Rajpurkar, Timothy Amrhein, Rajan Gupta, Safwan Halabi, Curtis Langlotz, Edward Lo, Joseph Mammarappallil, A. J. Mariano, Geoffrey Riley, Jayne Seekins, Luyao Shen, Evan Zucker, Matthew P. Lungren
Journal: npj Digital Medicine (2019)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Salvage CryoBalloon cryotherapy ablation for a duodenal adenoma
Authors: Kara L. Raphael, Petros C. Benias, Arvind J. Trindade
Journal: Endoscopy (2019)

A 73-year-old man was referred for therapy of a duodenal adenoma discovered incidentally for an esophagogastroduodenoscopy (EGD) performed for evaluation of gastroesophageal reflux disease. On EGD the polyp ([Fig. 1]) measured 3 cm and was sessile and slightly elevated (Paris classification 0-IIa). Preparations were made for endoscopic mucosal resection (EMR). A solution of 3 % hetastarch, normal saline, and methylene blue was injected into the submucosal layer of the distal aspect of the polyp. The distal aspect of the polyp lifted well. An attempt was made to lift the central and proximal component of the polyp, but the lift was not adequate to allow EMR. Attempts were made using a waterjet probe (ErbeJet 2; Erbe USA, Marietta, GA, USA) at high settings of 360 psi (Effect 25) and then 725 psi (Effect 50).
Rhodopsin Genomic Loci DNA Nanoparticles Improve Expression and Rescue of Retinal Degeneration in a Model for Retinitis Pigmentosa
Authors: Min Zheng, Rajendra N. Mitra, Ellen R. Weiss, Zongchao Han
Journal: Molecular Therapy (2019)

The use of gene therapy may allow replacement of the defective gene. Minigenes, such as cDNAs, are often used. However, these may not express normal physiological genetic profiles due to lack of crucial endogenous regulatory elements. We constructed DNA nanoparticles (NPs) that contain either the mouse or human full-length rhodopsin genomic locus, including endogenous promoters, all introns, and flanking regulatory sequences of the 15-16 kb genomic rhodopsin DNA inserts. We transduced the NPs into primary retinal cell cultures from the rhodopsin knockout (RKO) mouse in vitro and into the RKO mouse in vivo and compared the effects on different functions to plasmid cDNA NP counterparts that were driven by ubiquitous promoters. Our results demonstrate that genomic DNA vectors resulted in long-term high levels of physiological transgene expression over a period of 5 months. In contrast, the cDNA counterparts exhibited low levels of expression with sensitivity to the endoplasmic reticulum (ER) stress mechanism using the same transgene copy number both in vitro and in vivo. This study demonstrates for the first time the transducing of the rhodopsin genomic locus using compacted DNA NPs.
Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non–Small-Cell Lung Cancer
Authors: Jeffrey D. Bradley, Chen Hu, Ritsuko R. Komaki, Gregory A. Masters, George R. Blumenschein, Steven E. Schild, Jeffrey A. Bogart, Kenneth M. Forster, Anthony M. Magliocco, Vivek S. Kavadi, Samir Narayan, Puneeth Iyengar, Clifford G. Robinson, Raymond B. Wynn, Christopher D. Koprowski, Michael R. Olson, Joanne Meng, Rebecca Paulus, Walter J. Curran, Hak Choy
Journal: Journal of Clinical Oncology (2019)

PURPOSE RTOG 0617 compared standard-dose (SD; 60 Gy) versus high-dose (HD; 74 Gy) radiation with concurrent chemotherapy and determined the efficacy of cetuximab for stage III non–small-cell lung cancer (NSCLC). METHODS The study used a 2 × 2 factorial design with radiation dose as 1 factor and cetuximab as the other, with a primary end point of overall survival (OS). RESULTS Median follow-up was 5.1 years. There were 3 grade 5 adverse events (AEs) in the SD arm and 9 in the HD arm. Treatment-related grade ≥3 dysphagia and esophagitis occurred in 3.2% and 5.0% of patients in the SD arm v 12.1% and 17.4% in the HD arm, respectively ( P = .0005 and &lt; .0001). There was no difference in pulmonary toxicity, with grade ≥3 AEs in 20.6% and 19.3%. Median OS was 28.7 v 20.3 months ( P = .0072) in the SD and HD arms, respectively, 5-year OS and progression-free survival (PFS) rates were 32.1% and 23% and 18.3% and 13% ( P = .055), respectively. Factors associated with improved OS on multivariable analysis were standard radiation dose, tumor location, institution accrual volume, esophagitis/dysphagia, planning target volume and heart V5. The use of cetuximab conferred no survival benefit at the expense of increased toxicity. The prior signal of benefit in patients with higher H scores was no longer apparent. The progression rate within 1 month of treatment completion in the SD arm was 4.6%. For comparison purposes, the resultant 2-year OS and PFS rates allowing for that dropout rate were 59.6% and 30.7%, respectively, in the SD arms. CONCLUSION A 60-Gy radiation dose with concurrent chemotherapy should remain the standard of care, with the OS rate being among the highest reported in the literature for stage III NSCLC. Cetuximab had no effect on OS. The 2-year OS rates in the control arm are similar to the PACIFIC trial.
Characteristics of Americans With Primary Care and Changes Over Time, 2002-2015
Authors: David M. Levine, Jeffrey A. Linder, Bruce E. Landon
Journal: JAMA Internal Medicine (2019)

Receipt of primary care is associated with better health. 1,2espite the benefits of primary care, Americans' receipt of primary care, changes in receipt of primary care over time, and differences in receipt of primary care according to sociodemographic and clinical characteristics are not well known.Female 52 (51-52) 82 (81-83) 18 (17-19) 51 (51-52) 80 (79-81) 20 (19-21) 1 [Reference] Male 48 (48-49) 72 (70-73) 28 (27-30) 49 (48-49) 70 (68-71) 30 (29-32) 0.59 (0.57-0.60)Race/ethnicity Non-Latino white 71 (69-72) 82 (81-83) 18 (17-19) 64 (62-66) 79 (78-81) 21 (19-22) 1 [Reference] Latino 12 (11-13) 58 (55-61) 42 (39-45) 16 (14-18) 64 (62-66) 36 (34-38) 0.80 (0.77-0.84)Black 11 (10-12) 73 (70-76) 27 (24-30) 12 (11-13) 71 (69-73) 29 (27-31) 0.88 (0.84-0.93)
The Case for Waking
Authors: Janis Lou Harrington
Journal: JAMA (2019)

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
Impaired hemostatic activity of healthy transfused platelets in inherited and acquired platelet disorders: Mechanisms and implications
Authors: Robert H. Lee, Raymond Piatt, Ankita Dhenge, María L. Lozano, Verónica Palma-Barqueros, José Rivera, Wolfgang Bergmeier
Journal: Science Translational Medicine (2019)

Platelet transfusions can fail to prevent bleeding in patients with inherited platelet function disorders (IPDs), such as Glanzmann's thrombasthenia (GT; integrin αIIbβ3 dysfunction), Bernard-Soulier syndrome [BSS; glycoprotein (GP) Ib/V/IX dysfunction], and the more recently identified nonsyndromic RASGRP2 variants. Here, we used IPD mouse models and real-time imaging of hemostatic plug formation to investigate whether dysfunctional platelets impair the hemostatic function of healthy donor [wild-type (WT)] platelets. In Rasgrp2-/- mice or mice with platelet-specific deficiency in the integrin adaptor protein TALIN1 ("GT-like"), WT platelet transfusion was ineffective unless the ratio between mutant and WT platelets was ~2:1. In contrast, thrombocytopenic mice or mice lacking the extracellular domain of GPIbα ("BSS-like") required very few transfused WT platelets to normalize hemostasis. Both Rasgrp2-/- and GT-like, but not BSS-like, platelets effectively localized to the injury site. Mechanistic studies identified at least two mechanisms of interference by dysfunctional platelets in IPDs: (i) delayed adhesion of WT donor platelets due to reduced access to GPIbα ligands exposed at sites of vascular injury and (ii) impaired consolidation of the hemostatic plug. We also investigated the hemostatic activity of transfused platelets in the setting of dual antiplatelet therapy (DAPT), an acquired platelet function disorder (APD). "DAPT" platelets did not prolong the time to initial hemostasis, but plugs were unstable and frequent rebleeding was observed. Thus, we propose that the endogenous platelet count and the ratio of transfused versus endogenous platelets should be considered when treating select IPD and APD patients with platelet transfusions.
Influence of Fiber Stiffness on Meniscal Cell Migration into Dense Fibrous Networks
Authors: Kwang Hoon Song, Su‐Jin Heo, Ana P. Peredo, Matthew D. Davidson, Robert L. Mauck, Jason A. Burdick
Journal: Advanced Healthcare Materials (2019)

Abstract Fibrous scaffolds fabricated via electrospinning are being explored to repair injuries within dense connective tissues. However, there is still much to be understood regarding the appropriate scaffold properties that best support tissue repair. In this study, the influence of the stiffness of electrospun fibers on cell invasion into fibrous scaffolds is investigated. Specifically, soft and stiff electrospun fibrous networks are fabricated from crosslinked methacrylated hyaluronic acid (MeHA), where the stiffness is altered via the extent of MeHA crosslinking. Meniscal fibrochondrocyte (MFC) adhesion and migration into fibrous networks are investigated, where the softer MeHA fibrous networks are easily deformed and densified through cellular tractions and the stiffer MeHA fibrous networks support ≈50% greater MFC invasion over weeks when placed adjacent to meniscal tissue. When the scaffolds are sandwiched between meniscal tissues and implanted subcutaneously, the stiffer MeHA fibrous networks again support enhanced cellular invasion and greater collagen deposition after 4 weeks when compared to the softer MeHA fibrous networks. These results indicate that the mechanics and deformability of fibrous networks likely alter cellular interactions and invasion, providing an important design parameter toward the engineering of scaffolds for tissue repair.