tbuckley/cabot-search huggingface dataset:
Cutaneous Granulomatous Disease With Presence of Rubella Virus in Lesions
Authors: Julie Dhossche, Luke Johnson, Kevin White, Tracy Funk, Sabra Leitenberger, Ludmila Perelygina, Alfons Krol
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Setting Positive End-Expiratory Pressure in Mechanically Ventilated Patients Undergoing Surgery
Authors: Thomas Godet, Emmanuel Futier
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 19751: Development and Validation of a Triage Tool in Predicting Cardiac Arrest in the Emergency Department
Authors: Tsung-Chien Lu, Chu-Lin Tsai, Chien-Hua Huang, Chih-Hung Wang, Cheng-Chung Fang
Journal: Circulation (2017)

Introduction: In-hospital Cardiac Arrest (IHCA) has increasingly been recognized as a separate entity from out-of-hospital Cardiac Arrest with regard to epidemiology, clinical prediction, and outco...
Surveillance endoscopy after ureterosigmoidostomy
Authors: Matthijs Kramer, Peter D. Siersema, Joost P. H. Drenth
Journal: Endoscopy (2019)

A 37-year-old woman who underwent a bilateral ureterosigmoidostomy (USS) as a child for bladder exstrophy was scheduled for a surveillance sigmoidoscopy. At 17 cm from the anal verge, a sharply delineated hyperemic mucosal segment with small dilated vessels was seen ([Fig. 1]). Within this segment, an orifice was present where the ureter had been implanted during previous surgery; a pulsatile outflow of clear urine was visible ([Video 1]). Targeted biopsies revealed colonic type mucosa with mild fibrosis and an inflammatory infiltrate, but no dysplasia.
Vitamin C promotes the proliferation and effector functions of human γδ T cells
Authors: Léonce Kouakanou, Yan Xu, Christian Peters, Junyi He, Yangzhe Wu, Zhinan Yin, Dieter Kabelitz
Journal: Cellular and Molecular Immunology (2019)

γδ T cells are of interest as effector cells for cellular immunotherapy due to their HLA-non-restricted lysis of many different tumor cell types. Potential applications include the adoptive transfer of in vitro-expanded γδ T cells. Therefore, it is important to optimize the culture conditions to enable maximal proliferative and functional activity. Vitamin C (L-ascorbic acid) is an essential vitamin with multiple effects on immune cells. It is a cofactor for several enzymes, has antioxidant activity, and is an epigenetic modifier. Here, we investigated the effects of vitamin C (VC) and its more stable derivative, L-ascorbic acid 2-phosphate (pVC), on the proliferation and effector function of human γδ T cells stimulated with zoledronate (ZOL) or synthetic phosphoantigens (pAgs). VC and pVC did not increase γδ T-cell expansion within ZOL- or pAg-stimulated PBMCs, but increased the proliferation of purified γδ T cells and 14-day-expanded γδ T-cell lines in response to γδ T-cell-specific pAgs. VC reduced the apoptosis of γδ T cells during primary stimulation. While pVC did not prevent activation-induced death of pAg-restimulated γδ T cells, it enhanced the cell cycle progression and cellular expansion. Furthermore, VC and pVC enhanced cytokine production during primary activation, as well as upon pAg restimulation of 14-day-expanded γδ T cells. VC and pVC also increased the oxidative respiration and glycolysis of γδ T cells, but stimulus-dependent differences were observed. The modulatory activity of VC and pVC might help to increase the efficacy of γδ T-cell expansion for adoptive immunotherapy.
In vitro characterization and in vivo anti-tumor activity of human monoclonal antibodies to the RON-receptor tyrosine kinase
Authors: Jennifer O'Toole, Erik Corcoran, Wenzhi Tian, James Huber, Pinki Singh, James Tonra, Yan Wu, Dale Ludwig, Yaron Hadari, Nick Loizos
Journal: Cancer Research (2008)

3984   Neutralizing antibodies to the RON-receptor tyrosine kinase were generated and compared for their effects on multiple tumor cell lines and xenograft models. RON, known as the macrophage-stimulating protein receptor (MSP-R), belongs to the c-Met family of receptor tyrosine kinases. RON is normally expressed in multiple epithelial cell types and evidence suggests it has a role in cancer. It is highly expressed in several epithelial tumors and cell lines of the colon, lung, breast, stomach, ovary, pancreas, bladder, liver, and kidney. In addition, RON activation leads to activation of signaling pathways involved in tumorigenesis. An initial antibody termed 41A10, henceforth designated RON-1, was derived from a phage system and showed inhibition of RON-dependent cell-signaling and tumor growth. Here we report the identification of novel anti-RON antibodies generated from a transgenic mouse system. Antibodies RON-6 and RON-8 have an affinity for the RON-receptor that is 100 fold greater than RON-1. Specifically, RON-6 and RON-8 bind RON with a K D  of 4.1 x 10 -11  and 3.2 x 10 -11  M whereas RON-1 binds RON with a K D  of 7.7 x 10 -9  M. Phosphorylation of MAPK is a necessary step in cell growth and this pathway is activated by the RON receptor. RON-6 proved to be less active than RON-8 in cell-based assays at inhibiting RON and MAPK phosphorylation in transfected and tumor cell lines. The  in vivo  anti-tumor activity of RON-1, RON-6 and 8 was compared in colon (HT-29) and lung (NCI-H292) xenograft tumor models in nude mice. All antibodies showed evidence of efficacy but RON-8 consistently outperformed RON-1 and RON-6 by significantly inhibiting the growth of colon and lung xenograft tumors at 60 mg/kg administered twice a week. RON-8 also proved effective at inhibiting the growth of a pancreatic tumor xenograft (BXPC3). These data suggest RON-8 may be useful for the treatment of tumors that express RON.
Abstract 42: Lysosomal Membrane Permeabilization Contributes to Hyperglycemia-Induced Cardiomyocytes Dysfunction
Authors: Satoru Kobayashi, Yuan Huang, Tamayo Kobayashi, Qiangrong Liang
Journal: Circulation Research (2017)

Hyperglycemia is an independent risk factor for diabetic heart failure. However, the mechanisms that mediate hyperglycemia-induced cardiac damage remain poorly understood. Previous studies have shown an association between lysosomal dysfunction and diabetic heart failure. Lysosomal membrane permeabilization (LMP) is a prominent feature of lysosomal dysfunction. We examined if high glucose (HG) induces LMP in cardiomyocyte. Immunofluorescent microscopy showed the release of cathepsin D (CTSD) from lysosome under HG, suggesting that HG induces LMP. To determine whether LMP and the ensuing CTSD expression play a role in HG-induced cardiomyocyte injury, we treated cells with siRNA targeting CTSD or low dose of CTSD inhibitor pepstatinA (0.5ng/mL). Remarkably, both CTSD down-regulation approaches reduced HG-induced myocyte injury, as shown by elevated cleavage of Caspase3 and by propidium iodide staining. These results suggest that LMP and the ensuing CTSD expression mediate HG-induced cardiotoxicity. In addition, by using LMP/lysophagy reporter tfGalectin3, we found that HG-induced LMP was accompanied by impaired lysophagy, suggesting a failed elimination of damaged lysosomes by lysophagy, which may exacerbate HG-induced LMP. Indeed, the lysophagy inducer L-leucyl-L-leucine methyl ester (LLOMe) stimulated lysophagy flux, attenuated HG-induced LMP, and restored the beating frequency of HG-treated cardiomuyocytes. Together, these findings demonstrate a novel mechanism by which high glucose impairs lysophagy, induces LMP and triggers the release of CTSD, which collectively contribute to hyperglycemic cardiotoxicity.
Impact of broadening clinical trial eligibility criteria for advanced non-small cell lung cancer patients: Real-world analysis.
Authors: R. Donald Harvey, Wendy S. Rubinstein, Gwynn Ison, Sean Khozin, Li Chen, Robert S. Miller, Monika Jun, Edward Stepanski, Brigham Hyde, Thomas S. Uldrick, George Anthony Komatsoulis, Jeremy Roberts, Elizabeth Garrett-Mayer, Richard L. Schilsky, Caroline Schenkel, Edward S. Kim, Suanna S. Bruinooge
Journal: Journal of Clinical Oncology (2019)

LBA108 Background: Restrictive trial eligibility criteria limit data generalizability and patient opportunity to participate. We compared numbers and characteristics of patients (pts) eligible using traditional vs expanded criteria recommended by ASCO and Friends of Cancer Research. Methods: A retrospective, observational analysis used deidentified EHR data from ASCO’s CancerLinQ database. Study cohort included adult aNSCLC pts with ≥2 visits and ≥1 dose of systemic treatment post-advanced-disease diagnosis from 2011-2018. Recorded creatinine clearance (CrCl) or Cockcroft-Gault variables were required. Pts were grouped by traditional criteria (no brain metastases, no other malignancies and CrCl &gt;60 mL/min) and expanded criteria (brain metastases and other malignancies allowed and CrCl &gt;30 mL/min). Results: 10,500 pts were identified (Table). Median age 67.6 years [IQR 60.3-74.4]. 56% were male, and 65% white. 60% were Stage IV, 80% former or current smokers. 5005 (47.7%) pts were excluded by traditional exclusion criteria, while only 154 (1.5%) pts were excluded by expanded criteria. Expanded criteria patients were older (67.5 v 66.1, p&lt;0.001); and more likely to be female (44% v 40%), Stage IV (60% v 55%), have non-squamous histology (47% v 45%), and never smokers (16% v 13%). Additional analysis is needed to differentiate treated/stable vs. active brain metastases. Conclusions: Use of the ASCO-Friends expanded criteria would enable nearly twice as many aNSCLC pts to be considered for trial participation (4,851 patients, 46.2%). Narrower criteria should only be used based on compelling scientific rationale for exclusion. [Table: see text]
Associations of Gout and Baseline Serum Urate Level With Cardiovascular Outcomes: Analysis of the Coronary Disease Cohort Study
Authors: Lisa K. Stamp, Christopher Frampton, Jill Drake, Robert N. Doughty, Richard W. Troughton, A. Mark Richards
Journal: Arthritis & Rheumatology (2019)

Objective To determine whether gout and serum urate ( SU ) levels are associated with increased risk of death, time to first readmission for any cardiovascular event, or incident heart failure in individuals with cardiovascular disease. Methods Individuals presenting with an acute coronary syndrome ( ACS ) were enrolled in the Coronary Disease Cohort Study. Clinical data were collected from the medical records at the index hospital admission, and clinical, echocardiographic, and biochemical data were collected postdischarge. Gout was defined by self‐report, use of urate‐lowering therapy, or use of colchicine with evidence of gout on review of the medical record. The primary end points were all‐cause mortality, time to readmission for a cardiac ischemic event, and time to readmission for heart failure. Results Data from 1,514 participants were available. During the follow‐up period, 53 of 160 participants with gout (33.1%) and 298 of 1,354 participants without gout (22.0%) died. After adjustment for other factors known to be associated with mortality, there was no gout‐specific increase in risk of mortality (adjusted hazard ratio 0.98 [95% confidence interval 0.69–1.38]). Time to readmission for heart failure was significantly briefer in those with, compared to those without, gout (adjusted hazard ratio 1.42 [95% confidence interval 1.02–1.97]). Irrespective of whether a participant had gout or not, as SU level increased, there was an increased risk of death and readmission for either a cardiovascular event or heart failure. Conclusion Survival post‐ ACS is similar with and without the presence of gout. People with gout are at an increased risk of readmission for heart failure and have longer hospital stays. Risk of these events increases in parallel with increases in SU levels.
Leflunomide Inhibits c-Myc Signaling and Impairs Myeloma Cell Growth
Authors: Ralf Buettner, Corey James Morales, Enrico Caserta, Domenico Viola, Joycelynne M. Palmer, Xiwei Wu, Nagarajan Vaidehi, Hongzhi Li, Tim Synold, Amrita Krishnan, Flavia Pichiorri, Michael Rosenzweig, Steven T. Rosen
Journal: Blood (2017)
Cardiac and hepatic siderosis in myelodysplastic syndrome, thalassemia and diverse causes of transfusion‐dependent anemia: the TIMES study
Authors: P. Joy Ho, Devendra Hiwase, Raj Ramakrishna, Nicholas Viiala, Ann Solterbeck, Robert Traficante, Evren Zor, Othon L. Gervasio, Laura M. High, David M. Ross, Donald K. Bowden
Journal: HemaSphere (2019)

The significant morbidity and mortality associated with iron overload can be reduced by effective iron chelation. Magnetic resonance imaging (MRI) provides accurate and reproducible iron load assessment. The aim of this epidemiological study was to assess the prevalence and severity of cardiac and hepatic siderosis by MRI and to evaluate the impact of MRI on clinical management in patients with transfusion-dependent anemia and non-transfusion-dependent thalassemia (NTDT). We enrolled 243 patients with myelodysplastic syndromes (MDS), thalassemia major (TM), NTDT or other chronic anemia. Overall, 10% and 48% had cardiac and hepatic siderosis, respectively. Mean liver iron concentration (LIC) was above target range in all groups; mean myocardial T2∗ was normal. Hepatic siderosis was more prevalent than myocardial siderosis in patients with MDS, occurring in 54.4% and 4.4% of patients, respectively. As also observed in patients with NTDT or other anemia, hepatic siderosis was present in a large proportion of MDS patients who were chelation naïve (57.7%), as well as in patients receiving iron chelation therapy (ICT) (52.4%), despite a lower transfusion load compared with TM. Correlation between LIC and serum ferritin was observed across diseases; however, not all patients requiring ICT could be identified with serum ferritin alone, as serum ferritin underestimated LIC in 4.4% and overestimated LIC in 7.5% of patients. Exploratory analyses showed serum ferritin thresholds for liver siderosis detected by MRI at approximately 300 ng/mL higher in MDS than in TM. Most patients reported low-medium adherence to ICT; MRI assessment led to change in ICT in 46% of evaluable patients, including 52% of MDS patients. Accurate organ iron monitoring by MRI facilitated appropriate initiation of chelation, dose optimization and clinical decision making. Trial registration: ClinicalTrials.gov: NCT01736540.
Comparison of totally laparoscopic total gastrectomy and laparoscopic-assisted total gastrectomy: A systematic review and meta-analysis
Authors: Shuai Zhao, Kai Zheng, Jian-Chun Zheng, Tao-Tao Hou, Zhen-Ning Wang, Hui-Mian Xu, Cheng-Gang Jiang
Journal: International Journal of Surgery (2019)
Abstract 15830: ‘Out of Target’ Radiation Therapy Leads to Impaired Cardiac Contractile Reserve in the Mouse
Authors: Adolfo G Mauro, Stefano Toldo, Ross B Mikkelsen, Asim Alam, Elisabeth Weiss, David A Gewirtz, Benjamin W Van Tassell, Antonio Abbate, Eleonora Mezzaroma
Journal: Circulation (2015)

Introduction: Radiation therapy (XRT) used for the treatment of cancer, can expose the heart to the radiation beam causing cardiac injury. However, fatigue and exercise intolerance are common symptoms in patients treated with XRT for different types of cancer, in which the XRT field does not involve the heart. Hypothesis: We hypothesize that impaired cardiac reserve may occur even when the XRT field is distant from the heart (‘out of target effect’). Methods: C57BL/6J female mice underwent two different radiation treatments (20 Gray, single dose) using a Small Animal Radiation Research Platform: a) the isocenter was pointed to the right lung sparing the heart (‘out of target’) and b) the heart was chosen as isocenter, as positive control. An additional group of mice were sham-irradiated, as negative control. Transthoracic echocardiography was used to assess the left ventricular ejection fraction (LVEF) at baseline and the contractile reserve expressed as percentage change in the LVEF measured at rest (LVEFr) and 3 minutes after intraperitoneal administration of the β-adrenergic agonist, isoproterenol (LVEFi)[(LVEFi-LVEFr)/LVEFr]*100]. Results: Three days after radiation treatment irradiated and sham mice showed normal LVEF at rest. However, the ‘out of target’ irradiation group showed a significant impairment in cardiac contractile reserve compared with sham, and similar to the ‘on target’ group (Figure). Conclusions: ‘Out of target’ radiation therapy leads to impaired cardiac contractile reserve in the mouse.
BAL Cell Gene Expression in Severe Asthma Reveals Mechanisms of Severe Disease and Influences of Medications
Authors: Nathaniel Weathington, Michael E. O’Brien, Josiah Radder, Thomas C. Whisenant, Eugene R. Bleecker, William W. Busse, Serpil C. Erzurum, Benjamin Gaston, Annette T. Hastie, Nizar N. Jarjour, Deborah A. Meyers, Jadranka Milosevic, Wendy C. Moore, John R. Tedrow, John B. Trudeau, Hesper P. Wong, Wei Wu, Naftali Kaminski, Sally E. Wenzel, Brian D. Modena
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Gene expression of BAL cells, which samples the cellular milieu within the lower respiratory tract, has not been well studied in severe asthma.
Childhood Socioeconomic Disadvantage and Risk of Fatty Liver in Adulthood: The Cardiovascular Risk in Young Finns Study
Authors: Tomi T. Laitinen, Jussi Vahtera, Katja Pahkala, Costan G. Magnussen, Joel Nuotio, Nina Hutri‐Kähönen, Mika Kivimäki, Terho Lehtimäki, Eero Jokinen, Tomi Laitinen, Päivi Tossavainen, Jaana Pentti, Jorma S.A. Viikari, Markus Juonala, Olli T. Raitakari
Journal: Hepatology (2019)

Fatty liver is a preventable cause of liver failure, but early risk factors for adulthood fatty liver are poorly understood. We examined the association of childhood socioeconomic disadvantage with adulthood fatty liver and tested adulthood risk factors of fatty liver as possible mediators of this link. The study population comprised 2,042 participants aged 3‐18 years at baseline (1980) from the longitudinal Cardiovascular Risk in Young Finns Study. Follow‐up with repeated clinical examinations was 31 years. Childhood socioeconomic disadvantage was assessed using data from parents’ socioeconomic position and socioeconomic circumstances in participants’ residential neighborhoods, categorized as high versus low socioeconomic disadvantage. Fatty liver was determined by ultrasound during the last follow‐up (2011) at ages 34‐49 years. Childhood and adulthood risk factors, including metabolic biomarkers and lifestyle variables, were assessed in clinical examinations. A total of 18.9% of the participants had fatty liver in adulthood. High childhood socioeconomic disadvantage was associated with an increased risk of fatty liver (risk ratio [95% confidence interval], 1.42 [1.18‐1.70]; P = 0.0002). This association was robust to adjustment for age, sex, and childhood risk factors of fatty liver, including high body mass index, elevated insulin, and low birth weight (1.33 [1.09‐1.62]; P = 0.005). High childhood socioeconomic disadvantage was also associated with the development of risk factors of fatty liver in adulthood. Adulthood risk factors linking childhood socioeconomic disadvantage with fatty liver included waist circumference (proportion mediated of the total effect of childhood socioeconomic disadvantage, 45%), body mass index (40%), systolic blood pressure (29%), insulin (20%), physical activity (15%), triglycerides (14%), and red meat consumption (7%). Conclusion: Childhood socioeconomic disadvantage was associated with multiple risk factors of fatty liver and increased likelihood of fatty liver in adulthood.
Insulin-like growth factor 1 modulates the phosphorylation, expression, and activity of organic anion transporter 3 through protein kinase A signaling pathway
Authors: Jinghui Zhang, Zhou Yu, Guofeng You
Journal: Acta Pharmaceutica Sinica B (2019)

Organic anion transporter 3 (OAT3) plays a vital role in removing a broad variety of anionic drugs from kidney, thus avoiding their possible toxicity in the body. In the current study, we investigated the role of insulin-like growth factor 1 (IGF-1) in the regulation of OAT3. We showed that IGF-1 induced a dose- and time-dependent increase in OAT3 transport activity, which correlated well with an increase in OAT3 expression. The IGF-1-induced increase in OAT3 expression was blocked by protein kinase A (PKA) inhibitor H89. Moreover, IGF-1 induced an increase in OAT3 phosphorylation, which was also blocked by H89. These data suggest that the IGF-1 modulation of OAT3 occurred through PKA signaling pathway. To further confirm the involvement of PKA, we treated OAT3-expressing cells with PKA activator Bt2-cAMP, followed by examining OAT activity and phosphorylation. We showed that OAT3 activity and phosphorylation were much enhanced in Bt2-cAMP-treated cells as compared to that in control cells. Finally, linsitinib, an anticancer drug that blocks the IGF-1 receptor, abrogated IGF-1-stimulated OAT3 transport activity. In conclusion, our study demonstrated that IGF-1 regulates OAT3 expression and transport activity through PKA signaling pathway, possibly by phosphorylating the transporter.
Updated Cost-effectiveness Analysis of Evolocumab in Patients With Very High-risk Atherosclerotic Cardiovascular Disease
Authors: Gregg C. Fonarow, Ben van Hout, Guillermo Villa, Jorge Arellano, Peter Lindgren
Journal: JAMA Cardiology (2019)

In October 2018, evolocumab was made available at a reduced annual list price of $5850 in the United States. This 60% reduction was aimed at improving patient access by lowering patient copays. Shortly thereafter, the 2018 American College of Cardiology/American Heart Association cholesterol management guideline was released. An updated cost-effectiveness analysis of evolocumab in the United States may be therefore of interest to payers and prescribers.