tbuckley/cabot-search huggingface dataset:
Abstract #4013: Imaging a secretory protein in a pancreatic tumor xenograft model
Authors: Shi Ke, Wei Wang, Anshul Haldipur, Zhimin Tong, Arlin Cameron, Michel Mawad, Yoichi Matsuo, Sushovan Guha
Journal: Cancer Research (2009)

Neutrophil gelatinase-associated lipocalin (NGAL) or Lipocalin 2 is a 25-kDa secreted glycoprotein. NGAL is an acute phase protein and is upregulated in multiple inflammatory conditions including inflammatory bowel disease and acute renal injury. Interestingly, NGAL is also upregulated in neoplastic diseases including colorectal, breast, ovarian, pancreatic, and esophageal cancers. A recent study reported increased NGAL expression in early pancreatic intraepithelial neoplastic stages (PanIN-1 and PanIN-2). Thus, NGAL can be a biomarker of early neoplastic transformations in pancreatic ducts. The purpose of our study was to develop an antibody imaging agent and test the feasibility of imaging a secretory protein in a pancreatic tumor xenograft model. We labeled a monoclonal NGAL-specific antibody with a near infrared (NIR) dye and performed  in vitro  and  in vivo  imaging studies. Cell binding studies demonstrated that both pancreatic cancer cell lines AsPC-1 and Panc-1 were bound to NIR dye labeled NGAL antibody. The confocal imaging studies suggested that the NIR dye labeled NGAL antibody was also internalized by some cells. Nuclear extraction assays followed by western blots confirmed our confocal imaging findings. Cell fractionation assays demonstrated that the majority of NGAL antibody was localized in the cytosolic compartment and a small fraction of it was localized in the nuclear compartment. The whole body and organ imaging studies showed the anatomic location of the primary tumor (subcutaneous heterotopic model) in an intact animal as well as the dissected layout of the organs. The NIR images showed the distribution of NGAL-specific antibody. The whole body images distinctly showed the localization of the signal intensities in the primary tumor, liver, kidneys, and bladder. The images of the dissected organs also demonstrated antibody signals from the primary tumor, liver, kidneys, and bladder. These results confirmed the whole body imaging data. Interestingly, spleen also showed high signal intensity in the organ specific optical imaging studies. The overlaid images colocalized signals from different energies: white light/X-ray; white light/NIR; and X-ray/NIR. Tumor-to-background ratio analysis revealed that the tumor had a higher signal intensity than muscle with a mean tumor-to-muscle ratio of 1.18 (1.02-1.51, n=4). In conclusion, we demonstrated that the secretory protein can be successfully imaged using a NIR dye labeled antibody. The antibody not only can bind to the protein but also can be internalized into cancer cells. This work is supported in part by the grant from the Texas Medical Center Digestive Diseases Center (NIH DK56338) and the Department of Radiology. SK*, WW* These authors contributed equally to this work.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4013.
<i>Lactobacillus rhamnosus</i> GG versus Placebo for Acute Gastroenteritis in Children
Authors: David Schnadower, Phillip I. Tarr, T. Charles Casper, Marc H. Gorelick, J. Michael Dean, Karen J. O’Connell, Prashant Mahajan, Adam C. Levine, Seema R. Bhatt, Cindy G. Roskind, Elizabeth C. Powell, Alexander J. Rogers, Cheryl Vance, Robert E. Sapien, Cody S. Olsen, Melissa Metheney, Viani P. Dickey, Carla Hall-Moore, Stephen B. Freedman
Journal: New England Journal of Medicine (2018)

Acute gastroenteritis develops in millions of children in the United States every year, and treatment with probiotics is common. However, data to support the use of probiotics in this population are limited.We conducted a prospective, randomized, double-blind trial involving children 3 months to 4 years of age with acute gastroenteritis who presented to one of 10 U.S. pediatric emergency departments. Participants received a 5-day course of Lactobacillus rhamnosus GG at a dose of 1×1010 colony-forming units twice daily or matching placebo. Follow-up surveys were conducted daily for 5 days and again 14 days after enrollment and 1 month after enrollment. The primary outcome was moderate-to-severe gastroenteritis, which was defined as an illness episode with a total score on the modified Vesikari scale of 9 or higher (scores range from 0 to 20, with higher scores indicating more severe disease), within 14 days after enrollment. Secondary outcomes included the duration and frequency of diarrhea and vomiting, the duration of day-care absenteeism, and the rate of household transmission (defined as the development of symptoms of gastroenteritis in previously asymptomatic household contacts).Among the 971 participants, 943 (97.1%) completed the trial. The median age was 1.4 years (interquartile range, 0.9 to 2.3), and 513 participants (52.9%) were male. The modified Vesikari scale score for the 14-day period after enrollment was 9 or higher in 55 of 468 participants (11.8%) in the L. rhamnosus GG group and in 60 of 475 participants (12.6%) in the placebo group (relative risk, 0.96; 95% confidence interval, 0.68 to 1.35; P=0.83). There were no significant differences between the L. rhamnosus GG group and the placebo group in the duration of diarrhea (median, 49.7 hours in the L. rhamnosus GG group and 50.9 hours in the placebo group; P=0.26), duration of vomiting (median, 0 hours in both groups; P=0.17), or day-care absenteeism (median, 2 days in both groups; P=0.67) or in the rate of household transmission (10.6% and 14.1% in the two groups, respectively; P=0.16).Among preschool children with acute gastroenteritis, those who received a 5-day course of L. rhamnosus GG did not have better outcomes than those who received placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01773967 .).
AB0080 Differential effects of tr14 versus diclofenac on pro-resolving lipid mediators revealed by rnaseq
Authors: G. St. Laurent, I. Toma, M. Tackett, J. Zhou, M. Ri, D. Shtokalo, Y. Vyatkin, T. Jepson, K. Cesnulevicius, B. Seilheimer, T. Mccaffrey
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Anti-inflammatory agents are used widely in treating numerous pain and inflammatory conditions. With a focus on the specialised pro-resolving mediators (SPM) pathways in cutaneous wound repair in mice, the therapeutic activities of Tr14 (Traumeel), a multicomponent/multitarget natural product, and diclofenac (NSAID), a non-selective cyclooxygenase (COX) inhibitor were compared. COX inhibitors can block the synthesis of prostaglandins and thromboxanes from arachidonic acid, and can have important effects on the synthesis of resolvins and protectins produced by similar enzymes from eicosopentanoic and docosohexanoic acid substrates. Differential effects were identified via transcriptome analysis (RNAseq). <h3>Objectives</h3> To compare the transcriptomic changes after administration of Tr14 or diclofenac in a mouse cutaneous wound healing model, with particular emphasis on the SPM pathways, which include resolvins and protectins. <h3>Methods</h3> After abrasive wounding, the wounds were treated with topical Tr14 (34 mg/ml) in combination with subcutaneous Tr14 injections (9.5 mg/ml), or with subcutaneous Tr14 injections only, or topical diclofenac at clinically relevant doses (2 mg/ml). Skin samples were analysed for RNA transcript profiling by RNAseq at specific times (12 hour, 24 hour, 36 hour, 72 hour, 96 hour, 120 hour, 192 hour) after injury. Differentially expressed genes (DEGs) were computed at each time point between diclofenac vs control or Tr14 vs control, using EdgeR. <h3>Results</h3> At early time points (12–36 hour), Tr14-treated wounds, and to a lesser extent diclofenac-treated wounds, showed marked induction of 3 lipoxygenase enzyme mRNAs involved in SPM synthesis. Even more striking was a pronounced effect of Tr14 at 12–36 hours on Fpr1 and Fpr2 mRNAs, which are the transmembrane receptors for the SPM lipid mediators. Consistent with elevated levels of enzymes regulating SPM synthesis, and SPR receptors, there was a noticeable decrease in the mRNA levels of the p65/RelA subunit of NFkB at 72–96 hours. NFkB is a critical transcription factor in inflammation, regulating numerous cytokines and chemokines. <h3>Conclusions</h3> Tr14 and diclofenac had very different effects on the SPM synthetic pathway after cutaneous wounding. Tr14 stimulated mRNA levels of several key regulators of SPM synthesis, and had a marked effect on the mRNA levels of the SPM receptors. Tr14, <i>not</i> diclofenac, suppressed mRNA levels for NFkB subunit p65/RelA, which may explain some of the anti-inflammatory and proresolving properties of Tr14. <h3>Disclosure of Interest</h3> None declared
Efficacy and safety of modified ECF regimen as first-line chemotherapy in metastatic gastric adenocarcinoma: A phase II study
Authors: T. Chaudhuri, K.G. Babu, K.C. Lakshmaiah, L. Dasappa, L.A. Jacob, M.C.S. Babu, K.N. Lokesh, A.H. Rudresha, L.K. Rajeev, R. Patidar, V. Asati, R. Chethan, D. Koppaka, A. Anand
Journal: Annals of Oncology (2018)
Inconsistent Reporting of Potential Conflicts of Interest in <i>JAMA Pediatrics</i>
Authors: Mark B. McClellan
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Ban on legal highs fails to curb use among children
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The government’s ban on legal highs has failed to reduce their use among children and vulnerable adults and has driven their sale underground, an official Home Office review has found.1

The review assessed the impact of the 2016 Psychoactive Substances Act, which banned the production, distribution, sale, and supply of most psychoactive substances.

Sales of novel psychoactive substances (NPS; so called “legal highs”) in shops and online have been “largely eliminated” by the legislation, but this has driven the sale of the products underground, the review said. “The evidence suggests that the main source of supply for NPS is now …
Abstract 17482: Biventricular Cardiac Dysfunction in Neurocardiac Injury Assessed by Strain Imaging is Associated With In Hospital Mortality in Subarachnoid Hemorrhage
Authors: Nobuyuki Kagiyama, Masataka Sugahara, Nina E Hasselberg, Eliabeth A Crago, Theodore F Lagattuta, Khalil M Yousef, Marilyn T Hravnak, John Gorcsan
Journal: Circulation (2017)

Introduction: Aneurysmal subarachnoid hemorrhage (SAH) is associated with variable degrees of neuro-cardiac injury. Strain imaging is a sensitive means to quantify both left (LV) and right ventricular (RV) function. Effects of neuro-cardiac on biventricular function in SAH and their prognostic value are unknown. Hypothesis: We hypothesized that in SAH, LV and RV dysfunction can be detected by LV and RV speckle tracking echocardiography (STE) and are associated with prognosis. Methods: We studied 255 patients with acute SAH in the SAHMII study (R01NR04221). Using strain imaging obtained acutely (mean 2.3 days from bleed), LV global longitudinal strain (GLS) from 3 apical views and RV free wall strain from apical 4-chamber view were assessed. Strain values were presented in absolute values and LV strain < 17% and RV strain < 20% were defined as abnormal. In-hospital mortality was the outcome variable. Results: LV and RV strain were feasible in 221 (89%) and 159 (64%) patients (7 were excluded with previous ...
The Elusive Late Benefit of Biodegradable Polymer Drug-Eluting Stents
Authors: Sripal Bangalore
Journal: Circulation (2019)

Article, see p 325 D rug eluting stents (DES), the standard-of-care stents in contemporary percutaneous coronary intervention, significantly reduce the risk of restenosis in comparison with bare metal stents (BMS).However, first-generation durable polymer (DP) DES were associated with high rates of very late (>1 year) events such as restenosis, stent thrombosis, and neoatherosclerosis, events attributed to a persistent inflammation/hypersensitivity reaction to the polymer. 1 The solutions to this polymer-related problem proceeded in 3 directions: (1) development of more biocompatible DP that reduces inflammation and promotes faster healing; (2) development of biodegradable (BP) polymer that biodegrades after drug elution, leaving behind a BMS-like stent; and (3) development of polymer-free DES where the drug is delivered without a polymer and is therefore a BMS-like stent.The clinical gains from improvement in the polymer-related aspects of stent design have been apparent.The second-generation DP-DES have lower risk of restenosis, stent thrombosis, myocardial infarction (MI), and death in comparison with BMS or first-generation DP-DES. 2,3Despite these excellent results with the second-generation DP-DES, major adverse cardiovascular events continue to accrue beyond 1 year at a steady rate.This has been attributed to continued low-grade peri-strut inflammation and promotion of neoatherosclerosis with the second-generation DP-DES.As such, BP-DES were touted as the future of DES technology. 4linical trials of BP-DES showed lower restenosis and stent thrombosis in comparison with the first-generation DP-DES, although the results have been variable. 2However, the more important question has been the comparison of BP-DES with the second-generation DP-DES.Cumulative data from meta-analyses of randomized trials suggest, at best, the noninferiority of BP-DES in comparison with second-generation DP-DES. 5Given the short duration of these trials, many have posited that the benefits of BP-DES will be seen at longer duration of follow-up after the polymer fully biodegrades (over months to years depending on the polymer). 6he 10-year outcomes of the ISAR-Test 4 trial (Intracoronary Stenting and Angiographic Results: Test Efficacy of 3 Limus-Eluting Stents) in the current issue of Circulation 7 provide further insights into this question.The ISAR-Test 4 trial enrolled 2603 patients with coronary artery disease who were randomly assigned 2:1:1 to the Yukon Choice PC stent (a BP-DES coated on the abluminal surface of a stent [87 µm thick] with a unique microporous surface) versus the Xience stent (a second-generation DP-DES [81 µm thick]) versus the Cypher stent (a first-generation DP-DES [140 µm thick]).The trial showed noninferiority of the BP-DES in comparison with DP-DES at 1 year and concluded that "the results provide a framework for testing the potential clinical advantage of BP-DES over the medium to longterm." 6At 10 years follow-up, the second-generation DP-DES, and the BP-DES,
Abstract 11518: Diastolic Left Ventricular Dysfunction is a Common and Early Cardiac Abnormality in Hutchinson-Gilford Progeria Syndrome
Authors: Ashwin Prakash, Leslie B Gordon, Monica E Kleinman, Ralph D'Agostino, Joe Massaro, Mark W Kieran, Marie Gerhard-Herman, Leslie B Smoot
Journal: Circulation (2015)

Introduction: Hutchinson-Gilford progeria syndrome (HGPS) is associated with premature death due to cardiovascular events. However, little is known about the natural history of cardiac disease in this population. We prospectively evaluated children with HGPS to identify echocardiographic abnormalities in ventricular and valve function and to assess the effect of treatment on these abnormalities. Methods and Results: Transthoracic echocardiography was used to evaluate 51 children with HGPS (45 with classic type, 6 with non-classic type; 55% males) at a median age of 10.7 (2.4-19.8) years. Among the study population, 19 were evaluated prior to entry into an open label drug trial of the farnesyltransferase inhibitor lonafarnib while the other 32 were receiving combination therapy with lonafarnib, pravastatin and zoledronic acid (triple therapy) at the time of evaluation. As seen in the Table, diastolic dysfunction diagnosed using pulsed wave tissue Doppler was the most common cardiac abnormality at all ages, developing early and present universally beyond 12.1 years of age. Other cardiac abnormalities including left ventricular hypertrophy (LVH), LV systolic dysfunction, and mitral or aortic valve disease were less common and appeared later. Using multiple linear regression to control for age and gender, patients receiving triple therapy demonstrated less severe LV diastolic dysfunction evidenced by higher lateral E’ velocities (p=0.01) and lower mitral inflow E velocity/lateral E’ velocity ratio (p=0.006). Other cardiac abnormalities were not associated with triple therapy. Conclusions: In patients with Hutchinson-Gilford progeria syndrome, LV diastolic dysfunction is common and appears early. Other cardiac abnormalities are less common and appear at a later age. Triple therapy is associated with less severe diastolic dysfunction. Echocardiographic parameters of LV diastolic dysfunction may be useful endpoints in future clinical trials.
Comparison between robot-assisted radical prostatectomy and minimum incision endoscopic radical prostatectomy for high-risk prostate cancer following neoadjuvant therapy: A propensity score-matched analysis
Authors: A. Imai, H. Yamamoto, S. Hatakeyama, T. Yoneyama, Y. Hashimoto, C. Ohyama
Journal: Annals of Oncology (2018)
Serum Concentrations of 7α-hydroxy-4-cholesten-3-one Are Associated With Bile Acid Diarrhea in Patients With Crohn’s Disease
Authors: Robert Battat, Marjolijn Duijvestein, Niels Vande Casteele, Siddharth Singh, Parambir S. Dulai, Mark A. Valasek, Larry Mimms, Judson McFarland, Kelly D. Hester, Mark Renshaw, Anjali Jain, William J. Sandborn, Brigid S. Boland
Journal: Clinical Gastroenterology and Hepatology (2018)
Probiotics for Children with Gastroenteritis
Authors: J. Thomas LaMont
Journal: New England Journal of Medicine (2018)

In clinical practices for adults and children, probiotics — live bacteria that are intended to have a beneficial effect in the host — are frequently recommended to treat a wide variety of diarrheal diseases. The results of thousands of studies of probiotics have been published, and most of them have shown that probiotics are effective in treating or preventing various forms of acute and chronic diarrhea. Acute infectious gastroenteritis in children remains a major public health issue, particularly in low-income countries, where this condition accounts for substantial neonatal mortality. Follow-up from one study1 that enrolled more than 20,000 infants and . . .
FRI0115 Indirect standardised assessment of injection site pain following subcutaneous administration of citrate-free formulation of adalimumab and its biosimilar abp 501
Authors: E. Krishnan, N. Zhang, H. Wang, R. Kaushik
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In randomised double-blind studies in patients with rheumatoid arthritis (RA) and psoriasis (PsO), ABP 501, an approved adalimumab biosimilar, had significantly lower injection site pain (ISP) perception compared with the citrate-containing formulation (CCF) of adalimumab reference product (RP) (40 mg/0.8 mL); however, there have been no direct or indirect comparisons of ISP perception between ABP 501 and the CFF of the RP (40 mg/0.4 mL). <h3>Objectives</h3> To demonstrate that pain perception after injection of both the ABP 501 formulation and the CFF-RP formulation was lower than after CCF-RP. <h3>Methods</h3> We analysed ISP perception data after injection from two ABP 501 phase 3 studies, one in patients with RA (NCT01970475) and another in patients with PsO (NCT01970488) and 2 citrate-free RP formulation studies (NCT01561313, NCT01502423) where the "control" group received the CCF-RP. In all studies, patients were equally randomised between the 2 treatment arms. Patients were asked to rate the ISP perception on a visual analogue scale (VAS) on which the current pain level was marked from 0 cm (no pain) to 10 cm (worst possible pain). We calculated Cohen's d-statistic for difference in ISP perception with ABP 501 compared with CCF-RP for the 2 ABP 501 studies. Similar comparisons were performed between the ISP perception associated with CFF-RF and CCF-RF. These measures were subsequently compared in a descriptive manner. <h3>Results</h3> Both ABP 501 and CFF-RF were associated with lower ISP perception after injection with maximum reduction observed immediately post-injection. The 95% confidence intervals of relative reduction in ISP perception for ABP 501 formulation and the CFF-RP (table 1) were provided descriptively. <h3>Conclusions</h3> Compared with CCF-RP, both ABP 501 and CFF-RP were associated with lower injection site pain perception. <h3>Reference</h3> [1] Nash P, et al. Rheumatol Ther2016;3(2):257–270. <h3>Disclosure of Interest</h3> E. Krishnan Shareholder of: Amgen Inc., Employee of: Amgen Inc., N. Zhang Shareholder of: Amgen Inc., Employee of: Amgen Inc., H. Wang Shareholder of: Amgen Inc., Employee of: Amgen Inc., R. Kaushik Shareholder of: Amgen Inc., Employee of: Amgen Inc.