tbuckley/cabot-search huggingface dataset:
Abstract #850: Cytotoxic activity of two pleurocidin-like cationic antimicrobial peptides against human breast cancer cells
Authors: Ashley Hilchie, Aleksander Patrzykat, Susan Douglas, David Hoskin
Journal: Cancer Research (2009)

Cationic antimicrobial peptides are small peptides that constitute an important defense against microbial pathogens and, in some cases, also exhibit potent cytotoxic activity against cancer cells. Atlantic pleuronectid flatfish are a particularly rich source of cationic antimicrobial peptides, including NRC-03 and NRC-07, which are pleurocidin-like peptides derived from winter and yellowtail flounder, respectively. The purpose of this investigation was to evaluate the potential of NRC-03 and NRC-07 as novel cytotoxic agents for the treatment of breast cancer. Colorimetric MTT and LDH-release assays showed that NRC-03 and NRC-07 rapidly killed MDA-MB-231, MDA-MB-468, MCF-7 and T47D human breast cancer cells in a time- and dose-dependent manner. Additionally, NRC-03 and NRC-07 were cytotoxic towards cisplatin-resistant human ovarian cancer cell lines. Colorimetric hemolytic assays revealed that neither NRC-03 nor NRC-07 possessed hemolytic activity. Human fibroblasts and umbilical vein endothelial cells were not harmed by NRC-03 or NRC-07; however, high concentrations of NRC-03 and NRC-07 were lytic for human T cells and mammary epithelial cells, suggesting that both peptides require modification to enhance breast cancer cell selectivity. Fluorescent microscopy revealed that fluorochrome-labeled NRC-03 and NRC-07 rapidly bound to the surface of breast cancer cells, but not human dermal fibroblasts, suggesting that peptide binding was required for cell death. Propidium iodide staining, as well as scanning electron microscopy, showed that NRC-03 and NRC-07 rapidly caused pore formation in the cellular membrane of breast cancer cells, suggesting that cell death was mediated by membrane lysis. However, flow cytometric analysis of dihydroethidium- or DiOC 6 -stained breast cancer cells revealed that NRC-03- and NRC-07-mediated cytotoxicity was also associated with reactive oxygen species production and mitochondrial membrane destabilization, respectively. Nevertheless, the pan-caspase inhibitor BOC-D-FMK did not prevent NRC-03- and NRC-07-induced cytotoxicity, supporting the hypothesis that NRC-03 and NRC-07 act primarily through a membrane-lytic mechanism. We conclude that NRC-03 and NRC-07 warrant further investigation as novel therapeutic agents for the treatment of breast cancer.  Supported by Natural Science and Engineering Research Council of Canada, the Cancer Research Training Program, and the Canadian Breast Cancer Foundation - Atlantic Region    Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 850.
Comparison of Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation of G-CSF-Stimulated Bone Marrow Versus Non-Stimulated Bone Marrow Versus Peripheral Blood
Authors: Ilana Schlam, Samantha Buszek, Matan R Rothschild, Miguel Islas-Ohlmayer, James Essell
Journal: Blood (2017)
Boris Johnson is criticised for repeating claims that NHS will benefit from Brexit
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Michael Marmot, a leading public health expert, has censured the UK foreign secretary and Brexit campaigner Boris Johnson for repeating a claim that the NHS would benefit from at least £350m (€395m; $483m) extra income a week once it leaves the European Union.

Marmot said that the figure, which was infamously emblazoned on the Vote Leave campaign’s “battle bus” before the referendum, had twice been discredited by the UK Statistics Authority, and he accused Johnson of misleading the British people.

The rebuke came after Johnson told …
Efficacy and safety of fosfomycin plus imipenem versus vancomycin for complicated bacteraemia and endocarditis due to methicillin-resistant Staphylococcus aureus: a randomized clinical trial
Authors: J.M. Pericàs, A. Moreno, M. Almela, C. García-de-la-Mària, F. Marco, P. Muñoz, C. Peña, A. de Alarcón, A. del Río, A. Eworo, A. Cruceta, J.C. Paré, C.A. Mestres, J.M. Miró, José M. Miró, Asunción Moreno, Juan M. Pericàs, Juan Ambrosioni, Adrián Tellez, Marta Hernandez-Meneses, Ana del Río, Carlos Cervera, Francesc Marco, Cristina Garcia de la Mària, Yolanda Armero, Manel Almela, Carlos A. Mestres, Juan C. Paré, David Fuster, Ramón Cartañá, Salvador Ninot, Manel Azqueta, Marta Sitges, Jose Ramírez, Merce Brunet, Dolors Soy, Jaume Llopis, Carmen Peña, Oriol Gasch, Cristina Suarez, Miquel Pujol, Javier Ariza, Jordi Carratalà, Francisco Gudiol, Patricia Muñoz, Alia Eworo, Emilio Bouza, Arístides de Alarcón, Mercè Gurgui, Natividad Benito, Juan-Emilio Losa-Garcia, Enrique Navas, Jose R. Paño-Pardo, Belén Loeches, Jose R. Arribas, Miguel Montejo, Juan Galvez
Journal: Clinical Microbiology and Infection (2018)
Outpatient Worsening Heart Failure as a Target for Therapy
Authors: Stephen J. Greene, Robert J. Mentz, G. Michael Felker
Journal: JAMA Cardiology (2018)

<h3>Importance</h3> Hospitalizations for worsening heart failure (WHF) represent an enormous public health and financial burden, with physicians, health systems, and payers placing increasing emphasis on hospitalization prevention. In addition, maximizing time out of the hospital is an important patient-centered outcome. In this review, we discuss the concept of outpatient WHF, highlight the rationale and data for the outpatient treatment of WHF as an alternative to hospitalization, and examine opportunities and strategies for developing outpatient “interceptive” therapies for treatment of worsening symptoms and prevention of hospitalization. <h3>Observations</h3> Worsening heart failure has traditionally been synonymous with an episode of in-hospital care for worsening symptoms. While WHF often leads to hospitalization, many patients experience WHF in the outpatient setting and carry a similarly poor prognosis. These findings support WHF as a distinct condition, independent of location of care. For those that are hospitalized, most patients have an uncomplicated clinical course, with diuretics as the only intravenous therapy. Although complicated scenarios exist, it is conceivable that improved tools for outpatient management of clinical congestion would allow a greater proportion of hospitalized patients to receive comparable care outside the hospital. Most patients with WHF have a gradual onset of congestive signs and symptoms, offering a potential window in which effective therapy may abort continued worsening and obviate the need for hospitalization. To date, outpatient WHF has received minimal attention in randomized clinical trials, but this high-risk group possesses key features that favor effective clinical trial investigation. <h3>Conclusions and Relevance</h3> As the public health and economic burdens of heart failure continue to grow, recognizing the entity of outpatient WHF is critical. Efforts to reduce heart failure hospitalization should include developing effective therapies and care strategies for outpatient WHF. The outpatient WHF population represents a major opportunity for therapeutic advancements that could fundamentally change heart failure care delivery.
Quadrupling Inhaled Glucocorticoid Dose to Abort Asthma Exacerbations
Authors: Tricia McKeever, Kevin Mortimer, Andrew Wilson, Samantha Walker, Christopher Brightling, Andrew Skeggs, Ian Pavord, David Price, Lelia Duley, Mike Thomas, Lucy Bradshaw, Bernard Higgins, Rebecca Haydock, Eleanor Mitchell, Graham Devereux, Timothy Harrison
Journal: New England Journal of Medicine (2018)

Asthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma.We conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without add-on therapy, and who had had at least one exacerbation in the previous 12 months. We compared a self-management plan that included an increase in the dose of inhaled glucocorticoids by a factor of 4 (quadrupling group) with the same plan without such an increase (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma.A total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45%) in the quadrupling group as compared with 484 (52%) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.71 to 0.92; P=0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group.In this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN15441965 .).
Discounted Drugs for Needy Patients and Hospitals — Understanding the 340B Debate
Authors: Walid F. Gellad, A. Everette James
Journal: New England Journal of Medicine (2018)

In the latest chapter in a long-playing drama, Medicare is reducing payments to hospital outpatient departments for prescription drugs in the 340B Drug Pricing Program. The cuts have been lauded by patient advocacy groups and the drug industry but not by hospitals.
In vitro and therapeutic effects of green tea extract on oral leukoplakia
Authors: Yuko Sagesaka, Shoichi Inoue, Yoji Shimizu, Akira Katakura, Takashi Shibahara, Nobuo Takano, Noriyuki Suda
Journal: Cancer Research (2007)

1679   Leukoplakia is well known as a precancerous lesion of oral squamous cell carcinoma. Therefore, it is important to treat leukoplakia for preventing patients from oral cancer. In this study, we analyzed effects of green tea extract (GTE) on eight human oral cancer cell lines. Thereafter, we applied a GTE ointment for oral leukoplakia and investigated efficacy and histopathological changes.  IC50s of GTE and GTE ointment on eight cell lines ranged between 74.1 and 313 ug/ml and between 21.8 and 77.9 ug/ml, respectively. Thus, GTE ointment was more effective than GTE in vitro. From these results, we produced 10% GTE ointment and applied it to patients.  Ten consenting patients with oral leukoplakia after histopathologic examination of biopsy material (6 men and 4 women) between August 2005 and January 2006 were treated with 0.5 g of a 10% GTE ointment for at least 60 days by applying to the affected area three times a day. Each lesion was monitored macroscopically. The serum concentration of catechin was measured before, during, and after administration. In addition, biopsy was performed before and after administration, and immunohistochemical techniques (ki-67LI ) were used to ascertain changes in cellular proliferation and apoptosis. No clinical or laboratory adverse reactions were seen during or after administration. Macroscopic observations revealed leukoplakia disappeared, reduction or thinning of leukoplakia in four patients. The serum concentration of EGCg increased immediately after administration and remained high throughout the administration period. When leukoplakia disappeared histopathologically, the new oral tissue was histologically healthy, and even when leukoplakia did not disappear, favorable changes  in ki-67LI occurred before and after administration. These findings suggest the effectiveness of local GTE administration in the treatment of oral leukoplakia.
Prevalence of Irritable Bowel Syndrome and Chronic Fatigue 10 Years After Giardia Infection
Authors: Sverre Litleskare, Guri Rortveit, Geir Egil Eide, Kurt Hanevik, Nina Langeland, Knut-Arne Wensaas
Journal: Clinical Gastroenterology and Hepatology (2018)

Irritable bowel syndrome (IBS) is a complication that can follow gastrointestinal infection, but it is not clear if patients also develop chronic fatigue. We investigated the prevalence and odds ratio of IBS and chronic fatigue 10 years after an outbreak of Giardia lamblia, compared with a control cohort, and changes in prevalence over time.We performed a prospective follow-up study of 1252 laboratory-confirmed cases of giardiasis (exposed), which developed in Bergen, Norway in 2004. Statistics Norway provided us with information from 2504 unexposed individuals from Bergen, matched by age and sex (controls). Questionnaires were mailed to participants 3, 6, and 10 years after the outbreak. Results from the 3- and 6-year follow-up analyses have been published previously. We report the 10-year data and changes in prevalence among time points, determined by logistic regression using generalized estimating equations.The prevalence of IBS 10 years after the outbreak was 43% (n = 248) among 576 exposed individuals and 14% (n = 94) among 685 controls (adjusted odds ratio for development of IBS in exposed individuals, 4.74; 95% CI, 3.61-6.23). At this time point, the prevalence of chronic fatigue was 26% (n = 153) among 587 exposed individuals and 11% (n = 73) among 692 controls (adjusted odds ratio, 3.01; 95% CI, 2.22-4.08). The prevalence of IBS among exposed persons did not change significantly from 6 years after infection (40%) to 10 years after infection (43%; adjusted odds ratio for the change 1.03; 95% CI, 0.87-1.22). However, the prevalence of chronic fatigue decreased from 31% at 6 years after infection to 26% at 10 years after infection (adjusted odds ratio for the change 0.74; 95% CI, 0.61-0.90).The prevalence of IBS did not change significantly from 6 years after an outbreak of Giardia lamblia infection in Norway to 10 years after. However, the prevalence of chronic fatigue decreased significantly from 6 to 10 years afterward. IBS and chronic fatigue were still associated with giardiasis 10 years after the outbreak.
Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial
Authors: Richard E Pratley, Vanita R Aroda, Ildiko Lingvay, Jörg Lüdemann, Camilla Andreassen, Andrea Navarria, Adie Viljoen
Journal: The Lancet Diabetes & Endocrinology (2018)
Management of incidental adrenal tumours
Authors: Fahmy W F Hanna, Basil G Issa, Julius Sim, Brian Keevil, Anthony A Fryer
Journal: BMJ (2018)

### What you need to know

### Sources and selection criteria

References were selected from Medline search, focusing on published guidelines. Sub-references were selected to ensure full coverage of the areas identified within the initial search.

An incidental adrenal tumour, described in this article as an “adrenal incidentaloma,” is an adrenal mass discovered during imaging that was not performed for suspected adrenal disease. These are being detected more frequently in an ageing population1 through the increased use of computed tomography (eg, computed tomography urogram, or colonoscopy) and magnetic resonance imaging (MRI) scans with enhanced resolution.2

This article highlights the management of adrenal incidentalomas, collating recommendations from international guidelines, and is aimed at non-specialists.

Adrenal incidentalomas are defined as adrenal masses incidentally discovered during imaging that was not performed for suspected adrenal disease. Hence, an adrenal lesion discovered while investigating raised catecholamines would not be classified as an adrenal incidentaloma. Most definitions have restricted the diagnosis to lesions ≥10 mm34 unless there are clinical stigmas of adrenal hormone over-production identified after the detection of the lesion that warrant further investigation.

In view of variation in diagnostic criteria, referral patterns, and surgical rates, it is challenging to precisely classify the underlying adrenal incidentaloma pathology from published literature.2Figure 1 provides a simplified description of the adrenal gland components, their role, and the consequences of excess hormone production.



Fig 1 
The components of the adrenal gland and consequences of excess hormone production



Prevalence is estimated between ~2% (range 1.0%-8.7%) from autopsy studies3 …
WITHDRAWN: Efficacy and safety of topical oxymetazoline cream 1.0% for treatment of persistent facial erythema associated with rosacea: findings from the 2 phase 3, 29-day, randomized, controlled REVEAL trials
Authors: Linda Stein-Gold, Leon H Kircik, Zoe Diane Draelos, Philip Werschler, Janet DuBois, Edward Lain, Leslie Baumann, David J Goldberg, Joely Kaufman, Emil A Tanghetti, Nancy Alvandi, Emily Weng, David R Berk, Gurpreet Ahluwalia
Journal: Journal of the American Academy of Dermatology (2018)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
Abstract 15401: Electrical Vagal Nerve Stimulation Significantly Redresses Autonomic Balance, Lowers Pulmonary Vascular Resistance and Improves Survival in Rats With Pulmonary Arterial Hypertension
Authors: Keimei Yoshida, Keita Saku, Kazuhiro Kamada, Mariko Tanaka, Takuya Akashi, Kohtaro Abe, Takuya Kishi, Kenji Sunagawa, Hiroyuki Tsutsui
Journal: Circulation (2017)

Introductions: Autonomic imbalance play a crucial role in the pathophysiology of pulmonary arterial hypertension (PAH). Electrical vagal nerve stimulation (VNS) is known to redress autonomic balanc...
Outcome measures in coeliac disease trials: the Tampere recommendations
Authors: Jonas F Ludvigsson, Carolina Ciacci, Peter HR Green, Katri Kaukinen, Ilma R Korponay-Szabo, Kalle Kurppa, Joseph A Murray, Knut Erik Aslaksen Lundin, Markku J Maki, Alina Popp, Norelle R Reilly, Alfonso Rodriguez-Herrera, David S Sanders, Detlef Schuppan, Sarah Sleet, Juha Taavela, Kristin Voorhees, Marjorie M Walker, Daniel A Leffler
Journal: Gut (2018)

Objective A gluten-free diet is the only treatment option of coeliac disease, but recently an increasing number of trials have begun to explore alternative treatment strategies. We aimed to review the literature on coeliac disease therapeutic trials and issue recommendations for outcome measures. Design Based on a literature review of 10 062 references, we (17 researchers and 2 patient representatives from 10 countries) reviewed the use and suitability of both clinical and non-clinical outcome measures. We then made expert-based recommendations for use of these outcomes in coeliac disease trials and identified areas where research is needed. Results We comment on the use of histology, serology, clinical outcome assessment (including patient-reported outcomes), quality of life and immunological tools including gluten immunogenic peptides for trials in coeliac disease. Conclusion Careful evaluation and reporting of outcome measures will increase transparency and comparability of coeliac disease therapeutic trials, and will benefit patients, healthcare and the pharmaceutical industry.
A phase 1, multicenter, dose-escalation study of PRN1371, an irreversible covalent FGFR1-4 kinase inhibitor, in patients with advanced solid tumors, followed by expansion cohorts in patients with FGFR genetic alterations.
Authors: Sarina Anne Piha-Paul, Cinta Hierro, Jens Oliver Funk, Steven Gourlay, Patrick Smith, Eleni Venetsanakos, Funda Meric-Bernstam, Josep Tabernero
Journal: Journal of Clinical Oncology (2016)

TPS2602 Background: FGFR inhibition is a promising therapeutic approach in a number of solid tumors where genetic alterations of FGFR drive tumor cell proliferation, and survival. PRN1371 is an oral, potent, irreversible inhibitor of FGFR1-4 that has shown high potency against many FGFR-aberrant cell lines. Methods: Part A of this phase 1 clinical trial explores ascending doses of PRN1371 in adult patients with advanced solid tumors in a
Indoor bacteria and asthma in adults: a multicentre case–control study within ECRHS II
Authors: Juha Pekkanen, Maria Valkonen, Martin Täubel, Christina Tischer, Hanna Leppänen, Päivi M. Kärkkäinen, Helena Rintala, Jan-Paul Zock, Lidia Casas, Nicole Probst-Hensch, Bertil Forsberg, Mathias Holm, Christer Janson, Isabelle Pin, Thorarinn Gislason, Debbie Jarvis, Joachim Heinrich, Anne Hyvärinen
Journal: European Respiratory Journal (2018)

Both protective and adverse effects of indoor microbial exposure on asthma have been reported, but mostly in children. To date, no study in adults has used non-targeted methods for detection of indoor bacteria followed by quantitative confirmation.A cross-sectional study of 198 asthmatic and 199 controls was conducted within the European Community Respiratory Health Survey (ECRHS) II. DNA was extracted from mattress dust for bacterial analysis using denaturing gradient gel electrophoresis (DGGE). Selected bands were sequenced and associations with asthma confirmed with four quantitative PCR (qPCR) assays.15 out of 37 bands detected with DGGE, which had at least a suggestive association (p<0.25) with asthma, were sequenced. Of the four targeted qPCRs, Clostridium cluster XI confirmed the protective association with asthma. The association was dose dependent (aOR 0.43 (95% CI 0.22-0.84) for the fourth versus first quartile, p for trend 0.009) and independent of other microbial markers. Few significant associations were observed for the three other qPCRs used.In this large international study, the level of Clostridium cluster XI was independently associated with a lower risk of prevalent asthma. Results suggest the importance of environmental bacteria also in adult asthma, but need to be confirmed in future studies.
Motor Cortex Embeds Muscle-like Commands in an Untangled Population Response
Authors: Abigail A. Russo, Sean R. Bittner, Sean M. Perkins, Jeffrey S. Seely, Brian M. London, Antonio H. Lara, Andrew Miri, Najja J. Marshall, Adam Kohn, Thomas M. Jessell, Laurence F. Abbott, John P. Cunningham, Mark M. Churchland
Journal: Neuron (2018)