tbuckley/cabot-search huggingface dataset:
Contrasting the Genetic Background of Type 1 Diabetes and Celiac Disease Autoimmunity
Authors: Javier Gutierrez-Achury, Jihane Romanos, Sjoerd F. Bakker, Vinod Kumar, Esther C. de Haas, Gosia Trynka, Isis Ricaño-Ponce, Andrea Steck, Wei-Min Chen, Suna Onengut-Gumuscu, Suat Simsek, Marian Rewers, Chris J. Mulder, Ed Liu, Stephen S. Rich, Cisca Wijmenga
Journal: Diabetes Care (2015)

Type 1 diabetes (T1D) and celiac disease (CeD) cluster in families and can occur in the same individual. Genetic loci have been associated with susceptibility to both diseases. Our aim was to explore the genetic differences between individuals developing both these diseases (double autoimmunity) versus those with only one. We hypothesized that double autoimmunity individuals carry more of the genetic risk markers that are shared between the two diseases independently. SNPs were genotyped in loci associated with T1D (n = 42) and CeD (n = 28) in 543 subjects who developed double autoimmunity, 2,472 subjects with T1D only, and 2,223 CeD-only subjects. For identification of loci that were specifically associated with individuals developing double autoimmunity, two association analyses were conducted: double autoimmunity versus T1D and double autoimmunity versus CeD. HLA risk haplotypes were compared between the two groups. The CTLA4 and IL2RA loci were more strongly associated with double autoimmunity than with either T1D or CeD alone. HLA analyses indicated that the T1D high-risk genotype, DQ2.5/DQ8, provided the highest risk for developing double autoimmunity (odds ratio 5.22, P = 2.25 × 10−29). We identified a strong HLA risk genotype (DQ2.5/DQ8) predisposing to double autoimmunity, suggesting a dominant role for HLA. Non-HLA loci, CTLA4 and IL2RA, may also confer risk to double autoimmunity. Thus, CeD patients who carry the DQ2.5/DQ8 genotype may benefit from periodic screening of autoantibodies related to T1D.
Network Adequacy Standards and Health Insurance
Authors: Ronald L. Weiss
Journal: JAMA (2015)

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
Australia's law to gag doctors with concerns about asylum seekers is a failure of democracy
Authors: D. Berger
Journal: BMJ (2015)

David Berger criticises Australia for legislating to stop doctors blowing the whistle on substandard medical care given to innocent people seeking protection

“If you have nothing to hide, you have nothing to fear.” So runs the mantra of Western governments when they want us to accept mass surveillance of phones, email, and messaging.1 The script changes, however, when the boot is on the other foot. At the slightest chance of embarrassment or an awkward question to a minister governments do their utmost to control the flow of information to prevent disclosure, irrespective of any real implications for national security.

Recently we saw a typical manifestation of this dark art when Australia passed, with bipartisan support, the Border Force Act 2015.2 3 This regressive legislation will have the effect of gagging doctors working in Australia’s notoriously harsh onshore and offshore detention centres for people seeking asylum. Contravening the act, even by revealing the absence of basic sanitary conditions, may result in a two year prison sentence.4 5 6

Only because of disclosures to the press was the broken arm of a boy detained on Nauru properly reduced and internally fixed, after more than a …
A broad-spectrum integrative design for cancer prevention and therapy: The challenge ahead
Authors: Anupam Bishayee, Keith Block
Journal: Seminars in Cancer Biology (2015)

Despite exciting advances in targeted therapies, high drug costs, marginal therapeutic benefits and notable toxicities are concerning aspects of today's cancer treatments. This special issue of Seminars in Cancer Biology proposes a broad-spectrum, integrative therapeutic model to complement targeted therapies. Based on extensive reviews of the cancer hallmarks, this model selects multiple high-priority targets for each hallmark, to be approached with combinations of low-toxicity, low-cost therapeutics, including phytochemicals, adapted to the well-known complexity and heterogeneity of malignancy. A global consortium of researchers has been assembled to advance this concept, which is especially relevant in an era of rapidly expanding capacity for genomic tumor analyses, alongside alarming growth in cancer morbidity and mortality in low- and middle-income nations.
Intravenous Diuretic Therapy for the Management of Heart Failure and Volume Overload in a Multidisciplinary Outpatient Unit
Authors: Leo F. Buckley, Danielle M. Carter, Lina Matta, Judy W. Cheng, Craig Stevens, Roman M. Belenkiy, Laura J. Burpee, Michelle A. Young, Cynthia S. Weiffenbach, Jennifer A. Smallwood, Lynne W. Stevenson, Akshay S. Desai
Journal: JACC Heart Failure (2015)
Systematic discovery of complex insertions and deletions in human cancers
Authors: Kai Ye, Jiayin Wang, Reyka Jayasinghe, Eric-Wubbo Lameijer, Joshua F McMichael, Jie Ning, Michael D McLellan, Mingchao Xie, Song Cao, Venkata Yellapantula, Kuan-lin Huang, Adam Scott, Steven Foltz, Beifang Niu, Kimberly J Johnson, Matthijs Moed, P Eline Slagboom, Feng Chen, Michael C Wendl, Li Ding
Journal: Nature Medicine (2015)
Preparations and Appliances
Authors: H M MANN
Journal: BMJ (1950)

natural history " of the disease, which must run its course under controlled conditions.After this, the best result was achieved in most cases by bony ankylosis, and the best method was that of ischio-femoral arthrodesis as described by Brittain.In their anxiety to master the local disease they had perhaps taken too light a view of the disability inseparable from stiffness.Therefore operations providing complete excision when the disease was quiescent deserved serious consideration:
Saliva in studies of epidemiology of human disease: the <scp>UK B</scp>iobank project
Authors: John W. Galloway, Bart J. F. Keijser, David M. Williams
Journal: Periodontology 2000 (2015)

Abstract There has been immense interest in the uses of saliva in the diagnosis of systemic disease over the past decade and longer because it is recognized that saliva possesses great potential as a diagnostic fluid. In spite of this, the usefulness of saliva in studies of the epidemiology of human disease has still to be properly evaluated. This review describes the UK B iobank project and explores the scope to use this and other such cohort studies to gain important insights into the epidemiological aspects of systemic disease. The B iobank holds around 85,000 well‐characterized saliva samples, together with blood and urine samples, the results of a battery of physiological tests, a full medical history and a detailed description of the subject's lifestyle. This repository is a resource for insightful and highly powered oral and dental research.
IMMUNOLOGICAL STUDIES IN RELATION TO THE SUPRARENAL GLAND
Authors: David Perla, J. Marmorston-Gottesman
Journal: The Journal of Experimental Medicine (1929)

Epinephrine diluted with physiological salt solution or with isotonic glucose solutions and injected in amounts of 0.2 mg. per kilo twice daily into suprarenalectomized rats raises their antibody forming capacity. This result is not entirely dependent on the effect of the diluting fluid.
Influence of saliva on the oral microbiota
Authors: Philip D. Marsh, Thuy Do, David Beighton, Deirdre A. Devine
Journal: Periodontology 2000 (2015)

Abstract Saliva plays a major role in determining the composition and activity of the oral microbiota, via a variety of mechanisms. Molecules, mainly from saliva, form a conditioning film on oral surfaces, thus providing receptors for bacterial attachment. The attached cells use saliva components, such as glycoproteins, as their main source of nutrients for growth. Oral bacteria work sequentially and in a concerted manner to catabolize these structurally complex molecules. Saliva also buffers the pH in the biofilm to around neutrality, creating an environment which is conducive to the growth of many oral bacteria that provide important benefits to the host. Components of the adaptive and innate host defences are delivered by saliva, and these often function synergistically, and at sublethal concentrations, so a complex relationship develops between the host and the resident microbiota. Dysbiosis can occur rapidly if the flow of saliva is perturbed.
Abstract 3480: Combinatorial apoptotic activity of capsaicin and camptothecin in human small cell lung cancer
Authors: Haley E. Perry, Kathleen C. Brown, Cathryn D. Stevenson, William D. Rollyson, Cody A. Stover, Piyali Dasgupta
Journal: Cancer Research (2015)

Abstract Small cell lung cancer (SCLC) accounts for about 13% of all lung cancer cases and is the most aggressive form of lung cancer. Cisplatin and cisplatin-based combination therapies are the cornerstone of SCLC treatment. Platinum refractoriness is defined as disease which has persisted or progressed (grown) while receiving cisplatin chemotherapy. Patients with platinum resistant or refractory disease have very limited options, as the only standard chemotherapy with an FDA-approved drug, topotecan, has an objective response rate of approximately 3% and little or no survival benefit. Topotecan is a derivative of camptothecin. The objective of our study was to examine whether capsaicin could sensitize human SCLC cells to the apoptotic effects of camptothecin. We observed that the combination of capsaicin and camptothecin displays significantly higher apoptotic activity in human SCLC cell lines as compared to either agent alone. Chou-Talalay analysis showed that the interactions between capsaicin and camptothecin were synergistic. We also measured the effect of capsaicin-camptothecin combination on several Bcl-2 family proteins, namely Bcl-2, Bax, Bak, Bcl-XL, Mcl-1, etc. The results of our studies may be of importance in therapy of platinum-refractory SCLCs. Citation Format: Haley E. Perry, Kathleen C. Brown, Cathryn D. Stevenson, William D. Rollyson, Cody A. Stover, Piyali Dasgupta. Combinatorial apoptotic activity of capsaicin and camptothecin in human small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3480. doi:10.1158/1538-7445.AM2015-3480
Randomized Phase II study of the safety, efficacy and immune response of GVAX pancreas (with cyclophosphamide) and CRS-207 with or without nivolumab in patients with previously treated metastatic pancreatic adenocarcinoma (STELLAR)
Authors: Dung T Le, Todd S Crocenzi, Jennifer N Urum, Eric R Lutz, Daniel A Laheru, Elizabeth A Sugar, Robert H Vonderheide, George A Fisher, Andrew H Ko, Aimee L Murphy, Katherine McDougall, Sandy Ferber, Dirk G Brockstedt, Elizabeth M Jaffee
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts A heterologous prime-boost vaccination strategy using GVAX pancreas vaccine and CRS-207 is showing promise in patients with pancreatic adenocarcinoma (PDA) (Le, JCO 2015). Furthermore, blockade of the immune checkpoint programmed death-1 (PD-1) is active in some cancers.
Injection of new psychoactive substance snow blow associated with recently acquired HIV infections among homeless people who inject drugs in Dublin, Ireland, 2015
Authors: Coralie Giese, Derval Igoe, Zorina Gibbons, Caroline Hurley, Siobhan Stokes, Sinead McNamara, Orla Ennis, Kate O’Donnell, Eamon Keenan, Cillian De Gascun, Fiona Lyons, Mary Ward, Kostas Danis, Ronan Glynn, Allison Waters, Margaret Fitzgerald
Journal: Eurosurveillance (2015)

In February 2015, an outbreak of recently acquired HIV infections among people who inject drugs (PWID) was identified in Dublin, following similar outbreaks in Greece and Romania in 2011. We compared drug and risk behaviours among 15 HIV cases and 39 controls. Injecting a synthetic cathinone, snow blow, was associated with recent HIV infection (AOR: 49; p=0.003). Prevention and control efforts are underway among PWID in Dublin, but may also be needed elsewhere in Europe.
Feasibility and Efficacy of Tandem Autologous-Allogeneic Transplantation in a Cohort of 111 Patients Affected By High-Risk Hodgkin's and Non-Hodgkin's Lymphoma
Authors: Roberto Crocchiolo, Luca Castagna, Sabine Fuerst, Jean El Cheikh, Barbara Sarina, Stefania Bramanti, Angela Granata, Lucio Morabito, Laura Giordano, Sylvain Garciaz, Diane Coso, Reda Bouabdallah, Monica Balzarotti, Christian Chabannon, Carmelo Carlo-Stella, Armando Santoro, Didier Blaise
Journal: Blood (2014)
PD-009 Use of adjuvant chemotherapy after pancreatoduodenectomy for pancreatic cancer: a nationwide population-based study in the Netherlands
Authors: M. Bakens, Y. van Gestel, H. Laarhoven, G.-J. Creemers, M. Besselink, V. Lemmens, I. de Hingh
Journal: Annals of Oncology (2015)
Basing approval of drugs for type 2 diabetes on real world outcomes
Authors: Andrew McGovern, Robert Hinchliffe, Neil Munro, Simon de Lusignan
Journal: BMJ (2015)

Naci and colleagues rightly point out that although drugs are often approved on the basis of glucose lowering efficacy, we really need agents that reduce important outcomes such as symptomatic microvascular disease and cardiovascular events.1 The authors suggest that real world evidence of clinical effectiveness should be required from the drug industry, using routine healthcare data to monitor …
Oestradiol metabolism and androgen receptor genotypes are associated with right ventricular function
Authors: Corey E. Ventetuolo, Nandita Mitra, Fei Wan, Ani Manichaikul, R. Graham Barr, Craig Johnson, David A. Bluemke, Joao A.C. Lima, Hari Tandri, Pamela Ouyang, Steven M. Kawut
Journal: European Respiratory Journal (2015)

Sex hormones are linked to right ventricular (RV) function, but the relationship between genetic variation in these pathways and RV function is unknown. We performed a cross-sectional study of 2761 genotyped adults without cardiovascular disease. The relationships between RV measures and single nucleotide polymorphisms (SNPs) in 10 candidate genes were assessed. Urinary oestradiol (E2) metabolites produced by cytochrome P4501B1 (CYP1B1) and serum testosterone were measured in women and men respectively. In African-American (AA) women, the CYP1B1 SNP rs162561 was associated with RV ejection fraction (RVEF), such that each copy of the A allele was associated with a 2.0% increase in RVEF. Haplotype analysis revealed associations with RVEF in AA (global p&lt;7.2×10 −6 ) and white (global p=0.05) women. In white subjects, higher E2 metabolite levels were associated with significantly higher RVEF. In men, androgen receptors SNPs (rs1337080; rs5918764) were significantly associated with all RV measures and modified the relationship between testosterone and RVEF. Genetic variation in E2 metabolism and androgen signalling was associated with RV morphology in a sex-specific manner. The CYP1B1 SNP identified is in tight linkage disequilibrium with SNPs associated with pulmonary hypertension and oncogenesis, suggesting these pathways may underpin sexual dimorphism in RV failure.
Proton pump inhibitors affect the gut microbiome
Authors: Floris Imhann, Marc Jan Bonder, Arnau Vich Vila, Jingyuan Fu, Zlatan Mujagic, Lisa Vork, Ettje F Tigchelaar, Soesma A Jankipersadsing, Maria Carmen Cenit, Hermie J M Harmsen, Gerard Dijkstra, Lude Franke, Ramnik J Xavier, Daisy Jonkers, Cisca Wijmenga, Rinse K Weersma, Alexandra Zhernakova
Journal: Gut (2015)

<h3>Background and aims</h3> Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably <i>Clostridium difficile.</i> The gut microbiome plays an important role in enteric infections, by resisting or promoting colonisation by pathogens. In this study, we investigated the influence of PPI use on the gut microbiome. <h3>Methods</h3> The gut microbiome composition of 1815 individuals, spanning three cohorts, was assessed by tag sequencing of the 16S rRNA gene. The difference in microbiota composition in PPI users versus non-users was analysed separately in each cohort, followed by a meta-analysis. <h3>Results</h3> 211 of the participants were using PPIs at the moment of stool sampling. PPI use is associated with a significant decrease in Shannon9s diversity and with changes in 20% of the bacterial taxa (false discovery rate &lt;0.05). Multiple oral bacteria were over-represented in the faecal microbiome of PPI-users, including the genus <i>Rothia</i> (p=9.8×10<sup>−38</sup>). In PPI users we observed a significant increase in bacteria: genera <i>Enterococcus</i>, <i>Streptococcus</i>, <i>Staphylococcus</i> and the potentially pathogenic species <i>Escherichia coli</i>. <h3>Conclusions</h3> The differences between PPI users and non-users observed in this study are consistently associated with changes towards a less healthy gut microbiome. These differences are in line with known changes that predispose to <i>C. difficile</i> infections and can potentially explain the increased risk of enteric infections in PPI users. On a population level, the effects of PPI are more prominent than the effects of antibiotics or other commonly used drugs.
CAROTID ARTERY INTIMA MEDIA THICKNESS, BUT NOT CORONARY ARTERY CALCIUM, PREDICTS CORONARY VASCULAR RESISTANCE IN PATIENTS EVALUATED FOR CORONARY ARTERY DISEASE
Authors: Ibrahim Danad, Pieter G. Raijmakers, Parisa Kamali, Hendrik Harms, Mark Lubberink, Adriaan A. Lammertsma, yvo smulders, Igor Tulevski, Albert van Rossum, Paul Knaapen
Journal: Journal of the American College of Cardiology (2012)
Upregulation of oncogenic MUC1 by the EMT transcription factor brachyury mediates immunotherapy-resistance in tumor cells
Authors: Justin M David, Duane H Hamilton, Charli L Dominguez, Jeffrey Schlom, Claudia Palena
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Epithelial-mesenchymal transition (EMT) is a molecular and cellular program in which epithelial cells lose their well-differentiated phenotype and adopt mesenchymal characteristics. This process occurs during the progression of cancer to metastatic disease, and is also associated
Epigenetic regulation of gene expression by Ikaros, HDAC1 and Casein Kinase II in leukemia
Authors: C Song, X Pan, Z Ge, C Gowda, Y Ding, H Li, Z Li, G Yochum, M Muschen, Q Li, K J Payne, S Dovat
Journal: Leukemia (2015)

IKZF1 (Ikaros) encodes a DNA-binding protein that acts as a master regulatory of hematopoiesis and a tumor suppressor in acute lymphoblastic leukemia (ALL).1, 2, 3, 4 The deletion and/or mutation of Ikaros is associated with the development of B-cell acute lymphoblastic leukemia (B-ALL) with poor outcome.5, 6, 7, 8, 9, 10, 11 Ikaros directly associates with components of the histone deacetylase complex (NuRD), HDAC1, HDAC2 and Mi-2.12, 13, 14 Although Ikaros is hypothesized to regulate the transcription of target genes by recruiting the NuRD complex, the mechanism of Ikaros-mediated transcriptional regulation in leukemia is still unknown. Here we use a systems biology approach to determine the mechanism through which Ikaros and HDAC1 regulate gene expression in human B-ALL.
Dose-ranging evaluation of the serotonin antagonist dolasetron mesylate in patients receiving high-dose cisplatin.
Authors: M G Kris, S M Grunberg, R J Gralla, L Baltzer, S A Zaretsky, D Lifsey, L B Tyson, L Schmidt, W F Hahne
Journal: Journal of Clinical Oncology (1994)

PURPOSE This dose-ranging trial of intravenous dolasetron mesylate (MDL73,147EF) was performed to determine its adverse and antiemetic effects in patients receiving cisplatin at doses &gt; or = 100 mg/m2. PATIENTS AND METHODS Eighty-nine patients treated with initial cisplatin received a single intravenous dose of dolasetron mesylate administered over 20 minutes beginning 30 minutes before chemotherapy. The following four dose levels were studied: 1.8, 2.4, 3.0, and 5.0 mg/kg. Emesis and adverse effects were measured for 24 hours after cisplatin. RESULTS All adverse effects were mild and transient including loose stools, headache, serum AST/ALT elevations, and asymptomatic prolongation of ECG intervals. Among the dose levels, no-emesis rates from 24% to 52% were observed, and the percentage of patients having zero, one, or two emetic episodes ranged from 48% to 82%. Complete control of vomiting increased as the dose was escalated to 2.4 mg/kg, but did not improve further with higher doses. CONCLUSION Dolasetron mesylate can be administered safely at doses up to 5.0 mg/kg, with comparable complete protection rates and increased adverse effects at doses greater than 2.4 mg/kg. Antiemetic activity was seen after cisplatin. Trials comparing single infusions of dolasetron mesylate and ondansetron are under way.