tbuckley/cabot-search huggingface dataset:
Longitudinal Multiplexed Measurement of Quantitative Proteomic Signatures in Mouse Lymphoma Models Using Magneto-Nanosensors
Authors: Jung-Rok Lee, Iris Appelmann, Cornelius Miething, Tyler O. Shultz, Daniel Ruderman, Dokyoon Kim, Parag Mallick, Scott W. Lowe, Shan X. Wang
Journal: Theranostics (2018)

Cancer proteomics is the manifestation of relevant biological processes in cancer development.Thus, it reflects the activities of tumor cells, host-tumor interactions, and systemic responses to cancer therapy.To understand the causal effects of tumorigenesis or therapeutic intervention, longitudinal studies are greatly needed.However, most of the conventional mouse experiments are unlikely to accommodate frequent collection of serum samples with a large enough volume for multiple protein assays towards single-object analysis.Here, we present a technique based on magneto-nanosensors to longitudinally monitor the protein profiles in individual mice of lymphoma models using a small volume of a sample for multiplex assays.Methods: Drug-sensitive and -resistant cancer cell lines were used to develop the mouse models that render different outcomes upon the drug treatment.Two groups of mice were inoculated with each cell line, and treated with either cyclophosphamide or vehicle solution.Serum samples taken longitudinally from each mouse in the groups were measured with 6-plex magneto-nanosensor cytokine assays.To find the origin of IL-6, experiments were performed using IL-6 knock-out mice.Results: The differences in serum IL-6 and GCSF levels between the drug-treated and untreated groups were revealed by the magneto-nanosensor measurement on individual mice.Using the multiplex assays and mouse models, we found that IL-6 is secreted by the host in the presence of tumor cells upon the drug treatment. Conclusion:The multiplex magneto-nanosensor assays enable longitudinal proteomic studies on mouse tumor models to understand tumor development and therapy mechanisms more precisely within a single biological object.
Health-related quality of life in patients with breast cancer in Palestine: an assessment of a cross-sectional study using the EuroQoL-5 dimensions scale
Authors: Samah W Al-Jabi, Rayah Yahya, Ru'a Salameh, Haya Jabi, Warde Msaime, Mohammad Daraghmeh, Ala' Barakat, Sa'ed H Zyoud, Waleed M Sweileh
Journal: The Lancet (2018)
Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update
Authors: Randy A. Taplitz, Erin B. Kennedy, Eric J. Bow, Jennie Crews, Charise Gleason, Douglas K. Hawley, Amelia A. Langston, Loretta J. Nastoupil, Michelle Rajotte, Kenneth Rolston, Lynne Strasfeld, Christopher R. Flowers
Journal: Journal of Clinical Oncology (2018)

Purpose To provide an updated joint ASCO/Infectious Diseases Society of American (IDSA) guideline on outpatient management of fever and neutropenia in patients with cancer. Methods ASCO and IDSA convened an Update Expert Panel and conducted a systematic review of relevant studies. The guideline recommendations were based on the review of evidence by the Expert Panel. Results Six new or updated meta-analyses and six new primary studies were added to the updated systematic review. Recommendation Clinical judgment is recommended when determining which patients are candidates for outpatient management, using clinical criteria or a validated tool such as the Multinational Association of Support Care in Cancer risk index. In addition, psychosocial and logistic considerations are outlined within the guideline. The panel continued to endorse consensus recommendations from the previous version of this guideline that patients with febrile neutropenia receive initial doses of empirical antibacterial therapy within 1 hour of triage and be monitored for ≥ 4 hours before discharge. An oral fluoroquinolone plus amoxicillin/clavulanate (or clindamycin, if penicillin allergic) is recommended as empirical outpatient therapy, unless fluoroquinolone prophylaxis was used before fever developed. Patients who do not defervesce after 2 to 3 days of an initial, empirical, broad-spectrum antibiotic regimen should be re-evaluated and considered as candidates for inpatient treatment. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .
Traitement endoscopique des complications biliaires du kyste hydatique du foie: A propos de 45 cas
Authors: S Jardak, M Medhioub, S Ben Amor, L Hamzaoui, K Amal, MM Azouz
Journal: Endoscopy (2018)

Le kyste hydatique du foie (KHF) est une affection parasitaire due à Echinococcus granulosus et qui demeure endémique dans les pays du Maghreb. L'hydatidose hépatique peut causer une morbidité grave à cause des complications biliaires. Le développement des techniques d'endoscopie, notamment la sphinctérotomie endoscopique (SE) et le drainage biliaire, a permis d'améliorer la prise en charge de ces complications.
c-Rel is required for the development of thymic Foxp3(+) CD4 regulatory T cells (vol 206, pg 3001, 2009)
Authors: Iwao Isomura, Stephanie Palmer, Raelene J. Grumont, Karen Bunting, Gerard Hoyne, Nancy Wilkinson, Ashish Banerjee, Anna Proietto, Raffi Gugasyan, Li Wu, Alice McNally, Raymond J. Steptoe, Ranjeny Thomas, M. Frances Shannon, Steve Gerondakis
Journal: The Journal of Experimental Medicine (2010)
Association between proton pump inhibitors use and risk of gastric cancer in patients with GERD
Authors: Yen-Chun Peng, Lam-Ru Huang, Cheng-Li Lin, Wan-Yun Hsu, Chi-Sen Chang, Hong-Zen Yeh, Chia-Hung Kao
Journal: Gut (2018)

We read with interest the study by Cheung et al confirming the risk of proton pump inhibitors (PPIs) for gastric cancer regarding the patients after Helicobacter pylori (H. pylori) eradication with long-term PPIs use.1 Most concerns about the safety of PPIs pertain to the increased risk for enteric infections, fractures and nutritional deficiencies.2 To date, the association of PPIs use and risk of gastric cancer is still controversial in patients with gastro-oesophageal reflux diseases (GERD).

For GERD, PPIs are the mainstay of treatment in the management of patients with acid-related disorders.3 Thus, patients with GERD usually take long-term PPIs,and possibly carry the risk of gastric cancer. In the present study, we performed a case–control study to investigate the association of PPIs use and risk of gastric cancer using data from a nationwide population database, the National Health Insurance Research Database (NHIRD) in Taiwan.4 

This study also used a subdataset of the NHIRD, which comprises one million randomly sampled beneficiaries enrolled in the NHI programme in 2000 (Longitudinal Health Insurance Database …
O015 Il-17 blockade with secukinumab in peripheral spondyloarthritis impacts synovial immunopathology without compromising systemic immune responses
Authors: M van de Sande, L van Mens, S Menegatti, I Blijdorp, J de Jong, I Fluri, T Latuhihin, A van Kuijk, L Rogge, N Yeremenko, D Baeten
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Secukinumab (anti-IL-17A) is an effective therapy for ankylosing spondylitis(AS) and psoriatic arthritis (PsA), the prototypical forms of spondyloarthritis (SpA). <h3>Objectives</h3> This study assessed if secukinumab modulates the immunopathology of target lesions without blunting systemic immune responses, using peripheral SpA (pSpA) as model. <h3>Methods</h3> 20 active peripheral SpA patients were included in a 12 week open-label trial with secukinumab (300 mg weekly for 4 weeks followed by every 4 weeks). Outcomes included clinical response, cytokine production by peripheral blood cells using TruCulture technology, and histological and qPCR analysis of synovial biopsies before and after treatment. <h3>Results</h3> All patients completed the 12 week study, without SAEs or severe treatment-related AEs. The primary efficacy endpoint, EULAR DAS 28 response at wk 12, was achieved by 18/20 patients (10 good and 8 moderate responders), with rapid and significant improvements in all clinical disease activity measurements. Clinical improvement in joint counts was associated with histological decrease in synovial sublining macrophages (p=0.028) and neutrophils (p=0.004), sensitive synovial biomarkers of response in pSpA, as well as with decreased synovial expression of IL-17A (p=0.010) but not TNF. Systemically, secukinumab treatment decreased CRP (p&lt;0.01) and ESR (p&lt;0.01), as well as MMP-3 production in the truculture system (p&lt;0.01). With exception of IL-17A itself, however, the capacity of peripheral blood cells to produce a broad panel of cytokines and chemokines upon stimulation with microbial antigens was not affected. <h3>Conclusions</h3> This mechanism-of-action study in pSpA indicates that clinical improvement upon secukinumab treatment is paralleled by immunomodulation of the inflamed target tissues without compromising systemic immune responses. <h3>Disclosure of interest</h3> M. van de Sande Grant/research support from: Novartis, Eli Lilly, Boehringer Ingelheim, Consultant for: Abbvie, Novartis, Speakers bureau: x, L. van Mens: None declared, S. Menegatti: None declared, I. Blijdorp: None declared, J. de Jong: None declared, I. Fluri: None declared, T. Latuhihin: None declared, A. van Kuijk Grant/research support from: x, Consultant for: Novartis, Celgene, L. Rogge: None declared, N. Yeremenko: None declared, D. Baeten Grant/research support from: Pfizer, MSD, Abbvie, UCB, Novartis, Janssen, Boehringer Ingelheim, Consultant for: Pfizer, MSD, Abbvie, UCB, Novartis, Janssen, Boehringer Ingelheim, Eli Lily, Roche, BMS, Glenmark, Employee of: UCB
Response to: ’Elephant in the room' by Hartung et al
Authors: Rohit Aggarwal, Chester V Oddis
Journal: Annals of the Rheumatic Diseases (2018)

We read the letter to the editor ‘Elephant in the room’ by Hartung et al in response to our open-label pilot clinical trial report on the use of repository corticotropin injection (RCI) in refractory polymyositis (PM) and dermatomyositis (DM).1 2

First, the authors believe that the population studied may not be truly resistant given that only 3 of the 10 patients were treated with intravenous immunoglobulin (IVIg) before entering the trial. There are strong data to support that patients with myositis who have failed 40-60mg slow prednisolne taper and an average of 2.6 immunosuppressive drugs in addition to nearly 20 mg of prednisone at study entry are considered. In the largest international multicentre  randomised clinical trial done on PM and DM—the Rituximab in Myositis (RIM) trial, which included many international myositis experts, subjects failed an average of 3.1 immunosuppressive drugs in addition to at least 20 mg of prednisone.3 Our pilot cohort is clearly consistent with RIM trial entry criteria in terms of subject refractoriness. Further, there is no clear consensus definition of ‘refractory myositis’ and, in general, patients failing high dose glucocorticoids plus one additional immunosuppressive agent in adequate doses for a reasonable period of time can be considered ‘refractory’. Regarding IVIg, although we agree that IVIg is …
<b>E</b>ffect of pregnancy on disease flares in patients with systemic lupus erythematosus
Authors: Amanda M Eudy, Anna Maria Siega-Riz, Stephanie M Engel, Nora Franceschini, Annie Green Howard, Megan E B Clowse, Michelle Petri
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objective</h3> Prior studies found conflicting results about whether lupus is likely to flare during or after pregnancy. Using a large cohort of pregnant and non-pregnant women with lupus, we estimated the effect of pregnancy on disease flares in systemic lupus erythematosus. <h3>Methods</h3> Data were collected in the Hopkins Lupus Cohort 1987–2015. Women aged 14–45 years with &gt;1 measurement of disease activity were included. The time-varying exposures were classified as pregnancy, postpartum or non-pregnant/non-postpartum periods. Flares were defined as: (1) change in Physician Global Assessment (PGA)≥1 from previous visit and (2) change in Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI)≥4 from previous visit. A stratified Cox model estimated HRs with bootstrap 95% CIs. <h3>Results</h3> There were 1349 patients, including 398 pregnancies in 304 patients. There was an increased rate of flare defined by PGA during pregnancy (HR: 1.59; 95% CI 1.27 to 1.96); however, this effect was modified by hydroxychloroquine (HCQ) use, with the HR of flares in pregnancy compared with non-pregnant/non-postpartum periods estimated to be 1.83 (95% CI 1.34 to 2.45) for patients with no HCQ use and 1.26 (95% CI 0.88 to 1.69) for patients with HCQ use. The risk of flare was similarly elevated among non-HCQ users in the 3 months postpartum, but not for women taking HCQ after delivery. <h3>Conclusions</h3> Our study supports and extends previous findings that the incidence of flare is increased during pregnancy and within the 3 months postpartum. Continuing HCQ, however, appeared to mitigate the risk of flare during and after pregnancy.
Influenza Season and ARDS after Cardiac Surgery
Authors: Geert H Groeneveld, Judith van Paassen, Jaap T van Dissel, M Sesmu Arbous
Journal: New England Journal of Medicine (2018)

Flu Season and ARDS after Cardiac Surgery The acute respiratory distress syndrome was found to occur more frequently after cardiac surgery during influenza seasons than during non–influenza seasons. The authors suggest that subclinical influenza could be a risk factor for ARDS.
A common variant alters SCN5A–miR-24 interaction and associates with heart failure mortality
Authors: Xiaoming Zhang, Jin-Young Yoon, Michael Morley, Jared M. McLendon, Kranti A. Mapuskar, Rebecca Gutmann, Haider Mehdi, Heather L. Bloom, Samuel C. Dudley, Patrick T. Ellinor, Alaa A. Shalaby, Raul Weiss, W.H. Wilson Tang, Christine S. Moravec, Madhurmeet Singh, Anne L. Taylor, Clyde W. Yancy, Arthur M. Feldman, Dennis M. McNamara, Kaikobad Irani, Douglas R. Spitz, Patrick Breheny, Kenneth B. Margulies, Barry London, Ryan L. Boudreau
Journal: Journal of Clinical Investigation (2018)

SCN5A encodes the voltage-gated Na+ channel NaV1.5 that is responsible for depolarization of the cardiac action potential and rapid intercellular conduction. Mutations disrupting the SCN5A coding sequence cause inherited arrhythmias and cardiomyopathy, and single-nucleotide polymorphisms (SNPs) linked to SCN5A splicing, localization, and function associate with heart failure–related sudden cardiac death. However, the clinical relevance of SNPs that modulate SCN5A expression levels remains understudied. We recently generated a transcriptome-wide map of microRNA (miR) binding sites in human heart, evaluated their overlap with common SNPs, and identified a synonymous SNP (rs1805126) adjacent to a miR-24 site within the SCN5A coding sequence. This SNP was previously shown to reproducibly associate with cardiac electrophysiological parameters, but was not considered to be causal. Here, we show that miR-24 potently suppresses SCN5A expression and that rs1805126 modulates this regulation. We found that the rs1805126 minor allele associates with decreased cardiac SCN5A expression and that heart failure subjects homozygous for the minor allele have decreased ejection fraction and increased mortality, but not increased ventricular tachyarrhythmias. In mice, we identified a potential basis for this in discovering that decreased Scn5a expression leads to accumulation of myocardial reactive oxygen species. Together, these data reiterate the importance of considering the mechanistic significance of synonymous SNPs as they relate to miRs and disease, and highlight a surprising link between SCN5A expression and nonarrhythmic death in heart failure.
Prise de décision en réunion de concertation pluridisciplinaire pour les polypes coliques dégénérés: étude qualitative rétrospective des comptes-rendus d'endoscopie et d'anatomopathologie sur une période de deux ans en région «Franche-Comté»
Authors: B Morel, S Valmary-Degano, S Koch
Journal: Endoscopy (2018)

Le choix du traitement endoscopique ou chirurgical des polypes coliques dégénérés (PCD) repose sur des critères de risques d'envahissement sous-muqueux et ganglionnaire. Ces critères doivent figurer au sein des comptes-rendus d'endoscopie (CRE) et d'anatomopathologie (CRA). Nous avons rétrospectivement évalué leur qualité sur 2 ans en région Franche-Comté.
Commensal Microbes Induce Serum IgA Responses that Protect against Polymicrobial Sepsis
Authors: Joel R. Wilmore, Brian T. Gaudette, Daniela Gomez Atria, Tina Hashemi, Derek D. Jones, Christopher A. Gardner, Stephen D. Cole, Ana M. Misic, Daniel P. Beiting, David Allman
Journal: Cell Host & Microbe (2018)
TIA1 variant drives myodegeneration in multisystem proteinopathy with SQSTM1 mutations
Authors: YouJin Lee, Per Harald Jonson, Jaakko Sarparanta, Johanna Palmio, Mohona Sarkar, Anna Vihola, Anni Evilä, Tiina Suominen, Sini Penttilä, Marco Savarese, Mridul Johari, Marie-Christine Minot, David Hilton-Jones, Paul Maddison, Patrick Chinnery, Jens Reimann, Cornelia Kornblum, Torsten Kraya, Stephan Zierz, Carolyn Sue, Hans Goebel, Asim Azfer, Stuart H. Ralston, Peter Hackman, Robert C. Bucelli, J. Paul Taylor, Conrad C. Weihl, Bjarne Udd
Journal: Journal of Clinical Investigation (2018)

Multisystem proteinopathy (MSP) involves disturbances of stress granule (SG) dynamics and autophagic protein degradation that underlie the pathogenesis of a spectrum of degenerative diseases that affect muscle, brain, and bone. Specifically, identical mutations in the autophagic adaptor SQSTM1 can cause varied penetrance of 4 distinct phenotypes: amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Paget's disease of the bone, and distal myopathy. It has been hypothesized that clinical pleiotropy relates to additional genetic determinants, but thus far, evidence has been lacking. Here, we provide evidence that a TIA1 (p.N357S) variant dictates a myodegenerative phenotype when inherited, along with a pathogenic SQSTM1 mutation. Experimentally, the TIA1-N357S variant significantly enhances liquid-liquid-phase separation in vitro and impairs SG dynamics in living cells. Depletion of SQSTM1 or the introduction of a mutant version of SQSTM1 similarly impairs SG dynamics. TIA1-N357S-persistent SGs have increased association with SQSTM1, accumulation of ubiquitin conjugates, and additional aggregated proteins. Synergistic expression of the TIA1-N357S variant and a SQSTM1-A390X mutation in myoblasts leads to impaired SG clearance and myotoxicity relative to control myoblasts. These findings demonstrate a pathogenic connection between SG homeostasis and ubiquitin-mediated autophagic degradation that drives the penetrance of an MSP phenotype.
Clinical phenotypes of delirium during critical illness and severity of subsequent long-term cognitive impairment: a prospective cohort study
Authors: Timothy D Girard, Jennifer L Thompson, Pratik P Pandharipande, Nathan E Brummel, James C Jackson, Mayur B Patel, Christopher G Hughes, Rameela Chandrasekhar, Brenda T Pun, Leanne M Boehm, Mark R Elstad, Richard B Goodman, Gordon R Bernard, Robert S Dittus, E W Ely
Journal: The Lancet Respiratory Medicine (2018)
Gastropathie hypertensive: facteur pronostique au cours de la cirrhose?
Authors: N Elleuch, A Sabbek, H Jaziri, A Ben Slama, A Hammami, A Braham, S Ajmi, M Ksiaa, A Jmaa
Journal: Endoscopy (2018)

En matière d'hypertension portale (HTP) du cirrhotique, toute l'attention est accordée à la recherche et au traitement des varices oesophagiennes (VO) et gastriques. Classiquement décrite comme rarement responsable d'hémorragie digestive haute (HDH) aigue, la gastropathie d'hypertension portale (GHP) a toujours été négligée et peu d'études s'y sont intéressées.
Tezepelumab demonstrates clinically meaningful improvements in asthma control (ACQ-6) in patients with uncontrolled asthma: results from a phase 2b clinical trial
Authors: Jonathan Corren, Jane R. Parnes, Liangwei Wang, May Mo, Stephanie L. Roseti, Janet M. Griffiths, Sean O'Quinn, Rene van der Merwe
Journal: Journal of Allergy and Clinical Immunology (2018)
Ticks transmitting Lyme disease are found in a third of Britain, mainly the south
Authors: Nigel Hawkes
Journal: BMJ (2018)

Ticks responsible for transmitting Lyme disease are distributed widely around the UK, a team from Public Health England has found.1

Data from a surveillance scheme that has been running since 2005 showed that the number of sites where ticks have been found have nearly doubled from 2010 to 2016. Dividing Britain into squares of 10 km on each side, the 2016 data show that ticks were reported in 36% of the squares, up from 20% before 2010. In Greater London 80% of the grid squares contained ticks, compared with 67% in southeast England. The Midlands, by contrast, seemed relatively free of ticks.

The increases may result from better awareness of ticks, said the study authors, led by Benjamin Cull, but they …
Peter Dennis Sprackling
Authors: John Temple
Journal: BMJ (2018)

Peter Dennis Sprackling, a Nottingham general practitioner and medical educator who has died at the age of 84, came from a large farming family in Sussex. He trained at the Middlesex Hospital Medical School, qualified in 1958, and after house officer posts joined a small group practice in Nottingham “for a year” and stayed until retirement. He will be remembered by both patients and colleagues as an exceptional family doctor: cheerful, bright, and committed to improving patient care and to the NHS. One of his earliest memories was overhearing his parents discussing whether they could afford to take one of his siblings to the doctor.

Energetic and hardworking, Peter became the main driving force in the practice, which in the early 1970s he developed into Nottingham’s first primary health care team, with health visitors, district nurses and a midwife working from the practice premises. Over the years he attracted younger partners who shared his …