tbuckley/cabot-search huggingface dataset:
Natural moisturizing factor as a clinical marker in atopic dermatitis
Authors: Anouk E. M. Nouwen, Dilara Karadavut, Suzanne G. M. A. Pasmans, Niels J. Elbert, Lawrence D. N. Bos, Tamar E. C. Nijsten, Nicolette J. T. Arends, Mariëlle W. H. Pijnenburg, Senada Koljenović, Gerwin J. Puppels, Peter J. Caspers
Journal: Allergy (2019)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Journal editor fired for homophobic email signs off with creationist editorial
Authors: Owen Dyer
Journal: BMJ (2019)

The editor of the American Heart Association’s journal Circulation Research , who was fired over the allegedly homophobic contents of an email he sent, has used his final editorial in the journal to call on readers to reject evolution and “scientific materialism.”1

The association fired Roberto Bolli because of an email he sent to a local ballet company that called them “minions of Satan” for sending out an advertising flyer with a picture of two men holding hands.

In his final editorial Bolli wrote, “I pray that the wall that divides science from religion be taken down. I pray that we recognize that biology is, ultimately, theology.”

Bolli, who is also chief of cardiovascular medicine at the medical school at the University of Louisville, Kentucky, lost his job as editor after an email he …
THU0439 MEASUREMENT PROPERTIES OF PAIN CATASTROPHIZING SCALE IN PATIENTS WITH KNEE OSTEOARTHRITIS
Authors: Wei Jie Ong, Yu Heng Kwan, Julian Thumboo, Seng Jin Yeo, William Yeo, Ying Ying Leung
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Up to 20% of patients with knee osteoarthritis (OA) do not respond well to knee replacement surgery (KR) despite surgical success. We hypothesize that pain catastrophizing among these patients may affect KR outcomes. <h3>Objectives:</h3> To assess the validity and reliability of the Pain Catastrophizing Scale (PCS) in patients with knee osteoarthritis (OA) in Singapore. <h3>Methods:</h3> We used cross-sectional data from 675 knee OA patients enlisted for knee replacement surgery (KR) in a Singapore tertiary referral hospital from May to September 2018. Data was collected 2 weeks prior to KR. Analyses were guided by the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) framework. Internal consistency was assessed using Cronbach's alpha. Construct validity was assessed through seven <i>a priori</i> hypotheses by correlation of overall PCS score with other patient-reported outcomes. Structural validity was evaluated via confirmatory factor analysis using maximum likelihood method. Measurement invariance across gender subgroups was assessed using multi-group confirmatory factor analysis. <h3>Results:</h3> There were 675 patients (mean±SD age = 65.52±6.84 years, 70.37% female) with knee OA enlisted for KR (91.7% total, 8.3% unicompartmental). The mean±SD PCS score was 12.65±10.55, 0.14% and 8.63% ceiling and floor effects. PCS demonstrated high internal consistency (Cronbach's alpha=0.94). Construct validity was demonstrated by fulfilment of six out of seven (85%) a priori hypotheses. The PCS model showed good fit for a two-factor structure after accounting for appropriate modification indices (CFI=0.957, TLI=0.950, RMSEA=0.073, SRMR=0.043), demonstrating good structural validity. Measurement invariance across gender groups was demonstrated. <h3>Conclusion:</h3> This study supports internal consistency, construct validity and structure validity of PCS as a measure of pain catastrophizing in knee OA patients in Singapore. ** p &lt; 0.001; HADS: Hospital Anxiety and Depression Scale <h3>Disclosure of Interests:</h3> Wei Jie Ong: None declared, Yu Heng Kwan: None declared, Julian Thumboo: None declared, Seng Jin Yeo: None declared, William Yeo: None declared, Ying Ying Leung Grant/research support from: Abbvie, Novartis, Speakers bureau: Abbvie and Novartis, Speakers bureau: Novartis
A “managed approach” to sex workers’ health in Leeds
Authors: Madeleine A Crow, Jane Braunholtz-Speight, Emily Turner, Gemma Scire, Colin Dickinson, Anna Hartley
Journal: BMJ (2019)

In 2014 a “managed approach” model was introduced in a designated area of Leeds that aims to meet specific challenges of street based sex work, in partnership with third sector organisations.1 Specific operational rules in designated hours enable a strategic approach to managing enforcement around soliciting or kerb crawling. Police continue to enforce laws relating to indecency, crime, and antisocial behaviour. This managed …
Abstract 15715: Risk for Cardiovascular Events Following ‘Microsize’ versus Usual Myocardial Infarctions in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Zaid I Almarzooq, Lisandro D Colantonio, Peter M Okin, Joshua Richman, Todd M Brown, Emily B Levitan, Joanna Bryan, Monika M Safford
Journal: Circulation (2018)

Introduction: Microsize myocardial infarction (MI) is a recently described phenomenon consisting of events that meet rigorous criteria for MI but with very low peak troponin elevations (<0.5 ng/mL)...
AB1145 FULLY CONVOLUTIONAL NEURAL NETWORK-BASED SEGMENTATION OF INDIVIDUAL MUSCLES IN MR IMAGES USING MUSCLES AND BORDERS PARCELLATIONS
Authors: Joris Fournel, Arnaud Le Troter, Sandrine Guis, David Bendahan, Badih Ghattas
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Segmentation of individual muscles in MR images is challenging considering the poor contrast between muscles and the large variability between and within subjects. <h3>Objectives</h3> The segmentation performance of the Bayesian SegNet network was assessed for the four individual muscles of the quadriceps group. In addition to the classes corresponding to each muscle, we analyzed the effect of adding four additional classes corresponding to muscle borders. We also investigated the network performance taking into account each muscle individually or the whole set of muscles. The corresponding results were compared with those obtained using a conventional multi-atlas method. <h3>Methods</h3> For the training phase, a dataset of 500 images was used while the testing phase was performed for two other datasets with 140 images each. Four different variants of the same network were assayed considering simultaneous segmentation of individual muscles (On5), separate segmentation of individual muscles (Fn2) and the use of additional classes related to muscle borders in both cases (On9 and Fn3). <h3>Results</h3> All approaches largely outperformed the results of a multi-atlas strategy. The higher DSI values i.e. 0.96 ± 0.01 for the <i>rectus femoris</i> muscle, 0.93 ± 0.01 for the <i>vastus intermedius</i> muscle, 0.94 ± 0.03 for the <i>vastus lateralis</i> muscle and 0.96 ± 0.01 for the <i>vastus medialis</i> muscle were obtained with the On9 and Fn3 networks i.e. taking into account the muscle borders labels in addition to the muscle labels. <h3>Conclusion</h3> Deep-learning based methods are optimal for the segmentation of thigh muscles and the corresponding efficiency can be improved when considering labels for muscles together with borders. <h3> Disclosure of Interests</h3> None declared
Understanding Hyperlactatemia in Sepsis: Are We There Yet?
Authors: Marek Nalos, Robert Robergs
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

High plasma lactate is a useful indicator of shock, a canary in the coal mine, that is associated with increased mortality in sepsis. But instead of a harmful molecule per se, lactate is a central molecule in the intra and interorgan exchange of carbon and redox potential. (1) The study by Gattinoni et al., who presented a novel approach to the analysis of data from the ALBIOS study, adds to the required change of paradigm concerning lactate metabolism in sepsis. (2) The authors nicely demonstrated that there are multiple reasons for hyperlactataemia in sepsis and that the increased snapshot value we measure, reflects an imbalance between increased production and reduced consumption...
An amplicon-based sequencing framework for accurately measuring intrahost virus diversity using PrimalSeq and iVar
Authors: Nathan D. Grubaugh, Karthik Gangavarapu, Joshua Quick, Nathaniel L. Matteson, Jaqueline Goes De Jesus, Bradley J. Main, Amanda L. Tan, Lauren M. Paul, Doug E. Brackney, Saran Grewal, Nikos Gurfield, Koen K. A. Van Rompay, Sharon Isern, Scott F. Michael, Lark L. Coffey, Nicholas J. Loman, Kristian G. Andersen
Journal: Genome biology (2019)

How viruses evolve within hosts can dictate infection outcomes; however, reconstructing this process is challenging. We evaluate our multiplexed amplicon approach, PrimalSeq, to demonstrate how virus concentration, sequencing coverage, primer mismatches, and replicates influence the accuracy of measuring intrahost virus diversity. We develop an experimental protocol and computational tool, iVar, for using PrimalSeq to measure virus diversity using Illumina and compare the results to Oxford Nanopore sequencing. We demonstrate the utility of PrimalSeq by measuring Zika and West Nile virus diversity from varied sample types and show that the accumulation of genetic diversity is influenced by experimental and biological systems.
FRI0216 IGURATIMOD MIGHT BE AN ALTERNATIVE OPTION FOR REFRACTORY LUPUS NEPHRITIS: A PRELIMINARY OBSERVATIONAL STUDY
Authors: Qingran Yan, Yuening Kang, Ran Wang, Chunde Bao
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Despite significant advances in the management of patients with lupus nephritis (LN), a significant proportion of patients either do not respond to first-line immunosuppressive drugs, or relapse after initial remission. Iguratimod is a novel disease modifying anti-rheumatic drug that has been approved for treating rheumatoid arthritis in East Asia and has shown benefits in lupus animal model in our previous research.(1) <h3>Objectives:</h3> The aim of the present study was to make a preliminary observation on the efficacy and safety of iguratimod in treating refractory LN patients. <h3>Methods:</h3> We have enrolled adult refractory LN patients who were eligible if they experienced at least two times of failure or relapse before enrollment. Failure was defined as no response to one certain immunosuppressive drug for at least six months. After enrollment, we simply switched their previous immunosuppressant to daily iguratimod (25 mg twice per day), while keeping all other medications. Complete/partial remission (PR/CR) was used as the primary outcome. 24h urine protein, blood cell counts, liver and kidney function were routinely monitored. <h3>Results:</h3> A total of 20 refractory LN patients had been enrolled (18 female and 2 male patients) since 2015. At enrollment, the median proteinuria was 2.588g/24h (range: 0.98-13.79g/24h). None of them had overt extra-renal involvement. All of them had biopsy-proven LN (class III/IV/V) and two patients agreed repeated biopsy before switching to iguratimod. The median prednisone dosage was 10mg/d (range: 5-35mg/d). One patient was lost to follow-up and one withdrew from the study. Of the remaining 18 patients, 16 patients achieved PR/CR and 2 did not respond to iguratimod. Of the 16 patients who achieved remission, 3 had renal relapse after initial PR and 1 had extra-renal flare after initial CR. One PR patient withdrew from the study due to severe anemia and another due to incompliance. For the remaining 10 patients who were still in follow-up, the median follow-up was 84 weeks (range: 28-144 weeks), with 4 having CR and 6 PR. The median response duration (MRD) was 12 weeks. <h3>Conclusion:</h3> Out study provided preliminary but promising clinical evidence for iguratimod in treating refractory LN patients. A large randomized clinical trial is needed to establish its safety and efficacy for refractory LN. <h3>References:</h3> [1] Yan Q, Du F, Huang X, Fu Q, Chen S, Dai D, et al. Prevention of immune nephritis by the small molecular weight immunomodulator iguratimod in MRL/lpr mice. PLoS One. 2014;9(10):e108273. <h3>Disclosure of Interests:</h3> None declared
Enhancer connectome in primary human cells identifies target genes of disease-associated DNA elements
Authors: Maxwell R Mumbach, Ansuman T Satpathy, Evan A Boyle, Chao Dai, Benjamin G Gowen, Seung Woo Cho, Michelle L Nguyen, Adam J Rubin, Jeffrey M Granja, Katelynn R Kazane, Yuning Wei, Trieu Nguyen, Peyton G Greenside, M Ryan Corces, Josh Tycko, Dimitre R Simeonov, Nabeela Suliman, Rui Li, Jin Xu, Ryan A Flynn, Anshul Kundaje, Paul A Khavari, Alexander Marson, Jacob E Corn, Thomas Quertermous, William J Greenleaf, Howard Y Chang
Journal: Nature Genetics (2017)
Dietary iron variably modulates assembly of the intestinal microbiota in colitis-resistant and colitis-susceptible mice
Authors: Melissa Ellermann, Raad Z. Gharaibeh, Nitsan Maharshak, Ernesto Peréz-Chanona, Christian Jobin, Ian M. Carroll, Janelle C. Arthur, Scott E Plevy, Anthony A. Fodor, Cory R. Brouwer, R. Balfour Sartor
Journal: Gut Microbes (2019)

Iron deficiency, a common comorbidity of gastrointestinal inflammatory disorders such as inflammatory bowel diseases (IBD), is often treated with oral iron supplementation. However, the safety of oral iron supplementation remains controversial because of its association with exacerbated disease activity in a subset of IBD patients. Because iron modulates bacterial growth and function, one possible mechanism by which iron may exacerbate inflammation in susceptible hosts is by modulating the intestinal microbiota. We, therefore, investigated the impact of dietary iron on the intestinal microbiota, utilizing the conventionalization of germ-free mice as a model of a microbial community in compositional flux to recapitulate the instability of the IBD-associated intestinal microbiota. Our findings demonstrate that altering intestinal iron availability during community assembly modulated the microbiota in non-inflamed wild type (WT) and colitis-susceptible interleukin-10-deficient (Il10−/-) mice. Depletion of luminal iron availability promoted luminal compositional changes associated with dysbiotic states irrespective of host genotype, including an expansion of Enterobacteriaceae such as Escherichia coli. Mechanistic in vitro growth competitions confirmed that high-affinity iron acquisition systems in E. coli enhance its abundance over other bacteria in iron-restricted conditions, thereby enabling pathobiont iron scavenging during dietary iron restriction. In contrast, distinct luminal community assembly was observed with dietary iron supplementation in WT versus Il10−/- mice, suggesting that the effects of increased iron on the microbiota differ with host inflammation status. Taken together, shifts in dietary iron intake during community assembly modulate the ecological structure of the intestinal microbiota and is dependent on host genotype and inflammation status.
DNMT3A mutations are over-represented in young adults with NPM1 mutated AML and prompt a distinct co-mutational pattern
Authors: Luca Vincenzo Cappelli, Manja Meggendorfer, Frank Dicker, Sabine Jeromin, Stephan Hutter, Wolfgang Kern, Torsten Haferlach, Claudia Haferlach, Alexander Höllein
Journal: Leukemia (2019)
Ancient hybridization and strong adaptation to viruses across African vervet monkey populations
Authors: Hannes Svardal, Anna J Jasinska, Cristian Apetrei, Giovanni Coppola, Yu Huang, Christopher A Schmitt, Beatrice Jacquelin, Vasily Ramensky, Michaela Müller-Trutwin, Martin Antonio, George Weinstock, J Paul Grobler, Ken Dewar, Richard K Wilson, Trudy R Turner, Wesley C Warren, Nelson B Freimer, Magnus Nordborg
Journal: Nature Genetics (2017)
Dual Farnesyl and Geranylgeranyl Transferase Inhibitor Thwarts Mutant KRAS-Driven Patient-Derived Pancreatic Tumors
Authors: Aslamuzzaman Kazi, Shengyan Xiang, Hua Yang, Liwei Chen, Perry Kennedy, Muhammad Ayaz, Steven Fletcher, Christopher Cummings, Harshani R. Lawrence, Francisca Beato, Ya'an Kang, Michael P. Kim, Andrea Delitto, Patrick W. Underwood, Jason B. Fleming, Jose G. Trevino, Andrew D. Hamilton, Said M. Sebti
Journal: Clinical Cancer Research (2019)

Mutant KRAS is a major driver of pancreatic oncogenesis and therapy resistance, yet KRAS inhibitors are lacking in the clinic. KRAS requires farnesylation for membrane localization and cancer-causing activity prompting the development of farnesyltransferase inhibitors (FTIs) as anticancer agents. However, KRAS becomes geranylgeranylated and active when cancer cells are treated with FTIs. To overcome this geranylgeranylation-dependent resistance to FTIs, we designed FGTI-2734, a RAS C-terminal mimetic dual FT and geranylgeranyltransferase-1 inhibitor (GGTI).Immunofluorescence, cellular fractionation, and gel shift assays were used to assess RAS membrane association, Western blotting to evaluate FGTI-2734 effects on signaling, and mouse models to demonstrate its antitumor activity.FGTI-2734, but not the selective FTI-2148 and GGTI-2418, inhibited membrane localization of KRAS in pancreatic, lung, and colon human cancer cells. FGTI-2734 induced apoptosis and inhibited the growth in mice of mutant KRAS-dependent but not mutant KRAS-independent human tumors. Importantly, FGTI-2734 inhibited the growth of xenografts derived from four patients with pancreatic cancer with mutant KRAS (2 G12D and 2 G12V) tumors. FGTI-2734 was also highly effective at inhibiting, in three-dimensional cocultures with resistance promoting pancreatic stellate cells, the viability of primary and metastatic mutant KRAS tumor cells derived from eight patients with pancreatic cancer. Finally, FGTI-2734 suppressed oncogenic pathways mediated by AKT, mTOR, and cMYC while upregulating p53 and inducing apoptosis in patient-derived xenografts in vivo.The development of this novel dual FGTI overcomes a major hurdle in KRAS resistance, thwarting growth of patient-derived mutant KRAS-driven xenografts from patients with pancreatic cancer, and as such it warrants further preclinical and clinical studies.
Effect of a Russian-backbone live-attenuated influenza vaccine with an updated pandemic H1N1 strain on shedding and immunogenicity among children in The Gambia: an open-label, observational, phase 4 study
Authors: Benjamin B Lindsey, Ya Jankey Jagne, Edwin P Armitage, Anika Singanayagam, Hadijatou J Sallah, Sainabou Drammeh, Elina Senghore, Nuredin I Mohammed, David Jeffries, Katja Höschler, John S Tregoning, Adam Meijer, Ed Clarke, Tao Dong, Wendy Barclay, Beate Kampmann, Thushan I de Silva
Journal: The Lancet Respiratory Medicine (2019)
Clinical Activity, Tolerability, and Long-Term Follow-Up of Durvalumab in Patients With Advanced NSCLC
Authors: Scott J. Antonia, Ani Balmanoukian, Julie Brahmer, Sai-Hong I. Ou, Matthew D. Hellmann, Sang-We Kim, Myung-Ju Ahn, Dong-Wan Kim, Martin Gutierrez, Stephen V. Liu, Patrick Schöffski, Dirk Jäger, Rahima Jamal, Guy Jerusalem, Jose Lutzky, John Nemunaitis, Luana Calabrò, Jared Weiss, Shirish Gadgeel, Jaishree Bhosle, Paolo A. Ascierto, Marlon C. Rebelatto, Rajesh Narwal, Meina Liang, Feng Xiao, Joyce Antal, Shaad Abdullah, Natasha Angra, Ashok K. Gupta, Samir N. Khleif, Neil H. Segal
Journal: Journal of Thoracic Oncology (2019)

Durvalumab is a selective, high-affinity human immunoglobulin G1 monoclonal antibody that blocks programmed cell death ligand 1 (PD-L1) binding to programmed death 1. Here we report safety and clinical activity in the NSCLC cohort of a phase I/II trial that included multiple tumor types (Study 1108; NCT01693562).Patients with stage IIIB-IV NSCLC (squamous or nonsquamous) received durvalumab 10 mg/kg every 2 weeks for 12 months or until confirmed progressive disease or unacceptable toxicity. Primary objectives were safety and antitumor activity. Tumoral PD-L1 expression was assessed using the VENTANA SP263 Assay. Responses were assessed by blinded independent central review (Response Evaluation Criteria in Solid Tumors v1.1). Adverse events were graded according to National Cancer Institute's Common Terminology Criteria for Adverse Events (v4.03).Of 304 patients, 79.0% were previously treated. Confirmed objective response rate was 21.8% in patients with greater than or equal to 25% PD-L1 expression and 6.4% in those with less than 25%; 25.9% in first-line patients and 12.7% in previously treated patients; and 14.0% in squamous and 16.7% in nonsquamous disease. Median overall survival was 12.4 months and median progression-free survival was 1.7 months; both were numerically longer in the PD-L1 greater than or equal to 25% group than in the PD-L1 less than 25% group (overall survival 16.4 versus 7.6 months, respectively; progression-free survival 2.6 versus 1.4 months, respectively). Treatment-related adverse events occurred in 57.2%, were grade 3/4 in 10.2%, and led to discontinuation in 5.6%. One patient (0.3%) died of treatment-related pneumonia with underlying pneumonitis.Durvalumab was clinically active irrespective of histology in this mostly pretreated population, with a manageable safety profile. Response rates and survival appeared to be enhanced in patients with greater tumoral PD-L1 expression.
THU0263 NOVEL SUBSETS OF SLE PATIENTS ENRICHED FOR RENAL MANIFESTATIONS IDENTIFIED BY CLUSTERING WITH EXPANDED AUTOANTIBODY PROFILES OF NATIVE AMERICAN (NA), AFRICAN AMERICAN (AA), AND EUROPEAN AMERICAN (EA) SLE PATIENTS
Authors: Carla Guthridge, Tim Gross, Magdalene Quintero, Joseph Kheir, Joel Guthridge, Judith A. James
Journal: Annals of the Rheumatic Diseases (2019)

Results: CD14 + cells were the most abundant cells in the urine of LN patients.The mean numbers of urinary CD8+, CD4+ and CD14+ cells/ml were significantly higher in patients with LN (405.6 ± 200.0, 281.1 ± 195.3, and 1554.7 ± 606.8 respectively) than in those without (39.30± 17.56, 34.33 ± 16.41, and 161.17 ± 90.91 respectively).AUC for ROC = 1.0 for all 3 markers with CD8+ >85 cells/ml, CD4+ >80 cells/ml, and CD14+ >400cells/ml being observed exclusively in LN.The cell counts correlated significantly with the protein:creatinine ratio, but not with other markers of disease activity.The CD4:CD8 ratio was significantly lower in LN patients (0.69 ± 0.21) than in those without (0.91 ± 0.31).Urinary CD14+ cells seem to occur in much higher counts in Class IV (1736.7 ± 522.0) than Class III LN (898.5 ± 17.68) p=0.084.Figure 1 shows a dot plot of flow cytometric analysis of urinary T cells and monocytes in a patient with lupus nephritis showing increased both CD4+ and CD8+ T cells and monocytes(dim CD4 expression and CD14 positive(not shown)) Conclusion: Urinary CD8+, CD4+ and CD14+ cells are highly sensitive and specific markers for detecting proliferative LN.A low CD4:CD8 ratio provides a further clue.The cell counts correlate with proteinuria.CD14 cell counts may be a potential biomarker to differentiate between the different classes of proliferative LN.