tbuckley/cabot-search huggingface dataset:
Language Barriers and Hospitalized Children
Authors: Glenn Flores
Journal: JAMA Pediatrics (2020)

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PTU-005 Improving uk trainees’ proficiency in polypectomy: retrospective analysis of 4,965 dopys evaluations
Authors: A Rajendran, S Thomas-Gibson, R Rameshshanker, P Dunckley, N Sevdalis, A Haycock
Journal: Gut (2017)

Introduction  Directly Observed Polypectomy Skills (DOPyS) is a validated tool used to assess polypectomy skills (1). DOPyS has 34 parameters measuring technical and non-technical polypectomy skills and an overall polypectomy proficiency score on which a trainee is scored on a grade of 1–4. Trainees are certified as competent in level 1 (  Method  DOPyS evaluations documented were analysed to identify low-scoring parameters both during training and after attaining competency. Data from 707 trainees (4965 DOPyS) from Jan 2009 to Sept 2015 was examined. The low scoring parameters (scores 1 or 2) were identified during training (DOPyS overall score 1 or 2) and at competency (DOPyS Overall score 3 or 4). These were further analysed according to site, morphology and size of polyps removed.  Results  All 4965 DOPyS were entered into the analysis. 80% (3898) left sided polyps, 63% (3114) sessile polyps. Median size 6 mm and majority (68%) were  2 cm polyps.  Conclusion  Trainees in the UK consistently underperform on some non-technical skills (choice of technique, checking diathermy settings, photo-documentation) and technical skills (snare control, submucosal injection technique), irrespective of polyp size, site and morphology.  To improve proficiency of polypectomy skills, we suggest targeted interventions to increase the awareness of the required non-technical skills and specific focus during in-vivo training on the identified technical factors. This retrospective analysis of a large database is entirely novel in describing the detail of polypectomy skills that trainees lack during training and at competency. There is currently an ongoing prospective study to examine the learning curve for polypectomy skills.  Reference  Guptaet al, GIE (March 2012)  Disclosure of Interest  None Declared
Response by Williams et al to Letter Regarding Article, “Low-Attenuation Noncalcified Plaque on Coronary Computed Tomography Angiography Predicts Myocardial Infarction: Results From the Multicenter SCOT-HEART Trial (Scottish Computed Tomography of the HEART)”
Authors: Michelle C. Williams, David E. Newby, Damini Dey, Marc R. Dweck
Journal: Circulation (2020)
Abstract 124: A Machine-Learning Based Shock Advice Algorithm for Reliable Rhythm Diagnosis During Out-Of-Hospital Cardiac Arrest
Authors: Erik Alonso, Unai Irusta, Elisabete Aramendi, Beatriz Chicote, Carlos Corcuera, Andima Larrea, Jose Veintemillas, Mikel Olabarria, Daniel Alonso
Journal: Circulation (2019)

Introduction: In out-of-hospital cardiac arrest (OHCA) a reliable rhythm diagnosis by the automated external defibrillator (AED) allows for the delivery of correct therapy, a prompt defibrillation for shockable rhythms and resuming cardiopulmonary resuscitation for non-shockable rhythms. The aim of this study was to develop a machine-learning (ML) based shock advice algorithm (SAA) for reliable rhythm diagnosis during OHCA. Materials and methods: The study analyzed data from 853 OHCA patients treated with AEDs by the basic life support personnel in the Basque Health service (Osakidetza, Basque Country, Spain) between 2013 and 2015. The datased used in the study contained 4212 5-s ECG segments, 489 shockable and 3723 non-shockable, annotated by consensus between six clinicians. The dataset was split patient-wise into training (60%) and test (40%) sets. Each ECG segment was preprocessed and 15 well-known waveform features were computed. The SAA was composed of two blocks. First, a low electrical activity (LEA) detector based on the power of the ECG for a prompt diagnosis of asystole. Second, a shock/no-shock ML algorithm based on a hidden Markov model that made the shock/no-shock classification of those segments not detected as asystole by the LEA detector. The training set was used to select the most discriminative features and develop/optimize the SAA. The test set was used to measure the performance of the method in terms of sensitivity (SE) and specificity (SP), and to compare it with the performance of a commercial AED. This procedure was repeated 50 times to estimate the distributions of the performance metrics. Results: The method showed a mean (SD) SE and SP of 97.7% (1.0) and 99.1% (0.4), respectively. While the commercial AED presented a SE and SP of 94.2% (1.3) and 99.8% (0.1). Conclusions: Both methods were compliant with the American Heart Association’s requirements (SE&gt;90% and SP&gt;95%). However, our ML approach outperformed the SAA of the commercial AED, increasing the SE in 3.5-points with a decrease in SP of 0.7-points. Therefore, a ML based SAA algorithm can accurately make shock/no-shock diagnoses during OHCA and might improve the performance of current algorithms.
Preclinical evaluation of the anticancer activity of DRF-1042, a novel camptothecin analog targeting Topoisomerase-I.
Authors: Sriram Rajagopal, R. Ajaya Kumar, D. Subramanya, V. M. Sharma, T. V. R. S. Sastry, Peter J. Houghton, A. Venkateshwaralu, R. Rajagopalan
Journal: Cancer Research (2004)

3071  DRF 1042 is a novel 5 substituted (2’-hydroxy ethoxy) 20 (s) - campthotheicin (CPT). An additional chiral center at the 5th position makes this molecule unique among the campthothecin under development. DRF 1042 is a diasteriomeric mixture of 20(S), 5(R) and 20(S), 5(S) of approximate 1:1 ratio. DRF 1042 demonstrated superior lactone stability and good in vitro anticancer activity against a panel of human cancer cell lines including multi-drug resistance (MDR) phenotype. The hollow fibre studies in animals with DRF 1042 treatment showed favorable bioavailability, tolerance and significant anti-cancer activities against a panel of human cancer cell lines. In addition, in xenograft study, it showed good tumor regression activity against VCR5 and VCR5/topo resistant tumors. In clonogenic assay against murine, canine and human bone marrow cells, DRF 1042 treatment showed less mylosupression that supports the possibility of protracted dose schedule in both experimental and clinical studies. Recently concluded phase I study results of DRF 1042 in cancer patients have endorsed these preclinical findings. Additional preliminary findings suggest the use of this molecule in combination with conventional anti-cancer agent is possible and thereby enhancing the clinical utility of this molecule. Thus, DRF 1042 represent a new class of CPT analogue - well-tolerated, orally active molecule with good therapeutic potential for the treatment of cancer. DRL Publication No.332-A
Breast Cancer Survival Among Males by Race, Ethnicity, Age, Geographic Region, and Stage — United States, 2007–2016
Authors: Taylor D. Ellington, S. Jane Henley, Reda J. Wilson, Jacqueline W. Miller
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Breast cancer among males in the United States is rare; approximately 2,300 new cases and 500 associated deaths were reported in 2017, accounting for approximately 1% of all breast cancers.* Risk for male breast cancer increases with increasing age (1), and compared with women, men receive diagnoses later in life and often at a later stage of disease (1). Gradual improvement in breast cancer survival from 1976-1985 to 1996-2005 has been more evident for women than for men (1). Studies examining survival differences among female breast cancer patients observed that non-Hispanic White (White) females had a higher survival than non-Hispanic Black (Black) females (2), but because of the rarity of breast cancer among males, few studies have examined survival differences by race or other factors such as age, stage, and geographic region. CDC's National Program of Cancer Registries (NPCR)† data were used to examine relative survival of males with breast cancer diagnosed during 2007-2016 by race/ethnicity, age group, stage at diagnosis, and U.S. Census region. Among males who received a diagnosis of breast cancer during 2007-2016, 1-year relative survival was 96.1%, and 5-year relative survival was 84.7%. Among characteristics examined, relative survival varied most by stage at diagnosis: the 5-year relative survival for males was higher for cancers diagnosed at localized stage (98.7%) than for those diagnosed at distant stage (25.9%). Evaluation of 1-year and 5-year relative survival among males with breast cancer might help guide health care decisions regarding early detection of male breast cancer and establishing programs to support men at high risk for breast cancer and male breast cancer survivors.
Antiangiogenesis in Early-Stage Colon Cancer—Microscopically Busted
Authors: Howard S. Hochster
Journal: JAMA Network Open (2020)

Benoist Chibaudel, MD; Julie Henriques, MSc; Manel Rakez, MSc; Baruch Brenner, MD; Tae Won Kim, MD; Mercedes Martinez-Villacampa, MD; Javier Gallego-Plazas, MD; Andres Cervantes, MD; Katharine Shim, MD; Derek Jonker, MD; Veronique Guerin-Meyer, MD; Laurent Mineur, MD; Chiara Banzi, MD; Alice Dewdney, MD; Thitiya Dejthevaporn, MD; Haiko J. Bloemendal, MD; Arnaud Roth, MD, MD; Markus Moehler, MD; Enrique Aranda, MD; Eric Van Cutsem, MD; Josep Tabernero, MD; Hans-Joachim Schmoll, MD; Paulo M. Hoff, MD; Thierry André, MD; Aimery de Gramont, MD
Ethical Framework for Assessing Manual and Digital Contact Tracing for COVID-19
Authors: Bernard Lo, Ida Sim
Journal: Annals of Internal Medicine (2020)

The coronavirus disease 2019 (COVID-19) pandemic has challenged the traditional public health balance between benefiting the good of the community through contact tracing and restricting individual liberty. This article first analyzes important technical and ethical issues regarding new smartphone apps that facilitate contact tracing and exposure notification. It then presents a framework for assessing contact tracing, whether manual or digital: the effectiveness at mitigating the pandemic; acceptability of risks, particularly privacy; and equitable distribution of benefits and risks. Both manual and digital contact tracing require public trust, engagement of minority communities, prompt COVID-19 testing and return of results, and high adherence with physical distancing and use of masks.
Factors associated with adverse COVID-19 outcomes in patients with psoriasis—insights from a global registry–based study
Authors: Satveer K. Mahil, Nick Dand, Kayleigh J. Mason, Zenas Z.N. Yiu, Teresa Tsakok, Freya Meynell, Bola Coker, Helen McAteer, Lucy Moorhead, Teena Mackenzie, Maria Teresa Rossi, Raquel Rivera, Emmanuel Mahe, Andrea Carugno, Michela Magnano, Giulia Rech, Esther A. Balogh, Steven R. Feldman, Claudia De La Cruz, Siew Eng Choon, Luigi Naldi, Jo Lambert, Phyllis Spuls, Denis Jullien, Hervé Bachelez, Devon E. McMahon, Esther E. Freeman, Paolo Gisondi, Luis Puig, Richard B. Warren, Paola Di Meglio, Sinéad M. Langan, Francesca Capon, Christopher E.M. Griffiths, Jonathan N. Barker, Catherine H. Smith, Aadarsh Shah, Alberto Barea, Alberto Romero-Maté, Alekya Singapore, Alexandra Paolino, Alice Mwale, Ana Maria Morales Callaghan, Ana Martinez, Andrew DeCrescenzo, Andrew E. Pink, Ann Jones, Ann Sergeant, Annette Essex, Anthony Bewley, Areti Makrygeorgou, Astrid van Huizen, Beatriz Pérez-Suárez, Benhadou Farida, Birgitta Wilson Claréus, Carla Tubau Prims, Carrie Davis, Catherine Quinlan, Catriona Maybury, Gonzalez A. Cesar, Charlotte Barclay, Claudio Greco, Danielle Brassard, Deanna Cummings, Deepti Kolli, Vincent Descamps, Diana Ruiz Genao, Efrossini Carras, Elena Hawryluk, Eliseo Martínez-García, Elzbieta Klujszo, Emily Dwyer, Emmanuel Toni, Enikö Sonkoly, Enrique Loayza, Esteban Daudén, Fernando Valenzuela, Georgi Popov, Georgie King, Girard Celine, Gloria Aparicio, Graham A. Johnston, Gustavo Anibal Cardozo, Ian Pearson, Ignacio Yanguas, Jamie Weisman, Jennifer E. Carolan, Jenny Hughes, Jose-Maria Ortiz-Salvador, Jose-Manuel Carrascosa, Joseph J. Schwartz, Karina Jackson, Kathryn G. Kerisit, Keith Wu, Leila Asfour, Leontien de Graaf, Cécile Lesort, Lieve Meuleman, Liv Eidsmo, Lone Skov, Lorraine Gribben, Malcolm Rustin, Manel Velasco, Manisha Panchal, Manpreet Lakhan, Manuel D. Franco, Marie-Louise Svensson, Mark Vandaele, Maruska Marovt, Omid Zargari, Pablo De Caso, Paulo Varela, Peter Jenkin, Céline Phan, Philip Hampton, Portia Goldsmith, Rachel Bak, Reinhart Speeckaert, Ricardo Romiti, Richard Woolf, Rogelio Mercado-Seda, Rohima Khatun, Romana Ceovic, Rosa Taberner, Russell W. Cohen, Simina Stefanescu, Sarah Kirk, Saskia Reeken, Shanti Ayob, Silvia Pérez-Barrio, Stefano Piaserico, Susannah Hoey, Tiago Torres, Toomas Talme, Trupti V. Desai, Adrienne J. van Geest, Victoria King, Vito Di Lernia, Zahira Koreja, Vito Zeeshaan Hasab
Journal: Journal of Allergy and Clinical Immunology (2020)
Evaluation of Longitudinal Pain Study in Sickle Cell Disease (ELIPSIS) by patient-reported outcomes, actigraphy, and biomarkers
Authors: Debra D. Pittman, Patrick C. Hines, David Beidler, Denis Rybin, Andrew L. Frelinger, Alan D. Michelson, Ke Liu, Xiufeng Gao, Jennell White, Ahmar U. Zaidi, Robert J. Charnigo, Michael U. Callaghan
Journal: Blood (2020)
A MicroRNA Expression Signature as Prognostic Marker for Oropharyngeal Squamous Cell Carcinoma
Authors: Xinyi Liu, Ping Liu, Rebecca D Chernock, Zhenming Yang, Krystle A Lang Kuhs, James S. Lewis, Jingqin Luo, Hua Li, Hiram A Gay, Wade L Thorstad, Xiaowei Wang
Journal: JNCI Journal of the National Cancer Institute (2020)

Improved prognostication of oropharyngeal squamous cell carcinoma (OPSCC) may facilitate individualized patient management. The goal of this study was to develop and validate a prognostic signature based on microRNA sequencing (miRNA-seq) analysis.We collected tumor specimens for miRNA-seq analysis from OPSCC patients treated at Washington University in St Louis (n = 324) and Vanderbilt University (n = 130). OPSCC patients (n = 79) from The Cancer Genome Atlas Program were also included for independent validation. Univariate and multivariable Cox regression analyses were performed to identify miRNAs associated with disease outcomes. All statistical tests were 2-sided.By miRNA-seq profiling analysis, we identified a 26-miRNA signature. Based on computed risk scores of the signature, we classified the patients into low- and high-risk groups. In the training cohort, the high-risk group had much shorter overall survival compared with the low-risk group (hazard ratio [HR] = 3.80, 95% confidence interval [CI] = 2.37 to 6.10, P < .001). Subgroup analysis further revealed that the signature was prognostic for HPV-positive OPSCCs (HR = 3.07, 95% CI = 1.65 to 5.71, P < .001). Multivariable analysis indicated that the signature was independent of common clinicopathologic factors for OPSCCs. Importantly, the miRNA signature was a statistically significant predictor of overall survival in independent validation cohorts (The Cancer Genome Atlas Program cohort: HR = 6.05, 95% CI = 2.10 to 17.37, P < .001; Vanderbilt cohort: HR = 7.98, 95% CI = 3.99 to 15.97, P < .001; Vanderbilt HPV-positive cohort: HR = 8.71, 95% CI = 2.70 to 28.14, P < .001).The miRNA signature is a robust and independent prognostic tool for risk stratification of OPSCCs including HPV-positive OPSCCs.
Anti-tau scFvs Targeted to the Cytoplasm or Secretory Pathway Variably Modify Pathology and Neurodegenerative Phenotypes
Authors: Marshall S. Goodwin, Olga Sinyavskaya, Franklin Burg, Veronica O’Neal, Carolina Ceballos-Diaz, Pedro E. Cruz, Jada Lewis, Benoit I. Giasson, Peter Davies, Todd E. Golde, Yona Levites
Journal: Molecular Therapy (2020)

Immunotherapies designed to treat neurodegenerative tauopathies that primarily engage extracellular tau may have limited efficacy as tau is primarily intracellular. We generated tau-targeting single-chain variable fragments (scFvs) and intrabodies (iBs) from the phosphorylated tau-specific antibodies CP13 and PHF1 and the pan-tau antibody Tau5. Recombinant adeno-associated virus (rAAV) was utilized to express these antibody fragments in homozygous JNPL3 P301L tau mice. Two iBs (CP13i, PHF1i) and one scFv (PHF1s) abrogated tau pathology and delayed time to severe hindlimb paralysis. In a second tauopathy model (rTg4510), CP13i and PHF1i reduced tau pathology, but cognate scFvs did not. These data demonstrate that (1) disease-modifying efficacy does not require antibody effector functions, (2) the intracellular targeting of tau with phosphorylated tau-specific iBs is more effective than extracellular targeting with the scFvs, and (3) robust effects on tau pathology before neurodegeneration only resulted in modest disease modification as assessed by delay of severe motor phenotype. Immunotherapies designed to treat neurodegenerative tauopathies that primarily engage extracellular tau may have limited efficacy as tau is primarily intracellular. We generated tau-targeting single-chain variable fragments (scFvs) and intrabodies (iBs) from the phosphorylated tau-specific antibodies CP13 and PHF1 and the pan-tau antibody Tau5. Recombinant adeno-associated virus (rAAV) was utilized to express these antibody fragments in homozygous JNPL3 P301L tau mice. Two iBs (CP13i, PHF1i) and one scFv (PHF1s) abrogated tau pathology and delayed time to severe hindlimb paralysis. In a second tauopathy model (rTg4510), CP13i and PHF1i reduced tau pathology, but cognate scFvs did not. These data demonstrate that (1) disease-modifying efficacy does not require antibody effector functions, (2) the intracellular targeting of tau with phosphorylated tau-specific iBs is more effective than extracellular targeting with the scFvs, and (3) robust effects on tau pathology before neurodegeneration only resulted in modest disease modification as assessed by delay of severe motor phenotype.
Dual function of Langerhans cells in skin TSLP-promoted TFH differentiation in mouse atopic dermatitis
Authors: Pierre Marschall, Ruicheng Wei, Justine Segaud, Wenjin Yao, Pierre Hener, Beatriz Falcon German, Pierre Meyer, Cecile Hugel, Grace Ada Da Silva, Reinhard Braun, Daniel H. Kaplan, Mei Li
Journal: Journal of Allergy and Clinical Immunology (2020)
Coronaviruses: Innate Immunity, Inflammasome Activation, Inflammatory Cell Death, and Cytokines
Authors: SangJoon Lee, Rudragouda Channappanavar, Thirumala-Devi Kanneganti
Journal: Trends in Immunology (2020)

The innate immune system acts as the first line of defense against pathogens, including coronaviruses (CoVs). Severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV are epidemic zoonotic CoVs that emerged at the beginning of the 21st century. The recently emerged virus SARS-CoV-2 is a novel strain of CoV that has caused the coronavirus 2019 (COVID-19) pandemic. Scientific advancements made by studying the SARS-CoV and MERS-CoV outbreaks have provided a foundation for understanding pathogenesis and innate immunity against SARS-CoV-2. In this review, we focus on our present understanding of innate immune responses, inflammasome activation, inflammatory cell death pathways, and cytokine secretion during SARS-CoV, MERS-CoV, and SARS-CoV-2 infection. We also discuss how the pathogenesis of these viruses influences these biological processes.
THU0267 SERUM IGG2 LEVELS PREDICT VERY LONG-TERM PROTECTION FOLLOWING PNEUMOCOCCAL VACCINE IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
Authors: T. Goulenok, A. L. Gerard, M. Bahuaud, P. Aucouturier, H. Moins, T. Papo, K. Sacre
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic lupus erythematosus (SLE) patients are at increased risk for Streptococcus pneumoniae infection. Although pneumococcal vaccination is an attractive method to prevent invasive pneumococcal infection, vaccination coverage remains dramatically low in SLE. Moreover, the efficacy of vaccination may be reduced in SLE patients and sequential pneumococcal vaccination using new conjugated pneumococcal vaccines in combination with 23-valent pneumococcal polysaccharide vaccine (PPV23) is now advocated. However, limited study directly addressed the immune efficacy of such prime-and-boost strategy in SLE Objectives: We aimed to measure the immunological efficacy of the sequential pneumococcal vaccination using PCV13 in combination with PPV23 and identify factors associated with long-term immune protection following vaccination in SLE. Methods: SLE patients received PCV13 vaccine followed by PPSV23 vaccine 8 weeks later. Immune protection, defined by an antigen-specific IgG concentration ≥ 1.3 µg/mL for at least 70% of 7 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F), was assessed at baseline, 2 months, 12 months, and 36 months, defining very long-term protection. Results: 21 (40[25-75] years; 85.7% female) SLE patients received the sequential PCV13/PPV23 vaccines. Only 10 (47.6%) showed a sustained immune protection against pneumococcal infection 36 months after PCV13 shot (very long-term protected, VLTP). Eleven patients had no long-term protection (NLTP) with a seroconversion that never (n=6) or only transiently (n=5) occurred. SLE disease features, treatment received and immunological characteristic did not differ between VLTP and NLTP patients except for a lower serum IgG2 levels in NLTP (1.45 [1.30, 1.82] vs 3.30 [2.92, 4.44] g/L, p&lt;0.001). Noteworthy the ROC curve showed that the serum IgG2 level before vaccination (AUC 0.95 [95% CI: 0.84-1]; p=0.004) was predictive for very long-term protection. A baseline serum IgG2 level of 2.125µg/ml or more showed a sensitivity of 100% and a specificity of 90.9% for very long-term protection Conclusion: The benefit of sequential PCV13/PPV23 vaccination in SLE is limited. Baseline IgG2 serum level before vaccination is strongly indicative of very long term protection following vaccination Disclosure of Interests: None declared
Safety and efficacy of abatacept in early diffuse cutaneous systemic sclerosis (ASSET): open-label extension of a phase 2, double-blind randomised trial
Authors: Lorinda Chung, Cathie Spino, Richard McLain, Sindhu R Johnson, Christopher P Denton, Jerry A Molitor, Virginia D Steen, Robert Lafyatis, Robert W Simms, Suzanne Kafaja, Tracy M Frech, Vivien Hsu, Robyn T Domsic, Janet E Pope, Jessica K Gordon, Maureen D Mayes, Nora Sandorfi, Faye N Hant, Elana J Bernstein, Soumya Chatterjee, Flavia V Castelino, Ali Ajam, Yannick Allanore, Marco Matucci-Cerinic, Michael L Whitfield, Oliver Distler, Ora Singer, Amber Young, Vivek Nagaraja, David A Fox, Daniel E Furst, Dinesh Khanna
Journal: The Lancet Rheumatology (2020)
Cytokine Receptor-like Factor 2 (CRLF2) Overexpression in Myeloid Malignancies Secondary to Multiple Isodicentric Y Chromosomes: A Novel Cytogenetic Entity?
Authors: Abhishek Mangaonkar, Mrinal M. Patnaik, Kathleen Kaiser-Rogers, Kathleen Waldron Rao, Kevin Halling, Gavin Oliver, Michelle A. Elliott, Patricia Greipp, Daniel L. Van Dyke
Journal: Blood (2017)