tbuckley/cabot-search huggingface dataset:
OP0280 TEMPORAL TRENDS OF OPIOID USE AMONG INCIDENT OSTEOARTHRITIS PATIENTS IN CATALONIA, 2007-2016: A POPULATION-BASED COHORT STUDY
Authors: J. Xie, A. Turkiewicz, G. Collins, M. Englund, V. Y. Strauss, C. Reyes, D. Prieto-Alhambra
Journal: Annals of the Rheumatic Diseases (2020)

Background: Opioids are not recommended as first-line treatments for chronic pain management in osteoarthritis (OA), but recent data suggest they are commonly used in routine practice in North America and northern Europe. Objectives: To characterise the secular trends of opioid and strong opioids use in patients with incident OA from 2007 to 2016, and to explore the impact of patient characteristics on the use of opioid/s for OA. Methods: Data was obtained from the SIDIAP (The System for the Development of Research in Primary Care) database, which contains primary care records and pharmacy dispensing data for 80 % of the population in Catalonia (~ 6 million people). All persons aged 18 or older at the beginning of each calendar year with an incident OA diagnosis (including both peripheral and central joints) in the study period were included. Index date was the date of first OA diagnosis, and the observation period of opioid use was 1-year after index date. Opioids considered included codeine, tramadol, fentanyl, and morphine, with the latter three classified as strong opioids. The period prevalence of any opioid use was estimated in whole and sub-population stratified by sex, age, socio-economic status (U1 – U5, higher values of the indicator equivalent to deprivation) and residence area (rural/urban). Results: The 1-year prevalence of any opioid use among incident OA patients was around 15% from 2007 to 2012. After that, this figure grew by 10% approaching 25% in 2016. However, strong opioid use increased continuously to nearly triple, from 8% in 2007 to 20% in 2016. The different subgroups followed similar trends over time, with women 4% higher than men, oldest 10% higher than youngest, most deprived 6% higher than least deprived, and rural 1% higher than urban. Conclusion: The use of opioids (and especially strong opioids) has substantially increased in recent years among newly diagnosed OA patients in Catalonia. Our findings call for urgent action for safe opioid prescribing to avoid opioid abuse in OA patients especially amongst older women living in deprived areas. Figure 1. Trends of 1-year prevalence of opioid/s use among incident OA patients, whole and subgroup population. Disclosure of Interests: Junqing Xie: None declared, Aleksandra Turkiewicz: None declared, Gary Collins: None declared, Martin Englund Consultant of: Advisory Board 1 day (2019) Pfizer (Tanezumab)., Victoria Y Strauss: None declared, Carlen Reyes: None declared, Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen
How Tumor Cell Dedifferentiation Drives Immune Evasion and Resistance to Immunotherapy
Authors: Jinyang Li, Ben Z. Stanger
Journal: Cancer Research (2020)

Abstract Immunotherapy has revolutionized cancer treatment, yet most patients do not respond. While tumor antigens are needed for effective immunotherapy, a favorable tumor immune microenvironment is also critical. In this review, we discuss emerging evidence that tumor cells exploit cellular plasticity and dedifferentiation programs to avoid immune surveillance, which in turn drives metastatic dissemination and resistance to immunotherapy. A deeper understanding of these programs may provide novel opportunities to enhance the efficacy of existing immunotherapies.
Touch me if you can: The intangible but grounded nature of abstract concepts
Authors: Anna M. Borghi, Luca Tummolini
Journal: Behavioral and Brain Sciences (2020)

Abstract Thinking about what the senses cannot grasp is one of the hallmarks of human cognition. We argue that “intangible abstracta” are represented differently from other products of abstraction, that goal-derived categorization supports their learning, and that they are grounded also in internalized linguistic and social interaction. We conclude by suggesting different ways in which abstractness contributes to cement group cohesion.
UK response to covid-19: obfuscation, misrepresentation, and ignoring advice
Authors: Thomas C McAnea
Journal: BMJ (2020)

Where did the UK’s covid-19 plan go wrong?1 Politics. Despite repeated assurances that it was “following the science,” the government opted to prioritise managing the news process instead.

No government could ever be fully prepared for such an existential crisis as this pandemic. The implications for public health and our economy are enormous. The crisis has exposed how the …
Epitranscriptomics in Hematopoiesis and Hematologic Malignancies
Authors: Margalida Rosselló-Tortella, Gerardo Ferrer, Manel Esteller
Journal: Blood Cancer Discovery (2020)

Abstract Since the 1960s, a large number of chemical modifications have been identified in RNA molecules, establishing the RNA epigenetics field named “epitranscriptomics.” These chemical marks participate in several RNA metabolic processes; however, the biological relevance of many of these modifications and the many enzymes involved in their function is not completely understood. Emerging knowledge of the epitranscriptome (pseudouridine, N6-methyladenosine, and A-to-I editing) in hematopoiesis and hematologic malignancies reveals the requirement of these modifications in normal development and their alteration in disorders, leading to the development of new molecules and strategies to target the epitranscriptome as a novel therapeutic approach. RNA modifications are required for the correct development of hematopoietic cells, and their alteration can promote the development of malignancies or the transition from a low-grade to an aggressive disease. While we are expanding our understanding of the epitranscriptome of normal and malignant hematopoiesis, the number of potential new therapeutic interventions is rising.
Expert Perspectives On Clinical Challenges: Expert Perspectives: Challenges in Scleroderma
Authors: Robert W. Simms
Journal: Arthritis & Rheumatology (2020)

You are consulted to evaluate a 56-year-old woman with known Raynaud's phenomenon, finger swelling of several; months' duration, and new hypertension with a blood pressure of 160/100 mm/Hg. She also reports progressive shortness of breath. Physical examination reveals telangiectasias, sclerodactyly, and proximal skin sclerosis (thick shiny skin on the chest and upper arms), and bibasilar crackles are found on chest examination. Laboratory tests reveal evidence of microangiopathic hemolytic anemia, thrombocytopenia, and elevation of the serum creatinine level (previously normal), and chest computed tomography shows evidence of ground-glass opacification in both lower lung fields.
Heat-Related Deaths — United States, 2004–2018
Authors: Ambarish Vaidyanathan, Josephine Malilay, Paul Schramm, Shubhayu Saha
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Deaths attributable to natural heat exposure, although generally considered preventable (1), represent a continuing public health concern in the United States.During 2004-2018, an average of 702 heat-related deaths occurred in the United States annually.To study patterns in heat-related deaths by age group, sex, race/ethnicity, and level of urbanization, and to explore comorbid conditions associated with deaths resulting from heat exposure, CDC analyzed nationally comprehensive mortality data from the National Vital Statistics System (NVSS).*The rate of heat-related mortality tended to be higher among males, persons aged ≥65 years, non-Hispanic American Indian/Alaska Natives, and persons living in noncore nonmetropolitan and large central metropolitan counties.Natural heat exposure was a contributing cause of deaths attributed to certain chronic medical conditions and other external causes.Preparedness and response initiatives directed toward extreme heat events, currently underway at local, state, and national levels, can contribute to reducing morbidity and mortality associated with natural heat exposure.Successful public health interventions † to mitigate heat-related deaths include conducting outreach to vulnerable communities to increase awareness of heat-related symptoms and provide guidance for staying cool and hydrated, particularly for susceptible groups at risk such as young athletes and persons who are older or socially isolated (2).Improved coordination across various health care sectors could inform local activities to protect health during periods of high heat.For instance, jurisdictions can monitor weather conditions and syndromic surveillance data to guide timing of risk communication and other measures (e.g., developing and implementing heat response plans, facilitating communication and education activities) to prevent heat-related mortality in the United States.CDC also recommends that federal, state, local, and tribal jurisdictions open cooling centers or provide * https://www.cdc.gov/nchs/nvss/index.htm.† https://www.cdc.gov/disasters/extremeheat/index.html.access to public locations with air conditioning for persons in need of a safe, cool, environment during hot weather conditions.In light of the coronavirus disease 2019 (COVID-19) pandemic, CDC updated its guidance on the use of cooling centers to provide best practices (e.g., potential changes to staffing procedures, separate areas for persons with symptoms of COVID-19, and physical distancing) to reduce the risk for introducing and transmitting SARS COV-2, the virus that causes COVID-19, into cooling centers.§ Heat-related deaths among U.S. residents were identified using International Classification of Diseases, Tenth Revision (ICD-10) ¶ codes included in the NVSS multiple-cause-of-death §
Recent successes in therapeutics for Ebola virus disease: no time for complacency
Authors: Patrick L Iversen, Christopher D Kane, Xiankun Zeng, Rekha G Panchal, Travis K Warren, Sheli R Radoshitzky, Jens H Kuhn, Rajini R Mudhasani, Christopher L Cooper, Amy C Shurtleff, Farooq Nasar, Melek ME Sunay, Allen J Duplantier, Brett P Eaton, Elizabeth E Zumbrun, Sandra L Bixler, Shannon Martin, J Matthew Meinig, Chih-Yuan Chiang, Mariano Sanchez-Lockhart, Gustavo F Palacios, Jeffrey R Kugelman, Karen A Martins, Margaret L Pitt, Ian Crozier, David L Saunders
Journal: The Lancet Infectious Diseases (2020)

SummaryThe PALM trial in the Democratic Republic of the Congo identified a statistically significant survival benefit for two monoclonal antibody-based therapeutics in the treatment of acute Ebola virus disease; however, substantial gaps remain in improving the outcomes of acute Ebola virus disease and for the survivors. Ongoing efforts are needed to develop more effective strategies, particularly for individuals with severe disease, for prevention and treatment of viral persistence in immune-privileged sites, for optimisation of post-exposure prophylaxis, and to increase therapeutic breadth. As antibody-based approaches are identified and advanced, promising small-molecule antivirals currently in clinical stage development should continue to be evaluated for filovirus diseases, with consideration of their added value in combination approaches with bundled supportive care, their penetration in tissues of interest, the absence of interaction with glycoprotein-based vaccines, and filoviral breadth.
The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing
Authors: Sara Parsa, Ana Ortega-Molina, Hsia-Yuan Ying, Man Jiang, Matt Teater, Jiahui Wang, Chunying Zhao, Ed Reznik, Joyce P. Pasion, David Kuo, Prathibha Mohan, Shenqiu Wang, Jeannie M. Camarillo, Paul M. Thomas, Neeraj Jain, Javier Garcia-Bermudez, Byoung-kyu Cho, Wayne Tam, Neil L. Kelleher, Nicholas Socci, Ahmet Dogan, Elisa De Stanchina, Giovanni Ciriello, Michael R. Green, Sheng Li, Kivanc Birsoy, Ari M. Melnick, Hans-Guido Wendel
Journal: Nature Cancer (2020)
SAT0074 RHEUMATOID ARTHRITIS AT TREATMENT WITH BDMARD OR TSDMARD: VACCINATION RATES AND INCIDENCE OF RESPIRATORY INFECTIOUS DISEASES, RESULTS FROM A COHORT
Authors: R. Dos Santos Sobrín, E. Perez-Pampín, N. Pérez Gómez, A. Mera Varela
Journal: Annals of the Rheumatic Diseases (2020)

Background: Vaccination regimes have been evaluated for long time in rheumatic diseases, being a strong recommendation to vaccinate against Influenza and Pneumococcus (13 and 23-valent). Rheumatoid arthritis (RA) patients have higher rates of infectious diseases, caused by many reasons, being patient’s comorbidities, rheumatic disease and treatments used the most important 1-2 . Objectives: To analyze the incidence of respiratory infectious diseases in these patients regarding for vaccination status. Also prove the degree of accomplishment of vaccination calendar. Methods: Patients diagnosed of RA at treatment with bDMARD or tsDMARD, in Rheumatology Department of aforementioned hospital, during Influenza vaccination campaign in 2018 (October 2018 – February 2019) were included. Clinical, demographic and therapeutic data were reviewed. Stata 15.1 was used to perform statistical analysis. Results: 237 patients finally fulfilled inclusion criteria, excluding deceases or finished treatment (460 patients were diagnosed of RA and 954 patients conform all bDMARD and tsDMARD of Rheumatology Department). Mean age at beginning of vaccination campaign was 61,5 years old (SD 13,6). 79% were female. Mean time of diagnosis was 15,4 years (SD 9,4). 79,7% patients receive Influenza vaccine, although higher rates were found in Pneumococcal vaccine (86,9% 13-valent and 81,8% 23- valent). Most patients were at treatment with anti-TNF (57,2%, the most prevalent was etanercept 27,5% followed by adalimumab 11,0% and infliximab 10,2%). csDMARD concomitant was achieved by 67,4% patients (methotrexate 73%) and 61% receive corticosteroids. Only 3 patients got hospitalized by pneumonia. As opposed, 39 patients suffer from a respiratory infectious disease without hospitalization (mean of 1,33 infections/patient). After multivariate analysis, only 13-valent Pneumococcal vaccine is related statistically significant with higher rates of respiratory infectious diseases (Chi2=6,25 p=0,012; OR 2,86 CI95% 1,22 to 6,68). Other variables analyzed were kind of bDMARD/tsDMARD, Influenza vaccine, 23-valent Pneumococcal vaccine, concomitant csDMARD/corticosteroids, but no relationship was found. Conclusion: Vaccination status is still incomplete in majority of rheumatic patients. Its benefits have been explained in a variety of studies. That is the reason why, supporting this study, vaccination status must be checked in the daily practice. References: [1] 2019 update of EULAR recommendations for vaccination in adult patients with autoinmune inflammatory rheumatic diseases. Furer V, et al. Ann Rheum Dis. 2020;79:39-52. [2] Inmunización y quimioprofilaxis en pacientes con artritis reumatoide. Begazo A. J Sem Reu. 2013;14(2):36-42. Disclosure of Interests: None declared
Objective Measures Needed — Program Directors’ Perspectives on a Pass/Fail USMLE Step 1
Authors: Alan T. Makhoul, Matthew E. Pontell, Nishant Ganesh Kumar, Brian C. Drolet
Journal: New England Journal of Medicine (2020)

A large majority of U.S. residency program directors do not agree with changing scoring on the USMLE Step 1 exam to pass/fail, and they believe that scores on the Step 2 Clinical Knowledge exam will carry greater weight once the new system is implemented.
Association of Anti–Topoisomerase I Antibodies of the IgM Isotype With Disease Progression in Anti–Topoisomerase I–Positive Systemic Sclerosis
Authors: Maaike Boonstra, Jaap A. Bakker, Annette Grummels, Maarten K. Ninaber, Nina Ajmone Marsan, Corrie M. Wortel, Tom W. J. Huizinga, Suzana Jordan, Anna‐Maria Hoffman‐Vold, Oliver Distler, René E. M. Toes, Hans Ulrich Scherer, Jeska K. de Vries‐Bouwstra
Journal: Arthritis & Rheumatology (2020)

Objective Anti–topoisomerase I (anti–topo I) autoantibodies in systemic sclerosis (SSc) are associated with diffuse skin involvement and interstitial lung fibrosis. Thus far, however, the relationship between anti–topo I antibody response and disease course has not yet been fully evaluated. This study was undertaken to gain insight into the association between characteristics of the anti–topo I antibody response and clinical disease course in SSc patients positive for anti–topo I antibodies. Methods Levels of anti–topo I IgG, anti–topo I IgM, and anti–topo I IgA were assessed in consecutive serum samples obtained from patients at baseline who were positive for anti–topo I IgG in the Leiden Combined Care In Systemic Sclerosis (CCISS) cohort. One‐year disease progression was defined by a relevant increase in modified Rodnan skin thickness score (MRSS), decline in pulmonary function, development of digital ulcers, renal crisis, and pulmonary hypertension, and/or mortality. Validation was performed in SSc patients who were positive for anti–topo I from the Oslo University Hospital and University Hospital Zurich. Results Of the 103 patients with anti–topo I IgG in the CCISS cohort, clinical data were available to assess 1‐year disease progression in 81 patients. Of these 81 patients, 23 (28%) had disease progression. At baseline, patients with disease progression were significantly more often anti–topo I IgM–positive than those who did not experience disease progression (21 [91%] of 23 versus 33 [57%] of 58; P &lt; 0.01). This finding was confirmed in the independent validation samples. Conclusion In SSc patients who were anti–topo I IgG–positive, presence of anti–topo I IgM, which might be considered as a surrogate for an ongoing autoreactive B cell immune response, is associated with disease progression.
Skin pH–dependent <i>Staphylococcus aureus</i> abundance as predictor for increasing atopic dermatitis severity
Authors: Claudia Hülpüsch, Karolina Tremmel, Gertrud Hammel, Madhumita Bhattacharyya, Amedeo de Tomassi, Thomas Nussbaumer, Avidan U. Neumann, Matthias Reiger, Claudia Traidl‐Hoffmann
Journal: Allergy (2020)

Abstract Background Atopic eczema (atopic dermatitis, AD) is characterized by disrupted skin barrier associated with elevated skin pH and skin microbiome dysbiosis, due to high Staphylococcus aureus loads, especially during flares. Since S aureus shows optimal growth at neutral pH, we investigated the longitudinal interplay between these factors and AD severity in a pilot study. Method Emollient (with either basic pH 8.5 or pH 5.5) was applied double‐blinded twice daily to 6 AD patients and 6 healthy (HE) controls for 8 weeks. Weekly, skin swabs for microbiome analysis (deep sequencing) were taken, AD severity was assessed, and skin physiology (pH, hydration, transepidermal water loss) was measured. Results Physiological, microbiome, and clinical results were not robustly related to the pH of applied emollient. In contrast to longitudinally stable microbiome in HE, S aureus frequency significantly increased in AD over 8 weeks. High S aureus abundance was associated with skin pH 5.7‐6.2. High baseline S aureus frequency predicted both increase in S aureus and in AD severity (EASI and local SCORAD) after 8 weeks. Conclusion Skin pH is tightly regulated by intrinsic factors and limits the abundance of S aureus . High baseline S aureus abundance in turn predicts an increase in AD severity over the study period. This underlines the importance and potential of sustained intervention regarding the skin pH and urges for larger studies linking skin pH and skin S aureus abundance to understand driving factors of disease progression.
Differentiating the Differentiation Syndrome Associated with IDH Inhibitors in AML
Authors: Joshua F. Zeidner
Journal: Clinical Cancer Research (2020)

Isocitrate dehydrogenase (IDH) inhibitors have clinical activity in acute myeloid leukemia, in part, by differentiating blasts to mature myeloid cells. In the largest systematic analysis to date, differentiation syndrome was seen in 19% of patients treated with IDH inhibitors. Early recognition with uniform diagnostic criteria, as utilized in acute promyelocytic leukemia, may reduce subsequent complications.See related article by Norsworthy et al., p. 4280.
Solidarity in the wake of COVID-19: reimagining the International Health Regulations
Authors: Allyn L Taylor, Roojin Habibi, Gian Luca Burci, Stephanie Dagron, Mark Eccleston-Turner, Lawrence O Gostin, Benjamin Mason Meier, Alexandra Phelan, Pedro A Villarreal, Alicia Ely Yamin, Danwood Chirwa, Lisa Forman, Gorik Ooms, Sharifah Sekalala, Steven J Hoffman
Journal: The Lancet (2020)
Potential of Ethenone (Ketene) to Contribute to Electronic Cigarette, or Vaping, Product Use–associated Lung Injury
Authors: Kathleen R. Attfield, Wenhao Chen, Kristin J. Cummings, Peyton Jacob, Donal F. O’Shea, Jeff Wagner, Ping Wang, Jefferson Fowles
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Right Ventricular Function and Pulmonary Pressures as Independent Predictors of Survival in Patients With COVID-19 Pneumonia
Authors: Antonello D’Andrea, Raffaella Scarafile, Lucia Riegler, Biagio Liccardo, Fabio Crescibene, Rosangela Cocchia, Eduardo Bossone
Journal: JACC. Cardiovascular imaging (2020)
Vaccines against gastroenteritis, current progress and challenges
Authors: Hyesuk Seo, Qiangde Duan, Weiping Zhang
Journal: Gut Microbes (2020)

Enteric viral and bacterial infections continue to be a leading cause of mortality and morbidity in young children in low-income and middle-income countries, the elderly, and immunocompromised individuals. Vaccines are considered an effective and practical preventive approach against the predominantly fecal-to-oral transmitted gastroenteritis particularly in the resource-limited countries or regions where implementation of sanitation systems and supply of safe drinking water are not quickly achievable. While vaccines are available for a few enteric pathogens including rotavirus and cholera, there are no vaccines licensed for many other enteric viral and bacterial pathogens. Challenges in enteric vaccine development include immunological heterogeneity among pathogen strains or isolates, a lack of animal challenge models to evaluate vaccine candidacy, undefined host immune correlates to protection, and a low protective efficacy among young children in endemic regions. In this article, we briefly updated the progress and challenges in vaccines and vaccine development for the leading enteric viral and bacterial pathogens including rotavirus, human calicivirus, Shigella, enterotoxigenic Escherichia coli (ETEC), cholera, nontyphoidal Salmonella, and Campylobacter, and introduced a novel epitope- and structure-based vaccinology platform known as MEFA (multiepitope fusion antigen) and the application of MEFA for developing broadly protective multivalent vaccines against heterogenous pathogens.