tbuckley/cabot-search huggingface dataset:
OP0037 NON–ANTI-TNF BIOLOGIC AGENTS ARE ASSOCIATED WITH LESS MARKED PROGRESSION OF INTERSTITIAL LUNG DISEASE SECONDARY TO RHEUMATOID ARTHRITIS
Authors: N. Mena-Vázquez, F. Godoy-Navarrete, I. Añón Oñate, C. M. Romero-Barco, L. Pérez Albaladejo, A. Fernandez-Nebro
Journal: Annals of the Rheumatic Diseases (2020)

Background: Objectives: To analyze the effect of disease-modifying antirheumatic drugs (DMARDs) on the outcome of interstitial lung disease secondary to rheumatoid arthritis (ILD-RA). Methods: We performed a multicenter, prospective, observational study of patients with ILD-RA receiving DMARDs between 2015 and 2017. The patients were assessed using high-resolution computed tomography and lung function tests at baseline and at 24 months. The radiological assessment was centralized. The main outcome measure at 24 months was change in lung function (improvement, non-progression, progression, or death). We recorded the 28-joint Disease Activity Score 28 (DAS28) and adverse events. A logistic regression analysis was performed to identify factors associated with progression of ILD. Results: We included 70 patients with ILD-RA treated with DMARDs. The main baseline characteristics are shown in Table 1. After 24 months, lung disease did not progress in 40 patients (57.1%), improved in 8 (11.4%), and progressed in 21 (30.0%). One patient (1.4%) died. The factors associated with progression of ILD in the multivariate analysis were treatment with abatacept, tocilizumab, or rituximab (OR, 0.102 [95%CI, 0.015-0.686]), DAS28 (OR, 1.969 [95%CI, 1.005-3.857]), and smoking (OR, 6.937 [95%CI, 1.378-4.900]). During follow-up, 30 patients (42.9%) experienced an adverse event, which was severe in 12 cases (17.1%). Conclusion: Lung function is stable and inflammatory activity well controlled in most patients with ILD-RA receiving treatment with DMARDs. Non–anti-TNF DMARDs reduce the risk of progression of lung disease in 90% of patients, whereas the inflammatory activity of RA and smoking are associated with progression. Table: Variable Patients=70 Epidemiological characteristics Female sex, n (% ) 39 (55.7) Age, y, mean (SD ) 68.8 (7.8) Clinical-laboratory characteristics Smoking history Never smoked, n (% ) 23 (32.9) Smoked, n (% ) 47 (67.1) Time since diagnosis of RA, (months), mean (SD ) 161.0 (125.9) Diagnostic delay, (months), median (IQR ) 12.0 (5.9-24.0) Time since diagnosis of ILD, (months), mean (SD ) 42.3 (48.3) Positive rheumatoid factor (&gt;10), n (% ) 65 (92.0) Anticitrullinated protein antibody (&gt;20), n (% ) 58 (82.9) Synthetic DMARDs 64 (91.4) Methotrexate, n (% ) 30 (42.9) Leflunomide, n (% ) 16 (22.9) Sulfasalazine, n (% ) 8 (11.4) Hydroxychloroquine, n (% ) 10 (14.3) Biologic DMARDs 27 (38.1) Infliximab, n (% ) 1 (1.4) Etanercept, n (% ) 4 (5.7) Adalimumab, n (% ) 1 (1.4) Golimumab, n (% ) 1 (1.4) Certolizumab, n (% ) 0 (0.0) Tocilizumab, n (% ) 5 (6.2) Abatacept, n (% ) 5 (6.2) Rituximab, n (% ) 10 (14.3) Other immunosuppressants Mycophenolate, n (% ) 4 (5.7) Azathioprine, n (% ) 1 (1.4) Disclosure of Interests: None declared
Small Renal Mass Surveillance: Histology-specific Growth Rates in a Biopsy-characterized Cohort
Authors: Antonio Finelli, Douglas C. Cheung, Ashraf Al-Matar, Andrew J. Evans, Christopher G. Morash, Stephen E. Pautler, D. Robert Siemens, Simon Tanguay, Ricardo A. Rendon, Martin E. Gleave, Darrel E. Drachenberg, Joseph L. Chin, Neil E. Fleshner, Masoom A. Haider, John R. Kachura, Jenna Sykes, Michael A.S. Jewett
Journal: European Urology (2020)
Enhancer-gene rewiring in the pathogenesis of Quebec Platelet Disorder
Authors: Minggao Liang, Asim Usman Soomro, Subia Tasneem, Luis E Abatti, Azad Alizada, Xuefei Yuan, Liis Uusküla-Reimand, Lina Antounians, Sana Akhtar Alvi, Andrew David Paterson, Georges E Rivard, Ian C Scott, Jennifer A Mitchell, Catherine P M Hayward, Michael Davies Wilson
Journal: Blood (2020)
Underwater endoscopic submucosal dissection for a duodenal neuroendocrine tumor using pocket creation and ring-shaped thread countertraction methods
Authors: Mitsuhiro Kono, Yasuaki Nagami, Daiki Kitagawa, Taku Manabe, Masaki Ominami, Shusei Fukunaga, Yasuhiro Fujiwara
Journal: Endoscopy (2020)

A 55-year-old man was previously diagnosed with a neuroendocrine tumor (NET) following biopsy of a duodenal submucosal tumor. He was referred to our hospital for treatment of the lesion. Esophagogastroduodenoscopy revealed a submucosal tumor measuring 9 mm in diameter at the superior duodenal angle ([Fig. 1 a]). Endoscopic ultrasound (EUS) revealed a uniform, low echogenic tumor of 8.6 mm in the submucosal layer. Underwater endoscopic submucosal dissection (uESD) [1] using the pocket creation method (PCM) [2] and ring-shaped thread countertraction technique [3] was performed ([Fig. 2]; [Video 1]).
Illustrating your research: design basics for junior clinicians and scientists
Authors: Sarah Nersesian, Natasha Vitkin, Stephanie Grantham, Sheryl Bourgaize
Journal: BMJ (2020)

Communication in the fields of science, technology, engineering, and mathematics has historically been dominated by text based mediums. Scientific articles, textbooks, reviews, conference proceedings, and posters rely heavily on text to communicate scientific findings. Our current method of communication is framed primarily for those who conduct research, and we generally make little use of visual aids, which are arguably more effective.1 However, scientists and clinicians may struggle to translate scientific data into clear and informative graphics. As a group of biomedical postsecondary students and scientific illustrators interested in graphic design, we have consolidated and summarised the eight steps we use for creating eye-catching illustrations. These steps are intended as a practical resource for junior clinicians and scientists to use when creating scientific graphics, including manuscript figures, scientific poster presentations, and slides for oral presentations.

Most people interested in finding information now use online resources. The internet is full of relevant search results, so being able to capture an audience’s attention is crucial for knowledge translation. Some high impact journals, including Cell , now feature and request graphical abstracts, creating a prime opportunity to incorporate visual communication into scientific data presentation.2 Data suggest that clinicians and medical trainees respond more favourably to visual communication methods such as infographics rather than to traditional text based information. For trainees and junior clinicians, designing effective and clear visuals improves communication, knowledge dissemination, and application to real-life scenarios. Visual illustrations are more memorable than words, as stated in the “picture superiority effect.” Several hypotheses have been developed as to why visuals are more memorable.3

Catching readers’ attention is especially crucial when sharing scientific pieces on social media platforms, a key part of knowledge dissemination in today’s society. Scientific illustrations on social media are more accessible than text-heavy articles; a thorough illustration enables …
Comment on So et al. Autoantibody Reversion: Changing Risk Categories in Multiple-Autoantibody–Positive Individuals. Diabetes Care 2020;43:913–917
Authors: Ghadeer E. Alhamar, Rocky Strollo, Paolo Pozzilli
Journal: Diabetes Care (2020)

So et al. (1) have recently published an article in Diabetes Care stating that there is a small percentage of previously multiple-autoantibody–positive type 1 diabetes (T1D) at-risk individuals who reverted to 0 or 1 autoantibody positivity during follow-up visits. Although the proportion of “reverters” to “maintainers” was vastly different, they stated that the risk of progressing to T1D was decreased in these individuals according to the staging of preclinical T1D currently accepted. They went on to say that the 5-year cumulative risk …
OP0243 SERPINA3N LIMITS CARTILAGE DESTRUCTION IN OSTEOARTHRITIS BY INHIBITING MACROPHAGE-DERIVED LEUKOCYTE ELASTASE
Authors: A. Latourte, A. Combier, S. Jaulerry, C. Cherifi, Y. Jouan, H. K. Ea, M. Cohen Solal, E. Hay, P. Richette
Journal: Annals of the Rheumatic Diseases (2020)

Background: Interleukin-6 (IL-6) plays an important role in osteoarthritis (OA). Transcriptomic analyses (RNAseq) revealed that SerpinA3N, a serine protease inhibitor, is a key target of IL-6 in chondrocyte. Objectives: This study aimed to examine the role of SerpinA3N and Leukocyte Elastase (Elane), a serine protease targeted by SerpinA3N, in cartilage destruction during OA. Methods: The role of SerpinA3N was investigated in the destabilization of medial meniscus (DMM) model of murine OA with 1) mice with conditional inducible knockdown of Serpina3n in cartilage ( Col2 Cre ER ; Serpina3n fl/fl mice [ΔSerpina3n Col2 ]) and 2) C57BL/6 wild type (WT) mice treated with intra-articular injection of SerpinA3N (1,5 or 15 nM/week). OA joint lesions were assessed by histology (OARSI and synovitis scores) and micro-CT analysis (osteophyte volume, subchondral bone remodeling). Because serine proteases targeted by SerpinA3N are not produced by murine chondrocytes, Elane expression (qRT-PCR) was determined in murine macrophages (Raw) stimulated or not by IL-6 (100 ng/ml). Recombinant SerpinA3N (30 nM) and a specific Elane inhibitor, Sivelestat (100 µg/ml) were used on cartilage explants treated by conditioned medium of macrophages pre-treated or not by IL-6 (CM–IL-6). Cartilage catabolism was determined by histology and matrix metalloproteinase MMP-3 production was evaluated by Western Blot and immunohistochemistry (IHC). Weekly intra-articular injections of Sivelestat (1mM) were performed in the DMM to determine the role of Elane in OA. Results: ΔSerpina3n Col2 mice had more severe OA lesions than control littermates 6 weeks after DMM, with greater cartilage damage (mean±SD OARSI score: 5.6±0.4 vs 3.4±0.5, p=0.01), increased synovitis scores (3.0±0.3 vs 1.9±0.3, p=0.03) and bigger osteophytes (7.2±0.8x107 vs 3.8±0.8x107 µ3, p=0.048). Conversely, WT mice treated with intra-articular injections of SerpinA3N 15nM exhibited less severe cartilage loss than mice treated with PBS after DMM (OARSI score: 2.1±0.4 vs 3.9±0.5, p=0.02). Elane mRNA expression was increased in macrophages upon IL-6 stimulation. In cartilage explants, CM–IL-6 activated cartilage catabolism and MMP-3 production, and effect that was blunted by SerpinA3N and Sivelestat. Finally, mice treated with intra-articular injections of Sivelestat had less severe cartilage damage than those treated with PBS after DMM (OARSI score: 3.3±0.47 vs 5.8±0.53, p=0.0046). Conclusion: SerpinA3N protects against experimental OA via the inhibition of Elane, a pro-catabolic serine protease produced by macrophages. This results highlight the crosstalk between cartilage and surrounding macrophages and open up new therapeutic perspectives. Acknowledgments: This work has been supported by French Society of Rheumatology and ART Viggo association. Disclosure of Interests: None declared
Psychiatric disorder and gynaecological symptoms in middle aged women:: Authors' reply
Authors: D. Gath, S. Iles, A. Day, M. Osborn, G. Bungay
Journal: BMJ (1987)

highly variable.This surely also applies to bone accretion.In a remote complex of villages in western Transvaal, where all families are fairly poor and subsist on a similar frugal, near veg- etarian diet, we found considerable differences between children, aged 10-12 years", not only in cortical indices of metacarpal but also in haemo- globin, serum cholesterol, and albumin concentra- tions and transit time.Such variability could not be explained by differences in diet.It would seem that the determinants of bone mass are not understood fully and that bone mass is susceptible to little modification, whether in reach- ing maximal accretion or during subsequent loss with age.
Open letter to the ICO, CMOs and UK data providers: Reducing barriers to data access for research in the public interest - lessons from covid-19
Authors: F Carvallaro, F Lugg-Widger, R Cannings-John, K Harron, R McNally, AM Pollock, K Blakey, L Sharp, A O’Donnell, L Hayes, M Pearce, R Harbron, E Slack
Journal: BMJ (2020)
Resistance to PD1 blockade in the absence of metalloprotease-mediated LAG3 shedding
Authors: Lawrence P. Andrews, Ashwin Somasundaram, Jessica M. Moskovitz, Andrea L. Szymczak-Workman, Chang Liu, Anthony R. Cillo, Huang Lin, Daniel P. Normolle, Kelly D. Moynihan, Ichiro Taniuchi, Darrell J. Irvine, John M. Kirkwood, Evan J. Lipson, Robert L. Ferris, Tullia C. Bruno, Creg J. Workman, Dario A. A. Vignali
Journal: Science Immunology (2020)

Mechanisms of resistance to cancer immunotherapy remain poorly understood. Lymphocyte activation gene-3 (LAG3) signaling is regulated by a disintegrin and metalloprotease domain-containing protein-10 (ADAM10)- and ADAM17-mediated cell surface shedding. Here, we show that mice expressing a metalloprotease-resistant, noncleavable LAG3 mutant (LAG3
Abstract 12577: Markers of Residual Risk in Type 2 Diabetes and Stable Ischemic Heart Disease: Insights From the BARI 2D Trial
Authors: Brendan M Everett, Maria Brooks, Helen E Vlachos, Bernard Chaitman, Robert Frye, Deepak L Bhatt
Journal: Circulation (2016)

Background: In spite of aggressive preventive therapy, patients with type 2 diabetes (T2D) and stable ischemic heart disease (SIHD) remain at high risk for major cardiovascular events and death. Understanding the pathophysiologic determinants of that residual risk could help identify effective preventive therapies. Methods and Results: In this Ancillary Study of the BARI 2D trial, we examined the predictive value of biomarkers from 6 distinct pathophysiologic pathways in 2285 men and women with T2D and SIHD who were followed for a median (IQR) of 5.0 (4.1-6.0) years. The endpoint for this Ancillary Study was a composite of myocardial infarction, stroke, heart failure, or all-cause mortality. The 5-year Kaplan-Meier event rate was 31%. The pathophysiologic processes evaluated included dysglycemia (HbA1c), dyslipidemia (LDL-C), myocardial strain (NT-proBNP), myocardial injury (high-sensitivity cardiac troponin T [hsTnT]), subclinical inflammation (high-sensitivity C-reactive protein [hsCRP]), and nephropathy (presence/absence of macroalbuminuria). In Cox proportional hazards models adjusted for baseline risk factors, angiographic severity of disease, and ejection fraction, each marker except LDL-C was a significant predictor of outcome (Figure) in this population with 74% baseline statin use. After mutual adjustment for all 6 markers and baseline risk factors, the hazard ratio (95% CI) per 1-SD of natural logarithm transformed concentration was largest for NT-proBNP [1.29 (1.17, 1.42)], followed by hsTnT [1.16 (1.07, 1.26)], HbA1c [1.12 (1.03, 1.21)], and hsCRP [1.11 (1.03, 1.20). Macroalbuminuria was not a significant predictor after adjustment for the other markers (Figure). Conclusions: In this high-risk population of patients with type 2 diabetes and stable ischemic heart disease, strategies to target myocardial strain, myocardial injury, and subclinical inflammation may lead to improvements in cardiovascular outcome.
Assessment of Parking Fees at National Cancer Institute–Designated Cancer Treatment Centers
Authors: Anna Lee, Kanan Shah, Fumiko Chino
Journal: JAMA Oncology (2020)

The economic and personal distress resulting from the costs of cancer treatment has been referred to as financial toxicity.Nonmedical costs such as travel expenses are almost never reimbursed by insurance and can be a substantial out-of-pocket expense.This cross-sectional study aims to report parking fees at National Cancer Institute (NCI)-designated cancer treatment centers and to assess parking costs for the treatment duration of certain cancers.
ASXL3 bridges BRD4 to BAP1 complex and governs enhancer activity in small cell lung cancer
Authors: Aileen Patricia Szczepanski, Zibo Zhao, Tori Sosnowski, Young Ah Goo, Elizabeth Thomas Bartom, Lu Wang
Journal: Genome Medicine (2020)

Abstract Background Small cell lung cancer (SCLC) is a more aggressive subtype of lung cancer that often results in rapid tumor growth, early metastasis, and acquired therapeutic resistance. Consequently, such phenotypical characteristics of SCLC set limitations on viable procedural options, making it difficult to develop both screenings and effective treatments. In this study, we examine a novel mechanistic insight in SCLC cells that could potentially provide a more sensitive therapeutic alternative for SCLC patients. Methods Biochemistry studies, including size exclusion chromatography, mass spectrometry, and western blot analysis, were conducted to determine the protein-protein interaction between additional sex combs-like protein 3 (ASXL3) and bromodomain-containing protein 4 (BRD4). Genomic studies, including chromatin immunoprecipitation sequencing (ChIP-seq), RNA sequencing, and genome-wide analysis, were performed in both human and mouse SCLC cells to determine the dynamic relationship between BRD4/ASXL3/BAP1 epigenetic axis in chromatin binding and its effects on transcriptional activity. Results We report a critical link between BAP1 complex and BRD4, which is bridged by the physical interaction between ASXL3 and BRD4 in an SCLC subtype (SCLC-A), which expresses a high level of ASCL1 . We further showed that ASXL3 functions as an adaptor protein, which directly interacts with BRD4’s extra-terminal (ET) domain via a novel BRD4 binding motif (BBM), and maintains chromatin occupancy of BRD4 to active enhancers. Genetic depletion of ASXL3 results in a genome-wide reduction of histone H3K27Ac levels and BRD4-dependent gene expression in SCLC. Pharmacologically induced inhibition with BET-specific chemical degrader (dBET6) selectively inhibits cell proliferation of a subtype of SCLC that is characterized with high expression of ASXL3. Conclusions Collectively, this study provides a mechanistic insight into the oncogenic function of BRD4/ASXL3/BAP1 epigenetic axis at active chromatin enhancers in SCLC-A subtype, as well as a potential new therapeutic option that could become more effective in treating SCLC patients with a biomarker of ASXL3-highly expressed SCLC cells.
Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma
Authors: Aaron J. Grossberg, Linda C. Chu, Christopher R. Deig, Eliot K. Fishman, William L. Hwang, Anirban Maitra, Daniel L. Marks, Arnav Mehta, Nima Nabavizadeh, Diane M. Simeone, Colin D. Weekes, Charles R. Thomas
Journal: CA A Cancer Journal for Clinicians (2020)

Abstract Despite tremendous gains in the molecular understanding of exocrine pancreatic cancer, the prognosis for this disease remains very poor, largely because of delayed disease detection and limited effectiveness of systemic therapies. Both incidence rates and mortality rates for pancreatic cancer have increased during the past decade, in contrast to most other solid tumor types. Recent improvements in multimodality care have substantially improved overall survival, local control, and metastasis‐free survival for patients who have localized tumors that are amenable to surgical resection. The widening gap in prognosis between patients with resectable and unresectable or metastatic disease reinforces the importance of detecting pancreatic cancer sooner to improve outcomes. Furthermore, the developing use of therapies that target tumor‐specific molecular vulnerabilities may offer improved disease control for patients with advanced disease. Finally, the substantial morbidity associated with pancreatic cancer, including wasting, fatigue, and pain, remains an under‐addressed component of this disease, which powerfully affects quality of life and limits tolerance to aggressive therapies. In this article, the authors review the current multidisciplinary standards of care in pancreatic cancer with a focus on emerging concepts in pancreatic cancer detection, precision therapy, and survivorship.
Pathogenesis and management of myocardial injury in coronavirus disease 2019
Authors: Zhi‐Yao Wei, Yong‐Jian Geng, Ji Huang, Hai‐Yan Qian
Journal: European Journal of Heart Failure (2020)

The outbreak of coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, has become a major health crisis and a worldwide pandemic. COVID‐19 is characterized by high infectivity, long incubation period, diverse clinical presentations, and strong transmission intensity. COVID‐19 can cause myocardial injury as well as other cardiovascular complications, particularly in senior patients with pre‐existing medical conditions. The current review summarizes the epidemiological characteristics, potential mechanisms, clinical manifestations, and recent progress in the management of COVID‐19 cardiovascular complications.
AB0212 FLARE RISK AFTER DISCONTINUING LONG-TERM METHOTREXATE TREATMENT IN PATIENTS HAVING RHEUMATOID ARTHRITIS WITH LOW DISEASE ACTIVITY
Authors: S. H. Nam, J. S. Lee, S. J. Choi, W. J. Seo, J. S. Oh, S. Hong, Y. G. Kim, C. K. Lee, B. Yoo
Journal: Annals of the Rheumatic Diseases (2020)

Background: Several recent studies have reported that MTX could be discontinued in patients with low disease activity who are taking biologic DMARDs or tofacitinib. However, there are limited studies on whether MTX could be discontinued in patients with low disease activity who have taken MTX for a long term. Objectives: We investigated the disease flare rate in patients with rheumatoid arthritis (RA) who achieved low disease activity following long-term methotrexate (MTX) treatment and the factors related to flare. Methods: This retrospective longitudinal cohort study included patients with RA and low disease activity who were exposed to MTX for &gt;10 years. Disease flare was defined as an increase in DAS28 of &gt;1.2 within 6 months of discontinuation of MTX. Logistic regression analysis was performed to identify the factors associated with flare. Results: In total, 97 patients with RA were included in the study. The mean baseline DAS28 was 1.96 ± 0.56. The median cumulative MTX dose was 11.7g; the median duration of exposure to MTX was 19 years. Following MTX discontinuation, flare occurred in 43 (44.3%) patients; the mean time to flare was 98 ± 37.7 days. According to univariable logistic regression analysis, C-reactive protein, erythrocyte sedimentation rate (ESR) at discontinuation, the average ESR in the 6 months before discontinuation of MTX, a weekly dose of MTX before discontinuation, and use of other conventional synthetic DMARDs were associated with a higher risk of disease flare. In multivariable analysis, a weekly dose of MTX before discontinuation (OR, 1.014; 95% CI, 1.014–1.342; p = 0.031) was significantly associated with flare risk. Conclusion: Among patients with RA who achieved low disease activity with long-term treatment with MTX, more than half of the patients remained flare free after MTX discontinuation. A higher MTX dose before discontinuation was associated with a high flare risk. Disclosure of Interests: None declared