tbuckley/cabot-search huggingface dataset:
Changes in Disease Activity and Damage Over Time in Patients With Morphea
Authors: Jack C. O’Brien, Hugh Nymeyer, Allison Green, Heidi T. Jacobe
Journal: JAMA Dermatology (2020)

<h3>Importance</h3> Prospective studies of the disease course in patients with morphea are lacking, particularly those comparing adults and children. <h3>Objective</h3> To investigate the disease course in patients with morphea treated with standard-of-care therapy using validated clinical outcome measures. <h3>Design, Setting, and Participants</h3> Prospective cohort study of 130 adults and children from the Morphea in Adults and Children cohort with at least 2 years of clinical follow-up and Localized Scleroderma Cutaneous Assessment Tool scores recorded at each study visit. Study patients were seen at a tertiary referral center (UT Southwestern Medical Center, Dallas, Texas) from November 1, 2008, through April 1, 2016. The dates of analysis were May 2016 through July 2019. <h3>Exposures</h3> All patients received standard-of-care therapy. <h3>Main Outcomes and Measures</h3> Patterns in disease activity and recurrence were examined. The time to recurrence of morphea disease activity from the first visit with inactive disease was assessed using survival analysis with the log-rank test to compare differences between morphea subtypes. <h3>Results</h3> In total, 130 adults and children (663 study visits) were included in this study. The mean (SD) age of patients was 34.4 (23.8) years, and 101 of 130 (78%) were female. The mean (SD) follow-up was 4.3 (1.7) years. Fifty patients had at least 5 years of follow-up. Most patients were white individuals (96 of 130 [74%]) and had linear subtype (72 of 130 [55%]) or generalized subtype (40 of 130 [31%]). Overall, 13 of 30 (43%) with generalized subtype had recurrence of disease activity compared with 14 of 66 (21%) with linear subtype (hazard ratio, 3.28; 95% CI, 1.38-7.79). The median (interquartile range) time to first recurrence of disease activity after initial resolution of disease activity was 1.1 (0.8-1.9) years for generalized subtype and 2.3 (1.0-3.3) years for linear subtype. Of the 50 patients followed up for at least 5 years, 18 (36%) had recurrence of disease activity. <h3>Conclusions and Relevance</h3> Disease activity appeared to improve in most patients with morphea over 6 to 12 months using previously published treatment plans, underscoring their effectiveness. Sclerosis improved more slowly (over 2-5 years), often after discontinuation of treatment, but atrophy increased slightly as sclerosis subsided. Standard-of-care therapy appears to improve disease activity, which allows sclerosis to improve, and provides relative stability of other features of disease damage. A substantial number of patients, particularly those with generalized subtype, have a relapsing-remitting course over many years. Patients with morphea should be monitored for recurrent disease activity over extended periods.
Deprescribing in Epilepsy
Authors: Samuel W. Terman, Herm J. Lamberink, Kees P. J. Braun
Journal: JAMA Neurology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
ICD植え込み後の頻回作動に対しtriggered PVCのアブレーションが奏効した多発性心室性頻拍の1例 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: 曽我芳光, 山田貴之, 垣下幹夫, 沖野晋一, 安藤献児, 酒井孝裕, 野坂秀行, 延吉正清
Journal: Circulation (2004)
Database Inaccuracies and Disparities in Care Among Homeless Adults Hospitalized for Cardiovascular Conditions
Authors: Karthik Murugiah, Yongfei Wang, Harlan M. Krumholz
Journal: JAMA Internal Medicine (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Counterintuitive results from observational data: a case study and discussion
Authors: Erik Doty, David J Stone, Ned McCague, Leo Anthony G. Celi
Journal: BMJ (2019)

Objective  To explore the issue of counterintuitive data via analysis of a representative case in which the data obtained was unexpected and inconsistent with current knowledge. We then discuss the issue of counterintuitive data while developing a framework for approaching such findings.  Design  The case study is a retrospective analysis of a cohort of coronary artery bypass graft (CABG) patients. Regression was used to examine the association between perceived pain in the intensive care unit (ICU) and selected outcomes.  Setting  Medical Information Mart for Intensive Care-III, a publicly available, de-identified critical care patient database.  Participants  844 adult patients from the database who underwent CABG surgery and were extubated within 24 hours after ICU admission.  Outcomes  30 day mortality, 1 year mortality and hospital length of stay (LOS).  Results  Increased pain levels were found to be significantly associated with reduced mortality at 30 days and 1 year, and shorter hospital LOS. A one-point increase in mean pain level was found to be associated with a reduction in the odds of 30 day and 1 year mortality by a factor of 0.457 (95% CI 0.304 to 0.687, p  Conclusion  The finding of an association between increased pain and improved outcomes was unexpected and clinically counterintuitive. In an increasingly digitised age of medical big data, such results are likely to become more common. The reliability of such counterintuitive results must be carefully examined. We suggest several issues to consider in this analytic process. If the data is determined to be valid, consideration must then be made towards alternative explanations for the counterintuitive results observed. Such results may in fact indicate that current clinical knowledge is incomplete or not have been firmly based on empirical evidence and function to inspire further research into the factors involved.
Biodegradation behavior of micro-arc oxidation coating on magnesium alloy-from a protein perspective
Authors: Zhao-Qi Zhang, Li Wang, Mei-Qi Zeng, Rong-Chang Zeng, M. Bobby Kannan, Cun-Guo Lin, Yu-Feng Zheng
Journal: Bioactive Materials (2020)

Protein exerts a critical influence on the degradation behavior of absorbable magnesium (Mg)-based implants. However, the interaction mechanism between protein and a micro-arc oxidation (MAO) coating on Mg alloys remains unclear. Hereby, a MAO coating was fabricated on AZ31 Mg alloy. And its degradation behavior in phosphate buffer saline (PBS) containing bovine serum albumin (BSA) was investigated and compared with that of the uncoated alloy. Surface morphologies and chemical compositions were studied using Field-emission scanning electron microscope (FE-SEM), Fourier transform infrared spectrophotometer (FT-IR) and X-ray diffraction (XRD). The degradation behavior of the bare Mg alloy and its MAO coating was studied through electrochemical and hydrogen evolution tests. Cytotoxicity assay was applied to evaluate the biocompatibility of Mg alloy substrate and MAO coating. Results indicated that the presence of BSA decreased the degradation rate of Mg alloy substrate because BSA (RCH(NH2)COO‾) molecules combined with Mg2+ ions to form (RCH(NH2)COO)2Mg and thus inhibited the dissolution of Mg(OH)2 by impeding the attack of Cl‾ ions. In the case of MAO coated Mg alloy, the adsorption of BSA on MAO coating and the formation of (RCH(NH2)COO)2Mg exhibited a synergistic effect and enhanced the corrosion resistance of the coated alloy significantly. Furthermore, cell bioactive assay suggested that the MAO coating had good viability for MG63 cells due to its high surface area.
Clinical trial recommendations for potential Alport syndrome therapies
Authors: B. André Weinstock, David L. Feldman, Alessia Fornoni, Oliver Gross, Clifford E. Kashtan, Sharon Lagas, Rachel Lennon, Jeffrey H. Miner, Michelle N. Rheault, James F. Simon, Lisa Bonebrake, Marty Dunleavy, Phil Kumnick, Sharon Lagas, Gina Parziale, Janine Reed, André Weinstock, Susie Gear, Kristen Binaso, Raymond Manuel, James Simon, Gerald Appel, Melanie Blank, Winson Tang, Aliza Thompson, Roser Torra, Kenneth Lieberman, Christoph Licht, Karin Dahan, Kandai Nozu, Hirofumi Kai, Sharon Ricardo, Anne Pariser, David Feldman, Heather Cook, Melanie Chin, Angela Goldsberry, Colin Meyer, Lisa Anne Melia, Radko Komers, Michael Markels, Alex Mercer, Marco Prunotto, Bruce Morgenstern, Ali Hariri, Vijay Modur, Neil Turner, Oliver Gross, Rachel Lennon, Alessia Fornoni, Clifford Kashtan, Michelle Rheault, Colin Baigent, Stephano DeSacco, Laura Perin, Moumita Barua, Koichi Nakanishi, George Jarad, Jeffrey Miner
Journal: Kidney International (2020)

Alport syndrome is experiencing a remarkable increase in preclinical investigations. To proactively address the needs of the Alport syndrome community, as well as offer clarity for future clinical research sponsors, the Alport Syndrome Foundation hosted a workshop to generate consensus recommendations for prospective trials for conventional drugs. Opinions of key stakeholders were carefully considered, including those of the biopharmaceutical industry representatives, academic researchers, clinicians, regulatory agency representatives, and-most critically-patients with Alport syndrome. Recommendations were established for preclinical researchers, the use and selection of biomarkers, standards of care, clinical trial designs, trial eligibility criteria and outcomes, pediatric trial considerations, and considerations for patient engagement, recruitment, and treatment. This paper outlines their recommendations.
Soluble vascular endothelial growth factor receptor 2 (VEGFR2): New biomarker in advanced non-small cell lung cancer (NSCLC)?
Authors: E. Sanmartin, E. Jantus Lewintre, R. Sirera, M. Miñana, A. Navarro, A. Cabrera, A. Blasco, A. Pla, R. Rosell, C. Camps
Journal: Journal of Clinical Oncology (2009)

e22108 Background: An increase in VEGF expression in tumour or some blood compartments (i.e. serum or plasma) has been found in solid tumours of various origins. Several studies have suggested that ligands and receptors of the VEGFs/VEGFR system play an important role in tumour growth and is associated with metastasis and poor prognosis. The aim of our study was to investigate the usefulness of plasmatic VEGFR2 quantification as a new biomarker in advanced NSCLC. Methods: We studied 106 healthy controls (c) and 467 advanced NSCLC patients (p) (stage IIIB and IV) treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy and the plasmatic levels of the VEGFR2 were determined by ELISA. Results: In the NSCLC group, the median age was 59.9, range (31–80); 82% were males. The histological subtypes were: 31.4% squamous, 49.8% adenocarcinoma, 15.3% large cell and undifferentiated and 3.5% other. There was a significant difference in the plasmatic levels of VEGFR2 between c and p (mean± SEM): 6318±152 ng/ml and 8141± 119 ng/ml, respectively (p&lt;0.0001). On the other hand, we found no statistical differences according to sex, histology, or stage. The area under the ROC curve was 0.743 indicating that VEGFR2 is an adequate biomarker for the discrimination between c and p. Dividing the cohort in two subgroups according to VEGFR2 levels: high (&gt;9473,9 ng/ml) and low (≤ 9473,9 ng/ml), we found significant difference in terms of Time to Progression (TTP). Patients with higher levels of VEGFR2 had a median TTP of 204 days whereas in the group with lower expression the median was 164 days, (p= 0.039). Conclusions: In advanced NSCLC, we found higher levels of soluble VEGFR2 in p than in c. There was a correlation between higher expressions of soluble VEGFR2 with better prognosis, in terms of TTP, therefore a more thorough understanding in the role of the plasmatic quantification of this angiogenic receptor in advanced NSCLC p seems to be an important task. No significant financial relationships to disclose.
Not So FASt: Tumor Cells Resisting Death Drive CAR T-cell Dysfunction
Authors: Michael R. Green, Sattva S. Neelapu
Journal: Cancer Discovery (2020)

Abstract Summary: In this issue, Singh and colleagues describe a novel tumor-intrinsic mechanism of resistance to chimericantigen receptor (CAR) T-cell therapy targeting CD19 in B-cell malignancies. They show that reduced expression of death receptor genes in the tumors mediates resistance to killing by CAR T cells, leads to progressive CAR T-cell dysfunction, and is associated with unfavorable clinical outcome in patients. See related article by Singh et al., p. 552.
The COVID-19 pandemic and research shutdown: staying safe and productive
Authors: M. Bishr Omary, Jeetendra Eswaraka, S. David Kimball, Prabhas V. Moghe, Reynold A. Panettieri, Kathleen W. Scotto
Journal: Journal of Clinical Investigation (2020)

The coronavirus disease 2019 pandemic, caused by SARS-CoV-2, has caused severe disease outcomes and widespread infections not seen in terms of its case fatality rate and global economic impact since the 1918 to 1919 Spanish flu, with the latter leading to 675,000 deaths in the United States (US) (50 million worldwide) (1).The US currently has the largest number of SARS-CoV-2 infections in the world, with tremendous health, economic, and social ramifications, including closing of schools, businesses, and all public gatherings in order to maximize social distancing and prevent virus spread.Here, we address the major impact of the COVID-19 pandemic on biomedical research, the challenges created by the COVID-19 pandemic for research-intensive institutions (Figure 1A), and what investigators can do to maintain some level of research activity while keeping their coworkers and trainees safe and engaged (Figure 1B).
Control of brain tumor growth by reactivating myeloid cells with niacin
Authors: Susobhan Sarkar, Runze Yang, Reza Mirzaei, Khalil Rawji, Candice Poon, Manoj K. Mishra, Franz J. Zemp, Pinaki Bose, John Kelly, Jeff F. Dunn, V. Wee Yong
Journal: Science Translational Medicine (2020)

By rejuvenating the deficient activity of myeloid cells in glioblastoma, niacin improves the treatment of otherwise incurable brain tumors.
H3K79me2/3 controls enhancer–promoter interactions and activation of the pan-cancer stem cell marker PROM1/CD133 in MLL-AF4 leukemia cells
Authors: Laura Godfrey, Nicholas T. Crump, Sorcha O’Byrne, I-Jun Lau, Siobhan Rice, Joe R. Harman, Thomas Jackson, Natalina Elliott, Gemma Buck, Christopher Connor, Ross Thorne, David J. H. F. Knapp, Olaf Heidenreich, Paresh Vyas, Pablo Menendez, Sarah Inglott, Philip Ancliff, Huimin Geng, Irene Roberts, Anindita Roy, Thomas A. Milne
Journal: Leukemia (2020)

MLL gene rearrangements (MLLr) are a common cause of aggressive, incurable acute lymphoblastic leukemias (ALL) in infants and children, most of which originate in utero. The most common MLLr produces an MLL-AF4 fusion protein. MLL-AF4 promotes leukemogenesis by activating key target genes, mainly through recruitment of DOT1L and increased histone H3 lysine-79 methylation (H3K79me2/3). One key MLL-AF4 target gene is PROM1, which encodes CD133 (Prominin-1). CD133 is a pentaspan transmembrane glycoprotein that represents a potential pan-cancer target as it is found on multiple cancer stem cells. Here we demonstrate that aberrant PROM1/CD133 expression is essential for leukemic cell growth, mediated by direct binding of MLL-AF4. Activation is controlled by an intragenic H3K79me2/3 enhancer element (KEE) leading to increased enhancer-promoter interactions between PROM1 and the nearby gene TAPT1. This dual locus regulation is reflected in a strong correlation of expression in leukemia. We find that in PROM1/CD133 non-expressing cells, the PROM1 locus is repressed by polycomb repressive complex 2 (PRC2) binding, associated with reduced expression of TAPT1, partially due to loss of interactions with the PROM1 locus. Together, these results provide the first detailed analysis of PROM1/CD133 regulation that explains CD133 expression in MLLr ALL.
Citrulline Not a Major Determinant in the Recognition of Peptidylarginine Deiminase 2 and 4 by Autoantibodies in Rheumatoid Arthritis
Authors: Erika Darrah, Ryan L. Davis, Ashley M. Curran, Pooja Naik, Ruiqiang Chen, Chan Hyun Na, Jon T. Giles, Felipe Andrade
Journal: Arthritis & Rheumatology (2020)

Citrullinated proteins are hallmark targets of autoantibodies in rheumatoid arthritis (RA). Our study was undertaken to determine the effect of autocitrullination on the recognition of peptidylarginine deiminases (PADs) 2 and 4 by autoantibodies in RA.Autocitrullination sites in PAD2 and PAD4 were determined by mass spectrometry and literature review. Antibodies against native and autocitrullinated PADs in 184 patients with RA were detected by enzyme-linked immunosorbent assay. Linear regression analysis, outlier calculations, and competition assays were performed to evaluate antibody reactivity to native and citrullinated PADs.Autocitrullination of PAD2 and PAD4 was detected in 16 (48%) of 33 arginine residues and 7 (26%) of 27 arginine residues, respectively. Despite robust autocitrullination, autoantibodies bound similarly to native and citrullinated PAD2 or PAD4 (ρ = 0.927 and ρ = 0.903, respectively; each P < 0.0001). Although subsets of anti-PAD-positive sera were identified as exhibiting preferential recognition of native or citrullinated PAD2 (40.5% or 4.8%, respectively) or PAD4 (11.7% or 10.4%, respectively), competition assays confirmed that the majority of anti-PAD reactivity was attributed to a pool of autoantibodies that bound irrespective of citrullination status.Autocitrullination does not affect autoantibody reactivity to PADs in the majority of patients with RA, demonstrating that anti-PAD antibodies are distinct from anti-citrullinated protein antibodies in their dependence on citrullination for binding.
Dual neutralisation of interleukin-17A and interleukin-17F with bimekizumab in patients with active ankylosing spondylitis: results from a 48-week phase IIb, randomised, double-blind, placebo-controlled, dose-ranging study
Authors: Désirée van der Heijde, Lianne S Gensler, Atul Deodhar, Xenofon Baraliakos, Denis Poddubnyy, Alan Kivitz, Mary Katherine Farmer, Dominique Baeten, Nadine Goldammer, Jason Coarse, Marga Oortgiesen, Maxime Dougados
Journal: Annals of the Rheumatic Diseases (2020)

Objectives Bimekizumab selectively neutralises both interleukin (IL)-17A and IL-17F. We report efficacy and safety in a phase IIb dose-ranging study in patients with active ankylosing spondylitis (AS). Methods Adults with AS (fulfilling modified New York criteria) were randomised 1:1:1:1:1 to bimekizumab 16 mg, 64 mg, 160 mg, 320 mg or placebo every 4 weeks for 12 weeks (double-blind period). At week 12, patients receiving bimekizumab 16 mg, 64 mg or placebo were re-randomised 1:1 to bimekizumab 160 mg or 320 mg every 4 weeks to week 48; other patients continued on their initial dose (dose-blind period). The primary end point was Assessment of SpondyloArthritis international Society (ASAS) 40 response at week 12 (non-responder imputation (NRI) for missing data). Results 303 patients were randomised: bimekizumab 16 mg (n=61), 64 mg (n=61), 160 mg (n=60), 320 mg (n=61) or placebo (n=60). At week 12, significantly more bimekizumab-treated patients achieved ASAS40 vs placebo (NRI: 29.5%–46.7% vs 13.3%; p&lt;0.05 all comparisons; OR vs placebo 2.6–5.5 (95% CI 1.0 to 12.9)). A significant dose-response was observed (p&lt;0.001). The primary end point was supported by all secondary efficacy outcomes. At week 48, 58.6% and 62.3% of patients receiving bimekizumab 160 and 320 mg throughout the study achieved ASAS40, respectively (NRI); similar ASAS40 response rates were observed in re-randomised patients. During the double-blind period, treatment-emergent adverse events occurred in 26/60 (43.3%) patients receiving placebo and 92/243 (37.9%) receiving bimekizumab. Conclusions Bimekizumab provided rapid and sustained improvements in key outcome measures in patients with active AS, with no unexpected safety findings versus previous studies. Trial registration number NCT02963506 .
Plasma levels of trimethylamine-N-oxide can be increased with ‘healthy’ and ‘unhealthy’ diets and do not correlate with the extent of atherosclerosis but with plaque instability
Authors: Yen Chin Koay, Yung-Chih Chen, Jibran A Wali, Alison W S Luk, Mengbo Li, Hemavarni Doma, Rosa Reimark, Maria T K Zaldivia, Habteab T Habtom, Ashley E Franks, Gabrielle Fusco-Allison, Jean Yang, Andrew Holmes, Stephen J Simpson, Karlheinz Peter, John F O’Sullivan
Journal: Cardiovascular Research (2020)

The microbiome-derived metabolite trimethylamine-N-oxide (TMAO) has attracted major interest and controversy both as a diagnostic biomarker and therapeutic target in atherothrombosis.