tbuckley/cabot-search huggingface dataset:
Abstract 16459: Active MMP9 Associated to Low MMP9 Removal by Exosomes in the Serum Characterized Patients With Fatal Acute Myocardial Infarction
Authors: Maria Lourdes Higuchi, Camila R Moreno, Renata N Ikegami, Fabio S Yoshikawa, Jaqueline J Pereira, Suely A Palomino, Isabela J Bensenor, Paulo A Lotufo, Maria N Sato
Journal: Circulation (2018)

Introduction: Exosomes (Exos, vesicles <100nm) are known to be increased in circulating blood of patients with acute myocardial infarction (AMI) and MMP9 collagenase is increased in ruptured plaque...
Fully automated closed-loop glucose control compared with standard insulin therapy in adults with type 2 diabetes requiring dialysis: an open-label, randomized crossover trial
Authors: Charlotte K. Boughton, Afroditi Tripyla, Sara Hartnell, Aideen Daly, David Herzig, Malgorzata E. Wilinska, Cecilia Czerlau, Andrew Fry, Lia Bally, Roman Hovorka
Journal: Nature Medicine (2021)

Abstract We evaluated the safety and efficacy of fully closed-loop insulin therapy compared with standard insulin therapy in adults with type 2 diabetes requiring dialysis. In an open-label, multinational, two-center, randomized crossover trial, 26 adults with type 2 diabetes requiring dialysis (17 men, 9 women, average age 68 ± 11 years (mean ± s.d.), diabetes duration of 20 ± 10 years) underwent two 20-day periods of unrestricted living, comparing the Cambridge fully closed-loop system using faster insulin aspart (‘closed-loop’) with standard insulin therapy and a masked continuous glucose monitor (‘control’) in random order. The primary endpoint was time in target glucose range (5.6–10.0 mmol l −1 ). Thirteen participants received closed-loop first and thirteen received control therapy first. The proportion of time in target glucose range (5.6–10.0 mmol l −1 ; primary endpoint) was 52.8 ± 12.5% with closed-loop versus 37.7 ± 20.5% with control; mean difference, 15.1 percentage points (95% CI 8.0–22.2; P &lt; 0.001). Mean glucose was lower with closed-loop than control (10.1 ± 1.3 versus 11.6 ± 2.8 mmol l −1 ; P = 0.003). Time in hypoglycemia (&lt;3.9 mmol l −1 ) was reduced with closed-loop versus control (median (IQR) 0.1 (0.0–0.4%) versus 0.2 (0.0–0.9%); P = 0.040). No severe hypoglycemia events occurred during the control period, whereas one severe hypoglycemic event occurred during the closed-loop period, but not during closed-loop operation. Fully closed-loop improved glucose control and reduced hypoglycemia compared with standard insulin therapy in adult outpatients with type 2 diabetes requiring dialysis. The trial registration number is NCT04025775.
Contezolid: First Approval
Authors: Sheridan M. Hoy
Journal: Drugs (2021)

Contezolid (Youxitai ®), an orally administered oxazolidinone antibacterial agent, is being developed by Shanghai MicuRx Pharmaceutical Co., Ltd. for the treatment of multidrug-resistant (MDR) Gram-positive bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. In June 2021, it was approved by the National Medical Products Administration of China for the treatment of complicated skin and soft tissue infections (cSSTI), including, but not limited to, methicillin-susceptible S. aureus, MRSA, Streptococcus pyogenes and Streptococcus agalactiae. The recommended dosage of contezolid is 800 mg (i.e. two 400 mg tablets) every 12 h for 7-14 days. Contezolid is also undergoing clinical development for acute bacterial skin and skin structure infections (ABSSSI) in the USA, and for diabetic foot infections. This article summarizes the milestones in the development of contezolid leading to this first approval for the treatment of cSSTI.
A novel attention-guided convolutional network for the detection of abnormal cervical cells in cervical cancer screening
Authors: Lei Cao, Jinying Yang, Zhiwei Rong, Lulu Li, Bairong Xia, Chong You, Ge Lou, Lei Jiang, Chun Du, Hongxue Meng, Wenjie Wang, Meng Wang, Kang Li, Yan Hou
Journal: Medical Image Analysis (2021)
少数ショット学習はハイスループットスクリーンから個々の患者へ翻訳する薬物応答の予測モデルを創造する【JST・京大機械翻訳】
Authors: Ma Jianzhu, H Fong Samson, Luo Yunan, J Bakkenist Christopher, Shen John Paul, Mourragui Soufiane, F A Wessels Lodewyk, Hafner Marc, Sharan Roded, Peng Jian, Ideker Trey
Journal: Nature Cancer (2021)
P-272 Significance of adding oxaliplatin to postoperative adjuvant chemotherapy in elderly patients with colorectal cancer
Authors: Y. Nagata, R. Sawada, U. Ishimoto, M. Noguchi, S. Yatabe, Y. Takeda, M. Ohkuma, E. Nagasaki, K. Amano, M. Kosuge, K. Eto, M. Saruta
Journal: Annals of Oncology (2021)
Adapting interventions to new contexts—the ADAPT guidance
Authors: Graham Moore, Mhairi Campbell, Lauren Copeland, Peter Craig, Ani Movsisyan, Pat Hoddinott, Hannah Littlecott, Alicia O’Cathain, Lisa Pfadenhauer, Eva Rehfuess, Jeremy Segrott, Penelope Hawe, Frank Kee, Danielle Couturiaux, Britt Hallingberg, Rhiannon Evans
Journal: BMJ (2021)

Implementing interventions with a previous evidence base in new contexts might be more efficient than developing new interventions for each context. Although some interventions transfer well, effectiveness and implementation often depend on the context. Achieving a good fit between intervention and context then requires careful and systematic adaptation. This paper presents new evidence and consensus informed guidance for adapting and transferring interventions to new contexts.
SO-17 The global POLAR program: Top-line results of placebo-controlled studies of calmangafodipir on top of modified FOLFOX6 to prevent chemotherapy-induced peripheral neuropathy
Authors: C. Qvortrup, K. Muro, M. Lustberg, A. Persson, J. Näsström, S. Carlsson, F. Nagahama, P. Pfeiffer
Journal: Annals of Oncology (2021)
Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): an open-label, phase 2 trial
Authors: Johann S de Bono, Niven Mehra, Giorgio V Scagliotti, Elena Castro, Tanya Dorff, Adam Stirling, Arnulf Stenzl, Mark T Fleming, Celestia S Higano, Fred Saad, Consuelo Buttigliero, Inge M van Oort, A Douglas Laird, Marielena Mata, Hsiang-Chun Chen, Cynthia G Healy, Akos Czibere, Karim Fizazi
Journal: The Lancet Oncology (2021)
25912 Multifocal granular cell tumor affecting skin and scrotum in a child
Authors: Marcos Oro-Ayude, Laura Mesa-Álvarez, Carlos Álvarez-Álvarez, Carlos Feal, Beatriz González-Sixto, Queila Rodríguez-Jato, Carmen Couselo-Rodríguez, Diego Soto-García, Ángeles Flórez
Journal: Journal of the American Academy of Dermatology (2021)
Sleep and Diet: Mounting Evidence of a Cyclical Relationship
Authors: Faris M. Zuraikat, Rebecca A. Wood, Rocío Barragán, Marie-Pierre St-Onge
Journal: Annual Review of Nutrition (2021)

Two factors intrinsic to health are diet and sleep. These two behaviors may well influence one another. Indeed, that insufficient sleep adversely impacts dietary intakes is well documented. On the other hand, diet may influence sleep via melatonin and its biosynthesis from tryptophan. Experimental data exist indicating that provision of specific foods rich in tryptophan or melatonin can improve sleep quality. Whole diets rich in fruits, vegetables, legumes, and other sources of dietary tryptophan and melatonin have been shown to predict favorable sleep outcomes. Although clinical trials are needed to confirm a causal impact of dietary patterns on sleep and elucidate underlying mechanisms, available data illustrate a cyclical relation between these lifestyle factors. We recommend adopting a healthful diet to improve sleep, which may further promote sustained favorable dietary practices.
Asthma and COVID-19 risk: a systematic review and meta-analysis
Authors: Anthony P. Sunjaya, Sabine M. Allida, Gian Luca Di Tanna, Christine R. Jenkins
Journal: European Respiratory Journal (2021)

Individual case series and cohort studies have reported conflicting results in people with asthma on the vulnerability to and risk of mortality from coronavirus disease 2019 (COVID-19).Are people with asthma at a higher risk of being infected or hospitalised or poorer clinical outcomes from COVID-19?A systematic review and meta-analysis based on five main databases including the World Health Organization COVID-19 database between 1 December 2019 and 11 July 2021 on studies with a control (non-asthma) group was conducted. Prevalence and risk ratios were pooled using Sidik-Jonkman random-effects meta-analyses.51 studies with an 8.08% (95% CI 6.87-9.30%) pooled prevalence of people with asthma among COVID-19 positive cases. The risk ratios were 0.83 (95% CI 0.73-0.95, p=0.01) for acquiring COVID-19; 1.18 (95% CI 0.98-1.42, p=0.08) for hospitalisation; 1.21 (95% CI 0.97-1.51, p=0.09) for intensive care unit (ICU) admission; 1.06 (95% CI 0.82-1.36, p=0.65) for ventilator use; and 0.94 (95% CI 0.76-1.17, p=0.58) for mortality for people with asthma. Subgroup analyses by continent revealed a significant difference in risk of acquiring COVID-19, ICU admission, ventilator use and death between the continents.The risk of being infected with severe acute respiratory syndrome coronavirus 2 was reduced compared to the non-asthma group. No statistically significant differences in hospitalisation, ICU admission and ventilator use were found between groups. Subgroup analyses showed significant differences in outcomes from COVID-19 between America, Europe and Asia. Additional studies are required to confirm this risk profile, particularly in Africa and South America, where few studies originate.
Chemoprevention
Authors: P. Greenwald, G. Kelloff, C. Burch-Whitman, B. S. Kramer
Journal: CA A Cancer Journal for Clinicians (1995)

Chemoprevention has been shown to be an extremely promising approach to the prevention of invasive cancer. Through the identification of chemopreventive agents that inhibit or reverse the process of carcinogenesis, new strategies of early intervention can be developed for patients at high risk that potentially prevent the onset of invasive and metastatic phases of cancer. This articles reviews the present efforts in chemoprevention research, including the identification of promising agents, screening, and preclinical and clinical evaluations.
Prevention of vascular-allograft rejection by protecting the endothelial glycocalyx with immunosuppressive polymers
Authors: Erika M. J. Siren, Haiming D. Luo, Franklin Tam, Ashani Montgomery, Winnie Enns, Haisle Moon, Lyann Sim, Kevin Rey, Qiunong Guan, Jiao-Jing Wang, Christine M. Wardell, Mahdis Monajemi, Majid Mojibian, Megan K. Levings, Zheng J. Zhang, Caigan Du, Stephen G. Withers, Jonathan C. Choy, Jayachandran N. Kizhakkedathu
Journal: Nature Biomedical Engineering (2021)
United States trails other rich countries on almost every measure of health, report finds
Authors: Owen Dyer
Journal: BMJ (2021)

The US is a distant outlier in delivering quality healthcare, a study has found, lagging far behind 10 other high income countries in a broad comparison that measured outcomes, access to care, preventive services, waiting times, and the responses of thousands of doctors and patients to survey questions.

Norway, the Netherlands, and Australia took the top three places in the Commonwealth Fund’s survey of 11 countries.1

The US brought up the rear despite spending a much higher proportion of its gross domestic product on healthcare—16.8% compared with an average of 10% in the other nations: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, and the UK.

“In no other country does income inequality so profoundly limit access to care as …
Fatigue in patients with early rheumatoid arthritis undergoing treat-to-target therapy: predictors and response to treatment
Authors: Karen Holten, Nina Paulshus Sundlisater, Siri Lillegraven, Joseph Sexton, Lena Bugge Nordberg, Ellen Moholt, Hilde Berner Hammer, Till Uhlig, Tore K Kvien, Espen A Haavardsholm, Anna-Birgitte Aga
Journal: Annals of the Rheumatic Diseases (2021)

Objectives Fatigue is a frequent symptom in rheumatoid arthritis (RA) and has high impact on quality of life. We explored associations between disease activity and fatigue in patients with early RA during the initial 24 months of modern treat-to-target therapy and predictors of fatigue after 24 months of follow-up. Methods Data were obtained from the treat-to-target, tight control Aiming for Remission in Rheumatoid Arthritis: a Randomised Trial Examining the Benefit of Ultrasound in a Clinical Tight Control Regime (ARCTIC) trial. Fatigue was measured on a visual analogue scale (VAS) from 0 to 100 mm and defined as clinically relevant if VAS was ≥20 mm. Baseline predictors of fatigue at 24 months were analysed by multivariable logistic regression. Results 205 patients with fatigue data at baseline and 24 months were included. Median (25th, 75th percentiles) symptom duration was 5.4 months (2.8, 10.4), fatigue VAS 37.0 mm (13.0, 62.0) and mean Disease Activity Score (DAS) 3.4 (SD 1.1) at baseline. Prevalence of fatigue declined from 69% at baseline to 38% at 24 months. Fewer swollen joints (OR 0.92, 95% CI 0.87 to 0.98, p=0.006), lower power Doppler ultrasound score (OR 0.95, 95% CI 0.90 to 0.99, p=0.027) and higher patient global assessment (PGA) (OR 1.03, 95% CI 1.01 to 1.04, p&lt;0.001) increased the risk of clinically relevant fatigue at 24 months. Not achieving remission at 6 months was associated with a higher risk of reporting fatigue at 24 months. Conclusions Fatigue in patients with early RA was prevalent at disease onset, with a rapid and sustained reduction during treatment. Low objective disease activity and high PGA at baseline were predictors of clinically relevant fatigue at 24 months.
Targeting Aurora B kinase prevents and overcomes resistance to EGFR inhibitors in lung cancer by enhancing BIM- and PUMA-mediated apoptosis
Authors: Kosuke Tanaka, Helena A. Yu, Shaoyuan Yang, Song Han, S. Duygu Selcuklu, Kwanghee Kim, Shriram Ramani, Yogesh Tengarai Ganesan, Allison Moyer, Sonali Sinha, Yuchen Xie, Kota Ishizawa, Hatice U. Osmanbeyoglu, Yang Lyu, Nitin Roper, Udayan Guha, Charles M. Rudin, Mark G. Kris, James J. Hsieh, Emily H. Cheng
Journal: Cancer Cell (2021)
Subgroup-level network meta-analysis for efficacy of first-line immunotherapy-based treatments in advanced non-small cell lung cancer.
Authors: Fang Wu, Wentao Tian, Chenghui Cao, Jiawen Ke, Nuopei Tan, Yuwen Cai, Yue Zeng, Yue Pan, Xiaohan Liu, Lishu Zhao, Long Shu, Junqi Liu
Journal: Journal of Clinical Oncology (2021)

9064 Background: Immunotherapy has unequal efficacies in populations with different clinical or histological features. This study aims to explore inter-subgroup differences in responses to immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) and find the optimal treatments for each subgroup. Methods: We performed (network) meta-analyses of phase III random controlled trials, in which efficacies of 10 immunotherapy-based treatments were compared, including anti-programmed death receptor-1 (PD-1) (+chemotherapy), anti-programmed death ligand-1 (PD-L1) (+chemotherapy), anti-PD-L1+anti-cytotoxic T-lymphocyte protein 4 (CTLA-4), anti-PD-1+anti-CTLA-4 (+chemotherapy), anti-CTLA-4+chemotherapy, anti-PD-1+anti-angiogenic therapy (AT)+chemotherapy, and anti-PD-L1+AT+chemotherapy, for 19 subgroups by sex, age, smoking status, metastatic site (liver/brain/bone), histological type (squamous/non-squamous cancer), and PD-L1 expression, using hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and their 95% confidence intervals (CIs). Results: 22 studies comprised of 12678 patients with advanced NSCLC were included in our study. The results showed OS and PFS advantages of immunotherapy-based treatments in 16 out of 19 subgroups comparing with chemotherapy. Never-smokers (OS-HR 0.81, 95% CI 0.55-1.18; PFS-HR 0.73, 95% CI 0.51-1.07), ¡Ý75-year-old patients (OS-HR 0.9, 95% CI 0.71-1.13), and patients with liver metastases (OS-HR 0.88, 95% CI 0.77-1) showed indisposed responses to immunotherapy. In patients with PD-L1 tumor proportion score (TPS)&lt;1%, anti-CTLA-4+anti-PD-1 and anti-PD-1+anti-CTLA-4+chemotherapy had significant OS benefit comparing with anti-PD-L1 monotherapy (HR 0.6, 95% CI 0.44-0.81; HR 0.6, 95% CI 0.41-0.87; respectively) and anti-PD-L1+AT+chemotherapy (HR 0.66, 95% CI 0.48-0.92; HR 0.66, 95% CI 0.45-0.98; respectively). In patients with liver metastases, anti-PD-L1+AT+chemotherapy showed significant PFS advantage comparing with anti-PD-L1+chemotherapy (HR 0.51, 95% CI 0.33-0.77). As for other populations, anti-PD-1+chemotherapy showed wide-ranging promising efficacies in multiple subgroups. Conclusions: Patients with advanced NSCLC generally benefit from immunotherapy. Specific immunotherapy treatments should be applied according to different clinical or histological features. Meanwhile, we expect more preclinical and clinical studies to focus on therapeutic strategies for populations with impaired responses towards immunotherapy. Funding: CSCO-BMS Oncologic Research Foundation (Grant No. Y-BMS2019-100); Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (Grant No. 2017B030314120) and Guangdong Association of Clinical Trials (GACT); Changsha Science and Technology Bureau (Grant No. kq1907077).
Pooled safety analysis of tisagenlecleucel in children and young adults with B cell acute lymphoblastic leukemia
Authors: John E Levine, Stephan A Grupp, Michael A Pulsipher, Andrew C Dietz, Susana Rives, G Douglas Myers, Keith J August, Michael R Verneris, Jochen Buechner, Theodore W Laetsch, Henrique Bittencourt, Andre Baruchel, Michael W Boyer, Barbara De Moerloose, Muna Qayed, Stella M Davies, Christine L Phillips, Timothy A Driscoll, Peter Bader, Krysta Schlis, Patricia A Wood, Rajen Mody, Lan Yi, Mimi Leung, Lamis K Eldjerou, Carl H June, Shannon L Maude
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T cell therapy, has demonstrated efficacy in children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) in two multicenter phase 2 trials (ClinicalTrials.gov, NCT02435849 (ELIANA) and NCT02228096 (ENSIGN)), leading to commercialization of tisagenlecleucel for the treatment of patients up to age 25 years with B-ALL that is refractory or in second or greater relapse. Methods A pooled analysis of 137 patients from these trials (ELIANA: n=79; ENSIGN: n=58) was performed to provide a comprehensive safety profile for tisagenlecleucel. Results Grade 3/4 tisagenlecleucel-related adverse events (AEs) were reported in 77% of patients. Specific AEs of interest that occurred ≤8 weeks postinfusion included cytokine-release syndrome (CRS; 79% (grade 4: 22%)), infections (42%; grade 3/4: 19%), prolonged (not resolved by day 28) cytopenias (40%; grade 3/4: 34%), neurologic events (36%; grade 3: 10%; no grade 4 events), and tumor lysis syndrome (4%; all grade 3). Treatment for CRS included tocilizumab (40%) and corticosteroids (23%). The frequency of neurologic events increased with CRS severity (p&lt;0.001). Median time to resolution of grade 3/4 cytopenias to grade ≤2 was 2.0 (95% CI 1.87 to 2.23) months for neutropenia, 2.4 (95% CI 1.97 to 3.68) months for lymphopenia, 2.0 (95% CI 1.87 to 2.27) months for leukopenia, 1.9 (95% CI 1.74 to 2.10) months for thrombocytopenia, and 1.0 (95% CI 0.95 to 1.87) month for anemia. All patients who achieved complete remission (CR)/CR with incomplete hematologic recovery experienced B cell aplasia; however, as nearly all responders also received immunoglobulin replacement, few grade 3/4 infections occurred &gt;1 year postinfusion. Conclusions This pooled analysis provides a detailed safety profile for tisagenlecleucel during the course of clinical trials, and AE management guidance, with a longer follow-up duration compared with previous reports.
Pemphigoid gestationis
Authors: A.J. Kanwar
Journal: British Journal of Dermatology (2015)

ORIGINAL ARTICLE, p 120 Pemphigoid gestationis (PG) is a rare and self‐limiting immunobullous disorder of pregnancy, the exact pathogenesis of which has not been fully characterized. It is believed to result from a breakdown of the immunological tolerance of the mother to the fetoplacental unit resulting in autoantibodies to the main target antigen collagen XVII (BP180), which is presented to the maternal immune system by aberrantly expressed human leucocyte antigen (HLA) class II molecules in the placenta. Recent studies have demonstrated that these antibodies are mostly of the IgG4 subclass,1 unlike previous data supporting the role of IgG1 and IgG3 antibodies.2 These antibodies cross the placenta and cross‐react with collagen XVII in the maternal skin resulting in formation of immune complexes, activation of complement and inflammatory cell recruitment, with the release of inflammatory mediators resulting in blister formation on maternal skin. In most patients, antibodies target the extracellular noncollagenous (NC) 16A domain of BP180 antigen; however, in one study, the sera of nine of 15 patients with PG reacted with at least one additional antigenic site other than NC16A.3 In another study, about 10% of patients additionally showed antibodies to BP230 antigen, possibly due to the phenomenon of epitope spreading.4
Very low prevalence of ultrasound-detected tenosynovial abnormalities in healthy subjects throughout the age range: OMERACT ultrasound minimal disease study
Authors: Jeanette Trickey, Ilfita Sahbudin, Mads Ammitzbøll-Danielsen, Irene Azzolin, Carina Borst, Alessandra Bortoluzzi, George AW Bruyn, Philippe Carron, Coziana Ciurtin, Georgios Filippou, Jacek Fliciński, Daniela Fodor, Hélène Gouze, Marwin Gutierrez, Hilde Berner Hammer, Ellen-Margrethe Hauge, Annamaria Iagnocco, Kei Ikeda, Rositsa Karalilova, Helen Isobel Keen, Marion Kortekaas, Giuliana La Paglia, Gustavo Leon, Peter Mandl, Mihaela Maruseac, Marcin Milchert, Mohamed Atia Mortada, Esperanza Naredo, Sarah Ohrndorf, Carlos Pineda, Mads Nyhuus Bendix Rasch, Cristina Reátegui-Sokolova, Garifallia Sakellariou, Teodora Serban, Cesar A Sifuentes-Cantú, Maria S Stoenoiu, Takeshi Suzuki, Lene Terslev, Ilaria Tinazzi, Florentin Ananu Vreju, Ruth Wittoek, Maria-Antonietta D'Agostino, Andrew Filer
Journal: Annals of the Rheumatic Diseases (2021)

Objectives This study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range. Methods Adult HS (age 18–80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1–5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort. Results 939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA p&lt;0.001). In HS, there was no difference in the presence of ultrasound abnormalities between age groups. Conclusions Ultrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA.