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Joanne Pransky
Industrial Robot: the international journal of robotics research and application; https://doi.org/10.1108/ir-10-2021-0233

Abstract:
Purpose: The purpose of this paper is to provide a “Q&A interview” conducted by Joanne Pransky of Industrial Robot Journal as a method to impart the combined technological, business and personal experience of a prominent, robotic industry engineer-turned entrepreneur regarding his pioneering efforts in starting robotic companies and commercializing technological inventions. The paper aims to discuss these issues. Design/methodology/approach: The interviewee is Jack Morrison, CEO and Co-Founder, Scythe Robotics. Morrison shares how he and his co-founders started this innovative company, the milestones and challenges he’s faced and his long-term goals. Findings: Morrison received Bachelor of Arts degrees in Computer Science and German from Bowdoin College. He attended The George Washington University as a PhD student in Computer Science but left to co-found Replica Labs, a producer of software that turns any mobile phone into a high-quality 3D scanner. Morrison served as Replica’s CTO until it was acquired by Occipital in 2016, where he stayed on as a computer vision engineer until co-founding Scythe Robotics in April 2018. Originality/value: While mowing his lawn in Colorado, Jack Morrison had a sudden insight: what if he could apply the latest robotics technology he was so familiar with to the challenge of commercialized landscaping? In 2018, Morrison teamed up with Replica Labs co-founder Isaac Roberts and Occipital’s Davis Foster, to create Scythe Robotics, a company that builds autonomous robotics solutions for the $105bn commercial landscaping industry. In June 2021, Scythe Robotics emerged from stealth with over $18m in funding with its first commercial product: a transformational, all-electric, fully autonomous mower designed to keep crew productivity high while also increasing the quality of cut and worker safety. The machine features eight high dynamic range cameras and a suite of other sensors that enable it to operate safely in dynamic environments by identifying and responding to the presence of humans, animals and other potential obstacles. Simultaneously, the machine captures valuable property and mower performance data, which helps landscape contractors improve workflow, identify upsell opportunities, schedule more efficiently and manage labor costs. The all-electric powertrain is quiet, emissions-free and radically more reliable than gas-powered manual mowers. Scythe Robotics’ business model is based on Robot as a Service. Instead of buying machines outright, customers are billed by acres mowed. This massively reduces contractors’ expenses and eliminates substantial costs. Scythe Robotics is headquartered in Boulder, Colorado and has offices in Vero Beach, FL and Austin, TX. Scythe is the recipient of the 2020 ALCC (Associated Landscape Contractors CO) Innovation Winner and the 2021 Colorado OEDIT Advanced Industries Grantee.
Erin Shillington
Published: 13 November 2021
Abstract:
New Zealanders have a proud tradition of living close to nature (clean and green). This high interface with nature in traditional New Zealand dwellings is referred to as the “quarter-acre dream” by Mitchell (1972). However, the recent intensification of New Zealand cities has resulted in higher-density, multi-unit dwellings that have little interface with nature. As Auckland alone is expected to require an additional 400,000 homes within the next 30 years, a medium-density housing model that has a high nature-dwelling interface is potentially useful in reducing urban sprawl. In contrast, many Japanese houses are effectively integrated with nature. The number of case studies available through books, journals and on websites suggests that it is possible to group these dwellings under the heading “garden houses”. For the purpose of this research, the term “Japanese Garden House” refers to Japanese houses in which the garden is an integral part of the architecture, as opposed to a separate spatial entity. New Zealand walk-up apartments are analysed to show how this New Zealand housing model relates to nature in addition to revealing typical design elements. Thereafter, the adaptation of the Japanese Garden House for the New Zealand context is proposed as a mechanism to further connect urban dwellings with nature, thus increasing the interface between nature and inhabited space. The significant benefits this mechanism provides, including a positive effect on psychological and physiological wellbeing, are discussed. In order to adapt the features of Japanese Garden Houses to the New Zealand context, a detailed analysis of Japanese Garden Houses is undertaken to reveal design principles and strategies that characterise this type of dwelling. The analysis is limited to houses built in the last 15 years. An investigation, through design, is carried out to determine whether the Japanese Garden House models could be used to reconnect walk-up apartments with nature. The investigation is tested on a typical Auckland site. In a case study design, principles and strategies discovered through analysis of Japanese Garden Houses are applied and, adapted to fit walk-up apartments and the New Zealand context. The outcome is a valuable new New Zealand housing model and a set of guidelines presented as a matrix including key principles, strategies and a menu of solutions with the potential to be applied more broadly by other architects, developers and city councils.
Erin Shillington
Published: 13 November 2021
Abstract:
New Zealanders have a proud tradition of living close to nature (clean and green). This high interface with nature in traditional New Zealand dwellings is referred to as the “quarter-acre dream” by Mitchell (1972). However, the recent intensification of New Zealand cities has resulted in higher-density, multi-unit dwellings that have little interface with nature. As Auckland alone is expected to require an additional 400,000 homes within the next 30 years, a medium-density housing model that has a high nature-dwelling interface is potentially useful in reducing urban sprawl. In contrast, many Japanese houses are effectively integrated with nature. The number of case studies available through books, journals and on websites suggests that it is possible to group these dwellings under the heading “garden houses”. For the purpose of this research, the term “Japanese Garden House” refers to Japanese houses in which the garden is an integral part of the architecture, as opposed to a separate spatial entity. New Zealand walk-up apartments are analysed to show how this New Zealand housing model relates to nature in addition to revealing typical design elements. Thereafter, the adaptation of the Japanese Garden House for the New Zealand context is proposed as a mechanism to further connect urban dwellings with nature, thus increasing the interface between nature and inhabited space. The significant benefits this mechanism provides, including a positive effect on psychological and physiological wellbeing, are discussed. In order to adapt the features of Japanese Garden Houses to the New Zealand context, a detailed analysis of Japanese Garden Houses is undertaken to reveal design principles and strategies that characterise this type of dwelling. The analysis is limited to houses built in the last 15 years. An investigation, through design, is carried out to determine whether the Japanese Garden House models could be used to reconnect walk-up apartments with nature. The investigation is tested on a typical Auckland site. In a case study design, principles and strategies discovered through analysis of Japanese Garden Houses are applied and, adapted to fit walk-up apartments and the New Zealand context. The outcome is a valuable new New Zealand housing model and a set of guidelines presented as a matrix including key principles, strategies and a menu of solutions with the potential to be applied more broadly by other architects, developers and city councils.
Monti Valentina, Serpenti Fabio, Farina Lucia, Moiraghi Maria Luisa, Testi Maria Adele, Pruneri Giancarlo
Archives of Case Reports, Volume 5, pp 028-031; https://doi.org/10.29328/journal.acr.1001053

Abstract:
Chronic Lymphocytic Leukemia (CLL) is a common clonal neoplasm of small, mature B-lymphocytes. CLL is a heterogeneous disease with different clinical presentation, response to treatment and survival.
Sunghoon Hong, Asgar Ahadpour Dodaran, Taeyoon Kim, Jongyeong Kim, Van Men Huynh, Jooyong Lee, Soonchul Kwon
Journal of Coastal Research, Volume 114, pp 524-528; https://doi.org/10.2112/jcr-si114-106.1

Abstract:
Hong, S.; Dodaran, A.A.; Kim, T.; Kim, J.; Huynh, V.M.; Lee, J., and Kwon, S., 2021. Variation of irregular waves passing over an Artificial Coral Reef (ACR). In: Lee, J.L.; Suh, K.-S.; Lee, B.; Shin, S., and Lee, J. (eds.), Crisis and Integrated Management for Coastal and Marine Safety. Journal of Coastal Research, Special Issue No. 114, pp. 524–528. Coconut Creek (Florida), ISSN 0749-0208. To investigate the variation of irregular waves due to an Artificial Coral Reef (ACR), two-dimensional experiments on the wave steepness, wave period, and relative submergence were conducted. The results for the wave transmission coefficient under ACR installation indicated that the wave steepness and period conditions are closely related to wave attenuation, which has similar trends for general coastal structures, even under irregular wave conditions. Additionally, the total spectral energy decreased gradually, whereas an inconsistent peak-energy decrement occurred with a wave steepness of 0.032, which was expected because of spectral energy redistribution due to ACR. The correlation between the relative submergence and spectral energy was investigated via a spectral analysis. In high frequency domain (1.25∼2.25f/fp), the composition ratio of spectral energy increased with larger relative submergence, whereas opposite trend was observed in low frequency domain (0.25∼0.75f/fp). The main findings of this study can provide basic knowledge for understanding irregular wave variation over the ACR.
Peter Tugwell, David Tovey
Published: 1 September 2021
Journal of Clinical Epidemiology, Volume 137; https://doi.org/10.1016/j.jclinepi.2021.08.005

The publisher has not yet granted permission to display this abstract.
Corrigendum
, Johanna Elizabeth Chesham, Raphaelle Winsky-Sommerer, Nicola Jane Smyllie, Michael Harvey Hastings
Published: 5 August 2021
Frontiers in Neuroscience, Volume 15; https://doi.org/10.3389/fnins.2021.740799

Abstract:
A Corrigendum on Circadian Chimeric Mice Reveal an Interplay Between the Suprachiasmatic Nucleus and Local Brain Clocks in the Control of Sleep and Memory by Maywood, E. S., Chesham, J. E., Winsky-Sommerer, R., Smyllie, N. J., and Hastings, M. H. (2021). Front. Neurosci. 15:639281. doi: 10.3389/fnins.2021.639281 In the original article, there was an error in assignment of mouse strain identity. A correction has been made to **Materials and Methods**, **Animals and housing**, **Paragraph number 1**: All experiments were conducted in accordance with the UK Animals (Scientific Procedures) Act of 1986, with local ethical approval (MRC LMB, AWERB). Drd1a-Cre mice (Tg(Drd1-cre)EY266Gsat/Mmucd, RRID:MMRRC_030779-UCD) were purchased from the GENSAT project (Rockefeller University, New York, United States), through the Mutant Mouse Regional Resource Centers (MMRRC, United States). ROSA-YFP mice were provided by Dr. A. McKenzie (MRC LMB). Temporally chimeric mice were created by crossing Drd1a-Cre, ROSA26-EYFP mice with homozygotes for the floxed CK1ε Tau allele (Smyllie et al., 2016). All mice expressed the PER2::LUC bioluminescent reporter (Yoo et al., 2005) and had a C57/BL/6J background. This generated four genotypes: CRE-negative, CK1εWT/WT; CRE-positive, CK1εWT/WT; CRE-negative, CK1εTau/Tau (Tau controls); CRE-positive, CK1εTau/Tau (chimera). The first two groups were combined as WT, in light of no differences between them. Males aged 4–6 months old were used to avoid the estrous modulation of activity patterns. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Smyllie, N. J., Chesham, J. E., Hamnett, R., Maywood, E. S., and Hastings, M. H. (2016). Temporally chimeric mice reveal flexibility of circadian period-setting in the suprachiasmatic nucleus. Proc. Natl. Acad. Sci. U. S. A. 113, 3657–3662. doi: 10.1073/pnas.1511351113 PubMed Abstract | CrossRef Full Text | Google Scholar Yoo, S. H., Ko, C. H., Lowrey, P. L., Buhr, E. D., Song, E. J., Chang, S., et al. (2005). A noncanonical E-box enhancer drives mouse Period2 circadian oscillations in vivo. Proc. Natl. Acad. Sci. U. S. A. 102, 2608–2613. doi: 10.1073/pnas.0409763102 PubMed Abstract | CrossRef Full Text | Google Scholar Keywords: REM sleep, NREM sleep, electroencephalogram, circadian misalignment, suprachiasmatic nucleus Citation: Maywood ES, Chesham JE, Winsky-Sommerer R, Smyllie NJ and Hastings MH (2021) Corrigendum: Circadian Chimeric Mice Reveal an Interplay Between the Suprachiasmatic Nucleus and Local Brain Clocks in the Control of Sleep and Memory. Front. Neurosci. 15:740799. doi: 10.3389/fnins.2021.740799 Received: 13 July 2021; Accepted: 16 July 2021; Published: 05 August 2021. Edited and reviewed by: Natsuko Tsujino, University of Tsukuba, Japan Copyright © 2021 Maywood, Chesham, Winsky-Sommerer, Smyllie and Hastings. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Elizabeth Susan Maywood, [email protected]; Michael Harvey Hastings, [email protected]
, Boaz K. Karmazyn, Christine A. Waldrip, Mythreyi Chatfield, Mark E. Lockhart
Journal of the American College of Radiology, Volume 18; https://doi.org/10.1016/j.jacr.2021.03.021

The publisher has not yet granted permission to display this abstract.
, , Todd A. Schwartz
Published: 31 May 2021
Arthritis Care & Research, Volume 73, pp 919-920; https://doi.org/10.1002/acr.24714

The publisher has not yet granted permission to display this abstract.
S. Stauder, P. M. Peloso
Published: 19 May 2021
by BMJ
Annals of the Rheumatic Diseases, Volume 80, pp 841.2-842; https://doi.org/10.1136/annrheumdis-2021-eular.872

Abstract:
Background: Dual Energy CT Scan (DECT) can detect monosodium urate crystal deposits in multiple tissues. EULAR gout guidelines (Richette, 2020) recognized the value of DECT in making a clinical diagnosis when joint aspiration is difficult. DECT shows crystal deposits in almost 50% of gout patients without tophi (Dalbeth, 2017). Tophi are known to predict all-cause and cardiovascular mortality (Vincent 2017, Perez-Ruiz 2013) and it is plausible that DECT could as well. A prognostic measure should be reliable and valid. DECT validity would be evident for death, disability and distress. Objectives: This study used a best evidence synthesis approach to synthesize the evidence for DECT as a prognostic measure in gout. Methods: PUBMED and EMBASE were searched from initiation to December 2019; keywords (Dual Energy Computed Tomography OR DECT, gout, tophaceous gout, chronic gout, monosodium urate crystals OR monosodium urate burden OR tophi OR monosodium urate volume OR flares OR pain OR distress OR death OR disability OR function). Human studies in English were considered. Titles, abstracts and full articles were reviewed. A manual search of secondary sources was conducted. Key gaps identified were considered throughout 2020 when reviewing emerging articles and presentations. Data extraction was conducted by both authors; data presented represents consensus. Results: Of 344 articles, 81 titles/abstracts met screening inclusion criteria (24%) in the 2019 search; review of the full manuscript led to 41 articles selected (51%). Additionally, 3 key papers and 2 ACR 2020 presentations were identified through 2020. DECT is highly reliable with inter-class correlation coefficients >0.9. DECT has content validity. Dalbeth (2015) showed DECT and X-Rays findings correlated in tophaceous patients, r=0.70, p<0.001. Hand function correlates with DECT burden, with r2=0.59, p=0.024 (Dalbeth 2007). Dalbeth (2017) showed DECT associated with greater flares at 3 and 12 months (p<0.01) in 152 patients. Pascart (2018) confirmed that subjects with flares had nearly doubled DECT feet volumes (0.9 vs 2.1 cm3, p=0.05) versus those not flaring. Dalbeth (2017) showed abnormal DECT scans occurred in 47% of patients with normal uric acid (<6.0 mg/dL) without palpable tophi and in 90% with elevated uric acid and palpable tophi. DECT is very sensitive to change (Araujo 2015) with 95% volume reduction in 152 patients on pegloticase treated up to 12 months. Three studies show DECT is correlated to cardiovascular risk factor prevalence (Pascart 2020, Gamala 2018, Lee 2017). Marty-Ané reported that DECT volume predicts mortality (Marty-Ané ACR 2020). Limited evidence from 3 studies suggests that the minimum important volume for DECT is 1.0 cm3 at feet and ankles, including Pascart 2020. Conclusion: DECT imaging is highly reliable, has evidence for content validity and is highly sensitive to change. DECT appears to predict future gout flares, cardiovascular risk factor prevalence and mortality. Minimum important DECT volume approximates 1.0 cm3. DECT requires further study but appears to be a relevant outcome for clinical trials and staging gout patients. References: Authors Journal, Volume, Issue Year Araujo, E. G., Bayat, S., et al. RMD Open 2015 Dalbeth, N., Nicolaou, S., et al. Ann Rheum Dis, 77(3) 2017 Dalbeth, N., Aati, O., et al. Ann Rheum Dis, 74(6) 2015 Dalbeth, N., Collis, J., et al. Rheumatology, 46(12) 2007 Gamala, M., Linn-Rasker, S. P., et al. Clinical Rheumatol, 37(7) 2018 Lee, K., Ryu, S., et al. Clinical Rheumatol, 37 2017 Marty-Ané, A., Norberciak, L., et al. Arthritis Rheumatol 72 (supp 10) [abstract #0954] ACR 2020. 2020 Pascart, T., Ramon, A., et al. J Clin Med, 9(5) 2020 Pascart, T., Capon, B., et al. Arthritis Res and Therapy, 20(1) 2018 Perez-Ruiz, F., Martínez-Indart, L., et al. Ann Rheum Dis, 73(1) 2013 Richette, P., Doherty, M., et al. Ann Rheum Dis, 79(1) 2020 Vincent, Z., Gamble, G., et al. J Rheumatol, 44 (3) 2017 Disclosure of Interests: Sally Stauder: None declared, Paul M. Peloso Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc.
F. Cacciapaglia, E. De Lorenzis, M. G. Lazzaroni, A. Corrado, M. Fornaro, G. Natalello, F. Montini, A. Altomare, L. Urso, F. P. Cantatore, et al.
Published: 19 May 2021
by BMJ
Annals of the Rheumatic Diseases, Volume 80, pp 701.2-702; https://doi.org/10.1136/annrheumdis-2021-eular.3943

Abstract:
Background: Systemic Sclerosis (SSc) is a chronic rheumatic disease characterized by an autoimmune disorder with vasculopathy that leads to an excess in collagen and other extracellular matrix proteins deposition. This process results in progressive fibrotic and vascular damage of skin and visceral organs. According to observational studies conducted in last decades, mean survival of SSc patients had improved with significant changes in causes of death. Objectives: To assess the 10-years survival in a large Italian multicentre cohort of SSc patients in the last decade compared to previous periods published since the 1980s, and to identify features that can justify any change. Methods: We retrospectively analysed all medical records of our longitudinal SSc cohorts, fulfilling 1980 ARA and/or 2013 EULAR/ACR Classification Criteria, with a median (IQR) follow-up of 91.5 (51-120) months from 4 Scleroderma Units since January 2009. All clinical, laboratory and instrumental findings have been recorded and analysed. Survival rate was calculated with Kaplan-Meier curves and log-rank tests, and Cox proportional hazards models were used to identify any predictor. Then, observed SSc survival was compared to those previously published and to that expected in the general population, calculated using official data published on the website United Nation World Population Prospects (www.macrotrends.net/countries/ITA/italy/death-rate). Results: Of 912 SSc patients (91.6% female; mean (SD) age at first non-Raynaud symptom (RS) 51 (15.4) years; median (IQR) disease duration from non-RS 24 (0-84.7) months) diffuse cutaneous involvement was defined in 182 (20%) patients. Anti-centromere and anti-topoisomerase-I were detected in 390 (42.8%) and 302 (33.1%) patients, respectively, while 220 (24.1%) presented antibodies for other extractible nuclear antigens. Prevalent non-Raynaud manifestations were interstitial lung disease detected in 459 (50.3%), digital ulcers in 395 (43.3%) and oesophagopathy in 371 (40.7%) patients, respectively, while other gastrointestinal manifestations were reported in 234 (25.7%) patients. Chronic renal failure was observed in 61 (6.7%) patients and pulmonary arterial hypertension (PAH) was confirmed at right heart catheterization in 38 (4.2%) patients. Three hundred twenty-two (35.3%) patients received immunosuppressant, 215 (23.5%) assumed an endothelin receptor antagonist and/or a 5-phosphodiesterase inhibitor, and 72 (7.9%) were treated with a biologic agent. The global 10-years survival was 89.4%; female gender (HR 0.33, CI95% 0.17-0.67), diffuse cutaneous involvement (HR 2.14, CI95% 1.17-3.91), presence of pulmonary hypertension (HR 2.61, CI95%1.31-5.16) and older age at non-RS (HR 1.1, CI95% 1.06-1.12) affected survival. Furthermore, as compared to previous Italian studies, our cohort showed a significant improvement in rate (see Figure 1). Conclusion: Survival in SSc patients has improved in last 5 decades but still reduced compared to that expected in general population above all 5 years after diagnosis. Early diagnosis, with reduced renal involvement, along with better screening and innovative therapeutic strategies may explain these achievements. Figure 1. Ten-years survival in SSc patients since 2009 (left); comparison of survival across different Italian SSc cohorts (box: current analysis) (right). References: [1]Giordano M, et al. The Journal of Rheumatology. 1986; 13:911-916. [2]Ferri C, et al. Medicine. 2002; 81:139-53. [3]Vettori S, et al. Reumatismo. 2010; 62(3):202-209. [4]Ferri C, et al. Autoimmun Rev. 2014; 13(10):1026-34. Disclosure of Interests: None declared
F. Natalucci, F. Ceccarelli, T. Colasanti, G. Olivieri, A. I. Celia, C. Barbati, M. Speziali, F. Ucci, C. Pirone, C. Ciancarella, et al.
Published: 19 May 2021
by BMJ
Annals of the Rheumatic Diseases, Volume 80, pp 1073.1-1073; https://doi.org/10.1136/annrheumdis-2021-eular.3688

Abstract:
Background: Joint involvement represents one of the most frequent features in patients affected by Systemic Lupus Erythematosus (SLE). This manifestation is characterized by a great heterogeneity in phenotype and severity: the application of more sensitive imaging techniques identified an erosive damage in about 25% of patients (1). This damage has been associated with autoantibodies, such as anti-citrullinated (ACPA) and anti-carbamylated proteins (antiCarP), previously identified in patients Rheumatoid Arthritis (RA) patients. Recently, homocysteinylated alpha 1 antitrypsin (Hcy-1A1AT) has been identified as a new antigenic target of autoantibodies in seronegative RA patients: in detail, anti-homocysteinylated alpha 1 antitrypsin (anti – HATA) antibodies have been identified in 75.7% of patients (2). Objectives: In the present study, we aimed at determining the prevalence of anti – HATA in a cohort of SLE patients. Methods: We evaluated patients affected by SLE according to the 1997 ACR criteria. Demographic, clinical, and laboratory data were collected in a standardized computerized electronically filled form. Each subject underwent peripheral blood sample collection. Hcy-A1AT was obtained by in vitro modification of native A1AT and used as antigens by ELISA to test the presence of anti–HATA in sera obtained from enrolled subjects. Finally, we investigated the presence of ACPA and Rheumatoid Factor (RF) commercial ELISA kits and of anti-CarP (home-made ELISA) by a home-made ELISA in SLE patients’ sera. As control, we enrolled 40 patients affected by Osteoarthritis (OA) and 41 healthy subjects (HS). Results: The present analysis included 88 SLE patients (M/F 6/82 median age 47 years (IQR 17), median disease duration 156 months (IQR 180). Joint involvement was observed in 75 SLE patients (85.2%): in detail, 65 patients referred arthritis and the remaining 10 inflammatory arthralgias. We identified the presence of anti–HATA IgG in 38 SLE patients (43.2%). This prevalence was significantly higher in comparison with OA and HS subjects [15.0% (p<0.001) and 0% (p<0.0001), respectively; Figure 1A]. Focusing on the SLE cohort, no differences were observed between patients with and without joint involvement in anti–HATA IgG prevalence (41.3% versus 34.7%, respectively; p=0.34). However considering SLE patients according to the presence of arthralgia and arthritis, the prevalence of anti-HATA was significantly higher in patients with arthritis in comparison with those patients with arthralgias (46.1% versus 11.1%, p=0.02; figure 1B). Finally, no significant association between anti-HATA and the other tested autoantibodies (RF, ACPA, anti-CarP) was found. Conclusion: We evaluated the prevalence of anti-HATA in a cohort of SLE patients. The prevalence of these autoantibodies was significantly higher in SLE patients than in OA patients and in HS. The association with arthritis suggests a possible role for anti-HATA as biomarkers of SLE-related joint involvement. References: [1]Ceccarelli F. Perricone C. Cipriano E. et al. Joint involvement in systemic lupus erythematosus: From pathogenesis to clinical assessment. Seminar in Arthritis and Rheumatism, 47(1), 53 – 64. [2]Colasanti T. Sabatinelli D. Mancone et al. Homocysteinylated alpha 1 antitrypsin as an antigenic target of autoantibodies in seronegative rheumatoid arthritis patients. Journal of Autoimmunity 2020 Sep;113:102470. Disclosure of Interests: None declared
A. Bankole, S. Pachigolla
Published: 19 May 2021
by BMJ
Annals of the Rheumatic Diseases, Volume 80, pp 297.1-298; https://doi.org/10.1136/annrheumdis-2021-eular.127

Abstract:
Background: Glucocorticoids (GC) are used in the treatment of various inflammatory conditions and it is estimated that about 1% of US population is treated with long term steroids. High doses of GC particularly those used by rheumatologists have adverse effects on bone health and is associated with rapid bone loss resulting in Glucocorticoid induced Osteoporosis(GIO) and an increased risk of fractures. The risk of bone loss relates to high daily dose and the high cumulative dose of the GC. Despite the availability of effective preventative and treatment options, GIO is often under treated with many patients treated only after a fracture has occurred. Objectives: The purpose of this study was to examine if providing education to care providers lead to an improvement in the identification, evaluation, and treatment of GIO. Methods: This is a single center, prospective study that was performed at a university based tertiary referral center. Patients over 40 years, receiving a total cumulative dose of GC of >5 grams and/or a single dose of >30 mg of prednisone or equivalent was enrolled. A patient list was generated by our technology group. All providers received intervention in the form of an academic Journal Club, at which the current ACR guidelines regarding GIO was reviewed. Monthly reminders were shared with all providers within our monthly communications. All the pre and post interventional data was analyzed. The continuous variables were analyzed using T-test or Mann-Whitney U test. Categorical variables were analyzed using Chi-square Tests or Fisher’s exact tests. Statistical analysis was performed using SAS9.4, and p value <0.05 was considered statistically significant. Results: Post education, there was a statistically significant increase in vitamin D replacement and the use of bisphosphonates as well as a reduction in the use of bone mineral density (BMD) tests within the at risk group while on GC. Table 1. Glucocorticoid induced Osteoporosis (GIO) Pre-treatment(N=72) Post-treatment(N=54) p-value Demographics Age (years) 58.9 ± 19.2 64.2 ± 16.7 0.11 Body Mass Index 29.0 ± 6.7 29.4 ± 8.4 0.77 Gender (Female) 73.6% 74.1% 0.95 Race White 83.3% 77.8% 0.43 Hispanic 1.4% 5.6% 0.31 Insurance ANTHEM BCBS 16.9% 26.9% Commercial 11.3% 11.5% Medicaid 12.7% 9.6% Medicare 59.2% 51.9% 0.58 Medical History Osteoporosis 68.1% 64.8% 0.70 Osteoporotic Fracture 15.3% 11.1% 0.50 Vasculitis 26.4% 22.2% 0.59 Systemic Lupus Erythematosus 18.1% 13.0% 0.44 Rheumatoid Arthritis 12.5% 25.9% 0.05 Polymyalgia Rheumatica 6.9% 11.1% 0.41 Inflammatory Muscle Disease 18.1% 20.4% 0.74 Spondyloarthritis 1.4% 1.9% 0.99 Lab Results Serum Vitamin D (Normal) 41.3% (19/46) 52.8% (19/36) 0.3 GIO Prevention Measures Calcium 2.8% 13.0% 0.04 Vitamin D 18.1% 61.1% <0.01 Bisphosphonates 9.7% 35.2% <0.01 RANKL inhibitors 4.2% 11.1% 0.17 Bone Mineral Density 43.5% (10/23) 10.5% (2/19) 0.02 Conclusion: There was a significant improvement between the GIO pre and post-educational data, with increasing use of GIO preventive measures. Importantly, there was also a reduction in BMD testing of patients while still on GC. This research show the importance of provider education as a means of disseminating information and improving the quality of patient care. References: [1]Compston J. Glucocorticoid-induced osteoporosis: an update. Endocrine. 2018 Jul;61(1):7-16. doi: 10.1007/s12020-018-1588-2. [2]2017 American college of rheumatology guideline for the prevention and treatment of Glucocorticoid-induced Osteoporosis. Arthritis & Rheumatology Vol. 69, No. 8, august 2017, pp 1521-1537. DOI 10.1002/art.40137. [3]Fardet L, Petersen I, Nazareth I. Monitoring of patients on long-term glucocorticoid therapy: a population-based cohort study. Medicine (Baltimore). 2015 Apr;94(15):e647. doi: 10.1097/MD.0000000000000647. Disclosure of Interests: None declared
S. Lugo-Perez, J. R. Azpiri-López, I. J. Colunga-Pedraza, D. Á. Galarza-Delgado, A. B. Rodriguez-Romero, N. Guajardo-Jauregui, A. Cárdenas, H. Azpiri-Diaz, O. A. Cepeda-Ayala
Published: 19 May 2021
by BMJ
Annals of the Rheumatic Diseases, Volume 80, pp 511.1-511; https://doi.org/10.1136/annrheumdis-2021-eular.2790

Abstract:
Background: Patients with Rheumatoid Arthritis (RA) have a higher prevalence of cardiovascular diseases (1) and a strong association with abnormalities in the left ventricle (LV) geometry. Both concentric and eccentric remodeling have been determined as an independent factor for sudden cardiac arrest in the general population with normal or slightly decreased ventricular function (2) but there is still controversy about the factors involved and the pathophysiology in patients with RA. Objectives: The aim of the study is to determine the characteristics of LV geometry and the impact of RA. Methods: A cross-sectional, observational, and comparative study of fifty-two RA patients that fulfilled ACR / EULAR 2010 classification criteria, aged 40-75 years. Controls were included and matched by age, gender, and comorbidities. Subjects were evaluated using a transthoracic echocardiogram performed and reviewed by two certified echocardiographers. Ventricular geometry was evaluated with indexed left ventricular mass and relative wall thickness. Distribution was evaluated with the Kolmogorov-Smirnov test. Descriptive analysis was done using measures of central tendency. Chi square, Student’s t test and Mann-Whitney U test were used for comparations between groups. A logistic binary regression was performed with the traditional cardiovascular risk factors (CVRFs), age and RA diagnosis. A p value <0.05 was considered statistically significant. Results: No significant differences were found in the traditional CVRFs (type 2 diabetes mellitus, dyslipidemia, active smoking, and hypertension) (Table 1). Most of the subjects reported normal geometry in both groups (55.8% for RA group vs 64.0% for controls). A higher prevalence of eccentric hypertrophy was found in the RA group, 13 (25%) subjects versus 3 (6%) in the control group, p = 0.009. The binary regression showed that the diagnosis of RA was the only independent risk factor for the presence of eccentric hypertrophy, OR 7.22 95% CI (1.68-31.02, p = 0.008). Table 1. Demographic characteristics and echocardiographic findings. RA (n=52) Control (n=50) p Age, years ± DE 51.4 ±6.2 51.1 ± 5.5 NS Women, n (%) 51 (98.1) 49 (98.0) NS Active smoking, n (%) 8 (15.4) 8 (16.0) NS Dyslipidemia, n (%) 11 (21.2) 13 (26.0) NS Type 2 Diabetes Mellitus, n (%) 5 (9.6) 5 (10.0) NS HTN, n (%) 8 (15.4) 10 (20.0) NS BMI kg/m2, median (p25-p75) 27.8 (24.5-31.4) 28.3 (25.4-30.3) NS BSA, median (p25-p75) 1.7 (1.6-1.8) 1.8 (1.6-1.9) 0.003 Systolic blood pressure, mmHg (p25-p75) 119.5 (110.0-127.5) 120.0 (110.7-130.0) NS Echocardiography findings LVPWTd, median (p25-p75) 0.9 (0.8-1.0) 0.9 (0.8-1.0) NS LVIDd, median (p25-p75) 4.8 (4.3-5.2) 4.6 (4.5-4.9) NS LV mass, median (p25-p75) 131.2 (119.5-155.7) 131.2 (113.2-154.3) NS LV mass index, median (p25-p75) 78.6 (69.7-95.6) 76.0 (66.7-84.6) NS RWT, mean ± SD 0.4 ± 0.09 0.4 ± 0.07 NS NS, no significant; BMI, body mass index; BSA, body surface area; LVPWTd, left ventricular posterior wall thickness at end-diastole; LVIDd, left ventricular internal dimension at end-diastole; RWT, relative wall thickness. Conclusion: There is a higher prevalence of eccentric remodeling in patients with RA independently of traditional CVRF. The diagnosis of RA is an independent risk factor for the presence of eccentric hypertrophy that is associated with higher mortality. Treatment of cardiovascular comorbidities should be intensified in those patients with abnormalities in LV geometry in order to prevent cardiovascular diseases such as heart failure. References: [1]You S, Cho CS, Lee I, et al. A systems approach to rheumatoid arthritis. PLoS One 2012;7(12):e51508. doi: 10.1371/journal.pone.0051508 [2]Pascale V, Finelli R, Giannotti R, et al. Cardiac eccentric remodeling in patients with rheumatoid arthritis. Sci Rep 2018;8(1):5867. doi: 10.1038/s41598-018-24323-0 Disclosure of Interests: None declared
M. M. Sirufo, F. De Pietro, M. Raggiunti, M. De Martinis, L. Ginaldi
Published: 19 May 2021
by BMJ
Annals of the Rheumatic Diseases, Volume 80, pp 1246.1-1246; https://doi.org/10.1136/annrheumdis-2021-eular.2268

Abstract:
Background: Systemic Sclerosis (SSc) is a generalized and systemic autoimmune disease that affects the connective tissue of the skin and internal organs, especially kidneys, heart and lungs [1]. Objectives: Numerous data from recent literature confirm the regulatory action of vitamin D on the immune system and, therefore, how a deficit of this micronutrient can lead to alterations in the immune response, as is known to happen in many allergic and autoimmune diseases [2]. We studied the association between vitamin D levels and SSc, evaluating their correlation with the characteristic manifestations of the pathology. Methods: We dosed the serum levels of 25 hydroxy-vitamin D in 42 patients with SSc (average age 64.63 +/-7.33) and 40 healthy controls comparable for sex and age. The diagnosis of SSc was formulated in accordance to 2013 ACR/EULAR criteria. None of the subjects involved in the study took vitamin D products. Results: Patients’ vitamin D levels (26.22+/-9.82 ng/ml), although they tended to be lower than controls (27.80 +/- 16.53 ng/ml), showed no significant decrease. In patients with pulmonary fibrosis, vitamin D levels were 23.28 +/- 12.30 lower than in patients with trophic ulcers and compared to patients without complications 26.07 +/- 9.92, although with not statistically significant values. No statistically significant difference was found between vitamin D levels in patients with trophic ulcers compared to controls without complications. Conclusion: According to the studies in the literature, in our sample, vitamin D deficiency was therefore greater in patients with SSc, especially with pulmonary fibrosis, than in controls [3,4]. Vitamin D levels in diffused-type SSc patients were significantly lower than those in limited-type SSc patients. Further studies are needed to clarify the role that vitamin D deficiency plays in SSc, but lower vitamin D levels in these patients may suggest the need to monitor blood levels of vitamin D and supplement it appropriately. References: [1]De Martinis M, Ciccarelli F, Sirufo MM, Ginaldi L. An overview of environmental risk factors in systemic sclerosis. Expert Rev Clin Immunol. 2016;12(4):465-78. doi: 10.1586/1744666X.2016.1125782. Epub 2015 Dec 19. PMID: 26610037. [2]Yang, CY., Leung, P.S.C., Adamopoulos, I.E. et al. The Implication of Vitamin D and Autoimmunity: a Comprehensive Review. Clinic Rev Allerg Immunol 45, 217–226 (2013). https://doi.org/10.1007/s12016-013-8361-3. [3]Trombetta AC, SmithV, Gotelli E, Ghio M, Paolino S, Pizzorni C, et al. (2017) Vitamin D deficiency and clinical correlationsin systemic sclerosis patients: A retrospective analysis for possible future developments. PLoS ONE 12(6): e0179062.https://doi.org/10.1371/journal. pone.0179062. [4]Sarita Gupta, Vikram K. Mahajan, Rajinder S. Yadav1, Karaninder S. Mehta, Satya Bhushan1, et al. Evaluation of Serum Vitamin D Levels in Patients with Systemic Sclerosis and Healthy Controls: Results of a Pilot Study Article July 2018 DOI: 10.4103/idoj.IDOJ_328_17. Disclosure of Interests: None declared
L. Nacef, H. Ferjani, H. Riahi, Y. Mabrouk, E. Labbene, K. Maatallah, D. Kaffel, M. Bouaziz, W. Hamdi
Published: 19 May 2021
by BMJ
Annals of the Rheumatic Diseases, Volume 80, pp 1119.3-1120; https://doi.org/10.1136/annrheumdis-2021-eular.4183

Abstract:
Background: Patients with rheumatoid arthritis (RA) are at higher cardiovascular risk (CVR) than the general population due to chronic inflammation. Several factors, both modifiable and non-modifiable, can increase this risk. Intima-media thickness (IMT) was considered as a marker for atherosclerosis. Objectives: This study aimed to identify predictor factors of increasing IMT. Methods: The prospective study was carried out on patients with RA who met the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria. These patients were followed in the rheumatology department of the Kassab Institute. The socio-demographic data, biological and immunological parameters were collected. Framingham’s score quantified the cardiovascular risk at 10-years. Carotid Ultrasonography (US) using a high resolution B mode carotid measured intima-media thickness (IMT) as a subclinical marker of atherosclerosis. Carotid US was performed in the supine position, according to American Society of Echocardiography guidelines. IMT was measured in the left (LCC) and right (RCC) common carotid arteries, the left (LIC) and right (RIC) internal carotid arteries, and the left (LEC) and right (RIC) internal carotid arteries. An increased IMT was defined as ≥0.9 mm. We analyzed data by the SPSS statistical package. A p-value <0.05 was considered significant. Results: Of the 47 patients surveyed, 78.7% were female. The mean age was 52.5 ±11.06 [32-76]. The duration disease was 86.25 ±63 months [5-288] and was erosive in 81.6% of cases. The rheumatoid factor (RF) was positive in 57.8% of patients, and citrullinated antipeptide antibodies (ACPA) were present in 62.2%. Eight patients had a previous CV history (hypertension, diabetes or dyslipidemia) and 16.4% were active smokers. Among women, 43.6% were postmenopausal. ITM was significantly higher in men at LIC (0.037) and LEC (0.025). Older age was associated with increased ITM in LIC (p=0.046; r=0.295), LEC (p=0.05; r=0.412), RCC (p=0.034; r=0.317), and REC (p=0.009; r=0.382). The ITM for LCC, LIC, LEC, RCC, RIC, and REC was higher in postmenopausal women, with no significant difference (p=0.782, p=0.208, p=0.877, r=0.734, p=0.808, p=0.437, respectively). Among the modifiable factors, active smoking was associated with a higher ITM at the REC level (p=0.047). However, weight was not associated with an increased ITM (LCC: p=0.092; LIC: p=0.985; LEC: p=0.952; RCC: p=0.744; RIC: p=0.210; REC: p=0.510). In our study, there was no significant association between DAS28 disease activity or inflammatory marks and ITM (LCC: p=0.784; LIC: p=0.316; LEC: p=0.420; RCC: p=0.784; RIC: p=0.484; REC: p=0.754). Conclusion: In our study, the non-modifiable factors associated with increased ITM were advanced age and male gender. The modifiable factor impacting ITM was primarily active smoking. Surprisingly, disease activity and biological inflammation did not influence ITM. References: [1]S. Gunter and al. Arterial wave reflection and subclinical atherosclerosis in rheumatoid arthritis. Clinical and experimental rheumatology 2018; 36: clinical e.xperimental. [2]Aslan and al. Assessment of local carotid stiffness in seronegative and seropositive rheumatoid Arthritis. Scandinavian cardiovascular journal, 2017. [3]Martin i. Wah-suarez and al, carotid ultrasound findings in rheumatoid arthritis and control subjects: a case-control study. Int j rheum dis. 2018;1–7. Disclosure of Interests: None declared
Z. B. Özcan, F. S. Karaahmetoğlu, M. Z. Çiraci, H. H. Pençe, M. Vural, E. I. Üstün, A. Kural, S. Kuraş, B. Erdoğan
Published: 19 May 2021
by BMJ
Annals of the Rheumatic Diseases, Volume 80, pp 1086.1-1086; https://doi.org/10.1136/annrheumdis-2021-eular.1369

Abstract:
Background: The goal of treatment for patients with RA is achieve to remission, or at least a state of low disease activity. Exercise is recommended for patients with RA in addition to drug therapy. It has been found to be effective in greatly improving functionality and reducing cardiovascular risk without exacerbating disease activity. Therefore, it is recommended that all RA patients should be encouraged to include aerobic and resistant exercise training as part of their routine treatment (1). miRNAs(miRNA) are known to protect the pathophysiological process specific to RA. miRNA-146a is one of the miRNAs extensively studied in RA, its expression was found to be higher in the synovial fluid and synovial tissue of RA patients compared to healthy individuals (2). Many studies have found that miRNA-146a, along with miRNA-16 and miRNA155 may be related to disease pathology. It has also been found that high levels of miRNA-16 expression correlate with active disease and low levels of expression with inactive disease. It has been found that the increased level of miRNA-155 causes a problem in the modulation of arthritis It has been found that the expression level of miRNA-145 is increased in peripheral blood mononuclear cells of RA patients and synovium supporting osteoclastogenesis (3,4,5). Objectives: It is aimed to investigate the effect of exercise on microRNA expressions in patients with rheumatoid arthritis (RA). Methods: 30 patients and 30 healthy controls aged 18-60 years who met the 2010 ACR / EULAR RA criteria were included in the study. A program consisting of strengthening and stretching exercises 2 days a week was applied to the study group for 8 weeks. One day a week, 30 minutes of mild moderate walking was requested. Of the cases at the beginning and at the end of the treatment; 5-10 cc peripheral blood samples were taken into one EDTA tube. Then Numeric Rating Scale (NRS) was used for pain, 28-joint Disease Activity Score (DAS28) was used to calculate disease activity, Health Assessment Questionnaire (HAQ) was used to assess general health and Short Form-36 (SF-36) was used to evaluate quality of life. 5-10 cc peripheral blood samples were taken to only 1 EDTA tube of the control group. In the samples taken, gene expressions of miRNA-146a, miRNA-155, miRNA-16, miRNA-145 were determined by real-time PZR method. Results: There was a significant difference in DAS28, SF-36, NRS, HAQ scales before and after treatment in the RA group of patients (p 0.05). The expression level of MiRNA-146a does not differ significantly before and after treatment (p> 0.05). However, these two groups differ significantly with the control group (p 0.05). No significant difference was observed in the miRNA-155 and miRNA-16 expression levels in the pretreatment, posttreatment, and control groups (p> 0.05). Conclusion: Exercise therapy has a good effect on pain, disease activity, quality of life and general health in patients with RA. It has been found that exercise can affect vii some of the miRNAs involved in disease pathogenesis. However, more comprehensive studies are needed. References: [1]Cooney JK, Law RJ, Matschke V, Lemmey AB, Moore JP, Ahmad Y, et al. Benefits of exercise in rheumatoid arthritis. Journal of Aging Research. 2011. p. 14. [2]Abou-Zeid A, Saad M, Soliman E. MicroRNA 146a expression in rheumatoid arthritis: Association with tumor necrosis factor-alpha and disease activity. Genet Test Mol Biomarkers. 2011;15(11):807–12. [3]Murata K, Yoshitomi H, Tanida S, Ishikawa M, Nishitani K, Ito H, et al. Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis. Arthritis Res Ther. 2010;12(3):86. [4]Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EKL. Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther. 2008;10(4):101. [5]Evangelatos G, Fragoulis GE, Koulouri V, Lambrou GI. Micrornas in rheumatoid arthritis: From pathogenesis to clinical impact. Autoimmun Rev. 2019;18(11):102391. Disclosure of Interests: None declared
N. M. Elemam, M. Hachim, S. Hannawi, A. A. Maghazachi
Published: 19 May 2021
by BMJ
Annals of the Rheumatic Diseases, Volume 80, pp 412.1-412; https://doi.org/10.1136/annrheumdis-2021-eular.2075

Abstract:
Background: Rheumatoid arthritis (RA) is the most common inflammatory type of arthritis, with various immune players implicated in its pathogenesis. Natural killer (NK) cells are innate lymphocytes that showed controversial roles in RA, whether pathogenic or protective (Shegarfi, H. et al. 2012, Yap, H.-Y. et al. 2018). Previously, we were able to identify a gene signature in NK cells of RA patients that can aid in understanding the state of NK cells in RA disease and identify RA patients from healthy controls (Elemam, N.M. et al. 2019, Elemam, N.M. et al. 2020). Furthermore, this signature might facilitate the selection of biomarkers that can be used for early detection of RA and prediction of effectiveness of RA treatment. Objectives: In this study we aimed at exploring the effect of several RA therapeutic agents such as tocilizumab, rituximab and anti-TNFα (adalimumab, etanercept and golimumab) on the previously identified gene signature in NK cells of RA patients. Methods: Whole blood transcriptomic data from publicly available dataset (GSE93272) was used to predict the percentage of activated NK cells in the blood of RA patients using the software CIBERSORT. Then, a correlation analysis was done between the percentage of NK cells and number of days of receiving tocilizumab treatment. Whole blood samples were collected from the recruited 17 RA patients (satisfying the 2010 ACR/EULAR classification criteria for RA). NK cells were isolated using RosetteSep negative selection method and RNA was extracted and gene expression was assessed using qRT-PCR. RA patients taking tocilizumab, rituximab, or anti-TNFα (adalimumab, etanercept or golimumab but none of the patients received infliximab) were compared to those not receiving any biological DMARDs. Statistical analysis was done using Student’s t-test. Results: In silico analysis has shown that the percentage of activated NK cells is positively correlated with the number of days of tocilizumab therapy in RA patients, suggesting a direct enhancing effect of tocilizumab on NK cell activity. Then, it was crucial to investigate the effect of different biological DMARDs on NK gene expression in RA patients. All the investigated chemokines (CCL2, CXCL10, CXCL16, CXCR1, CXCR2, CXCR6 and CCR4) in the identified gene signature showed a significant change in RA patients receiving tocilizumab, rituximab, or anti-TNFα therapies. Furthermore, the other genes including RELA, ICAM, IL1RN, TLR3 and TLR10 were significantly changed in NK cells of RA patients receiving biological DMARDs in comparison to patients not receiving the treatments. However, some of the genes including CD56, BTK, IBTK, ITGB7, IL1B, PECAM-1, IL12RB2, IFNG and CKLF did not show a significant change upon receipt of biological DMARDs. Conclusion: In conclusion, NK cell activity and gene expression could be affected by the type of biological DMARDs received by RA patients. Therefore, this identified gene signature of NK cells could be used as a diagnostic tool to identify RA patients and a target for biological DMARDs in RA. References: [1]Elemam, N. M., M. Y. Hachim, S. Hannawi and A. A. Maghazachi (2019). “Natural Killer Cells Gene Expression Can Differentiate Rheumatoid Arthritis Patients from Healthy Controls [abstract].” ACR/ARP Annual Meeting, supplement of Arthritis & Rheumatology 71(suppl 10). [2]Elemam, N. M., M. Y. Hachim, S. Hannawi and A. A. Maghazachi (2020). “Differentially Expressed Genes of Natural Killer Cells Can Distinguish Rheumatoid Arthritis Patients from Healthy Controls.” Genes (Basel) 11(5). [3]Shegarfi, H., F. Naddafi and A. Mirshafiey (2012). “Natural killer cells and their role in rheumatoid arthritis: friend or foe?” TheScientificWorldJournal 2012: 491974-491974. [4]Yap, H.-Y., S. Z.-Y. Tee, M. M.-T. Wong, S.-K. Chow, S.-C. Peh and S.-Y. Teow (2018). “Pathogenic Role of Immune Cells in Rheumatoid Arthritis: Implications in Clinical Treatment and Biomarker Development.” Cells 7(10): 161. Figure 1. In silico analysis and correlation of NK cell activity with the number of days of Tocilizumab therapy in RA patients. Disclosure of Interests: None declared
P. Klemm, J. Bär, I. Aykara, K. Frommer, E. Neumann, U. Müller-Ladner, U. Lange
Published: 19 May 2021
by BMJ
Annals of the Rheumatic Diseases, Volume 80, pp 676.1-676; https://doi.org/10.1136/annrheumdis-2021-eular.1735

Abstract:
Background: More than 95% of patients with systemic sclerosis (SSc) suffer from Raynaud’s syndrome (RS) leading to digital ulcerations (DU). In severe RS, intravenous application of prostaglandins is required. Moreover, these patients profit from an additional non-pharmacological treatment using hyperthermia to increase vasodilatation and perfusion, and to reduce pain. Serial locally applied water-filtered infrared A radiation (sl-wIRAR) is a hyperthermia treatment modality using infrared heat radiation in the range of 780-1400nm with high tissue penetration and low thermal load on the skin surface [1]. wIRAR has both, temperature-dependent and non-dependent effects, which do not inherit thermal energy transfer and/or relevant temperature changes [1]. It is therefore not only used in acute and chronic wound healing as it promotes perfusion, alleviates pain and has anti-infectious effects [2], but is also used in oncology [3] and rheumatology [4]. Objectives: We conducted a randomized controlled trial with a follow-up visit after 2 weeks to evaluate the value of a high-frequent hyperthermia treatment using sl-wIRAR in comparison to a low-frequent hyperthermia treatment (our standard) in SSc patients with severe RS receiving Iloprost treatment. Methods: Eligible patients had SSc according to the 2013 ACR/EULAR classification criteria, were 18 to 80 years old and had RS requiring treatment with Iloprost in an in-patient setting. Key exclusion criteria were contraindications to any hyperthermia treatment such as infection or heat insensitivity. The trial was conducted at Campus Kerckhoff of Justus-Liebig University Giessen. Eligible patients were equally randomized to the intervention group (IG) receiving additional sl-wIRAR treatment (2 treatments for 30 min per day for 8 days) plus the standard of care (Iloprost treatment over 8 days plus daily carbon dioxide hand baths of 20 min) and the control group (CG) receiving only the standard of care. Primary outcome was the between-group difference in pain measured on a numeric rating scale (NRS) after intervention. Key secondary outcomes included a change in RS frequency, RS duration, and a change in Interleukin (IL) -6 and VEGF levels. Results: From 01.03.2020 to 31.12.2020 49 SSc patients met the inclusion criteria. 42 patients were enrolled (IG: 21, CG: 21). 38 patients (IG:19, CG: 19) completed the full trial period and were analyzed. There was no statistically significant between-group difference in pain levels (NRS) (p=0.284, Z -1.082 (Mann-Whitney U Test)) and thus the primary outcome was not met. Therefore, all p values for secondary outcomes are nominal. Intensity (Visual analogue scale 0-100mm) and duration (min) of RS were reduced in the IG (mean ± standard error) -14.579 ± 7.214 mm (p=0.058) and -2.917 ± 1.510 min (p=0.08), respectively. Intra- and inter-group comparison of IL-6 and VEGF levels showed no relevant change. Conclusion: The additive and frequent use of sl-wIRAR in the treatment of SSc patients with RS requiring Iloprost treatment does not improve outcomes regarding pain levels, RS intensity or frequency nor IL-6 and VEGF levels when compared to Iloprost treatment and low-frequent hyperthermia application. References: [1]Hoffmann G. Clinical applications of water-filtered infrared-A (wIRA) – a review. Phys Med Rehab Kuror. 2017;27(05):265–274. [2]Hoffmann G, Harte M, Mercer JB. Heat for wounds – water-fil- tered infrared-a (wIRA) for wound healing – a review. GMS Ger Med Sci. 2016;14:Doc08. [3]Notter M, Thomsen AR, Nitsche M, et al. Combined wIRA-hyperthermia and hypofractionated re-irradiation in the treatment of locally recurrent breast cancer: evaluation of therapeutic outcome based on a novel size classification. Cancers (Basel). 2020;12(3): 606. [4]Klemm P, Eichelmann M, Aykara I et al. Serial locally applied water-filtered infrared a radiation in axial spondyloarthritis – a randomized controlled trial, International Journal of Hyperthermia, 37:1, 965-970. Acknowledgements: We acknowledge the help of Carina Schreiyäck. This study was in part supported by the Dr. med. h.c. Erwin Braun Foundation, Basel, a charitable, nonprofit Swiss scientific foundation approved by the Swiss Federal Administration. The foundation supports clinical investigation of waterfiltered infrared-A. The foundation was not involved in any content- or decision-related aspect of the study. This study was prospectively registered at www.drks.de (German Registry of Clinical Studies): DRKS00021098 Disclosure of Interests: None declared
C. Chen, S. Yang, Z. Jiang, W. Wan, H. Zou, M. Liang
Published: 19 May 2021
by BMJ
Annals of the Rheumatic Diseases, Volume 80, pp 698.1-698; https://doi.org/10.1136/annrheumdis-2021-eular.3648

Abstract:
Background: Serum fibrotic markers for systemic sclerosis (SSc) remain limited. The Enhanced Liver Fibrosis (ELF) score, originally derived and validated in patients with chronic liver disease, is an algorithm combining 3 serum markers, known as procollagen type III amino terminal propeptide (PIIINP), tissue inhibitor of metalloproteinases 1 (TIMP-1), and hyaluronic acid (HA). The combined score was proved to be superior to the single components in reflecting the severity of liver fibrosis. However, the performance of ELF score and its components has not been fully validated in SSc. Objectives: To investigate PIIINP, TIMP-1, HA, and the combined algorithm ELF score as fibrotic markers for SSc skin involvement. Methods: Eighty SSc patients (44 dcSSc and 36 lcSSc), fulfilling the 2013 ACR/EULAR criteria with the absence of chronic liver diseases, were enrolled. Eighty age- and sex- matched healthy controls were also included. Serum PIIINP and HA levels were quantified by chemiluminescence immunoassay. Serum TIMP-1 levels were determined by enzyme-linked immunosorbent assay. The ELF score was calculated using the formula ELF score= 2.494 + 0.846*ln(HA) + 0.735*ln(PIIINP) + 0.391*ln(TIMP-1). Results were correlated with clinical profiles including modified Rodnan skin score (mRSS) and interstitial lung disease (ILD). Results: Compared with healthy controls, patients with SSc showed significantly elevated serum PIIINP (11.2±4.8 vs. 5.73±1.4μg/L, p<0.001), TIMP-I (123.7±78.6 vs. 67.8±26.5 ng/ml, p<0.001), and ELF score (10.5±0.9 vs. 9.7±0.4, P<0.001). Even higher levels of PIIINP, TIMP-1, and ELF score were observed in dcSSc patients, compared with lcSSc patients (p<0.001, p=0.024, p=0.003, respectively). No significant difference was found in the levels of serum HA between patients and controls. Strong correlations were observed between mRSS and ELF score (r=0.54, p<0.001), and between mRSS and PIIINP(r=0.62, p<0.001), whereas only weak correlations could be observed between mRSS and TIMP-1 (r=0.28, p=0.02), and between mRSS and HA (r=0.26, p=0.03). When stratified by ELF score, using cutoffs proposed for liver fibrosis and cirrhosis, SSc patients with ELF11.3 showed the highest (p<0.001). When stratified by serum PIIINP levels, using the 25th and 75th percentiles, SSc patients with serum PIIIINP levels14.0μg/L showed the highest (p<0.001). Neither the ELF score nor its components showed significant difference between patients with and without ILD. Conclusion: The ELF score could be used for reflecting the severity of overall skin involvement in SSc, and serum PIIINP also increased in parallel with the increase of mRSS. Longitudinal prospective studies exploring ELF score or serum PIIINP as fibrotic markers and outcome measures of SSc are warranted. References: [1]Lichtinghagen R, Pietsch D, Bantel H, et al. The Enhanced Liver Fibrosis (ELF) score: Normal values, influence factors and proposed cut-off values. Journal of Hepatology. 2013; 59: 236-42. [2]Abignano G, Blagojevic J, Bissell LA, et al. European multicentre study validates enhanced liver fibrosis test as biomarker of fibrosis in systemic sclerosis. Rheumatology. 2019; 58: 254-59. Figure 1. Correlations of mRSS with ELF score (A) and serum PIIINP (B) and distribution of mRSS among different ELF (C) and PIIINP (D) ranges. Acknowledgements: The authors have no acknowledgements to declare. Disclosure of Interests: None declared
F. Del Galdo, O. Distler, C. Denton, Y. Allanore, D. Wachtlin, M. Alves, D. Khanna
Published: 19 May 2021
by BMJ
Annals of the Rheumatic Diseases, Volume 80, pp 1244-1244; https://doi.org/10.1136/annrheumdis-2021-eular.1760

Abstract:
Background: The ACR Composite Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) was developed to measure the probability of improvement in response to treatment in patients with early diffuse cutaneous SSc (dcSSc), accounting for new/worsening cardiopulmonary involvement and/or renal crisis, and changes in modified Rodnan skin score, forced vital capacity, health assessment questionnaire disability index, and patient’s and physician’s global impressions. In patients with SSc-ILD, treatment response may be reflected as slower progression, stabilisation or improvement. Objectives: Using data from patients with dcSSc and ILD in the placebo group of the SENSCIS trial, we analysed the probability of improvement using the ACR CRISS score at week 52. We also evaluated whether the CRISS numerator could provide information on the spectrum of responses in this patient population. Methods: The SENSCIS trial enrolled subjects with SSc-ILD with onset of first non-Raynaud symptom ≤7 years before screening, FVC ≥40% predicted, and fibrotic ILD ≥10% extent on an HRCT scan. Subjects on prednisone ≤10 mg/day (or equivalent) and/or stable therapy with mycophenolate or methotrexate were allowed to participate. Subjects were randomised to receive nintedanib or placebo. Subjects were not randomised by use of mycophenolate. In patients randomised to receive placebo who had dcSSc and/or mRSS >15 at baseline, we analysed the ACR CRISS and its numerator at week 52 in subgroups by use of mycophenolate at baseline. Analyses were exploratory and descriptive. Results: Of 117 analysed subjects in the placebo group who had dcSSc and/or mRSS >15 at baseline, 60 (51.3%) were taking mycophenolate at baseline. Compared with patients not taking mycophenolate at baseline, those taking mycophenolate had a lower mean age (48.4 [SD 11.8] vs 53.1 [13.4] years), lower mean FVC % predicted (68.8 [17.0] vs 73.0 [14.6]), and a greater proportion were female (76.7% vs 71.9%); median time since first onset of non-Raynaud symptom was similar (3.9 vs 4.5 years, respectively) as was mean (SD) mRSS (16.5 [7.7] vs 15.9 [8.0], respectively). One patient (taking mycophenolate at baseline) had limited cutaneous SSc. At week 52, median (Q1, Q3) ACR CRISS score was 0.036 (0.001, 0.601) in subjects taking mycophenolate and 0.002 (0.000, 0.112) in subjects not taking mycophenolate at baseline, and mean (SD) ACR CRISS score was 0.28 (0.37) in subjects taking mycophenolate and 0.16 (0.31) in subjects not taking mycophenolate at baseline (Figure 1). In these groups, respectively, 25.0% and 14.0% of subjects had CRISS score >0.6 (considered improved) at week 52. The CRISS numerator provided a broader distribution of response values, but was not informative in this patient population. Conclusion: In exploratory analyses, among subjects with dcSSc and ILD who received placebo in the SENSCIS trial, the proportion considered improved at week 52 based on ACR CRISS score was numerically greater in patients taking than not taking mycophenolate at baseline. There remains a need for composite scores that provide better interpretation of the magnitude of response in patients with SSc. Acknowledgements: The SENSCIS trial was funded by Boehringer Ingelheim. Medical writing support was provided by FleishmanHillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). Disclosure of Interests: Francesco Del Galdo Speakers bureau: Actelion and AstraZeneca, Consultant of: Actelion, AstraZeneca, Boehringer Ingelheim, Capella BioScience, ChemomAb and Mitsubishi Tanabe Pharma, Grant/research support from: Capella BioScience, Kymab and Mitsubishi Tanabe Pharma, Oliver Distler Consultant of: AbbVie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Bayer, Blade Therapeutics, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos NV, GlaxoSmithKline, Glenmark Pharmaceuticals, Horizon (Curzion) Pharmaceuticals, Inventiva, IQVIA, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Target Bioscience, Topadur Pharma and UCB, Grant/research support from: Kymera Therapeutics and Mitsubishi Tanabe Pharma, Christopher Denton Speakers bureau: Boehringer Ingelheim, Corbus, Janssen, and Mallinckrodt Pharmaceuticals, Consultant of: Acceleron Pharma, Arxx Therapeutics, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos NV, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mallinckrodt Pharmaceuticals, Roche, Sanofi and UCB, Grant/research support from: Arxx Therapeutics, GlaxoSmithKline and Servier, Yannick Allanore Consultant of: Boehringer Ingelheim, Medsenic, Menarini and Sanofi, Grant/research support from: Alpine Pharmaceuticals, Daniel Wachtlin Employee of: Currently an employee of Boehringer Ingelheim, Margarida Alves Employee of: Currently an employee of Boehringer Ingelheim, Dinesh Khanna Shareholder of: Eicos Sciences, Inc. (less than 5%), Consultant of: Acceleron Pharma, Actelion, AbbVie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Gilead Sciences, Galapagos NV, Genentech/Roche, GlaxoSmithKline, Horizon Therapeutics, Merck, Mitsubishi Tanabe Pharma, Sanofi-Aventis and United Therapeutics, Grant/research support from: Bayer, Bristol-Myers Squibb, Horizon Therapeutics, Immune Tolerance Network, National Institutes of Health and Pfizer, Employee of: Chief Medical Officer- CiviBioPharma/Eicos Sciences, Inc.
E. Mozgovaya, S. Bedina, A. Trofimenko, M. Mamus, S. Spitsina, I. Zborovskaya
Published: 19 May 2021
by BMJ
Annals of the Rheumatic Diseases, Volume 80, pp 1062.1-1062; https://doi.org/10.1136/annrheumdis-2021-eular.3168

Abstract:
Background: According to modern concepts, rheumatoid arthritis (RA) refers to severe autoimmune rheumatic diseases. The activation of free radical oxidation processes is essential in the development of this disease [1]. Xanthine oxidoreductase is a significant reactive oxygen species source [2]. Despite the great advances in the treatment of rheumatoid arthritis (RA) associated with the introduction of innovative drugs and especially the improvement of the strategy for their use into clinical practice, glucocorticoids still remain an important component of RA pharmacotherapy in actual clinical practice. Objectives: to evaluate the changes in activities of xanthine oxidoreductase interconvertible forms (xanthine oxidase, ЕС 1.17.3.2 and xanthine dehydrogenase, ЕС 1.17.1.4) in lysed red blood cells of RA patients in relation with glucocorticoid treatment. Methods: 47 RA patients with verified RA and 30 healthy controls were enrolled in the study. The diagnosis was verified using the 2010 ACR/EULAR criteria 2010. All patients have moderate DAS28 scores. RA patients were randomized into 2 groups comparable in gender, age and the principal clinical manifestations. Methylprednisolone (Metipred, Orion Corp.), average dose 30 mg/day, and betamethasone (Diprospan, Schering-Plough), single dose7 mg, were administered intramuscularly in the respective groups. Хanthine oxidase (XO) and xanthine dehydrogenase (XDG) activities were measured in lysed red blood cells by spectrophotometric method as previously described [3]. The changes of these enzymes activities were studied in RA patients before and after the injection of glucocorticoids. Statistical comparison tests were selected in according to common guidelines, differences were considered significant when p<0.05. Central tendencies were expressed as means±SEM. Results: Mean age of patients in methylprednisolone group was 41.8±1.05 years, and mean RA duration (± SEM) was 7.9±0.21 years. Mean age of patients in diprospan group was 40.9±1.07 years, and mean RA duration was 8.0±0.33 years. Significant decreases of XO activity and increase of XDG activity were observed in lysed red blood cells of RA patients just after the injection of each glucocorticoid drug. Changes of the enzymatic activities in lysed red blood cells were more pronounced in methylprednisolone group. However enzymatic activity did not reach the level of healthy controls. As described previously, decreased XO activity and increased XDG activity were observed in plasma of RA patients just after the injection of the average therapeutic doses of glucocorticoids, as well as in lysed lymphocytes just after the injection of methylprednisolone [4]. Conclusion: Treatment with methylprednisolone and betamethasone can affect the balance of XO/XDG activity and increase the antioxidant potential of the blood. This effect can exert beneficial influence on autoimmune inflammation in RA. References: [1]Mateen S., et al. Increased reactive oxygen species formation and oxidative stress in rheumatoid arthritis. PLoS ONE 2016;11(4):e0152925. [2]Çimen M.Y., et al. Oxidant/antioxidant status of the erythrocytes from patients with rheumatoid arthritis. Clin Rheumatol 2000;19(4):275-277. [3]Zborovskaya I.A., et al. Influence of analgetics on plasma and lymphocytic activity of the purine metabolism enzymes in rheumatoid arthritis patients. Russian Journal of Pain 2018;3:47. [4]Mozgovaya E.E., et al. Xanthinoxidase and xanthine dehydrogenase activities in rheumatoid arthritis after glucocorticoid treatment. Osteoporosis International 2019;30(2):S433-434. Disclosure of Interests: None declared
E. Mozgovaya, A. Trofimenko, S. Bedina, S. Spitsina, M. Mamus, I. Zborovskaya
Published: 19 May 2021
by BMJ
Annals of the Rheumatic Diseases, Volume 80, pp 1444.1-1444; https://doi.org/10.1136/annrheumdis-2021-eular.3639

Abstract:
Background: Rheumatoid arthritis (RA) is severe autoimmune joint disease, accompanied by a wide variety of extra-articular manifestations. Anemia is one of the most common organ involvements in RA, being diagnosed in 36-65% patients. Iron metabolism alterations, shortened RBC lifespan, and impaired erythropoiesis in bone marrow are believed to play a leading role in RA-related anemia development. These processes in RA can be mediated by increased effect of proinflammatory cytokines, including IFNγ and TNFα, and similar mechanisms could contribute to high xanthine oxidoreductase (XOR) expression. This enzyme makes multiple pathophysiological effects, some of which can be related to the development of anemia in RA. Reactive oxygen species generated by XOR are capable, in particular, of damaging cell membranes, exerting influence on iron mobilization from ferritin in liver, and inducing changes in intestinal iron absorption. Objectives: Evaluation of changes in XOR interconvertible forms (xanthine oxidase and xanthine dehydrogenase) activities in RBC of RA patients. Methods: The research was carried out in agreement with the WMA Declaration of Helsinki principles. 75 RA patients with verified RA were enrolled in the study. The diagnosis was verified using the ACR/EULAR criteria (2010). The reference group consisted of 35 healthy individuals. Хanthine oxidase (XO, ЕС 1.17.3.2) and xanthine dehydrogenase (XDG, ЕС 1.17.1.4) activities were measured in lysed red blood cells by spectrophotometric method as previously described [1]. The enzymatic activities were expressed as nmol/min/ml and normalized to 1×109 cells/ml. Statistical comparison tests were selected in according to common guidelines. Central tendencies were expressed as means±SEM. Differences were considered significant when p<0.05. Results: Mean age of RA patients was 43.9±0.97 years, and mean RA duration was 8.5±0.3 years. Extra-articular manifestations were diagnosed in 32 (42.7%) RA patients and 17 (53.1%) of them had anemia. We revealed substantial changes in XO and XDG activities in lysed RBC of RA patients with anemia. Increased XO activity and decreased XDG activity were observed in comparison with healthy controls (р<0.001 for both enzymes). In parallel with the increase in DAS28 index, significant growth of XOD/XDG coefficient was observed, which was caused by both XOD activity elevation and XDG activity reduction in lysed RBC (p<0.001 for both enzymes). Enzymatic activities depended also on the extra-articular RA manifestations. Mean XO activity was higher and mean XDG activity were lower in patients with extra-articular manifestations (p<0.05 for both enzymes), but the extent of changes was substantially less comparing to anemia. Conclusion: Autoimmune inflammation in RA is accompanied by changes in enzymatic activities of XOR interconvertible forms and their ratio. Transformation of XDG into КО ultimately leads to significant increase in the generation of reactive oxygen species that have a damaging effect on lipids, proteins and other cellular components, and specifically in RBC. This fact may be one of the reasons for their premature damage and development of anemia in RA. References: [1]Zborovskaya I.A., et al. Influence of analgetics on plasma and lymphocytic activity of the purine metabolism enzymes in rheumatoid arthritis patients. Russian Journal of Pain 2018;3:47 Disclosure of Interests: None declared
E. Papichev, В. Zavodovsky, L. Seewordova, J. Polyakova, Y. Akhverdyan
Published: 19 May 2021
by BMJ
Annals of the Rheumatic Diseases, Volume 80, pp 487-488; https://doi.org/10.1136/annrheumdis-2021-eular.568

Abstract:
Background: Rheumatoid cachexia is an under-recognized pathological condition, which is characterized by a loss of muscle strength and can be presented as a low fat-free mass and normal or high BMI in patients with rheumatoid arthritis determined by dual-energy X-ray absorptiometry (DEXA) [1]. Though fetuin-A is one of a major noncollagen proteins in bone tissue it is of interest to clarify its association with rheumatoid cachexia. Objectives: To define the prevalence of rheumatoid cachexia in Caucasian patients with rheumatoid arthritis determined by DEXA method and to study the association of serum fetuin-A levels with body composition and rheumatoid cachexia in this group. Methods: 110 Caucasian patients with rheumatoid arthritis undergone DEXA with «Total Body» program. All patients fulfilled the 2010 ACR/EULAR classification criteria for rheumatoid arthritis. The diagnosis of rheumatoid cachexia was based on Engvall I.L. criteria: fat-free mass index less than 10th percentile with fat mass index above 25th percentile [1]. We used values for these indexes from the study performed in 2008 by Coin A. et al. on Italian population due to a lack of standard values [2]. Fetuin-A in serum was determined by enzyme-linked immunosorbent assay. 72 patients have been taking glucocorticoids for more than 3 months in dose equivalent or higher than 5 mg of prednisolone daily. Statistical analysis was performed using a software package “Statistica 12.0”. Parametric data is presented as M±St.dev, and nonparametric as Me [Q1-Q3]. Results: Rheumatoid cachexia was diagnosed in 25 patients (22,7%) with mean age of 52,2±8,14 years. The prevalence of cachexia was the same in groups of patients who took glucocorticoids (n=16, 22,2%) and who didn’t (n=9, 23,7%; p = 0,465). Median cumulative dose of oral glucocorticoids in patients with rheumatoid cachexia was higher but fell just short of statistical significance (8,0 [2,9-13,5] g vs 5,4 [0,2-11,6] g; Z=-1,42; p = 0,156). Median serum fetuin-A levels were only slightly significantly lower in patients with rheumatoid cachexia (757,7 [700,5-932,0] µg/ml vs 769,3 [660,3-843,4] µg/ml; Z=-1,35; p=0,175). Positive statistically significant correlations were observed between serum fetuin-A levels and bone mass in right (r=0,222, p = 0,027) and left (r=0,263, p = 0,008) lower limbs, trunk (r=0,268, p = 0,007), gynoid region (r=0,293, p = 0,003), both lower limbs (r=0,246, p = 0,014) and whole-body (r=0,235, p = 0,019). Conclusion: Rheumatoid cachexia was diagnosed in 22,7% of patients with rheumatoid arthritis. No association was observed between glucocorticoids intake and rheumatoid cachexia, despite the expected influence of them on muscle mass. We may suggest that occurrence and pathogenesis of this condition is complex and should be studied more precisely. It is well-known that patients with such condition have a higher risk for metabolic syndrome, arterial hypertension and mortality. We observed positive correlations between serum fetuin-A levels and bone mass in lower limbs, trunk, gynoid region and whole-body. Considering that fetuin-A is also associated with bone mineral density [3], it may be regarded as a marker of bone remodeling. References: [1]Engvall I.L., Elkan A.C., Tengstrand B., Cederholm T., Brismar K., Hafstrom I. Cachexia in rheumatoid arthritis is associated with inflammatory activity, physical disability, and low bioavailable insulin-like growth factor. Scand J Rheumatol. 2008; 37 (5): 321–328. [2]Coin A., Sergi G., Minicuci N., Giannini S., Barbiero E., Manzato E., Pedrazzoni M., Minisola S., Rossini M., Del Puente A., Zamboni M., Inelmen E.M., Enzi G. Fat-free mass and fat mass reference values by dual-energy X-ray absorptiometry (DEXA) in a 20-80 year-old Italian population. Clinical Nutrition. 2008; 27 (1): 87-94. [3]Sari, A., & Uslu, T. The relationship between fetuin-a and bone mineral density in postmenopausal osteoporosis. Turkish Journal of Rheumatology. 2013; 28 (3): 195-201. Disclosure of Interests: None declared
, Leslie J. Crofford
Published: 10 May 2021
Arthritis Care & Research, Volume 73, pp 765-766; https://doi.org/10.1002/acr.24641

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Corrigendum
Fiorella Carla Grandi, Lara De Tomasi,
Frontiers in Molecular Neuroscience, Volume 14; https://doi.org/10.3389/fnmol.2021.686790

Abstract:
A Corrigendum on Single-Cell RNA Analysis of Type I Spiral Ganglion Neurons Reveals a Lmx1a Population in the Cochlea by Grandi, F. C., De Tomasi, L., and Mustapha, M. (2020). Front. Mol. Neurosci. 13:83. doi: 10.3389/fnmol.2020.00083 In the original article, there was an error. Dr. Gopal Pramanik was acknowledged without his agreement. As per his request, we are removing his name and contribution from the acknowledgment paragraph. A correction has been made to the Acknowledgments. The corrected paragraph is shown below. “We sincerely thank Drs. Stefan Heller and Marta Milo for help with data analysis, and Dr. Walter Marcotti for helpful discussion. We also thank Dr. Kathleen J. Millen for generously providing the Lmx1a-cre mice and Dr. Theresa Zwingman for answering the many questions we had concerning these mice (Seattle Children's Research Institute Center for Integrative Brain Research, The University of Washington). We thank Dr. Joseph P. Sarsero (Murdoch Children's Research Institute, Australia) for sharing Peripherin-GFP mice with us and Dr. Lin Gan (Flaum Eye Institute, University of Rochester School of Medicine) for sharing Bhlhb5-cre line.” The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. Keywords: type I spiral ganglion neurons, single-cell transcriptome, Lmx1a, development, cochlea Citation: Grandi FC, De Tomasi L and Mustapha M (2021) Corrigendum: Single-Cell RNA Analysis of Type I Spiral Ganglion Neurons Reveals a Lmx1a Population in the Cochlea. Front. Mol. Neurosci. 14:686790. doi: 10.3389/fnmol.2021.686790 Received: 27 March 2021; Accepted: 01 April 2021; Published: 05 May 2021. Approved by: Copyright © 2021 Grandi, De Tomasi and Mustapha. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Mirna Mustapha, [email protected]
Published: 13 April 2021
Frontiers in Radiology, Volume 1; https://doi.org/10.3389/fradi.2021.629992

Abstract:
AI technologies and methodologies have started to empower all aspects of radiology in the past decade, from imaging data acquisition, to imaging data interpretation, and to clinical decision making. Despite exciting advancements made in the field of AI in radiology, there are also grand challenges associated with technological and translational aspects of AI in radiology (1). Following the Field Chief Editor Dr. Dinggang Shen's perspective in his statement of grand challenges in radiology1, here we elaborate four grand challenges in AI in radiology in more detail. Fast and high-quality radiological image acquisition has been a major challenge for decades and it remains as a grand challenge. How to speed up imaging data acquisition, such as MRI and CT scans, has been of major interest to improve efficiency and patient safety, among other considerations. In response, many AI technologies have been developed and reported for fast and high-quality radiological image reconstruction (2), with substantially smaller doses of intravenous contrast material and lower radiation dose in some scenarios. It is envisioned that these new imaging data acquisition technologies will continue to be developed for the benefits of patients, radiologists, and radiology clinical flow. Also, AI can play a major role in integrating and optimizing radiological data acquisition workflow, for instance, a recent successful example is the contactless patient positioning system during the COVID-19 pandemic (3), which automated calibration, positioning, and multi-view synthesis components that enable patient scans without physical proximity. This journal's specialty of AI in radiology will encourage and welcome contributions that address all aspects of AI-empowered imaging data acquisition. Modern AI systems in radiology typically rely on machine learning and deep learning algorithms that are trained and tested on a large number of annotated radiological images (4). Thanks to significant progresses made in the AI field, algorithms can now take advantage of accurately and reliably annotated imaging data. However, manual annotation of radiological images is still a key bottleneck in translating advanced AI algorithms into clinically useful systems. Typically, manual labeling and annotation processes in radiology AI systems are quite costly and time-consuming. Thus, developing effective automated labeling and annotation methods to produce high-quality training and testing data for radiology AI research and application is much needed (1). Recent efforts in integrating natural language processing (NLP) technologies and human-computer interaction (HCI) methodologies into radiology will be a promising direction to explore and pursue in the future. Although radiology AI systems are deemed to be promising in improving efficiency and accuracy, they require a sufficiently large, well-curated, well-integrated, and controlled dataset for training and testing AI algorithms. In particular, radiology AI systems for many human diseases/conditions are heavily dependent on a variety of co-factors such as disease stages or subtypes, patient populations, and genotypes, among many others. Given the large number of combinations of the co-factors, the data from one single institution are vastly insufficient for AI algorithms to achieve their full potential. In addition, in order to have complete and diversified data to minimize healthcare disparities, radiological data sharing among multiple institutions is required to meet such requirements. Unfortunately, the concerns of data security and patient privacy in data sharing and other social/economic considerations prevent people from sharing radiological data in a large scale effectively, which significantly prevents the clinical applications of radiology AI systems. This is a grand challenge for radiology AI that truly deserves attention and effort from all stakeholders to overcome. From a technical perspective, recent decentralized approaches such as blockchain and the InterPlanetary File System (IPFS)2 possess great promise in dealing with security and privacy concerns in data sharing and thus they are worthy of future exploration for radiological image sharing. Radiology AI systems are used by clinical radiologists during their daily practice, and thus AI systems and radiologists must adapt to each other and build up a co-worker relationship. However, it is known that such human-machine co-working is challenging, which is formulated as the human-technology frontier in the NSF's 10 big ideas3. There will be many research opportunities to understand and build the radiologist-AI system relationship, to design and develop new technologies to augment radiologist's performance, and to foster radiologist's lifelong and pervasive learning with AI systems. It is hopeful that these effective AI-radiologists co-working models will significantly increase radiologists' efficiency and reduce AI system errors and risks. TL wrote this article as a sole author. The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. 1. ^https://www.frontiersin.org/journals/radiology#about 2. ^https://ipfs.io/ 3. ^https://www.nsf.gov/news/special_reports/big_ideas/ 1. Langlotz CP, Allen B, Erickson BJ, Kalpathy-Cramer J, Bigelow K, Cook TS, et al. A roadmap for foundational research on artificial intelligence in medical imaging: from the 2018 NIH/RSNA/ACR/The Academy Workshop. Radiology. (2019) 291:781–91. doi: 10.1148/radiol.2019190613 PubMed Abstract | CrossRef Full Text | Google Scholar 2. The Ubiquity of AI at RSNA (2019). Available online at: https://www.appliedradiology.com/communities/Artificial-Intelligence/the-ubiquity-of-ai-at-rsna-2019 3. Karanam S, Li R, Yang F, Hu W, Chen T, Wu Z. Towards contactless patient positioning. IEEE Trans Med Imaging. (2020) 39:2701–10. doi:...
Arizona Mustikarini, Desi Adhariani
Published: 6 April 2021
Meditari Accountancy Research; https://doi.org/10.1108/medar-11-2020-1062

Abstract:
Purpose This study aims to review the auditor-client relationship (ACR) literature spanning 1976 to 2019 to provide future research directions. Design/methodology/approach The study analysed 140 articles from the Web of Science database, authored by 259 scholars across 28 countries and published in 47 journals. It identified three major research streams to understand the ACR dynamics: auditor tenure, ACR attributes and auditor-client negotiation. Findings Three major findings emerged based on this review. First, few studies examine auditor-client negotiation relative to other streams; thus, it offers scope for further research. Second, given that various fields have used diverse frameworks as theoretical underpinnings in prior studies, continuing this trend can better portray ACR from multiple perspectives. Finally, despite strong international regulations on ACR aspects such as auditor independence, tenure and rotation, implementation in several countries warrants special considerations, specifically on legal enforcement and investor protection, given diverse cultures and country-level institutional environments. Originality/value This study contributes to the synthesis of existing and emerging research streams and provides future research suggestions.
Justin Mellette
Abstract:
Chapter 2 focuses on Erskine Caldwell and seeks to complicate understandings of his best-known works Tobacco Road and God's Little Acre. Though often derided for mocking the poor and using them as comic relief, Caldwell works to instil a sense of anger in readers as he reveals the economic plight of tenant farming during the Great Depression. In addition, the chapter looks at Caldwell's nonfiction work, including his phototext You Have Seen Their Faces, written with photographer Margaret Bourke-White, and contrasts its cultural context with the comparatively better known Let Us Now Praise Famous Men. In addition, the chapter considers Caldwell's journalism, which originally raised national attention to the plight of the farmers he later immortalized in his fiction. Finally, the chapter closes by considering Caldwell’s later career and fall from critical favour.
Angalla Affleck Romaric Ledier, Lamini Norbert, Ntsiba Honoré, Akoli Ekoya, Nkouala Kidédé Chabel, Omboumahou Bakale Francina, Salémo Anah Précieu
European Scientific Journal, ESJ, Volume 17, pp 51-51; https://doi.org/10.19044/esj.2021.v17n3p51

Abstract:
Objective: To describe characteristics of complementary and alternative medicine (CAM) in patients with knee osteoarthritis. Materials and Methods: A cross-sectional, descriptive, and analytical study was carried out on patients with knee osteoarthritis. This was followed by Rheumatology consultation at the University Hospital of Brazzaville from 2017 to 2018 within a period of one (1) year. The diagnosis of knee osteoarthritis was made European Scientific Journal, ESJ ISSN: 1857-7881 (Print) e - ISSN 1857-7431 January 2021 edition Vol.17, No.3 www.eujournal.org 53 on the basis of ACR 1986 criteria. The elements of the CAM were obtained by questioning the patients. Results: Out of the one hundred and five cases, 101 were female (96.2%) and 4 were male (3.8%). The sex ratio was 0.03. The mean age was 56, 44 +/- 10, 29 years (range 30-80 years). Knee osteoarthritis was bilateral (86.7%), unilateral right (9.5%) and left (3.8%). 68 patients (64.8%) used CAM, 97.1% women and 2.9% men. 77.5% of patients used CAM during the diagnosis, 15.5% before diagnosis, and 7% after. The type of CAM are: massages of essential oils (72%), scarifications (61%), thermal cures (51.5%), phytotherapy (22%), cupitherapy (17.6 %), and acupuncture in 10.3% of cases. 58.2% of patients used CAM to relieve pain, 18.4% to cure, 15.3% to improve function, and 7.1% of cases to reduce the side effects of treatment. Conclusion: Our study reports a great diversity of CAM types used in knee osteoarthritis, which is dominated by essential oils in topical application. Objectif : Rapporter les caractères de la médecine complémentaire et alternative (CAM) chez les patients gonarthrosiques. Matériels et Méthodes : Etude transversale, descriptive et analytique portant sur les patients présentant une gonarthrose et suivis en consultation de Rhumatologie au CHU de Brazzaville de 2017 à 2018, soit 1 an. Le diagnostic de gonarthrose était retenu sur la base des critères ACR 1986. Les éléments de la CAM ont été obtenus par l’interrogatoire des patients. Résultats : Nous avons inclus cent cinq cas, dont 101 de sexe féminin (96,2%) et 4 cas de sexe masculin (3,8%). Le sexe ratio était de 0,03. L’âge moyen était de 56 ,44+/-10 ,29 ans (extrêmes European Scientific Journal, ESJ ISSN: 1857-7881 (Print) e - ISSN 1857-7431 January 2021 edition Vol.17, No.3 www.eujournal.org 52 30-80 ans). Le siège de la gonarthrose était bilatéral (86,7%), unilatéral droit (9,5%) et gauche (3,8%).68 patients (64,8%) ont fait recours à la CAM dont 97,1% des femmes et 2,9% d’hommes. 77,5% des patients ont utilisé la CAM au cours de l’annonce du diagnostic, 15,5% avant le diagnostic et 7% après. Le type de la CAM était : les massages d’huiles essentielles (72%) des cas, les scarifications (61%), les cures thermales (51,5%), la phytothérapie (22%), la cupitherapie (17,6%) et l’acupuncture dans 10,3% des cas. 58,2% des patients utilisaient la CAM pour soulager la douleur, 18,4% pour guérir,15,3% pour améliorer la fonction et 7,1% des cas pour atténuer les effets secondaires des traitements. Conclusion : Notre étude rapporte la grande diversité des types de CAM utilisés dans la gonarthrose, dominés par les huiles essentielles en application topique.
Katherine J. Aney,
Published: 14 January 2021
The Journal of Pathology; https://doi.org/10.1002/path.5619

Abstract:
The prognosis for pancreatic ductal adenocarcinoma (PDAC) remains dismal. Multiple genome wide association studies (GWAS) have implicated the nuclear receptor NR5A2 in modulating PDAC risk, but mechanisms for this association are not understood. NR5A2 is a transcription factor that maintains acinar cell identity, and heterozygous loss of Nr5a2 in mice accelerates oncogenic KRAS‐driven formation of pancreatic intraepithelial neoplasia (PanIN), a PDAC precursor derived from acinar cells. In a recent issue of The Journal of Pathology, Cobo et al. characterize a novel mouse model that uses Ptf1a:Cre to drive oncogenic Kras as well as heterozygous Nr5a2 inactivation. In addition to the expected PanIN lesions, these mice exhibited a surprising phenotype: large pancreatic cystic lesions which have not been previously reported. Comparing expression of oncogenic Kras and heterozygous Nr5a2 in various mouse models reveals several possible explanations for these cystic lesions. Importantly, these differences across mouse models suggest that NR5A2 may contribute to PDAC precursors in ways beyond its previously characterized acinar cell autonomous role. These observations highlight that pathways implicated by GWAS may have roles in unexpected cell types, and an understanding of these roles will be critical to guide new preventive and treatment strategies for PDAC. This article is protected by copyright. All rights reserved.
Two centuries of the Russian classics, Volume 3; https://doi.org/10.22455/2686-7494-2021-3-3-6-21

Abstract:
The article discusses two points of view on the primary education, literacy — I. S. Turgenev’s and A. A. Fet’s. The author describes the landmark clash between Turgenev and Fet, and also shows the mood and plans of both writers in the early 1860s. In August 1860, in anticipation of the abolition of serfdom, while in England, on the Isle of Wight, Turgenev conceived and drew up a “Draft Program for the Society for the Promotion of Literacy and Primary Education”. And Fet, forced to leave literature as a result of “persecution” of “pure art”, acquired 200 acres of black soil in the Mtsensk district. On the eve of the abolition of serfdom, the poet, who did not have his own estate and serfs, found himself in the position of a farmer, who had to endure fully on his own experience the endless troubles associated with the introduction of reforms in all spheres of economic and political life. His journalism touched upon a variety of issues, one of which was literacy. Fet’s opinion on this issue looks paradoxical. However, he was not alone, urging not to equate literacy, education and upbringing, giving preference to the moral upbringing of the people in solving the problem. A similar position was taken by V. I. Dal, whose letter to the publisher of the journal “Russkaya Beseda” A. I. Koshelev is analyzed in the article.
Published: 1 January 2021
Radiology, Volume 298, pp 28-35; https://doi.org/10.1148/radiol.2020202903

Abstract:
Inaugural consensus statements were developed and endorsed by the American College of Radiology (ACR) and the National Kidney Foundation to improve and standardize the care of patients with kidney disease who have indication(s) to receive ACR-designated group II or group III intravenous gadolinium-based contrast media (GBCM). The risk of nephrogenic systemic fibrosis (NSF) from group II GBCM in patients with advanced kidney disease is thought to be very low (zero events following 4931 administrations to patients with estimated glomerular filtration rate [eGFR] <30 mL/min per 1.73 m2; upper bounds of the 95% confidence intervals: 0.07% overall, 0.2% for stage 5D chronic kidney disease [CKD], 0.5% for stage 5 CKD and no dialysis). No unconfounded cases of NSF have been reported for the only available group III GBCM (gadoxetate disodium). Depending on the clinical indication, the potential harms of delaying or withholding group II or group III GBCM for an MRI in a patient with acute kidney injury or eGFR less than 30 mL/min per 1.73 m2 should be balanced against and may outweigh the risk of NSF. Dialysis initiation or alteration is likely unnecessary based on group II or group III GBCM administration. This article is a simultaneous joint publication in Radiology and Kidney Medicine. The articles are identical except for stylistic changes in keeping with each journal’s style. Either version may be used in citing this article. © 2020 RSNA and the National Kidney Foundation published by Elsevier Inc. This is an open access article under the CC BY NC-ND license.
Miaomiao Han, Yiqiang Chen, Juntao Li, Yuanyang Dong, Zhiqiang Miao, Jianhui Li,
Published: 26 December 2020
by 10.1002
Journal of the Science of Food and Agriculture, Volume 101, pp 3917-3926; https://doi.org/10.1002/jsfa.11053

Abstract:
BACKGROUND Trivalent chromium (Cr) is involved in carbohydrate, lipid, protein and nucleic acid metabolism in animals. This study evaluated the effects of different organic Cr forms with Cr methionine (CrMet), Cr picolinate (CrPic), Cr nicotinate (CrNic), and Cr yeast (Cr‐yeast) at the level of 400 μg kg−1 Cr, on growth performance, lipid metabolism, antioxidant status, breast amino acid and fatty acid profiles of broilers. In total, 540 one‐day‐old Arbor Acres male broilers were randomly assigned to five treatments with six replicates (18 broilers per replicate) until day 42. RESULTS The results showed growth performance was not affected by Cr sources. The Cr‐yeast group had lower serum cortisol levels than the CrNic group (P < 0.05). Besides, Cr‐yeast increased methionine and cysteine content in breast compared with the control group. Liver malondialdehyde content was lower in the CrMet group than the CrPic group on day 42 (P < 0.05). The n‐3 polyunsaturated fatty acid (PUFA) values were increased, but the n‐6/n‐3 PUFA ratio was decreased in both CrMet and CrNic groups (P < 0.05). There were no significant effects on broilers’ serum antioxidant status and breast total essential amino acid content among all treatments. CONCLUSIONS Diets supplemented with organic Cr could regulate lipid metabolism, and improve amino acid and fatty acid profiles in broiler breast. Moreover, Cr‐yeast was the most effective source in improving methionine and cysteine content, whereas CrMet was more effective than CrNic in increasing n‐3 PUFA value and decreasing n‐6/n‐3 PUFA ratio in breast meat and effectively strengthened liver antioxidant ability than CrPic. © 2020 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Corrigendum
, J. A. A. S. Jayaweera, W. Kumbukgolla, M. V. M. L. Jayasundara
Frontiers in Cellular and Infection Microbiology, Volume 10; https://doi.org/10.3389/fcimb.2020.631515

Abstract:
A Corrigendum onAssociation of Hantavirus Infections and Leptospirosis With the Occurrence of Chronic Kidney Disease of Uncertain Etiology in the North Central Province of Sri Lanka: A Prospective Study With Patients and Healthy Persons by Sunil-Chandra NP, Jayaweera JAAS, Kumbukgolla W and Jayasundara MVML (2020). Front. Cell. Infect. Microbiol. 10:556737. doi: 10.3389/fcimb.2020.556737 In the original article, there was an error in the ethical clearance number. The correct number for ethical clearance is ERC/2012/33. A correction has been made to Materials and Methods, Paragraph 3: According to CKDu case definition, an individual identified with an albumin-to-creatinine ratio (ACR) ≥ 30 mg/g urine creatinine during the initial visit and at a follow-up visit, a normal glycosylated hemoglobin (HbA1c <6.5%), not on treatment for diabetes, no elevated blood pressure, and no past history of kidney disease or snake bite were included. Patients with other known causes of chronic kidney disease (CKD) and those who did not consent were excluded from the study (16,13). Studies involving human patients/participants were reviewed and approved by the Research, Ethical Review and Higher degree committee of the faculty of Medicine and Allied Sciences, Rajarata University, Sri Lanka. Patients/participants provided their written informed consent to participate in this study (ERC/2012/33). The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. Keywords: hantaviruses, leptospira, sero-prevalence, chronic kidney disease, CKDu Citation: Sunil-Chandra NP, Jayaweera JAAS, Kumbukgolla W and Jayasundara MVML (2020) Corrigendum: Association of Hantavirus Infections and Leptospirosis With the Occurrence of Chronic Kidney Disease of Uncertain Etiology in the North Central Province of Sri Lanka: A Prospective Study With Patients and Healthy Persons. Front. Cell. Infect. Microbiol. 10:631515. doi: 10.3389/fcimb.2020.631515 Received: 20 November 2020; Accepted: 25 November 2020;Published: 17 December 2020. Approved by: Frontiers Editorial Office, Frontiers Media SA, Switzerland Copyright © 2020 Sunil-Chandra, Jayaweera, Kumbukgolla and Jayasundara. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: N. P. Sunil-Chandra, [email protected]
Journal of Neuro-Ophthalmology, Volume 40, pp 572-577; https://doi.org/10.1097/wno.0000000000001147

Abstract:
In this issue of Journal of Neuro-Ophthalmology, M. Tariq Bhatti, MD, and Mark L. Moster, MD will discuss the following 6 articles: Li L, Dmytriw AA, Krings T, Feng Y, Jiao L. Visualization of the human intracranial vasa vasorum in vivo using optical coherence tomography. JAMA Neurol. 2020;77:903–905. Lee KE, Zehri A, Soldozy S, Syed H, Catapano JS, Maurer R, Albuquerque FC, Liu KC, Wolfe SQ, Brown S, Levitt MR, Fargen KM. Dural venous sinus stenting for treatment of pediatric idiopathic intracranial hypertension. J Neurointerv Surg. [published online ahead of print July 30, 2020] doi:10.1136/neurintsurg-2020-016183. Matza MA, Fernandes AD, Stone JH, Unizony SH. Ustekinumab for the treatment of giant cell arteritis. Arthritis Care Res (Hoboken). [published online ahead of print April 5, 2020] doi:10.1002/acr.24200. Kunchok A, Aksamit AJ Jr, Davis JM III, Kantarci OH, Keegan BM, Pittock SJ, Weinshenker BG, McKeon A. Association between tumor necrosis factor inhibitor exposure and inflammatory central nervous system events. JAMA Neurol. 2020;77:937–946. Mac Grory B, Nackenoff A, Poli S, Spitzer MS, Nedelmann M, Guillon B, Preterre C, Chen CS, Lee AW, Yaghi S, Stretz C, Azher I, Paddock J, Bakaeva T, Greer DM, Shulman JG, Kowalski RG, Lavin P, Mistry E, Espaillat K, Furie K, Kirshner H, Schrag M. Intravenous fibrinolysis for central retinal artery occlusion: a cohort study and updated patient-level meta-analysis. Stroke. 2020;51:2018–2025. Lopez-Chiriboga S, Sechi E, Buciuc M, Chen JJ, Pittock SJ, Lucchinetti CF, Flanagan EP. Long-term outcomes in patients with myelin oligodendrocyte glycoprotein immunoglobulin G–associated disorder. JAMA Neurol. [published online ahead of print August 31, 2020] doi:10.1001/jamaneurol.2020.3115.
, Eric Y. Chang, Alice S. Ha, Roger J. Bartolotta, Matthew Bucknor, Tushar Chandra, Karen C. Chen, Tetyana Gorbachova, Bharti Khurana, Alan K. Klitzke, et al.
Journal of the American College of Radiology, Volume 17; https://doi.org/10.1016/j.jacr.2020.09.014

The publisher has not yet granted permission to display this abstract.
Asteray Ayenew,
Published: 12 October 2020
Abstract:
Background Globally, a total of 13.6 million women have died due to maternal causes from 1990 to 2015. Majority of these deaths occurred in resource-limited countries. Among the causes of these deaths, obstructed and prolonged labor covers the highest percentage, which could be prevented by cost-effective and affordable health interventions like partograph use. Therefore, this systematic review and meta-analysis aimed to assess the level of partograph utilization among obstetric care providers and its associated factors in Ethiopia. Method for this review, we used the standard PRISMA checklist guideline. Different online databases were used for the review: PubMed/Medline, Google Scholar, EMBASE, Cochrane Library, HINARI, WHO Afro Library Databases, and African Online Journals. Based on the adapted PICO principles, different search terms were applied to achieve and access all the essential articles. Microsoft Excel was used for data entrance and Stata version 11.0 (Stata Corporation, College Station, Texas, USA) for data analysis.Result Nineteen studies were included in this systematic review and meta-analysis with a total of 6237 obstetric care providers. The overall pooled prevalence of partograph utilization was 59.95% (95%CI: 46.8–73.09, I2 =99.4%, P 2 =28.8%, P=0.198), presence of supervision (AOR = 3.21; 95%CI: 2.22–4.66, I2=0.0%, p=0.742), Basic Emergency Obstetric and Newborn Care (BEmONC) training (AOR = 2.90; 95% CI: 2.19–3.84, I2=36.9%, P=0.13), Knowledge of partograph (AOR=2.5; 95%CI: 1.6–3.8, I2=64.58%, P=0.024), on-the-job refresher training on partograph (AOR =5.7; 95%CI:2.5–12.9, I2=87.8%, P2=0.0%, P=0.58), and working at health center (AOR=3.50; 95%CI: 2.49–4.92, I2=49.1%, P=0.08) were the determinant factors for partograph use among obstetric acre providers in Ethiopia.Conclusion The overall pooled prevalence of partograph utilization among obstetric care providers was low. Therefore, supportive supervision, providing Basic Emergency Obstetric and Newborn Care training, on-the-job refresher training on partograph, and promoting midwifery profession are strongly recommended to increase the use of partograph.
Jasper Kennedy, Jordan D. Perchik,
Journal of the American College of Radiology, Volume 18, pp 93-102; https://doi.org/10.1016/j.jacr.2020.09.019

The publisher has not yet granted permission to display this abstract.
T. V. Korotaeva
Published: 21 September 2020
Modern Rheumatology Journal, Volume 14; https://doi.org/10.14412/1996-7012-2020-3-50-56

Abstract:
Objective: to analyze the data available in the literature on the efficacy and safety of ixekizumab (IXE) and adalimumab (ADA) via their direct comparisons in the treatment of psoriatic arthritis (PsA).Patients and methods. The results of the SPIRIT H2H study were analyzed, the aim of which was to investigate the potential superiority of IXE to ADA for arthritis and skin manifestations in a group of patients with active PsA, stable plaque psoriasis with an inadequate response to synthetic disease-modifying antirheumatic drugs (sDMARDs) who had not previously received biological agents (BAs).Design: a 52-week multicenter, randomized, parallel-group study. The patients were randomized 1:1 to open IXE or ADA administration groups for 52 weeks. This review presents the data obtained at 24-week follow-up.Of the 684 screened patients, 566 (82.7%) were included in the study; moreover, the distribution of the patients was equal between the ADA (n=283) and IXE (n=283) groups. At 6 months, 269 (95%) patients in the ADA group and 262 (93%) in the IXE one continued to participate in the study. Efficacy analysis was made based on the achievement of the primary endpoint that was considered to be related to the relative number of patients, who had simultaneously achieved improvements in the joints and skin according to the ACR50 and PASI100 criteria.Results and discussion. At 24 weeks, the proportion of patients who had simultaneously achieved ACR50 and PASI100 responses was significantly higher in the IXE group (36%) than in the ADA one (28%) (p=0.036). It was found that the IXE group was not inferior to the ADA one in terms of ACR50 response rates (in 51% (IXE) and 47% (ADA) patients) and was superior in achieving PASI100 response rates (in 60% (IXE) and 47% (ADA) patients) (p=0.001). The IXE group was recorded to have a higher response than the ADA group and in terms of other manifestations of the disease: the severity of skin and nail psoriasis, enthesitis, remission achievement, minimal and very low disease activity, and improved quality of life. Comparable effectiveness was noted for the effect of the drugs on dactylitis, as well as for the simultaneous achievement of remission and low disease activity in psoriatic arthritis according DAPSA. Serious adverse events (SAEs) were recorded in 8.5% (ADA) and 3.5% (IXE) patients.The safety and tolerability of both BAs corresponded to their previously presented safety profile. The findings were also confirmed at 52-week follow-up, presented at the Meetings of the American College of Rheumatology in November 2019 and the European League Against Rheumatism in June 2020, and published in the leading journals of rheumatology.Conclusion. The first randomized placebo-controlled study (SPIRIT H2H) directly comparing the two BAs with different mechanisms of action demonstrated the advantage of IXE over ADA in simultaneously reducing the activity of arthritis and psoriasis and showed their comparable efficacy comparable efficacy regarding joint symptoms. The use of IXE versus ADA was accompanied by the more frequent achievement of a combined endpoint related to the signs of joint and skin damages in patients with PSA, as well as by the quantitatively lower frequency of SAEs in patients with active PSA who had failed previous sDMARD therapy. The findings are of great importance for clinical practice from the point of view of the reasonable choice of a treatment strategy in these patients.
James K. Nelson, Brent L. Donham
2020 ASEE Virtual Annual Conference Content Access Proceedings; https://doi.org/10.18260/1-2--35041

Abstract:
Extended Abstract Cybersecurity is an emerging field with significant implications as the use of interconnected devices increases. In 2011 the Cisco Internet Business Solutions Group [1] reported that sometime between 2008 and 2009 the number of connected devices exceeded the world population. Within major telecommunications companies, the mix of services provided is changing. Data for ATT, as presented by the Wall Street Journal, [2] show a decrease in wireline services and the increase in wireless services. Although wireless services segment grew by six percent, the revenue from wireless services grew by 166 percent. Also of interest in these data is the growth of the “Other” business sector, which includes streaming and online services. That segment nearly tripled in the decade reported. This segment indicates that not only are individuals connecting more devices, they are utilizing more on-line resources. The internet of things has its complement in the industrial internet of things (IIOT), also characterized as “operational technology” to distinguish it from information technology. The nation’s infrastructure and economy (e.g., transportation, electrical grid, manufacturing) is increasingly dependent on securing the interface between IT and OT within the broader internet of things. Each of these devices and connections represents a potential entry point for individuals with malicious intentions. As such, many contend that cybersecurity is national security. This validity of this contention has been evident with the recent ransom attacks recently occurring in several Texas jurisdictions. A direct result of the growth of the number of Internet connected devices and the inherent security risks is the need for more individuals trained in the field of cybersecurity and related operational technologies. [name] is a 2,000-acre [name] System that integrates education, research, and work-force training in a first of its kind model the state of Texas. By assembling a diverse spectrum of engineering and technology tenants into one location, the campus fosters collaboration between enterprises that seek to shape the future through transformation, innovation and education. The educational programs at [name] focus on collaboration between two-year and four-year [name] System institutions providing powerful opportunities for students. At a recent meeting of the [name] External Academic Advisory Council, cybersecurity was identified as a needed strategic initiative. In response to recommendations made by the External Academic Advisory Council, the [name] Academic Alliance developed the [name] Cybersecurity Alliance to provide for quality control and coordination of program offerings at [name]. The purpose of the [name] Cybersecurity Alliance is to: 1. Provide a venue through which relevant academic and training programs that satisfy industry needs are offered and that enable the students to develop demonstrable hands-on skills; 2. Provide a mechanism by which industry involvement in the offerings can be ensured; and 3. Educate the region about career pathways in cybersecurity, and the vast opportunities within those careers. Presented in this paper is the development and implementation of the [name] Cybersecurity Alliance and the comprehensive programs that are offered through the Alliance. Included is the new bachelor’s degree program in cybersecurity, which was developed from a “clean sheet” with significant industry involvement. Also presented are the initial professional development courses that are being offered. The physical laboratory spaces that have been purpose-built enabling students to obtain hands-on experience as part of the academic and professional development programs are also discussed. A strong component in the development of each of these pieces was the active involvement the public and private sector.
Mona A Hana, Sahar A Sharaf, Mohamed M Ismail, Marwa F Mira, Marwa Taha, Mai M Mostafa, Hend M Soliman
Sri Lanka Journal of Child Health, Volume 49; https://doi.org/10.4038/sljch.v49i3.9146

Abstract:
Background: Diabetic nephropathy (DN) is the main cause of morbidity and mortality in young adults with type 1 diabetes mellitus (T1DM). The accuracy of albuminuria has been frequently questioned as a predictor and prognosticator of renal injury. Therefore, new urinary markers were investigated for the early detection of DN.Objectives: To assess the potential value of urinary interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) as early markers for detection of DN in children and adolescents with T1DM.Method: This case-control study was conducted on 50 children and adolescents with T1DM, aged ≤ 18 years. Patients were classified according to their albumin/creatinine ratio (ACR) into two groups; normo-albuminuric and albuminuric group, together with 25 age and sex-matched healthy controls. ACR, urinary IL-6 and TNF-α levels were assayed for the patients and controls.Results: Urinary interleukin-6/creatinine (IL-6/Cr) ratio of albuminuric patients was significantly higher compared to normo-albuminuric patients or controls. Urinary IL-6/Cr ratio ≥ 0.24 pg/mg showed a significant cutoff value to detect albuminuria with 72% sensitivity and 52% specificity (p= 0.04). While, we did not observe different urinary tumour necrosis factor-alpha/creatinine (TNF-α/Cr) ratio in the studied groups, or between albuminuric and normo-albuminuric patients or controlsConclusions: Urinary IL-6/Cr ratio seems to be a promising new marker for early detection of DN in patients with T1DM, while urinary TNF-α /Cr ratio showed no significant difference between diabetic patients and controls.Sri Lanka Journal of Child Health, 2020; 49(3): 269-275
, Ghufran Aref Saeed, Tamer Ibrahim Elholiby, Mohamed Ashfaque Kukkady, Safaa Saeed Al Mazrouei
Published: 4 September 2020
Radiology Case Reports, Volume 15, pp 2171-2174; https://doi.org/10.1016/j.radcr.2020.07.031

Abstract:
Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). Convalescent plasma has not yet been approved for use in patients with COVID-19 infection; however, it is regulated as an investigational product. This is a case report of a 55-year-old male, with COVID-19 pneumonia who has received convalescent plasma as part of a treatment plan which showed significant radiological and clinical improvement post-treatment.
Emily Ann Marasco, Laleh Behjat
2013 ASEE Annual Conference & Exposition Proceedings pp 23.385.1-23.385.4; https://doi.org/10.18260/1-2--19399

Abstract:
Developing a cross-disciplinary curriculum for the integration of engineering and design in elementary education Studies have shown that by upper elementary or junior high school grades, students,especially female students, have already decided that the domains of science, mathematics,engineering and technology (STEM) do not interest them [1] [2]. Additional literature showsthat children believe engineers are responsible for repairing and installing technical items, butnot as involved in innovation and design [3] [4]. However, our research indicates that over 90%of post-secondary students entering engineering agree or strongly agree that engineers “designcool things” and “make interesting stuff.” In this paper, we propose to include engineering and design concepts in the studymaterial of elementary schools, to increase the level of interest of students in STEM areas anddecrease the disconnect between children’s perceptions of engineering and reality. We havedeveloped a series of cross-disciplinary modules that are designed to teach STEM concepts aspart of the regular curriculum activities. These modules allow elementary teachers to educatetheir students about engineering principles in the context of English, social studies, fine arts andphysical education curricula. By combining STEM material with other subjects areas, wepropose to (A) increase the appeal of STEM to children who have expressed interest in othersubjects, and (B) provide new methods of learning for children who may struggle with thetechnicality and lack of creativity found in more traditional STEM education. Our modules are specifically designed to improve the learning outcomes found inelementary introduction to electricity. We first identified the primary scientific objectives for therelevant grade and have combined these objectives with content from the rest of the curricula inthree cross-curricular modules:1. Concept learning: In this module, the students will learn the basic concepts of electricity,electrons movement, basic switches, storage of electricity, electric potential, and transfer ofenergy. Students will demonstrate their learning using physical activity, experimentation withwater, and expression through written art, such as the creation of a poem, short story or essay.2. Applications: Students will learn about the historical and social applications of electricity,including the national history of communication and computers. This module includes a hands-on design project that will allow them to create their own communication device. Students willalso learn about the mathematical binary patterns necessary for “speaking computer language.”3. Creative design: Students will express their new knowledge through an artistic exhibition.Students will demonstrate their understanding of electricity concepts through the creation of“circuit art” using a variety of conductive materials. This activity allows the children toreinforce their knowledge in the context of open-ended design, and encourages engineeringdesign and experimentation. By embedding engineering into other areas of education, both students and teachers areable to approach STEM from a creative, sociological and historical angle. These projects areintended to provide elementary school teachers with the means to deliver technical content in acreative and interesting manner. It is our hope that this cross-disciplinary work will help toimprove elementary students’ attitudes towards STEM subjects and the engineering profession.References:[1] Arnot, M., Gray, J., James, M., Rudduck, J., & Duveen, G. (1998). Recent research ongender and educational performance. London: OFSTED.[2] Bussière, P., Cartwright, F., & Knighton, T. (2004). The performance of Canada’s youth inMathematics, Reading, Science and problem solving: 2003 first findings for Canadians aged 15.Ottawa: Human Resources and Skills Development Canada, Council of Ministers of Education,Canada and Statistics Canada.[3] Capobianco, B. M., Diefes-Dux, H. A., Mena, I., & Weller, J. (2011). What is an engineer?Implications of elementary school student conceptions for engineering education. Journal ofEngineering Education, 100(2), 304-328.[4] Cunningham, C. M., Lachapelle, C. P., & Lindgren-Streicher, A. (2005). Assessingelementary school students’ conceptions of engineering and technology. ASEE AnnualConference and Exposition. Portland, OR.
Asteray Ayenew,
Published: 3 September 2020
Abstract:
Background: Globally, a total of 13.6 million women have died due to maternal causes from 1990 to 2015. Majority of these deaths occurred in resource-limited countries. Among the causes of these deaths, obstructed and prolonged labor covers the highest percentage, which could be prevented by cost-effective and affordable health interventions like partograph use. Therefore, this systematic review and meta-analysis aimed to assess the level of partograph utilization among obstetric care providers and its associated factors in Ethiopia. Method: for this review, we used the standard PRISMA checklist guideline. Different online databases were used for the review: PubMed, Google Scholar, EMBASE, Cochrane Library, HINARI, WHO Afro Library Databases, and African Online Journals. Based on the adapted PICO principles, different search terms were applied to achieve and access all the essential articles. Microsoft Excel was used for data entrance and Stata version 11.0 (Stata Corporation, College Station, Texas, USA) for data analysis.Result: Nineteen studies were included in this systematic review and meta-analysis with a total of 6237 obstetric care providers. The overall pooled prevalence of partograph utilization was 59.95% (95%CI: 46.8–73.09, I2 =99.4%, P 2 =28.8%, P=0.198), presence of supervision (AOR = 3.21; 95%CI: 2.22–4.66, I2=0.0%, p=0.742), Basic Emergency Obstetric and Newborn Care (BEmONC) training (AOR = 2.90; 95% CI: 2.19–3.84, I2=36.9%, P=0.13), Knowledge of partograph (AOR=2.5; 95%CI: 1.6–3.8, I2=64.58%, P=0.024), on-the-job refresher training on partograph (AOR =5.7; 95%CI:2.5–12.9, I2=87.8%, P2=0.0%, P=0.58), and working at health center (AOR=3.50; 95%CI: 2.49–4.92, I2=49.1%, P=0.08) were the determinant factors for partograph use among obstetric acre providers in Ethiopia.Conclusion: The overall pooled prevalence of partograph utilization among obstetric care providers was low. Therefore, supportive supervision, providing Basic Emergency Obstetric and Newborn Care training, on-the-job refresher training on partograph, and promoting midwifery profession are strongly recommended to increase the use of partograph.
, A. Oates, H. Patel, S. McGuirk, K. Johnson
Published: 30 July 2020
Clinical Radiology, Volume 75, pp 870-871; https://doi.org/10.1016/j.crad.2020.07.015

The publisher has not yet granted permission to display this abstract.
V. V. Tsurko, , N. V. Malysheva
Meditsinskiy sovet = Medical Council; https://doi.org/10.21518/2079-701x-2020-8-144-152.

Abstract:
Gout, one of the most common forms of inflammatory arthritis, is characterized by severe joint pain, which often interferes with daily activities. In recent years, further research on its causes and on improving diagnosis, treatment and prevention has been ongoing. It is known that gout usually occurs due to the accumulation of sodium monourate crystals in joints due to high levels of serum uric acid. In 2019, the Annals of the Rheumatic Diseases journal published new data on imaging and clinical diagnostics methods based on the principles of evidence-based medicine. Formulated by experts, they were adopted as a consensus of the European League Against Rheumatism (EULAR). The American College of Rheumatology (ACR) has now developed new strategies to treat and prevent gout. On May 11, 2020, the Arthritis & Rheumatology Journal presented guidelines for the management of gout patients, including the treatment of acute gout attack, indications for urate-lowering therapy and instructions for its optimal use, as well as recommendations on lifestyle and drugs that are often prescribed to patients with comorbidity. The purpose of this review is to summarize current knowledge with a focus on recent advances in the algorithm for managing acute and chronic gout patients.
V. V. Tsurko, , N. V. Malysheva
Meditsinskiy sovet = Medical Council; https://doi.org/10.21518/2079-701x-2020-8-144-152

Abstract:
Gout, one of the most common forms of inflammatory arthritis, is characterized by severe joint pain, which often interferes with daily activities. In recent years, further research on its causes and on improving diagnosis, treatment and prevention has been ongoing. It is known that gout usually occurs due to the accumulation of sodium monourate crystals in joints due to high levels of serum uric acid. In 2019, the Annals of the Rheumatic Diseases journal published new data on imaging and clinical diagnostics methods based on the principles of evidence-based medicine. Formulated by experts, they were adopted as a consensus of the European League Against Rheumatism (EULAR). The American College of Rheumatology (ACR) has now developed new strategies to treat and prevent gout. On May 11, 2020, the Arthritis & Rheumatology Journal presented guidelines for the management of gout patients, including the treatment of acute gout attack, indications for urate-lowering therapy and instructions for its optimal use, as well as recommendations on lifestyle and drugs that are often prescribed to patients with comorbidity. The purpose of this review is to summarize current knowledge with a focus on recent advances in the algorithm for managing acute and chronic gout patients.
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