Study protocol for a randomised controlled trial of diacerein versus placebo to treat knee osteoarthritis with effusion-synovitis (DICKENS).

BACKGROUND: There is an unmet need for treatments for knee osteoarthritis (OA). Effusion-synovitis is a common inflammatory phenotype of knee OA and predicts knee pain and structural degradation. Anti-inflammatory therapies, such as diacerein, may be effective for this phenotype. While diacerein is recommended for alleviating pain in OA patients, evidence for its effectiveness is inconsistent, possibly because studies have not targeted patients with an inflammatory phenotype. Therefore, we will conduct a multi-centre, randomised, placebo-controlled double-blind trial to determine the effect of diacerein on changes in knee pain and effusion-synovitis over 24 weeks in patients with knee OA and magnetic resonance imaging (MRI)-defined effusion-synovitis. METHODS: We will recruit 260 patients with clinical knee OA, significant knee pain, and MRI-detected effusion-synovitis in Hobart, Melbourne, Adelaide, and Perth, Australia. They will be randomly allocated to receive either diacerein (50mg twice daily) or identical placebo for 24 weeks. MRI of the study knee will be performed at screening and after 24 weeks of intervention. The primary outcome is improvement in knee pain at 24 weeks as assessed by a 100-mm visual analogue scale (VAS). Secondary outcomes include improvement in volumetric (ml) and semi-quantitative (Whole-Organ Magnetic Resonance Imaging Score, 0-3) measurements of effusion-synovitis using MRI over 24 weeks, and improvement in knee pain (VAS) at 4, 8, 12, 16, and 20 weeks. Intention-to-treat analyses of primary and secondary outcomes will be performed as the primary analyses. Per protocol analyses will be performed as the secondary analyses. DISCUSSION: This study will provide high-quality evidence to determine whether diacerein improves pain, changes disease trajectory, and slows disease progression in OA patients with effusion-synovitis. If diacerein proves effective, this has the potential to significantly benefit the substantial proportion (up to 60%) of knee OA patients with an inflammatory phenotype. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry ACTRN12618001656224 . Registered on 08 October 2018.

Researchers' perception and response to the open access resources (OAR) in higher learning institutions of Tamil Nadu, India

PurposeThe purpose of this study is to report the results of a survey conducted at Bharathidasan and Alagappa Universities to determine the research scholars' awareness, use of Open Access (OA) resources, reasons for using, impact of OA on the research scholars' research, satisfaction and problems faced.Design/methodology/approachIn this study, a self-assessed questionnaire was developed to collect data from the research scholars pursuing their research degrees from Bharathidasan and Alagappa Universities of Tamil Nadu, India. A total of 400 research scholars from various disciplines responded were used for analysis.FindingsThe results indicated that the majority of research scholars aware of few OA resources to a large extent and afraid to redistribute the sources as they fear of copyright issues. Easy to use, more informative and global research at one place were the major reasons for accessing the resources. The research scholars were aware of OA features and OA's impact such as freedom to use, modify, resources available with source code, reliability, self-archiving, quick publishing, more citations etc. Delay in downloading and lack of computer terminals to access the resources were the major issues faced by the research scholars. On the whole, the researchers are considering OA model as an alternative to business model and expect the university librarians to promote and enhance the accessibility of OA resources.Practical implicationsThe outcomes of the results will enable the librarians and authorities in universities to formulate appropriate decisions to remove the issues faced by the research scholars and develop a framework for new literacy instructions.Originality/valueThe study undertaken is new to the Indian continent and the Tami Nadu state in particular. The findings of the study will be useful to improve the awareness level and use of OA resources effectively.

Development of a non-contact mobile screening center for infectious diseases: Effects of ventilation improvement on aerosol transmission prevention.

Under the global landscape of the prolonged COVID-19 pandemic, the number of individuals who need to be tested for COVID-19 through screening centers is increasing. However, the risk of viral infection during the screening process remains significant. To limit cross-infection in screening centers, a non-contact mobile screening center (NCMSC) that uses negative pressure booths to improve ventilation and enable safe, fast, and convenient COVID-19 testing is developed. This study investigates aerosol transmission and ventilation control for eliminating cross-infection and for rapid virus removal from the indoor space using numerical analysis and experimental measurements. Computational fluid dynamics (CFD) simulations were used to evaluate the ventilation rate, pressure differential between spaces, and virus particle removal efficiency in NCMSC. We also characterized the airflow dynamics of NCMSC that is currently being piloted using particle image velocimetry (PIV). Moreover, design optimization was performed based on the air change rates and the ratio of supply air (SA) to exhaust air (EA). Three ventilation strategies for preventing viral transmission were tested. Based on the results of this study, standards for the installation and operation of a screening center for infectious diseases are proposed.

Tracking Openness and Topic Evolution of COVID-19 Publications January 2020-March 2021: Comprehensive Bibliometric and Topic Modeling Analysis.

BACKGROUND: The COVID-19 outbreak highlighted the importance of rapid access to research. OBJECTIVE: The aim of this study was to investigate research communication related to COVID-19, the level of openness of papers, and the main topics of research into this disease. METHODS: Open access (OA) uptake (typologies, license use) and the topic evolution of publications were analyzed from the start of the pandemic (January 1, 2020) until the end of a year of widespread lockdown (March 1, 2021). RESULTS: The sample included 95,605 publications; 94.1% were published in an OA form, 44% of which were published as Bronze OA. Among these OA publications, 42% do not have a license, which can limit the number of citations and thus the impact. Using a topic modeling approach, we found that articles in Hybrid and Green OA publications are more focused on patients and their effects, whereas the strategy to combat the pandemic adopted by different countries was the main topic of articles selecting publication via the Gold OA route. CONCLUSIONS: Although OA scientific production has increased, some weaknesses in OA practice, such as lack of licensing or under-researched topics, still hold back its effective use for further research.

Mesenchymal Stromal Cell Secretome for the Treatment of Immune-Mediated Inflammatory Diseases: Latest Trends in Isolation, Content Optimization and Delivery Avenues.

Considering the high prevalence and the complex pharmacological management of immune-mediated inflammatory diseases (IMIDs), the search for new therapeutic approaches for their treatment is vital. Although the immunomodulatory and anti-inflammatory effects of mesenchymal stromal cells (MSCs) have been extensively studied as a potential therapy in this field, direct MSC implantation presents some limitations that could slow down the clinical translation. Since the beneficial effects of MSCs have been mainly attributed to their ability to secrete a plethora of bioactive factors, their secretome has been proposed as a new and promising pathway for the treatment of IMIDs. Formed from soluble factors and extracellular vesicles (EVs), the MSC-derived secretome has been proven to elicit immunomodulatory effects that control the inflammatory processes that occur in IMIDs. This article aims to review the available knowledge on the MSC secretome, evaluating the advances in this field in terms of its composition, production and application, as well as analyzing the pending challenges in the field. Moreover, the latest research involving secretome administration in IMIDs is discussed to provide an updated state-of-the-art for this field. Finally, novel secretome delivery alternatives are reviewed, paying special attention to hydrogel encapsulation as one of the most convenient and promising strategies.

Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders.

Over recent years, mesenchymal stem/stromal cells (MSCs) and their potential biomedical applications have received much attention from the global scientific community in an increasing manner. Firstly, MSCs were successfully isolated from human bone marrow (BM), but in the next steps, they were also extracted from other sources, mostly from the umbilical cord (UC) and adipose tissue (AT). The International Society for Cellular Therapy (ISCT) has suggested minimum criteria to identify and characterize MSCs as follows: plastic adherence, surface expression of CD73, D90, CD105 in the lack of expression of CD14, CD34, CD45, and human leucocyte antigen-DR (HLA-DR), and also the capability to differentiate to multiple cell types including adipocyte, chondrocyte, or osteoblast in vitro depends on culture conditions. However, these distinct properties, including self-renewability, multipotency, and easy accessibility are just one side of the coin; another side is their huge secretome which is comprised of hundreds of mediators, cytokines, and signaling molecules and can effectively modulate the inflammatory responses and control the infiltration process that finally leads to a regulated tissue repair/healing or regeneration process. MSC-mediated immunomodulation is a direct result of a harmonic synergy of MSC-released signaling molecules (i.e., mediators, cytokines, and chemokines), the reaction of immune cells and other target cells to those molecules, and also feedback in the MSC-molecule-target cell axis. These features make MSCs a respectable and eligible therapeutic candidate to be evaluated in immune-mediated disorders, such as graft versus host diseases (GVHD), multiple sclerosis (MS), Crohn's disease (CD), and osteoarthritis (OA), and even in immune-dysregulating infectious diseases such as the novel coronavirus disease 2019 (COVID-19). This paper discussed the therapeutic applications of MSC secretome and its biomedical aspects related to immune-mediated conditions. Sources for MSC extraction, their migration and homing properties, therapeutic molecules released by MSCs, and the pathways and molecular mechanisms possibly involved in the exceptional immunoregulatory competence of MSCs were discussed. Besides, the novel discoveries and recent findings on immunomodulatory plasticity of MSCs, clinical applications, and the methods required for their use as an effective therapeutic option in patients with immune-mediated/immune-dysregulating diseases were highlighted.

Osteoarthritis Research Society International (OARSI): Past, present and future.

We provide a detailed account of the origin and establishment of the Osteoarthritis Research Society International (OARSI) and celebrate its history from inception to the current day. We discuss the mission, vision and strategic objectives of OARSI and how these have developed and evolved over the last 3 decades. We celebrate the achievements of the society as we approach its 30th birthday, honor the entire presidential line and respectfully pay tribute to the past presidents who are no longer with us. We reflect on the strong foundations of our society, OARSI's efforts to disseminate understanding of the health, disability and economic burdens of osteoarthritis (OA) to policymakers, and the exciting initiatives to make the society inclusive and international. We thank our corporate and industrial sponsors, who have supported us over many years, without whom our annual congresses would not have been possible. We celebrate our longstanding strategic partnership with our publisher, Elsevier, and the successful launch of our new journal Osteoarthritis and Cartilage Open, the most significant new development in our dissemination toolbox. For the first time in the history of the organization, our annual congress was cancelled in April 2020 and the 2021 meeting will be virtual. Despite the numerous challenges posed by the ongoing COVID-19 pandemic and the need to adapt quickly to a rapidly changing landscape, we must remain optimistic about the future. We will take advantage of new exciting opportunities to advance our mission and vision to enhance the quality of life of persons with OA.

Open Access of COVID-19-related publications in the first quarter of 2020: a preliminary study based in PubMed.

Background: The COVID-19 outbreak has made funders, researchers and publishers agree to have research publications, as well as other research outputs, such as data, become openly available. In this extraordinary research context of the SARS CoV-2 pandemic, publishers are announcing that their coronavirus-related articles will be made immediately accessible in appropriate open repositories, like PubMed Central, agreeing upon funders' and researchers' instigation. Methods: This work uses Unpaywall, OpenRefine and PubMed to analyse the level of openness of articles about COVID-19, published during the first quarter of 2020. It also analyses Open Access (OA) articles published about previous coronavirus (SARS CoV-1 and MERS CoV) as a means of comparison. Results: A total of 5,611 COVID-19-related articles were analysed from PubMed. This is a much higher amount for a period of 4 months compared to those found for SARS CoV-1 and MERS during the first year of their first outbreaks (335 and 116 articles, respectively).  Regarding the levels of openness, 88.8% of the SARS CoV-2 papers are freely available; similar rates were found for the other coronaviruses. Deeper analysis showed that (i) 67.4% of articles belong to an undefined Bronze category; (ii) 76.4% of all OA papers don't carry any license, followed by 10.4% which display restricted licensing. These patterns were found to be repeated in the three most frequent publishers: Elsevier, Springer and Wiley. Conclusions: Our results suggest that, although scientific production is much higher than during previous epidemics and is open, there is a caveat to this opening, characterized by the absence of fundamental elements and values ​​on which Open Science is based, such as licensing.