The COVID-19 pandemic has caused devastating loss of life and a healthcare crisis worldwide. SARS-CoV-2 is the causative pathogen of COVID-19 and is transmitted mainly through the respiratory tract, where the virus infects host cells by binding to the ACE2 receptor. SARS-CoV-2 infection is associated with acute pneumonia, but neuropsychiatric symptoms and different brain injuries are also present. The possible routes by which SARS-CoV-2 invades the brain are unclear, as are the mechanisms underlying brain injuries with the resultant neuropsychiatric symptoms in patients with COVID-19. Ferroptosis is a unique iron-dependent form of non-apoptotic cell death, characterized by lipid peroxidation with high levels of glutathione consumption. Ferroptosis plays a primary role in various acute and chronic brain diseases, but to date, ferroptosis in COVID-19-related brain injuries has not been explored. This review discusses the mechanisms of ferroptosis and recent evidence suggesting a potential pathogenic role for ferroptosis in COVID-19-related brain injury. Furthermore, the possible routes through which SARS-CoV-2 could invade the brain are also discussed. Discoveries in these areas will open possibilities for treatment strategies to prevent or reduce brain-related complications of COVID-19.

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COVID-19 caused by SARS-CoV-2 can cause various systemic diseases such as acute pneumonia with cytokine storm. Constituted of necroptosis, pyroptosis, and ferroptosis, regulated necrosis constitutes the cell death patterns under the low apoptosis condition commonly observed in COVID-19. Regulated necrosis is involved in the release of cytokines like TNF-α, IL-1 β, and IL-6 and cell contents such as alarmins, PAMPs, and DAMPs, leading to more severe inflammation. Uncontrolled regulated necrosis may explain the poor prognosis and cytokine storm observed in COVID-19. In this review, the pathophysiology and mechanism of regulated necrosis with the double-edged sword effect in COVID-19 are thoroughly discussed in detail. Furthermore, this review also focuses on the biomarkers and potential therapeutic targets of the regulated necrosis pathway in COVID-19, providing practical guidance to judge the severity, prognosis, and clinical treatment of COVID-19 and guiding the development of clinical anti-SARS-CoV-2 drugs.

T h e objectives of this systematic review were (1) to identify and systematically classify the existing tourism climate indices (TCIs), (2) to compare the climate factors and weights of TCIs, and (3) to summarize the methodology defects of developing TCIs. Specifically, the purpose of this study is to identify all the tourism climate indices developed and thereafter comparing them w i t h t h e i n c l u d i n g c l i m a t e f a c t o r s (temperature, precipitation, sunshine, air INPLASY 1

Background: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory arthropathy. Recommendations for RA, specifically on pharmacotherapy, are essential in clinical practice. However, the direction and strength of recommendations are controversial across current clinical practice guidelines (CPGs) of RA.Objective: To systematically analyze the consistency of recommendations regarding pharmacotherapy of RA across CPGs.Methods: 11 electronic databases and websites were comprehensively searched from inception to 14 March 2022, to identify CPGs for diagnosis, therapy, and management of RA. Unambiguous and discrete specifications of the population-intervention-comparison (PIC) framework were used to classify the recommendations. Based on the PIC framework, consistency analyses across CPGs on pharmacotherapy of RA were performed. Two researchers reached a consensus on coding the direction and strength of each recommendation.Results: Finally, 26 CPGs were included in this study, and 14 of them, which included pharmacotherapy, were performed consistency analysis. 1) 64 recommendations from 14 CPGs were classified into 18 PICs. 2) Seven PICs (38%) were consistent in direction and strength, 10 PICs (56%) were consistent in direction but inconsistent in strength, and one PIC (6%) was inconsistent in direction (hydroxychloroquine, HCQ). 3) Sensitivity analysis tested the robustness, and the inconsistency remained high.Conclusion: The direction was highly consistent among the recommendations of pharmacotherapy for RA, but the strength was highly inconsistent. Reasons for the inconsistency need to be further investigated, and consistent recommendations could guide the pharmacotherapy of RA in clinical practice.

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