TYPE I INTERFERON SCORE IS ASSOCIATED WITH THE SEVERITY AND POOR PROGNOSIS IN ANTI-MDA5 ANTIBODY-POSITIVE DERMATOMYOSITIS PATIENTS

BackgroundAnti-MDA5 antibody-positive dermatomyositis (anti-MDA5+DM) is a rare autoimmune disease associated with a high mortality rate due to rapid-progressive interstitial lung disease (RP-ILD), particularly in East Asia[1]. MDA5, acts as a cytoplasmic sensor of viral RNA, thus activating antiviral responses including the type I interferon (IFN) signaling pathway[2]. The involvement of type 1 IFN in the pathogenesis of MDA5+DM has been proposed based on the significantly elevated expression of its downstream stimulated genes(ISG) in muscle, skin, lung, and peripheral blood[3;4]. Janus kinase inhibitor, which targets the IFN pathway, combined with glucocorticoid could improve the survival of early-stage MDA5+DM-ILD patients[5]. In clinical practice, there is still an urgent demand for sensitive biomarkers to facilitate clinical risk assessment and precise treatment.ObjectivesThis study aimed to investigate the clinical significance of interferon score, especially IFN-I score, in patients with anti-MDA5+DM.MethodsDifferent subtypes of idiopathic inflammatory myopathy, including anti-MDA5+DM(n=61), anti-MDA5-DM(n=20), antisynthetase syndrome(ASS,n=22),polymyositis(PM,n=6) and immune-mediated necrotizing myopathy(IMNM,n=9), and 58 healthy controls were enrolled.. A multiplex quantitative real-time PCR(RT-qPCR) assay using four TaqMan probes was utilized to evaluate two type I ISGs (IFI44, MX1, which are used for IFN-I score), one type II ISG (IRF1), and one housekeeping gene (HRPT1). Clinical features and disease activity index were compared between high and low IFN-I score groups in 61 anti-MDA5+DM patients. The association between laboratory findings and the predictive value of baseline IFN-I score level for mortality was analyzed.ResultsThe IFN scores were significantly higher in patients with anti-MDA5+DM than in HC (Figure 1A). The IFN-I score correlated positively with serum IFN α(r = 0.335, P =0.008), ferritin (r = 0.302, P = 0.018), and Myositis Disease Activity Assessment Visual Analogue Scale (MYOACT) score(r=0.426, P=0.001). Compared with patients with low IFN-I scores, patients with high IFN-I scores showed increased MYOACT score, CRP, AST, ferritin, and the percentages of plasma cells (PC%) but decreased lymphocyte count, natural killer cell count, and monocyte count. The 3-month survival rate was significantly lower in patients with IFN-I score > 4.9 than in those with IFN-I score ≤ 4.9(72.9% vs. 100%, P=0.044)(Figure 1B).ConclusionIFN score, especially IFN-I score, detected by multiplex RT-qPCR, can be a valuable biomarker for monitoring disease activity and predicting mortality in anti-MDA5+DM patients.References[1]I.E. Lundberg, M. Fujimoto, J. Vencovsky, R. Aggarwal, M. Holmqvist, L. Christopher-Stine, A.L. Mammen, and F.W. Miller, Idiopathic inflammatory myopathies. Nat Rev Dis Primers 7 (2021) 86.[2]G. Liu, J.H. Lee, Z.M. Parker, D. Acharya, J.J. Chiang, M. van Gent, W. Riedl, M.E. Davis-Gardner, E. Wies, C. Chiang, and M.U. Gack, ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity. Nat Microbiol 6 (2021) 467-478.[3]G.M. Moneta, D. Pires Marafon, E. Marasco, S. Rosina, M. Verardo, C. Fiorillo, C. Minetti, L. Bracci-Laudiero, A. Ravelli, F. De Benedetti, and R. Nicolai, Muscle Expression of Type I and Type II Interferons Is Increased in Juvenile Dermatomyositis and Related to Clinical and Histologic Features. Arthritis Rheumatol 71 (2019) 1011-1021.[4]Y. Ye, Z. Chen, S. Jiang, F. Jia, T. Li, X. Lu, J. Xue, X. Lian, J. Ma, P. Hao, L. Lu, S. Ye, N. Shen, C. Bao, Q. Fu, and X. Zhang, Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic implications. Nat Commun 13 (2022) 6458.[5]Z. Chen, X. Wang, and S. Ye, Tofacitinib in Amyopathic Dermatomyositis–Associated Interstitial Lung Disease. New England Journal of Medicine 381 (2019) 291-293.AcknowledgementsThis work was supported by the National Natural Science Foundation of China [81974251], and Shanghai Hospital Develop ent Center, Joint Research of New Advanced Technology Project [SHDC12018106]Disclosure of InterestsNone Declared.

Dynamic Group Difference Coding Based on Thermal Infrared Face Image for Fever Screening

Recently, noncontact temperature measurement methods based on infrared face perception have received widely attentions since fever screening plays an important role in the early prediction of respiratory infections, such as SARS, H1N1, and COVID-19. However, the performance of these methods always significantly degrades when facing the changes of environment. Thus, the majority of these methods leverage the block-body and sensors to reduce the influence of environment changes. It is a pity that the increased instrument complexity leads to higher costs and failure rate. To address the aforementioned issues, this article presents a novel fever screening method, named dynamic group difference coding (DGDC), which is based on the analysis about the influencing factors. The key idea of DGDC is to compute the temperature differences between the target person and the recently passed crowd (dynamic group). Specifically, we develop the face temperature encoder (FTE) to describe the face temperature and thus construct the difference matrix of the embedding feature between the target person and the dynamic group. Multilayer perceptions (MLP) are employed to capture the intrinsic information by characterizing the difference matrix in vertical and horizontal directions, respectively. Finally, we provide a dataset of thermal infrared face (TIF) images and conduct extensive experiments to demonstrate the advantages of the proposed method over the competing methods. © 1963-2012 IEEE.

A microchamber-free and enzyme-free digital assay based on ultrabright fluorescent microspheres

Digital analysis is an effective single-molecule detection method and has attracted extensive attention in the field of bioassays. However, most digital assays require microchambers for signal compartmentalization. Herein, we developed a microchamber-free and enzyme-free digital assay by labeling paramagnetic beads directly with ultrabright fluorescent microspheres. In this assay, a DNA sandwich analysis was firstly performed on the bead to label a fluorescent microsphere. Then, the beads were loaded on the glass slide to form a monolayer film for signal readout. The whole analysis process does not require the participation of enzymes and the preparation of microchambers, which greatly simplifies the experimental steps and saves the costs. Furthermore, by introducing non-enzymatic hybridization chain reaction (HCR) and biotinylated DNA-conjugated gold nanoparticles (Au NPs-Bio), the capture efficiency and analytical sensitivity were improved. As a proof of concept, single-stranded DNA (ssDNA) of SARS-CoV-2 fragment was chosen as a model, and a detection limit of 1.5 fM was achieved. Spiked and recovery experiments on human serum and saliva samples validated the good performance of the proposed digital assay in real biological samples. The proposed assay provides a facile way of signal generation and readout for digital analysis. © 2023 Elsevier B.V.

Itinerary Card Anti-cheating Beyond OCR

Since the COVID-19 pandemic, the itinerary card has become so pertinent to our lives that we need to show our itinerary card whether we take public transport or enter public places. The traditional way to manually check and record the information on the itinerary card is inefficient. It easily leads to congestion at the entrance, especially in high-traffic areas. In addition, some people even falsify their itinerary codes to evade mandatory testing or quarantine for COVID-19. Therefore, an efficient itinerary checking method is needed to alleviate the crowded problem, reduce cross-infection, and intelligently detect itinerary cheating. To address these issues, we propose a deep-learning-based method combined with OCR techniques. This method consists of five parts, including ROI locating, color classification, OCR, information pooling, and anti-cheating. The proposed scheme can extract the itinerary information on the itinerary card and check it. It also provides a certain anti-cheating function. Experimental results show that the proposed scheme can efficiently check the information on the itinerary card with high accuracy. © 2022 IEEE.

Spatio-temporal Transmission of COVID-19 Pandemic in Susceptible-exposed of Small-world Network Model

This paper proposes the Susceptible-exposed of Small-world Network Model (SSEM) by combining the Susceptible-Exposed-Infectious-Recovered (SEIR) model with the Small-world Network (SN) model. The scenarios of COVID-19 propagation in urban public transport network was set by the specific model parameters. A study area, Huicheng District, Huizhou City, Guangdong Province, China, was selected to estimate the temporal and spatial distribution characteristics of COVID-19 within 12 hours based on SSEM. The results show that, without taking protective measures, if the two infectious source were in a bus, after 12 hours, 324 bus stations, 762 infected people and 68.85km2 were covered in the study area. The results of this study will provide a reference for the future study of COVID-19 virus transmission mechanism in the small enclosed environment. © 2021 IEEE.

The Effects of Online Supervisory Feedback on Student-Supervisor Communications during the COVID-19

This study focuses on online supervisory written feedback on PhD supervisees’ performance, given explicitly through online communication, particularly during the first wave of COVID-19. This unusual situation has brought many different effects on students’ academic lives. This scenario has influenced both students’ and teachers’ mutual communication. A directed qualitative content analysis (DQCA) approach was adapted from previous research and modified for the present context. The current study planned to bring forth the supervisee and supervisors’ perception of the communication and feedback process, considering that online feedback and communication has been a new experience for most students. According to the findings, teachers/supervisors give feedback on students’ production, whereas teacher-student communication also seemed crucial for the performance improvising of learners. The result brought forth a wide range of social, educational, and surprisingly psychological issues both supervisees and supervisors faced during online communication during COVID-19. © 2022 The Author(s).

COVID-19 and social inequality in China: the local-migrant divide and the limits of social protections in a pandemic

The existing literature suggests that external shocks, such as pandemics, stimulate people's demand for social protections and prompt them to favor short-term social consumption over long-term investments. However, this argument may not apply fully in a society with an urban-rural divide in addition to an unequal welfare system. Through a telephone survey conducted in July 2020, this study sought to investigate public opinions on the social policy response to the coronavirus disease pandemic in China. Quantitative evidence showed large economic hardship among the respondents, who expressed a strong expectation for labor market interventions instead of social assistance. This study reveals that the preexisting inequalities in people's access to welfare benefits have led local residents and migrants to develop differential preferences for social policies. This attitudinal heterogeneity is illustrative of the inequalities in the Chinese welfare system as well as of the labor market dynamics that have resulted from massive internal migration and the informalization of the workforce. The division between locals and migrants in China's urban welfare system has shaped a demarcation of welfare preferences between the two groups through peculiar interpretive feedback effects.

Incidence of adverse reactions to COVID-19 vaccination: A meta-analysis of randomized controlled trials

Objective: To systematically evaluate the incidence of adverse reactions to coronavirus disease 2019 (COVID-19) vaccination. Methods: We systematically searched PubMed, Embase, The Cochrane Library, Web of Science, CNKI, WanFang Data, and VIP Database from the inception of each database to August 31, 2021. Randomized controlled clinical trials (RCTs) on the safety of different types of COVID-19 vaccines were retrieved and analyzed. A random or fixed-effects model was used with an odds ratio as the effect size. The quality of each reference was evaluated. The incidence of the adverse reactions of the placebo group and the vaccination group was compared. Heterogeneity and publication bias were taken care of by meta-regression and sub-group analyses. Results: A total of 13 articles were included, with 81 287 subjects. Compared with the placebo group, the vaccination group showed a higher combined risk ratio (RR) of total adverse reactions (RR=1.67, 95% CI: 1.46-1.91, P<0.01), local adverse reactions (RR=2.86, 95% CI: 2.11-3.87, P<0.01), systemic adverse reactions (RR=1.25, 95% CI: 0.92-1.72, P=0.16), pain (RR=2.55, 95% CI: 1.75-3.70, P<0.01), swelling (RR=4.16, 95% CI: 1.71-10.17, P=0.002, fever (RR=2.34, 95% CI: 1.84-2.97, P<0.01), fatigue (RR=1.36, 95% CI: 1.32-1.41, P<0.01) and headache (RR=1.22, 95% CI: 1.18-1.26, P<0.01). The subgroup analysis showed the incidence of adverse reactions of the vaccination group after injection of the three COVID-19 vaccines (inactivated viral vaccines, mRNA vaccines and adenovirus vector vaccines) was higher than that of the placebo group, and the difference between the placebo group and the vaccination group in the mRNA vaccine subgroup and the adenovirus vector vaccine subgroup was statistically significant (P<0.01). The incidence of adverse reactions after injection of COVID-19 vaccine in subgroups of different ages was significantly higher than that in the placebo group (P<0.01). Conclusions: COVID-19 vaccines have a good safety, among which adenovirus vector vaccine has the highest incidence of adverse reactions. Both adolescents and adults vaccinated with novel coronavirus vaccine have a certain proportion of adverse reactions, but the symptoms are mild and can be relieved by themselves. Our meta-analysis can help boost global awareness of vaccine safety, promote mass vaccination, help build regional and global immune barriers and effectively curb the recurrency of COVID-19.

Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity.

Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.

Application architecture of product information traceability based on blockchain technology and a lightweight secure collaborative computing scheme

In the course of the rapid development of e-commerce in China, the problems of information asymmetry, unclear market responsibilities and traceability of product information in B2C sales have been restricting the long-term development of China's online retail market. In the special period when novel coronavirus is raging, e-commerce is very consequential for related medical industries such as surgical masks. Given the gradual development of blockchain technology, it can be explored to employ this technology as a basis to solve the problem of information traceability in the B2C sales process, and through the blockchain's distributed storage architecture, lightweight digital signature algorithm, consistency algorithm and other technologies to make up for product security vulnerabilities, to prevent information from being tampered with. Nevertheless, the authenticity, reliability and integrity of blockchain information transmission can also be solved by the EPC system network technology and Hash Encryption Algorithm. In this paper, we design a product information traceability application framework based on blockchain technology, aiming at the urgent need to solve the product traceability of mask enterprises during the current new crown epidemic. Also, for the corresponding scenarios in e-commerce, we propose a lightweight cooperation scheme based on blockchain technology and give security analysis. Based on lightweight cryptography, our scheme achieves identity-based authentication, peer-to-peer communication and secure collaborative computing. © 2020 IEEE.

Effect of early initiation of blood purification in ICU adults with severe COVID-19

Background: Cytokine storm induced by SARS-CoV-2 was considered as one of the main mechanisms of multiple organs dysfunction in Covid-19. Blood purification could remove excess cytokines or other harmful substances and then attenuate target organs injury. In this prospective single-center cohort study, we aimed to assess the efficacy of early initiation of blood purification in ICU adults with severe Covid-19. Methods: Sixty-two patients in early stage of severe Covid-19 in ICU(Tongji Hospital, Wuhan, China) from Feb.9.2020 to Mar.24.2020 were recruited and divided into two subgroups: 20 patients initiated blood purification including CVVH(/HP) after ICU admission, and the other 42 patients who had not received RRT unless reached traditional RRT indication, were served as control. The primary outcome was in-hospital all-causeResults: The 20 patients initiated early RRT after 6.4±3.6 days from ICU admission. The mean cumulative treatment time was 50.0±42.2 hours, the net ultrafiltration rate was 65.5±65.2ml/h. One patient in control group also received RRT after ICU admission due to AKI. No statistic difference was found in the two subgroups in baseline. 61.3% patients died during hospitalization. The median survival time was 12 days and the average observation time was 19 days. Kaplan-Meier analysis showed that the in-hospital allcause mortality of early RRT patients was lower than control group(50.5% vs 66.7%, p=0.040). Univariate analysis and Cox proportional hazard regression also confirmed that early initiation of RRT was an independent protective factor(HR 0.21, 95%CI 0.06- 0.74, p=0.014) for in-hospital all-cause death of severe Covid-19 after adjusting by SpO2, lymphocyte proportion, albumin, LogNT-proBNP, LogInterleukin-6, mechanical ventilation and use of glucocorticoid. A figure that shows the course of disease indicates that early initiation of blood purification may decrease the death without multiple organs injuries(39% vs 0%, p=0.037). Conclusions: Early initiation of blood purification could probably reduce the mortality of severe Covid-19. It was implied that it could delay occurs and reduce degrees of target organs injuries by cutting the peak load of cytokine storm. Further research in basic and clinical were needed to clarify the mechanism of blood purification in cytokine storm-related diseases.

Kidney injury in icu adults with severe COVID-19

Background: The SARS-CoV-2 infected humans through the angiotensin converting enzyme (ACE-2) receptor. Kidney, which highly expressed ACE-2, became one of the main target organs attacked by SARS-CoV-2. In this cross-sectional study, we aimed to explore renal injury in ICU adults with severe coronavirus disease 2019 (Covid-19). Methods: Fifty-three severe Covid-19 adults, admitted into ICU (Tongji Hospital, Wuhan, China) from Feb.9.2020 to Mar.24.2020, were finally included in analysis. Baseline demographic, clinical characteristics, laboratory examination data and prognosis were all recorded. Results: Mean age of 53 patients was 67.5±15.2 yrs, including 34 men and 19 women. The predominant comorbid conditions were as follows: hypertension in 26 patients (50.0%), diabetes mellitus in 11 patients (21.2%), cardiovascular diseases in 5 patients (9.6%) and chronic kidney disease in 2 patients (3.8%). The mean serum creatinine at baseline was 67.2±26.7 μmol/L, while the baseline urine routine before hospitalization was uninformed. In the period of whole ICU stay, most patients presented abnormal urine routine: 93.2% of patients had proteinuria (+/- 9.1%, 1+ 40.9%, 2+ 31.8% and 3+ 11.4%, respectively) and 97.7% had hematuria. 20 of 53 patients (37.7%) with mean age of 72.2±9.9 yrs diagnosed as hospital-acquired acute kidney injury, according to KDIGO 2012 AKI diagnosis creatinine criteria. In those AKI patients, 5(25%), 7(35.0%) and 8(40%) reached AKI stage I, II and III, respectively. AKI was diagnosed after 25.0±12.8 days since onset of Covid-19 and after 7.8±5.6 days since ICU admission. The mean duration of AKI course was 7.9±7.1 days. Finally, 16 of 20 patients with AKI (80.0%) died in ICU. The survival time of AKI patients was 32.9±14.6 days since onset of Covid-19 and 15.7±9.4 days since ICU admission. The in-hospital all-cause mortality of AKI patients was higher than non-AKI patients (80.0% vs 29.4%, p=0.004). Only one (5.0%) patient recovered from AKI during ICU stay (serum creatinine reduced ≥50%). Conclusions: Kidney injury including abnormal urine routine and increased serum creatinine presented in almost all severe Covid-19 patients. AKI event could predict poor prognosis with severe Covid-19. We should increase awareness of kidney injury in patients with severe COVID-19.