EVALUATION OF RESPONSE TO ADJUVANTED RECOMBINANT ZOSTER VACCINATION IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING UPADACITINIB: RESULTS FROM A RANDOMIZED TRIAL SUB-STUDY

BackgroundUpadacitinib (UPA) is an oral JAK inhibitor (JAKi) approved for the treatment of RA. JAKi have been associated with an elevated risk of herpes zoster (HZ) in patients (pts) with RA. The adjuvanted recombinant zoster vaccine (RZV, Shingrix) was shown to be well-tolerated and effective in preventing HZ in adults aged ≥ 50 years.[1] The efficacy and safety of RZV have not been studied in pts with RA while on UPA in combination with MTX.ObjectivesTo assess the immunogenicity of RZV in pts with RA receiving UPA 15 mg once daily (QD) with background MTX.MethodsEligible adults aged ≥ 50 years with RA enrolled in the ongoing SELECT-COMPARE phase 3 trial (NCT02629159) received two RZV doses, administered at the baseline and week (wk) 12 visits. Pts should have been on stable doses of UPA 15 mg QD and background MTX for ≥ 8 wks before the first vaccination and ≥ 4 wks after the second vaccination. Antibody titers were collected pre-vaccination (baseline), 4 wks post-dose 1 vaccination (wk 4), and 4 wks post-dose 2 vaccination (wk 16). The primary endpoint was the proportion of pts with a humoral response to RZV defined as ≥ 4-fold increase in pre-vaccination concentration of anti-glycoprotein E [gE] titer levels at wk 16. Secondary endpoints included humoral response to RZV at wk 4 and the geometric mean fold rise (GMFR) in anti-gE antibody levels at wks 4 and 16. Cell-mediated immunogenicity to RZV was an exploratory endpoint evaluated by the frequencies of gE-specific CD4+ [2+] T cells (CD4+ T cells expressing ≥ 2 of 4 activation markers: IFN-γ, IL-2, TNF-α, and CD40 ligand) measured by flow cytometry at wks 4 and 16 in a sub-cohort of pts.ResultsOf the 95 pts who received ≥ 1 RZV dose, 93 (98%) received both RZV doses. Pts had a mean (standard deviation) age of 62.4 (7.5) years. The median (range) disease duration was 11.7 (4.9–41.6) years and duration of UPA exposure was 3.9 (2.9–5.8) years. At baseline, all but 2 pts were receiving concomitant MTX and half (50%) were taking an oral corticosteroid (CS) at a median daily dose of 5.0 mg. One pt discontinued UPA by wk 16. Blood samples were available from 90/93 pts. Satisfactory humoral responses to RZV occurred in 64% (95% confidence interval [CI]: 55–74) of pts at wk 4 and 88% (81–95) at wk 16 (Figure 1). Age (50–< 65 years: 85% [95% CI: 75–94];≥ 65 years: 94% [85–100]) and concomitant CS (yes: 87% [77–97];no: 89% [80–98]) use at baseline did not affect humoral responses at wk 16. GMFR in anti-gE antibody levels compared with baseline values were observed at wks 4 (10.2 [95% CI: 7.3–14.3]) and 16 (22.6 [15.9–32.2]). Among the sub-cohort of pts, nearly two-thirds achieved a cell-mediated immune response to RZV (wk 4: n = 21/34, 62% [95% CI: 45–78];wk 16: n = 25/38;66% [51–81]). Within 30 days post-vaccination of either RZV dose, no serious adverse events (AEs) (Table 1) or HZ were reported. AEs that were possibly related to RZV were reported in 17% of pts. One death occurred more than 30 days after wk 16 due to COVID-19 pneumonia.ConclusionMore than three-quarters (88%) of pts with RA receiving UPA 15 mg QD on background MTX achieved a satisfactory humoral response to RZV at wk 16. In a subgroup of pts, two-thirds (66%) achieved a cell-mediated immune response to RZV at wk 16. Age and concomitant CS use did not negatively affect RZV response.Reference[1]Syed YY. Drugs Aging. 2018;35:1031–40.Table 1. Safety Results Through 30-Days Post-RZV Vaccination in UPA-Treated PatientsEvent, n (%)UPA 15 mg QD (N = 95)Any AE38 (40%)AE with reasonable possibility of being related to UPAa13 (14%)AE with reasonable possibility of being related to RZVa16 (17%)Severe AEb1 (1%)Serious AE0AE leading to discontinuation of UPA0Death0AE, adverse event;QD, once daily;RZV, adjuvanted recombinant zoster vaccine;UPA, upadacitinib.aAs assessed by the investigator.bHypersensitivity.AcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, review, and approval of the . All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsKevin Winthrop Consultant of: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB, Grant/research support from: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB, Justin Klaff Shareholder of: AbbVie, Employee of: AbbVie, Yanxi Liu Shareholder of: AbbVie, Employee of: AbbVie, CONRADO GARCIA GARCIA: None declared, Eduardo Mysler Speakers bureau: AbbVie, Amgen, AstraZeneca, BMS, Eli Lilly, GlaxoSmithKline, Pfizer, Roche, and Sandoz, Consultant of: AbbVie, Amgen, AstraZeneca, BMS, Eli Lilly, GlaxoSmithKline, Pfizer, Roche, and Sandoz, Alvin F. Wells Consultant of: AbbVie, Amgen, BMS, Eli Lilly, Novartis, Pfizer, and Sanofi, Xianwei Bu Shareholder of: AbbVie, Employee of: AbbVie, Nasser Khan Shareholder of: AbbVie, Employee of: AbbVie, Michael Chen Shareholder of: AbbVie, Employee of: AbbVie, Heidi Camp Shareholder of: AbbVie, Employee of: AbbVie, Anthony Cunningham Consultant of: GSK, Merck Sharp & Dohme, and BioCSL/Sequirus.

LONG-TERM EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS: 3-YEAR RESULTS FROM THE PHASE 3 SELECT-PsA 1 STUDY

BackgroundUpadacitinib (UPA) improved symptoms in patients (pts) with psoriatic arthritis (PsA) with prior inadequate response or intolerance to ≥1 non-biologic disease-modifying antirheumatic drug (nbDMARD-IR) through week (wk) 104 or 2 years of treatment in SELECT-PsA 1 [1].ObjectivesTo evaluate efficacy and safety of UPA vs adalimumab (ADA) through wk 152 or 3 years from the ongoing long-term open-label extension of SELECT-PsA 1.MethodsPts were randomized to receive UPA 15 mg (UPA15) or UPA 30 mg (UPA30) once daily, ADA 40 mg (ADA) every other wk, or placebo (PBO). At wk 24, PBO pts switched to UPA15 or UPA30. Following approval of UPA15, the protocol was amended so pts on UPA30 switched to UPA15 (earliest at wk 104). Efficacy was assessed through wk 152, and safety through June 13, 2022.ResultsOf 1704 pts randomized, 911 completed 152 wks of treatment. The proportions of pts achieving.≥20%/50%/70% improvement in American College of Rheumatology criteria (ACR20/50/70), minimal disease activity (MDA), and ≥75%/90%/100% improvement in Psoriasis Area and Severity Index at wk 152 were generally consistent with those at wk 1041. UPA had greater ACR20/50/70 and MDA responses vs ADA, and a greater mean change from baseline (BL) in Health Assessment Questionnaire-Disability Index, pt's assessment of pain, and Bath Ankylosing Spondylitis Disease Activity Index vs ADA. Change from BL in modified total Sharp/van der Heijde score were similar between UPA30 and ADA, and numerically higher with UPA15 (Table 1). The overall UPA safety profile remained unchanged (Figure 1) [1,2]. UPA had numerically higher rates of serious infection (SI), herpes zoster (HZ), anemia, lymphopenia, creatine phosphokinase (CPK) elevation, and non-melanoma skin cancer (NMSC) vs ADA. Increases for SI, HZ, anemia, and CPK elevation with UPA were dose dependent. Rates of major adverse cardiovascular events, venous thromboembolism, and malignancy excluding NMSC were low and generally similar across groups. The most common cause of death was COVID-19.ConclusionEfficacy of UPA in nbDMARD-IR pts with PsA was maintained through 3 years of treatment. No new safety signals were identified.References[1]McInnes IB, et al. Rheumatol Ther 2022;1–18 [Epub ahead of print].[2]McInnes IB, et al. RMD Open 2021;7(3):e001838.Table 1.Efficacy endpoints at wk 152UPA15 (n=429)UPA30a (n=423)ADA (n=429)Proportion of pts (%)NRIAONRIAONRIAOACR20/50/7064.6/52.0/35.9*89.8/71.6/ 48.263.1/54.1*/ 35.787.9/74.4/ 47.861.1/46.6/ 28.786.2/65.2/ 39.8Minimal disease activity37.555.143.5*60.335.950.2PASI75/90/100b50.5/42.5/32.269.2/58.5/ 43.458.1/46.7/3 7.678.6/63.5/ 50.954.0/40.8/ 30.379.6/59.9/ 44.6Resolution of enthesitis by Leeds Enthesitis Indexc50.475.248.973.846.077.0Resolution of dactylitis by Leeds Dactylitis Indexd65.495.266.197.965.497.1Change from BLeMMRMAOMMRMAOMMRMAOHealth Assessment Questionnaire- Disability Index-0.51-0.55-0.53*-0.58-0.45-0.49Pt's assessment of pain (numeric rating scale)-3.3*-3.5-3.3*-3.6-2.8-3.0Bath Ankylosing Spondylitis Disease Activity Indexf-3.09-3.27-3.16-3.54-2.81-2.71Modified total Sharp/van der Heijde score0.210.190.050.040.090.09aFollowing a protocol amendment, all pts on UPA30 switched to UPA15 (earliest switch at wk 104);data are presented by originally randomized group. bPts with psoriasis affecting ≥3% of body surface area at BL. cPts with LEI >0 at BL;resolution LEI=0. dPts with LDI >0 at BL;resolution LDI=0. eData shown as MMRM (least squares mean) and AO (mean). fPts with psoriatic spondylitis at BL. n value ranges: UPA15 (99–429), UPA30 (95–423), ADA (89–429). Nominal *p<0.05 UPA vs ADA.ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology criteria;ADA, adalimumab;AO, as observed;BL, baseline;MMRM, mixed effect model repeated measurement;NRI, non-responder imputation;PASI75/90/100, ≥75%/90%/100% improvement in Psoriasis Area and Severity Index;pt, patient;UPA15/30, upadacitinib 15/30 mg once daily;wk, weekAcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Carl Davies, MSc, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of InterestsIain McInnes Grant/research support from: AbbVie, AstraZeneca, Bristol Myers Squibb, Celgene, Eli Lilly, Evelo, Causeway Therapeutics, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, and UCB Pharma, Koji Kato Employee of: AbbVie and may hold stock or options, Marina Magrey Consultant of: BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, BMS, and UCB Pharma, Joseph F. Merola Consultant of: AbbVie, Arena, Avotres, Biogen, Bristol Myers Squibb, Celgene, Dermavant, Eli Lilly, EMD Sorono, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma, Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Celgene, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB Pharma, Derek Haaland Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, Grant/research support from: AbbVie, Adiga Life Sciences, Amgen, Bristol Myers Squibb, Can-Fite Biopharma, Celgene, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron, Sanofi-Genzyme, UCB;and has received honoraria or other fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, and UCB Pharma, Yihan Li Employee of: AbbVie and may hold stock or options, Yanxi Liu Employee of: AbbVie and may hold stock or options, Jianzhong Liu Employee of: AbbVie and may hold stock or options, Ralph Lippe Employee of: AbbVie and may hold stock or options, Peter Wung Employee of: AbbVie and may hold stock or options.

Authentic leadership and employees' job performance: mediation effect of positive employee health

In light of global competition and the COVID-19 pandemic, organizations are encountering an increasingly challenging and unpredictable environment. Consequently, employees are experiencing heightened levels of job strain. This study aims to explore the impact of various organizational mechanisms on promoting positive employee health within the organization, ultimately affecting employees' job performance. The findings of this study indicate that authentic leadership and the absence of organizational politics are significant predictors of positive employee health. Moreover, positive employee health has a positive influence on supervisor-rated job performance through its effect on job engagement. This study serves as a valuable resource for organizations, shedding light on the fundamental factors that contribute to positive employee health. It also raises managers' awareness of the importance of nurturing and sustaining employees' emotional and physical well-being to maintain competitiveness in the market. © 2023 Antai College of Economics and Management, Shanghai Jiao Tong University.

A Study on the Influence of Task-driven Instruction on Learning Outcomes in Online Learning under COVID-19

Interest in online learning is increasing due to its advantages and pedagogical potential. However, few studies have investigated the effects of task-driven instruction on learning outcomes. This study examines the effectiveness of the application of task-driven instruction as a means of verifying that the use of task-driven instruction in online learning is effective by comparing changes in students' grades, intrinsic motivation, perceived social presence, and perceived cognitive load before and after the application of the method. Eighty high school students (33 males) were recruited for this experiment. Prior to the experiment, the purpose and steps of the study were explained frankly and candidly, problems and risks that might arise from participation in the study were pointed out, the benefits that would result from participation in the study were explained, and the possibility of voluntarily withdrawing from the study at any time was clearly communicated and approved by the study subjects or guardians. They were divided into experimental group I and control group II, with 40 students in each group. The results of the study showed that after the implementation of the instruction, the experimental group I performed significantly better than the control group II. In addition, the experimental group II outperformed the control group II in terms of perceived intrinsic motivation, social presence, and cognitive load. © 2023 ACM.

Association of interleukin-6 and CD4+ T cells and two-week prognosis of patients with COVID-19: a predictive role.

OBJECTIVE:  The aim of this study was to determine the association of inflammation and immune responses with the outcomes of patients at various stages, and to develop risk stratification for improving clinical practice and reducing mortality. PATIENTS AND METHODS: We included 77 patients with primary outcomes of either death or survival. Demographics, clinical features, comorbidities, and laboratory tests were compared. Linear, logistic, and Cox regression analyses were performed to determine prognostic factors. RESULTS: The average age was 59 years (35-87 years). There were 12 moderate cases (16.2%), 42 severe cases (54.5%), and 23 critical cases (29.9%); and 41 were male (53.2%). Until March 20, 68 cases were discharged (88.3%), and nine critically ill males (11.7%) died. Interleukin-6 (IL-6) levels on the 1st day were compared with IL-6 values on the 14th day in the severe and the critically ill surviving patients (F=4.90, p=0.034, ß=0.35, 95% CI: 0.00-0.10), and predicted death in the critically ill patients (p=0.028, ß=0.05, OR: 1.05, 95% CI: 1.01-1.10). CD4+ T-cell counts at admission decreased the hazard ratio of death (p=0.039, ß=-0.01, hazard ratio=0.99, 95% CI: 0.98-1.00, and median survival time 13.5 days). CONCLUSIONS: The present study demonstrated that IL-6 levels and CD4+ T-cell count at admission played key roles of predictors in the prognosis, especially for critically ill patients. High levels of IL-6 and impaired CD4+t cells are seen in severe and critically ill patients with COVID-19.

HOCl Rapidly Kills Corona, Flu, and Herpes to Prevent Aerosol Spread.

The COVID-19 pandemic has escalated the risk of SARS-CoV-2 transmission in the dental practice, especially as droplet-aerosol particles are generated by high-speed instruments. This has heightened awareness of other orally transmitted viruses, including influenza and herpes simplex virus 1 (HSV1), which are capable of threatening life and impairing health. While current disinfection procedures commonly use surface wipe-downs to reduce viral transmission, they are not fully effective. Consequently, this provides the opportunity for a spectrum of emitted viruses to reside airborne for hours and upon surfaces for days. The objective of this study was to develop an experimental platform to identify a safe and effective virucide with the ability to rapidly destroy oral viruses transported within droplets and aerosols. Our test method employed mixing viruses and virucides in a fine-mist bottle atomizer to mimic the generation of oral droplet-aerosols. The results revealed that human betacoronavirus OC43 (related to SARS-CoV-2), human influenza virus (H1N1), and HSV1 from atomizer-produced droplet-aerosols were each fully destroyed by only 100 ppm of hypochlorous acid (HOCl) within 30 s, which was the shortest time point of exposure to the virucide. Importantly, 100 ppm HOCl introduced into the oral cavity is known to be safe for humans. In conclusion, this frontline approach establishes the potential of using 100 ppm HOCl in waterlines to continuously irrigate the oral cavity during dental procedures to expeditiously destroy harmful viruses transmitted within aerosols and droplets to protect practitioners, staff, and other patients.

Coronavirus murine hepatitis virus strain 3 induces intestinal injury via caspase 3 dependent apoptosis

Background: Diarrhea was typical symptoms of the coronavirus disease 2019 (COVID-19). However, the underlying mechanism had not been fully understood. Aim(s): The study aimed to explore the mechanism of intestinal injury during COVID-19 in a coronavirus murine hepatitis virus strain 3 (MHV-3) induced acute mouse model. Method(s): MHV-3 induced acute infection Balb/cJ mice model was established. Intestine samples were collected at indicated time points as 0 h, 24 h, 48 h and 60 h post infection. The mRNA and protein expression of IL1b, TNFalpha, IL6, caspase 3 and cleaved caspase 3 were examined by real-time quantitative PCR (qPCR) and western blot respectively. The intestine injury and apoptosis were measured by HE staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Moreover, Z-DEVD-FMK (caspase 3 inhibitor) pre-treated MHV-3 infection mice model were established, in which the apoptosis of intestine was evaluated as well. Meanwhile, the murine intestinal cell MODE-K was infected by MHV-3 in vitro for evaluation of virus induced apoptosis. Result(s): Post MHV-3 infection, the histopathology of intestine tissue showed extraordinary injury with time dependence, as well as high level of TUNEL positivity. The mRNA levels of inflammatory cytokine IL1b, TNFalpha and IL6 were significantly increased. The protein expressions of caspase 3 and cleaved caspase 3 in the intestine was found significantly elevated from 24 to 48 h post MHV-3 infection. Z-DEVD-FMK pretreatment inhibited caspase 3 and cleaved caspase 3 expression and decreased TUNEL positivity. Meanwhile, alleviated gut injury and inhibited TNFalpha expression were observed. In vitro treated by MHV-3, intestinal cell line MODE-K showed nine-fold increase of apoptosis by comparison with saline treated ones. The expressions of apoptosis crucial protein caspase3 and cleaved caspase3 significantly elevated, as well as TNFalpha. Conclusion(s): Coronavirus murine hepatitis virus strain 3 induces intestinal injury via caspase 3 dependent apoptosis, which might shed light on the treatment of intestinal complications in COVID-19.

Network Public Opinion Detection During the Coronavirus Pandemic: A Short-Text Relational Topic Model

Online social media provides rich and varied information reflecting the significant concerns of the public during the coronavirus pandemic. Analyzing what the public is concerned with from social media information can support policy-makers to maintain the stability of the social economy and life of the society. In this article, we focus on the detection of the network public opinions during the coronavirus pandemic. We propose a novel Relational Topic Model for Short texts (RTMS) to draw opinion topics from social media data. RTMS exploits the feature of texts in online social media and the opinion propagation patterns among individuals. Moreover, a dynamic version of RTMS (DRTMS) is proposed to capture the evolution of public opinions. Our experiment is conducted on a real-world dataset which includes 67,592 comments from 14,992 users. The results demonstrate that, compared with the benchmark methods, the proposed RTMS and DRTMS models can detect meaningful public opinions by leveraging the feature of social media data. It can also effectively capture the evolution of public concerns during different phases of the coronavirus pandemic. © 2021 Association for Computing Machinery.

The relationship between crude oil futures and exchange rates in the context of the Covid-19 shock: a tale of two markets

We examine the high-frequency intraday return and volatility transmission between crude oil futures prices and exchange rates during the 2020 Covid-19 pandemic in the context of two markets: the newly established renminbi-denominated Shanghai International Energy Exchange in China and the US-dollar-denominated Brent market in the United Kingdom. By controlling for the influence of the stock markets, our findings reveal significant disparities in return linkages, yet fairly comparable volatility transmission patterns. The International Energy Exchange shows no return linkages with exchange rates except before the shock, while Brent consistently shows return spillovers from crude oil futures prices to exchange rates. In both markets, the volatility spillovers from exchange rates to crude oil futures prices are unidirectional prior to the shock but become bidirectional as a result of the shock. Nevertheless, both the return and volatility spillover patterns in China resemble those in the United Kingdom when utilizing offshore instead of onshore exchange rates. Such similarities in return and volatility spillovers can also be observed during the 2022 Covid-19 shock that emerged in Shanghai. These findings have significant practical implications. © Infopro Digital Limited 2023.

Characteristics of Traditional Chinese Medicine Syndromes and Treatments of COVID-19 Patients from Two Hospitals Based on "Treatment of Disease in Accordance with Three Conditions".

Objective: To explore the guidance value of "treatment of disease in accordance with three conditions" theory in the prevention and treatment of corona virus disease 2019 (COVID-19) based on the differences of syndromes and traditional Chinese medicine (TCM) treatments in COVID-19 patients from Xingtai Hospital of Chinese Medicine of Hebei province and Ruili Hospital of Chinese Medicine and Dai Medicine of Yunnan province and discuss its significance in the prevention and treatment of the unexpected acute infectious diseases. Method(s): Demographics data and clinical characteristics of COVID-19 patients from the two hospitals were collected retrospectively and analyzed by SPSS 18.0. The information on formulas was obtained from the hospital information system (HIS) of the two hospitals and analyzed by the big data intelligent processing and knowledge service system of Guangdong Hospital of Chinese Medicine for frequency statistics and association rules analysis. Heat map-hierarchical clustering analysis was used to explore the correlation between clinical characteristics and formulas. Result(s): A total of 175 patients with COVID-19 were included in this study. The 70 patients in Xingtai, dominated by young and middle-aged males, had clinical symptoms of fever, abnormal sweating, and fatigue. The main pathogenesis is stagnant cold-dampness in the exterior and impaired yin by depressed heat, with manifest cold, dampness, and deficiency syndromes. The therapeutic methods highlight relieving exterior syndrome and resolving dampness, accompanied by draining depressed heat. The core Chinese medicines used are Poria, Armeniacae Semen Amarum, Gypsum Fibrosum, Citri Reticulatae Pericarpium, and Pogostemonis Herba. By contrast, the 105 patients in Ruili, dominated by young females, had atypical clinical symptoms, and most of them were asymptomatic patients or mild cases. The main pathogenesis is dampness obstructing the lung and the stomach, with obvious dampness and heat syndromes. The therapeutic methods are mainly invigorating the spleen, resolving dampness, and dispersing Qi with light drugs. The core Chinese medicines used are Poria, Atractylodis Macrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma, Coicis Semen, Platycodonis Radix, Lonicerae Japonicae Flos, and Pogostemonis Herba. Conclusion(s): The differences in clinical characteristics, TCM syndromes, and medication of COVID-19 patients from the two places may result from different regions, population characteristics, and the time point of the COVID-19 outbreak. The "treatment of disease in accordance with three conditions" theory can help to understand the internal correlation and guide the treatments.Copyright © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Multiplex Assays Enable Simultaneous Detection and Identification of SARS-CoV-2 Variants of Concern in Clinical and Wastewater Samples

The targeted screening and sequencing approaches for COVID-19 surveillance need to be adjusted to fit the evolving surveillance objectives which necessarily change over time. We present the development of variant screening assays that can be applied to new targets in a timely manner and enable multiplexing of targets for efficient implementation in the laboratory. By targeting the HV69/70 deletion for Alpha, K417N for Beta, K417T for Gamma, and HV69/70 deletion plus K417N for sub-variants BA.1, BA.3, BA.4, and BA.5 of Omicron, we achieved simultaneous detection and differentiation of Alpha, Beta, Gamma, and Omicron in a single assay. Targeting both T478K and P681R mutations enabled specific detection of the Delta variant. The multiplex assays used in combination, targeting K417N and T478K, specifically detected the Omicron sub-variant BA.2. The limits of detection for the five variants of concern were 4-16 copies of the viral RNA per reaction. Both assays achieved 100% clinical sensitivity and 100% specificity. Analyses of 377 clinical samples and 24 wastewater samples revealed the Delta variant in 100 clinical samples (nasopharyngeal and throat swab) collected in November 2021. Omicron BA.1 was detected in 79 nasopharyngeal swab samples collected in January 2022. Alpha, Beta, and Gamma variants were detected in 24 wastewater samples collected in May-June 2021 from two major cities of Alberta (Canada), and the results were consistent with the clinical cases of multiple variants reported in the community. © 2023 The Authors. Published by American Chemical Society.

REAL-WORLD EFFECTIVENESS OF mRNA, SUBUNIT, AND VECTOR-BASED VACCINES AGAINST COVID-19

Background: Limited Covid-19 vaccine effectiveness (VE) studies address the mRNA, adenoviral vector-based, and protein subunit vaccines and their mix and match in real-world settings. BNT162v2 (Pfizer-BioNTech), mRNA- 1273 (Moderna), AZD1222 (AstraZeneca), and locally produced MVC-COV1901 (Medigen) are provided under the National Vaccination Program. Taiwan maintained a low circulation of Covid-19 infection until a major epidemic Omicron BA.2, began in April 2022. The study aimed to estimate the VE against moderate and severe (severity) and fatal diseases (death) associated with SARS-CoV-2 among individuals administered one, two, and three doses of vaccination and categorized by vaccine type combinations in this predominantly infection-naive population. Method(s): The study included CDC's administrative records from National Immunization Information System and National Infectious Disease Reporting System from March 21, 2021, to September 30, 2022. Criteria for Covid-19 severity followed WHO's guidelines, and the committee reviewed the records. The study calculated each individual's last administered date to disease onset (incidence rate (IR) per 100,000 person-days) to explore the incidence rate to compare the presence of risk probabilities. Multiple logistic regression was used for vaccine effectiveness analysis. Result(s): Of 23,933,482 individuals included in the study, and 6,202,496 infections, 30,976 severity, and 10,851 deaths were observed. Compared with three doses administered, three doses of AZD1222 or it as primary series plus mRNA or protein-based vaccines were at higher risk of severity (IR: 0.390-0.762), followed by mRNA-1273 (IR: 0.316-0.471), MVC-COV1901 (IR: 0.044-0.196) and BNT162v2 (IR: 0.061-0.197). As for the death outcome, AZD1222 was at higher fatal risk (IR: 0.127-0.269), followed by mRNA-1273 (IR: 0.086-0.125), MVC-COV1901 (IR: 0.013-0.064) and BNT162v2 (IR: 0.015-0.045). VE against the severity of AZD1222 or it as primary series ranged from 65.9% to 77.7%;mRNA vaccines ranged from 86.4% to 96.1%;and protein-based vaccines ranged from 91.4% to 96.2%. A similar pattern of VE against death ranged from 60.9% to 73.7%, 88.2% to 96.2%, and 90.3% to 95.6%. Conclusion(s): Individuals who received their primary series as AZD1222 might not have adequate protection against Covid-19 severity so encourage those vulnerable groups to receive additional booster doses. The study also indicated that protein subunit vaccines provide similar protection against severity and death as mRNA vaccines. (Table Presented).

Predictors of COVID-19 vaccination hesitancy in China: a meta-analysis.

OBJECTIVES: This study aimed to examine predictors and moderators of COVID-19 vaccine hesitancy in Chinese cultural contexts. STUDY DESIGN: A meta-analysis and meta-regression analyses were conducted to examine the associations between predictors and vaccine hesitancy as well as moderators that may impact these associations. METHODS: We searched relevant articles from January 1, 2020, to May 12, 2022, in the databases of Web of Science, PubMed, ProQuest, ProQuest Dissertations & Theses Global and CNKI. Weighted average effect sizes (e.g., odds ratio) and 95% confidence intervals were computed in Comprehensive Meta-Analysis 3.0 using random-effects models. Heterogeneity tests were conducted prior to moderation analyses. RESULTS: Results from 161 studies in 73 published articles (N = 705,957) were meta-analyzed. Perceived risk of COVID-19 infection, health status, medical workers' recommendation, recommendations from family and friends, and vaccine coverage among relatives and friends were significantly associated with COVID-19 vaccine hesitancy in Chinese cultural contexts. Participant age, operationalization of vaccine hesitancy, and the time of each study exerted significant moderation effects. CONCLUSIONS: Both individual and relational factors influence vaccine hesitancy in Chinese cultural contexts Future vaccine promotion initiatives should focus on risk perceptions as well as influence from medical professionals, family and friends.

Functional Nanomaterials for Electrochemical SRAS-CoV-2 Biosensors: a Review

The pandemic outbreak of COVID-19 has posed a threat to public health globally, and rapid and accurate identification of the viruses is crucial for controlling COVID-19. In recent years, nanomaterial-based electrochemical sensing techniques hold immense potential for molecular diagnosis with high sensitivity and specificity. In this review, we briefly introduced the structural characteristics and routine detection methods of SARS-CoV-2, then summarized the associated properties and mechanisms of the electrochemical biosensing methods. On the above basis, the research progress of electrochemical biosensors based on gold nanomaterials, oxide nanomaterials, carbon-based nanomaterials and other nanomaterials for rapid and accurate detection of virus were reviewed. Finally, the future applications of nanomaterial-based biosensors for biomolecular diagnostics were pointed out.

Revenge buying after the lockdown: Based on the SOR framework and TPB model

With the end of the pandemic and the lifting of the lockdown, the consumer market experienced revenge buying. The purpose of this study is to investigate the causes of revenge buying using the stimulus-organ-response (SOR) framework and the theory of planned behavior (TPB) model. Structural equation modeling was used to analyze data collected from 350 residents of Shanghai, China, after the city's lockdown was lifted. The findings imply that perceived scarcity, perceived susceptibility, and social influence regarding the lockdown can stimulate in-dividuals' anxiety, inducing behavioral intentions and ultimately leading to revenge buying consumer behavior. Theoretically, this study provides a novel explanation of revenge buying behavior. Additionally, conclusions offer ramifications for management and implementation strategies for dealing with revenge buying after sudden disasters.

Speech Recognition Using Intelligent Piezoresistive Sensor Based on Polystyrene Sphere Microstructures

Rapid advances in wearable sensing technology have demonstrated unprecedented opportunities for artificial intelligence. In comparison with the traditional hand-held electrolarynx, a wearable and intelligent artificial throat with sound-sensing ability is a more comfortable and versatile method to assist disabled people with communication. Herein, a piezoresistive sensor with a novel configuration is demonstrated, which consists of polystyrene (PS) spheres as microstructures sandwiched between silver nanowires and reduced graphene oxide layers. In fact, changes in the device's conducting patterns are obtained by spay-coating the various weight ratios and sizes of the PS microspheres, which is a fast and convenient way to establish microstructures for improving sensitivity. The wearable artificial throat device also exhibits high sensitivity, fast response time, and ultralow intensity level detection. Moreover, the device's excellent mechanical-electrical performance allows it to detect subtle throat vibrations that can be converted into controllable sounds. In this case, an intelligent artificial throat is achieved by combining a deep learning algorithm with a highly flexible piezoresistive sensor to successfully recognize five different words (help, sick, patient, doctor, and COVID) with an accuracy exceeding 96%. Herein, new opportunities in voice control as well as other human-machine interface applications are opened.

Amélioration des critères combinés issus d'un domaine patient et de domaines de la maladie dans la dermatite atopique (DA) modérée à sévère et traités par upadacitinib

Introduction (contexte de la recherche) Un algorithme relatif à la stratégie treat-to-target a récemment été développé pour guider l'utilisation des thérapies systémiques en vue du contrôle de la maladie chez l'adulte atteint d'une DA. Cet algorithme a mis en avant des critères visant à définir un objectif cible initial acceptable à 3 mois ainsi qu'un objectif cible optimal à 6 mois. Objectif Les objectifs de cette analyse sont d'utiliser l'algorithme lié à la stratégie treat-to-target pour évaluer l'efficacité de l'upadacitinib (UPA), chez des patients adultes atteints d'une DA modérée à sévère, traités par UPA 15mg ou 30mg par voie orale en monothérapie 1 fois par jour ;à partir des données poolées des études de phase III, randomisées, contrôlées en double aveugle vs placebo : Measure Up 1 (MU1, NCT03569293) et Measure Up 2 (MU2, NCT03607422) ;ainsi que de déterminer la proportion de patients atteints d'une DA modérée à sévère ayant obtenu une amélioration≥1 des principaux domaines de la DA (signes, symptômes et qualité de vie) aux semaines 2 et 16 dans les études MU1 et MU2. Méthodes L'atteinte de ces critères sous UPA (15mg et 30mg) en monothérapie, 1 fois par jour a été comparée au placebo chez les patients adultes, en utilisant les données poolées des études MU1et MU2 et l'imputation des non-répondeurs en intégrant l'imputation multiple pour les valeurs manquantes liées à l'épidémie de COVID-19. Résultats Une proportion plus élevée de patients traités par UPA (15mg et 30mg) vs placebo (p<0,001 pour tous) a atteint l'objectif cible initial acceptable de 3 mois à la semaine 2 (78,9 %, 82,6 % vs 25,0 %) et la semaine 16 (72,5 %, 80,2 % vs 22,9 %) ;et l'objectif cible optimal de 6 mois à la semaine 2 (52,8 %, 64,3 % vs 6,3 %) et la semaine 16 (56,2 %, 70,1 % vs 13,9 %). Conclusions Ces résultats semblent indiquer qu'UPA (15mg et 30mg) administré par voie orale, 1 fois par jour pourrait améliorer la prise en charge conventionnelle des patients souffrant d'une DA modérée à sévère, en permettant d'atteindre l'objectif cible optimal à 6 mois (signes, symptômes et qualité de vie) dès 16 semaines et même dès 2 semaines chez la plupart des patients.

Outsourcing or reshoring? A manufacturer?s sourcing strategy in the presence of government subsidy

Multinational firms can outsource to contract manufacturers in low-labor-cost regions. However, in recent years, several developed countries and regions have subsidized their local manufacturers (LM[s], she) to encourage reshoring for external benefit (e.g., creating more domestic jobs or improving industrial struc-ture), especially after the COVID-19 pandemic started. This paper investigates the sourcing problem of an LM with brand premium in the presence of government subsidy and differences in labor costs. An LM faces three options: producing in-house, outsourcing to an original brand manufacturer (OBM, he), which sells competitive substitutes without brand premium, or outsourcing to a non-competing contract manu-facturer (NCM). We find that, first, the LM chooses reshoring if the external benefit or brand premium is sufficiently high. Second, if the LM decides to outsource, she chooses the OBM (NCM) if her brand pre-mium is high (low). Third, the government prefers to subsidize LM reshoring or outsourcing to an NCM. If the government intends to induce LM to reshore, the subsidy should be at a moderate level. Interestingly, when the LM has a low brand premium but chooses outsourcing, the government still subsidizes her to improve her competitiveness.(c) 2022 Elsevier B.V. All rights reserved.

The transformation of microclimate adaption in public spaces by smart ventilation approach: a case study of Eastern Banlieue memory industrial Park, China

With the normalization of the COVID-19 pandemic prevention and control, there is an urgent need to develop a healthy urban public space. However, because of the fast urbanization process with a series of problems, such as PM2.5 air pollution, the Urban Heat Island, and the relatively high frequency of static winds under the influence of its topography, the ventilation problem in the public spaces of Chengdu is of great importance. Along these lines, in this work, the history of theoretical research on urban ventilation is summarized and reviewed first to evaluate the urban wind environment. Second, so far, qualitative methods are mainly adopted for the evaluation methods of microclimate adaptation. However, the practical application has achieved few results. Meanwhile, there is still a lack of comprehensive and unified research on the multi-element of human microclimate comfort in public space. For this reason, the urban ventilation assessment system was established in this work according to the physical, physiological, and psychological aspects, with 9 indices selected and ranked. Then, an optimization strategy for rebuilding the urban public space was proposed for improving the wind environment microclimate adaption on three levels: macro city-regional level, meso block linear space, and micro space node. By taking Eastern Banlieue Memory Industrial Park as an example, the statistical data were systematically investigated on the spot from the results of 249 wind environment questionnaires, and 30 Delphi expert consultation questionnaires. Combined with the Computational Fluid Dynamics (CFD) simulation, the results reveal that most public spaces in the study area were below 0.6 m/s in more than 80% of the public space, and wind-based environmental problems obviously exist without any ventilation improvement measures. Combined with the background of the carbon peak era, the ventilation environment of the urban public space is not conducive to using active ventilation equipment. The solution of a complete set of regional intelligent ventilation systems was thoroughly discussed here, while some innovative sustainable systematic solutions and urban ventilation furniture combined with a geothermal heat pump and cloud data platform were formulated.