Inherited deficiency of the OAS-RNase L pathway in children with MIS-C

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic dsRNA-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the ssRNA-degrading RNase L. Consistent with the absence of pneumonia in these patients, epithelial cells and fibroblasts defective for this pathway restricted SARS-CoV-2 normally. This contrasted with IFNAR1-deficient cells from patients prone to hypoxemic pneumonia without MIS-C. Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNASEL deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or SARS-CoV- 2 stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-but not RNase L- deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by MAVS deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.Copyright © 2023 Elsevier Inc.

Performance of in-duct bipolar ionization devices on pollutant removal and potential byproduct formation in indoor environments

The COVID-19 pandemic has highlighted the importance of indoor air quality (IAQ) since SARS-CoV-2 may be transmitted through virus-laden aerosols in poorly ventilated spaces. Multiple air cleaning technologies have been developed to mitigate airborne transmission risk and improve IAQ. In-duct bipolar ionization technology is an air cleaning technology that can generate ions for inactivating airborne pathogens and increasing particle deposition and removal while without significant byproducts generated. Many commercial in-duct ionization systems have been developed but their practical performance on pollutant removal and potential formation of byproducts have not been investigated comprehensively. The results in this study showed that the in-duct bipolar ionization technology can significantly improve the particle removal efficiency of the regular filter, while no significant ozone and ion were released to the indoor air. © 2022 17th International Conference on Indoor Air Quality and Climate, INDOOR AIR 2022. All rights reserved.

Expert consensus on diagnosis and treatment of adult mental stress-induced hypertension in China (2022 Revision): Part B

Mental stress has been recognized as an essential risk factor for hypertension. Therefore, experts specializing in cardiology, psychiatry, and Traditional Chinese Medicine organized by the Psycho-cardiology Group, College of Cardiovascular Physicians of Chinese Medical Doctor Association, and Hypertension Group of the Chinese Society of Cardiology proposed the expert consensus on the diagnosis and treatment of adult mental stress-induced hypertension in March 2021, which includes the epidemiology, etiology, diagnosis, and treatment of the mental stress-induced hypertension. This consensus will hopefully facilitate the clinical practice of this disorder. In addition, the COVID-19 pandemic has become one of the primary global sources of psychosocial stressors since the beginning of 2020, and the revision of this expert consensus in 2022 has increased the relevant content. This consensus consists of two parts. The sections of Part A include (I) Background and epidemiological characteristics, (II) Pathogenesis, and (III) Diagnosis. The sections of Part B contain (IV) Treatment recommendations, and (V) Prospects. This article presents Part B of the consensus. © 2022 Heart and Mind ;Published by Wolters Kluwer - Medknow.

Expert consensus on diagnosis and treatment of adult mental stress induced hypertension in China (2022 revision): Part A

Mental stress has been recognized as an essential risk factor for hypertension. Therefore, experts specializing in cardiology, psychiatry, and Traditional Chinese Medicine organized by the Psycho-Cardiology Group of College of Cardiovascular Physicians of Chinese Medical Doctor Association and Hypertension Group of Chinese Society of Cardiology proposed the expert consensus on the diagnosis and treatment of adult mental stress-induced hypertension in March 2021, which includes the epidemiology, etiology, diagnosis, and treatment of the mental stress-induced hypertension. This consensus will hopefully facilitate the clinical practice of this disorder. In addition, the COVID-19 pandemic has become one of the primary global sources of psychosocial stressors since the beginning of 2020, and the revision of this expert consensus in 2022 has increased the relevant content. This consensus consists of Part A and Part B. Part A includes (I) Background and epidemiological characteristics, (II) Pathogenesis, and (III) Diagnosis and Part B includes (IV) Treatment recommendations and (V) Prospects. This part presents the content of Part A. © 2022 Heart and Mind ;Published by Wolters Kluwer - Medknow.

Nationwide evaluation of energy and indoor air quality predictive control and impact on infection risk for cooling season

Since the coronavirus disease 2019, the extended time indoors makes people more concerned about indoor air quality, while the increased ventilation in seeks of reducing infection probability has increased the energy usage from heating, ventilation, and air-conditioning systems. In this study, to represent the dynamics of indoor temperature and air quality, a coupled grey-box model is developed. The model is identified and validated using a data-driven approach and real-time measured data of a campus office. To manage building energy usage and indoor air quality, a model predictive control strategy is proposed and developed. The simulation study demonstrated 18.92% energy saving while maintaining good indoor air quality at the testing site. Two nationwide simulation studies assessed the overall energy saving potential and the impact on the infection probability of the proposed strategy in different climate zones. The results showed 20%–40% energy saving in general while maintaining a predetermined indoor air quality setpoint. Although the infection risk is increased due to the reduced ventilation rate, it is still less than the suggested threshold (2%) in general. © 2022, Tsinghua University Press.

Estimation of infection risk through airborne transmission in large open spaces with different air distributions

Respiratory diseases such as COVID-19 can be spread through airborne transmission, which is highly dependent on the airflow pattern of the studied room. Indoor air is typically not perfectly mixed even using a mixing ventilation, especially in large spaces. Airflow patterns in large open spaces such as hotel banquet rooms and open plan offices, are of particular concern, as these spaces usually accommodate more occupants and thus have the potential to spread diseases more rapidly leading to outbreaks. Therefore, understanding airflow patterns in large open spaces can help to estimate the detailed infection risk at certain locations in the space, which can prevent the spread of virus and track the potential new infections. This study estimated airflow patterns in a typical banquet room under theatre and banquet scenarios, and a large open plan office using computational fluid dynamics (CFD) simulations. Typical ventilation and air distribution approaches, as well as room layouts and occupant configurations in these scenarios were studied and applied in simulations. According to current results, the air distribution in a typical hotel banquet room with mixing ventilation can be very complicated, particularly for the banquet scenario. For a typical theatre scenario, under typical ventilation design, people sitting in the middle and lateral area were exposed to the highest infection risk. The front rows may be exposed to short-range transmission as well. For a banquet scenario, people sitting on the same table were more likely to be cross contaminated. But cross-table infection was still possible. The results can provide guidance on designing ventilation and air distribution approaches in large spaces with similar settings. © The Authors, published by EDP Sciences. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (http://creativecommons.org/licenses/by/4.0/)

Nationwide evaluation of energy and indoor air quality predictive control and impact on infection risk for cooling season

Since the coronavirus disease 2019, the extended time indoors makes people more concerned about indoor air quality, while the increased ventilation in seeks of reducing infection probability has increased the energy usage from heating, ventilation, and air-conditioning systems. In this study, to represent the dynamics of indoor temperature and air quality, a coupled grey-box model is developed. The model is identified and validated using a data-driven approach and real-time measured data of a campus office. To manage building energy usage and indoor air quality, a model predictive control strategy is proposed and developed. The simulation study demonstrated 18.92% energy saving while maintaining good indoor air quality at the testing site. Two nationwide simulation studies assessed the overall energy saving potential and the impact on the infection probability of the proposed strategy in different climate zones. The results showed 20%-40% energy saving in general while maintaining a predetermined indoor air quality setpoint. Although the infection risk is increased due to the reduced ventilation rate, it is still less than the suggested threshold (2%) in general.

Automotive Components Localization and De-globalization Purchasing Strategy

Due to impact for Coronavirus, Automotive industry faced challenges from global supply chain. Localization and De-globalization topic become more and more important. Automotive component purchasing strategy will be focused on localization. Target to keep whole supply chain safety and reduce additional risk and cost. © 2022 IEEE.

Updated results of a multicenter first-in-human study of BCMA/CD19 dual-targeting fast CAR-T GC012F for patients with relapsed/refractory multiple myeloma (RRMM)

Background: GC012F is a B cell maturation antigen (BCMA)/CD19 dual-targeting CAR-T developed on the novel FasT CAR-T platform with overnight manufacturing and designed to improve depth of response and efficacy. Data was presented at ASCO and EHA 2021 for initial 19 pts. We present updated data for study (NCT04236011;NCT04182581) with longer follow up and 9 additional pts treated (n = 28) in 3 different dose levels. Methods: From October 2019 to November 2021, 28 heavily pretreated RRMM pts (age 27-76) median of 5 prior lines (range 2-9) were treated on a single-arm, open label, multicenter Investigator Initiated Trial receiving a single infusion of GC012F. 89.3% (25/ 28) were high risk (HR- mSMART), 8 pts had EM disease, 3 had never achieved a CR including after transplant, 1 pts presented with plasma cell leukemia, 24/28 pts were refractory to last therapy, 3 pts primary refractory. 9/28 pts had received prior anti-CD38, 27/28 pts prior IMiDs. 26/28 pts were refractory to PI, 26/28 pts to IMiDs. After lymphodepletion over 2-3 days (30 mg/m2/d, 300mg/ m2/d Flu/Cy) GC012F was administered as single infusion at 3 dose levels: 1x105/kg (DL1) n = 2, 2x105/kg (DL2) n = 10 and 3x105/kg (DL3) n = 16. Results: As of Jan 26th 2022, 28 pts - median follow-up (f/ u) 6.3 mths (1.8-29.9) - had been evaluated for response. Overall response rate (ORR) in DL1 was 100% (2/2)- DL 2 -80% (8/10) DL 3 -93.8% (15/16) with 27 pts MRD negative by flow cytometry (sensitivity 10-4-10-6). 100% of MRD assessable pts (27/27) achieved MRD negativity. One patient out of 28 could not get assessed. At d28, 21/24 assessable patients were MRD negative (81.5%), 4/ 28 pts could not get d28 MRD assessment f/u due to COVID-19 restrictions however were assessed at a later timepoint. To date best response is MRD- sCR in 21/28 patients(75.0%) across all dose levels. Some pts after short f/u show responses that are still deepening. Cytokine Release Syndrome (CRS) was mostly low grade: gr 0 n = 3 (10.7%), gr 1-2 n = 23 (82.1%), gr 3 n = 2 (7.1%) - no gr 4/5 CRS and no ICANs were observed (Graded by ASBMT criteria). Median duration of CRS was 3 d (1-8 d). PK results showed no difference amongst dose levels DL1 to DL3. Overall, CAR-T median Tmax was 10 d (range 8-14 d), median peak copy number (Cmax) was 97009 (16,011-374,346) copies /μg DNA with long duration of persistence of up to d793 (data cut-off). CAR-T geometric mean AUC0-28 for DL1, DL2 and DL3 were 468863, 631540 and 581620 copies/μg DNA×day, respectively. Pts continue to be monitored for safety and efficacy including DOR. Conclusions: BCMA-CD19 dual FasT CAR-T GC012F continues to provide deep and durable responses with a favorable safety profile in additional RRMM pts across all dose levels demonstrating a very high MRD negativity rate including in pts refractory to anti-CD38, PI and IMIDs. GC012F is currently being studied in earlier lines of therapy as well as additional indications.

Hikikomori: A Society-Bound Syndrome of Severe Social Withdrawal

Background: Hikikomori, a severe and often prolonged social withdrawal observed primarily in young people, was first described in Japan, but cases have now been reported in many other countries. Methods: A review paper on hikikomori has been prepared following the literature searches in 3 databases. Search terms related to hikikomori included epidemiology, globalization, diagnosis, treatment, comorbidity, and COVID-19. Conclusions: Hikikomori was first reported in Japan and has been described in detail by researchers there, but there are now reports in many countries of hikikomori-like cases. It occurs primarily in young people, often men in their late teens and early twenties who isolate themselves, sometimes confining themselves to their homes for months or even years. It has been proposed that hikikomori has increased in recent years in part because of advances in information technology that result in decreased socialization. Hikikomori was originally considered a non-psychotic phenomenon, but comorbidity with psychiatric disorders is often present and should be considered during diagnosis. Considerable efforts have been made in recent years to establish reliable, widely applicable guidelines for the diagnosis and treatment of hikikomori. There is very little information with regard to neurobiology, although involvement of the immune system, oxidative stress, and the social brain network has been proposed. It is widely agreed that hikikomori must be treated in a multi-dimensional fashion, with family support very important. Lessons learned from these treatment approaches are relevant to the potential increased risk of social withdrawal arising from COVID-19 pandemic lockdowns.

Genomic and phylogenetic analysis of the ORF7b gene from a Chinese feline infectious peritonitis virus isolate

FCoV viruses exhibit great genetic diversity, leading to the presence of FIPV-causing variants. Current molecular evolution analysis and genetic variation studies of FCoV in China are predominately focused on gene encoding the spike protein or other structural proteins, while few studies have evaluated genetic variations in nonstructural FCoV genes, which can play an important role in disease pathogenesis. In this study, the gene encoding the open reading frame (ORF) 7b nonstructural FCoV protein of the Chinese Fujian strain FJLY20201 was amplified from the ascitic fluid of a Chinese domestic cat infected with FIPV and compared with ORF 7b from previously published FCoV strains. Multiple sequence alignment revealed that FJLY20201 exhibited high identity with other Chinese FCoV strains. Phylogenetic analyses indicated that the Chinese strains did not differentiate between type I and type II serotypes of FCoV based on S proteins. In addition, they formed clades and differed genetically from strains originating outside China. This study provides the molecular epidemiology data about the ORF 7b genes of FCoV strains in China. Our results show that the identity of ORF 7b genes was closer between the Chinese isolates, and suggest that variation in ORF 7b is more dependent on geographical origin.

Reduced Probability of 2020 June July Persistent Heavy Mei-yu Rainfall Event in the Middle to Lower Reaches of the Yangtze River Basin under Anthropogenic Forcing

Anthropogenic forcing has approximately halved the probability of 2020 June-July persistent heavy mei-yu rainfall event based on HadGEM3-GA6 simulations without considering the COVID-induced aerosol emission reduction.

Improving Generalizability in Limited-Angle CT Reconstruction with Sinogram Extrapolation

Computed tomography (CT) reconstruction from X-ray projections acquired within a limited angle range is challenging, especially when the angle range is extremely small. Both analytical and iterative models need more projections for effective modeling. Deep learning methods have gained prevalence due to their excellent reconstruction performances, but such success is mainly limited within the same dataset and does not generalize across datasets with different distributions. Hereby we propose ExtraPolationNetwork for limited-angle CT reconstruction via the introduction of a sinogram extrapolation module, which is theoretically justified. The module complements extra sinogram information and boots model generalizability. Extensive experimental results show that our reconstruction model achieves state-of-the-art performance on NIH-AAPM dataset, similar to existing approaches. More importantly, we show that using such a sinogram extrapolation module significantly improves the generalization capability of the model on unseen datasets (e.g., COVID-19 and LIDC datasets) when compared to existing approaches. © 2021, Springer Nature Switzerland AG.

Data-driven time series forecasting for social studies using spatio-temporal graph neural networks

Time series forecasting with additional spatial information has attracted a tremendous amount of attention in recent research, due to its importance in various real-world applications on social studies, such as conflict prediction and pandemic forecasting. Conventional machine learning methods either consider temporal dependencies only, or treat spatial and temporal relations as two separate autoregressive models, namely, space-time autoregressive models. Such methods suffer when it comes to long-term forecasting or predictions for large-scale areas, due to the high nonlinearity and complexity of spatio-temporal data. In this paper, we propose to address these challenges using spatio-temporal graph neural networks. Empirical results on Violence Early Warning System (ViEWS) dataset and U.S. Covid-19 dataset indicate that our method significantly improved performance over the baseline approaches. © 2021 ACM.

“We are all in this together:” police use of social media during the COVID-19 pandemic

Purpose: Previous studies consistently indicate that police agencies tend to use social media to assist in criminal investigations, to improve police-community relations and to broadcast both crime- and non-crime-related tips promotive of public safety. To date, little research has examined what content the police tended to post on their social media sites during the COVID-19 pandemic. Design/methodology/approach: By selecting the 14 most widely attended police agencies' Facebook accounts, the current study collects and analyzes a sample of 2,477 police Facebook postings between February 1 and May 31, 2020. By using a mix-method approach, the study addresses three research questions: 1) What kinds of messages did the police tend to post on their Facebook pages before and during this pandemic? 2) What types of COVID-related police Facebook postings were made? 3) How did the public react to COVID-19-related police Facebook postings? Findings: The findings suggest that the police have come to believe that social media can be used as an effective police−public communicative tool in stressful times. The findings also suggest that social media platforms have become a routinized tool of police−public communications which can, to some appreciable extent, substitute for the in-person contacts traditionally relied upon in community policing. Originality/value: This study of police use of social media explores the question of whether the use of these media can serve as an effective tool to connect the police with the public under circumstances where in-person contacts are greatly constrained. Some public policy implications emerging from the findings reported are discussed, along with implications for further research along these lines. © 2021, Emerald Publishing Limited.

Clinical Results of a Multicenter Study of the First-in-Human Dual BCMA and CD19 Targeted Novel Platform Fast CAR-T Cell Therapy for Patients with Relapsed/Refractory Multiple Myeloma

Introduction To further improve efficacy and duration of response of CAR-T therapy for Relapsed/Refractory Multiple Myeloma (R/R MM), we have designed a dual FasT CAR-T targeting both B cell maturation antigen (BCMA), a well-established MM target, and CD19, which is expressed on MM cells and their progenitors. Here we report early results from the first-in-human multicenter clinical study (NCT04236011;NCT04182581) to determine safety, pharmacokinetics (PK) and efficacy of BCMA-CD19-directed FasT CAR-T (GC012F) in patients with R/R MM. Methods The BCMA-CD19 dual CAR was constructed by linking BCMA and CD19 scFv, joined by a CD8 hinge, transmembrane domain, co-stimulatory domain and CD3z. Peripheral blood (PB) mononuclear cells were obtained by leukapheresis, T cells were isolated and CAR-T cells were manufactured (FasT CAR platform). From September 2019 to April 2020, we enrolled 16 heavily pretreated R/R MM patients (Age range 27-71), with a median of 5 prior lines of therapies (range 2-7), 93.8% (15/16) of these patients were high risk as defined by mSMART criteria, 5 had extramedullary disease. 4 out of 16 patients had received prior anti CD38 therapy, 93.8% (15/16) patients had received prior IMiD, all patients received at least 1 prior PI and corticosteroids with 3 patients being primary refractory to last therapy. Prior to CAR-T infusion patients received a conditioning regimen over 3 days of 30 mg/m2/d fludarabine and 300 mg/m2/d cyclophosphamide. CAR-T cells were administered in a single infusion at 3 dose levels 1x105/Kg (DL1) (1 patients), 2x105/Kg (DL2) (9 patients) and 3x105/Kg (DL3) (6 patients). Results As of July 17th 2020, all 16 patients were evaluable for response assessment, 15 out of 16 patients responded to treatment (ORR 93.8%) in all dose levels with the earliest response observed at day 28. Best response to date is MRD- CR/sCR in 9/16 patients (56.3%). In DL3 100% (6/6) of patients achieved sCR, 3 at data cut off had been confirmed by PET-CT. In all response evaluable patients, 78.6% (11/14) were MRD- by flow at month 1, and 100% at month 3 (11/11) and 6 (10/10) (sensitivity by flow cytometry measured at 10-4 in 7 patients, and at 10-6 in 9 patients tested by EuroFlow with at least 1.08x107 cells analyzed). At data cut off, the median follow up time was 7.3 months, the longest follow up was 10 months post infusion. CAR-T PK in PB was monitored by qPCR and flow cytometry. The CAR-T median proliferation peak was reached on Day10 (Day8-Day14), and the median peak copy number was 140,982 (16,011-374,346) copies /ug DNA. GC012F showed an acceptable safety profile with 14 out of 16 patients experiencing a cytokine release syndrome (CRS) grade 1-2 (n=14, 87.5%) and 2 grade 3 (n=2, 12.5%). The median duration of CRS was 4 days (1-8 days). No neurotoxicity of any grade was observed. One patient (DL2) presented with fever and died shortly after Day 78 of unknown cause during the COVID-19 Pandemic. Two patients had progression of extramedullary disease while achieving MRD negativity at month 1 and 3, respectively. At landmark analysis at 6 months, all patients in DL3 had achieved and maintained MRD- sCR including patients heavily pretreated including Daratumumab - among them 83.3% (5/6) patients in DL3 had high risk features according to mSMART criteria, and 5 out of 6 patients in DL3 were assessed by 10-6 Euroflow for MRD. The study is still enrolling patients and we will continue to be monitoring safety and efficacy including duration of response. Conclusion The data of BCMA-CD19 dual FasT CAR-T showed an early and high response rate with 93.8% ORR to date with a promising early high MRD-sCR rate in the highest dose level DL3 (100%) which was sustained with a median duration of follow up of 7.3 months at cut off. The data shows very promising activity of the BCMA-CD19 dual FasT CAR-T with a favorable safety profile in R/R MM patients. 93.8% (15/16) of the treated patients exhibited high risk features - a specifically difficult to treat patient population which remains a high unmet medical need in Mul iple Myeloma. This data indicates that BCMA-CD19 dual FasT CAR-T (GC012F) may present an effective new treatment option for patients with R/R MM including those with high-risk features who failed multiple prior therapies including anti-CD38. The study is still ongoing and enrolling patients, we will update the results as they become available. Disclosures: Zhao: Gracell Biotechnologies Ltd: Current Employment. Han: Gracell Biotechnologies Co., Ltd.: Current Employment. Chen: Gracell Biotechnologies Ltd: Current Employment. Xu: Gracell Biotechnologies Ltd: Current Employment. Zhang: Gracell Biotechnologies Ltd: Current Employment. He: Gracell Biotechnologies Co., Ltd.: Current Employment. Shi: Gracell Biotechnologies Ltd: Current Employment. Han: Gracell Biotechnologies Co., Ltd.: Current Employment. Ye: Gracell Biotechnologies Co., Ltd.: Current Employment. Wang: Gracell Biotechnologies Ltd: Current Employment. Liu: Gracell Biotechnologies Co., Ltd.: Current Employment. Shen: Gracell Biotechnologies Ltd: Current Employment. Cao: Gracell Biotechnologies Ltd: Current Employment. Sersch: Gracell Biotechnologies Co., Ltd.: Current Employment.

Expert recommendation on medical nutrition support of Coronavirus Disease 2019 in elderly patients

Coronavirus Disease 2019(COVID-19) is a class B infectious disease, with a high proportion of elderly patients, and the prognosis of elderly patients is poor. Most of the elderly patients have the characteristics of coexistence of multiple chronic diseases, poor organ reserve capacity, and low immunity. Once they are infected, the nutritional problems are more serious, and multiple organ dysfunction is more likely to be induced. Medical nutrition support is the basic treatment for the elderly patients with COVID-19. According to the nutritional status, organ function, metabolic capacity and underlying diseases, individualized nutritional treatment plan should be designed for precise treatment so as to improve the cure rate and reduce mortality. Nutritional treatment is one of the comprehensive treatment methods for COVID-19, which is quite important in elderly patients and should be paid enough attention. © 2020 Chinese Medical Association

Erratum to: Screening for and Managing the Person with Frailty in Primary Care: ICFSR Consensus Guidelines (The journal of nutrition, health & aging, (2020), 10.1007/s12603-020-1492-3)

The authors apologize for a typing error that occurred in the September 2020 article that changes the meaning of a sentence. Correction: Page 921, right column, 2nd paragraph, line 8, change «match» to «watch» so it reads, «Primary care providers should watch for frailty development due to physical inactivity during the COVID-19 pandemic (47).» In addition, the author listed as “C. Won Won” wishes to be known as “C.W. Won.” © 2020, The Journal of Nutrition, Health & Aging.