Active rehabilitation of coronary artery disease: today and tomorrow.

In 2020, the European Association of Preventive Cardiology proposed the important role of exercise-based cardiac rehabilitation (CR) in the management of cardiovascular and metabolic diseases, and called on everyone to take action. This paper discusses the current status and future perspective of individualized active exercise-based CR for coronary artery disease (CAD) from 4 dimensions, including the basic and clinical research progress of exercise-based CR for CAD, evidence on the benefits of exercise-based CR on ameliorating CAD complications, the exercise-based CR guidelines in different countries, and the implementation of exercise-based CR under coronavirus disease 2019 pandemic, so as to provide reference for research and clinical work.Copyright © 2022, Second Military Medical University Press. All rights reserved.

Decreasing case fatality rates for patients with cirrhosis infected with SARS-CoV-2: a national COVID cohort collaborative (N3C) study

Background: The virulence and severity of SARS-CoV-2 infections have decreased over time in the general population due to vaccinations and improved antiviral treatments. Whether a similar trend has occurred in patients with cirrhosis is unclear. We used the National COVID Cohort Collaborative (N3C) to describe the outcomes over time in this patient population. Method(s): We utilized the N3C data set with uncensored dates of service to identify all chronic liver disease (CLD) patients with and without cirrhosis who had SARS-CoV-2 infection as of 9/10/2022. We described the observed 30-day case fatality rate by month of infection. We used adjusted Cox survival analyses to calculate relative hazard of death by month of infection compared to infection in March 2020 at the onset of the COVID-19 pandemic. Result(s): We identified 110,477 total CLD patients infected with SARS-CoV-2 between 3/2020-7/2022: 25,067 (23%) with cirrhosis and 85,410 (77%) without cirrhosis. Of the 110,477 total CLD patients, 39,595 (36%) were vaccinated and 70,882 (64%) unvaccinated. The overall observed 30-day case fatality rate during the entire study period was 1.4% (1,198) for CLD patients without cirrhosis and 7.7% (1,930) for those with cirrhosis. The observed 30-day case fatality rate by month of infection is displayed in Fig. 1. Compared to infection in March 2020, the adjusted hazard of death at 30 days for infection in July 2022 was HR 0.083 (95% CI 0.026-0.27) for CLD patients without cirrhosis and HR 0.32 (95% CI 0.17-0.61) for those with cirrhosis. Conclusion(s): In this N3C study, we found that the observed 30-day case fatality rate decreased progressively for both CLD patients with and without cirrhosis. Yet, the decrease in all-cause mortality was four times greater for patients without cirrhosis compared to those with cirrhosis. Despite improvements in SARS-CoV-2 treatments, patients with cirrhosis remain at risk of adverse outcomes. (Figure Presented).

Active rehabilitation of coronary artery disease: today and tomorrow

In 2020, the European Association of Preventive Cardiology proposed the important role of exercise-based cardiac rehabilitation (CR) in the management of cardiovascular and metabolic diseases, and called on everyone to take action. This paper discusses the current status and future perspective of individualized active exercise-based CR for coronary artery disease (CAD) from 4 dimensions, including the basic and clinical research progress of exercise-based CR for CAD, evidence on the benefits of exercise-based CR on ameliorating CAD complications, the exercise-based CR guidelines in different countries, and the implementation of exercise-based CR under coronavirus disease 2019 pandemic, so as to provide reference for research and clinical work.Copyright © 2022, Second Military Medical University Press. All rights reserved.

Parents' willingness to vaccinate their children aged 3-11 years with the COVID-19 booster vaccine in Nanjing

Objective To investigate parents' acceptance to the COVID-19 vaccine booster shots for their children aged 3-11 years in Nanjing based on the theory of planned behavior and to provide a scientific theoretical basis for carrying out COVID-19 booster vaccination among children of this age group. Methods A total of 1 286 parents of children aged 3-11 years in Nanjing were selected by multistage stratified cluster sampling. A questionnaire survey based on the theory of planned behavior was used to investigate their willingness to vaccinate their children with the COVID-19 booster dose and structural equation model was used to conduct data analysis. Results About 90.2% of parents were willing to give their children a booster dose of the COVID-19 vac￣cine. The model constructed based on the theory of planned behavior could explain 42.2% of the variance of vaccination acceptance. Attitudes and perceived behavioral control had a direct positive effect on parents' acceptance to booster dose of the COVID-19 vac￣cine path coefficients were 0.47 and 0.18 P<0.01 The direct effect of subjective norms on vaccination acceptance was not sta￣tistically significant Perceived behavioral control and subjective norms could have indirect positive effects on vaccination accept￣ance through attitudes path coefficients were 0.27 and 0.13 P<0.01 . Conclusion Parents in Nanjing have a higher acceptance to vaccinate their children aged 3-11 years with the COVID-19 vaccine booster dose. The theory of planned behavior shows a good explanatory ability on parents' acceptance to vaccinate their children and attitude plays an important role in the formation of vacci￣nation acceptance. © 2022 Chinese Journal of School Health. All right reserved.

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.

Single stock trading with deep reinforcement learning: A comparative study

In this paper, we apply Deep Reinforcement Learning (DRL) methods to automate the trading of single stock. The A2C, PPO, DDPG, TD3 and SAC deep reinforcement learning models are built and studied comparatively. Shanghai Composite Index (SH00001) is used as the trading stock, where the stock data before the Covid-19 is used as the training set, and the data after the Covid-19 is used as the testing (trading) set to back-test the performance of these models. Experimental results show that the DDPG, TD3, and SAC models outperform the benchmark, among which the DDPG model shows the most obvious advantages in returns and risk control, achieving a cumulative return rate of 25%, while the TD3 and SAC models achieve a cumulative return rate of 16-17%. The A2C and PPO models have inferior performance comparing to the benchmark. © 2022 ACM.

Positive Pressure Testing Booths Development and Deployment in Response to the COVID-19 Outbreak

The COVID-19 pandemic left an unprecedented impact on the general public health, resulting in hundreds of thousands of deaths in the U.S. alone. Nationwide testing plans were initiated with drive-through being the currently dominant testing approach, which, however, exhausts personal protective equipment supplies, and is unfriendly to individuals not owning a vehicle. Walkup positive pressure testing booths are a safe alternative, whereby a health care provider situated on the inside of an enclosed and positively pressurized booth swabs a patient on the outside through chemical resistant gloves. The booths, however, are too prohibitively priced on the market to allow for nationwide deployment. To mitigate this, we present in this paper a safe, accessible, mobile, and affordable design of positive-pressure COVID-19 testing booths. The booths have successfully passed the Centers for Disease Control and Prevention and Health care Infection Control Practices Advisory Committee pressure, air exchange, and air quality requirements for positive-pressure rooms, following the guidelines for environmental infection control in health care facilities. The booths are manufactured using primarily off-the-shelf components from U.S. vendors with minimized customization, and the final bill of materials does not surpass USD 3,900. Since August 2019, five booths were deployed and used at the Johns Hopkins University School of Nursing, Baltimore City Health Department, and two community health centers in Baltimore. No health care provider was infected when using our booths, which have shown to facilitate walkup testing with decreased personal protective equipment consumption, reduced risk of infection, and enhanced accessibility to lower-income communities and nondrivers. Copyright © 2022 by ASME.

Using Lidar and Historical Similar Meteorological Fields to Evaluate the Impact of Anthropogenic Control on Dust Weather During COVID-19

Asian dust can be transported at least one full circuit around the globe. During the transportation, dust can interact with local air-borne dust and pollutants, and has a profound impact on the environment. A novel coronavirus (COVID-19) has been affecting human activities worldwide since early 2020. The Chinese government has implemented emergency control measures. Since April 2020, control measures to reduce anthropogenic emissions have been gradually reduced. The optical properties of aerosols during the dust transport were affected by meteorological conditions, local environmental conditions and human activities. Therefore, two dust weather processes in March 2018 and March 2020 were screened under similar meteorological fields and transportation paths, which were mainly affected by human activities. Based on lidar data, in East China, compared with 2018, the average aerosol optical depth (AOD) of all types of aerosols at 0-4 km in 2020 decreased by 55.48%, while the AOD of dust aerosols decreased by 43.59%. The average particle depolarization ratio and color ratio decreased by 40.33 and 10.56% respectively. Due to the reduction of anthropogenic emissions in China (detected by lidar), the concentration of surface PM2.5 decreased by 57.47%. This indicated that due to the decrease in human activities caused by COVID-19 control measures, the optical properties of aerosols were significantly reduced during dust weather process in eastern China. However, in the Pacific region, compared with 2018, the AOD values of 0-1 km layer and 1-6 km layer in 2020 increased by 56.4% and decreased by 29.2% respectively. The difference between the two contributions of dust aerosols was very small. Meanwhile, compared with 2018, China's near surface pollutants decreased significantly in 2020, indicating that the near surface AOD of the Pacific in 2020 was mainly contributed by local pollutants. This study was of great significance to the study of long-range and cross regional transport of pollutants.

Simulation analysis of epidemic trend for Covid-19 based on SEIRS model

The current novel coronavirus disease 2019 (COVID-19) outbreak in global has provided an opportunity to understand the spread of this pandemic linked to healthcare settings. It is very important to predict the trend of epidemic situation for timely response. In this paper, we proposed a Susceptible-Exposed-Infectious-Recovered-Susceptible (SEIRS) model to simulate and forecast the trend of COVID-19 epidemic in China. The simulation results provide a good fit to the actual number and peak time of confirmed epidemic in Hubei province, and the simulation results also show that the epidemic of Hubei province would decline in early June. However, there are some differences between the simulation results and the real situation of other regions in China, because this model does not consider human intervention strategy. In a word, our SEIRS dynamic model is effective in simulating and predicting the COVID-19 epidemic in Hubei province, China, it has meaningful reference for the prevention and control of the pandemic situation which is raging all over the world. ©2020 IEEE

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.