Prophylactic Corticosteroid Use with Axicabtagene Ciloleucel (Axi-Cel) in Patients (Pts) with Relapsed/ Refractory Large B-Cell Lymphoma (R/R LBCL): 2-Year Follow-up of Zuma-1 Cohort 6

Background: The ZUMA-1 safety management Cohort 6 (N=40), which evaluated whether prophylactic corticosteroids and earlier corticosteroids and/or tocilizumab could improve safety outcomes, demonstrated an improved safety profile (no Grade >=3 cytokine release syndrome [CRS];15% Grade >=3 neurologic events [NEs]) vs pivotal Cohorts 1+2, without compromising response rate or durability (95% ORR, 80% CR rate, and 53% ongoing response rate with >=1 y of follow-up;Oluwole, et al. ASH 2021. 2832). Here, 2-y updated outcomes are reported. Method(s): Eligible pts with R/R LBCL underwent leukapheresis (followed by optional bridging therapy) and conditioning chemotherapy, then a single axi-cel infusion. Pts received corticosteroid prophylaxis (once-daily oral dexamethasone 10 mg on Days 0 [before axi-cel], 1, and 2) and earlier corticosteroids and/or tocilizumab for CRS and NE management vs Cohorts 1+2 (Oluwole, et al. Br J Haematol. 2021). The primary endpoints were incidence and severity of CRS and NEs. Secondary endpoints included ORR (investigator-assessed), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and chimeric antigen receptor (CAR) T-cell levels in blood. Result(s): As of December 16, 2021, the median follow-up time for the 40 treated pts was 26.9 mo. Since the 1-y analysis, no new CRS events were reported (no pts had Grade >=3 CRS to date). The incidence of Grade >=3 NEs increased from 15% to 18%between the 1-y and 2-y analyses. Two new NEs occurred in 2 pts: 1 pt had Grade 2 dementia (onset on Day 685 and ongoing at time of data cutoff;not related to axi-cel) and 1 had Grade 5 axi-cel-related leukoencephalopathy. Since the 1-y analysis, 6 new infections were reported (Grades 1, 2, and 5 COVID-19 [n=1 each], Grade 3 Pneumocystis jirovecii pneumonia [n=1], Grade 3 unknown infectious episode with inflammatory syndrome [n=1], and Grade 2 herpes zoster [n=1]). In total, 8 deaths occurred since the 1-y analysis (progressive disease [n=5], leukoencephalopathy [n=1], and COVID-19 [n=2]). The ORR was 95% (80% CR), which was unchanged from the 1-y analysis. Median DOR and PFS were since reached (25.9 mo [95% CI, 7.8-not estimable] and 26.8 mo [95% CI, 8.7-not estimable], respectively). Median OS was still not reached. Kaplan- Meier estimates of the 2-y DOR, PFS, and OS rates were 53%, 53%, and 62%, respectively. Of 18 pts (45%) in ongoing response at data cutoff, all achieved CR as the best response. By Month 24, 14/20 pts with evaluable samples (70%) had detectable CAR T cells (vs 23/36 pts [64%] in Cohorts 1+2). Conclusion(s): With 2 y of follow-up, the ZUMA-1 Cohort 6 toxicity management strategy continued to demonstrate an improved long-term safety profile of axi-cel in pts with R/R LBCL. Further, responses remained high, durable, and similar to those observed in Cohorts 1+2 (Locke, et al. Lancet Oncol. 2019).Copyright © 2023 American Society for Transplantation and Cellular Therapy

A Bayesian two-stage group sequential scheme for ordinal endpoints

Ordinal endpoints are common in clinical studies. For example, many clinical trials for evaluating COVID-19 infection therapies have adopted an ordinal scale as recommended by the World Health Organization. Despite their importance in clinical studies, design methods for ordinal endpoints are limited;in practice, a dichotomized approach is often used for simplicity. Here, we introduce a Bayesian group sequential scheme to assess ordinal endpoints, which considers a proportional-odds (PO) model, a nonproportional-odds (NPO) model, and a PO/NPO-switch model to handle various scenarios. Extensive simulations are conducted to demonstrate desirable performance, and the R package BayesOrdDesign has been made publicly available.

The reliability and integrity of overall survival data based on follow-up records only and potential solutions to the challenges

Overall survival (OS) is considered the standard clinical endpoint to support effectiveness claims in new drug applications globally, particularly for lethal conditions such as cancer. However, the source and reliability of OS in the setting of clinical trials have seldom been doubted and discussed. This study first raised the common issue that data integrity and reliability are doubtful when we collect OS information or other time-to-event endpoints based solely on simple follow-up records by investigators without supporting material, especially since the 2019 COVID-19 pandemic. Then, two rounds of discussions with 30 Chinese experts were held and 12 potential source scenarios of three methods for obtaining the time of death of participants, including death certificate, death record and follow-up record, were sorted out and analysed. With a comprehensive assessment of the 12 scenarios by legitimacy, data reliability, data acquisition efficiency, difficulty of data acquisition, and coverage of participants, both short-term and long-term recommended sources, overall strategies and detailed measures for improving the integrity and reliability of death date are presented. In the short term, we suggest integrated sources such as public security systems made available to drug inspection centres appropriately as soon as possible to strengthen supervision. Death certificates provided by participants' family members and detailed standard follow-up records are recommended to investigators as the two channels of mutual compensation, and the acquisition of supporting materials is encouraged as long as it is not prohibited legally. Moreover, we expect that the sharing of electronic medical records and the legal disclosure of death records in established health registries can be realized with the joint efforts of the whole industry in the long-term. The above proposed solutions are mainly based on the context of China and can also provide reference for other countries in the world. © 2022 The Authors

Assessing the asymptomatic proportion of SARS-CoV-2 infection with age in China before mass vaccination

Some asymptomatic individuals carrying SARS-CoV-2 can transmit the virus and contribute to outbreaks of COVID-19. Here, we use detailed surveillance data gathered during COVID-19 resurgences in six cities of China at the beginning of 2021 to investigate the relationship between asymptomatic proportion and age. Epidemiological data obtained before mass vaccination provide valuable insights into the nature of pathogenicity of SARS-CoV-2. The data were collected by multiple rounds of city-wide PCR testing with contact tracing, where each patient was monitored for symptoms through the whole course of infection. The clinical endpoint (asymptomatic or symptomatic) for each patient was recorded (the pre-symptomatic patients were classified as symptomatic). We find that the proportion of infections that are asymptomatic declines with age (coefficient = -0.006, 95% CI: -0.008 to -0.003, p < 0.01), falling from 42% (95% CI: 6-78%) in age group 0-9 years to 11% (95% CI: 0-25%) in age group greater than 60 years. Using an age-stratified compartment model, we show that this age-dependent asymptomatic pattern, together with the distribution of cases by age, can explain most of the reported variation in asymptomatic proportions among cities. Our analysis suggests that SARS-CoV-2 surveillance strategies should take account of the variation in asymptomatic proportion with age.

SEIQRW Model for COVID-19 and Optimal Control Based on Data-Driven

Combining the transmission characteristics of the SARS-CoV-2, an SEIQRW COVID-19 transmission dynamics model is proposed that considers "susceptible, exposed, infected, quarantined, recovered and environmental virus". The basic reproduction number R0 was calculated according to the next-generation matrix method, the stability of the equilibrium point was analyzed by applying the Hurwitz criterion and matrix theory, and the optimal control strategy was found by using the Pontryagin maximum principle. Numerical simulations verify the theoretical results, sensitivity analysis determines the importance of parameters to R0, and fitting verify that the model with environmental virus is more consistent with the actual data than the model without environmental virus. Optimal control shows that control measures can effectively reduce the spread of the novel coronavirus to humans through the environment. © 2022, Editorial Department of Journal of North University of China (Natural Science Edition). All right reserved.

Explosive Cyber Security Threats During COVID-19 Pandemic and a Novel Tree-Based Broad Learning System to Overcome

The rapid spread of the COVID-19 has not only affected personal health and economy, but also revolutionized people's lifestyles. As more people turn to work and socialize online, the development of unmanned technologies based on the Internet of Vehicles (IoV), such as unmanned delivery, unmanned vehicles, unmanned transportation, etc., will become an inevitable trend. However, all kinds of intelligent terminals for unmanned equipment require a large amount of data interaction with devices such as cloud servers, mobile terminals, and roadside terminals, which poses cyber security risks. Furthermore, the outbreak of COVID-19 has prompted people to put forward higher demands for the security of network communications. Unfortunately, the current intrusion detection methods based on machine learning still have weaknesses such as low accuracy and low efficiency when faced with unbalanced data distribution. To solve the above problems, we propose a novel Tree-based BLS (TBLS) intrusion detection method according to the idea of ensemble learning and decision tree (CART and J48). The performance of TBLS was tested on the NSL-KDD dataset and the UNSW-NB15 dataset respectively, which contain a variety of malicious traffic types for attacks on the IoV. The results show that our proposed method can achieve higher accuracy rate and lower false alarm rate, compared with the existing 16 solutions. IEEE

Safe distance mathematical calculation and quantitative analysis on Covid-19 using einstein equation and gaussian distribution

Most of the diseases caused by virus mainly spread through droplets in the air. The pathogen bearing droplets go deep into people's lungs and cause infection. In this paper, we analyze the safe distance, the minimum range to keep droplets containing virus particles from entering lungs, and thereby carrying the virus inside the lung. Einstein equation for diffusivity of a particle and the wide of the Gaussian distribution of the particles in Brownian movement are used in the calculation of the range a viruscontaining mucosal vary droplet can reach. Moreover, we used datas recorded in a previous paper named "Visualization of sneeze ejecta: steps of fluid fragmentation leading to respiratory droplets" by B. E. Scharfman et. all to generate our results. © 2021 Institute of Physics Publishing. All rights reserved.

Observation of Unconventional Charge Density Wave without Acoustic Phonon Anomaly in Kagome Superconductors AV(3)Sb(5) (A = Rb, Cs)

The combination of nontrivial band topology and symmetry-breaking phases gives rise to novel quantum states and phenomena such as topological superconductivity, quantum anomalous Hall effect, and axion electrodynamics. Evidence of intertwined charge density wave (CDW) and superconducting order parameters has recently been observed in a novel kagome material AV(3)Sb(5) (A = K, Rb, Cs) that features a Z(2) topological invariant in the electronic structure. However, the origin of the CDW and its intricate interplay with the topological state has yet to be determined. Here, using hard-x-ray scattering, we demonstrate a three-dimensional CDW with 2 x 2 x 2 superstructure in (Rb, Cs)V3Sb5. Unexpectedly, we find that the CDW fails to induce acoustic phonon anomalies at the CDW wave vector but yields a novel Raman mode that quickly damps into a broad continuum below the CDW transition temperature. Our observations exclude strong electron-phonon-coupling-driven CDW in AV(3)Sb(5) and support an unconventional CDW that was proposed in the kagome lattice at van Hove filling.

Research on the path of university curriculum resources construction under the background of education informationization

Information technology is an important force to promote economic and social change. Information technology is not only used in human production and life, but also gradually infiltrated into higher education and teaching. Under novel coronavirus pneumonia, the path of university curriculum resources construction is discussed in this paper. The construction of a more rational and abundant information curriculum resource is achieved through the classification and integration of university education curriculum resources, which fully meets the needs of College Teaching in the special period. © 2021 ACM.

Design and production of environmentally degradable quaternary ammonium salts

Quaternary ammonium compounds (QACs) are a class of cationic surfactants routinely used for the disinfection of industries, institutions and households, and have seen a sharp increase in use during the COVID-19 pandemic. However, current commercial QACs consist of only stable chemical bonds such as C-N, C-C, and C-H, which makes their natural degradation rather difficult. Recent studies suggest that emerging negative environmental impacts, such as systemic antibiotics resistance and toxicity to living organisms, are directly associated with prolonged exposure to QACs. Here we report a new class of QAC which contains relatively volatile chemical functional groups such as ester and thioether bonds. Degradation kinetics in aqueous solutions suggests that the stability of these QACs depends not only on their intrinsic hydrophobicity but also on external environmental factors such as pH, temperature and ion presence. The microbicidal effects of QACs containing carbon chains with various lengths were also tested, one of which, named "Ephemora", is highly active against a broad spectrum of microbes including fungi, bacteria and viruses, for instance, methicillin-resistant Staphylococcus aureus (MRSA). The easy synthesis and purification of Ephemora starting from inexpensive commercially available reagents, together with its excellent antimicrobial activity and ability to degrade in natural waters over time, make its large-scale commercial production possible.

Predictors of mechanical ventilation for COVID-19: combined data from three designated hospitals.

OBJECTIVE: Whether patients with COVID-19 require invasive mechanical ventilation (MV) is not yet clear. This article summarizes the clinical treatment process and clinical data of patients with COVID-19 and analyzes the predictive factors for mechanical ventilation for these patients. MATERIALS AND METHODS: A retrospective study was carried out from January 5, 2020, to March 23, 2020, including 98 patients with COVID-19 treated at three designated hospitals in Huangshi City, Hubei Province. Data collection included demographics, previous underlying diseases, clinical manifestations, laboratory examinations, imaging examination results, diagnosis, and prognosis. This study presents a summary of the patients' overall clinical characteristics and clarifies the predictive factors for MV in patients with COVID-19. RESULTS: There were 56 males and 42 females included in this study. The mortality rate was 26.53% (26/98). Fever, cough, and chest tightness were the most common symptoms (64.3%, 37.8%, and 12.2%, respectively). Thirty cases required MV, 30.61% of the total cases, and the mortality rate was 73.33%. The univariate comparison showed that dyspnea, acute physiologic assessment, chronic health evaluation (APACHE II) score, and the ratio between arterial blood oxygen partial pressure (PaO2) and oxygen concentration (FiO2) (P/F) were statistically different between the MV group and the non-MV group (p < 0.05). CONCLUSIONS: Results showed the following: dyspnea; increased white blood cell count; decreased platelets; lowered albumin levels; increased urea nitrogen; increased levels of myocardial enzymes Creatine Kinase (CK), Creatine Kinase, MB Form (CKMB) and lactate dehydrogenase (LDH); increased lactate, and lowered blood calcium tests. These findings may indicate that the patients have an increased probability of needing MV support. A cutoff value for the initial APACHE II score of >11.5 and the initial PaO2/FiO2 ratio of <122.17 mmHg should be considered for MV support for patients with COVID-19.

Mathematical Modeling of Business Reopening When Facing SARS-CoV-2 Pandemic: Protection, Cost, and Risk

The sudden onset of the coronavirus (SARS-CoV-2) pandemic has resulted in tremendous loss of human life and economy in more than 210 countries and territories around the world. While self-protections such as wearing masks, sheltering in place, and quarantine policies and strategies are necessary for containing virus transmission, tens of millions of people in the U.S. have lost their jobs due to the shutdown of businesses. Therefore, how to reopen the economy safely while the virus is still circulating in population has become a problem of significant concern and importance to elected leaders and business executives. In this study, mathematical modeling is employed to quantify the profit generation and the infection risk simultaneously from a business entity's perspective. Specifically, an ordinary differential equation model was developed to characterize disease transmission and infection risk. An algebraic equation is proposed to determine the net profit that a business entity can generate after reopening and take into account the costs associated of several protection/quarantine guidelines. All model parameters were calibrated based on various data and information sources. Sensitivity analyses and case studies were performed to illustrate the use of the model in practice. The results show that with a combination of necessary infection protection measures implemented, a business entity may stand a good opportunity to generate a positive net profit while successfully controlling the within-business infection prevalence under that in the general population. The use of personal protective equipment (PPE) is also found of significant importance, especially at the early stage of business reopening. © Copyright © 2020 Miao, Gao, Feng, Zhong, Zhu, Wu, Swartz, Luo, DeSantis, Lai, Bauer, Pérez, Rong and Lairson.