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Extracellular vesicles (EVs) are nano-sized membranous particles secreted by cells. EVs have been classified into subpopulations according to their presumed biogenesis pathway, but their detailed biogenesis mechanisms still need to be fully elucidated. Enveloped viruses are another type of cell-derived nano-vesicles, and their biogenesis processes are much better known than that of EVs. Recently, studies on the similarity between enveloped viruses and EVs have been increasingly reported. The biogenesis of EVs could be better understood if these similarities are adequately investigated. In this study, we utilized a single vesicle imaging technique to visualize the protein expressions of individual nano-sized vesicles and analyzed expression patterns within single vesicles. Using this technique, we identified unique tetraspanin expression patterns in single EVs and that these patterns were closely related to their subcellular origins. The expression of CD9 or CD81 in EVs implied that they originated from the plasma membrane, and the expression of CD63 in EVs implied that they originated from endosomal organelles. We further analyzed the tetraspanin expressions of two different types of virus-like particles (VLPs) and demonstrated that the HIV-Gag-induced VLPs were more similar to EVs than SARS-CoV-2-NP/M/E-induced VLPs. In addition, HIV-Gag-GFP-expressing VLPs were highly colocalized with CD9, CD63, and CD81 signals, whereas SARS-CoV-NP-GFP-expressing VLPs were not. Based on these observations, we could assume that tetraspanin-expressing EVs might be produced through a similar process by which HIV is produced. © 2023
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Background and Aims: The novel coronavirus (COVID-19), discovered in December 2019, has now spread throughout the world. Studies have shown that patients with cancer have a higher risk of COVID-19 and are more likely to develop severe symptoms and progress to exacerbation. Head and neck tumors, as the major disease entities to be encountered in a cancer-specialized hospital, have a large number of cases of complex disorders, and some of them are highly malignant with rapid progress, for which the treatment cannot be delayed. Moreover, the operations involving the mouth, throat and airway are unavoidable during the diagnosis and treatment process of head and neck tumors, which may increase the risk of COVID-19 infection between doctors and patients. Therefore, this study was conducted to mainly investigate the appropriate diagnosis and treatment of head and neck tumors and prevention and control strategies of COVID-19 in a cancer-specialized hospital amid the COVID-19 pandemic. Methods: The clinical data of 38 patients with head and neck malignant tumors admitted for therapy by scheduled appointment in Zhejiang Cancer Hospital from February 1th, 2020 to February 22rd, 2020 were retrospectively analyzed. In our center, the time-phased appointments were implemented, patients were appropriately diverted based on the diagnosis and treatment guidelines and clinical practice, and the hospitalization indications were rigorously adhered to. All admitted patients received surgery or chemotherapy on the premise of exclusion of COVID-19 by detailed epidemiological investigation, nucleic acid detection and chest CT scan. During hospitalization, the epidemic prevention and control measures were strictly implemented, the treatment process was carefully observed, and the temperature monitoring and management were paid particular attention. After discharge, the outcomes of patients were followed up and the patients received medical advice and post-discharge treatment through internet-based hospitals or other online channels. Results: Among the 38 patients with head and neck tumors, 17 cases were males and 21 were females, with an average age of 49 years. There were 21 cases of thyroid cancer, 6 cases of oral malignancies, 3 cases of salivary gland cancer, 2 cases of laryngeal cancer, 2 cases of hypopharyngeal cancer, and 1 case each of cervical esophageal cancer, lymphoma, nasopharyngeal cancer and of angiosarcoma. COVID-19 was excluded in all 38 patients upon admission. Thirty-one patients underwent surgical treatment and the other 7 patients were subjected to chemotherapy. Fever occurred in 3 patients during the process of treatment, which included fever associated with agranulocytosis in 1 case, fever caused by tumor necrosis and infection in 1 case and fever caused by wound infection in 1 case. Patients generally had an uneventful treatment course and recovered well. No COVID-19 infection was found in patients and medical staff during hospitalization and at the end of 2 weeks after discharge from hospital. Conclusion: In the situation of COVID-19 pandemic, rational distribution of patients as well as scientific prevention and control based on the diagnosis and treatment guidelines and clinical practice, making full use of the advantages of "internet + medical service", to protect cancer patients from virus while engage in the fight against the epidemic, providing psychological support to the patients, and minimizing the impact of the epidemic on treatment and ensuring the continuity of treatment are feasible strategies for the clinical treatment of head and neck tumors. © 2020 by the Author(s).
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Background: Improved physical fitness is important for preventing COVID-19-related mortality. So, combined training can effectively increase peak oxygen consumption, physical fitness, body composition, blood pressure, and the healthrelated characteristics of adults; however, its impact in the elderly remains unclear. Methods: This systematic review and meta-analysis aimed to evaluate the effects of combined training on older adults. Four electronic databases (PubMed, Scopus, Medline, and Web of Science) were searched (until April 2021) for randomized trials comparing the effect of combined training on cardiorespiratory fitness, physical fitness, body composition, blood pressure, and cardiometabolic risk factors in older adults. Results: Combined training significantly improved peak oxygen consumption compared to no exercise (WMD = 3.10, 95% CI: 2.83 to 3.37). Combined resistance and aerobic training induced favorable changes in physical fitness (timed up-and-go = -1.06, 30-s chair stand = 3.85, sit and reach = 4.43, 6-minute walking test = 39.22, arm curl = 4.60, grip strength = 3.65, 10-m walk = -0.47, maximum walking speed = 0.15, one-leg balance = 2.71), body composition (fat mass = -2.91, body fat% = -2.31, body mass index = -0.87, waist circumference = -2.91), blood pressure (systolic blood pressure = -8.11, diastolic blood pressure = -4.55), and cardiometabolic risk factors (glucose = -0.53, HOMA-IR = -0.14, high-density lipoprotein = 2.32, total cholesterol = -5.32) in older individuals. Finally, the optimal exercise prescription was ≥ 30 min/session × 50-80% VO2peak, ≥ 3 times/week for ≥ 12 weeks and resistance intensity 70-75% one-repetition maximum, 8-12 repetitions × 3 sets. Conclusions: Combined training improved VO2peak and some cardiometabolic risk factors in older populations. The dose-effect relationship varied between different parameters. Exercise prescriptions must be formulated considering individual needs during exercise.
Contexte: L'amélioration de la condition physique est importante pour prévenir la mortalité liée au COVID-19. Ainsi, l'entraînement combiné peut augmenter efficacement la consommation maximale d'oxygène, la forme physique, la composition corporelle, la tension artérielle et les caractéristiques liées à la santé des adultes; cependant, son impact chez les personnes âgées reste incertain. Méthodes: Cette revue systématique et cette méta-analyse visaient à évaluer les effets de l'entraînement combiné chez les personnes âgées. Quatre bases de données électroniques (PubMed, Scopus, Medline et Web of Science) ont été consultées (jusqu'en avril 2021) pour trouver des essais randomisés comparant l'effet d'un entraînement combiné sur l'aptitude cardiorespiratoire, la forme physique, la composition corporelle, la tension artérielle et les facteurs de risque cardiométabolique chez les personnes âgées. Résultats: Au total, 37 publications ont été incluses dans cette étude. L'entraînement combiné a considérablement amélioré la consommation maximale d'oxygène par rapport à l'absence d'exercice (DMP = 3,10, IC95 % : 2,83 à 3,37). La combinaison résistance + entraînement aérobie a entraîné des changements favorables dans la forme physique (démarrage chronométré = −1,06, position assise pendant 30 s = 3,85, position assise et lever = 4,43, test de marche de 6 minutes = 39,22, flexion des bras = 4,60, adhérence force = 3,65, marche de 10 m = −0,47, vitesse de marche maximale = 0,15, équilibre sur une jambe = 2,71), composition corporelle (masse grasse = −2,91, pourcentage de graisse corporelle = −2,31, indice de masse corporelle = −0,87, taille circonférence = −2,91), tension artérielle (pression artérielle systolique = −8,11, pression artérielle diastolique = −4,55) et facteurs de risque cardiométabolique (glucose = −0,53, HOMA-IR = −0,14, lipoprotéines de haute densité = 2,32, cholestérol total = −5,32) chez les personnes âgées. Enfin, la prescription d'exercice optimale était ≥ 30 min/séance × 5080 % VO2pic, ≥ 3 fois/semaine pendant ≥ 12 semaines et résistance à une intensité de 7075 % une répétition maximale, 812 répétitions × 3 séries. Conclusions: L'entraînement combiné a amélioré la VO2pic et certains facteurs de risque cardiométabolique chez les populations âgées. La relation dose-effet variait entre les différents paramètres. Les prescriptions d'exercice doivent être formulées en tenant compte des besoins individuels pendant l'exercice.
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Falls, considered a serious health-related concern for the elderly people, are associated with multiple diverse and dynamic needs for the elderly people themselves, their caregivers, their family members, and healthcare professionals. The modern-day Internet of Everything lifestyle is characterized by people using the internet for a multitude of reasons which also includes seeking and sharing information related to such needs. Such activity on the internet results in the generation of tremendous amounts of web behavior-based Big Data which can be studied and analyzed to investigate the trends in the underlining needs and the associated web search interests. The COVID-19 pandemic that the world is facing right now has impacted the elderly population to a significant extent. In fact, the elderly population is considered a demographic group that is most likely to get infected by this virus and develop serious symptoms, which could lead to hospitalizations and death. There hasn't been any study conducted in the field of aging research thus far that investigates how the COVID-19 pandemic may or may not have impacted the needs related to fall detection in the elderly. This work aims to address this research challenge. A dedicated methodology based on Google Trends is proposed in this paper that studies the web behavior-based Big Data related to fall detection from different countries both before and after the pandemic. The preliminary results presented from the analysis of the web behavior-based Big Data from 14 countries - USA, India, Germany, United Kingdom, Spain, Australia, Indonesia, Malaysia, Thailand, South Africa, Canada, Philippines, Sweden, and Ireland, which are amongst the countries worst hit by COVID-19, shows evidence that the pandemic had an impact towards increasing the web search interests related to fall detection in multiple countries. © 2022 ACM.
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OBJECTIVE: We aimed to assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on the incidence of intussusception. MATERIALS AND METHODS: Literature search of the PubMed and EMBASE databases was conducted for articles published in English until August 5, 2022. RESULTS: Overall, 127 articles were retrieved, and five studies from South Korea (n=4) and the United States of America (n=1) containing clinical data from single-center medical records to nationwide databases were ultimately included in the systematic review. All the included studies reported that the incidence of intussusception decreased significantly during the pandemic period compared with the pre-pandemic period. The communicable disease incidence tended to decrease even as the incidence of non-communicable diseases did not significantly change. There was no significant difference in the time to diagnosis between the pre-pandemic and pandemic periods; however, the time to radiologic reduction was significantly longer or not depending on the study. CONCLUSIONS: The COVID-19 pandemic significantly reduced the incidence of intussusception in children, supporting the hypothesis that infection plays a major role in the etiology of intussusception. Future studies in the late pandemic or post-pandemic era, which would represent the level of implementation of non-pharmaceutical interventions and social distancing as well as additional data from various countries will be needed.
Subject(s)
COVID-19 , Intussusception , Child , United States , Humans , Pandemics , COVID-19/epidemiology , Incidence , SARS-CoV-2 , Intussusception/epidemiologyABSTRACT
Compounds with antimicrobial activity have gained much attention in research due to the outbreak of coronavirus disease 2019 (COVID-19). Quaternary ammonium salts (QASs) are an emerging group of antibacterial agents that are used as disinfectants. Many studies have been carried out involving the applications of QASs as antifouling agents for the inhibition of biofilm growth on medical implants and antibacterials on surfaces and in an aquatic environment. In investigating the antibacterial activity of QASs, we addressed the structure-activity relationship and the physicochemical factors. This review is focused on the fine-tuning of the chemical structures of QASs for their applications as wide antibacterial agents. [GRAPHICS] .
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OBJECTIVE: The US risdiplam expanded access program (EAP; NCT04256265) was opened to provide individuals with Type 1 or 2 spinal muscular atrophy (SMA) who had no satisfactory treatment options access to risdiplam prior to commercial availability. The program was designed to collect safety data during risdiplam treatment. METHODS: Patients were enrolled from 23 non-preselected sites across 17 states and treated with risdiplam orally once daily. Eligible patients had a 5q autosomal recessive Type 1 or 2 SMA diagnosis, were aged ≥2 months at enrollment, and were ineligible for available and approved SMA treatments or could not continue treatment due to a medical condition, lack/loss of efficacy, or the COVID-19 pandemic. RESULTS: Overall, 155 patients with Type 1 (n = 73; 47.1%) or 2 SMA (n = 82; 52.9%) were enrolled and 149 patients (96.1%) completed the EAP (defined as obtaining access to commercial risdiplam, if desired). The median treatment duration was 4.8 months (range, 0.3-9.2 months). The median patient age was 11 years (range, 0-50 years), and most patients (n = 121; 78%) were previously treated with a disease-modifying therapy. The most frequently reported adverse events were diarrhea (n = 10; 6.5%), pyrexia (n = 7; 4.5%), and upper respiratory tract infection (n = 5; 3.2%). The most frequently reported serious adverse event was pneumonia (n = 3; 1.9%). No deaths were reported. INTERPRETATION: In the EAP, the safety profile of risdiplam was similar to what was reported in pivotal risdiplam clinical trials. These safety data provide further support for the use of risdiplam in the treatment of adult and pediatric patients with SMA.
Subject(s)
COVID-19 Drug Treatment , Muscular Atrophy, Spinal , Adult , Azo Compounds/therapeutic use , Child , Humans , Muscular Atrophy, Spinal/drug therapy , Pandemics , PyrimidinesABSTRACT
We propose an agent-to-agent contagion-immunity formulation that can simulate detailed COVID-19 spreading within moving crowds. Specifically, we develop a diffusion-based disease contagion model for discrete systems that considers the effect of health interventions, such as social distancing, immunity, and vaccination. We integrate our contagion-immunity formulation with the governing equations of motion for crowd dynamics for investigating the distribution of disease in crowds with different numbers of people. For the same crowd simulation, our model can interactively simulate virus spread for different initial distributions of infected people. To the best of our knowledge, our work is the first to simulate the disease contagion within moving crowds in computer graphics. Our numerical results for the number of infected people in unprotected dense crowds agree with the SIS model, while our model provides richer information for disease spread and shows that vaccination is the best health intervention to prevent infection. © 2021 ACM.
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We report the discovery of KMT-2020-BLG-0414Lb, with a planet-to-host mass ratio q (2) = 0.9-1.2 x 10(-5) = 3-4 circle plus at 1 sigma, which is the lowest mass-ratio microlensing planet to date. Together with two other recent discoveries (4 less than or similar to q/q (circle plus) less than or similar to 6), it fills out the previous empty sector at the bottom of the triangular (log s, log q) diagram, where s is the planet-host separation in units of the angular Einstein radius theta E. Hence, these discoveries call into question the existence, or at least the strength, of the break in the mass-ratio function that was previously suggested to account for the paucity of very low-q planets. Due to the extreme magnification of the event, A (max) similar to 1450 for the underlying single-lens event, its light curve revealed a second companion with q (3) similar to 0.05 and ;log s (3);similar to 1, i.e., a factor similar to 10 closer to or farther from the host in projection. The measurements of the microlens parallax pi (E) and the angular Einstein radius theta E allow estimates of the host, planet and second companion masses, (M (1), M (2), M (3)) similar to (0.3 M (circle dot), 1.0 M (circle plus), 17 M-J ), the planet and second companion projected separations, (a (perpendicular to,2), a (perpendicular to,3)) similar to (1.5, 0.15 or 15) au, and system distance D (L) similar to 1 kpc. The lens could account for most or all of the blended light (I similar to 19.3) and so can be studied immediately with high-resolution photometric and spectroscopic observations that can further clarify the nature of the system. The planet was found as part of a new program of high-cadence follow-up observations of high-magnification events. The detection of this planet, despite the considerable difficulties imposed by COVID-19 (two KMT sites and OGLE were shut down), illustrates the potential utility of this program.
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Objective: To evaluate the performance and application of a fast nucleic acid detection system for testing severe acute respiratory syndrome virus 2 (SARS-COV-2). Methods: Clinical samples were collected from February to July 2020 from Beijing Center for Diseases Prevention and Control and the Laboratory Department of China-Japan Friendship Hospital, to evaluate the sensitivity, specificity, anti-interference ability, precision and clinical sample coincidence rate of fast nucleic acid detection system for SARS-CoV-2. The analytical sensitivity was determined by a dilution series of 20 replications for each concentration. Analytical specificity study was performed by testing organisms whose infection produces symptoms similar to those observed at the onset of corona virus disease 2019 (COVID-19), and of the normal or pathogenic microflora that may be present in specimens collected. Potential interference substances were evaluated with different concentration in the interference study. Precision study was conducted by estimating intra-and inter-batch variability. Clinical evaluation was performed by testing 230 oropharyngeal swab specimens and 95 sputum specimens in fast nucleic acid detection system, comparing with conventional real-time fluorescent quantitative PCR (RT-qPCR) and clinical diagnostic results. Results: The analytical sensitivity of SARS-CoV-2 using fast nucleic acid detection system was 400 copies/ml. The result is negative for testing with the organisms that may likely in the circulating area or causing similar symptoms with SARS-CoV-2 and human nucleic acid, indicating that no cross reactivity with organisms. The results of precision test showed that the Coefficient of variation of Ct value of high, medium and low concentration samples was 1.90%-3.92%, and all of them were less than 5% in intra-and inter-batch testing. The results of the samples were still positive after adding the potential interfering substances, indicating that the possible interfering substances in the samples had no effect on the results. 98.46% and 97.85% diagnosis results of fast nucleic acid detection system were consistent with RT-qPCR and clinical diagnostic results, respectively. Conclusion: The fast nucleic acid detection system based on molecular parallel reaction can be used as a selection method for SARS-CoV-2 testing.
Subject(s)
COVID-19 , Nucleic Acids , COVID-19 Testing , Humans , RNA, Viral , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Sensitivity and SpecificityABSTRACT
Objectives: Racism toward Asian ethnicities dates back to the 19th century. Such sentiments continue to have a presence and impact on Asian American youth. The objective of this presentation is to review the historical and current context of anti-Asian racism, understand how experiences of racism impact identity and mental health in Asian American youth, and identify approaches for clinicians to manage and treat Asian youth populations with cultural humility. Methods: The presenter will review the historical, social, and political contexts of anti-Asian racism in the United States and draw on themes and experiences gathered from facilitating university-based discussion groups among Asian/Asian American transitional-aged youth (TAY) students to explore the impact of anti-Asian racism and culture on mental health and identity. Results: Throughout US history, perceptions of Asians as a threat to America, commonly termed the “yellow peril,” resulted in the passage of laws barring migration and naturalization, as well as executive orders resulting in internment of Asian citizens. Today, anti-Asian racism manifests in the perpetuation of the “model minority” stereotype and rising attacks on Asian people during the COVID-19 pandemic. In the facilitated discussion groups of Asian/Asian American TAY students, emerging themes include forms of violence experienced during COVID-19, issues with the model minority stereotype, burden of acculturation with subsequent loss of cultural identity, and cultural clashes between Eastern collectivist and Western individualist values. These themes reflect the ongoing struggles of Asian students reconciling one’s identity, self-esteem, connection to one’s family and community, and experiences of mental illness. Conclusions: Anti-Asian racism impacts Asian American youth in multiple ways, particularly on their development of identity, sense of self, and mental well-being. Mental health clinicians need to be aware of the history of anti-Asian racism and the ways it is expressed today, and to gain insight into our own biases in order to best treat our Asian American populations. DEI, COLST, SREG
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Objective: The purpose of this study was to evaluate how a virtual interview process influences the Obstetrics and Gynecology fellowship match at a single institution. Materials and Methods: During the COVID-19 pandemic, the University of California Los Angeles (UCLA) OBGYN Department conducted all interviews in a virtual setting. Applicants and faculty completed 20 and 13-question surveys, respectively. A 5-point Likert scale was used for survey responses. The fellowship interviewees included those applying to the Reproductive Endocrinology and Infertility, Maternal Fetal Medicine, Gynecologic Oncology, Female Pelvic Medicine and Reconstructive Surgery, and Family Planning programs. Demographic data was collected and descriptive statistics were used to analyze data. Comparative analyses were performed with t-tests. Results: Surveys were distributed to 45 faculty members and 131 applicants with a response rate of 95.6% (n=43) and 46.6% (n=61), respectively. Of respondents, 83.7% (n=36) of faculty and 88.6% (n=54) of applicants agreed or strongly agreed that the video conference interviews (VCI) allowed them to accurately represent themselves (p=0.48). The majority of the applicants (62.3%, n=38) had a good understanding of the program’s culture after VCI. Over 70% (n=78) of applicants and faculty agreed or strongly agreed that they were able to form connections over VCI. Both applicants (67.2%, n=41) and faculty (83.7%, n=36) reported that the VCI helped them decide whether the program or candidate, respectively, was a good fit (p=0.98). Conclusions: Our data demonstrate that the majority of respondents could accurately represent themselves and form connections over VCI. Most importantly, both faculty and interviewees agreed that the VCI process helped to find a good match between applicant and program across all OBGYN fellowship programs. Given that in-person interviews require a significant amount of resources including time, unpredictable residency coverage issues, money, and coordination of travel, VCI is a viable option for fellowship interviews. Future studies should determine a standardized and evidenced-based approach for VCI. Impact Statement: The virtual interview model may be considered a long-term solution for fellowship interviews given the financial costs to the applicants and the time burden of the fellowship interview process for both the applicants and the residency programs. It will be important to optimize the VCI process so that applicants and departments can feel confident that the VCI process mirrors the match results of an in-person interview. Future research should investigate the impact of VCI on other avenues of training including the medical school and residency selection processes.
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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.
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Background: Coronavirus disease 2019 (COVID-19) has made 'untact' life a new standard (next normal) way of life, minimizing physical contacts among people. Emotional exchanges between people are rapidly being replaced by contact through the Internet, social networks, and over-the-top services. Current Concepts: People are expressing more stress and anxiety that are caused by fear of infection, and also embitterment due to perceived distrust and injustice is increasing. In the era of COVID-19, it is necessary and important to manage burnout, depression, and anxiety symptoms of medical staff and quarantine personnel. The pandemic and the resulting social changes intensifies loneliness, leading to deterioration in mental and physical health. The World Health Organization has warned that loneliness and social isolation are leading to the exacerbation of physical illness and increased mortality due to suicide and other mental health problems. Discussion and Conclusion: It is needed to establish a next standard of mental health service such as untact diagnosis and follow-up support system. Government and society should establish a sustainable system even after the COVID-19 crisis, rather than stopgap measures made with people's sacrifice as collateral.
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This paper describes the results of our Neural Network (NN) models that predict annual wages based on the combination and levels of 35 different skills possessed by wage earners. These models can estimate the value of skills for skill-based compensation systems. They can be used by employers to determine how much to compensate different combinations of skills and by employees to estimate what they should be paid. Finally, governments can use the models to support the development and analysis of labor policies. We collect and integrate official U.S. Government data on 35 general job skills with the annual wage data for over 900 standard occupations. The skills data is then used as inputs to train an artificial intelligence (Al) neural network (NN) models. The resulting NN models train to above 70 percent accuracy in predicting annual wage levels based on the combination and levels of 35 different skills. This research makes use of authoritative U.S. Government data in new ways that can be used to better understand the connections between general skills and their relationships to wages. The need for these types of analytical tools is all the more important as changes in the job market have been severely impacted by the COVID 19 pandemic and are increasingly at risk of being replaced by automation. © 2021 Otto James et al., published by Sciendo 2021.
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Sentiment analysis is one of the key tasks of natural language understanding. Most of sentiment analysis researches revolve around sentiment classification of subjective texts. However, research in the field of sentiment evolution analysis for complex interactive texts are notable. Sentiment evolution models the dynamics of sentiment orientation over time, it can predict the stage of event development. In this paper, we propose a sentiment evolution method based on a joint model to analyze the dynamics and interactions of individual sentiment on social media such as Weibo. The model contains two modules, sentiment encoder module based on pre-training model and time series prediction module based on Long Short-Term Memory(LSTM). We conducted experiments on real-world datasets which were crawled from Weibo. The experiment demonstrated a case study that analyzed the sentiment dynamics of topics related to COVID-19. Experimental results show that our method achieve an accuracy of 88.0%, which are about 14.7% higher than the existing methods. © 2021 IEEE.
ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gained tremendous attention due to its high infectivity and pathogenicity. The 3-chymotrypsin-like hydrolase protease (Mpro) of SARS-CoV-2 has been proven to be an important target for anti-SARS-CoV-2 activity. To better identify the drugs with potential in treating coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 and according to the crystal structure of Mpro, we conducted a virtual screening of FDA-approved drugs and chemical agents that have entered clinical trials. As a result, 9 drug candidates with therapeutic potential for the treatment of COVID-19 and with good docking scores were identified to target SARS-CoV-2. Consequently, molecular dynamics (MD) simulation was performed to explore the dynamic interactions between the predicted drugs and Mpro. The binding mode during MD simulation showed that hydrogen bonding and hydrophobic interactions played an important role in the binding processes. Based on the binding free energy calculated by using MM/PBSA, Lopiravir, an inhibitor of human immunodeficiency virus (HIV) protease, is under investigation for the treatment of COVID-19 in combination with ritionavir, and it might inhibit Mpro effectively. Moreover, Ombitasvir, an inhibitor for non-structural protein 5A of hepatitis C virus (HCV), has good inhibitory potency for Mpro. It is notable that the GS-6620 has a binding free energy, with respect to binding Mpro, comparable to that of ombitasvir. Our study suggests that ombitasvir and lopinavir are good drug candidates for the treatment of COVID-19, and that GS-6620 has good anti-SARS-CoV-2 activity. © 2021 Fujian Institute of Research of the Structure of Matter. All rights reserved.
ABSTRACT
As the COVID-19 epidemic began to worsen in the first months of 2020, stringent lockdown policies were implemented in numerous cities throughout the world to control human transmission and mitigate its spread. Although traffic density reduction inside the city was felt subjectively, there has thus far been no objective and quantitative study of its variation to reflect the intracity population flows and their corresponding relationship with lockdown policy stringency from the view of remote sensing images with the high resolution under 1m. Accordingly, we here provide a quantitative investigation of the traffic density reduction before and after lockdown was implemented in six cities (Wuhan, Milan, Madrid, Paris, New York, and London) around the world heavily affected by the COVID-19 epidemic, which is accomplished by extracting vehicles from the multi-temporal high-resolution remote sensing images. A novel vehicle detection model combining unsupervised vehicle candidate extraction and deep learning identification was specifically proposed for the images with the resolution of 0.5m. Our results indicate that traffic densities were reduced by an average of approximately 50% (and as much as 75.96%) in these six cities following lockdown. The influences on traffic density reduction rates are also highly correlated with policy stringency, with an R