Immunotherapy: ALLOGENEIC UMBILICAL CORD BLOOD REGULATORY T CELLS DECREASE INFLAMMATION AND PRESERVE ANTI-TUMOR ACTIVITY OF CAR T CELLS

Background & Aim: With larger accessibility and increased number of patients being treated with CART cell therapy, real-world toxicity continues to remain a significant challenge to its widespread adoption. We have previously shown that allogeneic umbilical cord blood derived (UCB) regulatory T cells (Tregs) can resolve uncontrolled inflammation and can treat acute and immune mediated lung injury in a xenogenic model as well as in patients suffering from COVID-19 acute respiratory distress syndrome. The unique properties of UCB Tregs including: i) lack of plasticity when exposed to inflammatory micro-environments;ii) no requirement for HLA matching;iii) long shelf life of cryopreserved Tregs;and iv) immediate product availability for on demand treatment, makes them an attractive source for treating acute inflammatory syndromes. Therefore, we hypothesized that add-on therapy with UCB derived Tregs may resolve uncontrolled inflammation responsible for CART cell therapy associated toxicity. Methods, Results & Conclusion(s): UCB Tregs were added in 1:1 ratio to CART cells, where no interference in their ability to kill CD19+ Raji cells, was detected at different ratios : 8:1 (80.4% vs. 81.5%);4:1 (62.0% vs. 66.2%);2:1 (50.1% vs. 54.7%);1:1 (35.4% vs. 44.1%) (Fig 1A). In a xenogenic B cell lymphoma model, multiple injections of Tregs were administered after CART injection (Fig 1B), which did not impact distribution of CD8+ T effector cells (Fig 1C) or CART cells cells (Fig 1D) in different organs. No decline in the CAR T levels was observed in the Tregs recipients (Fig 1E). Specifically, no difference in tumor burden was detected between the two arms (Fig 2A). No tumor was detected in CART+Tregs in liver (Fig 2B) or bone marrow (Fig 2C). A corresponding decrease in multiple inflammatory cytokines in peripheral blood was observed in CART+Tregs when compared to CART alone (Fig 2D). Here we show "proof of concept" for add-on therapy with Tregs to mitigate hyper-inflammatory state induced by CART cells without interference in their on-target anti-tumor activity. The timing of Tregs administration after CART cells have had sufficient time for forming synapse with tumor cells allows for preservation of their anti-tumor cytotoxicity, such that the infused Tregs home to the areas of tissue damage to bind to the resident antigen presenting cells which in turn collaborate with Tregs to resolve inflammation. Such differential distribution of cells allow for a Treg "cooling blanket" and lays ground for clinical study. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy

Myocardium damage and electrocardiogram characteristics of patients infected with SARS-CoV-2 Omicron variant in Zhuhai

Aim To explore the myocardial damage, abnormal electrocardiogram characteristics of patients infected with SARS-CoV-2 Omicron variant in Zhuhai. Methods 84 patients with SARS-CoV-2 Omicron variant (Omicron variant group) admitted to the Fifth Affiliated Hospital of Sun Yat-sen University from January 13 to March 20, 2022 were included, and 88 patients with non SARS-CoV-2 Omicron variant (non-Omicron variant group) from January 17 to February 17, 2020 were included. A retrospective study was conducted to compare myocardial damage, abnormal electrocardiogram and clinical characteristics between the two groups. Results The mean age of patients in Omicron variant group was smaller than that in non-Omicron variant group [(36. 6±15. 6) years vs. (49. 8±14. 3) years, P<0. 01], and the proportion of patients with body temperature, systolic blood pressure and fever at admission was lower than that of non-Omicron variant group (P<0. 05). The neutrophil / lymphocyte ratio [(2. 93 (3. 03, 5. 81) vs. 7. 06 (2. 32, 11. 27), P<0. 001], interleukin-2 (IL-2) and interleukin-6 (IL-6) levels in Omicron variant group were significantly lower than those in non-Omicron variant group (P<0. 01). Cardiac troponin I (cTnI) was negative in Omicron variant group, and the concentrations of cTnI, creatine kinase-MB isozyme (CK-MB) and N-terminal pro-brain natriuretic peptide (NT-proB-NP) and the proportion of patients with elevated levels were significantly lower than those of non-Omicron variant group (P<0. 01). The incidence of abnormal electrocardiogram in Omicron variant group was also significantly lower than that in non-Omicron variant group (25. 0% vs. 42. 0%, P = 0. 001), sinus tachycardia, atrial premature beats and T wave changes were the main symptoms. Atrial premature beats, T wave changes, ST segment depression and bundle branch block were the main symptoms in non-Omicron variant group. Conclusions The patients infected with SARS-CoV-2 Omicron variant in Zhuhai may not have obvious myocardial damage because most of the patients have been vaccinated with COVID-19 vaccine. The incidence of abnormal electrocardiogram is also significantly lower than that of non-Omicron variant group, mainly sinus tachycardia, atrial premature beats and T wave changes. © 2022, Editorial Office of Chinese Journal of Arteriosclerosis. All rights reserved.

Pre-Service Science Teachers' Understanding of Socio-Scientific Issues Instruction through a Co-Design and Co-Teaching Approach Amidst the COVID-19 Pandemic

This qualitative case study explores the development of pre-service science teachers' (PSTs) understanding of Socio-Scientific Issues (SSI) instruction. The study utilized a conceptual framework of SSI-based instruction and a three-phase approach involving co-designing solutions, co-designing curriculum materials, and co-teaching classes. Primary data sources included PSTs' interviews and reflective journals, while artifacts, field notes, and curriculum materials served as secondary data sources. Thematic analysis was used to analyze the data of six PSTs in a teacher preparation program. We found that the PSTs' understanding of SSI instruction was enhanced in 12 features of three core aspects: design elements, learner experiences, and teacher attributes. "Engaging in higher-order practices" was the most prominent feature, observed across all three phases. The three-phase approach played a crucial role in promoting PSTs' understanding of SSI instruction, with each phase guiding their understanding in distinct ways. Particularly, the co-designing solutions phase facilitated the development of PSTs' "awareness of the social considerations associated with the issue". While the co-designing curriculum materials phase was effective in promoting their understanding of "scaffolding for practice: providing scaffolding for higher-order practices. "The co-teaching classes phase played a crucial role in facilitating their understanding of "willingness to position oneself as a knowledge contributor rather than the sole authority".

Synergy between stock prices and investor sentiment in social media

The underlying assumption of using investor sentiment to predict stock prices, stock market returns, and liquidity is that of synergy between stock prices and investor sentiment. However, this synergistic relationship has received little attention in the literature. This paper investigates the synergistic pattern between stock prices and investor sentiment using social media messages from stock market investors and natural language processing techniques. At the macro level, we reveal extremely significant positive synergy between investor sentiment and stock prices. That is, when a stock price rises, investor sentiment rises, and when a stock price falls, investor sentiment falls. However, this synergy may be reversed or even disappear over a specific time period. Through a segmented measurement of the synergy between stock prices and investor sentiment over the course of a day, we also find that investor sentiment on social media is forward looking. This provides theoretical support for using investor sentiment in stock price prediction. We also examine the effect of lockdowns, the most draconian response to COVID-19, on synergy between stock prices and investor sentiment through causal inference machine learning. Our analysis shows that external anxiety can significantly affect synergy between stock prices and investor sentiment, but this effect can promote either positive or negative synergy. This paper offers a new perspective on stock price forecasting, investor sentiment, behavioral finance, and the impact of COVID-19 on the stock markets. Copyright (c) 2022 Borsa Istanbul Anonim S, irketi. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

The Behavioral Intention of Hospitals to Promote Sustainable Development of Green Healthcare from the Perspective of Organizational Stakeholders during the COVID-19 Epidemic: A Case Study of Hospitals in Taiwan

When the World Health Organization (WHO) analyzed the culprits of global warming, it was found that in developed countries with relatively few high-polluting heavy industries, the medical sector is one of the sources of high-density carbon emissions. Therefore, the medical industry has a noticeable impact on the environment. Amid the current COVID-19 epidemic, this study adopts the theory of planned behavior (TPB), widely used in decision-making science. We selected a regional teaching hospital with 339 employees in Taiwan to obtain valid questionnaire data. We explore the comparative analysis of different intra-organizational stakeholders' "attitudes,” "subjective norms,” and "perceived behavioral control” on the hospital's behavioral intention to promote green healthcare. The results show that the TPB model has reliable explanatory power. All three factors have a positive and significant effect on promoting green hospital behavior. Among them, perceived behavioral control was the most notable. A comparative analysis of the differences among stakeholders in the research model shows that "medical administrators” and "nursing staff” have a higher proportion of significant influence effects in various hypotheses, highlighting the critical roles of these two groups in promoting green hospitals. This research policy suggests that the cross-departmental staff in the hospital put forward green innovation ideas, strengthen internal environmental education and management, establish a good incentive system for front-line nursing staff, and implement the sustainable development strategy of the hospital. © 2023 by the authors.

COVID-19 and systemic anti-cancer therapy.

The corona virus disease 2019 (COVID-19) pandemic continues to severely impact healthcare systems around the world, and patients with cancer are even worse affected owing to compromised immune status and greater exposure risk. In the present review, we retrieved the relevant literature including guidelines and consensuses directly related to the purpose of this study from the PubMed database, and then summarized the research data on cancer and COVID-19, aiming to discuss the personal protection, systemic anti-cancer therapy, outcome of co-infection, and the clinical management strategy in this population. We found that patients with malignant tumors had a higher chance of suffering COVID-19, co-infection of whom had an even worse clinical prognosis, especially for those with lung cancer or hematologic cancers. Systemic chemotherapy may delay the clearance of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) virus of human body, and thus have a negative impact on the clinical outcomes of COVID-19, while certain endocrine therapy and targeted drugs having limited or no impact. There has been no sufficient evidence for the impact of immune checkpoint therapy on the outcomes of COVID-19 till now. It is of great value to strengthen the personal protection of patients, adjust the anti-tumor treatments rationally and optimize the clinical management processes.Copyright © 2022, Editorial Office of China Oncology. All rights reserved.

Anti-pathogen stainless steel combating COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits strong stability on conventional stainless steel (SS) surface, with infectious virus detected even after two days, posing a high risk of virus transmission via surface touching in public areas. In order to mitigate the surface toughing transmission, the present study develops the first SS with excellent anti-pathogen properties against SARS-COV-2. The stabilities of SARS-CoV-2, H1N1 influenza A virus (H1N1), and Escherichia coli (E.coli) on the surfaces of Cu-contained SS, pure Cu, Ag-contained SS, and pure Ag were investigated. It is discovered that pure Ag and Ag-contained SS surfaces do not display apparent inhibitory effects on SARS-CoV-2 and H1N1. In comparison, both pure Cu and Cu-contained SS with a high Cu content exhibit significant antiviral properties. Significantly, the developed anti-pathogen SS with 20 wt% Cu can distinctly reduce 99.75% and 99.99% of viable SARS-CoV-2 on its surface within 3 and 6 h, respectively. In addition, the present anti-pathogen SS also exhibits an excellent inactivation ability for H1N1 influenza A virus (H1N1), and Escherichia coli (E.coli). Interestingly, the Cu ion concentration released from the anti-pathogen SS with 10 wt% and 20 wt% Cu was notably higher than the Ag ion concentration released from Ag and the Ag-contained SS. Lift buttons made of the present anti-pathogen SS are produced using mature powder metallurgy technique, demonstrating its potential applications in public areas and fighting the transmission of SARS-CoV-2 and other pathogens via surface touching.

Prompt Learning for Multi-modal COVID-19 Diagnosis

The outbreak of COVID-19 pandemic has spread rapidly and severely affected all aspects of human lives. Recent researches has shown artificial intelligence and deep learning based approaches have achieved successful results in detecting diseases. How to accurately and quickly detect COVID-19 has always been the core topic of research. In this paper, we propose a novel approach based on prompt learning for COVID-19 diagnosis. Different from the traditional 'pre-training, fine-tuning' paradigm, we propose the prompt-based method that redefine the COVID-19 diagnosis as a masked predict task. Specifically, we adopt an attention mechanism to learn the multi-modal representation of medical image and text, and manually construct a cloze prompt template and a label word set. Selecting the label word corresponding to the maximum probability by pre-training language model. Finally, mapping the prediction results to the disease categories. Experimental results show that our proposed method obtains obvious improvement of 1.2% in terms of Mi-F1 score compared with the state-of-the-art methods. © 2022 IEEE.

Does COVID-19 Affect the Accessibility of Outdoor Sports Venues? A Case Study in Nanchang, China

The COVID-19 pandemic has been a great challenge to society, the economy, and population health. It has become a significant public health event and social problem. Exploring the impact of COVID-19 on the accessibility of outdoor sports venues is crucial for people's health. Based on spatial theory, the quantitative and qualitative analyses of outdoor sports venues' spatial distribution and accessibility were conducted, and the epidemic's impact on them was analyzed. The results show that: (1) The existing outdoor sports venues in Nanchang show a distribution pattern of "sparse in the north and south, and strong aggregation in the middle”. (2) As a result of the epidemic, the center of the standard deviation ellipse in outdoor sports sites shifted to the southeast, while the number of open venues decreased by 68%. (3) Before COVID-19, the entire study area could achieve full coverage by driving for 17 min, riding for 70 min, or walking for 119 min. After COVID-19, the time increased to 29, 109, and 193 min, respectively. (4) Under the high-risk scenario of COVID-19, the average walking time for people to reach outdoor sports venues increased from 6.2 min to 14.0 min in the study area, with an increase of 126%. Finally, according to the findings of this study, recommendations were made on how government departments could build or re-open outdoor sports venues during and after this epidemic. © 2023 by the authors.

Prompt Learning for Multi-modal COVID-19 Diagnosis

The outbreak of COVID-19 pandemic has spread rapidly and severely affected all aspects of human lives. Recent researches has shown artificial intelligence and deep learning based approaches have achieved successful results in detecting diseases. How to accurately and quickly detect COVID-19 has always been the core topic of research. In this paper, we propose a novel approach based on prompt learning for COVID-19 diagnosis. Different from the traditional 'pre-training, fine-tuning' paradigm, we propose the prompt-based method that redefine the COVID-19 diagnosis as a masked predict task. Specifically, we adopt an attention mechanism to learn the multi-modal representation of medical image and text, and manually construct a cloze prompt template and a label word set. Selecting the label word corresponding to the maximum probability by pre-training language model. Finally, mapping the prediction results to the disease categories. Experimental results show that our proposed method obtains obvious improvement of 1.2% in terms of Mi-F1 score compared with the state-of-the-art methods. © 2022 IEEE.

Potential of Antibody-Dependent Cellular Cytotoxicity in Acute and Recovery Phases of SARS-CoV-2 Infection

Background:Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic that has resulted in millions of casualties. Although researchers have reported the existence of neutralizing antibodies and viral T cell immunity against SARS-CoV-2, little is known about the presence of antibody-dependent cellular cytotoxicity (ADCC) and its role in combating SARS-CoV-2 infection.Methods:Nineteen acute COVID-19 patients at the First Affiliated Hospital of Guangzhou Medical University from January to February, 2020 and 55 recovery COVID-19 patients at the Second Peoples Hospital of Changde City from February, 2020 to February, 2021 were recruited in this study. Longitudinal plasma samples were collected. A virus-specific ADCC assay was performed to study the COVID-19 plasma samples. The correlations between ADCC and total IgG titer, including anti-RBD, anti-N, and neutralizing antibody titer were analyzed.Results:A high level of ADCC with 0.86% of IFN-γ+CD107a+NK cells induced by anti RBD antibodies and with 0.54% of IFN-γ+CD107a+NK cells induced by anti N antibodies was observed. This activity peaked at 3 weeks after disease onset with 1.16% and 0.63% of IFN-γ+CD107a+NK cells induced by anti RBD and anti N antibodies respectively, declined to 0.32% and 0.32% of IFN-γ+CD107a+NK cells respectively after more than 2 months, and persisted for 12 months after disease onset. The ADCC did not aggravate the severity of COVID-19 in terms of sequential organ failure assessment, although ADCC decreased with the age of COVID-19 patients. Interestingly, ADCC response is not correlated with neutralizing antibody titer or total IgG titers against S protein RBD and N protein in acute patients. ADCC in recovered patients showed a significant correlation with anti RBD IgG titer (R2 = 0.33, P < 0.001).Conclusion:Antibodies from COVID-19 patients against the N protein and S protein RBD domains could stimulate high levels of ADCC response. Our results provide evidence that vaccination should not only focus on neutralizing antibodies but also binding antibodies that may facilitate the antiviral function of ADCC, especially in the elderly. © 2022 Journal of Bone and Joint Surgery Inc.. All rights reserved.

COVID-19 accelerated digital transformation: The case of Meituan

The outbreak of the COVID-19 pandemic caused disruptions in supply chains. While most existing research suggests ways to improve organizational resilience, our research raises the question of whether the pandemic has accelerated digital transformation at the organizational level. Using the case of Meituan in China, we investigate the supply chain disruptions caused by COVID-19, the strategies taken by Meituan to address the problems and their strategic implications. Starting as a fast food delivery company, Meituan has developed into a leading online shopping platform in China specialized in using digital technologies to provide on-demand delivery services. Our research on Meituan during COVID-19 shows that companies can leverage emerging technologies to improve business models and deliver long-term strategic benefits through digital transformation, rather than focusing solely on improving organizational resilience to reduce uncertainty risk. © 2022 International Consortium for Electronic Business. All rights reserved.

Resistance Analyses of Patient Viral Samples from the Remdesivir Phase 3 Adaptive COVID-19 Treatment Trial-1 (ACTT-1)

Background. Remdesivir (RDV) is a broad-spectrum nucleotide analog prodrug approved for the treatment of COVID-19 in non-hospitalized and hospitalized adult as well as pediatric patients with clinical benefit demonstrated in multiple Phase 3 trials. Here we present SARS-CoV-2 resistance analyses from the Phase 3 ACTT-1 placebo-controlled clinical trial in hospitalized adults. Methods. Oro- or nasopharyngeal swab samples in ACTT-1 study were collected on Day 1, 3, 5, 8, 11, 15, and 29. All participants with >80th and 50% of participants with < 20th percentile of cumulative viral shedding underwent resistance analysis in both the RDV and placebo arm. The SARS-CoV-2 genome was sequenced using next generation sequencing. Phenotyping was conducted using virus isolation from clinical samples or generation of select site-directed mutants (SDMs) in a SARS-CoV-2 replicon system. Results. The majority of the sequencing data were obtained from participants with 80th percentile of cumulative viral shedding from the RDV and placebo arms as shown in Table 1. Among participants with both baseline and postbaseline sequencing data, emergent substitutions in nsp12 were observed in 12 of 31 participants (38.7%) treated with RDV and 12 of 30 participants (40.0%) in the placebo arm. The nsp12 substitutions that emerged in the RDV arm were only observed in one participant each, and the majority were present as mixtures with wildtype sequence. The following nsp12 mutations emerged in the RDV treatment group and were successfully phenotyped as clinical isolates or SDMs with low to no fold change in RDV susceptibility: A16V (0.8-fold), P323L+V792I (2.2-fold), C799F (2.5-fold), K59N (1.0-fold), and K59N+V792I (3.4-fold). V792I and C799F were identified previously in vitro in resistance selection experiments (Stevens Sci Transl Med 2022). In addition, for D684N and V764L identified in the RDV arm, the recovery of neither clinical isolates nor SDMs for phenotypic analysis were successful. Conclusion. The similar rate of emerging nsp12 substitutions in participants treated with RDV compared to placebo and the minimal to no change in RDV susceptibility among the treatment-emergent nsp12 substitutions support a high barrier to RDV resistance development in COVID-19 patients.

EDP-235, A Potent and Once-daily Oral Antiviral, Demonstrates Excellent Penetration into Macrophages and Monocytes, with the Potential for Mitigation of Cytokine Storm in High-Risk COVID-19 Patients

Background. Macrophages, including lung alveolar macrophages (AM), and monocytes are the first lines of defense against SARS-CoV-2. Several reports have suggested that SARS-CoV-2 can hijack AM and monocytes for replication and viral spread, which may, in turn, drive the cytokine storm associated with severe COVID-19. Herein, we describe one of many advantageous features that EDP-235, a novel and potent SARS-CoV-2 3C-like protease (3CLpro) inhibitor under development as a once-daily oral antiviral therapy for COVID-19, displays - excellent penetration into macrophages and monocytes. Methods. Intracellular uptake of EDP-235 was tested side-by-side with nirmatrelvir in rat lung AM, human monocytes and human macrophages. To determine the in vivo drug distribution into lung AM, rats were dosed orally with 25 mg/kg of EDP-235 or nirmatrelvir and plasma andAMdrug levels were analyzed by LC/MS/MS. Results. The ratios of intracellular to extracellular concentrations of EDP-235 in rat lung AM, human monocytes and human macrophages were 22.8, 22.7 and 30.5, respectively. In contrast, nirmatrelvir had ratios of 1.2 to 1.5 in these cells. Consistent with the in vitro observations, EDP-235 showed favorable rat AM penetration with an AUC0-24 ratio of 28.4 (AM over plasma), and nirmatrelvir had much less rat AM penetration with an AUC0-24 ratio of 0.5 (AM over plasma). EDP-235 had respective AUC0-24 values of 9.6 and 271.9 h*mug/mL in rat plasma and AM, while the AUC0-24 values of nirmatrelvir in rat plasma and AM were 2.7 and 1.2 h*mug/mL, respectively. Conclusion. EDP-235, a novel and potent SARS-CoV-2 3CL protease inhibitor, demonstrated excellent penetration into monocytes and macrophages, including lung AM. EDP-235 has the potential to eliminate the viral replication of SARS-CoV-2 in these critical immune cells, thus mitigating macrophage-mediated cytokine storm in high-risk COVID-19 patients. Clinical trials with EDP-235 for COVID-19 treatment and prevention are ongoing.

Viral and Immunologic biomarkers of COVID-19 improve risk stratification and identify patients most likely to benefit from therapy with remdesivir

Background. ACTT-1 demonstrated clinical efficacy of remdesivir (RDV) in hospitalized patients with COVID-19;subgroup analyses suggested those most likely to benefit presented with milder clinical illness. To further clarify what subsets of hospitalized patients might benefit from RDV, we analyzed virological and immunological biomarkers in this previously reported cohort. Methods. Serum and upper respiratory tract (URT) swabs were collected on Day 1, 3, 5, 8, and 11 while hospitalized;Day 15 and 29 as able were collected and tested for quantitative RNA (URT and plasma), serum nucleoprotein (NPR), IL-6, CRP through Day 6, and serostatus (baseline only). Participants with a baseline and at least one subsequent sample were used in this analysis. Associations of all these biomarkers with clinical outcomes (mortality, recovery) and response to therapy were assessed. Of the 1062 participants in ACTT-1, 642 had baseline and at least one subsequent sample within 6 days of randomization (Fig 1, Table 1). Results. RDV-treated patients with moderate/severe disease who had elevated baseline NPR levels recovered faster (RRR 1.95 vs 1.04, p = 0.01);similar trends were noted for plasma and URT RNA levels (Fig 2A);mortality treatment effects by viral load subgroups (high or low) were not seen (Fig 2B). In patients with less severe illness, RDV treatment was associated with an accelerated decline in NPR (difference -0.062 log10 pg/ml per day, p = 0.003) and plasma RNA levels (difference -0.040 log10 pg/ml per day, p = 0.004. Fig 3A), and a decrease in the proportion of patients with increasing and/or persistent viral loads (Fig 3B). Patients with increasing/persistent viral loads also took longer to recover than those with decreasing viral loads, irrespective of disease severity: RRR for plasma RNA 0.45, 95% CI 0.28-0.73, RRR for NPR 0.44, 95% CI 0.22-0.88 for moderate/severe disease;RRR for plasma RNA 0.26, 95% CI 0.10 - 0.70 , RRR for NPR n.e. (no recoveries) for critical disease (Fig 4). Conclusion. Our study demonstrates a systemic antiviral effect of remdesivir, shows the prognostic value of viral and immunologic biomarkers for mortality and failure to recover, and identifies a group of hospitalized patients with COVID-19 most likely to benefit from remdesivir treatment. (Figure Presented).

BNT162b2 mRNA SARS-CoV- 2 vaccination does not cause upregulation of endothelial activation markers or hypercoagulability: A prospective, single-arm, longitudinal study

Background: Reports of thrombosis post COVID-19 mRNA vaccination have sparked concerns about safety. Aim(s): We prospectively evaluated blood samples of 18 participants who had received 2 doses of the BNT162b2 mRNA vaccine to determine if vaccination results in endothelial activation or hypercoagulability. Method(s): 18 participants who received the BNT162b2 vaccine were enrolled. Participants completed a questionnaire on their cardiovascular and thrombotic risk factors. Blood samples were collected at three time points: Pre-vaccination (day of vaccination), a median of 17 (IQR 16-18) days after the first dose and a median of 9 (IQR 7.5-14.5) days after the second dose of BNT162b2 vaccine. Endothelial markers included ICAM-1, VCAM-1 and P-selectin. Coagulation tests included PT and aPTT with clot waveform analysis, von Willebrand factor levels, Factor VIII and D-dimer levels. Statistical tests of association between endothelial and coagulation parameters were performed with repeated measures ANOVA and Mauchly's test of sphericity. Result(s): The median age of the participants was 35 years (IQR 31 -44), and 14 (78%) were female. 15 did not have any cardiovascular risk factors. There was a statistically significant increase in median ICAM levels post first (66.1ng/ml) and second dose of vaccination (69.5ng/ml)(p = 0.04), although this remained within the normal limit of ICAM levels. A statistically significant decrease in median PT (p = 0.005) and aPTT (p = 0.03) was observed post vaccination, with a corresponding statistically significant increase in aPTT clot waveform analysis (CWA) for maximum acceleration (max2)(p = 0.03) and maximum deceleration (max2)(p = 0.04) post first and second dose of vaccination. However, all evaluated endothelial and coagulation parameters remain within the reference ranges (Table 1). Conclusion(s): Our findings provide reassuring preliminary data that BNT162b2 vaccination does not result in endothelial activation or hypercoagulability. Mild variations in endothelial markers and coagulation parameters, though statistically significant, remain within the reference ranges and may be related to an inflammatory immune response to vaccination. (Table Presented).

The Localization of International Anti-pandemic Aid Through Decentralized NGOs: The Example of Nanjing’s Aid to the International Cities of Peace in Africa During the COVID-19 Pandemics

This chapter discusses the special significance of localized aid during the COVID-19 pandemic, and demonstrates the feasibility and effectiveness of the localization of aid and community governance through decentralized NGOs by examining the example of the actions taken by Nanjing University (the UNESCO Chair on Peace Studies), Nanjing, China, and the International Cities of Peace in assisting Africa’s Cities of Peace in the fight against the COVID-19 pandemic. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Remote Assessment of Physical Function in Adults with Cerebral Palsy: A Feasibility Study

Background and Objective(s): In pediatric-onset conditions such as cerebral palsy (CP), physical function may continue to decline with age. For many individuals, however, these changes may not be addressed by health care providers once patients transition to adulthood. This has been further exacerbated by COVID-19 which has limited or suspended non-essential, in-person clinical visits. As a result, remote delivery of health care has taken on greater importance. The purpose of this study was to determine the feasibility of remotely assessing physical function in adults with cerebral palsy. The Short Physical Performance Battery (SPPB) was used as the primary outcome assessment since it covers balance, functional strength, and mobility. Study Design: Prognosis study with a cross-sectional design. Study Participants & Setting: Twenty adults with CP (Mean age=44.1+/-10.8) and GMFCS I to III were recruited using CP support groups on social media sites. The assessments were performed in the participant's home and monitored using video conferencing software. Participants were given written instructions as to how to set up their at-home testing area so that their movements could be properly observed. Materials/Methods: All components of the SPPB were administered, including timed measures of balance (side by side, semi-tandem, tandem), gait speed, and repeated chair stand. Additional tests included the Timed Up and Go, the Romberg Test, and the reaching and manipulation components of the Wolf Motor Function Test (WMFT). Result(s): Feasibility was assessed based on the number of participants who were able to complete all assessments, do so safely without any adverse events such as loss of balance, and complete the assessments so that their scores fell within the standardized norms. The average testing time was 32 +/-6.9 min. Nineteen adults (95%) completed all assessments. Sixteen (80%) adults were able to complete the assessments without any adverse events (momentary loss of balance). Ten adults had SPPB scores that fell within the normative SPPB range. Lower SPPB scores were indicative of a slower working pace or the use of an assistive device (e.g., posterior walker). All 20 participants fell within the normative values for the 9 WMFT items. Conclusions/Significance: This feasibility study shows that remote assessment of physical function can be performed accurately and efficiently in adults with CP who do not use assistive devices. For those with more limited mobility, assessing function remotely may still be of value. However, it is important that assessments of physical function are designed or adapted for those with mobility differences. Future studies are needed that incorporate modifications to existing assessment methods to gain a better understanding of physical ability in adults with CP regardless of functional status.

Patient- and provider-level factors associated with telehealth utilization across a multisite, multiregional cancer practice

Background: In response to the COVID-19 pandemic, many cancer practices adopted telehealth, including telephone and video appointments. Following a period of initial expansion that began in March 2020, sustained telehealth integration has emerged across the Mayo Clinic Cancer Practice (MCCP) in 2021. The primary objective of this study was to identify factors associated with utilization of telehealth appointments. Methods: A cross-sectional, multi-site, retrospective analysis was conducted across MCCP - a multisite, multiregional cancer practice with tertiary referral campuses in Minnesota, Florida, and Arizona, as well as rural, community-based hospitals and clinics throughout the Upper Midwest. Multivariable models were used to examine the association of patient- and provider-level variables with telehealth utilization. Results: Outpatient appointments conducted in July - August 2019 (n = 32,932) were compared with those from 2020 (n = 33,662) and 2021 (n = 35,486). The rate of telehealth appointment utilization increased from <0.01% in 2019 to 11.0% in 2020 and 14.0% in 2021. The strongest provider-level predictor of telehealth utilization was female physician provider type (OR 1.06, 95% CI 1.01 to 1.11;P = 0.0297), a trend consistently observed across career stages, practice locations and settings in 2020 and 2021. Additionally, while the rate of telehealth utilization was not significantly different at referral and community-based campuses in 2020, providers at referral campuses were significantly more likely to utilize telehealth than community-based campuses in 2021 (OR 1.1, 95% CI 1.01 to 1.12;P = 0.0289). Regarding patient-level factors, rural residence (defined by Rural-Urban Commuting Area codes), which accounted for 44.2% of the patient population, was significantly associated with lower telehealth utilization as compared to patients with urban residences, particularly for video appointments (OR 1.04, 95% CI 1.02 to 1.07;P < 0.0001). Notably, the disparity in telehealth utilization between rural and urban populations was found to be less pronounced in 2021 as compared to 2020. Conclusions: Multivariable analysis across a multi-site, multi-regional cancer practice identified several factors associated with increased telehealth utilization. These included female physician provider type, referral-based campuses, and patients residing in urban settings. A detailed understanding of the factors that influence telehealth utilization - a method of care delivery which represents a “new normal” across many cancer practices - will be essential to enable continued equitable access to high-quality, high-impact, patient-centered cancer care.

The safety assessment of COVID-19 vaccine injection in patients with colorectal cancer

Background: With the unprecedented morbidity and mortality associated with the COVID-19 pandemic, vaccine against COVID-19 has been more and more popularized in general population. However, the safety of COVID-19 vaccine injection in patients with malignant tumors, such as colorectal cancer (CRC), remains unclear. Methods: During January 2021 and January 2022, 148 CRC patients treated in the department of colorectal surgery in the Sixth Affiliated Hospital of Sun Yat-sen University were enrolled in this cohort. The clinical data and COVID-19 vaccine injection outcome data was collected and analyzed retrospectively. Patients who received at least one dose of COVID-19 vaccine injection were set as an observation group and those who did not get any vaccine injection were set as a control group. The median follow-up time was 8.0 months, vaccine-related adverse events (VRAEs) were collected by questionnaire. The disease progression status of CRC was also compared between the two groups. Results: Eighty-three CRC (male: female 44:39) patients enrolled in this study have got at least one dose of COVID-19 vaccine injection, with a median follow-up time of 8.0 (2.0-13.0) months and no VRAEs reported. Among the vaccinated patients, 51 patients were injected with inactivated vaccine (Sinovac Life Sciences Co., Ltd.), 10 patients were vaccinated with inactivated vaccine (Beijing Institute of Biological Products Co., Ltd.), others were injected another inactivated vaccine (Chengdu Institute of Biological Products Co., Ltd.). The reasons of the 65 patients (male: female 36:29) who did not injected COVID-19 vaccine including: 53 patients had a concern that vaccination will affect the progress of CRC, 8 patients had a concern of old age to get vaccinated and 4 patients did not give any reason. As for disease progression, 14 patients in the observation group had tumor recurrence or progression, while 8 patients in control group reported tumor recurrence or progression, with a median follow-up time of 8.0 (2.0-13.0) months. There was no significant difference in short-term disease progression between the observation group and the control group (P = 0.439). Conclusions: Under the background of COVID-19 pandemic and vaccination of general population, it might be necessary for the patients with malignant disease, such as CRC, to get vaccinated due to whose weaken immune system. COVID-19 vaccine injection is safe for CRC patients and COVID-19 vaccination would not affect the patients' prognosis.