ABSTRACT
Air pollution, especially the continual increase in atmospheric particulate matter (PM), is a global environmental challenge. To reduce the PM concentration, a remarkable amount of machine learning-based research has been proposed. However, increasing the accuracy of the predictions and providing clear interpretations of the predictions are challenging. In particular, no studies have addressed models that predict and interpret PM before and during the COVID-19 pandemic. In this paper, we present a two-step predictive and explainable model to obtain insights into reducing PM. We first use attentive multi-task learning to predict the air quality of cities. To accurately predict the concentration of particles with sizes of similar to 10 mu m or similar to 2.5 mu m (PM10 and PM2.5, respectively), we demonstrate a performance difference between single-task and multi-task learning, as well as among the state-of-the art methods. The proposed attentive model with multi-task learning outperformed the others in terms of accuracy performance. We then used Shapley additive explanations, a representative explainable artificial intelligence framework, to interpret and determine the significance of features for predicting PM10 and PM2.5. We demonstrated the superiority of the proposed approach in predicting and explaining both PM10 and PM2.5 concentrations, and observed a statistically significant difference in air pollution before and during the COVID-19 pandemic.
ABSTRACT
The present study investigated patrons' intricate psychological process for hotel brand choice and preference. This research uncovered hotel selection attributes in shaping brand loyalty through customer experience, brand trust, brand attachment, age, and gender in the post-pandemic world. This paper categorized hotel selection attributes into that vacationers appreciate in the domestic tourism context. The findings indicated the significant effect of hotel selection attributes on customer experience, which in turn affect brand preference. Also, the moderating effect of age was identified in the relationship between hotel selection attributes and customer experience. This research is among the first to revisit hotel selection attributes for domestic tourism amid the pandemic and the way to cultivate the loyalty toward a hotel brand.
ABSTRACT
Multinational firms can outsource to contract manufacturers in low-labor-cost regions. However, in recent years, several developed countries and regions have subsidized their local manufacturers (LM[s], she) to encourage reshoring for external benefit (e.g., creating more domestic jobs or improving industrial struc-ture), especially after the COVID-19 pandemic started. This paper investigates the sourcing problem of an LM with brand premium in the presence of government subsidy and differences in labor costs. An LM faces three options: producing in-house, outsourcing to an original brand manufacturer (OBM, he), which sells competitive substitutes without brand premium, or outsourcing to a non-competing contract manu-facturer (NCM). We find that, first, the LM chooses reshoring if the external benefit or brand premium is sufficiently high. Second, if the LM decides to outsource, she chooses the OBM (NCM) if her brand pre-mium is high (low). Third, the government prefers to subsidize LM reshoring or outsourcing to an NCM. If the government intends to induce LM to reshore, the subsidy should be at a moderate level. Interestingly, when the LM has a low brand premium but chooses outsourcing, the government still subsidizes her to improve her competitiveness.(c) 2022 Elsevier B.V. All rights reserved.
ABSTRACT
Sentiment classification is a valid measure to monitor public opinion on the COVID-19 epidemic. This study provides a significant basis for preventing the spread of adverse public opinion. Firstly, in epidemic texts, we use a convolutional neural network and bidirectional long short-term memory neural network BiLSTM model to classify and analyze the sentiment of the comment texts about the epidemic situation on Weibo. Secondly, embedded in the model layer to generate adversarial samples and extract semantics. Then, semantic information is weighted using the attention mechanism. Finally, the RMS optimizer is used to update the neural network weights iteratively. According to comparative experiments, the experimental results show that such four evaluation metrics as accuracy, precision, recall, and f1-score with our proposed model have obtained better classification performance. © 2022 IEEE.
ABSTRACT
Human mobility triggers how fast and where infectious diseases spread and modelling community flows helps assess the impact of social distancing policies and advance our understanding of community behaviour in such circumstances. This study investigated the relationship between human mobility and the surging incidence of COVID-19 in India. We performed a generalised estimating equation with a Poisson log-linear model to analyse the daily mobility rate and new cases of COVID-19 between 14 March and 11 September 2020. We found that mobility to grocery and retail locations was significantly associated (p < 0.01) with the incidence of COVID-19, these being crowded and unorganised in most parts of India. In contrast, visits to parks, workplaces, and transit stations did not considerably affect the changing COVID-19 cases over time. In particular, workplaces equipped with social distancing protocols or low-density open spaces are much less susceptible to the spread of the virus. These findings suggest that human mobility data, geographic information, and health geography modelling have significant potential to inform strategic decision-making during pandemics because they provide actionable knowledge of when and where communities might be exposed to the disease.
ABSTRACT
Since the outbreak of COVID-19, tourists have been increasingly concerned over various risks of international travel, while knowledge of the pandemic appears to vary significantly. In addition, as travel restrictions continue to impact adversely on international tourism, tourism efforts should be placed more on the domestic markets. Via structural equation modeling, this study unearthed different risk factors impacting Korean travelers' choices of alternative local destinations in the post-pandemic era. In addition, this study extended the goal-directed behavior framework with the acquisition of perceived risk and knowledge of COVID-19, which was proven to hold a significantly superior explanatory power of tourists' decisions of local alternatives over foreign countries during the COVID-19 pandemic. Furthermore, desire was found to play an imminent mediating role in the conceptual mod-el, maximizing the impact of perceived risk on travel intentions. Henceforth, this research offers meaningful theoretical implication as the first empirical study to deepen the goal-directed behaviour framework with perceived risk and knowledge in the context of post-COVID-19 era. It also serves as insightful knowledge for Korean tourism authorities and practitioners to understand local tourists' decision-making processes and tailor effective recovery strategy for domestic tourism.”. © 2023, Tech Science Press. All rights reserved.
ABSTRACT
Gastronomy tourism is a critical driver of regional economic development and socio-cultural renaissance. It has been advocated as part of the tourism recovery initiatives in regards to boosting the worldwide economy in the wake of the COVID-19 pandemic. Using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) protocol, 397 empirical articles from leading hospitality and tourism journals were systematically examined. This review brought attention to significant developments by using a combination of descriptive analysis, conceptual framework, and topic modeling. Several salient literature gaps and future research directions were amalgamated by utilizing the theory, context, characteristics, and methodology (TCCM) framework. © 2023 Informa UK Limited, trading as Taylor & Francis Group.
ABSTRACT
BACKGROUND: Disinfection is one of the most effective ways to block the rapid transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Due to the prolonged coronavirus disease 2019 (COVID-19) pandemic, disinfectants have become crucial to prevent person-to-person transmission and decontaminate hands, clothes, facilities and equipment. However, there is a lack of accurate information on the virucidal activity of commercial disinfectants. AIM: To evaluate the virucidal efficacy of 72 commercially available disinfectants constituting 16 types of ingredients against SARS-CoV-2. METHODS: SARS-CoV-2 was tested with various concentrations of disinfectants at indicated exposure time points as recommended by the manufacturers. The 50% tissue culture infectious dose assay was used to calculate virus titre, and trypan blue staining and CCK-8 were used to assess cell viability after 3-5 days of SARS-CoV-2 infection. FINDINGS: This study found that disinfectants based on 83% ethanol, 60% propanol/ethanol, 0.00108-0.0011% sodium dichloroisocyanurate and 0.497% potassium peroxymonosulfate inactivated SARS-CoV-2 effectively and safely. Although disinfectants based on 0.05-0.4% benzalkonium chloride (BAC), 0.02-0.07% quaternary ammonium compound (QAC; 1:1), 0.4% BAC/didecyldimethylammonium chloride (DDAC), 0.28% benzethonium chloride concentrate/2-propanol, 0.0205-0.14% DDAC/polyhexamethylene biguanide hydrochloride (PHMB) and 0.5% hydrogen peroxide inactivated SARS-CoV-2 effectively, they exhibited cytotoxicity. Conversely, disinfectants based on 0.04-4% QAC (2:3), 0.00625% BAC/DDAC/PHMB, and 0.0205-0.14% and 0.0173% peracetic acid showed approximately 50% virucidal efficacy with no cytotoxicity. Citric acid (0.4%) did not inactivate SARS-CoV-2. CONCLUSION: These results indicate that most commercially available disinfectants exert a disinfectant effect against SARS-CoV-2. However, re-evaluation of the effective concentration and exposure time of certain disinfectants is needed, especially citric acid and peracetic acid.
ABSTRACT
Working with study participants in community-based clinical trials during COVID-19 pandemic has created diverse challenges to study teams. Globally, COVID-related restrictions were implemented including country-wide lockdowns and social distancing, and study teams had to quickly adjust their study protocols to work in a virtual environment. Meeting virtually for recruitment activities or intervention delivery may be particularly challenging when the target group is older adults—one of the vulnerable populations to experience the digital divide due to limited digital access and limited digital literacyThis symposium covers the lessons learned related to use of digital technology in participant recruitment and intervention delivery across a range of populations, including community-dwelling Korean American older adults to African American older women living with pain and low mood, caregivers of persons living with heart failure, and low-income cancer survivors with multiple chronic conditions. The discussion will include 1) findings from screening over 1,000 older Korean Americans to enroll them into a multi-site community-based trial, 2) lessons in diversifying intervention delivery methods to African American older women, 3) the integration of virtual modality into a self-care and social support intervention for caregivers of persons with heart failure, and 4) the deployment of mHealth to deliver a home-based exercise program to ethnically diverse low-income cancer survivors with co-morbid conditions in the setting of the COVID-19 pandemic. This symposium seeks to build the evidence related to recruitment and intervention delivery targeting diverse groups of older adults in community settings using technology by sharing common challenges, experiences, and opportunities.
ABSTRACT
Page 5452. In the "2.1. Preparation of CCM-CDs" section in the Experimental Section, "Curcumin (CCM;0.30 g) and citric acid (0.60 g) were ground uniformly, sealed, and hydrothermally treated in a 25 mL Teflon-lined autoclave at 180 C for 1 h." was incorrectly written. It should be "Curcumin (CCM;0.30 g) and citric acid (0.60 g) were ground uniformly, sealed, and hydrothermally treated in a 25 mL Teflon-lined autoclave at 180 C for 1.5 h.". This change does not affect the conclusion of this paper. Page 5455. In the caption of Figure 6c, "Virus titers calculated in the presence and absence of EDA-CDs or CCMCDs. The pictures were taken at 12 hpi." was incorrectly written. It should be "Virus titers calculated in the presence and absence of EDA-CDs or CCM-CDs. The pictures were taken at 9 hpi.". In addition, the fluorescence images of the DAPI and Merge in the EDA-CDs (125 g/mL) group (Figure 6a) were chosen by mistake when the artwork was submitted. These changes do not affect the conclusion of this paper. The revised Figure 6a, which now shows the correct images from the original data source, is as follows: (Figure Present). © 2022 American Chemical Society. All rights reserved.
ABSTRACT
In the COVID-19 pandemic, vaccines have emerged as the most effective tool to protect people from COVID-19. However, there is a limited study of adverse events (AEs) for COVID-19 vaccines among people with type 2 diabetes. The purpose of this study is to report the common adverse events following the COVID-19 vaccines, mRNA-1273, BNT162b2, and JNJ-78436735 in diabetic patients. We collected data for common adverse events to the COVID-19 vaccines using Vaccine Adverse Event Reporting System (VAERS). To identify the people with and without diabetes, we used the Natural language processing algorithms. After a 1:3 propensity score matching, we used 6,829 people with type 2 diabetes and 20,487 healthy control groups. Multiple logistic regression analysis was performed to obtain the odds ratio for 25 common AEs in order of high frequency. The most common AEs were pain (17.9%), headache (16.6%), pyrexia (13.4%), chills (12.4%), fatigue (12.0%), dizziness (11.0%). In particular, AEs of the dysmenorrhea in women were rare (0.14%), but a 15-fold higher frequency was observed in patients with diabetes (0.45% versus 0.03%) than in those with controls. The risk of all common AEs following both mRNA vaccines was significantly lower (OR = 0.87, 95% CI = 0.77–0.97, P = 0.015) than that after one viral vector vaccine, as well as the risk among males (OR = 0.56, 95% CI = 0.53–0.59, P < 0.001) was lower than among females. In conclusion, the risk of common adverse events among people with type 2 diabetes was low after both mRNA vaccines and in males. These findings might have implications for safe vaccine use. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.
ABSTRACT
The COVID-19 pandemic prompted many discussions about how people's trust in science shaped our ability to address the crisis. Early in the pandemic, our research team set out to understand how trust in science relates to support for public health guidelines, and to identify some trusted sources of science. In this essay, we share our findings and offer ideas about what might be done to strengthen the public's trust in science. Notably, our research shows a stark partisan divide: Republicans had lower support for public health guidelines, and their trust in science and institutions such as the Centers for Disease Control and Prevention and the National Institutes of Health eroded over time. Meanwhile, Democrats' trust in science has remained high throughout the pandemic. In the context of this divide, we explore how trust in various information sources, from governmental institutions to the media, relates to trust in science, and suggest that the best avenue for rebuilding trust might be through empowering local institutions and leaders to help manage future crises.
ABSTRACT
This research aims to explore the intricate nature of the association between green attitudes and well-being in the workplace. Based on the basic human value theory, this study attempted to unearth the moderating effects of its two main bipolar segments, namely self-transcendence-self-enhancement and openness to change-conservation. A quantitative approach with a sample of 1,532 hospitality employees from 35 European countries was used. We found that a green attitude contributes to deriving employee well-being. Further, we found empirical support for the influence of human values, in the sense that this relationship is reinforced among the workers who are more altruistic and receptive to changes. Moreover, this research suggests strategies oriented to reduce environmental degradation and achieve sustainable development in the hospitality sector. This article provides ideas to cope with the challenges posed by COVID-19, particularly in the hospitality industry seriously damaged by the pandemic where the future of many jobs is in jeopardy. © 2022, Tech Science Press. All rights reserved.
ABSTRACT
Purpose: To investigate the mechanisms of action of Wei-Sheng-Fang-Yi-Bao-Dan (WSFYBD) in the treatment of COVID-19 and depression using network pharmacology and molecular docking. Method(s): First, the bioactive components and target genes of WSFYBD were retrieved from TCMSP database. The relevant gene targets of depression and COVID-19 were obtained from databases. The core WSFYBD genes for treatment were separately obtained by determining gene intersection. Cytoscape 3.8.0 software was used to draw the visual interactive networks. STRING database was employed to construct protein-protein interaction networks, while Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were used to determine the function and pathway of target genes via a Bioconductor/R. Finally, AutoDockTools software was employed for molecular docking. Result(s): A total of 105 potential bio-active components and 35 target genes of WSFYBD for COVID-19 therapy were identified. Also, 1905 GO entries (p < 0.05) and 158 related signal pathways (p < 0.05) for COVID-19 were obtained. Similarly, 114 potential bio-active components of WSFYBD and 127 potential therapeutic targets of depression were identified. Moreover, 1948 GO entries (p < 0.05) and 177 related signal pathways for depression were retrieved (p < 0.05). Docking results showed the main bio-active components were closely bound to the core targets. Conclusion(s): The mechanisms for treating COVID-19 show that WSFYBD directly acts on SARS-CoV-2 virus to prevent it from entering the host cell, or inhibits virus replication. Secondly, WSFYBD ameliorates depression by acting on key targets that control over-activated cytokines. Therefore, WSFYBD has potentials for the management of COVID-19 and depression. Copyright © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. © 2022 The authors. This work is licensed under the Creative Commons Attribution 4.0 International License.
ABSTRACT
Due to influence of COVID-19, telemedicine is becoming more and more important. High-quality medical videos can provide a physician with a better visual experience and increase the accuracy of disease diagnosis, but this requires a dramatic increase in bandwidth compared to that required by regular videos. Existing adaptive video-streaming approaches cannot successfully provide high-resolution video-streaming services under poor or fluctuating network conditions with limited bandwidth. In this paper, we propose a super-resolution-empowered adaptive medical video streaming in telemedicine system (named SR-Telemedicine) to provide high quality of experience (QoE) videos for the physician while saving the network bandwidth. In SR-Telemedicine, very low-resolution video chunks are first transmitted from the patient to an edge computing node near the physician. Then, a video super-resolution (VSR) model is employed at the edge to reconstruct the low-resolution video chunks into high-resolution ones with an appropriate high-resolution level (such as 720p or 1080p). Furthermore, the neural network of VSR model is designed to be scalable and can be determined dynamically. Based on the time-varying computational capability of the edge computing node and the network condition, a double deep Q-Network (DDQN)-based algorithm is proposed to jointly select the optimal reconstructed high-resolution level and the scale of the VSR model. Finally, extensive experiments based on real-world traces are carried out, and the experimental results illustrate that the proposed SR-Telemedicine system can improve the QoE of medical videos by 17–79% compared to three baseline algorithms. © 2022 by the authors.
ABSTRACT
Background: CSCC is highly immune-responsive;a prior pilot study demonstrated a high rate of pathologic complete response (pCR) or major pathologic response (MPR, ≤10% viable tumor), using cemiplimab anti-programmed death 1 (PD-1) therapy in the neoadjuvant setting. Here, we present the primary analysis of a confirmatory, open-label, multicenter, Phase 2, single-arm trial of neoadjuvant cemiplimab in pts with resectable Stage II–IV (M0) CSCC. Methods: Pts received cemiplimab 350 mg IV q3W for up to 4 doses before surgery. The primary endpoint was pCR rate per independent central pathologic review (ICPR). Key secondary endpoints included MPR rate per ICPR, objective response rate (ORR;complete response [CR] + partial response [PR]) per RECIST v1.1, investigator-assessed pCR and MPR, safety and tolerability. Results: At data cutoff date of 01 Dec 2021, 79 pts were enrolled (67 male;median age 73.0 yrs [range, 66.0–81.0];ECOG performance status 0 (n=60) and 1 (n=19) with stage II (n=5), III (n=38), or IV(M0) (n =36) disease;62 pts received all 4 doses (median number of doses given (Q1:Q3), 4 (4:4);70 pts underwent surgery. The study met its primary endpoint: pCR was observed in 40 (50.6%) pts (95% confidence interval [CI], 39.1–62.1%). MPR was observed in an additional 10 (12.7%) pts (95% CI, 6.2–22.0%). ORR was 68.4% (95% CI, 56.9–78.4) (5 CR, 49 PR, 16 stable disease, 8 progressive disease (PD), 1 non evaluable. Reasons 9 pts did not have surgery: 3 responders declined surgery, 2 lost to follow-up or noncompliance, 2 had inoperable PD, 2 due to AE. Fourteen (17.7%) pts experienced Grade ≥3 AE. Four pts died due to AEs: 1 exacerbation of cardiac failure, 2 myocardial infarctions, and 1 COVID-19 pneumonia. The most common AEs regardless of attribution (all grades) were fatigue (30.4%), rash maculo-papular (13.9%), diarrhea (13.9%) and nausea (13.9%). Conclusions: The pCR + MPR of 63.3% by ICPR in pts with Stage II–IV (M0) CSCC is the highest observed in a multicenter anti-PD-1 neoadjuvant monotherapy study for any solid tumor type. The safety profile of neoadjuvant cemiplimab is consistent with previous anti-PD-1 monotherapy experience. Ongoing follow-up will describe disease-free survival. Clinical trial identification: NCT04154943. Editorial acknowledgement: Medical writing support was provided by John G Facciponte, PhD, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc., and Sanofi. Legal entity responsible for the study: Regeneron Pharmaceuticals, Inc., and Sanofi. Funding: Regeneron Pharmaceuticals, Inc., and Sanofi. Disclosure: N. Gross: Financial Interests, Personal, Research Grant: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Advisory Board: PDS Biotechnology, Shattuck Labs and Genzyme;Financial Interests, Personal, Advisory Role: PDS Biotechnology, Shattuck Labs and Genzyme. D.M. Miller: Financial Interests, Personal, Advisory Role: Castle Biosciences, EMD Serono, Merck KGaA, Merck Sharpe & Dome, Pfizer, Regeneron, Sanofi Genzyme;Financial Interests, Personal, Ownership Interest: Checkpoint Therapeutics;Financial Interests, Personal, Research Grant: Kartos Therapeutics, NeoImmune Tech, Inc., Regeneron Pharmaceuticals, Inc. N. Khushanlani: Financial Interests, Personal, Research Grant: Regeneron Pharmaceuticals, Inc., Bristol Myers Squibb, HUYA Bioscience International, Merck, Novartis, GlaxoSmithKline, Celgene, Amgen;Financial Interests, Personal, Advisory Board: EMD Serono, Regeneron Pharmaceuticals, Inc., Genentech, AstraZeneca (data safety monitoring committee), Merck, Array Biopharma, Jounce Therapeutics, Immunocore, Bristol Myers Squibb, HUYA Bioscience International;Financial Interests, Personal, Other, honoraria: Sanofi;Financial Interests, Personal, Stocks/Shares: Bellicum Pharmaceuticals, Mazor Robotics, Amarin, Transenetrix. V. Divi: Financial Interests, Institutional, Research Grant: Genentech. E.S. Ruiz: Financial Interests, Personal, Advisory Board: Genentech, Leo Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Sanofi;Financial Int rests, Personal, Advisory Role, consulting fees: Genentech, Leo Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Sanofi;Financial Interests, Personal, Member of the Board of Directors: Checkpoint Therapeutics. E.J. Lipson: Financial Interests, Personal, Other, Advisory board and consulting fees: Bristol Myers-Squibb, Eisai, Genentech, Immunocore, Instil Bio, MacroGenics, Merck, Natera, Nektar Therapeutics, Odonate Therapeutics, OncoSec, Pfizer, Rain Therapeutics, Regeneron, Sanofi;Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Merck, Regeneron. F. Meier: Financial Interests, Personal, Other, Travel support, speaker’s fees or advisor’s honoraria: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche and Sanofi;Financial Interests, Personal, Research Grant: Novartis and Roche. P.L. Swiecicki: Financial Interests, Institutional, Research Grant: Ascentage Pharma, Pfizer;Financial Interests, Personal, Advisory Board: Prelude Therapeutics, Elevar Therapeutics, Regeneron Pharmaceuticals. J.L. Atlas: Financial Interests, Personal, Advisory Role: Regeneron Pharmaceuticals, Inc., Sanofi, and Bristol Myers Squibb. J.L. Geiger: Financial Interests, Institutional, Research Grant: Alkermes, Debio, Merck, Regeneron Pharmaceuticals, Inc., and Roche/Genentech;Financial Interests, Personal, Advisory Role: Exelixis, Merck and Regeneron Pharmaceuticals, Inc. A. Hauschild: Financial Interests, Personal and Institutional, Other, Institutional grants, speaker’s honoraria and consultancy fees: Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Provectus and Roche;Financial Interests, Institutional, Other, Institutional grants and consultancy fees: EMD Serono, Philogen and Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Advisory Role: OncoSec Medical. J.H. Choe: Financial Interests, Personal, Advisory Role: Exelixis, Coherus Biosciences, Regeneron Pharmaceuticals, Inc. B.G.M. Hughes: Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, Eisai, Merck Sharp & Dohme, Pfizer and Roche;Financial Interests, Institutional, Research Grant: Amgen. S. Yoo: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. K. Fenech: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. M.D. Mathias: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. H. Han: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. M.G. Fury: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. D. Rischin: Financial Interests, Institutional, Research Grant: Regeneron Pharmaceuticals, Inc., Genentech, Sanofi, Kura Oncology, Roche, Merck Sharp & Dohme, Merck KGaA, Bristol Myers Squibb, GlaxoSmithKline, ALX Oncology;Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi, GlaxoSmithKline, Bristol Myers Squibb;Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi, GlaxoSmithKline, Bristol Myers Squibb. All other authors have declared no conflicts of interest.
ABSTRACT
Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer with an incidence of 1 million cases per year in the US. While the surgical cure rate for CSCC is >95%, some patients have high risk of recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension, and prior treatment. Postoperative radiation therapy (RT) is recommended for these patients, but relapse with locoregional recurrence or distant metastases may still occur. C-POST is evaluating the efficacy of cemiplimab as adjuvant therapy for patients with high-risk CSCC. Here, we provide a summary of the most recent study protocol amendment. C-POST is a randomized, placebo-controlled, double-blind, multicenter Phase 3 study to evaluate cemiplimab as adjuvant treatment for patients with high-risk CSCC, based on surgical and clinicopathologic findings, who completed surgery and postoperative RT (minimum total dose 50 Gy, within 10 weeks before randomization) (NCT03969004). Patients with at least one of the following high-risk features are eligible: (1) nodal disease with (a) extracapsular extension and at least one node ≥20 mm or (b) at least three lymph nodes positive on surgical pathology report, regardless of extracapsular extension;(2) in-transit metastases;(3) T4 lesion;(4) perineural invasion;and (5) recurrent CSCC with at least one other risk factor. Patients with CSCC involvement in at least three lymph nodes (feature 1b) were added to the eligibility criteria, as this group was found to be at similar risk of CSCC recurrence as the initially planned study population. Protocol amendment now allows patients with chronic lymphocytic leukemia (CLL) who are not on active treatment to be enrolled. The study has two parts. In Part 1 (blinded), patients are randomly assigned 1:1 to receive cemiplimab 350 mg or placebo intravenously every 3 weeks for 12 weeks, followed by cemiplimab 700 mg or placebo every 6 weeks for 36 weeks. In optional Part 2 (unblinded), patients in the placebo arm who experience disease recurrence and patients in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 are eligible to receive open-label cemiplimab 350 mg Q3W for up to 96 weeks. The trial is expected to enroll 412 patients from about 100 sites in North and South America, Europe, and Asia-Pacific regions. Key primary objective is to compare disease-free survival;secondary objectives include evaluating overall survival, freedom from locoregional relapse, and distant relapse with adjuvant cemiplimab versus placebo in patients with high-risk CSCC. This study is once again open for enrolment following interruptions owing to the COVID-19 pandemic. Not applicable (trial in progress) Not applicable (trial in progress) [ FROM AUTHOR] Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
ABSTRACT
Background: CSCC is the second most common skin cancer with an estimated incidence of 1 million cases per year in the US. While the surgical cure rate for CSCC is > 95%, some pts have high risk of recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension (ECE), and prior treatment. Postoperative RT is recommended for these pts but relapse with locoregional recurrence or distant metastases may still occur. C-POST is evaluating the efficacy of cemiplimab as adjuvant therapy for pts with high-risk CSCC. Here, we provide summary of the most recent study protocol amendment. Methods: C-POST is a randomized, placebo-controlled, double-blind, multicenter Phase 3 study to evaluate cemiplimab as adjuvant treatment for pts with high-risk CSCC, based on surgical and clinicopathologic findings, who completed surgery and postoperative RT (minimum total dose 50Gy, within 10 weeks before randomization) (NCT03969004). Pts with at least one of the following high-risk features are eligible: (1) nodal disease with (a) ECE and at least one node ≥20 mm or (b) at least three lymph nodes positive on surgical pathology report, regardless of ECE;(2) in-transit metastases;(3) T4 lesion;(4) perineural invasion;and (5) recurrent CSCC with at least one other risk factor. Pts with CSCC involvement in at least three lymph nodes (feature 1b) were added to the eligibility criteria, as this group was found to be at similar risk of CSCC recurrence as the initially planned study population. Protocol amendment now allows patients with chronic lymphocytic leukemia (CLL) who are not on active treatment to be enrolled. The study has two parts. In Part 1 (blinded), pts are randomly assigned 1:1 to receive cemiplimab 350 mg or placebo intravenously every 3 weeks for 12 weeks, followed by cemiplimab 700 mg or placebo every 6 weeks for 36 weeks. In optional Part 2 (unblinded), pts in the placebo arm who experience disease recurrence and pts in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 are eligible to receive open-label cemiplimab for up to 96 weeks. The trial is expected to enrol 412 pts from about 100 sites in North and South America, Europe, and Asia-Pacific regions. Key primary objective is to compare disease-free survival;secondary objectives include evaluating overall survival, freedom from locoregional relapse, and distant relapse with adjuvant cemiplimab versus placebo in patients with high-risk CSCC. This study is once again open for enrolment following interruptions owing to the COVID-19 pandemic.
ABSTRACT
Background: Despite the use of multiple lines of targeted therapy has revolutionized treatment for HER2-positive breast cancer, these methods still have limited efficacy for triple-positive breast cancer (TPBC), which calls for persistent exploration for optimized treatment strategy. This MUKDEN-01 prospective trial aimed to evaluate the efficacy of oral, chemo-sparing neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib, which also meet the need for treatment convenience under COVID-19 pandemic, for patients with TPBC. Methods: The MUKDEN 01 was an investigator-initiated, multicentre, single arm, prospective phase II trial, which was performed at twelve hospitals in China( NCT04486911). Treatment-naïve patients with stage II-III tumors that according to the AJCC 8th edition criteria were eligible. Patients were treated with each cycle of 4 weeks with oral administration of pyrotinib 320 mg, and letrozole 2.5mg once daily for 4 weeks, and dalpiciclib 125 mg once daily for three weeks, followed by one week off, for five cycles. The primary endpoint was pathological complete response (pCR) in the breast and axilla (ypT0/is ypN0). Secondary endpoints included pCR in the breast (ypT0/is). residual cancer burden (RCB) score, Ki67 index change at surgery compared with baseline, and safety. Safety was analyzed in all patients, who received treatment. The study is still ongoing, and the enrollment has been completed. Results: Between June 20, 2020 and Sep. 6, 2021, 68 patients were screened for eligibility and 61 patients were recruited into this first stage of study. After surgery, 18 (29.5%, 95% CI 18.5-42.6) out of 61 patients achieving tpCR(ypT0/is ypN0), 21 (34.4%, 95% CI 22.7-47.7) patients achieved bpCR(ypT0/is). The patients with excellent pathologic response (RCB 0-1) to the combined therapy accounted for 54.1% (33/61, 95% CI 40.9-66.9). Mean Ki67 expression was reduced from 38.7% (95%CI: 31.3-46.0) at baseline to 19.3% (95% CI:13.6- 25.0;p=0.0001) in the surgical samples. The most frequent grade 3 AE were neutropenia (35 [57%]), leukopenia (13 [21%]), diarrhea (9 [15%]) and oral mucositis (4 [7%]). There were five grade 4 neutropenia (8%) and one grade 4 increased AST (2%), but without other SAE and death throughout the study. Conclusions: Neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib yielded a pCR rate comparable to standard chemotherapy plus dual HER2 blockade in TPBC patients. The combined therapy was also well-tolerated and provided a chemo-sparing neoadjuvant approach for TPBC patients. To our knowledge, this is the first study to evaluate the therapeutic efficacy of a chemo-free neoadjuvant treatment with HER2 TKI pyrotinib and letrozole plus CDK4/6 inhibitor dalpiciclib for TPBC patients. Further validation in a large-scale randomized controlled trial is warranted.
ABSTRACT
This study uses the Qingdao International Beer Festival as an example to grasp the festival travelers' experience quality. It investigates the critical relations among image factors in forming loyalty intentions for the festival. A psychometric process with qualitative and quantitative approaches is utilized. Community support and perceived risk of virus infection are uncovered as significant moderators, broadening the developed theoretical framework. The proposed theoretical and managerial implications provide orientations for scholars and practitioners in the field of festivals on how to design appropriate festival products and cultivate festive brands during the with-coronavirus era.