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1.
Frontiers in Public Health ; 10:1011592, 2022.
Article in English | MEDLINE | ID: covidwho-2163183

ABSTRACT

Background: Non-pharmaceutical interventions (NPIs) against COVID-19 may prevent the spread of other infectious diseases. Our purpose was to assess the effects of NPIs against COVID-19 on infectious diarrhea in Xi'an, China.

2.
Analytical Chemistry ; 13:13, 2022.
Article in English | MEDLINE | ID: covidwho-2160134

ABSTRACT

Addressing the spread of coronavirus disease 2019 (COVID-19) has highlighted the need for rapid, accurate, and low-cost diagnostic methods that detect specific antigens for SARS-CoV-2 infection. Tests for COVID-19 are based on reverse transcription PCR (RT-PCR), which requires laboratory services and is time-consuming. Here, by targeting the SARS-CoV-2 spike protein, we present a point-of-care SERS detection platform that specifically detects SARS-CoV-2 antigen in one step by captureing substrates and detection probes based on aptamer-specific recognition. Using the pseudovirus, without any pretreatment, the SARS-CoV-2 virus and its variants were detected by a handheld Raman spectrometer within 5 min. The limit of detection (LoD) for the pseudovirus was 124 TU muL-1 (18 fM spike protein), with a linear range of 250-10,000 TU muL-1. Moreover, this assay can specifically recognize the SARS-CoV-2 antigen without cross reacting with specific antigens of other coronaviruses or influenza A. Therefore, the platform has great potential for application in rapid point-of-care diagnostic assays for SARS-CoV-2.

3.
5th International Conference on Pattern Recognition and Artificial Intelligence, PRAI 2022 ; : 966-972, 2022.
Article in English | Scopus | ID: covidwho-2120524

ABSTRACT

In this paper, the compatibility rules and drug combinations of Tibetan medicine prescriptions are explored, and the possible anti-epidemic mechanism is analyzed from the perspectives of biological network and signaling pathway, so as to provide reference for scientifically elaborating the potential value of ancient Tibetan medicine in preventing epidemic diseases. Association rules and clustering analysis are used for Tibetan drug mining. A total of 18 prescriptions involving 113 Tibetan medicinal materials were included, and 26 high-frequency Tibetan medicinal materials with the statistical frequency ≥3 are included, most of which are medicinal materials for clearing heat, detoxicating, eliminating plague. Thirteen potential drug combinations are obtained through association rule analysis. The KMean clustering and hierarchical clustering were used for clustering analysis to obtain five drug clusters, and the "Bamusaeconcretiosilicea - Carthami Flos"combination was selected for network pharmacology research by comparing the two methods. After drug target and pathway analysis, "Bamusaeconcretiosilicea - Carthami Flos"through MAPK cascade, response to oxygen level, reactive oxygen species metabolism process, PI3K-Akt signaling pathway, NF- κ B signaling pathway, cytokine-cytokine Receptor interaction and calcium signaling pathways have certain feasibility for the treatment of immune disease fever in three aspects: immune response, inflammatory response, and oxidative stress. © 2022 IEEE.

4.
Sustainability (Switzerland) ; 14(18), 2022.
Article in English | Scopus | ID: covidwho-2055362

ABSTRACT

In 2020, COVID-19 swept across the globe. To reduce the social harms caused by this public health event, nonprofit organizations (NPOs) cooperated with medical enterprises to produce reserves of emergency medical supplies. In practice, this cooperation was challenged by the different goals of NPOs and medical enterprises and the asymmetry of information between these parties. Enterprises are prone to irregularities or speculative behaviors that can result in insufficient production capacity during public health events, which increase disaster risks. Based on the principal–agent relationship of NPOs and enterprises, this study analyzed a game model between NPOs and enterprises under information asymmetry;constructed an incentive model for reserve emergency medical supply production capacity;and solved the optimal reward and punishment coefficients of NPOs, optimal effort level of enterprises, and benefits of disaster reduction. The study also verified the validity of the model using numerical examples and a sensitivity analysis. In taking up the findings of the study, this paper discusses the effects of several important exogenous variables on the optimal decision strategies of NPOs and enterprises and offers management-related insights for NPOs. © 2022 by the authors.

5.
2022 Ieee International Conference on Communications Workshops (Icc Workshops) ; : 427-432, 2022.
Article in English | Web of Science | ID: covidwho-2042753

ABSTRACT

Social distancing can reduce the infection rates in respiratory pandemics such as COVID-19. Traffic intersections are particularly suitable for monitoring and evaluation of social distancing behavior in metropolises. Hence, in this paper, we propose and evaluate a real-time privacy-preserving social distancing analysis system (B-SDA), which uses bird's-eye view video recordings of pedestrians who cross traffic intersections. We devise algorithms for video pre-processing, object detection, and tracking which are rooted in the known computer-vision and deep learning techniques, but modified to address the problem of detecting very small objects/pedestrians captured by a highly elevated camera. We propose a method for incorporating pedestrian grouping for detection of social distancing violations, which achieves 0.92 F1 score. B-SDA is used to compare pedestrian behavior in pre-pandemic and during-pandemic videos in uptown Manhattan, showing that the social distancing violation rate of 15.6% during the pandemic is notably lower than 31.4% prepandemic baseline.

6.
HemaSphere ; 6:2024-2025, 2022.
Article in English | EMBASE | ID: covidwho-2032143

ABSTRACT

Background: MZL is the second most common lymphoma in older pts. Choosing an optimal treatment can be challenging because of patient-or disease-related risk factors and treatment-related toxicities (Curr Opin Oncol. 2019;31(5):386-393). Zanubrutinib is a potent, irreversible next-generation Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target kinase inhibition, which may improve efficacy outcomes and minimize toxicities, such as cardiac arrythmias and bleeding events. Zanubrutinib received accelerated approval from the United States FDA for the treatment of pts with R/R MZL (Haematologica . 2022;107(1):35-43). Aims: We aim to present a subgroup analysis of efficacy and safety of zanubrutinib in pts aged ≥65 years with R/R MZL enrolled in MAGNOLIA (BGB-3111-214;NCT03846427). Methods: MAGNOLIA is a phase 2, multicenter, single-arm study of adults with R/R MZL who had received ≥1 line of therapy including ≥1 CD20-directed regimen. All were treated with zanubrutinib 160 mg twice daily until disease progression or unacceptable toxicity. Use of long-term antiplatelet and anticoagulation agents was permitted. The primary endpoint was overall response rate (ORR;complete response [CR] and partial response [PR]) determined by an independent review committee (IRC) in accordance with the Lugano classification. Secondary endpoints include ORR by investigator assessment (INV), duration of response (DOR), progression-free survival (PFS), and safety. All pts gave informed consent. Results: As of 18 January 2021, a total of 68 pts were enrolled (Table). Forty (61%) pts were ≥65 years old with a median age of 73 (range, 65-85);18 pts were ≥75 years old. Median number of prior therapies was 2 (range, 1-6) and 10 (25%) pts were refractory to last therapy. Most pts received prior rituximab + cyclophosphamide + vincristine + prednisone (48%) or bendamustine + rituximab (30%), while 5 (13%) pts received rituximab monotherapy. MZL subtypes included extranodal (n=17, 43%), nodal (n=14, 35%), and splenic (n=8, 20%). Median duration of treatment was 14.4 months (mo;range, 0.9-19.6). At a median follow-up of 15.8 mo (range, 2.8-21.8), ORR by IRC was 75% (CR 25%, PR 50%;Table). Responses were observed in all subtypes, with an ORR of 71%, 86%, and 75% in extranodal, nodal, and splenic subtypes, respectively (CR 41%, 21%, and 0%, respectively). Median DOR and PFS were not reached;15-month PFS was 87% and 12-month DOR was 93%. Most (63%) pts are continuing zanubrutinib. Treatment discontinuation due to disease progression was 28% by INV. Most common treatmentemergent adverse events (AEs) observed in ≥20% of pts include contusion (28%), diarrhea (25%), and constipation (20%). Grade ≥3 neutropenia occurred in 5% of pts. The most common infection was upper respiratory tract infection (10%). Two (5%) pts discontinued zanubrutinib due to unrelated fatal AEs (COVID-19 pneumonia and myocardial infarction in a patient with pre-existing coronary artery disease). Atrial fibrillation/flutter and hypertension occurred in 2 (5%) pts each and did not lead to treatment discontinuation. No pts required dose reductions, or experienced major or serious hemorrhage. Image: Summary/Conclusion: The safety profile of zanubrutinib observed in older pts was consistent with previously published results (Clin Cancer Res . 2021;27(23):6323-6332). Zanubrutinib was well tolerated and effective, as demonstrated by a high response rate and durable disease control in older pts with R/R MZL.

7.
Atmosphere ; 13(7):18, 2022.
Article in English | Web of Science | ID: covidwho-1987635

ABSTRACT

PM2.5 and PM10 in the atmosphere seriously affect human health and air quality, a situation which has aroused widespread concern. In this paper, we analyze the temporal and spatial distribution of PM2.5 and PM10 concentrations from 2016 to 2021 based on real-time monitoring data. In addition, we also explore the influence of meteorological conditions on pollutants. The results show that PM2.5 and PM10 concentrations are similarly distribution in temporal and spatial from 2016 to 2021, and the average concentrations of both show a decreasing trend. The ratio of PM2.5 to PM10 is decreasing, indicating that the proportion of fine particles is declining. PM2.5 and PM10 concentrations are higher in spring and winter, but lower in summer. Spatially, it shows a gradual shift from the characteristic of "high in the south and low in the north" to a uniform homogenization across districts. The spatial distribution of PM2.5 and PM10 mass concentrations is synchronous by applying empirical orthogonal functions (EOF). The first EOF pattern exhibits a consistent characteristic of high in the southeast and low in the northwest. The second pattern EOF reflects the effect of impairing PM2.5 concentrations in the southeast during the winter of 2016-2018. The PM2.5 and PM10 concentrations are significantly negatively correlated with wind speed and precipitation in both spring and winter. On the other hand, from the perspective of the circulation situation, the southeasterly and weak westerly wind in spring produce convergence resulting in higher particulate matter concentrations in the south than in the north in Beijing. The westerly wind is flatter at 700 hPa geopotential height, which is conducive to the formation of stationary weather. The vertical direction of airflow in spring and winter is dominated by convergence and sinking, indicating the weak dispersion ability of the atmosphere. The reason for the accumulation of particulate matter at the surface is investigated, which is beneficial to provide the theoretical basis for air quality management and pollution control in Beijing.

8.
Asian J Androl ; 2022.
Article in English | PubMed | ID: covidwho-1975058

ABSTRACT

Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19);however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022;13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.

9.
Frontiers in Pharmacology ; 13:926189, 2022.
Article in English | MEDLINE | ID: covidwho-1974672

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) continues to spread globally. Due to the higher risk of mortality, the treatment of severe or critical patients is a top priority. Traditional Chinese medicine (TCM) treatment has played an extremely important role in the fight against COVID-19 in China;a timely evidence summary on TCM in managing COVID-19 is crucial to update the knowledge of healthcare for better clinical management of COVID-19. This study aimed to assess the effects and safety of TCM treatments for severe/critical COVID-19 patients by systematically collecting and synthesizing evidence from randomized controlled trials (RCTs) and observational studies (e.g., cohort). Methods: We searched nine databases up to 19th March 2022 and the reference lists of relevant publications. Pairs of reviewers independently screened studies, extracted data of interest, and assessed risk of bias. We performed qualitative systematic analysis with visual presentation of results and compared the direction and distribution of effect estimates for each patient's important outcome. We performed sensitivity analyses to observe the robustness of results by restricting analysis to studies with low risk of bias.

10.
2022 IEEE International Conference on Communications Workshops, ICC Workshops 2022 ; : 427-432, 2022.
Article in English | Scopus | ID: covidwho-1973477

ABSTRACT

Social distancing can reduce the infection rates in respiratory pandemics such as COVID-19. Traffic intersections are particularly suitable for monitoring and evaluation of social distancing behavior in metropolises. Hence, in this paper, we propose and evaluate a real-time privacy-preserving social distancing analysis system (B-SDA), which uses bird's-eye view video recordings of pedestrians who cross traffic intersections. We devise algorithms for video pre-processing, object detection, and tracking which are rooted in the known computer-vision and deep learning techniques, but modified to address the problem of detecting very small objects/pedestrians captured by a highly elevated camera. We propose a method for incorporating pedestrian grouping for detection of social distancing violations, which achieves 0.92 F1 score. B-SDA is used to compare pedestrian behavior in pre-pandemic and during-pandemic videos in uptown Manhattan, showing that the social distancing violation rate of 15.6% during the pandemic is notably lower than 31.4% prenandemic baseline. © 2022 IEEE.

11.
Journal of the Operational Research Society ; 2022.
Article in English | Scopus | ID: covidwho-1960658

ABSTRACT

This study addresses two key issues, ie, the “cold-start problem” in transmission prediction of new or rare epidemics and the collaborative allocation of emergency medical resources considering multiple objectives. These two issues have not yet been well addressed in data-driven emergency medical resource allocation systems. A decision support prediction-then-optimization framework combing deep learning and optimization is developed to address these two issues. Two transfer learning based convolutional neural network models are built for epidemic transmission predictions in the initial and the subsequent outbreak regions using transfer learning to deal with the “cold-start problem”. A prediction-driven collaborative emergency medical resource allocation model is built to address the issue of collaborative decisions by simultaneously considering the inter- and intra-echelon resource flows in a multi-echelon system and considering the efficiency and fairness as the objective functions. A case study of the COVID-19 pandemic shows that combining transfer learning and convolutional neural networks can improve the performances of epidemic transmission predictions, and good predictions can improve both the efficiency and fairness of emergency medical resource allocation decisions. Moreover, the computational results show that the prediction errors are asymmetrically amplified in the optimization stage, and the shortage of the resource reserve quantity mediates the asymmetrical amplification effect. © Operational Research Society 2022.

12.
Drug Evaluation Research ; 45(1):186-192, 2022.
Article in Chinese | Scopus | ID: covidwho-1912086

ABSTRACT

Coronavirus disease 2019 (COVID-19) is still spreading worldwide. At present, no specific drug has been developed for the virus. Ulinastatin plays an important role in anti-inflammatory. Clinically, it is mainly used in acute pancreatitis, shock and disseminated intravascular coagulation. It also has the effects of antioxidant stress, anticoagulation and immune regulation, which may be of great significance to reduce the severity and mortality of COVID-19. Combined with the pharmacological effect of ulinastatin and its clinical application in the treatment of COVID-19 complications such as acute respiratory distress syndrome and sepsis lung injury, this paper discusses the feasibility of its application in COVID-19, so as to provide help for the clinical treatment and new drug research and development of this disease. © 2022 Tianjin Press of Chinese Herbal Medicines. All Rights Reserved.

13.
Telematics and Informatics ; 71, 2022.
Article in English | Scopus | ID: covidwho-1873284

ABSTRACT

This study examines the effects of self-generated and other-generated electronic word-of-mouth communication (eWOM) in inoculating individuals against potential misinformation. A three-phase between-subject experiment (N = 543) was conducted to compare the persuasive effects of inoculation messages combined with different eWOM content (self-generated, other-generated, and inoculation only) over two health topics (Covid-19 vaccine and e-cigarette). The results show that exposure to inoculation messages did not significantly increase resistance to misinformation. But inoculation messages combined with other-generated eWOM helped the participants develop more negative attitudes toward alternative smoking immediately after exposure to the inoculation stimuli. The participants who wrote eWOM after exposure to inoculation messages were more resistant to the attack of misinformation in Phase 3. Self-generated and other-generated eWOM did not significantly differ in their persuasive effects in any phases. The findings extend the literature on the effects of WOM in the inoculation process and offer theoretical implications over inoculation theory in online contexts. The study provides empirical guidance on using inoculation messages to combat misinformation in social media. © 2022 Elsevier Ltd

14.
J Gen Intern Med ; 37(8): 1988-1995, 2022 06.
Article in English | MEDLINE | ID: covidwho-1782932

ABSTRACT

BACKGROUND: The incidence of persistent clinical symptoms and risk factors in Post-Acute Sequelae of SARS-CoV-2 (PASC) in diverse US cohorts is unclear. While there are a disproportionate share of COVID-19 deaths in older patients, ethnic minorities, and socially disadvantaged populations in the USA, little information is available on the association of these factors and PASC. OBJECTIVE: To evaluate the association of demographic and clinical characteristics with development of PASC. DESIGN: Prospective observational cohort of hospitalized and high-risk outpatients, April 2020 to February 2021. PARTICIPANTS: One thousand thirty-eight adults with laboratory-confirmed symptomatic COVID-19 infection. MAIN MEASURES: Development of PASC determined by patient report of persistent symptoms on questionnaires conducted 60 or 90 days after COVID-19 infection or hospital discharge. Demographic and clinical factors associated with PASC. KEY RESULTS: Of 1,038 patients with longitudinal follow-up, 309 patients (29.8%) developed PASC. The most common persistent symptom was fatigue (31.4%) followed by shortness of breath (15.4%) in hospitalized patients and anosmia (15.9%) in outpatients. Hospitalization for COVID-19 (odds ratio [OR] 1.49, 95% [CI] 1.04-2.14), having diabetes (OR, 1.39; 95% CI 1.02-1.88), and higher BMI (OR, 1.02; 95% CI 1-1.04) were independently associated with PASC. Medicaid compared to commercial insurance (OR, 0.49; 95% CI 0.31-0.77) and having had an organ transplant (OR 0.44, 95% CI, 0.26-0.76) were inversely associated with PASC. Age, race/ethnicity, Social Vulnerability Index, and baseline functional status were not associated with developing PASC. CONCLUSIONS: Three in ten survivors with COVID-19 developed a subset of symptoms associated with PASC in our cohort. While ethnic minorities, older age, and social disadvantage are associated with worse acute COVID-19 infection and greater risk of death, our study found no association between these factors and PASC.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Aged , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , Comorbidity , Humans , Inpatients , Outpatients , United States/epidemiology
15.
Open Forum Infectious Diseases ; 8(SUPPL 1):S425, 2021.
Article in English | EMBASE | ID: covidwho-1746396

ABSTRACT

Background. The American Academy of Pediatrics recommends tuberculin skin tests (TSTs) or interferon gamma release assays (IGRAs) to test for tuberculosis (TB) infection in children ≥2 years old, and prioritizes IGRA testing in Bacille Calmette-Guerin vaccine recipients due to cross-reactivity. TSTs require a return visit, which frequently results in loss to follow up. Growing evidence supports accuracy of IGRA testing in pediatric patients, including young children, leading to calls for preferential use of IGRA over TST. We sought to evaluate trends in IGRA use in children over time. Methods. We identified all TB infection tests conducted in children 5-17 years old at 2 academic medical systems in Boston from October 2015-January 2021. TSTs were identified using medication administration records, and IGRAs were identified using laboratory records. We computed the proportion of tests per month that were IGRA and TST. We used Pearson correlation to determine the association between month of testing and proportion of tests that were IGRAs. Results. 21,471 TB infection tests were obtained from 16,778 patients during our timeframe. Median age of testing was 13.4 years (IQR 9.2 - 16.2 years). During the study period, there was a significant increase in the monthly proportion of TB infection tests that were IGRAs (Pearson correlation coefficient 0.92, P < 0.001). The total number of tests performed per month also increased, with seasonal increases in testing in late summer and early fall and a substantial decline in testing early in the COVID-19 pandemic. Tuberculosis infection tests and proportion IGRA. Total number of tuberculosis infection tests per month and proportion of tests that were interferon gamma release assays, from October 2015 - January 2021. Conclusion. Use of IGRAs among patients age 5-17 years of age increased significantly overall and compared to TST in two large Boston healthcare systems over a 5-year period. These results suggest a shift towards blood-based TB infection testing in a low-burden setting, which may improve completion of the pediatric TB infection care cascade. Future research is needed to determine reasons for changing testing modalities, and similar patterns in other settings.

16.
Education Finance and Policy ; 17(1):188-199, 2022.
Article in English | Web of Science | ID: covidwho-1613132

ABSTRACT

State budgets temporarily crashed amid the COVID-19 pandemic and economic shutdown, placing education funding at risk. To demonstrate implications for school finance, we show that (1) school districts are racially segregated along class lines;(2) higher-poverty districts receive a greater share of funds from state, as opposed to local sources, making them especially vulnerable during economic downturns;and (3) many states made across-the-board K-12 budget reductions following the Great Recession, but those cuts disproportionately impacted high-poverty districts. A decade later, state legislators may face similar fiscal challenges. Instead of enacting across-the-board cuts, states can identify specific funding programs that already benefit lower-poverty districts or wealthier students. We demonstrate how this approach would work under different state finance models and offer recommendations for state policy makers.

17.
Blood ; 138:738, 2021.
Article in English | EMBASE | ID: covidwho-1582381

ABSTRACT

SARS-COV-2 (COVID-19) has resulted in over 4 million deaths worldwide. While vaccination has decreased mortality, there remains a need for curative therapies for active infections. Uncertainties regarding the duration of post-vaccination immunity and the rapidity of mutational evolution by this virus suggest that it is unwise to rely on preventative measures alone. Humoral and cellular immunity provide selective pressure for the emergence of variant strains which have eliminated target epitopes. Elimination of immunodominant epitopes provides the strongest advantage to newly emerging strains and, consequently, immunodominant epitopes would be expected to be preferentially eliminated compared to subdominant epitopes in emerging variants. Immunologic treatments for SARS-COV-2 need to be continuously reassessed as new sequence information becomes available. TVGN-489 is a clinical grade product consisting of highly enriched, highly potent CD8+ CTLs recognizing peptides derived from COVID-19 gene/ORF products in an HLA restricted manner. CTLs are generated from apheresis products from individuals who have recovered from COVID-19 infections. Lymphocytes are serially primed and selected using APCs from these donors pulsed with small numbers of peptides encoded by the COVID-19 genome predicted or demonstrated to bind to specific HLA class I alleles. The resulting products are typically >95% CD3+/CD8+, >60% positive by tetramer staining and demonstrate strong cytolytic activity with >60% lysis of peptide pulsed targets typically at an effector to target ratio of 3:1 (See Figure). Given the immunologic pressure to lose dominant target epitopes, we assessed whether the peptides derived from genomic sequences from early SARS-COV-2 strains (and successfully used to generate CTLs from donors infected with these early strains) were still present in the more recently evolved Delta variant. Seven peptides were used to generate CTL products restricted by HLA-A*02:01, the most common allele worldwide. These peptides are derived from the spike (S) and nucleocapsid (N) proteins as well as ORF3a and ORF1ab. The contributions of these peptides to the overall cytotoxicity and tetramer staining range from 2% to 18% without clear immunodominance by one of these peptides. Though identified in early viral strains, these sequences persist in 97.5%-100% of the more than 120 Delta variant sequences present in the NIH database. For HLA-A*01:01, eight peptides derived from the matrix (M) protein as well as ORF1ab and ORF3a were utilized to generate CTLs. Seven of the eight peptides showed binding similar to what was seen with the HLA-A*02:01 peptides (1% to 18%). However, in contrast to HLA-A*02:01, an immunodominant peptide (TTDPSFLGRY, ORF1ab 1637-1646) was noted which was responsible for over half of the observed tetramer binding. This region of ORF1ab was mutated in the Delta variant resulting in loss of this immunodominant epitope from nearly 93% of the Delta genomic sequences in the NIH database. The remaining subdominant peptides were all preserved in 100% of the sequences. Given the growing number of Delta cases, it will be essential to remove this peptide from the HLA-A*01:01 peptide pool used to stimulate SARS-COV-2-specific CD8+ CTLs to avoid encouraging the expansion of cells which would recognize early strains of the virus, but not Delta variants. The remaining CTLs, generated in the absence of TTDPSFLGRY, should be capable of eradicating Delta as well as the earlier prototypic strains of COVID-19. The loss of immunodominant epitopes is not surprising in a virus such as SARS-COV-2, with a high frequency of mutation. This provides an example of immunologic escape similar to what has been described for the Delta variant in the case of HLA-A24. These data are consistent with the hypothesis that immunodominant epitopes will be preferentially eliminated as the virus continues to evolve. They further illustrate the need to monitor viral sequences and to tune the production of CTLs in order to ensure that they can continue to recognize and e fectively treat newly emerging variants of COVID-19. [Formula presented] Disclosures: No relevant conflicts of interest to declare. OffLabel Disclosure: The drug is Cytotoxic T lymphocytes that are specific to COVID-19. Preclinical data.

19.
Proceedings of the ACM on Interactive, Mobile, Wearable and Ubiquitous Technologies ; 5(3), 2021.
Article in English | Scopus | ID: covidwho-1438130

ABSTRACT

For the past several decades, machine learning has played an important role in sports science with regard to player performance and result prediction. However, it is still challenging to quantify team-level game performance because there is no strong ground truth. Thus, a team cannot receive feedback in a standardized way. The aim of this study was twofold. First, we designed a metric called LAX-Score to quantify a collegiate lacrosse team's athletic performance. Next, we explored the relationship between our proposed metric and practice sensing features for performance enhancement. To derive the metric, we utilized feature selection and weighted regression. Then, the proposed metric was statistically validated on over 700 games from the last three seasons of NCAA Division I women's lacrosse. We also explored our biometric sensing dataset obtained from a collegiate team's athletes over the course of a season. We then identified the practice features that are most correlated with high-performance games. Our results indicate that LAX-Score provides insight into athletic performance beyond wins and losses. Moreover, though COVID-19 has stalled implementation, the collegiate team studied applied our feature outcomes to their practices, and the initial results look promising with regard to better performance. © 2021 ACM.

20.
HemaSphere ; 5(SUPPL 2):358-359, 2021.
Article in English | EMBASE | ID: covidwho-1393436

ABSTRACT

Background: BCR signaling mediated through Bruton's tyrosine kinase (BTK) plays a critical role in the development and maintenance of marginal zone lymphoma (MZL). BTK inhibitors have established activity in relapsed/refractory (R/R) MZL with the phase 2 study of ibrutinib demonstrating an objective response rate (ORR) of 48% (Noy et al. Blood. 2017;129:2224-2232). Zanubrutinib is a potent and highly specific next-generation BTK inhibitor designed with greater selectivity for BTK vs TEC- and EGFRfamily kinases, which are thought to be related to off-target toxicities. Therapeutic activity of zanubrutinib was established in an early-phase study (BGB-3111-AU-003) of 20 patients (pts) with R/R MZL demonstrating an ORR of 80%, with a complete response (CR) rate of 15%, and partial response (PR) rate of 65% (Tedeschi et al. EHA 2020, abstract 2804). Aims: To present initial efficacy and safety results in pts with R/R MZL enrolled in MAGNOLIA (BGB-3111-214). Methods: MAGNOLIA is a phase 2, multicenter, single-arm study of adults with R/R MZL who had received ≥1 line of therapy including ≥1 CD20-directed regimen. All were treated with zanubrutinib 160 mg twice daily until disease progression or unacceptable toxicity. Use of long-term antiplatelet and anticoagulation agents was permitted. The primary end point was ORR determined by an independent review committee in accordance with the Lugano classification. Secondary end points include ORR by investigator assessment, duration of response (DOR), progression-free survival (PFS), and safety. Results: As of January 11, 2021, 68 pts were enrolled and treated. Median age was 70 years (range, 37-95), with 28% aged ≥75 years. Subtypes included extranodal (mucosa-associated lymphoid tissue;38%), nodal (38%), splenic (18%), and indeterminate (6%) MZL. Median number of prior therapies was 2 (range, 1-6) and 32% of pts had disease that was refractory to last therapy. Median duration of drug exposure was 59.1 weeks (range, 3.7-84.1). Sixty-six pts were evaluable for efficacy. At a median study follow-up of 15.5 months (range, 1.6-21.7), investigator-assessed ORR (CR + PR) was 74% (CR 24%, PR 50%, stable disease 17%). Responses were observed in all subtypes, with an ORR of 68%, 84%, 75%, and 50% in extranodal, nodal, splenic, and indeterminate subtypes, respectively. CR rate was 36% for extranodal MZL, 20% for nodal, 8% for splenic, and 25% for indeterminate subtype. Median DOR and PFS were not reached;15-month PFS was 68% and 12-month DOR was 81%. IRC review is ongoing. Twenty-eight (41%) pts discontinued treatment: 20 due to disease progression, 1 withdrew consent, 3 required prohibited medications, 4 due to adverse events (AEs;2 due to COVID-19 pneumonia, 1 due to pyrexia attributed to disease transformation, and 1 due to myocardial infarction [MI]). The most common (≥10%) treatment-emergent AEs reported were diarrhea (22%), bruising (21%), constipation (15%), pyrexia (13%), abdominal pain (12%), upper respiratory tract infection (12%), back pain (10%), and nausea (10%). Most AEs were grade 1 or 2. Neutropenia was the most common grade ≥3 AE (10%). Two pts died from COVID-19 pneumonia and 1 pt with pre-existing coronary artery disease died from MI. No fatal AEs were considered related to zanubrutinib. All-grade AEs of interest included neutropenia (13%), thrombocytopenia (13%), atrial fibrillation/flutter (3%), and hypertension (3%). No major/serious hemorrhage was reported. No AEs led to dose reductions. Summary/Conclusion: Zanubrutinib demonstrated high response rates and durable disease control with a favorable safety profile in pts with R/R MZL.

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