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2.
Scientific Reports ; 12(1):22293, 2022.
Article in English | MEDLINE | ID: covidwho-2186032

ABSTRACT

Analytical tools to study cell physiology are critical for optimizing drug-host interactions. Real time pulse chase NMR spectroscopy, RTPC-NMR, was introduced to monitor the kinetics of metabolite production in HEK 293T cells treated with COVID-19 vaccine-like lipid nanoparticles, LNPs, with and without mRNA. Kinetic flux parameters were resolved for the incorporation of isotopic label into metabolites and clearance of labeled metabolites from the cells. Changes in the characteristic times for alanine production implicated mitochondrial dysfunction as a consequence of treating the cells with lipid nanoparticles, LNPs. Mitochondrial dysfunction was largely abated by inclusion of mRNA in the LNPs, the presence of which increased the size and uniformity of the LNPs. The methodology is applicable to all cultured cells.

3.
3rd ACM SIGSPATIAL International Workshop on Spatial Computing for Epidemiology, SpatialEpi 2022 ; : 26-34, 2022.
Article in English | Scopus | ID: covidwho-2153137

ABSTRACT

Time series prediction models have played a vital role in guiding effective policymaking and response during the COVID-19 pandemic by predicting future cases and deaths at the country, state, and county levels. However, for emerging diseases, there is not sufficient historic data to fit traditional supervised prediction models. In addition, such models do not consider human mobility between regions. To mitigate the need for supervised models and to include human mobility data in the prediction, we propose Spatial Probabilistic Contrastive Predictive Coding (SP-CPC) which leverages Contrastive Predictive Coding (CPC), an unsupervised time-series representation learning approach. We augment CPC to incorporate a covariate mobility matrix into the loss function, representing the relative number of individuals traveling between each county on a given day. The proposal distribution learned by the algorithm is then sampled by the Metropolis-Hastings algorithm to give a final prediction of the number of COVID-19 cases. We find that the model applied to COVID-19 data can make accurate short-term predictions, more accurate than ARIMA and simple time-series extrapolation methods, one day into the future. However, for longer-term prediction windows of seven or more days into the future, we find that our predictions are not as competitive and require future research. © 2022 ACM.

6.
American Journal of Transplantation ; 22(Supplement 3):528, 2022.
Article in English | EMBASE | ID: covidwho-2063394

ABSTRACT

Purpose: Alcohol use after liver transplant is associated with higher rates of graft loss and increased mortality;however, there is limited data regarding the factors that influence biochemically confirmed relapse. We aimed to evaluate the association between social determinants of health (SDOH) and biochemical alcohol relapse in patients who have been transplanted for alcohol-associated liver disease (ALD). Method(s): This single-center, retrospective cohort study examined patients with ALD who were transplanted between 2018-2021. The primary outcome was biochemical alcohol relapse as measured by systematic phosphatidylethanol (PEth) testing. SDOH including race, ethnicity, income, employment, social support, education level, public vs private health insurance, mental health comorbidities, and comorbid illicit substance use were assessed for their association with the outcome using logistic regression analyses. Additionally, temporal trends in biochemical relapse related to the Covid-19 pandemic were evaluated using a cut point of April 2020 to differentiate between pre-pandemic and pandemic groups. Result(s): Seventy-five patients were transplanted for ALD over the study period, of whom 71 had biochemical PEth measurements (95%). Of these 71 patients, 21% were female with a mean (+/-SD) age of 52.9 (+/-10.4) years and 49% of the study population identified as Hispanic ethnicity. At the time of transplant listing, 73% were unemployed, 65% had public insurance, and 62% were married or had a stable co-companion. Over 64 person-years of follow up, 10 (15%) patients had biochemical relapse after transplant. Older age was protective OR=0.94 (95% CI 0.88-0.99;p=0.05), while non-Hispanic white race OR=6.29 (95% CI 1.22-32.51;p=0.03), and prior illicit substance use OR=4.2 (95% CI 1.05-16.90;p=0.04) were associated with an increased risk of relapse. Patients identifying as non-Hispanic white had non-significant trends toward lower household income, decreased social support, and higher rates of comorbid mental illness. Severe acute alcohol hepatitis, time from last drink to listing, SIPAT and AUDIT score were not associated with increased risk of relapse. The risk of relapse increased during the Covid-19 pandemic from 4.3% pre-Covid-19 to 18.8% during Covid-19 with a trend towards statistical significance OR=5.1 (95% CI 0.60-42.8;p=0.13). Conclusion(s): Non-Hispanic white race, younger age, and illicit substance use were associated with increased rates of biochemical alcohol relapse and may be explained by SDOH;however, conventional metrics including >6 months from last drink to listing and lower SIPAT score were not predictive of biochemical relapse.

7.
Analytical Chemistry ; 94(33):11591-11599, 2022.
Article in English | Web of Science | ID: covidwho-2016508

ABSTRACT

The COVID-19 pandemic has led to a global crisis with devastating effects on public healthcare and the economy. Sensitive detection of SARS-CoV-2 is the key to diagnose and control its spread. The spike (S) protein is an abundant viral transmembrane protein and a suitable target protein for the selective recognition of SARS-CoV-2. Here, we report that with bovine serum albumin prescreening, a specific phage peptide targeting SARS-CoV-2 S1 protein was biopanned with the pIII phage display library. The identified phage #2 expressing the to the target with a dissociation constant of 3.45 +/- 0.58 nM. Furthermore, the identified peptide shows good specificity with a binding site at the N-terminal domain of the S1 subunit through a hydrogen bond network and hydrophobic interaction, supported by molecular docking. Then, a sandwiched phage-based enzyme-linked chemiluminescence immunoassay (ELCLIA) was established by using phage #2 as a bifunctional probe capable of SARS-CoV-2 S1 antigen recognition and signal amplification. After optimizing the conditions, the proposed phage ELCLIA exhibited good sensitivity, and as low as 78 pg/mL SARS-CoV-2 S1 could be detected. This method can be applied to detect as low as 60 transducing units (TU)/mL SARS-CoV-2 pseudovirus in 50% saliva. Therefore, specific phage peptides have good prospects as powerful biological recognition probes for immunoassay detection and biomedical applications.

8.
25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2021 ; : 1605-1606, 2021.
Article in English | Scopus | ID: covidwho-2012142

ABSTRACT

The great advances in silicon photonic-sensing technology have made it an attractive platform for wide sensing applications. The small size of chip and detection system makes photonic microring resonator can be used in clinic for quick detection of disease. Here, we employ the high sensitivity of the photonic sensor toward the change of refractive index for the detection of SARS-CoV-2 virus spike proteins and botulinum toxin in water. The system require very small amount of sample 50uL with high sensitivity, in short 1hr without pre-treatment required. The measurement can be automatic with minimum manpower involved. Moreover, the system can be multiplexed to detect a few target analytes at the same time in one sample. © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

9.
Frontiers in Cell and Developmental Biology ; 10, 2022.
Article in English | EMBASE | ID: covidwho-1968991

ABSTRACT

After over a decade of development, mRNA has recently matured into a potent modality for therapeutics. The advantages of mRNA therapeutics, including their rapid development and scalability, have been highlighted due to the SARS-CoV-2 pandemic, in which the first two clinically approved mRNA vaccines have been spotlighted. These vaccines, as well as multiple other mRNA therapeutic candidates, are modified to modulate their immunogenicity, stability, and translational efficiency. Despite the importance of mRNA modifications for harnessing the full efficacy of mRNA drugs, the full breadth of potential modifications has yet to be explored clinically. In this review, we survey the field of mRNA modifications, highlighting their ability to tune the properties of mRNAs. These include cap and tail modifications, nucleoside substitutions, and chimeric mRNAs, each of which represents a component of mRNA that can be exploited for modification. Additionally, we cover clinical and preclinical trials of the modified mRNA platform not only to illustrate the promise of modified mRNAs but also to call attention to the room for diversifying future therapeutics.

10.
Annals of Blood ; 7, 2022.
Article in English | Scopus | ID: covidwho-1964904

ABSTRACT

The severe acute respiratory syndrome (SARS) coronavirus disease known as coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2 has caused a global pandemic since late 2019. As of 7 February 2020, more than 106 million people have been infected, and approximately 2,317 thousand people have died due to SARS-CoV-2 across 200 countries. Unfortunately, to date, many aspects of pathogenesis, infection, clinical manifestations and treatment methods remain unclear, no specific antiviral drugs or vaccines have been reported for patients with COVID-19 infection. Most patients with severe infections require supportive organ function therapies in the intensive care unit (ICU). Passive antibody therapies such as convalescent plasma (CP) therapy have been proved to be effective in the treatment of many infectious diseases such as SARS and Middle East respiratory syndrome (MERS), which are also assumed as a promising strategy in the treatment of critically ill COVID-19 patients. With the increasing investigation, the objective understanding of COVID-19 prevention, treatment and comorbid disease is beneficial for the application of the strategy applied in the clinical trials. Herein, we briefly discuss the current therapeutic approaches for patients with COVID-19, especially focuses on the application of therapeutic plasma exchange (TPE) for selected critically ill patients, aiming to provide some guidance for the treatment of severe COVID-19. © Annals of Blood. All rights reserved.

11.
Global Spine Journal ; 12(3):61S-62S, 2022.
Article in English | EMBASE | ID: covidwho-1938247

ABSTRACT

Introduction: The impact of idiopathic scoliosis on exercise and activities of affected adolescents are not well-documented. The aim of this study was to assess the self-reported physical activity (PA) of patients with Adolescent Idiopathic Scoliosis (AIS) in Hong Kong. Materials and Methods: This was an observational, cross-sectional study conducted at a scoliosis clinic in a tertiary referral centre in Hong Kong. Patients referred from the Hong Kong Scoliosis School Screening Programme were consecutively recruited and asked to fill in the Chinese-translated version of the Paffenbarger Physical Activity Questionnaire (PPAQ) online. Details included flights of stairs climbed, city blocks walked, and frequency, duration and intensity of sporting activities were recorded, from which a Physical Activity Index (PAI) in kilocalories/week (kcal/week) was calculated. The PAI provides an estimate of the total energy expenditure of the subject. Radiographic data including Cobb angles and region of major curve, and anthropometric data was collected from routine clinical examinations. Results: 33 male (mean age = 14.6 ± 1.84) and 102 female (mean age = 13.2 ± 1.46) were included in the study. The mean BMI of male patients was 17.3 ± 2.2 kg/m2, and that of females was 18.0 ± 3.06 kg/m2, both of which are classified as underweight. 64 patients had a mild Cobb angle (10°-24.9°), 52 had a moderate Cobb angle (25°-39.9°) and 17 had a severe Cobb angle (>40°). In terms of PA, 72 patients (53%) reported participation in yearly PA activity excluding physiotherapy and mandatory physical education classes, and 55 (40.7%) in weekly PA that caused sweating, increased heart rate and shortness of breath. The 80 patients that did not participate in any PA were asked to provide reasons for their lack of physical activity. 30% of patients reported "lack of time" and 16.3% reported "laziness". Other reasons include lack of interest (6.3%), the COVID pandemic (2.5%) and being unfit (5%). A Physical Activity Index (PAI) in kcal/week was calculated based on subjects' answers to flights of stairs climbed, city blocks walked and sporting activities. Patients that were unable to provide a numerical answer to such questions were excluded from the PAI calculations. 113 PAIs were calculated, with a mean of 2611.2 ± 5009.4 kcal/week, and a median of 1128.4 kcal/week. 48 patients (42.5%) expended under 1000 kcal/week, 30 patients (26.5%) expended 1000-2000 kcal/week, 21 patients (18.6%) expended 2000-4000 kcal/week, and 14 patients (12.4%) expended over 4000kcal/week. According to the WHO guidelines on Physical Activity and Sedentary Behavior, PA recommendations for children and adolescents include 60 minutes of moderate-to-vigorous-intensity PA per day, which totals to 365 hours per week. Only 2 patients fulfilled this criterion. Conclusion: Adolescents with AIS in Hong Kong exhibited a wide range of PA levels. However, the majority of AIS patients in this study did not participate adequate physical activity according to WHO guidelines. Further studies are required to correlate if AIS negatively impacted on their motivation to participate in physical activities and exercises.

12.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927699

ABSTRACT

BACKGROUND: Approximately 173,000 persons live on the Navajo Nation (NN) and 14.7% live in multi-generational households. One-third of the Nation's residents are children and 44% live in poverty. The median household income is $27,389 with 1/3 having incomes < $15,000/year. The first confirmed case of COVID-19 on the NN was identified March 17, 2020. The Navajo government took swift action to combat COVID-19 by declaring a public health state of emergency which established the Navajo Department of Health Command Operations Center, closed the government offices except for essential employees, ceased inperson classroom instruction for all schools located within the borders of the NN and issued travel restriction for governmental employees. Even with strong public health efforts, Navajo Nation saw the highest per capita infection rate in the US during May of 2020 with 2450/100,000 versus New York 2119/100,000. METHODS: The Community Asthma Program is an NHLBI funded program working to improve health outcomes for children with asthma on the NN. We sought to determine the impact of COVID- 19 on the families of children with asthma who were participating in our study. RESULTS: Sixty-six of 193 families (34%) were interviewed about their pandemic experience. The average age of the child with asthma was 13.5 (SD=3.9) and 33% were female. On average, 5.2 people lived in each house (SD=2.1). Results of the interviews are shown in the table. Our data indicate that most Diné children with asthma in our study did not contract COVID-19. However, the pandemic had a significant impact on them and their families. Many family members contracted COVID-19, some children lost family members, and half of interviewed parents reported a decline in their child's mental health. Responses suggest that Navajo families may have been less able to work remotely than the US population at large, perhaps increasing stress for families. Despite the trauma from COVID-19, families adopted strategies to cope with the pandemic. Most diligently followed health guidelines including washing hands, wearing masks, and social distancing. One in four families sought the help of a traditional healer. Many accessed medical care through telehealth and most were able to obtain asthma medications when needed. More recently, as the pandemic subsides, parents indicate that their outlook and mental health have significantly improved. CONCLUSION. Despite significant challenges, our research indicated resilience among Navajo families and we heard stories of positive community structures and relationships that are particular to the Diné culture. (Figure Presented).

13.
2nd International Conference on Applied Mathematics, Modelling, and Intelligent Computing, CAMMIC 2022 ; 12259, 2022.
Article in English | Scopus | ID: covidwho-1923093

ABSTRACT

This paper focuses on the main factors affecting the number of COVID-19 deaths. By correlation analysis, the number of people vaccinated and the number of infection cases are the main factors of the number of deaths. A prediction model on the number of deaths using these factors and linear regression is therefore built. The model was next used to predict and compare the number of COVID-19 deaths with actual data in several countries. Additional influences were further analyzed for countries with poor fits. © 2022 SPIE

14.
Hong Kong Med J ; 28(2): 188-190, 2022 04.
Article in English | MEDLINE | ID: covidwho-1918129
15.
Chinese Pharmacological Bulletin ; 36(12):1629-1636, 2020.
Article in Chinese | EMBASE | ID: covidwho-1863008

ABSTRACT

At present, coronavirus disease-19 (COVID-19) caused by novel coronavirus (SARS-CoV-2) has been spreading around the world, but no specific therapeutic drug or vaccine has been developed for the virus. By collecting the latest literature and searching related database websites, the biological charac¬teristics and main targets of SARS-CoV-2, the clinical therapeu¬ tic drugs and the latest drug research were reviewed to provide information for clinical treatment and provide reference for the research and development of new drugs against SARS-CoV-2.

17.
Chinese Journal of Applied Clinical Pediatrics ; 36(24):1913-1917, 2021.
Article in Chinese | Scopus | ID: covidwho-1765983

ABSTRACT

Since December 2019, the novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) infection has broken out worldwide, causing enormous social and economic burdens. Sudden exacerbations in SARS - CoV -2 infected people may be caused by infection - related cytokine storms. The basic state of the body and the strength of the immune response determine the prognosis of SARS-CoV-2. The interaction between proinflammatory factors and anti - inflammatory factors, and continued proinflammatory response cause lung edema, exudation, progression to acute respiratory distress syndrome involving the lung tissues and organs, multi - organ failure, and even death. The efficacy of antiviral therapy alone for immune complications like cytokine storm during viral infection is not ideal, and the targeted therapy of cytokines has become a potentially popular therapeutic strategy. Early identification and appropriate treatment of immune complications contribute to reduce the morbidity and mortality of severe viral infections. © 2021 Heilongjiang Institute of Science and Technology Information. All rights reserved.

18.
4th International Conference on Digital Medicine and Image Processing, DMIP 2021 ; : 40-44, 2021.
Article in English | Scopus | ID: covidwho-1741707

ABSTRACT

Motivation: Coronavirus disease (COVID-19) struck the world in late 2019 and caused millions of deaths worldwide as an infectious disease caused by the SARS-CoV-2 virus. An effective and early diagnosis is truly pivotal, and thus, many studies were initiated for that. The existing studies have some limitations such as only focusing on one type of omics data. The study aims to develop a computational model which studies COVID-19 with the integration of metabolomics and proteomics data, therefore reaching the goal of detecting the virus early in the stage. Methods: The computational framework for integrating multi-omics data (CoFIM) consists of two parts. The first part is a statistical analysis of datasets. In this study, a series of statistical analyses including univariate and multivariate analyses were conducted to identify a number of potential biomarkers after pulling the data of severe patients and non-severe patients from a proteomic and metabolomics dataset of sera samples of COVID-19 patients. The second part is a machine learning model that was conducted to predict a patient's disease progression and provide more insightful information to understand the disease. Results: CoFIM integrates both proteomic and metabolomics data and provides a customizable and scalable framework to analyze the multi-omics data. CoFIM is demonstrated on the COVID-19 dataset and a number of biomarkers were detected. Several new protein biomarkers (IGKV1-12, PCOLCE, PGLYRP2, PCYOX1, LUM, IGHV1-46) were detected. We believe CoFIM will be widely used for multi-omics data analysis. © 2021 ACM.

19.
3rd IEEE Eurasia Conference on Biomedical Engineering, Healthcare and Sustainability, ECBIOS 2021 ; : 74-76, 2021.
Article in English | Scopus | ID: covidwho-1713984

ABSTRACT

We are experiencing heavy COVID-19 outbroke globally since January 2020. In Taiwan, because its low infection rate (< 0.01%), there was not enough evidence for diagnosis through medical imaging. At present, chest X-ray is widely used in lung infection diagnoses. This study uses deep learning methods to assist doctors in classifying COVID-19 disease from chest X-ray images. After pre-processing, the images were put into the VGG16 model to automaticallyclassify into three categories to assist the radiologist in the treatment of the disease. The results show that the classification accuracy was 78%. Detail analyses disclosed that this accuracy can be improved by rectifying the unbalanced images problem. In addition, choosing proper image pre-processing algorithms has a high tendency to generate better results. © 2021 ECBIOS 2021. All rights reserved.

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