scholarly journals Deep sequence modelling for predicting COVID-19 mRNA vaccine degradation

2021 ◽  
Vol 7 ◽  
pp. e597
Author(s):  
Talal S. Qaid ◽  
Hussein Mazaar ◽  
Mohammed S. Alqahtani ◽  
Abeer A. Raweh ◽  
Wafaa Alakwaa

The worldwide coronavirus (COVID-19) pandemic made dramatic and rapid progress in the year 2020 and requires urgent global effort to accelerate the development of a vaccine to stop the daily infections and deaths. Several types of vaccine have been designed to teach the immune system how to fight off certain kinds of pathogens. mRNA vaccines are the most important candidate vaccines because of their capacity for rapid development, high potency, safe administration and potential for low-cost manufacture. mRNA vaccine acts by training the body to recognize and response to the proteins produced by disease-causing organisms such as viruses or bacteria. This type of vaccine is the fastest candidate to treat COVID-19 but it currently facing several limitations. In particular, it is a challenge to design stable mRNA molecules because of the inefficient in vivo delivery of mRNA, its tendency for spontaneous degradation and low protein expression levels. This work designed and implemented a sequence deep model based on bidirectional GRU and LSTM models applied on the Stanford COVID-19 mRNA vaccine dataset to predict the mRNA sequences responsible for degradation by predicting five reactivity values for every position in the sequence. Four of these values determine the likelihood of degradation with/without magnesium at high pH (pH 10) and high temperature (50 degrees Celsius) and the fifth reactivity value is used to determine the likely secondary structure of the RNA sample. The model relies on two types of features, namely numerical and categorical features, where the categorical features are extracted from the mRNA sequences, structure and predicted loop. These features are represented and encoded by numbers, and then, the features are extracted using embedding layer learning. There are five numerical features depending on the likelihood for each pair of nucleotides in the RNA. The model gives promising results because it predicts the five reactivity values with a validation mean columnwise root mean square error (MCRMSE) of 0.125 using LSTM model with augmentation and the codon encoding method. Codon encoding outperforms Base encoding in MCRMSE validation error using the LSTM model meanwhile Base encoding outperforms codon encoding due to less over-fitting and the difference between the training and validation loss error is 0.008.

2019 ◽  
Vol 25 (13) ◽  
pp. 1443-1454 ◽  
Author(s):  
Maria L. Guevara ◽  
Stefano Persano ◽  
Francesca Persano

Cancer vaccines have been widely explored as a key tool for effective cancer immunotherapy. Despite a convincing rationale behind cancer vaccines, extensive past efforts were unsuccessful in mediating significantly relevant anti-tumor activity in clinical studies. One of the major reasons for such poor outcome, among others, is the low immunogenicity of more traditional vaccines, such as peptide-, protein- and DNA- based vaccines. Recently, mRNA emerged as a promising alternative to traditional vaccine strategies due to its high immunogenicity, suitability for large-scale and low-cost production, and superior safety profile. However, the clinical application of mRNA-based anti-cancer vaccines has been limited by their instability and inefficient in vivo delivery. Recent technological advances have now largely overcome these issues and lipid-based vectors have demonstrated encouraging results as mRNA vaccine platforms against several types of cancers. This review intends to provide a detailed overview of lipid-based vectors for the development of therapeutic mRNA-based anti-tumor vaccines.


2021 ◽  
Vol 20 (2) ◽  
pp. 463-464
Author(s):  
Musa Mohd Nordin ◽  
Husna Musa

As the number of COVID-19 cases continues to rise with over 65 million recorded cases and more than 1.5 million mortalities as of early December, the race against time to find a vaccine intensifies. In recent years, there has been growing interest in mRNA-based technology for the development of prophylactic vaccines against infectious diseases and even for cancers and allergies. The prospects for mRNA vaccines are very promising because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. However, until now, no vaccines using this technology have made it this far in clinical trials thus there have been concerns on the therapeutic and possible adverse effects and claims especially on social media that the vaccines will alter the DNA. This article discusses the unique attributes of mRNA vaccines and current challenges and expectations within the context of the COVID-19 pandemic. Bangladesh Journal of Medical Science Vol.20(2) 2021 p.463-464


2013 ◽  
Vol 135 (8) ◽  
Author(s):  
Vít Průša ◽  
K. R. Rajagopal ◽  
U. Saravanan

Practically all experimental measurements related to the response of nonlinear bodies that are made within a purely mechanical context are concerned with inhomogeneous deformations, though, in many experiments, much effort is taken to engender homogeneous deformation fields. However, in experiments that are carried out in vivo, one cannot control the nature of the deformation. The quantity of interest is the deformation gradient and/or its invariants. The deformation gradient is estimated by tracking positions of a finite number of markers placed in the body. Any experimental data-reduction procedure based on tracking a finite number of markers will, for a general inhomogeneous deformation, introduce an error in the determination of the deformation gradient, even in the idealized case, when the positions of the markers are measured with no error. In our study, we are interested in a quantitative description of the difference between the true gradient and its estimate obtained by tracking the markers, that is, in the quantitative description of the induced error due to the data reduction. We derive a rigorous upper bound on the error, and we discuss what factors influence the error bound and the actual error itself. Finally, we illustrate the results by studying a practically interesting model problem. We show that different choices of the tracked markers can lead to substantially different estimates of the deformation gradient and its invariants. It is alarming that even qualitative features of the material under consideration, such as the incompressibility of the body, can be evaluated differently with different choices of the tracked markers. We also demonstrate that the derived error estimate can be used as a tool for choosing the appropriate marker set that leads to the deformation gradient estimate with the least guaranteed error.


Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 501
Author(s):  
Ignasi Esteban ◽  
Carmen Pastor-Quiñones ◽  
Lorena Usero ◽  
Montserrat Plana ◽  
Felipe García ◽  
...  

Over 36 million people worldwide are infected with HIV. Antiretroviral therapy (ART) has proven to be highly effective to prevent HIV-1 transmission, clinical progression and death. Despite this success, the number of HIV-1 infected individuals continues increasing and ART should be taken for life. Therefore, there are two main priorities: the development of preventive vaccines to protect from HIV acquisition and achieve an efficient control of HIV infection in the absence of ART (functional cure). In this sense, in the last few years, there has been a broad interest in new and innovative approaches such as mRNA-based vaccines. RNA-based immunogens represent a promising alternative to conventional vaccines because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. Some mRNA-based vaccines platforms against infectious diseases have demonstrated encouraging results in animal models and humans. However, their application is still limited because the instability and inefficient in vivo delivery of mRNA. Immunogens, design, immunogenicity, chemical modifications on the molecule or the vaccine delivery methods are all crucial interventions for improvement. In this review we, will present the current knowledge and challenges in this research field. mRNA vaccines hold great promises as part of a combined strategy, for achieving HIV functional cure.


Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Xiangyu Ou ◽  
Xue Chen ◽  
Xianning Xu ◽  
Lili Xie ◽  
Xiaofeng Chen ◽  
...  

X-ray imaging is a low-cost, powerful technology that has been extensively used in medical diagnosis and industrial nondestructive inspection. The ability of X-rays to penetrate through the body presents great advances for noninvasive imaging of its internal structure. In particular, the technological importance of X-ray imaging has led to the rapid development of high-performance X-ray detectors and the associated imaging applications. Here, we present an overview of the recent development of X-ray imaging-related technologies since the discovery of X-rays in the 1890s and discuss the fundamental mechanism of diverse X-ray imaging instruments, as well as their advantages and disadvantages on X-ray imaging performance. We also highlight various applications of advanced X-ray imaging in a diversity of fields. We further discuss future research directions and challenges in developing advanced next-generation materials that are crucial to the fabrication of flexible, low-dose, high-resolution X-ray imaging detectors.


Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 244
Author(s):  
Md. Motiar Rahman ◽  
Nan Zhou ◽  
Jiandong Huang

The mRNA-based vaccine approach is a promising alternative to traditional vaccines due to its ability for prompt development, high potency, and potential for secure administration and low-cost production. Nonetheless, the application has still been limited by the instability as well as the ineffective delivery of mRNA in vivo. Current technological improvements have now mostly overcome these concerns, and manifold mRNA vaccine plans against various forms of malignancies and infectious ailments have reported inspiring outcomes in both humans and animal models. This article summarizes recent mRNA-based vaccine developments, advances of in vivo mRNA deliveries, reflects challenges and safety concerns, and future perspectives, in developing the mRNA vaccine platform for extensive therapeutic use.


Author(s):  
Catiane Souza ◽  
Erik Menger Silveira ◽  
Emanuelle Francine Detogni Schmit ◽  
Edgar Santiago Wagner Neto ◽  
Letícia Miranda Resende da Costa ◽  
...  

Body image is an important parameter of body satisfaction and needs to be evaluated with instruments developed and validated for a specific population. The aim of this study was to develop and validate a scale to assess body image in Brazilian women. A scale consisting of 11 silhouettes was prepared. Content validation was performed by seven experts from different health areas. To assess repeatability (two consecutive assessments) and reproducibility (reassessment after one week), an intentional sample stratified into four groups according to the characterization of Brazilian women regarding nutritional status was selected. Participants were 125 women aged 18-55 years and body mass index (BMI) between 18.5 and 38.6 kg/m2. The Kappa coefficient (k) was used to assess repeatability and reproducibility, considering the isolated responses of the current body, ideal body and the difference between them, assumed as satisfactory when k≥0.6. For all trials, α=0.05. During the content validation phase, the instrument developed was changed following the evaluators’ suggestions and it was considered very suitable by six of seven evaluators. The Kappa coefficient was good in isolated issues and in the difference between them in both repeatability and reproducibility. The Body Image Scale was considered a valid content, with good repeatability and reproducibility. Considering the instrument as low cost and of rapid implementation/evaluation, it may be used to evaluate the body image of Brazilian women with BMI between 18.5 and 38.6 kg/m2, in different contexts. 


2021 ◽  
Author(s):  
Jesse Adams ◽  
Dong Yan ◽  
Jimin Wu ◽  
Vivek Boominathan ◽  
Sibo Gao ◽  
...  

Abstract Lenless microscopes that form images using simple, compact optics, along with associated computational algorithms provide several advantages: small, inexpensive form factors, large fields of view (FOV), and the ability to refocus an image after capture. To date, however, lensless microscopy has yet to be demonstrated for in vivo biological imaging. The primary challenge with in vivo bio-imaging is these dense, low-contrast scenes cannot be accurately reconstructed with existing lensless techniques. To overcome this challenge, we designed an optical phase mask that creates a point-spread function consisting of high-contrast contours with a broad spatial frequency spectrum. Here we show that this “contour” phase mask enables in vivo imaging where previous lensless imaging technologies have failed. As a proof of concept, we demonstrate 3D imaging of a behaving invertebrate, functional calcium imaging in mouse cortex, and in vivo imaging of microvasculature in the human oral mucosa. Together these results demonstrate the ability of lensless imaging to operate in realistic biological imaging applications ranging from pre-clinical animal models to clinical biomedical imaging. Overall, this “Bio-FlatScope” is a clinically relevant imaging technique with advantages of 3D computational refocusing in a low-cost, small form factor that is useful for low-resource settings and difficult-to-reach areas of the body.


Materials ◽  
2021 ◽  
Vol 14 (12) ◽  
pp. 3164
Author(s):  
Noshad Peyravian ◽  
Maziar Malekzadeh Kebria ◽  
Jafar Kiani ◽  
Peiman Brouki Milan ◽  
Masoud Mozafari

Identifying new and even more precise technologies for modifying and manipulating selectively specific genes has provided a powerful tool for characterizing gene functions in basic research and potential therapeutics for genome regulation. The rapid development of nuclease-based techniques such as CRISPR/Cas systems has revolutionized new genome engineering and medicine possibilities. Additionally, the appropriate delivery procedures regarding CRISPR/Cas systems are critical, and a large number of previous reviews have focused on the CRISPR/Cas9–12 and 13 delivery methods. Still, despite all efforts, the in vivo delivery of the CAS gene systems remains challenging. The transfection of CRISPR components can often be inefficient when applying conventional delivery tools including viral elements and chemical vectors because of the restricted packaging size and incompetency of some cell types. Therefore, physical methods such as microfluidic systems are more applicable for in vitro delivery. This review focuses on the recent advancements of microfluidic systems to deliver CRISPR/Cas systems in clinical and therapy investigations.


Author(s):  
Dongqiang Ye ◽  
Xiaole Sun ◽  
Cui Zhang ◽  
Shen Zhang ◽  
Xini Zhang ◽  
...  

Foot and ankle joints are complicated anatomical structures that combine the tibiotalar and subtalar joints. They play an extremely important role in walking, running, jumping and other dynamic activities of the human body. The in vivo kinematic analysis of the foot and ankle helps deeply understand the movement characteristics of these structures, as well as identify abnormal joint movements and treat related diseases. However, the technical deficiencies of traditional medical imaging methods limit studies on in vivo foot and ankle biomechanics. During the last decade, the dual fluoroscopic imaging system (DFIS) has enabled the accurate and noninvasive measurements of the dynamic and static activities in the joints of the body. Thus, this method can be utilised to quantify the movement in the single bones of the foot and ankle and analyse different morphological joints and complex bone positions and movement patterns within these organs. Moreover, it has been widely used in the field of image diagnosis and clinical biomechanics evaluation. The integration of existing single DFIS studies has great methodological reference value for future research on the foot and ankle. Therefore, this review evaluated existing studies that applied DFIS to measure the in vivo kinematics of the foot and ankle during various activities in healthy and pathologic populations. The difference between DFIS and traditional biomechanical measurement methods was shown. The advantages and shortcomings of DFIS in practical application were further elucidated, and effective theoretical support and constructive research direction for future studies on the human foot and ankle were provided.


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