Designing neoantigen cancer vaccines, trials, and outcomes.

Neoantigen vaccines are based on epitopes of antigenic parts of mutant proteins expressed in cancer cells. These highly immunogenic antigens may trigger the immune system to combat cancer cells. Improvements in sequencing technology and computational tools have resulted in several clinical trials of neoantigen vaccines on cancer patients. In this review, we have looked into the design of the vaccines which are undergoing several clinical trials. We have discussed the criteria, processes, and challenges associated with the design of neoantigens. We searched different databases to track the ongoing clinical trials and their reported outcomes. We observed, in several trials, the vaccines boost the immune system to combat the cancer cells while maintaining a reasonable margin of safety. Detection of neoantigens has led to the development of several databases. Adjuvants also play a catalytic role in improving the efficacy of the vaccine. Through this review, we can conclude that the efficacy of vaccines can make it a potential treatment across different types of cancers.

Binned Data Provide Better Imputation of Missing Time Series Data from Wearables.

The presence of missing values in a time-series dataset is a very common and well-known problem. Various statistical and machine learning methods have been developed to overcome this problem, with the aim of filling in the missing values in the data. However, the performances of these methods vary widely, showing a high dependence on the type of data and correlations within the data. In our study, we performed some of the well-known imputation methods, such as expectation maximization, k-nearest neighbor, iterative imputer, random forest, and simple imputer, to impute missing data obtained from smart, wearable health trackers. In this manuscript, we proposed the use of data binning for imputation. We showed that the use of data binned around the missing time interval provides a better imputation than the use of a whole dataset. Imputation was performed for 15 min and 1 h of continuous missing data. We used a dataset with different bin sizes, such as 15 min, 30 min, 45 min, and 1 h, and we carried out evaluations using root mean square error (RMSE) values. We observed that the expectation maximization algorithm worked best for the use of binned data. This was followed by the simple imputer, iterative imputer, and k-nearest neighbor, whereas the random forest method had no effect on data binning during imputation. Moreover, the smallest bin sizes of 15 min and 1 h were observed to provide the lowest RMSE values for the majority of the time frames during the imputation of 15 min and 1 h of missing data, respectively. Although applicable to digital health data, we think that this method will also find applicability in other domains.

Isolation, Detection and Analysis of Circulating Tumour Cells: A Nanotechnological Bioscope.

Cancer is one of the dreaded diseases to which a sizeable proportion of the population succumbs every year. Despite the tremendous growth of the health sector, spanning diagnostics to treatment, early diagnosis is still in its infancy. In this regard, circulating tumour cells (CTCs) have of late grabbed the attention of researchers in the detection of metastasis and there has been a huge surge in the surrounding research activities. Acting as a biomarker, CTCs prove beneficial in a variety of aspects. Nanomaterial-based strategies have been devised to have a tremendous impact on the early and rapid examination of tumor cells. This review provides a panoramic overview of the different nanotechnological methodologies employed along with the pharmaceutical purview of cancer. Initiating from fundamentals, the recent nanotechnological developments toward the detection, isolation, and analysis of CTCs are comprehensively delineated. The review also includes state-of-the-art implementations of nanotechnological advances in the enumeration of CTCs, along with future challenges and recommendations thereof.

Smart Consumer Wearables as Digital Diagnostic Tools: A Review.

The increasing usage of smart wearable devices has made an impact not only on the lifestyle of the users, but also on biological research and personalized healthcare services. These devices, which carry different types of sensors, have emerged as personalized digital diagnostic tools. Data from such devices have enabled the prediction and detection of various physiological as well as psychological conditions and diseases. In this review, we have focused on the diagnostic applications of wrist-worn wearables to detect multiple diseases such as cardiovascular diseases, neurological disorders, fatty liver diseases, and metabolic disorders, including diabetes, sleep quality, and psychological illnesses. The fruitful usage of wearables requires fast and insightful data analysis, which is feasible through machine learning. In this review, we have also discussed various machine-learning applications and outcomes for wearable data analyses. Finally, we have discussed the current challenges with wearable usage and data, and the future perspectives of wearable devices as diagnostic tools for research and personalized healthcare domains.

Types of spectroscopy and microscopy techniques for cancer diagnosis: a review.

Cancer is a life-threatening disease that has claimed the lives of many people worldwide. With the current diagnostic methods, it is hard to determine cancer at an early stage, due to its versatile nature and lack of genomic biomarkers. The rapid development of biophotonics has emerged as a potential tool in cancer detection and diagnosis. Using the fluorescence, scattering, and absorption characteristics of cells and tissues, it is possible to detect cancer at an early stage. The diagnostic techniques addressed in this review are highly sensitive to the chemical and morphological changes in the cell and tissue during disease progression. These changes alter the fluorescence signal of the cell/tissue and are detected using spectroscopy and microscopy techniques including confocal and two-photon fluorescence (TPF). Further, second harmonic generation (SHG) microscopy reveals the morphological changes that occurred in non-centrosymmetric structures in the tissue, such as collagen. Again, Raman spectroscopy is a non-destructive method that provides a fingerprinting technique to differentiate benign and malignant tissue based on Raman signal. Photoacoustic microscopy and spectroscopy of tissue allow molecule-specific detection with high spatial resolution and penetration depth. In addition, terahertz spectroscopic studies reveal the variation of tissue water content during disease progression. In this review, we address the applications of spectroscopic and microscopic techniques for cancer detection based on the optical properties of the tissue. The discussed state-of-the-art techniques successfully determines malignancy to its rapid diagnosis.

Deep learning-based image processing in optical microscopy.

Optical microscopy has emerged as a key driver of fundamental research since it provides the ability to probe into imperceptible structures in the biomedical world. For the detailed investigation of samples, a high-resolution image with enhanced contrast and minimal damage is preferred. To achieve this, an automated image analysis method is preferable over manual analysis in terms of both speed of acquisition and reduced error accumulation. In this regard, deep learning (DL)-based image processing can be highly beneficial. The review summarises and critiques the use of DL in image processing for the data collected using various optical microscopic techniques. In tandem with optical microscopy, DL has already found applications in various problems related to image classification and segmentation. It has also performed well in enhancing image resolution in smartphone-based microscopy, which in turn enablse crucial medical assistance in remote places.

Elucidating Methods for Isolation and Quantification of Exosomes: A Review.

Exosomes are the smallest extracellular vesicles present in most of the biological fluids. They are found to play an important role in cell signaling, immune response, tumor metastasis, etc. Studies have shown that these vesicles also have diagnostic and therapeutic roles for which their accurate detection and quantification is essential. Due to the complexity in size and structure of exosomes, even the gold standard methods face challenges. This comprehensive review discusses the various standard methods such as ultracentrifugation, ultrafiltration, size-exclusion chromatography, precipitation, immunoaffinity, and microfluidic technologies for the isolation of exosomes. The principle of isolation of each method is described, as well as their specific advantages and disadvantages. Quantification of exosomes by nanoparticle tracking analysis, flow cytometry, tunable resistive pulse sensing, electron microscopy, dynamic light scattering, and microfluidic devices are also described, along with the applications of exosomes in various biomedical domains.

Structural and molecular basis of the interaction mechanism of selected drugs towards multiple targets of SARS-CoV-2 by molecular docking and dynamic simulation studies- deciphering the scope of repurposed drugs.

The repurposing of FDA approved drugs is presently receiving attention for COVID-19 drug discovery. Previous studies revealed the binding potential of several FDA-approved drugs towards specific targets of SARS-CoV-2; however, limited studies are focused on the structural and molecular basis of interaction of these drugs towards multiple targets of SARS-CoV-2. The present study aimed to predict the binding potential of six FDA drugs towards fifteen protein targets of SARS-CoV-2 and propose the structural and molecular basis of the interaction by molecular docking and dynamic simulation. Based on the literature survey, fifteen potential targets of SARS-CoV-2, and six FDA drugs (Chloroquine, Hydroxychloroquine, Favipiravir, Lopinavir, Remdesivir, and Ritonavir) were selected. The binding potential of individual drug towards the selected targets was predicted by molecular docking in comparison with the binding of the same drugs with their usual targets. The stabilities of the best-docked conformations were confirmed by molecular dynamic simulation and energy calculations. Among the selected drugs, Ritonavir and Lopinavir showed better binding towards the prioritized targets with minimum binding energy (kcal/mol), cluster-RMS, number of interacting residues, and stabilizing forces when compared with the binding of Chloroquine, Favipiravir, and Hydroxychloroquine, later drugs demonstrated better binding when compared to the binding with their usual targets. Remdesvir showed better binding to the prioritized targets in comparison with the binding of Chloroquine, Favipiravir, and Hydroxychloroquine, but showed lesser binding potential when compared to the interaction between Ritonavir and Lopinavir and the prioritized targets. The structural and molecular basis of interactions suggest that the FDA drugs can be repurposed towards multiple targets of SARS-CoV-2, and the present computational models provide insights on the scope of repurposed drugs against COVID-19.

Elucidating the microscopic and computational techniques to study the structure and pathology of SARS-CoVs.

Severe Acute Respiratory Syndrome Coronaviruses (SARS-CoVs), causative of major outbreaks in the past two decades, has claimed many lives all over the world. The virus effectively spreads through saliva aerosols or nasal discharge from an infected person. Currently, no specific vaccines or treatments exist for coronavirus; however, several attempts are being made to develop possible treatments. Hence, it is important to study the viral structure and life cycle to understand its functionality, activity, and infectious nature. Further, such studies can aid in the development of vaccinations against this virus. Microscopy plays an important role in examining the structure and topology of the virus as well as pathogenesis in infected host cells. This review deals with different microscopy techniques including electron microscopy, atomic force microscopy, fluorescence microscopy as well as computational methods to elucidate various prospects of this life-threatening virus.