The purpose of this mini-review is to make an update about the present and future applications of saliva as a diagnostic biofluid in many fields of science such as dentistry, medicine and pharmacotherapy. Using saliva as a fluid for diagnostic purposes would be a huge breakthrough for both patients and healthcare providers since saliva collection is easy, non-invasive and inexpensive. We will go through the current main diagnostic applications of saliva, and provide a highlight on the emerging, newly developing technologies and tools for cancer screening, detection and monitoring. AbstractIn this review, we provide an update on the current and future applications of saliva for diagnostic purposes. There are many advantages of using saliva as a biofluid. Its collection is fast, easy, inexpensive, and non-invasive. In addition, saliva, as a ''mirror of the body,'' can reflect the physiological and pathological state of the body. Therefore, it serves as a diagnostic and monitoring tool in many fields of science such as medicine, dentistry, and pharmacotherapy. Introduced in 2008, the term ''Salivaomics'' aimed to highlight the rapid development of knowledge about various ''omics'' constituents of saliva, including: proteome, transcriptome, micro-RNA, metabolome, and microbiome. In the last few years, researchers have developed new technologies and validated a wide range of salivary biomarkers that will soon make the use of saliva a clinical reality. However, a great need still exists for convenient and accurate point-of-care devices that can serve as a non-invasive diagnostic tool. In addition, there is an urgent need to decipher the scientific rationale and mechanisms that convey systemic diseases to saliva. Another promising technology called liquid biopsy enables detection of circulating tumor cells (CTCs) and fragments of tumor DNA in saliva, thus enabling non-invasive early detection of various cancers. The newly developed technology-electric field-induced release and measurement (EFIRM) provides near perfect detection of actionable mutations in lung cancer patients. These recent advances widened the salivary diagnostic approach from the oral cavity to the whole physiological system, and thus point towards a promising future of salivary diagnostics for personalized individual medicine applications including clinical decisions and post-treatment outcome predictions.

Congestive heart failure (CHF) is a leading cause of death in the United States affecting approximately 670,000 individuals. Due to the prevalence of CHF related issues, it is prudent to seek out methodologies that would facilitate the prevention, monitoring, and treatment of heart disease on a daily basis. This paper describes WANDA (Weight and Activity with Blood Pressure Monitoring System); a study that leverages sensor technologies and wireless communications to monitor the health related measurements of patients with CHF. The WANDA system is a three-tier architecture consisting of sensors, web servers, and back-end databases. The system was developed in conjunction with the UCLA School of Nursing and the UCLA Wireless Health Institute to enable early detection of key clinical symptoms indicative of CHF-related decompensation. This study shows that CHF patients monitored by WANDA are less likely to have readings fall outside a healthy range. In addition, WANDA provides a useful feedback system for regulating readings of CHF patients.

Saliva is a non-invasive biofluid, which is easy to collect, transport, and store. Because of its accessibility and connection to systemic diseases, saliva is one of the best candidates for the advancement of point-of-care medicine, where individuals are able to easily monitor their health status by using portable convenient tools such as smartphones. There are a variety of scenarios with which saliva can be used: studies have been conducted on using saliva to measure stress hormones, enzyme levels, developmental disease biomarkers, and even cancer mutations. If validated biomarkers were combined with high-quality detection tools, saliva would open up a new frontier in high-quality healthcare, allowing physicians and patients to work together for real-time health monitoring and high-impact personalized preventative medicine. One of the most exciting emerging frontiers of saliva is liquid biopsy, which is a non-invasive means to assess the presence and characteristics of cancer in a patient. This article will review current basic knowledge of biomarkers, review their relation to different diseases and conditions, and explore liquid biopsy for point-of-care applications.

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Previous efforts to evaluate the detection of human papilloma viral (HPV) DNA in whole saliva as a diagnostic measure for HPV-associated oropharyngeal cancer (HPV-OPC) have not shown sufficient clinical performance. We hypothesize that salivary exosomes are packaged with HPV-associated biomarkers, and efficient enrichment of salivary exosomes through isolation can enhance diagnostic and prognostic performance for HPV-OPC. In this study, an acoustofluidic (the fusion of acoustics and microfluidics) platform was developed to perform size-based isolation of salivary exosomes. These data showed that this platform is capable of consistently isolating exosomes from saliva samples, regardless of viscosity variation and collection method. Compared with the current gold standard, differential centrifugation, droplet digital RT-PCR analysis showed that the average yield of salivary exosomal small RNA from the acoustofluidic platform is 15 times higher. With this high-yield exosome isolation platform, we show that HPV16 DNA could be detected in isolated exosomes from the saliva of HPV-associated OPC patients at 80% concordance with tissues/biopsies positive for HPV16. Overall, these data demonstrated that the acoustofluidic platform can achieve high-purity and high-yield salivary exosome isolation for downstream salivary exosomeebased liquid biopsy applications. Additionally, HPV16 DNA sequences in HPV-OPC patients are packaged in salivary exosomes and their isolation will enhance the detection of HPV16 DNA.

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Fused PET/MRI is more reliable for focal invasion assessment and tumor size delineation in advanced BSCC compared with PET/CT, MRI, and CT. PET/CT has the lowest confidence level, which may limit its use in the clinical setting.