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(SD2022-260) Selective Imaging and Inhibition of SARS-CoV-2 Infected Cells, Using A Tunable Protease-Responsive Modular-Peptide-Conjugated AIEgen

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious threat to human health without effective treatment. There is an urgent need for both real-time tracking and precise treatment of the SARS-CoV-2 infected cells to mitigate and ultimately prevent viral transmission. However, selective and responsive triggering and tracking of the therapeutic processin infected cells remains challenging.

(SD2022-066) Simultaneous assessment of afferent and efferent visual pathways using multi‐focal steady‐state visual evoked potenital method to facilitate the diagnosis and prognosis of individuals with neurological diseases.

Researchers from UC San Diego have developed a patent-pending wearable device for concurrently assessing afferent and efferent visual functions. The invention details novel mobile brain-computer interfacing methods and systems for concurrently assessing afferent and efferent visual functions.

(SD2023-036) Matrix-insensitive approach for protease detection

Researchers at UC San Diego have developed a dipeptide composed of two arginine (Arg-Arg) that is capable of inducing the assembly of citrate-capped gold nanoparticles (AuNPs-citrate). Surprisingly, the resulting Arg-Arg-AuNPs are stable over time as the peptide protects the particles from degradation. The assemblies can even be dried without any loss of particles. The assembly of AuNPs-citrate changes their optical properties and the color of the suspension turns from red to blue. Importantly, the assemblies can be dissociated with thiolated polyethylene glycol (HS-PEGs) molecules which leads to the recovery of the initial optical properties of the AuNPs, i.e. the red color of the suspension. Surprisingly, we have observed that such dissociation of AuNPs assemblies is not sensitive to the composition of the medium. It can thus be performed in biological fluids such as pure plasma, saliva, urine, bile, cell lysates or even sea water.

(SD2022-320) Method to improve the sampling rate for photoacoustic imaging

High-frequency photoacoustic tomography (> 20 MHz) is becoming increasingly important in biomedical applications. However, it requires data acquisition (DAQ) to have commensurately high sampling rate, which imposes challenges to hardwires and increases the cost of building a PA imaging system. For example, the sampling rate should be higher than 80 MHz to cover 100% bandwidth of a 26-MHz transducer (Nuquist limit). A commercial PA imaging system such as Vevo LAZR X (Fujifilm VISUALSONICS Inc. ON, Canada) with 80-MHz sampling rate can cost more than 990,000$ in the United States.Many PA groups use clinical ultrasound DAQs, which are low cost but also have a low sampling rate, e.g., the iu22 system’s sampling rate is 32 MHz.

(SD2021-262) A wearable tool for colorimetric monitoring of proteases

Facemasks in congregate settings prevent the transmission of SARS-CoV-2 and help control the ongoing COVID-19 global pandemic because face coverings can arrest transmission of respiratory droplets. While many groups have studied face coverings as personal protective equipment, these respiratory droplets can also serve as a diagnostic fluid to report on health state; surprisingly, studies of face coverings from this perspective are quite limited.

(SD2020-421) Virtual Electrodes for Imaging of Cortex-Wide Brain Activity: Decoding of cortex-wide brain activity from local recordings of neural potentials

As an important tool for electrophysiological recordings, neural electrodes implanted on the brain surface have been instrumental in basic neuroscience research to study large-scale neural dynamics in various cognitive processes, such as sensorimotor processing as well as learning and memory. In clinical settings, neural recordings have been adopted as a standard tool to monitor the brain activity in epilepsy patients before surgery for detection and localization of epileptogenic zones initiating seizures and functional cortical mapping. Neural activity recorded from the brain surface exhibits rich information content about the collective neural activities reflecting the cognitive states and brain functions. For the interpretation of surface potentials in terms of their neural correlates, most research has focused on local neural activities.   From basic neuroscience research to clinical treatments and neural engineering, electrocorticography (ECoG) has been widely used to record surface potentials to evaluate brain function and develop neuroprosthetic devices. However, the requirement of invasive surgeries for implanting ECoG arrays significantly limits the coverage of different cortical regions, preventing simultaneous recordings from spatially distributed cortical networks. However, this rich information content of surface potentials encoded for the large-scale cortical activity remains unexploited and little is known on how local surface potentials are correlated with the spontaneous neural activities of distributed large-scale cortical networks. Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:8.0pt; mso-para-margin-left:0in; line-height:107%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

(SD2021-212) A tool to assess and monitor wound health -

Researchers from UC San Diego have developed a patent-pending device that solves all these major limitations. It is a quick, inexpensive, non-radiative, non-invasive,  point-of-care imaging modality.  The inventors created a fast,  point-of-care imaging technique that can image deep within soft tissues. This technique can be used to monitor. wound health over long periods of time.  This ultrasound imaging technology is poised to become a medical imaging tool to measure, and visualize wound size, progression, tunneling, and skin graft integration or rejection.

(SD2022-014) Neural Signal Detection of Immune Responses: miniaturized wireless data streaming system to detect early infection

A promising area of clinical research has been growing in wearable diagnostics that has proven to be a powerful tool in healthy physiological as well as disease diagnostics. As the field grows and develops, a number of specializations are already emerging including diagnostics focused on: cardiac dysfunction, epilepsy, and most recently infectious disease detection.

(SD2019-220) Spatiotemporal resolution enhancement of biomedical images

Cardiac MRI is the clinical reference standard for visual and quantitative assessment of heart function. Specifically, cine balanced steady-state free precession (SSFP) can yield cardiac images with high myocardium–blood pool contrast for evaluation of left ventricular (LV) function. However, MRI suffers from long acquisition times, often requiring averaging across multiple heartbeats, and necessitates a trade-off among spatial resolution, temporal resolution, and scan time. Clinically, radiologists are forced to balance acquisition time with resolution to fit clinical needs, and certain applications such as real-time imaging may require small acquisition matrices. Image scaling is typically performed by using conventional upscaling methods, such as Fourier domain zero padding and bicubic interpolation. These methods, however, do not readily recover spatial detail, such as the myocardium–blood pool interface or delineation of papillary muscles.

(SD2021-055) Mass Spectrometry-Based Detection of Beta Lactam Hydrolysis Enables Rapid Detection of Beta Lactamase Mediated Antibiotic Resistance

Beta-lactam antibiotics account for the majority of antibiotics used worldwide. Resistance by beta-lactamase expression is a serious and growing threat. The typical workflow in a clinical microbiology laboratory leading to identification of antibiotic resistant organisms consists of 1) sample plating and mixed growth, 2) pathogen isolation and growth, 3) identification of the organism by biochemical tests or  Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF), and finally 4) observed growth in antibiotic containing media to determine antibiotic susceptibility/resistance patterns. This workflow requires 36 to 72 hours, involves multiple manual steps, and may not detect inducible resistance. The evolution and spread of antibiotic resistance among human pathogens represents a serious public health threat. Faster identification of the presence of antibiotic resistant organisms is a key component in the effort to reduce the spread of antibiotic resistance, as evidenced by the inclusion of diagnostic development in the CDC’s national strategy to combat antibiotic resistance. Given the clinical challenges that beta-lactamase expressing pathogens present, there is a clear need for faster identification to both enable effective treatment and to enact isolation precautions preventing further spread of resistant organisms Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:8.0pt; mso-para-margin-left:0in; line-height:107%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

(SD2021-057) Electro-optical mechanically flexible microprobes for minimally invasive interfacing with intrinsic neural circuits

Microelectrodes are the gold standard for measuring the activity of individual neurons at high temporal resolution in any nervous system region and central to defining the role of neural circuits in controlling behavior.Microelectrode technologies such as the Utah or Michigan arrays, have allowed tracking of distributed neural activity with millisecond precision. However, their large footprint and rigidity lead to tissue damage and inflammation that hamper long-term recordings. State of the art Neuropixel and carbon fiber probes have improved on these previous devices by increasing electrode density and reducing probe dimensions and rigidity.Although these probes have advanced the field of recordings, next-generation devices should enable targeted stimulation in addition to colocalized electrical recordings. Optogenetic techniques enable high-speed modulation of cellular activity through targeted expression and activation of light-sensitive opsins. However, given the strong light scattering and high absorption properties of neural tissue optogenetic interfacing with deep neural circuits typically requires the implantation of large-diameter rigid fibers, which can make this approach more invasive than its electrical counterpart.Approaches to integrating optical and electrical modalities have ranged from adding fiber optics to existing Utah arrays to the Optetrode or other integrated electro-optical coaxial structures. These technologies have shown great promise for simultaneous electrical recordings and optical stimulation in vivo. However, the need to reduce the device footprint to minimize immune responses for long-term recordings is still present.

(SD2021-402) Fully Automated Deep Learning‐Based Background Phase Error Correction for Abdominopelvic 4D Flow MRI

4D Flow MRI has become increasingly valuable for the qualitative and quantitative assessment of cardiovascular disease. Since all measurements can be obtained following image acquisition without the need for targeted ultrasonographic windows or placement of 2D phase contrast planes at the time of the exam, 4D Flow provides versatility that can be essential in the diagnostic process.However, the correction of magnetic eddy current-related background phase error remains a critical bottleneck in abdominal applications.

(SD2021-221) Automated deep correction of MRI phase‐error

Time-resolved 3D phase-contrast MRI with three-dimensional velocity encoding (4D Flow MRI) has become increasingly valuable for the evaluation of cardiovascular disease. While cardiothoracic and neurovascular applications have grown rapidly, a limiting factor for abdominal applications is the correction of magnetic eddy current-related background phase error, which can be more challenging to reliably correct in abdominopelvic regions due to complex vascular and soft tissue geometry. Phase-error correction is essential for both quantification of blood flow as well as for visualization.

(SD2021-401) Automated Correction of Background Phase Error for Cerebrovascular 4D Flow MRI

Currently, there are no automated solutions for phase‐error correction that are effective for brain imaging.

Development of Biomarker Panel and Methods to Monitor Kidney Health

It has been shown that intensive BP lowering results in higher blood creatinine, which is typically indicative of decreased kidney function, thereby causing physicians concern that the patient is suffering from kidney damage. However, an increase in blood creatinine levels may also be due to changes in blood flow, a hemodynamic effect that is benign to the patient. Sodium glucose transporter 2 (SGLT2) inhibitors are a relatively new class of drugs for treating type 2 diabetes, which have been shown to result in lower risk for progression to dialysis in long-term follow-up. However, when patients first begin a therapeutic regimen of SGLT2 inhibitors, they typically experience an acute change in blood flow to the kidney, which results in a rise in serum creatinine. This causes concerns to practitioners that the drug may be harming the kidneys, rather than being beneficial long term. While some patients may indeed experience intrinsic kidney damage due to marked reductions in blood flow, resulting in cessation of SGLT2 inhibitor therapy and the benefit associated therewith, there is currently no way to differentiate between these two patterns of creatinine change. Thus, a need exists for diagnostic test to differentiate intrinsic kidney damage from hemodynamic changes in patients taking SGLT2 inhibitors for diabetes mellitus.

New Non-Invasive Markers To Assess Efficacy Of Anti-Integrin Therapies

Inflammatory bowel disease is a chronic disease, which affects the lower bowel parts or the entire GI tract, causing symptoms like abdominal pain, diarrhea, fever and weight loss. An estimated two million people in North America suffer from IBD seemingly caused by an overactive mucosal immune system. Crohn’s Disease and ulcerative colitis (UC) are the major groups of inflammatory conditions that make up IBD and are incurable, serious and chronic organic diseases of the intestinal tract.   Recently, anti-integrin monoclonal antibodies have been approved by the FDA as therapeutic agents for treatment of IBD and there are a number of phase three clinical trials ongoing using monoclonal antibody therapy. The immune system responds to the inflammation that is part of the immunopathology of IBD and acts by recruiting inflammatory cells to the intestinal lesions.  Intergrins, specifically alpha 4-β7, plays a key role in mediating leukocyte trafficking from the circulation to the vascular endothelial barrier in gut-associate lymphoid tissue with the ligand MAdCAM-1. The use of anti-integrin therapy targeting alpha 4-β7 reduces the number of immune cells to the gut endothelium. However, the precise identity of the cell subsets depleted from the intestinal lamina by these anti-integrin drugs have not been identified. Thus, there is an unmet need to further develop tools that allow for the identification of the critical effector cell subsets targeted by these drugs in the intestine.

Development of Methods and Assay for Measurement of Total Oxidized Phospholipid (OxPL)

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States. It can be broadly sub-classified into nonalcoholic fatty liver (NAFL), which is thought to have minimal risk of progression to cirrhosis, and nonalcoholic steatohepatitis (NASH), which is thought to have an increased risk of progression to cirrhosis. The current diagnostic gold standard for differentiating whether a patient with NAFLD has NAFL versus NASH is liver biopsy. However, liver biopsy is an invasive procedure, which is limited by sampling variability, cost, and may be complicated by morbidity and even death, although rare. Accurate, non-invasive, biomarkers for the detection of liver disease and liver disease progression e.g., progression to NASH, are currently also not available.

Detecting Cardiovascular Disease Using Noninvasive Imaging of the Eye

Cardiovascular disease is the leading cause of mortality and disability worldwide. It is also prevalent, affecting 9% of the population over 20 years of age. Patients with cardiovascular risk factors can reduce their risk of developing catastrophic cardiovascular events such as heart attack and stroke through lifestyle modification and medications. Unfortunately for many, the disease may go undiagnosed until the occurrence of serious events. Identifying biomarkers of subclinical ischemia can help identify patients with occult cardiovascular disease.

(SD2020-238) Blood Flow Velocimetry via Data Assimilation of Medical Imaging

Cardiovascular disease (CVD) is a tremendous burden on the population in terms of morbidity and mortality, as well as on the healthcare system in terms of cost. Various forms of CVD including atherosclerosis, valve and ventricular dysfunction, aneurysms, and thrombogenesis can be identified by measuring localized abnormalities in blood flow. Accordingly, the ability to noninvasively interrogate physiological flows enables identification and diagnosis of disease, monitoring of the effects of therapy, and research on the hemodynamic nature of CVD and its associated interventions. In the clinic, blood flow measurements are primarily made using phase contrast magnetic resonance imaging (PC-MRI) and ultrasonic color Doppler imaging. Certain limitations of these techniques for patients who have contraindications or suffer from arrhythmias, as well as the desire for volumetric flow information necessitate the development of a new modality for blood flow velocimetry.

Use of UBA7 and its Regulated Genes as Novel Biomarkers in Treating Human Cancers

Human Ubiquitin-like modifier-activating enzyme 7 (UBA7) is a protein is involved in protein modification, specifically involving the pathway for protein ubiquitination. The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. UBA7  encodes a member of the E1 ubiquitin-activating enzyme family. Moreover, ubiquitination and ubiquitin-like post-translational modifications (PTMs) regulate activity and stability of oncoproteins and tumor suppressors. Biomarkers are very important as companion diagnostic tools to guide clinical practice in treating human cancers, especially for targeted therapies. In the era of precision medicine, it is important for development companion diagnostic tools that can guide clinical practice for treating human cancers using targeted therapies.

Breast Milk Biomarkers for Child Chronic Health Disorders

Autism Spectrum Disorder (ASD) is a developmental disorder associated with difficulties in social interaction and communication as well as repetitive behavior. ASD is thought to be the result of genetic and environmental factors that affect approximately 1 in 59 children in the US, and 25 million people worldwide. The current method of diagnosis for ASD involves evaluations and tests performed by a team of specialists.  The latest forms of diagnosis can detect ASD as early as 18 months. However, more standard methods take until 4 years of age before the diagnosis of ASD is confirmed. There remains an unmet need to develop a reliable and accurate diagnostic methods for early detection for a child at risk with chronic and/or developmental disorders, such as ASD, so that an early intervention measures will be applied before the first symptoms appear.

Chip-Based Detection Of Diabetes Related Biomarkers

A major goal in disease screening, diagnosis, and control has been to develop bioassay platforms capable of simultaneous measurements of different analytes in a single assay. Significant advances toward multiplexed biomarker detection chips based on either immunoassays or enzymatic bioassays have thus been reported. However, the combination of enzymatic and immunoassay sensing into a single disposable system has hitherto not been addressed.

Expression-based Diagnosis of Autism Spectrum Disorder and Potential Prognosis of other Complex Diseases

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with prenatal and early postnatal biological onset. Genetic factors contribute to the predisposition and development of ASD with estimated heritability rates of 50-83%. Large-scale genetic studies have implicated several hundred risk (rASD) genes that appear to be associated with many different pathways, cell processes, and neurodevelopmental stages. This highly heterogeneous genetic landscape has raised challenges in elucidating the biological mechanisms involved in the disorder. While rigorous proof remains lacking, current evidence suggests that rASD genes fall into networks and biological processes that modulate one or more critical stages of prenatal and early postnatal brain development, including neuronal proliferation, migration, neurite growth, synapse formation and function. However, these insights are mostly gained from focused studies on single rASD genes or based on transcriptome data of non-ASD brains, leaving an incomplete picture of rASD-induced molecular changes at the individual level and relationships with early-age clinical heterogeneity.

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