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(SD2021-430) Deep learning volumetric deformable registration: CNN-based Deformable Registration Facilitates Fast and Accurate Air Trapping Measurements at Inspiratory and Expiratory CT

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; mso-font-kerning:1.0pt; mso-ligatures:standardcontextual;} Researchers from UC San Diego developed a patent-pending convolutional neural network (CNN)-based deformable registration algorithm to reduce computation time for analysis of medical images such as CT and MRI. These fast, fully-automated CNN-based lung deformable registration algorithms can facilitate translation of measurements into clinical practice, potentially improving the diagnosis and severity assessment of small airway diseases.

COMPOUNDS FOR MODULATING EPITHELIAL 15-(S)-LIPOXYGENASE-2 AND METHODS OF USE FOR SAME

Lipoxygenases (LOX) are enzymes that catalyze the peroxidation of certain fatty acids. The cell membrane is mostly made of lipids (which include fatty acids), and peroxidation can cause damage to the cell membrane. The human genome contains six functional LOX genes that encode for six LOX enzyme variants, or isozymes. The role that each LOX isozyme plays in health and disease varies greatly, spanning issues such as asthma, diabetes, and stroke. LOX enzymes are extremely difficult to target due to high hydrophobicity. Potential leads are often ineffective because they are either not readily soluble or not selective for a particular LOX enzyme.  Studies have implicated human epithelial 15-lipoxygenase-2 (h15-LOX-2, ALOX15B) in various diseases. h15-LOX-2 is highly expressed in atherosclerotic plaques and is linked to the progression of macrophages to foam cells, which are present in atherosclerotic plaques. h15-LOX-2 mRNA levels are also highly elevated in human macrophages isolated from carotid atherosclerotic lesions in symptomatic patients. Children with cystic fibrosis had reduced levels of h15-LOX-2, which affects the lipoxin A4 to leukotriene B4 ratio. Furthermore, the interactions of h15-LOX-2 and PEBP1 changes the substrate specificity of h15-LOX-2 from free polyunsaturated fatty acids (PUFA) to PUFA-phosphatidylethanolamines (PE), leading to the generation of hydroperoxyeicosatetraenoic acid (HpETE) esterified into PE (HpETE-PE). Accumulation of these hydroperoxyl membrane phospholipids has been shown to cause ferroptotic cell death, which implicates h15-LOX-2 in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.  

Rapid optical detection system for SARS-CoV-2 and other pathogens

Researchers at UC Irvine have developed an optical detection system for SARS-CoV-2 and other pathogens that features improvements in screening time, cost, sensitivity, and practicality. As vaccine availability, economic pressure, and mental health considerations has gradually returned society to pre-pandemic activities that require frequent and close interactions, it is imperative that SARS-CoV-2 detection systems remain effective.

Aerosol Ionization For Charge Detection Mass Spectrometry Ion Mobility Analysis

Existing screening tools for respiratory pathogens, including PCR-based methods and antibody-based methods, are generally time-consuming to perform and analyze, difficult to manufacture at scale, and reliant on a detailed understanding of the targeted pathogen. Additionally, these traditional methods give little insight into the extent to which an individual is capable of spreading the disease. All of these features hamstring early responses to emerging pathogens and early-stage epidemics, as can be seen from the ongoing SARS-COV-2 pandemic. To address these problems, researchers at UC Berkeley have developed a device which ionizes large biomolecules from aerosol droplets and routes them to the inlet of a mass spectrometer or ion mobility spectrometer for identification based on size and/or mass. This can serve as the basis for a screening tool which measures the concentration of pathogenic particles, including common respiratory viruses and bacteria, in the breath. Results from this test could be read out in a matter of seconds, and it does not depend on detailed knowledge of the pathogen in question. Researchers have demonstrated the efficacy of such a device in detecting both large human proteins and virus-sized styrofoam particles.

Peptide Inhibitors of Human Voltage Gated Proton Channel hHv1 Activity to Reduce Inflammation

Human voltage-gated proton channels (hHv1) are implicated in a wide range of biological responses, including capacitation of sperm and stimulation of the innate immune response. Human sperm undergo a process called capacitation in the female reproductive tract, whereby intracellular pH rises and stimulates a progesterone-induced Ca2+ influx.  Researchers at the University of California, Irvine have discovered that this calcium influx is controlled by albumin activation of Hv1 voltage-gated proton channels.  Albumin activation of hHV1 in neutrophils also supports production and release of reactive oxygen species and protease during the immune respiratory burst.  These findings demonstrating a stimulatory role of albumin in both sperm and neutrophils has led to new therapeutic approaches to fertility and the treatment of inflammatory diseases.

Fem1b Inhibitors

UC Berkeley researchers have discovered novel, specific Fem1b inhibitors. Fem1b is essential in lymphoma and lung cancer cells.  Fem1b inhibition could be beneficial in cancer, metabolic disease, obesity, diabetes and other diseases. 

Anti-microbial, Immune-modulating, Naturally-derived Adjunctive Therapies

Researchers at the University of California, Davis have developed adjunctive therapies applicable to multiple types of infectious conditions. These therapies – derived from compounds found in natural herbs - also have potential prophylactic efficacy.

MicroRNA regulation of airway mucins for treatment of lung diseases

This invention describes a novel therapeutic microRNA target regulating mucus production for the management of symptoms caused by a range of lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, and the common cold. Recently, a specific miRNA, along with its highly homologous family members, has been shown to be dysregulated in asthmatic subjects. To modulate the effect of these miRNAs, antagomirs (which target specific endogenous miRNAs and dampen their effect) or miRNA mimics can be administered via an inhaler, allowing for the regulation of mucus production. This invention is at the preclinical stage, and in vivo testing in a mouse model of asthma has shown that treatment with a specific miRNA antagomir results in a significant reduction of airway mucus production. While there are currently no effective therapies targeting mucus production in the airways, miRNAs are a promising new avenue for therapeutic intervention as they are fast-acting and reversible. 

Mapping Ciliary Activity Using Phase Resolved Spectrally Encoded Interferometric Microscopy

Researchers at UCI have developed an imaging technique that can monitor and measure small mobile structures called cilia in our airways and in the oviduct. This invention will serve as a stepping stone for study of respiratory diseases, oviduct ciliary colonoscopy and future clinical translations.

Use of inhibitors and cell based therapies to combat a fatal immune response in COVID-19

UC researchers sought to define the host immune response, the “cytokine storm” , that has been implicated in fatal COVID-19 using an AI-based approach. Over 45,000 publicly available transcriptomic datasets of viral pandemics were analyzed to extract a 166-gene signature. The signature was surprisingly conserved in all viral pandemics, including COVID-19, inspiring the nomenclature ViP-signature. A subset of 20-genes classified disease severity in respiratory pandemics. The ViP signatures pinpointed airway epithelial and myeloid cells as the major contributors of an IL-15 cytokine storm, and epithelial and NK cell destruction as determinants of severity/fatality. They also helped formulate precise therapeutic goals to reduce disease symptoms and severity. Thus, the ViP signatures provide a quantitative and qualitative framework for titrating the immune response in viral pandemics and may serve as a powerful unbiased tool in our armamentarium to rapidly assess disease severity and vet candidate drugs. 

Development of a Thermal Endoscope for ENT Clinical Diagnostics

There is a clinical need for improved visual inspection for ENT diagnosis and surgeries. Endoscopy is required to access locations of ENT conditions. However, the assessment and identification of ENT abnormalities and pathologies remain challenging due to the difficult-to- reach ENT locations and the complex nature of the related pathologies. An imaging technique that could provide additional information, high contrast, and quantitative data about the patient condition will be useful, especially to assist ENT clinicians in diagnosis and surgeries and to avoid the need to resort to more expensive imaging techniques (e.g., CT scans, ultrasound imaging,MRI).

Live Attenuated Vaccine Against Group A Streptococcus Infection

Streptococcus pyogenes (group A Streptococcus [GAS]) is a leading health and economic burden worldwide, with an estimated 700 million infections occurring annually. Among these are 18.1 million severe cases that result in over 500,000 deaths. Despite active research, a protective vaccine remains elusive, leaving antimicrobial agents as the sole pharmacological intervention against GAS. To date, penicillin remains a primary drug of choice for combating GAS infections. However, despite no apparent emergence of resistant isolates, the rate of treatment failures with penicillin has increased to nearly 40% in certain regions of the world. Due to the high prevalence of GAS infection and the decreasing efficacy of the available repertoire of countermeasures, it is critical to investigate alternative approaches against GAS infection. An emerging strategy for combating pathogenic bacteria involves targeting virulence. To avoid immune clearance, GAS expresses a wide variety of secreted and cell-associated virulence factors to facilitate survival during infection. Despite decades of inquiry into the role and regulation of GAS virulence factors, the function and potential importance of many proteins involved in pathogenicity remain unknown.

Peptide Inhibitors of Idiopathic Pulmonary Fibrosis

Researchers at the University of California, Davis have developed a peptide that targets fibrogenic pathways in order to treat idiopathic pulmonary fibrosis. 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;}

A Fully‐automated Deep Learning System (software code) for the Detection, Prognosis, and Visualization of Pulmonary Disease.

The majority of state‐of‐the‐art lung segmentation algorithms in the literature do not simultaneously segment lungs, lung lobes, and airway in a single algorithm. Additionally, automated algorithms typically perform the segmentation task on a series of 2D slices, which can reduce segmentation accuracy of anatomical structures (i.e. lung lobes) that may require contextual information across all three spatial dimensions. Many existing algorithms also have not been validated on chest CTs across a wide variety of conditions to evaluate algorithm generalizability. Currently, quantification of respiratory measurements requires a radiologist, trained analyst, or technician to recognize, identify, and manually annotate anatomical landmarks such as the lung lobes or airway in the chest. A fully‐automated deep learning system may eliminate the need for manual analysis, thereby improving efficiency and expanding applicability to a large number of CTs.

TRM: HIF-1 alpha KO Mice (CRE)

Hypoxia-inducible factor 1-alpha is a transcriptional regulator of the adaptive response to hypoxia. When activated under hypoxic conditions, it can turn on over 40 genes involved in a variety of physiological activities. The dysregulation or alteration by mutation can lead to pathophysiology in areas of energy metabolism, cancer, cell survival and tumor invasion.

Techniques for Improving Positron Emission Tomography Image Quality and Tracking Real-Time Biological Processes

Researchers at the University of California, Davis have developed methodologies that perform dynamic PET imaging and provide opportunities for tracing blood flow and other biological systems in real-time.

Engineered Biomaterial to Prevent Endothelial Inflammation

Researchers at the University of California, Davis have developed a biocompatible material to mimic the glycocalyx, the natural layer of molecules that coats the outside of endothelial cells. This technology can be used to treat inflammation in diseases characterized by dysfunction in leukocyte-endothelial cell interactions.

Small Molecule Pendrin Inhibitors for Treatment of Inflammatory Airway Diseases and Diuretic Resistance

Small molecule pendrin inhibitors for treating inflammatory lung diseases.

A Simple Integrated Device For Assessing Lung Health

Chronic lung diseases, like asthma, impose critical challenges on both the patients and the physicians due to the complexity of the diseases. Not only are these diseases tough to accurately assess, many of the diseases can be impacted by other physical and sociological factors. Perhaps a greater difficulty lies in measuring the effectiveness and compliance of the medications including inhaled medications. The invention discovered at the University of California, Irvine, is an “all-in-one,” portable device that offers complete assessment of lung health. It also incorporates a novel technology for monitoring the effectiveness and compliance of a medication, thereby, providing a personalized treatment and care plan for adults and children with asthma.

Endoscopic Optical Coherence Tomography As A Minimally Invasive Lung Cancer Screening Tool To Guide Diagnosis And Therapy

Current diagnostic procedures for lung cancer are invasive, time-consuming, and subjective. UCI researchers have developed a quick, non-invasive lung cancer diagnostic device which uses optical coherence tomography (OCT) and can improve lung cancer diagnosis and outcomes.

“CT Mucus Score” - A New Scoring System that Quantifies Airway Mucus Impaction Using CT Scans

A novel method to measure airway mucus plugging using CT images from patients with asthma or chronic obstructive pulmonary disease (COPD) patients.

Novel Gut Microbiome-based Diagnostic and Therapeutic for Neonates at Risk of Childhood Atopy and Asthma

UCSF researchers have developed a novel gut microbiome-based diagnostic test and targeted treatment for early-life identification of atopy or asthma risk in children.

Potent TMEM16A Small Molecule Treatment for Inflammatory and Reactive Airway Diseases, Asthma, Hypertension, Pain and Cancer

A novel class of 2-acylamino-cycloalkylthiophene-3-carboxylic acid arylamides (AACTs) as potent TMEM16A inhibitors

Novel Use of Chitinases for Treatment of Lung Inflammatory and Fibrotic Diseases

A novel approach for the treatment of lung inflammatory and fibrotic diseases by increased or repaired chitinase function in lung tissues

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