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.

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. 

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).

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.

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.

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.

Enteric disease and respiratory diseases are major problems worldwide which greatly impact human health, as well as animal health. Current vaccine approaches are limited by numerous factors, including production costs, efficacy, safety, requirement of adjuvants, and storage conditions. 

In normal immunologic function, the body appropriately balances cAMP-regulated pathways. However, UC investigators have found that when cAMP levels in dendritic cells are too low or too high, there is a bias, respectively, toward either Th2 or Th17 response and the immunopathologies associated with each pathway.

Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, in part due to contraction and increased proliferation of pulmonary artery smooth muscle cells (PASMC). PAH causes symptoms such as shortness of breath, fatigue and chest pain. As the condition worsens, its symptoms may limit physical activity and can result in enhanced morbidity and early mortality. PAH results in added stress on the heart with strain and weakness of the right ventricle. The heart may become so weak that it can no longer pump sufficient blood, resulting in heart failure, the most common cause of death associated with PAH. Since the second messenger 3’5’-cyclic adenosine monophosphate (cAMP) produces relaxation and decreases proliferation of PASMC, drugs that activate G protein-coupled receptors (GPCRs) to stimulate Gαs or to inhibit Gαi, both of which effects will increase cAMP, may provide therapeutic approaches to treat PAH and such GPCRs may be novel therapeutic targets. The GPCR targets revealed here may prove of benefit to the large number of patients with various types of pulmonary hypertension who share the same vascular pathology.

Bronchial asthma is a chronic and heterogeneous inflammatory disorder of the conducting airways with immune and non-immune etiologies. Although the underlying molecular basis of asthma is not completely understood, inflammation is a key pathological feature of bronchial asthma. The increasing prevalence in Western countries (approximately 15% of children and 8% of adults) supports the vast resources deployed to find treatments and drugs that act upon pathways not targeted in current therapies are of particular interest.

Virtually all lung disease is characterized to some extent by disruption of alveolar ventilation (VA) and perfusion (Q) (VA/Q) matching, resulting in gas exchange inefficiency. The only fully quantitative technique considered to be the “gold-standard” at the moment is MIGET (multiple inert gas elimination technique), which quantifies the overall distribution of ventilation or perfusion as a function of VA/Q ratio. However, MIGET is technically very demanding, highly invasive, and does not provide spatial information.

Quantification of pulmonary blood flow (PBF) is essential for the assessment of efficient gas exchange. The ability to quantitatively evaluate changes in regional PBF (rPBF) can enhance our understanding of the relationship between lung structure and function in both health and disease. Aerial spin labeling (ASL) is a powerful MRI technique for noninvasive perfusion imaging of organs. It uses arterial blood water as the endogenous contrast agent without the exposure of ionizing radiation, the limitation of spatial or temporal resolution, or the need for an exogenous contrast agent, making possible for this non-invasive procedure to be widely available at relatively low cost. Pulsed ASL techniques have been validated for cerebral blood flow; however, because of the high pulsatility of PBF, ASL acquisition and data analysis differ significantly between the lung and the brain.

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