Multiscale computational model predicts how environmental changes and treatments affect microvascular remodeling in fibrotic disease.

Investigating the molecular, cellular, and tissue-level changes caused by disease, and the effects of pharmacological treatments across these biological scales, necessitates the use of multiscale computational modeling in combination with experimentation. Many diseases dynamically alter the tissue microenvironment in ways that trigger microvascular network remodeling, which leads to the expansion or regression of microvessel networks. When microvessels undergo remodeling in idiopathic pulmonary fibrosis (IPF), functional gas exchange is impaired and lung function declines.

EXPLORING DIFFERENTIAL GENE EXPRESSION PROFILES OF DERO (ALLODERO) HYLAE IN THEIR PARASITIC AND FREE-LIVING FORMS.

Parasitism is ubiquitous, yet little is known about the evolutionary mechanisms that lead to a parasitic lifestyle. Facultative parasites can switch between free-living and parasitic lifestyles, which may provide an opportunity for researchers to study the genetic mechanisms underlying a transition to parasitism. The oligochaete Dero (Allodero) hylae is a facultative parasite commonly found within the ureter of various anuran species, such as the Cuban tree frog (Osteopilus septentrionalis).

Spatial analysis reveals targetable macrophage-mediated mechanisms of immune evasion in hepatocellular carcinoma minimal residual disease.

Hepatocellular carcinoma (HCC) frequently recurs from minimal residual disease (MRD), which persists after therapy. Here, we identified mechanisms of persistence of residual tumor cells using post-chemoembolization human HCC (n = 108 patients, 1.07 million cells) and a transgenic mouse model of MRD.

Heart-liver transplantation using the en bloc technique: A single-center experience over two decades.

Background: Combined heart-liver transplantation (CHLT) is a definitive therapy reserved for patients with concomitant heart failure and advanced liver disease. A limited number of centers perform CHLT, and even fewer use the en bloc implantation technique. Here we review clinical outcomes and immunoprotective effects following CHLT and describe our institution's more than two decades of experience in performing the en bloc technique.

Pediatric Combined Heart-liver Transplantation: A Single-center Long-term Experience.

Background: Combined heart liver transplant (CHLT) continues to gain attention as a surgical treatment for patients with end-stage heart and liver disease but remains rare. We present our institutional longitudinal experience with up to 14 y of follow-up, focused on long-term outcomes in CHLT recipients.

Methods: We conducted a single-institutional, retrospective review from January 1, 2010, to December 31, 2023, including 7 patients ages 7-17 y who underwent CHLT.

Distinct Type 1 Immune Networks Underlie the Severity of Restrictive Lung Disease after COVID-19.

The variable etiology of persistent breathlessness after COVID-19 have confounded efforts to decipher the immunopathology of lung sequelae. Here, we analyzed hundreds of cellular and molecular features in the context of discrete pulmonary phenotypes to define the systemic immune landscape of post-COVID lung disease. Cluster analysis of lung physiology measures highlighted two phenotypes of restrictive lung disease that differed by their impaired diffusion and severity of fibrosis.

Multiscale computational model predicts how environmental changes and drug treatments affect microvascular remodeling in fibrotic disease.

Investigating the molecular, cellular, and tissue-level changes caused by disease, and the effects of pharmacological treatments across these biological scales, necessitates the use of multiscale computational modeling in combination with experimentation. Many diseases dynamically alter the tissue microenvironment in ways that trigger microvascular network remodeling, which leads to the expansion or regression of microvessel networks. When microvessels undergo remodeling in idiopathic pulmonary fibrosis (IPF), functional gas exchange is impaired due to loss of alveolar structures and lung function declines.

Machine Learning of Plasma Proteomics Classifies Diagnosis of Interstitial Lung Disease.

Distinguishing connective tissue disease-associated interstitial lung disease (CTD-ILD) from idiopathic pulmonary fibrosis (IPF) can be clinically challenging. To identify proteins that separate and classify patients with CTD-ILD and those with IPF. Four registries with 1,247 patients with IPF and 352 patients with CTD-ILD were included in analyses.

High-dimensional comparison of monocytes and T cells in post-COVID and idiopathic pulmonary fibrosis.

Introduction: Up to 30% of hospitalized COVID-19 patients experience persistent sequelae, including pulmonary fibrosis (PF).

Methods: We examined COVID-19 survivors with impaired lung function and imaging worrisome for developing PF and found within six months, symptoms, restriction and PF improved in some (Early-Resolving COVID-PF), but persisted in others (Late-Resolving COVID-PF). To evaluate immune mechanisms associated with recovery versus persistent PF, we performed single-cell RNA-sequencing and multiplex immunostaining on peripheral blood mononuclear cells from patients with Early- and Late-Resolving COVID-PF and compared them to age-matched controls without respiratory disease.

Alcohol Use in Liver Transplant Recipients With Alcohol-related Liver Disease: A Comparative Assessment of Relapse Prediction Models.

Background: The selection of liver transplant (LT) candidates with alcohol-related liver disease (ALD) is influenced by the risk of alcohol relapse (AR), yet the ability to predict AR is limited. We evaluate psychosocial factors associated with post-LT AR and compare the performance of high-risk alcoholism risk (HRAR), sustained alcohol use post-LT (SALT), and the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) scores in predicting relapse.

Methods: A retrospective analysis of ALD patients undergoing LT from 2015 to 2021 at a single US transplant center was performed.

Associations of Plasma Omega-3 Fatty Acids With Progression and Survival in Pulmonary Fibrosis.

Background: Preclinical experiments suggest protective effects of omega-3 fatty acids and their metabolites in lung injury and fibrosis. Whether higher intake of omega-3 fatty acids is associated with disease progression and survival in humans with pulmonary fibrosis is unknown.

Research Question: What are the associations of plasma omega-3 fatty acid levels (a validated marker of omega-3 nutritional intake) with disease progression and transplant-free survival in pulmonary fibrosis?

Study Design And Methods: Omega-3 fatty acid levels were measured from plasma samples of patients with clinically diagnosed pulmonary fibrosis from the Pulmonary Fibrosis Foundation Patient Registry (n = 150), University of Virginia (n = 58), and University of Chicago (n = 101) cohorts.

Allometrically scaling tissue forces drive pathological foreign-body responses to implants via Rac2-activated myeloid cells.

Small animals do not replicate the severity of the human foreign-body response (FBR) to implants. Here we show that the FBR can be driven by forces generated at the implant surface that, owing to allometric scaling, increase exponentially with body size. We found that the human FBR is mediated by immune-cell-specific RAC2 mechanotransduction signalling, independently of the chemistry and mechanical properties of the implant, and that a pathological FBR that is human-like at the molecular, cellular and tissue levels can be induced in mice via the application of human-tissue-scale forces through a vibrating silicone implant.

Cas9-mediated knockout of Ndrg2 enhances the regenerative potential of dendritic cells for wound healing.

Chronic wounds impose a significant healthcare burden to a broad patient population. Cell-based therapies, while having shown benefits for the treatment of chronic wounds, have not yet achieved widespread adoption into clinical practice. We developed a CRISPR/Cas9 approach to precisely edit murine dendritic cells to enhance their therapeutic potential for healing chronic wounds.

Interstitial Lung Disease and Sarcoidosis.

Interstitial lung disease (ILD), a clinically recognized group of diseases resulting in pulmonary fibrosis, affects up to 200 individuals per 100,000 in the United States. Sarcoidosis has a wide range of clinical manifestations including pulmonary fibrosis. Health disparities are prevalent in both ILD and sarcoidosis around socioeconomic status, race, gender, and geographic location.

Long COVID and Unemployment in Hawaii.

The state of Hawaii has seen 390,000 COVID-19 cases and nearly 1900 deaths since the start of the pandemic. Although the negative impact of the pandemic on employment has been widely documented, this paper demonstrates that those who were infected and suffer from lingering symptoms (i.e.