Development of a small cell lung cancer organoid model to study cellular interactions and survival after chemotherapy.

Small-cell-lung-cancer (SCLC) has the worst prognosis of all lung cancers because of a high incidence of relapse after therapy. While lung cancer is the second most common malignancy in the US, only about 10% of cases of lung cancer are SCLC, therefore, it is categorized as a rare and recalcitrant disease. Therapeutic discovery for SCLC has been challenging and the existing pre-clinical models often fail to recapitulate actual tumor pathophysiology.

Small cell lung cancer co-culture organoids provide insights into cancer cell survival after chemotherapy.

Small-cell-lung-cancer (SCLC) has the worst prognosis of all lung cancers because of a high incidence of relapse after therapy. We developed a bioengineered 3-dimensional (3D) SCLC co-culture organoid as a phenotypic tool to study SCLC tumor kinetics and SCLC-fibroblast interactions during relapse. We used functionalized alginate microbeads as a scaffold to mimic lung alveolar architecture and co-cultured SCLC cell lines with primary adult lung fibroblasts (ALF).

Targeting PEA3 transcription factors to mitigate small cell lung cancer progression.

Small cell lung cancer (SCLC) remains a lethal disease with a dismal overall survival rate of 6% despite promising responses to upfront combination chemotherapy. The key drivers of such rapid mortality include early metastatic dissemination in the natural course of the disease and the near guaranteed emergence of chemoresistant disease. Here, we found that we could model the regression and relapse seen in clinical SCLC in vitro.

Transcriptional analysis of cystic fibrosis airways at single-cell resolution reveals altered epithelial cell states and composition.

Cystic fibrosis (CF) is a lethal autosomal recessive disorder that afflicts more than 70,000 people. People with CF experience multi-organ dysfunction resulting from aberrant electrolyte transport across polarized epithelia due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF-related lung disease is by far the most important determinant of morbidity and mortality.

Direct Exposure to SARS-CoV-2 and Cigarette Smoke Increases Infection Severity and Alters the Stem Cell-Derived Airway Repair Response.

Current smoking is associated with increased risk of severe COVID-19, but it is not clear how cigarette smoke (CS) exposure affects SARS-CoV-2 airway cell infection. We directly exposed air-liquid interface (ALI) cultures derived from primary human nonsmoker airway basal stem cells (ABSCs) to short term CS and then infected them with SARS-CoV-2. We found an increase in the number of infected airway cells after CS exposure with a lack of ABSC proliferation.

Direct exposure to SARS-CoV-2 and cigarette smoke increases infection severity and alters the stem cell-derived airway repair response.

Most demographic studies are now associating current smoking status with increased risk of severe COVID-19 and mortality from the disease but there remain many questions about how direct cigarette smoke exposure affects SARS-CoV-2 airway cell infection. We directly exposed mucociliary air-liquid interface (ALI) cultures derived from primary human nonsmoker airway basal stem cells (ABSCs) to short term cigarette smoke and infected them with live SARS-CoV-2. We found an increase in the number of infected airway cells after cigarette smoke exposure as well as an increased number of apoptotic cells.

Distinct Spatiotemporally Dynamic Wnt-Secreting Niches Regulate Proximal Airway Regeneration and Aging.

Our understanding of dynamic interactions between airway basal stem cells (ABSCs) and their signaling niches in homeostasis, injury, and aging remains elusive. Using transgenic mice and pharmacologic studies, we found that Wnt/β-catenin within ABSCs was essential for proliferation post-injury in vivo. ABSC-derived Wnt ligand production was dispensable for epithelial proliferation.

Modeling Progressive Fibrosis with Pluripotent Stem Cells Identifies an Anti-fibrotic Small Molecule.

Progressive organ fibrosis accounts for one-third of all deaths worldwide, yet preclinical models that mimic the complex, progressive nature of the disease are lacking, and hence, there are no curative therapies. Progressive fibrosis across organs shares common cellular and molecular pathways involving chronic injury, inflammation, and aberrant repair resulting in deposition of extracellular matrix, organ remodeling, and ultimately organ failure. We describe the generation and characterization of an in vitro progressive fibrosis model that uses cell types derived from induced pluripotent stem cells.

Reliability of various observers in determining common radiographic parameters of adult hip structural anatomy.

Background: Radiographic evaluation of the hip is extremely important in the diagnosis and treatment decisionmaking process for pre-arthritic hip disease. Many different radiographic measurements have been described as indicators of underlying structural hip deformity. The purpose of this study was to determine the interobserver and intraobserver reliability of various musculoskeletal physicians in performing selected measurements of adult structural hip anatomy.

The relationship between scapular notching and reverse shoulder arthroplasty prosthesis design.

Background: Inferior scapular notching is a common radiographic complication of reverse shoulder arthroplasty. The purpose of this study is to determine the impact of prosthesis design on the incidence and severity of notching.

Materials And Methods: Eighty-eight patients (mean age, 72 years) who underwent reverse shoulder arthroplasty with a minimum of 12 months' follow-up (mean, 31 months) were retrospectively reviewed.

Arthroscopic treatment of isolated type II SLAP lesions: biceps tenodesis as an alternative to reinsertion.

Background: Overhead athletes report an inconsistent return to their previous level of sport and satisfaction after arthroscopic SLAP lesion repair.

Hypothesis: Arthroscopic biceps tenodesis offers a viable alternative to the repair of an isolated type II SLAP lesion.

Study Design: Cohort study; Level of evidence, 3.

THA with highly cross-linked polyethylene in patients 50 years or younger.

Unlabelled: Highly cross-linked polyethylene has been associated with low in vitro wear, but also has decreased in vitro ultimate yield strength. We therefore asked whether highly cross-linked polyethylene would result in lower outcome scores, wear, or early failure in a young patient population. Seventy THAs in 64 patients were performed using a highly cross-linked (electron beam-irradiated to 9 Mrads) acetabular liner and a cobalt-chrome femoral head.

Troublesome stress fractures of the foot and ankle.

Athletes engaged in repetitive activity with recent increases in training or competition are at risk for stress fractures of the foot and ankle. Physical and radiographic findings are often unremarkable and diagnosis may be difficult. Although many of these injuries may be managed symptomatically, certain types of stress fractures are at higher risk for delayed union, nonunion, or refracture without aggressive immobilization or surgical fixation.

Roles of Se and NO in apoptosis of hepatoma cells.

Mice inoculated with hepatoma cell (H22) suspension subcutaneously at their right axilla were administered orally with kappa-selenocarrageenan (Se) solution, the inoculated hepatoma's growth was suppressed. Different concentrations of Se solution added in human hepatoma cell line culture could inhibit proliferation and induce apoptosis in hepatoma cells. Meanwhile Se solution could increase the activity of glutathione peroxidase (GSH-Px) in the mice's plasma and the content of NO in the mice's sera and the hepatoma cell culture supernatant as well.

A cost-effectiveness analysis of shipboard telemedicine.

Background: The U.S. Navy is considering the installation of telemedicine equipment on more than 300 ships.