Developmental regulation of dermal adipose tissue by BCL11b.

The distinct anatomic environment in which adipose tissues arise during organogenesis is a principle determinant of their adult expansion capacity. Metabolic disease results from a deficiency in hyperplastic adipose expansion within the dermal/subcutaneous depot; thus, understanding the embryonic origins of dermal adipose is imperative. Using single-cell transcriptomics throughout murine embryogenesis, we characterized cell populations, including cells, that regulate the development of dermal white adipose tissue (dWAT).

Transcriptional regulation of adipocyte lipolysis by IRF2BP2.

Adipocyte lipolysis controls systemic energy levels and metabolic homeostasis. Lipolysis is regulated by post-translational modifications of key lipolytic enzymes. However, less is known about the transcriptional mechanisms that regulate lipolysis.

Progressive Encephalopathy With New Pulmonary Opacities in an Immunocompromised Host.

A 48-year-old man with history of recent travel to central Mexico and immunosuppression sought treatment with a 1-month-long history of progressive headache, fatigue, word-finding difficulties, and night sweats. The patient had a history of end-stage renal disease; he had undergone a kidney transplantation 7 years prior with good graft function with immunosuppression with tacrolimus, everolimus, and low-dose prednisone. At an outside hospital, he recently had been treated with empiric antibiotics for meningitis, but these were discontinued given the low suspicion for a bacterial cause.

Myeloid-derived miR-6236 potentiates adipocyte insulin signaling and prevents hyperglycemia during obesity.

Adipose tissue macrophages (ATMs) influence obesity-associated metabolic dysfunction, but the mechanisms by which they do so are not well understood. We show that miR-6236 is a bona fide miRNA that is secreted by ATMs during obesity. Global or myeloid cell-specific deletion of miR-6236 aggravates obesity-associated adipose tissue insulin resistance, hyperglycemia, hyperinsulinemia, and hyperlipidemia.

Graph Perceiver Network for Lung Tumor and Bronchial Premalignant Lesion Stratification from Histopathology.

Bronchial premalignant lesions (PMLs) precede the development of invasive lung squamous cell carcinoma (LUSC), posing a significant challenge in distinguishing those likely to advance to LUSC from those that might regress without intervention. This study followed a novel computational approach, the Graph Perceiver Network, leveraging hematoxylin and eosin-stained whole slide images to stratify endobronchial biopsies of PMLs across a spectrum from normal to tumor lung tissues. The Graph Perceiver Network outperformed existing frameworks in classification accuracy predicting LUSC, lung adenocarcinoma, and nontumor lung tissue on The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium datasets containing lung resection tissues while efficiently generating pathologist-aligned, class-specific heatmaps.

Multiple External Cervical Resorption Lesions in Patient with Graft versus Host Disease Treated with Systemic Bleomycin: A Case Report.

The phenomenon of multiple external cervical root resorption (ECRR) lesions in a single patient is rare but may have a link with the chemotherapeutic agent bleomycin. This case details an adult male with multiple ECRR lesions that developed following chemotherapy. His treatment regimen for Hodgkin's lymphoma included the chemotherapeutic antibiotic bleomycin, which has previously been linked with development of multiple ECRR lesions.

Hydrogel-Embedded Precision-Cut Lung Slices Model Lung Cancer Premalignancy Ex Vivo.

Lung cancer is the leading global cause of cancer-related deaths. Although smoking cessation is the best prevention, 50% of lung cancer diagnoses occur in people who have quit smoking. Research into treatment options for high-risk patients is constrained to rodent models, which are time-consuming, expensive, and require large cohorts.

She didn't start the fire: Mammary duct epithelial cells suppress adipocyte thermogenesis.

Male and female mice display highly divergent responses to cold-induced thermogenic beiging of subcutaneous adipose tissues. Recently in Nature, Patel et al. showed that mammary duct epithelial cells respond to cold-induced sympathetic activity, triggering the secretion of lipocalin 2 (LCN2) to inhibit thermogenic differentiation of adjacent mammary adipocytes.

Phase Ib trial of inhaled iloprost for the prevention of lung cancer with predictive and response biomarker assessment.

Introduction: Iloprost, a prostacyclin analog, has lung cancerpreventive activity in preclinical models and improved dysplasia in former smokers in a phase IIb trial. Oral iloprost is currently unavailable. We performed a phase Ib trial of inhaled iloprost in former smokers to assess tolerance and compliance.

Lung adenocarcinoma promotion by air pollutants.

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development. Here we propose that environmental particulate matter measuring ≤2.

Tissue-engineered models of lung cancer premalignancy.

Lung cancer is the leading global cause of cancer-related deaths. Although smoking cessation is the best preventive action, nearly 50% of all lung cancer diagnoses occur in people who have already quit smoking. Research into treatment options for these high-risk patients has been constrained to rodent models of chemical carcinogenesis, which are time-consuming, expensive, and require large numbers of animals.

Durable responses to alectinib in murine models of EML4-ALK lung cancer requires adaptive immunity.

Lung cancers bearing oncogenic EML4-ALK fusions respond to targeted tyrosine kinase inhibitors (TKIs; e.g., alectinib), with variation in the degree of shrinkage and duration of treatment (DOT).

Novel EGFR-mutant mouse models of lung adenocarcinoma reveal adaptive immunity requirement for durable osimertinib response.

Lung cancers bearing oncogenically-mutated EGFR represent a significant fraction of lung adenocarcinomas (LUADs) for which EGFR-targeting tyrosine kinase inhibitors (TKIs) provide a highly effective therapeutic approach. However, these lung cancers eventually acquire resistance and undergo progression within a characteristically broad treatment duration range. Our previous study of EGFR mutant lung cancer patient biopsies highlighted the positive association of a TKI-induced interferon γ transcriptional response with increased time to treatment progression.

An international collaborative approach to learning histology using a virtual microscope.

Histology is often taught in higher education settings using online virtual microscopes (VM). This study aimed to develop and evaluate the use of VM in teaching on a BSc degree at the University of Nottingham by surveying students and staff. A key development was the use of an e-workbook so that students were actively engaged in creating their own bespoke revision material.

Making a Painless Drain: Proof of Concept.

Chest tubes account for a large proportion of postoperative pain after cardiothoracic operations. The objective of this study was to develop a novel, cost-effective, easy-to-use, lidocaine-eluting coating to reduce pain associated with postoperative chest tubes. A lidocaine-eluting hydrogel was developed by dispersing lidocaine-loaded nanoparticles in an aqueous solution containing gelatin (5%).

Developing, Implementing, and Evaluating an Artificial Intelligence-Guided Mental Health Resource Navigation Chatbot for Health Care Workers and Their Families During and Following the COVID-19 Pandemic: Protocol for a Cross-sectional Study.

Background: Approximately 1 in 3 Canadians will experience an addiction or mental health challenge at some point in their lifetime. Unfortunately, there are multiple barriers to accessing mental health care, including system fragmentation, episodic care, long wait times, and insufficient support for health system navigation. In addition, stigma may further reduce an individual's likelihood of seeking support.

PPARgamma agonism inhibits progression of premalignant lesions in a murine lung squamous cell carcinoma model.

The N-nitroso-trischloroethylurea (NTCU)-induced mouse model of squamous lung carcinoma recapitulates human disease from premalignant dysplasia through invasive tumors, making it suitable for preclinical chemoprevention drug testing. Pioglitazone is a peroxisome proliferator-activated receptor γ (PPARγ) agonist shown to prevent lung tumors in preclinical models. We investigated pioglitazone's effect on lesion development and markers of potential preventive mechanisms in the NTCU model.

Inflammatory adipose activates a nutritional immunity pathway leading to retinal dysfunction.

Age-related macular degeneration (AMD), the leading cause of irreversible blindness among Americans over 50, is characterized by dysfunction and death of retinal pigment epithelial (RPE) cells. The RPE accumulates iron in AMD, and iron overload triggers RPE cell death in vitro and in vivo. However, the mechanism of RPE iron accumulation in AMD is unknown.

Lung cancer: Premalignant biology and medical prevention.

Lung cancer (both adenocarcinoma and squamous cell) progress through a series of pre-malignant histologic changes before the development of invasive disease. Each of these carcinogenic cascades is defined by genetic and epigenetic alterations in pulmonary epithelial cells. Additionally, alterations in the immune response, progenitor cell function, mutational burden, and microenvironmental mediated survival of mutated clones contribute to the risk of pre-malignant lesions progressing to cancer.

MITI minimum information guidelines for highly multiplexed tissue images.

The imminent release of tissue atlases combining multi-channel microscopy with single cell sequencing and other omics data from normal and diseased specimens creates an urgent need for data and metadata standards that guide data deposition, curation and release. We describe a Minimum Information about highly multiplexed Tissue Imaging (MITI) standard that applies best practices developed for genomics and other microscopy data to highly multiplexed tissue images and traditional histology.

Genotype-phenotype correlations in alpha-sarcoglycanopathy: a systematic review.

Background: Mutations in the alpha-sarcoglycan gene cause limb-girdle muscular dystrophy 2D, an autosomal recessive muscle wasting disorder primarily affecting the muscles of the shoulder and pelvic girdles. To date, no previous study has collated all known mutations in alpha-sarcoglycan and mapped these to the associated phenotypes.

Aims: To examine for correlations between mutation locations, or mutation type, and the phenotype caused in all reported mutations in alpha-sarcoglycan.