Integrating AI-Powered Digital Pathology and Imaging Mass Cytometry Identifies Key Classifiers of Tumor Cells, Stroma, and Immune Cells in Non-Small Cell Lung Cancer.

Unlabelled: Artificial intelligence (AI)-powered approaches are becoming increasingly used as histopathologic tools to extract subvisual features and improve diagnostic workflows. On the other hand, hi-plex approaches are widely adopted to analyze the immune ecosystem in tumor specimens. Here, we aimed at combining AI-aided histopathology and imaging mass cytometry (IMC) to analyze the ecosystem of non-small cell lung cancer (NSCLC).

Two pediatric observations of spinal extradural arteriovenous fistulas presenting with epidural hemorrhages and cord compression.

We report two cases of acute spinal cord compression in children with low-flow spinal epidural arteriovenous fistulas (SEAVFs) and discuss the clinical presentation and management of these vascular anomalies. While most low-flow SEAVFs without radiculomedullary drainage are benign lesions typically diagnosed incidentally, we suggest that asymptomatic lesions may warrant aggressive management in specific circumstances, including lesions diagnosed at an early age or in patients under anticoagulation therapy. Our observations also emphasize that patients with a "spontaneous" epidural hemorrhage should undergo dedicated preoperative or postoperative vascular imaging to identify a possible underlying vascular anomaly.

Distinct responses of newly identified monocyte subsets to advanced gastrointestinal cancer and COVID-19.

Monocytes are critical cells of the immune system but their role as effectors is relatively poorly understood, as they have long been considered only as precursors of tissue macrophages or dendritic cells. Moreover, it is known that this cell type is heterogeneous, but our understanding of this aspect is limited to the broad classification in classical/intermediate/non-classical monocytes, commonly based on their expression of only two markers, i.e.

Elevated Intrarenal Resistive Index Predicted Faster Renal Function Decline and Long-Term Mortality in Non-Proteinuric Chronic Kidney Disease.

Background. Intrarenal resistive index (RI) ≥ 0.80 predicts renal outcomes in proteinuric chronic kidney disease (CKD).

Histopathological and Immune Prognostic Factors in Colo-Rectal Liver Metastases.

Prognostic studies are increasingly providing new tools to stratify colo-rectal liver metastasis patients into clinical subgroups, with remarkable implications in terms of clinical management and therapeutic choice. Here, the strengths and hurdles of current prognostic tools in colo-rectal liver metastasis are discussed. Alongside more classic histopathological parameters, which capture features related to the tumor component, such as tumor invasion, tumor growth pattern and regression score, we will discuss immune mediators, which are starting to be considered important features.

Manipulation of Glucose Availability to Boost Cancer Immunotherapies.

The orchestration of T cell responses is intimately linked to the execution of metabolic processes, both in homeostasis and disease. In cancer tissues, metabolic alterations that characterize malignant transformation profoundly affect the composition of the immune microenvironment and the accomplishment of an effective anti-tumor response. The growing understanding of the metabolic regulation of immune cell function has shed light on the possibility to manipulate metabolic pathways as a strategy to improve T cell function in cancer.

The neuro-immune axis in cancer: Relevance of the peripheral nervous system to the disease.

The peripheral nervous system and the immune system are critically involved in the surveillance of our body, having the ability to sense the environment, recognize danger signals and orchestrate an appropriate response. Despite the fact that these two systems have been historically considered autonomous entities, a large body of evidence has shown how they interact in many homeostatic responses and how these interactions are critically involved in pathologic contexts too, including inflammation, infection and autoimmunity. In the context of cancer, where it is already known that inflammation plays a key role, the cross-regulation of immune cells and neural components is still somewhat unexplored.

Macrophage morphology correlates with single-cell diversity and prognosis in colorectal liver metastasis.

It has long been known that in vitro polarized macrophages differ in morphology. Stemming from a conventional immunohistology observation, we set out to test the hypothesis that morphology of tumor-associated macrophages (TAMs) in colorectal liver metastasis (CLM) represents a correlate of functional diversity with prognostic significance. Density and morphological metrics of TAMs were measured and correlated with clinicopathological variables.

Multiplexed Optical Sensors in Arrayed Islands of Cells for multimodal recordings of cellular physiology.

Cells typically respond to chemical or physical perturbations via complex signaling cascades which can simultaneously affect multiple physiological parameters, such as membrane voltage, calcium, pH, and redox potential. Protein-based fluorescent sensors can report many of these parameters, but spectral overlap prevents more than ~4 modalities from being recorded in parallel. Here we introduce the technique, MOSAIC, Multiplexed Optical Sensors in Arrayed Islands of Cells, where patterning of fluorescent sensor-encoding lentiviral vectors with a microarray printer enables parallel recording of multiple modalities.

Dysregulation of NIPBL leads to impaired RUNX1 expression and haematopoietic defects.

The transcription factor RUNX1, a pivotal regulator of HSCs and haematopoiesis, is a frequent target of chromosomal translocations, point mutations or altered gene/protein dosage. These modifications lead or contribute to the development of myelodysplasia, leukaemia or platelet disorders. A better understanding of how regulatory elements contribute to fine-tune the RUNX1 expression in haematopoietic tissues could improve our knowledge of the mechanisms responsible for normal haematopoiesis and malignancy insurgence.

Metabolome of Pancreatic Juice Delineates Distinct Clinical Profiles of Pancreatic Cancer and Reveals a Link between Glucose Metabolism and PD-1 Cells.

Better understanding of pancreatic diseases, including pancreatic ductal adenocarcinoma (PDAC), is an urgent medical need, with little advances in preoperative differential diagnosis, preventing rational selection of therapeutic strategies. The clinical management of pancreatic cancer patients would benefit from the identification of variables distinctively associated with the multiplicity of pancreatic disorders. We investigated, by H nuclear magnetic resonance, the metabolomic fingerprint of pancreatic juice (the biofluid that collects pancreatic products) in 40 patients with different pancreatic diseases.

Macrophages at the crossroads of anticancer strategies.

Macrophages are essential elements in the tumor microenvironment, where they can promote tumor growth but also influence the efficacy of anticancer strategies. In conventional therapies, chemotherapy and radiotherapy, TAMs play a dichotomous role, contributing to antitumor activity or hindering the efficacy of cytoreductive therapies. Macrophages express checkpoint ligands and are therefore targets of immunotherapy approaches based on checkpoint inhibitors.

Health Care Expenditures of Medicare Beneficiaries with Normal Pressure Hydrocephalus.

Background: Normal pressure hydrocephalus (NPH) is an underdiagnosed and undertreated condition affecting the elderly population and with costs associated with its surgical management reported to be less than those associated with conservative management.

Objective: To determine if the rate of diagnosis of NPH has improved over the last decade, the rate of treatment has increased, and if surgical treatment costs and socioeconomic factors related to receipt of treatment have changed over time compared with conservative therapy.

Methods: A retrospective study based on data from a nationally representative random sample of 2,378,637 Medicare beneficiaries (2006-2010) was performed.

Large-Scale Production of Mature Neurons from Human Pluripotent Stem Cells in a Three-Dimensional Suspension Culture System.

Human pluripotent stem cells (hPSCs) offer a renewable source of cells that can be expanded indefinitely and differentiated into virtually any type of cell in the human body, including neurons. This opens up unprecedented possibilities to study neuronal cell and developmental biology and cellular pathology of the nervous system, provides a platform for the screening of chemical libraries that affect these processes, and offers a potential source of transplantable cells for regenerative approaches to neurological disease. However, defining protocols that permit a large number and high yield of neurons has proved difficult.

Rapid cellular turnover in adipose tissue.

It was recently shown that cellular turnover occurs within the human adipocyte population. Through three independent experimental approaches--dilution of an inducible histone 2B-green fluorescent protein (H2BGFP), labeling with the cell cycle marker Ki67 and incorporation of BrdU--we characterized the degree of cellular turnover in murine adipose tissue. We observed rapid turnover of the adipocyte population, finding that 4.

A high-efficiency system for the generation and study of human induced pluripotent stem cells.

Direct reprogramming of human fibroblasts to a pluripotent state has been achieved through ectopic expression of the transcription factors OCT4, SOX2, and either cMYC and KLF4 or NANOG and LIN28. Little is known, however, about the mechanisms by which reprogramming occurs, which is in part limited by the low efficiency of conversion. To this end, we sought to create a doxycycline-inducible lentiviral system to convert primary human fibroblasts and keratinocytes into human induced pluripotent stem cells (hiPSCs).