An estrogen receptor signaling transcriptional program linked to immune evasion in human hormone receptor-positive breast cancer.

Unlabelled: T cells are generally sparse in hormone receptor-positive (HR+) breast cancer, potentially due to limited antigen presentation, but the driving mechanisms of low T cell abundance remains unclear. Therefore, we defined and investigated programs ('gene modules'), related to estrogen receptor signaling (ERS) and immune signaling using bulk and single-cell transcriptome and multiplexed immunofluorescence of breast cancer tissues from multiple clinical sources and human cell lines. The ERS gene module, dominantly expressed in cancer cells, was negatively associated with immune-related gene modules TNFα/NF-κB signaling and type-I interferon (IFN-I) response, which were expressed in distinct stromal and immune cell types, but also, in part, expressed and preserved as a cancer cell-intrinsic mechanisms.

psudo: Exploring Multi-Channel Biomedical Image Data with Spatially and Perceptually Optimized Pseudocoloring.

Over the past century, multichannel fluorescence imaging has been pivotal in myriad scientific breakthroughs by enabling the spatial visualization of proteins within a biological sample. With the shift to digital methods and visualization software, experts can now flexibly pseudocolor and combine image channels, each corresponding to a different protein, to explore their spatial relationships. We thus propose psudo, an interactive system that allows users to create optimal color palettes for multichannel spatial data.

Visinity: Visual Spatial Neighborhood Analysis for Multiplexed Tissue Imaging Data.

New highly-multiplexed imaging technologies have enabled the study of tissues in unprecedented detail. These methods are increasingly being applied to understand how cancer cells and immune response change during tumor development, progression, and metastasis, as well as following treatment. Yet, existing analysis approaches focus on investigating small tissue samples on a per-cell basis, not taking into account the spatial proximity of cells, which indicates cell-cell interaction and specific biological processes in the larger cancer microenvironment.

Narrative online guides for the interpretation of digital-pathology images and tissue-atlas data.

Multiplexed tissue imaging facilitates the diagnosis and understanding of complex disease traits. However, the analysis of such digital images heavily relies on the experience of anatomical pathologists for the review, annotation and description of tissue features. In addition, the wider use of data from tissue atlases in basic and translational research and in classrooms would benefit from software that facilitates the easy visualization and sharing of the images and the results of their analyses.

Scope2Screen: Focus+Context Techniques for Pathology Tumor Assessment in Multivariate Image Data.

Inspection of tissues using a light microscope is the primary method of diagnosing many diseases, notably cancer. Highly multiplexed tissue imaging builds on this foundation, enabling the collection of up to 60 channels of molecular information plus cell and tissue morphology using antibody staining. This provides unique insight into disease biology and promises to help with the design of patient-specific therapies.

Minerva: a light-weight, narrative image browser for multiplexed tissue images.

Advances in highly multiplexed tissue imaging are transforming our understanding of human biology by enabling detection and localization of 10-100 proteins at subcellular resolution (Bodenmiller, 2016). Efforts are now underway to create public atlases of multiplexed images of normal and diseased tissues (Rozenblatt-Rosen et al., 2020).

High-Protein Hypocaloric Nutrition for Non-Obese Critically Ill Patients.

High-protein hypocaloric nutrition, tailored to each patient's muscle mass, protein-catabolic severity, and exogenous energy tolerance, is the most plausible nutrition therapy in protein-catabolic critical illness. Sufficient protein provision could mitigate the rapid muscle atrophy characteristic of this disease while providing urgently needed amino acids to the central protein compartment and sites of tissue injury. The protein dose may range from 1.

Summary Points and Consensus Recommendations From the International Protein Summit.

The International Protein Summit in 2016 brought experts in clinical nutrition and protein metabolism together from around the globe to determine the impact of high-dose protein administration on clinical outcomes and address barriers to its delivery in the critically ill patient. It has been suggested that high doses of protein in the range of 1.2-2.

Will We Ever Agree on Protein Requirements in the Intensive Care Unit?

The precise value of the normal adult protein requirement has long been debated. For many reasons-one of them being the difficulty of carrying out long-term nutrition experiments in free-living people-uncertainty is likely to persist indefinitely. By contrast, the controlled environment of the intensive care unit and relatively short trajectory of many critical illnesses make it feasible to use hard clinical outcome trials to determine protein requirements for critically ill patients in well-defined clinical situations.

Nutrition in critical illness: a current conundrum.

Critically ill people are unable to eat. What's the best way to feed them? Nutrition authorities have long recommended providing generous amounts of protein and calories to critically ill patients, either intravenously or through feeding tubes, in order to counteract the catabolic state associated with this condition. In practice, however, patients in modern intensive care units are substantially underfed.

Appropriate vitamin D loading regimen for patients with advanced lung cancer.

Background: Most patients attending cancer clinics have hypovitaminosis D. Correcting or preventing this abnormal condition could mitigate the emotional and physical complications of their disease, but clinical trials of vitamin D therapy in this setting are hindered by the unavailability of safe, effective and practical loading dose regimens.

Methods: In this single arm open-label pharmacokinetic trial, outpatients with advanced lung cancer consumed 20,000 IU vitamin D daily with the largest meal of the day for 14 days followed by 10,000 IU per day for a further 7 days.

A simple method for plasma total vitamin C analysis suitable for routine clinical laboratory use.

Background: In-hospital hypovitaminosis C is highly prevalent but almost completely unrecognized. Medical awareness of this potentially important disorder is hindered by the inability of most hospital laboratories to determine plasma vitamin C concentrations. The availability of a simple, reliable method for analyzing plasma vitamin C could increase opportunities for routine plasma vitamin C analysis in clinical medicine.

Human Protein and Amino Acid Requirements.

Human protein and amino acid nutrition encompasses a wide, complex, frequently misunderstood, and often contentious area of clinical research and practice. This tutorial explains the basic biochemical and physiologic principles that underlie our current understanding of protein and amino acid nutrition. The following topics are discussed: (1) the identity, measurement, and essentiality of nutritional proteins; (2) the definition and determination of minimum requirements; (3) nutrition adaptation; (4) obligatory nitrogen excretion and the minimum protein requirement; (5) minimum versus optimum protein intakes; (6) metabolic responses to surfeit and deficient protein intakes; (7) body composition and protein requirements; (8) labile protein; (9) N balance; (10) the principles of protein and amino acid turnover, including an analysis of the controversial indicator amino acid oxidation technique; (11) general guidelines for evaluating protein turnover articles; (12) amino acid turnover versus clearance; (13) the protein content of hydrated amino acid solutions; (14) protein requirements in special situations, including protein-catabolic critical illness; (15) amino acid supplements and additives, including monosodium glutamate and glutamine; and (16) a perspective on the future of protein and amino acid nutrition research.

High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

Background: Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.

Methods And Findings: We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response.

What is the best nutritional support for critically ill patients?

Optimum nutritional support in critical illness remains controversial. A recent review of nutritional interventions in the ICU concluded that few of them improved clinical outcomes. In our view, it is a serious shortcoming of these trials that they focused on calories, falling far short of current recommendations for protein provision.

Effects of vitamin C and vitamin D administration on mood and distress in acutely hospitalized patients.

Background: Hypovitaminosis C and D are highly prevalent in acute-care hospitals. Malnutrition with regard to these vitamins has been linked to mood disturbance and cognitive dysfunction.

Objective: The objective was to determine whether vitamin C or D supplementation improves mood state or reduces psychological distress in acutely hospitalized patients with a high prevalence of hypovitaminosis C and D.