The SagA of E faecium

An enzyme that remodels the cell wall of Enterococcus faecium helps these gut bacteria to divide and generate peptide fragments that enhance the immune response against cancer

New Insights About Immune Populations in Gastrointestinal GVHD

Jarosch et al.have deeply characterized immune cell infiltrates in gastrointestinal (GI) biopsies from individuals with GI graft-versus-host disease (GI-GvHD) using single-cell RNA sequencing and ChipCytometry. Individuals with severe GI-GvHD demonstrated increased clonally expanded cytotoxic CD8 T cells in GI biopsies

The Microbiome and Its Impact on Allogeneic Hematopoietic Cell Transplantation

Allogeneic hematopoietic cell transplantation (alloHCT) is a standard curative therapy for a variety of benign and malignant hematological diseases. Previously, patients who underwent alloHCT were at high risk for complications with potentially life-threatening toxicities, including a variety of opportunistic infections as well as acute and chronic manifestations of graft-versus-host disease (GVHD), where the transplanted immune system can produce inflammatory damage to the patient. With recent advances, including newer conditioning regimens, advances in viral and fungal infection prophylaxis, and novel GVHD prophylactic and treatment strategies, improvements in clinical outcomes have steadily improved. One modality with great potential that has yet to be fully realized is targeting the microbiome to further improve clinical outcomes.In recent years, the intestinal microbiota, which includes bacteria, fungi, viruses, and other microbes that reside within the intestinal tract, has become established as a potent modulator of alloHCT outcomes. The composition of intestinal bacteria, in particular, has been found in large multicenter prospective studies to be strongly associated with GVHD, treatment-related mortality, and overall survival. Murine studies have demonstrated a causal relationship between intestinal microbiota injury and aggravated GVHD, and more recently, clinical interventional studies of repleting the intestinal microbiota with fecal microbiota transplantation have emerged as effective therapies for GVHD. How the composition of the intestinal bacterial microbiota, which is often highly variable in alloHCT patients, can modulate GVHD and other outcomes is not fully understood. Recent studies, however, have begun to make substantial headway, including identifying particular bacterial subsets and/or bacterial-derived metabolites that can mediate harm or benefit. Here, the authors review recent studies that have improved our mechanistic understanding of the relationship between the microbiota and alloHCT outcomes, as well as studies that are beginning to establish strategies to modulate the microbiota with the hope of optimizing clinical outcomes

Dietary Fiber and Gut Bacteria Shape Infection Susceptibility

Gut microbiota composition has been reported to affect pathogen susceptibility but its specific effects, the underlying mechanisms and the potential influence of the diet remain unexplored. In their recent study, Desai and colleagues (Wolter et al, 2024), explore the complex interaction between diet, the gut microbiota and pathogen susceptibility, highlighting a diet-dependent role of the mucin-degrading microbe Akkermansia muciniphila

Miniature, Lightweight, One-Time-Opening Valve

The figure depicts the main parts of a prototype miniature, lightweight, onetime- opening valve. Like some other miniature one-time-opening valves reported in previous issues of NASA Tech Briefs, this valve is opened by melting a material that blocks the flow path. This valve is designed to remain closed at some temperature between room temperature and cryogenic temperature until the time of opening. The prototype valve includes a 1/8-in. (3-mm) aluminum tube, one end of which is plugged with a solder comprising about 37 weight percent of lead and 63 weight percent of tin. The tube and the solder both have a coefficient of thermal expansion of 23 micron/m-K at room temperature. Before plugging, the interior surface of the plug end of the tube is cleaned with a commercial flux paste developed specifically for preparing aluminum for bonding with lead/tin solder. The solder is then melted into the cleaned end of the tube, forming the plug. In a test, the plugged tube was pressurized to 1,000 psi (6.9 MPa) with helium and leak-tested. It was then cooled to a temperature of 77 K (about 196 C) and again leak-tested at the same pressure. Finally, at a lower pressure, the plugged end of the tube was heated to about 200 C (the melting temperature of the solder is 183 C), causing the solder plug to be ejected (see figure). It has been estimated that in a subsequent version of the valve, the plug could be melted by electrical heating, using a nichrome wire having a mass of only 10 g

Microbiome Influencers of Checkpoint Blockade-Associated Toxicity

Immunotherapy has greatly improved cancer outcomes, yet variability in response and off-target tissue damage can occur with these treatments, including immune checkpoint inhibitors (ICIs). Multiple lines of evidence indicate the host microbiome influences ICI response and risk of immune-related adverse events (irAEs). As the microbiome is modifiable, these advances indicate the potential to manipulate microbiome components to increase ICI success. We discuss microbiome features associated with ICI response, with focus on bacterial taxa and potential immune mechanisms involved in irAEs, and the overall goal of driving novel approaches to manipulate the microbiome to improve ICI efficacy while avoiding irAE risk

Sparse tree-based clustering of microbiome data to characterize microbiome heterogeneity in pancreatic cancer

There is a keen interest in characterizing variation in the microbiome across cancer patients, given increasing evidence of its important role in determining treatment outcomes. Here our goal is to discover subgroups of patients with similar microbiome profiles. We propose a novel unsupervised clustering approach in the Bayesian framework that innovates over existing model-based clustering approaches, such as the Dirichlet multinomial mixture model, in three key respects: we incorporate feature selection, learn the appropriate number of clusters from the data, and integrate information on the tree structure relating the observed features. We compare the performance of our proposed method to existing methods on simulated data designed to mimic real microbiome data. We then illustrate results obtained for our motivating data set, a clinical study aimed at characterizing the tumor microbiome of pancreatic cancer patients

survivalContour: Visualizing Predicted Survival via Colored Contour Plots

Advances in survival analysis have facilitated unprecedented flexibility in data modeling, yet there remains a lack of tools for illustrating the influence of continuous covariates on predicted survival outcomes. We propose the utilization of a colored contour plot to depict the predicted survival probabilities over time. Our approach is capable of supporting conventional models, including the Cox and Fine–Gray models. However, its capability shines when coupled with cutting-edge machine learning models such as random survival forests and deep neural networks. Availability and implementation We provide a Shiny app at https://biostatistics.mdanderson.org/shinyapps/survivalContour/ and an R package available at https://github.com/YushuShi/survivalContour as implementations of this tool