IL-7R licenses a population of epigenetically poised memory CD8 T cells with superior antitumor efficacy that are critical for melanoma memory.

Recurrence of advanced melanoma after therapy is a major risk factor for reduced survival, and treatment options are limited. Antitumor immune memory plays a critical role in preventing melanoma recurrence and memory T cells could be a potent cell-based therapy, but the identity, and functional properties of the required immune cells are incompletely understood. Here, we show that an IL-7R tumor-specific CD8 population is critical for antitumor memory and can be epigenetically augmented to drive powerful antitumor immune responses.

Cutting Edge: IL-21 and Tissue-Specific Signals Instruct Tbet+CD11c+ B Cell Development following Viral Infection.

Tbet+CD11c+ B cells, also known as age-associated B cells (ABCs), are pivotal contributors to humoral immunity following infection and in autoimmunity, yet their in vivo generation is incompletely understood. We used a mouse model of systemic acute lymphocytic choriomeningitis virus infection to examine the developmental requirements of ABCs that emerged in the spleen and liver. IL-21 signaling through STAT3 was indispensable for ABC development.

Inflammasome activation in infected macrophages drives COVID-19 pathology.

Severe COVID-19 is characterized by persistent lung inflammation, inflammatory cytokine production, viral RNA and a sustained interferon (IFN) response, all of which are recapitulated and required for pathology in the SARS-CoV-2-infected MISTRG6-hACE2 humanized mouse model of COVID-19, which has a human immune system. Blocking either viral replication with remdesivir or the downstream IFN-stimulated cascade with anti-IFNAR2 antibodies in vivo in the chronic stages of disease attenuates the overactive immune inflammatory response, especially inflammatory macrophages. Here we show that SARS-CoV-2 infection and replication in lung-resident human macrophages is a critical driver of disease.

Analysis of Survival Among Adults With Early-Onset Colorectal Cancer in the National Cancer Database.

Importance: While increased adherence to colorectal cancer (CRC) screening guidelines in the US has been associated with significant reductions in cancer incidence in US individuals aged 50 years and older, the incidence of CRC among those aged younger than 50 years has been steadily increasing. Understanding the survival among individuals with early-onset CRC compared with those aged 50 years and older is fundamental to informing treatment approaches and understanding the unique biological distinctiveness within early-onset CRC.

Objective: To characterize the overall survival for individuals with early-onset CRC.

Dickkopf-2 regulates the stem cell marker LGR5 in colorectal cancer via HNF4α1.

Enhanced stemness in colorectal cancer has been reported and it contributes to aggressive progression, but the underlying mechanisms remain unclear. Here we report a Wnt ligand, Dickkopf-2 (DKK2) is essential for developing colorectal cancer stemness. Genetic depletion of in intestinal epithelial or stem cells reduced tumorigenesis and expression of the stem cell marker genes including in a model of colitis-associated cancer.

Paracrine orchestration of intestinal tumorigenesis by a mesenchymal niche.

The initiation of an intestinal tumour is a probabilistic process that depends on the competition between mutant and normal epithelial stem cells in crypts. Intestinal stem cells are closely associated with a diverse but poorly characterized network of mesenchymal cell types. However, whether the physiological mesenchymal microenvironment of mutant stem cells affects tumour initiation remains unknown.

Identifying the low risk patient in surgical intensive and intermediate care units using continuous monitoring.

Background: Continuous predictive monitoring has been employed successfully to predict subclinical adverse events. Should low values on these models, however, reassure us that a patient will not have an adverse outcome? Negative predictive values of such models could help predict safe patient discharge. The goal of this study was to validate the negative predictive value of an ensemble model for critical illness (using previously developed models for respiratory instability, hemorrhage, and sepsis) based on bedside monitoring data in the intensive care units and intermediate care unit.

External validation in an intermediate unit of a respiratory decompensation model trained in an intensive care unit.

Background: Preventing urgent intubation and upgrade in level of care in patients with subclinical deterioration could be of great utility in hospitalized patients. Early detection should result in decreased mortality, duration of stay, and/or resource use. The goal of this study was to externally validate a previously developed, vital sign-based, intensive care unit, respiratory instability model on a separate population, intermediate care patients.

A novel report of hatching plasticity in the phylum Echinodermata.

Hatching plasticity occurs in response to a wide range of stimuli across many animal taxa, including annelids, arthropods, mollusks, and chordates. Despite the prominence of echinoderms in developmental biology and more than 100 years of detailed examination of their development under a variety of conditions, environmentally cued hatching plasticity has never been reported in the phylum Echinodermata. Here we report plasticity in the timing and stage of hatching of embryos of the sand dollar Echinarachnius parma in response to reductions in salinity.