Impact of trauma center status on radiology resident performance in detecting non-accidental trauma on the WIDI SIM exam.

Purpose: To evaluate whether adult and pediatric trauma center status, as well as the presence of dedicated child protection teams, influences radiology resident performance in detecting non-accidental trauma on the Emergent/Critical Care Imaging Simulation (WIDI SIM) exam.

Materials And Methods: We retrospectively analyzed 639 WIDI SIM exam scores for four pediatric non-accidental trauma cases completed by radiology residents across 33 programs. Residents were stratified by level (R1-R4) and institutional factors, including adult trauma center status, pediatric trauma center status, and child protection team presence.

Correlation between adult trauma center status and radiology resident performance on trauma cases in the WIDI SIM exam.

Purpose: To assess whether adult trauma center status influences radiology resident performance on trauma cases in the Emergent/Critical Care Imaging SIMulation (WIDI SIM) exam.

Materials And Methods: This retrospective study analyzed 29,290 WIDI SIM exam scores from 110 adult trauma cases across 55 radiology residency programs. Residents were categorized by training level-R1 (n = 17,801), R2 (n = 9,136), R3 (n = 1,826), R4 (n = 527)-and by their program's adult trauma center designation: Level 1 (n = 20,121), Level 2 (n = 1,870), Level 3 (n = 1,029), Level 4 (n = 487), and no trauma designation (n = 5,834).

CD94 natural killer cells potentiate pulmonary ischaemia-reperfusion injury.

Background: Pulmonary ischaemia-reperfusion injury (IRI) is a major contributor to poor lung transplant outcomes. We recently demonstrated a central role of airway-centred natural killer (NK) cells in mediating IRI; however, there are no existing effective therapies for directly targeting NK cells in humans.

Methods: We hypothesised that a depleting anti-CD94 monoclonal antibody (mAb) would provide therapeutic benefit in mouse and human models of IRI based on high levels of (CD94) transcripts in bronchoalveolar lavage samples from lung transplant patients.

Spleen Tyrosine Kinase (SYK) negatively regulates ITAM-mediated human NK cell signaling and CD19-CAR NK cell efficacy.

NK cells express activating receptors that signal through ITAM-bearing adapter proteins. The phosphorylation of each ITAM creates binding sites for SYK and ZAP70 protein tyrosine kinases to propagate downstream signaling including the induction of influx. While all immature and mature human NK cells co-express SYK and ZAP70, clonally driven memory or adaptive NK cells can methylate genes and signaling is mediated exclusively using ZAP70.

Challenges in diagnosis of calcaneal fractures: an examination using the WIDI SIM platform.

Introduction: The calcaneus is the most commonly fractured tarsal bone. Diagnosis is often challenging due to subtle radiographic changes and requires timely identification to prevent complications, including subtalar arthritis, neurovascular injury, malunion, osteomyelitis, and compartment syndrome. Treatment varies based on fracture type, with non-surgical methods for non-displaced stress fractures and surgical interventions for displaced or intra-articular fractures.

High-dimensional single-cell analysis of human natural killer cell heterogeneity.

Natural killer (NK) cells are innate lymphoid cells (ILCs) contributing to immune responses to microbes and tumors. Historically, their classification hinged on a limited array of surface protein markers. Here, we used single-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to dissect the heterogeneity of NK cells.

Five decades of natural killer cell discovery.

The first descriptions of "non-specific" killing of tumor cells by lymphocytes were reported in 1973, and subsequently, the mediators of the activity were named "natural killer" (NK) cells by Rolf Kiessling and colleagues at the Karolinska Institute in 1975. The activity was detected in mice, rats, and humans that had no prior exposure to the tumors, major histocompatibility complex (MHC) antigen matching of the effectors and tumor cells was not required, and the cells responsible were distinct from MHC-restricted, antigen-specific T cells. In the ensuing five decades, research by many labs has extended knowledge of NK cells beyond an in vitro curiosity to demonstrate their in vivo relevance in host defense against tumors and microbial pathogens and their role in regulation of the immune system.

Pretreatment with IL-15 and IL-18 rescues natural killer cells from granzyme B-mediated apoptosis after cryopreservation.

Human natural killer (NK) cell-based therapies are under assessment for treating various cancers, but cryopreservation reduces both the recovery and function of NK cells, thereby limiting their therapeutic feasibility. Using cryopreservation protocols optimized for T cells, here we find that ~75% of NK cells die within 24 h post-thaw, with the remaining cells displaying reduced cytotoxicity. Using CRISPR-Cas9 gene editing and confocal microscopy, we find that cryopreserved NK cells largely die via apoptosis initiated by leakage of granzyme B from cytotoxic vesicles.

Hepatocellular carcinoma after direct-acting antivirals for hepatitis C is associated with KIR-HLA types predicting weak NK cell-mediated immunity.

Background And Aims: Second-generation direct-acting antivirals (2G DAA) to cure HCV have led to dramatic clinical improvements. HCV-associated hepatocellular carcinoma (HCC), however, remains common. Impaired immune tumor surveillance may play a role in HCC development.

PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways.

Poliovirus receptor-related 2 (PVRL2, also known as nectin-2 or CD112) is believed to act as an immune checkpoint protein in cancer; however, most insight into its role is inferred from studies on its known receptor, poliovirus receptor (PVR)-related immunoglobulin domain protein (PVRIG, also known as CD112R). Here, we study PVRL2 itself. PVRL2 levels were found to be high in tumor cells and tumor-derived exosomes.

Integrative systems biology reveals NKG2A-biased immune responses correlate with protection in infectious disease, autoimmune disease, and cancer.

Infection, autoimmunity, and cancer are principal human health challenges of the 21 century. Often regarded as distinct ends of the immunological spectrum, recent studies hint at potential overlap between these diseases. For example, inflammation can be pathogenic in infection and autoimmunity.

ITAM-based receptors in natural killer cells.

The ability of cells of the immune system to acquire features such as increased longevity and enhanced secondary responses was long thought to be restricted to cells of the adaptive immune system. Natural killer (NK) cells have challenged this notion by demonstrating that they can also gain adaptive features. This has been observed in both humans and mice during infection with cytomegalovirus (CMV).

An assessment of radiology resident competency in identifying suppurative retropharyngeal lymphadenitis: an examination using the WIDI SIM platform.

Background And Purpose: Suppurative retropharyngeal lymphadenitis is a retropharyngeal space infection almost exclusively seen in the young (4-8 years old) pediatric population. It can be misdiagnosed as a retropharyngeal abscess, leading to unnecessary invasive treatment procedures. This retrospective study aims to assess radiology residents' ability to independently identify CT imaging findings and make a definitive diagnosis of suppurative retropharyngeal lymphadenitis in a simulated call environment.

Cellular Iron Deficiency Disrupts Thyroid Hormone Regulated Gene Expression in Developing Hippocampal Neurons.

Background: Developing neurons have high thyroid hormone and iron requirements to support their metabolically demanding growth. Early-life iron and thyroid-hormone deficiencies are prevalent and often coexist, and each independently increases risk of permanently impaired neurobehavioral function in children. Early-life dietary iron deficiency reduces thyroid-hormone concentrations and impairs thyroid hormone-responsive gene expression in the neonatal rat brain, but it is unclear whether the effect is cell-intrinsic.

An NKG2A biased immune response confers protection for infection, autoimmune disease, and cancer.

Infection, autoimmunity, and cancer are the principal human health challenges of the 21st century and major contributors to human death and disease. Often regarded as distinct ends of the immunological spectrum, recent studies have hinted there may be more overlap between these diseases than appears. For example, pathogenic inflammation has been demonstrated as conserved between infection and autoimmune settings.

Genomic Variant Is Associated with NKG2D-mediated Acute Lung Injury and Death.

Acute lung injury (ALI) carries a high risk of mortality but has no established pharmacologic therapy. We previously found that experimental ALI occurs through natural killer (NK) cell NKG2D receptor activation and that the cognate human ligand, MICB, was associated with ALI after transplantation. To investigate the association of a common missense variant, , with ALI.

CCR5 drives NK cell-associated airway damage in pulmonary ischemia-reperfusion injury.

Primary graft dysfunction (PGD) limits clinical benefit after lung transplantation, a life-prolonging therapy for patients with end-stage disease. PGD is the clinical syndrome resulting from pulmonary ischemia-reperfusion injury (IRI), driven by innate immune inflammation. We recently demonstrated a key role for NK cells in the airways of mouse models and human tissue samples of IRI.

Cellular Iron Deficiency Disrupts Thyroid Hormone Regulated Gene Expression in Developing Hippocampal Neurons.

Background: Developing neurons have high thyroid hormone and iron requirements to support their metabolism and growth. Early-life iron and thyroid hormone deficiencies are prevalent, often coexist, and increase the risk of permanently impaired neurobehavioral function in children. Early-life dietary iron deficiency reduces thyroid hormone levels and impairs thyroid hormone-responsive gene expression in the neonatal rat brain.

Hypoimmune induced pluripotent stem cells survive long term in fully immunocompetent, allogeneic rhesus macaques.

Genetic engineering of allogeneic cell therapeutics that fully prevents rejection by a recipient's immune system would abolish the requirement for immunosuppressive drugs or encapsulation and support large-scale manufacturing of off-the-shelf cell products. Previously, we generated mouse and human hypoimmune pluripotent (HIP) stem cells by depleting HLA class I and II molecules and overexpressing CD47 (B2MCIITACD47). To determine whether this strategy is successful in non-human primates, we engineered rhesus macaque HIP cells and transplanted them intramuscularly into four allogeneic rhesus macaques.

The interweaved signatures of common-gamma-chain cytokines across immunologic lineages.

"γc" cytokines are a family whose receptors share a "common-gamma-chain" signaling moiety, and play central roles in differentiation, homeostasis, and communications of all immunocyte lineages. As a resource to better understand their range and specificity of action, we profiled by RNAseq the immediate-early responses to the main γc cytokines across all immunocyte lineages. The results reveal an unprecedented landscape: broader, with extensive overlap between cytokines (one cytokine doing in one cell what another does elsewhere) and essentially no effects unique to any one cytokine.

Exhausted intratumoral Vδ2 γδ T cells in human kidney cancer retain effector function.

Gamma delta (γδ) T cells reside within human tissues including tumors, but their function in mediating antitumor responses to immune checkpoint inhibition is unknown. Here we show that kidney cancers are infiltrated by Vδ2 γδ T cells, with equivalent representation of Vδ1 and Vδ1 cells, that are distinct from γδ T cells found in normal human tissues. These tumor-resident Vδ2 T cells can express the transcriptional program of exhausted αβ CD8 T cells as well as canonical markers of terminal T-cell exhaustion including PD-1, TIGIT and TIM-3.

The CD16 and CD32b Fc-gamma receptors regulate antibody-mediated responses in mouse natural killer cells.

Natural killer (NK) cells are innate lymphocytes capable of mediating immune responses without prior sensitization. NK cells express Fc-gamma receptors (FcγRs) that engage the Fc region of IgG. Studies investigating the role of FcγRs on mouse NK cells have been limited due to lack specific reagents.

CD16 natural killer cells in bronchoalveolar lavage are associated with antibody-mediated rejection and chronic lung allograft dysfunction.

Acute and chronic rejections limit the long-term survival after lung transplant. Pulmonary antibody-mediated rejection (AMR) is an incompletely understood driver of long-term outcomes characterized by donor-specific antibodies (DSAs), innate immune infiltration, and evidence of complement activation. Natural killer (NK) cells may recognize DSAs via the CD16 receptor, but this complement-independent mechanism of injury has not been explored in pulmonary AMR.