Entrustment and EPAs for Artificial Intelligence (AI): A Framework to Safeguard the Use of AI in Health Professions Education.

In this article, the authors propose a repurposing of the concept of entrustment to help guide the use of artificial intelligence (AI) in health professions education (HPE). Entrustment can help identify and mitigate the risks of incorporating generative AI tools with limited transparency about their accuracy, source material, and disclosure of bias into HPE practice. With AI's growing role in education-related activities, like automated medical school application screening and feedback quality and content appraisal, there is a critical need for a trust-based approach to ensure these technologies are beneficial and safe.

AI-assisted human clinical reasoning in the ICU: beyond "to err is human".

Diagnostic errors pose a significant public health challenge, affecting nearly 800,000 Americans annually, with even higher rates globally. In the ICU, these errors are particularly prevalent, leading to substantial morbidity and mortality. The clinical reasoning process aims to reduce diagnostic uncertainty and establish a plausible differential diagnosis but is often hindered by cognitive load, patient complexity, and clinician burnout.

Vitamin D constrains inflammation by modulating the expression of key genes on Chr17q12-21.1.

Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D-mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.

Assessing the potential of GPT-4 to perpetuate racial and gender biases in health care: a model evaluation study.

Background: Large language models (LLMs) such as GPT-4 hold great promise as transformative tools in health care, ranging from automating administrative tasks to augmenting clinical decision making. However, these models also pose a danger of perpetuating biases and delivering incorrect medical diagnoses, which can have a direct, harmful impact on medical care. We aimed to assess whether GPT-4 encodes racial and gender biases that impact its use in health care.

Randomized Phase 2 Placebo-Controlled Trial of Nintedanib for the Treatment of Radiation Pneumonitis.

Purpose: Radiation pneumonitis (RP) is the most common dose-limiting toxicity for thoracic radiation therapy. Nintedanib is used for the treatment of idiopathic pulmonary fibrosis, which shares pathophysiological pathways with the subacute phase of RP. Our goal was to investigate the efficacy and safety of nintedanib added to a prednisone taper compared with a prednisone taper alone in reducing pulmonary exacerbations in patients with grade 2 or higher (G2+) RP.

Mouse phospholipid phosphatase 6 regulates dendritic cell cholesterol, macropinocytosis, and allergen sensitization.

Lipid phosphate phosphatases are a family of enzymes with diverse cellular metabolic functions. Phospholipid phosphatase 6 (PLPP6) is a regulator of cellular polyisoprenyl phosphates; however, its functions remain to be determined. Here, mouse PLPP6 was characterized to possess similar catalytic properties as the human enzyme.

Inflammation resolution circuits are uncoupled in acute sepsis and correlate with clinical severity.

Sepsis is a critical illness characterized by dysregulated inflammatory responses lacking counter-regulation. Specialized proresolving mediators are agonists for antiinflammation and for promoting resolution, and they are protective in preclinical sepsis models. Here, in human sepsis, we mapped resolution circuits for the specialized proresolving mediators resolvin D1 and resolvin D2 in peripheral blood neutrophils and monocytes, their regulation of leukocyte activation and function ex vivo, and their relationships to measures of clinical severity.

FcεR1-expressing nociceptors trigger allergic airway inflammation.

Background: Lung nociceptor neurons amplify immune cell activity and mucus metaplasia in response to an inhaled allergen challenge in sensitized mice.

Objective: We sought to identify the cellular mechanisms by which these sensory neurons are activated subsequent to allergen exposure.

Methods: We used calcium microscopy and electrophysiologic recording to assess whether vagal neurons directly respond to the model allergen ovalbumin (OVA).

Plasma Levels of Proresolving and Prophlogistic Lipid Mediators: Association With Severity of Respiratory Failure and Mortality in Acute Respiratory Distress Syndrome.

Objectives: Acute respiratory distress syndrome is characterized by an overly exuberant inflammatory state in the lung. Specialized proresolving mediators are endogenous agonists for the resolution of lung inflammation and injury in health, yet their association with acute respiratory distress syndrome severity and outcomes remains to be defined. In the current study, we investigate associations between plasma levels of specialized proresolving mediators and acute respiratory distress syndrome severity and mortality.

Novel platform leveraging electronic medical record (EMR) to triage patients admitted with high-grade immune-related adverse events (irAEs) to the immune-toxicity (ITOX) service.

Background: The incidence of high-grade immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICIs) is increasing due to the rapid expansion of indications for their use. There is an urgent need for a feasible approach of identifying patients with high-grade irAEs to ensure early detection and proper management of this unique set of toxicities.

Methods: We established one of the first inpatient services that are specifically devoted to mitigating irAEs.

Cysteinyl maresins regulate the prophlogistic lung actions of cysteinyl leukotrienes.

Background: Cysteinyl leukotrienes (CysLTs) are potent prophlogistic mediators in asthmatic patients; however, inhibition of CysLT receptor 1 is not a consistently effective treatment, suggesting additional regulatory mechanisms. Other cysteinyl-containing lipid mediators (LMs) derived from docosahexaenoic acid, namely maresin conjugates in tissue regeneration (MCTRs), were recently discovered. Therefore their production and actions in the lung are of considerable interest.

Calcitonin Gene-Related Peptide Negatively Regulates Alarmin-Driven Type 2 Innate Lymphoid Cell Responses.

Neuroimmune interactions have emerged as critical modulators of allergic inflammation, and type 2 innate lymphoid cells (ILC2s) are an important cell type for mediating these interactions. Here, we show that ILC2s expressed both the neuropeptide calcitonin gene-related peptide (CGRP) and its receptor. CGRP potently inhibited alarmin-driven type 2 cytokine production and proliferation by lung ILC2s both in vitro and in vivo.

A Model of Self-limited Acute Lung Injury by Unilateral Intra-bronchial Acid Instillation.

Selective intra-bronchial instillation of hydrochloric acid (HCl) to the murine left mainstem bronchus causes acute tissue injury with histopathologic findings similar to human acute respiratory distress syndrome (ARDS). The resulting alveolar edema, alveolar-capillary barrier damage, and leukocyte infiltration predominantly affect the left lung, preserving the right lung as an uninjured control and allowing animals to survive. This model of self-limited acute lung injury enables investigation of tissue resolution mechanisms, such as macrophage efferocytosis of apoptotic neutrophils and restitution of alveolar-capillary barrier integrity.

Neutrophil cytoplasts induce T17 differentiation and skew inflammation toward neutrophilia in severe asthma.

Severe asthma is a debilitating and treatment refractory disease. As many as half of these patients have complex neutrophil-predominant lung inflammation that is distinct from milder asthma with type 2 eosinophilic inflammation. New insights into severe asthma pathogenesis are needed.

Early Intravascular Events Are Associated with Development of Acute Respiratory Distress Syndrome. A Substudy of the LIPS-A Clinical Trial.

Rationale: Acute respiratory distress syndrome (ARDS) is a devastating illness with limited therapeutic options. A better understanding of early biochemical and immunological events in ARDS could inform the development of new preventive and treatment strategies.

Objectives: To determine select peripheral blood lipid mediator and leukocyte responses in patients at risk for ARDS.

Specialized Proresolving Mediators in Innate and Adaptive Immune Responses in Airway Diseases.

Airborne pathogens and environmental stimuli evoke immune responses in the lung. It is critical to health that these responses be controlled to prevent tissue damage and the compromise of organ function. Resolution of inflammation is a dynamic process that is coordinated by biochemical and cellular mechanisms.

15-epi-Lipoxin A, Resolvin D2, and Resolvin D3 Induce NF-κB Regulators in Bacterial Pneumonia.

Specialized proresolving mediators (SPMs) decrease NF-κB activity to prevent excessive tissue damage and promote the resolution of acute inflammation. Mechanisms for NF-κB regulation by SPMs remain to be determined. In this study, after LPS challenge, the SPMs 15-epi-lipoxin A (15-epi-LXA), resolvin D1, resolvin D2, resolvin D3, and 17-epi-resolvin D1 were produced in vivo in murine lungs.

Phospholipase D isoforms differentially regulate leukocyte responses to acute lung injury.

Phospholipase D (PLD) plays important roles in cellular responses to tissue injury that are critical to acute inflammatory diseases, such as the acute respiratory distress syndrome (ARDS). We investigated the expression of PLD isoforms and related phospholipid phosphatases in patients with ARDS, and their roles in a murine model of self-limited acute lung injury (ALI). Gene expression microarray analysis on whole blood obtained from patients that met clinical criteria for ARDS and clinically matched controls (non-ARDS) demonstrated that PLD1 gene expression was increased in patients with ARDS relative to non-ARDS and correlated with survival.

Erratum: The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation.

This corrects the article DOI: 10.1038/nature24029.

The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation.

Type 2 innate lymphoid cells (ILC2s) both contribute to mucosal homeostasis and initiate pathologic inflammation in allergic asthma. However, the signals that direct ILC2s to promote homeostasis versus inflammation are unclear. To identify such molecular cues, we profiled mouse lung-resident ILCs using single-cell RNA sequencing at steady state and after in vivo stimulation with the alarmin cytokines IL-25 and IL-33.

Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia.

Acute lung injury is a life-threatening condition caused by disruption of the alveolar-capillary barrier leading to edema, influx of inflammatory leukocytes, and impaired gas exchange. Specialized proresolving mediators biosynthesized from essential fatty acids, such as docosahexaenoic acid, have tissue protective effects in acute inflammation. Herein, we found that the docosahexaenoic acid-derived mediator resolvin D3 (RvD3): 4S,11R,17S-trihydroxydocosa-5Z,7E,9E,13Z,15E,19Z-hexaenoic acid was present in uninjured lungs, and increased significantly 24 to 72 hours after hydrochloric acid-initiated injury.