Lundsgaardschwartz3817

CD8 T cells play an essential role in defense against viral and bacterial infections and in tumor immunity. Deciphering T cell loss of functionality is complicated by the conspicuous heterogeneity of CD8 T cell states described across experimental and clinical settings. By carrying out a unified analysis of over 300 assay for transposase-accessible chromatin sequencing (ATAC-seq) and RNA sequencing (RNA-seq) experiments from 12 studies of CD8 T cells in cancer and infection, we defined a shared differentiation trajectory toward dysfunction and its underlying transcriptional drivers and revealed a universal early bifurcation of functional and dysfunctional T cell states across models. Experimental dissection of acute and chronic viral infection using single-cell ATAC (scATAC)-seq and allele-specific single-cell RNA (scRNA)-seq identified state-specific drivers and captured the emergence of similar TCF1+ progenitor-like populations at an early branch point, at which functional and dysfunctional T cells diverge. Our atlas of CD8 T cell states will facilitate mechanistic studies of T cell immunity and translational efforts.

The ACR Data Science Institute conducted its first annual survey of ACR members to understand how radiologists are using artificial intelligence (AI) in clinical practice and to provide a baseline for monitoring trends in AI use over time.

The ACR Data Science Institute sent a brief electronic survey to all ACR members via email. Invitees were asked for demographic information about their practice and if and how they were currently using AI as part of their clinical work. They were also asked to evaluate the performance of AI models in their practices and to assess future needs.

Approximately 30% of radiologists are currently using AI as part of their practice. Large practices were more likely to use AI than smaller ones, and of those using AI in clinical practice, most were using AI to enhance interpretation, most commonly detection of intracranial hemorrhage, pulmonary emboli, and mammographic abnormalities. Of practices not currently using AI, 20% plan to purchase AI tools in the next 1 to 5 years.

The survey results indicate a modest penetrance of AI in clinical practice. Information from the survey will help researchers and industry develop AI tools that will enhance radiological practice and improve quality and efficiency in patient care.

The survey results indicate a modest penetrance of AI in clinical practice. Information from the survey will help researchers and industry develop AI tools that will enhance radiological practice and improve quality and efficiency in patient care.

The objective of this study was to assess whether a history of malignancy affects the incidence of extrathoracic malignancies and lung cancer in patients undergoing CT lung cancer screening (LCS).

All patients who underwent a LCS CT between June 2014 and August 2018 in a single health care system were included. History of prior nonskin malignancy was extracted from billing records. Subsequent diagnoses of malignancy were extracted from clinical pathology reports. Risk for subsequent malignancy was compared between patients with and those without prior malignancy and evaluated using multivariate logistic regression including age and history of malignancy.

A total of 5,835 LCS CT studies were included, and 1,243 (21%) were performed on patients with diagnoses of malignancy before CT. For the 4,592 scans performed on patients without histories of malignancy, 87 patients (1.9%) were diagnosed with lung cancer and 68 (1.5%) were diagnosed with nonlung malignancies in the following year. Among patients with hCS.Cerebral cavernous malformations (CCMs) are vascular disorders that affect up to 0.5% of the total population. About 20% of CCMs are inherited because of familial mutations in CCM genes, including CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10, whereas the etiology of a majority of simplex CCM-affected individuals remains unclear. Here, we report somatic mutations of MAP3K3, PIK3CA, MAP2K7, and CCM genes in CCM lesions. In particular, somatic hotspot mutations of PIK3CA are found in 11 of 38 individuals with CCMs, and a MAP3K3 somatic mutation (c.1323C>G [p.Ile441Met]) is detected in 37.0% (34 of 92) of the simplex CCM-affected individuals. Strikingly, the MAP3K3 c.1323C>G mutation presents in 95.7% (22 of 23) of the popcorn-like lesions but only 2.5% (1 of 40) of the subacute-bleeding or multifocal lesions that are predominantly attributed to mutations in the CCM1/2/3 signaling complex. Benzylpenicillin potassium mw Leveraging mini-bulk sequencing, we demonstrate the enrichment of MAP3K3 c.1323C>G mutation in CCM endothelium. Mechanistically, beyond the activation of CCM1/2/3-inhibited ERK5 signaling, MEKK3 p.Ile441Met (MAP3K3 encodes MEKK3) also activates ERK1/2, JNK, and p38 pathways because of mutation-induced MEKK3 kinase activity enhancement. Collectively, we identified several somatic activating mutations in CCM endothelium, and the MAP3K3 c.1323C>G mutation defines a primary CCM subtype with distinct characteristics in signaling activation and magnetic resonance imaging appearance.The genital area is not routinely included in the total-body skin examination (TBSE) despite malignancies and inflammatory conditions involving the genital skin. This article explores some of the reasons for this omission and highlights why examining the genital area during routine dermatologic evaluation is important. It also provides an approach to performing the genital examination that can be adapted for everyday practice.Vibrio vulnificus is a motile, gram-negative, halophilic, aquatic bacterium that is part of the normal estuarine microbiome and typically is found in warm coastal waters. Infection with the pathogen typically is due to consumption of contaminated seafood or exposure to contaminated seawater. Vibrio vulnificus has a mortality rate of almost 33% in the United States and is responsible for more than 95% of seafood-related deaths in the United States. Vibrio vulnificus can cause a vast spectrum of diseases, such as gastroenteritis, cellulitis, necrotizing fasciitis, and sepsis. Gastroenteritis is self-limited, whereas septicemia often is fatal. Gastroenteritis and septicemia are caused by ingestion of contaminated shellfish, whereas wound infections and necrotizing fasciitis are caused by exposure to contaminated seawater or handling of contaminated seafood. Septicemia is the most common presentation of V vulnificus and accounts for the most fatalities from the bacteria. Prompt diagnosis and treatment are vital to prevent mortality.