How artificial intelligence could transform emergency care.

Artificial intelligence (AI) in healthcare is the ability of a computer to perform tasks typically associated with clinical care (e.g. medical decision-making and documentation). AI will soon be integrated into an increasing number of healthcare applications, including elements of emergency department (ED) care. Here, we describe the basics of AI, various categories of its functions (including machine learning and natural language processing) and review emerging and potential future use-cases for emergency care. For example, AI-assisted symptom checkers could help direct patients to the appropriate setting, models could assist in assigning triage levels, and ambient AI systems could document clinical encounters. AI could also help provide focused summaries of charts, summarize encounters for hand-offs, and create discharge instructions with an appropriate language and reading level. Additional use cases include medical decision making for decision rules, real-time models that predict clinical deterioration or sepsis, and efficient extraction of unstructured data for coding, billing, research, and quality initiatives. We discuss the potential transformative benefits of AI, as well as the concerns regarding its use (e.g. privacy, data accuracy, and the potential for changing the doctor-patient relationship).

Perforin-like protein PPLP2 permeabilizes the red blood cell membrane during egress of Plasmodium falciparum gametocytes.

Egress of malaria parasites from the host cell requires the concerted rupture of its enveloping membranes. Hence, we investigated the role of the plasmodial perforin-like protein PPLP2 in the egress of Plasmodium falciparum from erythrocytes. PPLP2 is expressed in blood stage schizonts and mature gametocytes. The protein localizes in vesicular structures, which in activated gametocytes discharge PPLP2 in a calcium-dependent manner. PPLP2 comprises a MACPF domain and recombinant PPLP2 has haemolytic activities towards erythrocytes. PPLP2-deficient [PPLP2(-)] merozoites show normal egress dynamics during the erythrocytic replication cycle, but activated PPLP2(-) gametocytes were unable to leave erythrocytes and stayed trapped within these cells. While the parasitophorous vacuole membrane ruptured normally, the activated PPLP2(-) gametocytes were unable to permeabilize the erythrocyte membrane and to release the erythrocyte cytoplasm. In consequence, transmission of PPLP2(-) parasites to the Anopheles vector was reduced. Pore-forming equinatoxin II rescued both PPLP2(-) gametocyte exflagellation and parasite transmission. The pore sealant Tetronic 90R4, on the other hand, caused trapping of activated wild-type gametocytes within the enveloping erythrocytes, thus mimicking the PPLP2(-) loss-of-function phenotype. We propose that the haemolytic activity of PPLP2 is essential for gametocyte egress due to permeabilization of the erythrocyte membrane and depletion of the erythrocyte cytoplasm.

The Igf2/H19 muscle enhancer is an active transcriptional complex.

In eukaryotic cells, gene expression is mediated by enhancer activation of RNA polymerase at distant promoters. Recently, distinctions between enhancers and promoters have been blurred by the discovery that enhancers are associated with RNA polymerase and are sites of RNA synthesis. Here, we present an analysis of the insulin-like growth factor 2/H19 muscle enhancer. This enhancer includes a short conserved core element that is organized into chromatin typical of mammalian enhancers, binds tissue-specific transcription factors and functions on its own in vitro to activate promoter transcription. However, in a chromosomal context, this element is not sufficient to activate distant promoters. Instead, enhancer function also requires transcription in cis of a long non-coding RNA, Nctc1. Thus, the insulin-like growth factor 2/H19 enhancer is an active transcriptional complex whose own transcription is essential to its function.