Layperson's performance on an unconversant type of AED device: A prospective crossover simulation experimental study.

BACKGROUND: Diverse models of automated external defibrillators (AEDs) possess distinctive features. This study aimed to investigate whether laypersons trained with one type of AED could intelligently use another initial contact type of AED with varying features. METHODS: This was a prospective crossover simulation experimental study conducted among college students. Subjects were randomly trained with either AED1 (AED1 group) or AED2 (AED2 group), and the AED operation performance was evaluated individually (Phase I test). At the 6-month follow-up AED performance test (Phase II test), half of the subjects were randomly switched to use another type of AED, which formed two switches (Switch A: AED1-1 group vs. AED2-1 group; Switch B: AED2-2 group vs. AED1-2 group). RESULTS: A total of 224 college students participated in the study. In the phase I test, a significantly higher proportion of successful defibrillation and shorter shock delivery time to achieve successful defibrillation was observed in the AED2 group than in the AED1 group. In the phase II test, no statistical differences were observed in the proportion of successful defibrillation in Switch A (51.4% vs. 36.6%, P=0.19) and Switch B (78.0% vs. 53.7%, P=0.08). The median shock delivery time within participants achieving successful defibrillation was significantly longer in the switched group than that of the initial group in both Switch A (89 [81-107] s vs. 124 [95-135] s, P=0.006) and Switch B (68 [61.5-81.5] s vs. 95.5 [55-131] s, P<0.001). CONCLUSION: College students were able to effectively use AEDs different from those used in the initial training after six months, although the time to shock delivery was prolonged.

A clinical decision model based on machine learning for ptosis.

BACKGROUND: To establish a decision model based on two- (2D) and three-dimensional (3D) eye data of patients with ptosis for developing personalized surgery plans. METHODS: Data of this retrospective, case-control study was collected from March 2019 to June 2019 at the Department of Ophthalmology, Shanghai Ninth People's Hospital, and then the patients were followed up for 3 months. One hundred fifty-two complete feature eyes from 100 voluntary patients with ptosis and satisfactory surgical results were selected, with 48 eyes excluded due to any severe condition or improper collection and shooting angle. Three experimental schemes were set as follows: use 2D distance alone, use 3D distance alone, and use two distances at the same time. The five most common evaluation indicators used in the binary classification problem to test the decision model were accuracy (ACC), precision, recall, F1-score, and area under the curve (AUC). RESULTS: For diagnostic discrimination, recall of "3D", "2D" and "Both" schemes were 0.875, 0.875 and 0.938 respectively. And precision of the three schemes were 0.8333, 0.7778 and 1.0000 for the surgical procedure classification. Values of "Both" scheme that combined 2D and 3D data were the highest in two classifications. CONCLUSIONS: In this study, 3D eye data are introduced into clinical practice to construct a decision model for ptosis surgery. Our decision model presents exceptional prediction effect, especially when 2D and 3D data employed jointly.

Mechanistic insights into the effect of phosphorylation on Ras conformational dynamics and its interactions with cell signaling proteins.

Ras undergoes interconversion between the active GTP-bound state and the inactive GDP-bound state. This GTPase cycle, which controls the activities of Ras, is accelerated by Ras GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (SOS). Oncogenic Ras mutations could affect the GTPase cycle and impair Ras functions. Additionally, Src-induced K-Ras Y32/64 dual phosphorylation has been reported to disrupt GTPase cycle and hinder Ras downstream signaling. However, the underlying mechanisms remain unclear. To address this, we performed molecular dynamics simulations (~30 µs in total) on unphosphorylated and phosphorylated K-Ras4B in GTP- and GDP-bound states, and on their complexes with GTPase cycle regulators (GAP and SOS) and the effector protein Raf. We found that K-Ras4B dual phosphorylation mainly alters the conformation at the nucleotide binding site and creates disorder at the catalytic site, resulting in the enlargement of GDP binding pocket and the retard of Ras-GTP intrinsic hydrolysis. We observed phosphorylation-induced shift in the distribution of Ras-GTP inactive-active sub-states and recognized potential druggable pockets in the phosphorylated Ras-GTP. Moreover, decreased catalytic competence or signal delivery abilities due to reduced binding affinities and/or distorted catalytic conformations of GAP, SOS and Raf were observed. In addition, the allosteric pathway from Ras/Raf interface to the distal Raf L4 loop was compromised by Ras phosphorylation. These results reveal the mechanisms by which phosphorylation influences the intrinsic or GAP/SOS catalyzed transformations between GTP- and GDP-bound states of Ras and its signal transduction to Raf. Our findings project Ras phosphorylation as a target for cancer drug discovery.