Search

Single-molecule experiments are a unique tool to characterize the structural dynamics of biomolecules. However, reconstructing molecular details from noisy single-molecule data is challenging. Simulation-based inference (SBI) is a powerful framework for analyzing complex experimental data, integrating statistical inference, physics-based simulators, and machine learning. Recent advances in deep learning have accelerated the development of new SBI methods, enabling the application of Bayesian inference to an ever-increasing number of scientific problems. Here, we review the nascent application of SBI to the analysis of single-molecule experiments. We introduce parametric Bayesian inference and discuss its limitations. We then overview emerging deep learning-based SBI methods to perform Bayesian inference for complex models encoded in computer simulators. We illustrate the first applications of SBI to single-molecule force spectroscopy and cryo-electron microscopy experiments. SBI allows us to leverage powerful computer algorithms modeling complex biomolecular phenomena to connect scientific models and experiments in a principled way., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: American Academy of Pediatrics guidelines recommend that febrile infants at low risk for invasive bacterial infection be discharged from the emergency department (ED) if primary care provider (PCP) follow-up occurs within 24 hours. We aimed to (1) assess the association between having electronic health record (EHR) documentation of a PCP and ED disposition and (2) describe documentation of potential barriers to discharge and plans for post-discharge follow-up in low-risk febrile infants., Methods: We conducted a secondary analysis of a multicenter, cross-sectional study of low-risk febrile infants. Descriptive statistics characterized ED disposition on the basis of the day of the visit, EHR documentation of PCP, scheduled or recommended PCP follow-up, and barriers to discharge., Results: Most infants (3565/4042, 90.5%) had EHR documentation of a PCP. Compared with discharged infants, a similar proportion of hospitalized infants had EHR documentation of PCP (90.3% vs 91.2%, P = .47). Few infants (1.5%) had barriers to discharge documented. Of the 3360 infants (83.1%) discharged from the ED, 1544 (46.0%) had documentation of scheduled or recommended 24-hour PCP follow-up. Discharged infants with weekday visits were more likely than those with weekend visits to have documentation of scheduled or recommended 24-hour follow-up (50.0% vs 35.5%, P < .001)., Conclusions: Most infants had a documented PCP, yet fewer than half had documentation of a scheduled or recommended 24-hour follow-up. A dedicated focus on determining post-ED care plans that are safe and patient-centered may improve the quality of care for this population., (Copyright © 2024 by the American Academy of Pediatrics.)

Importance: Febrile infants at low risk of invasive bacterial infections are unlikely to benefit from lumbar puncture, antibiotics, or hospitalization, yet these are commonly performed. It is not known if there are differences in management by race, ethnicity, or language., Objective: To investigate associations between race, ethnicity, and language and additional interventions (lumbar puncture, empirical antibiotics, and hospitalization) in well-appearing febrile infants at low risk of invasive bacterial infection., Design, Setting, and Participants: This was a multicenter retrospective cross-sectional analysis of infants receiving emergency department care between January 1, 2018, and December 31, 2019. Data were analyzed from December 2022 to July 2023. Pediatric emergency departments were determined through the Pediatric Emergency Medicine Collaborative Research Committee. Well-appearing febrile infants aged 29 to 60 days at low risk of invasive bacterial infection based on blood and urine testing were included. Data were available for 9847 infants, and 4042 were included following exclusions for ill appearance, medical history, and diagnosis of a focal infectious source., Exposures: Infant race and ethnicity (non-Hispanic Black, Hispanic, non-Hispanic White, and other race or ethnicity) and language used for medical care (English and language other than English)., Main Outcomes and Measures: The primary outcome was receipt of at least 1 of lumbar puncture, empirical antibiotics, or hospitalization. We performed bivariate and multivariable logistic regression with sum contrasts for comparisons. Individual components were assessed as secondary outcomes., Results: Across 34 sites, 4042 infants (median [IQR] age, 45 [38-53] days; 1561 [44.4% of the 3516 without missing sex] female; 612 [15.1%] non-Hispanic Black, 1054 [26.1%] Hispanic, 1741 [43.1%] non-Hispanic White, and 352 [9.1%] other race or ethnicity; 3555 [88.0%] English and 463 [12.0%] language other than English) met inclusion criteria. The primary outcome occurred in 969 infants (24%). Race and ethnicity were not associated with the primary composite outcome. Compared to the grand mean, infants of families that use a language other than English had higher odds of the primary outcome (adjusted odds ratio [aOR]; 1.16; 95% CI, 1.01-1.33). In secondary analyses, Hispanic infants, compared to the grand mean, had lower odds of hospital admission (aOR, 0.76; 95% CI, 0.63-0.93). Compared to the grand mean, infants of families that use a language other than English had higher odds of hospital admission (aOR, 1.08; 95% CI, 1.08-1.46)., Conclusions and Relevance: Among low-risk febrile infants, language used for medical care was associated with the use of at least 1 nonindicated intervention, but race and ethnicity were not. Secondary analyses highlight the complex intersectionality of race, ethnicity, language, and health inequity. As inequitable care may be influenced by communication barriers, new guidelines that emphasize patient-centered communication may create disparities if not implemented with specific attention to equity.

Objectives: Anaphylaxis requires prompt assessment and management with epinephrine to reduce its morbidity and mortality. This study examined the prehospital management of pediatric anaphylactic reactions in Northeast Ohio., Methods: This is a retrospective chart review using emergency medical service (EMS) run charts of patients 18 years and younger from February 2015 to April 2019. Patient charts with the diagnosis of "anaphylaxis" or "allergic reaction" were reviewed and confirmed that symptoms met anaphylaxis criteria. Information regarding epinephrine administration before EMS arrival and medications given by EMS providers was collected. Analysis was performed using descriptive statistics., Results: From 646 allergic/anaphylactic reaction EMS run charts, 150 (23%) met the guideline criteria for anaphylaxis. The median patient age was 12 years. Only 57% (86/150) of these patients received intramuscular epinephrine, and the majority received it before EMS arrival. Epinephrine was administered by EMS to 32% (30/94; 95% confidence interval [CI], 22.7% to 42.3%) of patients who had not already received epinephrine. The odds of receiving prehospital epinephrine were significantly lower for patients 5 years and younger (risk difference [RD], -0.23; 95% CI, -0.43 to -0.04), those with no history of allergic reaction (RD, -0.20; 95% CI, -0.38 to -0.03), those who presented with lethargy (RD, -0.43; 95% CI, -0.79 to -0.06), and those whose trigger was a medication or environmental allergen (RD, -0.47; 95% CI, -0.72 to -0.23 for each)., Conclusions: Emergency medical service providers in this region demonstrated similar use of epinephrine as reported elsewhere. However, 43% (64/150) of pediatric patients meeting anaphylaxis criteria did not receive prehospital epinephrine, and 10% (15/150) received no treatment whatsoever. Efforts to improve EMS provider recognition and prompt epinephrine administration in pediatric cases of anaphylaxis seem necessary., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Resources such as computed tomography (CT) scanners are sometimes shared when separate adult and pediatric emergency departments (EDs) exist in proximity., Objectives: To assess the impact of American College of Surgeons Level I trauma verification of an adult ED on the timeliness of nontrauma CT scans in a pediatric and adult ED that share a CT scanner., Methods: ED patient records were retrospectively reviewed to determine the time from order to completion of nontrauma CT scans. We compared the timeliness of CT scan completion between the year leading up to the adult ED being verified as a Level I Trauma Center (2015), and the 2 subsequent years (2016-2017)., Results: The median time for nontrauma CT completion in the adult ED prior to Level I verification was 39 min, compared with 50 min and 49 min for the subsequent 2 years (p < 0.001). Similarly, the median time for completion of nontrauma CT scans in the pediatric ED increased from 33 min to 41 min and 39 min (p < 0.001). The proportion of patients who received CT scans within 30 min from order decreased after adult ED trauma upgrade, from 40% in 2015 to 30% and 32% (p < 0.001) in the 2 subsequent years. The pediatric ED showed similar results, with 48% of patients receiving CT scans within 30 min in 2015, compared with 34% in 2016 and 35% in 2017 (p < 0.001)., Conclusions: Level I trauma verification of the adult ED adversely affected the timeliness of nontrauma CT scans in the EDs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Firearm injury prevention training is lacking in pediatric residency programs., Description: This study aimed to evaluate a web-based curriculum teaching residents how to provide injury prevention anticipatory guidance, emphasizing firearm injury prevention. Ninety-two residents participated and completed pretesting. Residents in the intervention group completed the curriculum, posttesting, and 6-month follow-up testing. Residents in the nonintervention group completed 6-month follow-up testing. Pre- and posttest comparisons between and within each group were made., Evaluation: Baseline knowledge of the participants was high, and no significant change in knowledge was shown in either group. Changes in attitude were noted regarding physician role in providing firearm injury anticipatory guidance in the intervention group, which persisted at 6 months. Participants completing the curriculum showed significant improvement for all self-efficacy questions in the immediate and 6-month follow-up testing., Conclusions: Participants reported changes in attitudes and in confidence in their ability to provide firearm injury prevention counseling after completion of a web-based curriculum.